MEDI-CAL DRUG USE REVIEW (DUR) BOARD

State of California DEPARTMENT OF HEALTH CARE SERVICES

Notice is hereby given that the Medi-Cal DUR Board will conduct a public meeting on Tuesday, September 19, 2017, at the following location:

Department of Health Care Services 1500 Capitol Avenue Training Rooms A+B Sacramento, CA 95814

Medi-Cal Drug Use Review Board Meeting Agenda September 19, 2017 9:30 AM-12:30 PM

Report Agenda Item Presenter Time Type*

C 1. Welcome/Introduction Pauline Chan, RPh, MBA 930- 935

A 2. Call to Order/Review and Approval of Previous Minutes Robert Mowers, PharmD 935- from May 16, 2017 940

3. Old Business A a. Review of Action Items from Previous Board Meeting: Pauline Chan, RPh, MBA 940- i. Submission of FFY 2016 DUR Annual Report to CMS and Hannah Orozco, 945 ii. Ingredient Duplication (ID) Alert PharmD iii. Late Refill (LR) Alert iv. Additive Toxicity (AT) Alert v. DUR Educational Outreach: Early Refill vi. DUR Educational Outreach: Fluoroquinolones vii. DUR Educational Outreach: OTC viii. DUR Educational Outreach: Triptans

4. New Business R/D a. Global DUR Board Dorothy Uzoh, PharmD 945- and Paul Nguyen, PharmD 1005

R/A/D b. Board Activities: DUR Board 1005- i. DUR Bylaws 1015 ii. Summary of DUR Board Conference Call iii. DUR Board Elections

R/A/D c. Quarterly Report: 2Q2017 (April – June 2017) Amanda Fingado, MPH 1015- d. Review of Physician Administered Drugs (PADs): 1045 1Q2017 e. Prospective DUR i. Review of DUR Alerts for New GCNs: 2Q2017 ii. Ingredient Duplication (ID) Alert: EMTRICITABINE iii. Summary Report: Updates to Prospective DUR f. Review of DUR Educational Outreach to Providers i. Outcomes: Early Refill ii. Outcomes: Fluoroquinolones iii. Updated Outcomes: Metabolic Monitoring – 2016

R/A/D g. Academic Detailing Pilot Project: Late Refill Shalini Lynch, PharmD 1045- h. Review of DUR Publications 1110 i. DUR Bulletin (August, 2017): QT Prolongation ii. Discussion/Recommendations for Future Bulletins

R/D i. PCSK9 Inhibitors for Treatment of High Cholesterol: Jeffrey A. Tice, MD [UCSF] 1110- Update on Clinical Efficacy and Cost-Effectiveness and Dhruv S. Kazi, MD, 1140 MSc, MS [UCSF and ZSFGH] R/D j. Low-Dose Aspirin Usage Among Fee-For-Service (FFS) Zhiwei Yu, MPH 1140- Medi-Cal Population [Office of the Medical 1155 Director, DHCS]

R/D k. Pharmacy Update Pauline Chan, RPh, MBA 1155- i. Codeine/Tramadol Age Restrictions 1225 ii. Opioid Quantity Limits Policy Change iii. Triptan Quantity Limits Policy Change iv. DHCS $90M Grant to Fight Opioid Crisis v. Academic Detailing Conference: October 12, 2017 vi. Child/Adult Core Set – CMS Report vii. Review of FFY 2018 DUR Annual Report to CMS

C 5. Public Comments 1225- 1230

6. Consent Agenda I a. Meeting feedback b. Next meeting: November 21, 2017 DHCS Training Rooms B+C 1500 Capitol Avenue Sacramento, CA 95814 c. Proposed DUR Board Meeting Dates for 2018: Tuesday, February 20, 2018 Tuesday, May 15, 2018 Tuesday, September 18, 2018 Tuesday, November 20, 2018

7. Adjournment 1230

* REPORT TYPE LEGEND: A: Action; R: Report; I: Information; C: Comment; D: Discussion ** Comments from the public are always appreciated. However, comments will be limited to five minutes per individual.

Picture identification is required to gain access into the California Department of Health Services building. However, your security information will not be provided to the DUR Board.

You can obtain the DUR Board agenda from the Medi-Cal DUR Main Menu Web site (http://files.medi-cal.ca.gov/pubsdoco/dur/dur_home.asp).

MEDI-CAL DRUG USE REVIEW BOARD MEETING MINUTES Tuesday, May 16, 2017 9:30 a.m. – 12:30 p.m.

Location: Department of Health Care Services 1500 Capitol Avenue Training Rooms A+B Sacramento, CA 95814

Topic Discussion 1) WELCOME/  The meeting was called to order by the Chair of the Board, Dr. Robert Mowers. INTRODUCTION  Board members present: Drs. Andrew Wong, Randall Stafford, Robert Mowers, Patrick Finley, Timothy Albertson, Janeen McBride, and Marilyn Stebbins.  Board members absent: none.  Board members and attendees introduced themselves.  Pauline Chan, RPh and Dorothy Uzoh, PharmD were present from DHCS Pharmacy Benefits Division.  Hannah Orozco, PharmD (Conduent) announced that the DUR Board meeting is being recorded and encouraged everyone to sign the attendance sheet.  Ms. Chan also reported that the annual conflict of interest attestation forms were distributed to the Board and will need to be completed and turned in before the next DUR Board meeting.  Dr. Mowers stated that he is viewing a paper copy of the agenda and packet in order to follow the agenda and attachments being presented. However, he would like to acknowledge that personal computing devices are being used by some to view the same material electronically. This statement is required by Open Meeting rules.

2) CALL TO  The Medi-Cal Drug Use Review Board (the “Board”) reviewed the February 21, 2017 ORDER/ minutes. Dr. Wong noted he had minor edits and motioned that the minutes be approved REVIEW AND with these changes. There was no discussion. The Board voted unanimously to approve the APPROVAL OF minutes as edited by Dr. Wong. FEBRUARY 2016 MINUTES AYE: Albertson, Finley, McBride, Mowers, Stafford, Stebbins, Wong NAY: None ABSTAIN: None ABSENT: None

ACTION ITEM: Incorporate Dr. Wong’s edits into the minutes and post to the DUR website.

3) OLD BUSINESS a. Review of Action Items from Previous Board Meeting: i. Update on Additive Toxicity Alert – Dr. Orozco reported that the previous DUR Board recommendations regarding additive toxicity alerts are currently in progress. In addition, Amanda Fingado, MPH (UCSF) will be presenting drugs that still need a final additive toxicity alert decision for further discussion later in the meeting.

1

4) NEW BUSINESS a. Board Activities: i. Buprenorphine study – Dr. Stafford provided an update on his project facilitating increased BUPRENORPHINE prescribing. The intervention will include an online provider training program coupled with academic detailing by a pharmacist. Dr. Stafford described that the online training component will have clinical vignettes, evidence-based strategies, linkage to a coach, and information regarding the benefits of weaning and tapering patients off of opioids. Dr. Stafford explained that using a spoke and hub model, there will be an emphasis on referrals, then returning the patient to the provider. Remaining questions to be discussed with DHCS include how to incentivize providers for participating in the training.

Dr. Stebbins asked if prescribers who treat cancer patients would be excluded. Dr. Stafford said that prescribers would be included if they had a certain number of patients with high prescribing of opioids but they will look at excluding cancer patients at the patient level, rather than at the provider level.

b. DUR Annual Report to the Centers for Medicare & Medicaid Services (CMS) – Ms. Chan and Dr. Orozco reviewed the DUR annual report for Federal fiscal year (FFY) 2016, which is due to CMS by June 30, 2017. Ms. Chan highlighted several sections within the annual report survey, including the following:  Page 3, question 5: Starting in FFY 2017 the DUR program will begin to follow-up with pharmacy providers at least annually.  Page 9, questions 3 and 4: Ms. Chan reported the generic utilization percentage for FFY 2017 was 69.9%, representing 9.2% of expenditures. Ms. Fingado stated that these data are always skewed somewhat in the California data, as many of the carved- out drugs are branded medications.  Page 10, question 4: Ms. Chan reported the estimated cost savings of the DUR program to be 6.5%. Ms. Fingado reviewed the methodology and calculations for cost savings, which is included in Attachment 5. Dr. Stafford asked what the range of cost savings is for other states. Ms. Fingado stated that California is in the bottom quarter of state DUR programs, as all of the Prospective DUR alerts can be overridden at the point of sale. Ms. Fingado also reported that other states have more robust interventions that generate cost savings from retrospective DUR. Ms. Chan agreed that cost savings are not limited to prospective DUR and that California will be able to calculate retrospective cost savings for the first time in the FFY 2017 report. Allen Schaad, RPh (California State Board of Pharmacy) asked Ms. Fingado to explain the parameters used to calculate prospective DUR cost savings. Ms. Fingado stated that the values are conservative in comparison to other states and reflect that only a percentage of cancelled claims will end up as paid claims. Lisa Ashton, PharmD (Johnson & Johnson) commented that the calculations used to determine cost savings from prospective DUR account for multiple overrides on one claim. Dr. McBride confirmed these calculations do not include physician-administered drugs (PADs).  Page 11, questions 2 through 4: Ms. Chan reported that the DHCS Audits & Investigation Branch (IB) runs the lock-in program, as defined under 22CCR §50793. Dr. McBride said she would like to hear more about this program at a future DUR Board meeting.  Page 12, question 7: Ms. Chan reported that the DHCS Audits & Investigation Branch (IB) uses all available information to develop and work cases, initiates audits, and assists in investigations. This includes review of claims data and trending reports for both controlled and non-controlled drugs.  Page 13, question 2: Ms. Chan stated that CURES 2.0 became operational during FFY 2016, improving ease of registration and access. She also reported that both the California State Board of Pharmacy and the Medical Board of California have enacted requirements for mandatory review of CURES.  Page 15, question 1 and page 16, question 2: Ms. Chan stated that effective July 2017, the maximum days’ supply of opioids has changed to 25 days.  Page 23, question 5: Ms. Chan clarified that while many MCOs have targeted 2

intervention programs for the misuse or abuse of controlled substances, the question refers to all MCOs, so the answer for FFY 2016 is no. Ms. Chan also reported that each managed health care plan will be required to submit a DUR annual report, starting in FFY 2018. She stated that CMS plans to host a call this summer with the states that volunteered to be part of the committee to develop the FFY 2018 annual report.  Page 37: Ms. Chan talked about the Pharmacy Quality Alliance (PQA) quality metrics expert panel that reviewed similar measures as the DUR educational article on opioids, benzodiazepines, and skeletal muscle relaxants. The PQA panel reviewed opioids, benzodiazepines, skeletal muscle relaxants, and other sedative/hypnotic drugs.  Page 39: Ms. Chan highlighted findings from a retrospective DUR review of HIV antiretroviral medications, which found that only 10% of utilizing beneficiaries had continuous eligibility in the Medi-Cal fee-for-service program. Ms. Chan suggested this may be a topic that will be important to revisit in the future when DUR could include all beneficiaries.  Page 50, table 1: Ms. Chan pointed out the predominance of psychotropic drugs because of those drugs being carved out for Medi-Cal managed care beneficiaries.  There was no further discussion. The Board motioned to approve the FFY 2016 DUR Annual Report to CMS. The motion was seconded and carried unanimously.

AYE: Albertson, Finley, McBride, Mowers, Stafford, Stebbins, Wong NAY: None ABSTAIN: None ABSENT: None

ACTION ITEM: The DUR Board recommendation to approve and submit the FFY 2016 DUR Annual Report to CMS will be submitted to DHCS.

c. Biennial Report – 2016: Ms. Fingado presented the biennial report for 2016, which provides detailed evaluations of the following seventeen DUR educational articles, which were published between October 2012 and September 2014:  YOU Can Influence Influenza Rates! Recommend Vaccination for Everyone 6 Months of Age and Older – November 2012  Prevent Pertussis: Improve the Adult Tdap Vaccination Rate – November 2012  Over-the-Counter Eye Drops and Nasal Sprays: Drug Safety Communication – November 2012  Improving the Quality of Care: Updated Guidelines for Migraine Prevention – February 2013  Alert: April 27, 2013 is National Prescription Drug Take-Back Day – March 2013  Improving the Quality of Care: Therapeutic Monitoring in Diabetes – April 2013  Drug Safety Communication: Post-Operative Codeine Use in Children – July 2013  Drug Safety Communication: Valproate Use in Pregnant Women – July 2013  Improving the Quality of Care: Therapeutic Monitoring of Anticonvulsants – August 2013  Immunization Update: The 2013 – 2014 Influenza Season – October 2013  Immunization Update: Tdap Vaccination with Every Pregnancy – November 2013  Improving the Quality of Care: Medication Management in Asthma – December 2013  Alert: Updated Clinical Recommendations for Incretin Therapy – January 2014  Clinical Review: Diagnosis and Treatment of Cough in Children and Adults – March 2014  Improving the Quality of Care: Appropriate Monitoring of Medication Therapy – May 2014  In the News: Prescription Drug Abuse and Diversion of Controlled Substances – August 2014  2014 Immunization Updates: Influenza, Tdap and HPV – September 2014

3

While most metrics showed change in the right direction since the articles were originally published, Ms, Fingado identified the following three areas that may warrant additional evaluation in the future:

 Migraine quality-of-care: The total number of utilizing beneficiaries in the Medi-Cal fee-for-service program with a paid claim for a triptan during a one-year time period decreased by 7.9% since the original DUR educational article, which is a lesser rate than the overall number of utilizing beneficiaries during this same time period in the fee- for-service program (decreased by 23.1%). A review of selected migraine quality-of-care benchmarks evaluated in the original article found several areas in which performance was worse during the biennial review than in the original article. For example, among beneficiaries with a paid claim for a triptan, more than half (52.5%) did not have a coded diagnosis for migraine, up 19.5% from the original article, and only 32.1% had two or more claims for a migraine preventive medication (a 19.5% decrease since the original article). In addition, in the biennial review, a greater percentage of beneficiaries with a paid claim for a triptan had more than 12 paid claims for triptans and a greater percentage of beneficiaries had cardiac contraindications in comparison to the original article. There continue to be no established standardized quality measures for migraine, which may be contributing to the selected measures in these evaluations not showing improvement over time.  Monitoring rates for ACE inhibitors/ARBs: Despite a decrease in the total number of utilizing beneficiaries in the Medi-Cal fee-for-service program, there has been a large increase in the number of utilizing beneficiaries with paid claims for at least 180 treatment days with an ACE inhibitor or ARB, up 31% since the original DUR article was published. In comparison, the total numbers of utilizing beneficiaries with paid claims for at least 180 treatment days of diuretics and/or DIGOXIN decreased during this same timeframe. Monitoring rates for all three classes of drugs increased since the original article, with monitoring rates now between 84% and 86%. While these rates are an across-the-board improvement from the original article, they still fall just under the minimum performance level established by DHCS.  Use of controlled substances: Three of the top 20 drugs by total utilizing beneficiaries posted increases in comparison to the original article: DIAZEPAM, OXYCODONE, and CODEINE WITH ACETAMINOPHEN. A previous DUR retrospective review found the timing of the increase in utilizing beneficiaries with a paid claim for CODEINE WITH ACETAMINOPHEN corresponded to the rescheduling of HYDROCODONE WITH ACETAMINOPHEN effective October 6, 2014. In addition, Ms. Fingado reported that the following eight drugs listed in the top 20 posted increases in the percentage of beneficiaries with more than two prescribers in comparison to the original article: PHENOBARBITAL, HYDROMORPHONE, MORPHINE, METHADONE and all four drugs in the stimulant drug class. However, she did point out the limitations of these data included the following: 1) these data were based only on total paid claims instead of by quantity, so a utilizing beneficiary could have multiple prescriptions for small quantities of controlled substances; and 2) prescribers at the same site were not excluded, so if a patient saw different prescribers from the same practice it may appear they were receiving controlled substances by multiple providers, even when care has been coordinated within one location.

Ms. Chan asked if the Board liked the way the biennial report was being presented. She stated that this is a key report for the DUR program to measure effectiveness. Dr. Stebbins said that it seems like a huge amount of work, and is appreciative that the information isn’t just filed away and that there is documented follow-up of our work. Dr. Stafford stated that he appreciates a review of areas that were addressed prior to his appointment as a Board member.

4

d. Quarterly Report – 1Q2017 (January – March 2017): Ms. Fingado reported that in 2017 Q1 there was a slight increase (2%) in total utilizing beneficiaries and total paid claims in comparison to the prior quarter (2016 Q4). However, she also reported that during this same time period the 65 years and older age group posted decreases in both total utilizing beneficiaries (decreased by 4%) and total paid claims (decreased by 5%). Ms. Fingado stated that this decrease among the older age group may have impacted claims for over- the-counter medications, which are covered under Medi-Cal for all beneficiaries who are dually-eligible for both Medicare and Medicaid. Of the six over-the-counter drugs in the top 20 drugs by the percentage of utilizing beneficiaries with a paid claim, four of them posted across-the-board decreases. Ms. Fingado also reported that in comparison to the prior-year quarter (2016 Q1) there was an 11% decrease in total utilizing beneficiaries and a 15% decrease in total paid claims. She stated that QUETIAPINE FUMARATE and OLANZAPINE posted across-the-board increases in the percentage of utilizing beneficiaries with a paid claim and total paid claims from both the prior quarter and prior-year quarter (both are carved-out drugs) and the following six drugs posted across-the-board decreases: ASPIRIN, DOCUSATE SODIUM, FOLIC ACID, HYDROCODONE/ACETAMINOPHEN, ACETAMINOPHEN and CEPHALEXIN.

e. Review of Physician Administered Drugs (PADs) – 4Q2016 (October – December 2016): Ms. Fingado showed a summary of paid claims for physician-administered drugs for the 4th quarter of 2016, which includes paid claims with dates of services between October 1, 2016, and December 31, 2016. These data were presented in three tables: 1) the top 20 drugs by total reimbursement paid, 2) the top 20 drugs by utilizing beneficiaries, and 3) the top 20 drugs by reimbursement paid per utilizing beneficiary. Ms. Fingado reported increases in both total utilizing beneficiaries (an 8% increase) and total paid claims (a 2% increase) from 3Q2016 to 4Q2016 in the category “PHYSICIAN ADMINISTERED DRUG – NDC NOT REQUIRED,” which can be attributed to the influenza vaccine. Within this same category, Ms. Fingado pointed out decreases in both total utilizing beneficiaries (a 19% decrease) and total paid claims (a 17% decrease) from 4Q2015 to 4Q2016. Ms. Fingado stated that this decrease is most likely due to an 18% decrease in utilizing beneficiaries in the 0 – 18 year age group and an 8% decrease in utilizing beneficiaries in the 65 years and older age group during this same time period.

f. Prospective DUR reports were presented by Amanda Fingado

i. Review of DUR Alerts for New GCNs in 1Q2017 (January – March 2017)  At each DUR Board meeting, a list of new GCN additions with prospective DUR alerts turned on other than ER and DD will be provided to the DUR Board for review. For this meeting, the DUR Board reviewed the alert profiles of the following GCNs: • GCN # 076651: MELPHALAN HCL/BETADEX SBES – Drug Pregnancy (PG) • GCN #076637: ENALAPRIL MALEATE – Drug Allergy (DA), Drug Pregnancy (PG), Therapeutic Duplication (TD), Late Refill (LR), Ingredient Duplication (ID), High Dose (HD), Low Dose (LD) • GCN #067915: FENTANYL CITRATE/DEXTROSE 5%/PF – Drug Allergy (DA), Drug-Disease (MC), Therapeutic Duplication (TD), Additive Toxicity (AT), Ingredient Duplication (ID), High Dose (HD), Low Dose (LD) • GCN #069931: FENTANYL CITRATE-0.9 % NACL/PF – Drug Allergy (DA), Drug-Disease (MC), Therapeutic Duplication (TD), Additive Toxicity (AT), Ingredient Duplication (ID), High Dose (HD), Low Dose (LD) • GCNs #077086 and #077087: MARAVIROC – Drug-Disease (MC) • GCN #069034: POTASSIUM CL/LIDO/0.9 % NACL – Drug-Disease (MC), Therapeutic Duplication (TD), Ingredient Duplication (ID), High Dose (HD) • GCN #068087: MIDAZOLAM IN D5W – Drug Pregnancy (PG) • GCNs #068694 and #068695: MIDAZOLAM – Drug Pregnancy (PG) • GCN #077135: MORPHINE SULFATE IN 0.9 % NACL – Drug Allergy (DA), 5

Drug-Disease (MC), Therapeutic Duplication (TD), Additive Toxicity (AT), Ingredient Duplication (ID), High Dose (HD), Low Dose (LD) • GCN #077141: NICOTINE POLACRILEX – Drug Pregnancy (PG) • GCNs #077053, #077054, and #077055: MORPHINE SULFATE IN 0.9 % NACL – Drug Allergy (DA), Drug-Disease (MC), Therapeutic Duplication (TD), Additive Toxicity (AT), Ingredient Duplication (ID), High Dose (HD), Low Dose (LD)  There was no discussion. A motion was made – and seconded – to accept these alert profile recommendations. The motion was carried.

AYE: Albertson, Finley, McBride, Mowers, Stafford, Stebbins, Wong NAY: None ABSTAIN: None ABSENT: None

ii. Review of Prospective DUR Criteria: Quetiapine + Ingredient Duplication (ID) Alert  Ms. Fingado reported that a review of the top prospective DUR alerts by volume revealed that the ingredient duplication (ID) alert for QUETIAPINE was responsible for the most prospective DUR alerts in 2016, with a total of 198,982 alerts (representing 22% of the 898,937 ingredient duplication alerts that year). All of the adjudicated alerts were overrides (no cancellations). Ms. Fingado also stated that concomitant use of multiple doses of quetiapine is not contraindicated. In fact, clinical guidelines for QUETIAPINE monotherapy recommend that the dose be changed in increments of 25 mg, 50 mg, and/or 100 mg, depending on patient response and tolerability, until optimum benefit is reached. Additionally, when tapering or using as adjunctive therapy, gradual titration is recommended for patient safety reasons. Ms. Fingado also reported that a total of 138 drugs generated ID alerts in 2016.  The remaining top 20 drugs (besides quetiapine) for ID alerts by volume include: ACETAMINOPHEN, ALBUTEROL, ARIPIPRAZOLE, BENZTROPINE, CHLORPROMAZINE, CLOZAPINE, DIVALPROEX, EMTRICITABINE, GABAPENTIN, HALOPERIDOL, LEVOTHYROXINE, LITHIUM, LURASIDONE, NORETHINDRONE-E.ESTRADIOL-IRON, OLANZAPINE, PALIPERIDONE, RISPERIDONE, SERTRALINE, and ZIPRASIDONE.  Dr. Mowers proposed that turning off the ID alert for QUETIAPINE will not do harm. He suggested that DUR alerts should be aimed at what is clinically relevant and turning off the ID may decrease alert fatigue. Dr. Finley noted that the 25mg and 50mg formulations of QUETIAPINE were not being represented disproportionately. Therefore, Dr. Finley thought it unlikely QUETIAPINE is being used to treat insomnia.  Ms. Fingado stated that she had reviewed how other states address QUETIAPINE in prospective DUR and found another state that had recently turned off ingredient duplication, except in cases where the duplication included two extended-release formulations of QUETIAPINE. She found that in 2016, there were less than 100 beneficiaries with paid claims for two different extended release products during the entire year so the potential concurrent use of two different extended-release formulations was very low.  There was no further discussion. Dr. Stebbins motioned to remove the ID alert for QUETIAPINE. The motion was seconded and carried.

AYE: Albertson, Finley, McBride, Mowers, Stafford, Stebbins, Wong NAY: None ABSTAIN: None ABSENT: None

ACTION ITEM: The DUR Board recommendation to turn off the ingredient duplication (ID) alert for quetiapine will be submitted to DHCS.

6

 Dr. Finley suggested looking at other psychotropic medications appearing on the ID alert list and creating a similar report. Dr. Stafford suggested looking at all the drugs listed in the Top 20 except for ACETAMINOPHEN, ALBUTEROL, and GABAPENTIN.  There was no discussion. A motion was made – and seconded – to review the ID alert data for additional drugs. The motion was carried.

AYE: Albertson, Finley, McBride, Mowers, Stafford, Stebbins, Wong NAY: None ABSTAIN: None ABSENT: None

ACTION ITEM: The DUR Board recommendation to review the top 20 drugs by volume of ingredient duplication (ID) alerts in 2016 (excluding ACETAMINOPHEN, ALBUTEROL, GABAPENTIN, and QUETIAPINE) will be submitted to DHCS.

iii. Review of Prospective DUR Criteria: Late Refill (LR) Alert  Ms. Fingado reported that the late refill (LR) alert is the 4th most common alert by total number of alerts in the Medi-Cal fee-for-service program. She stated that by allowing overrides of all LR alerts, access to needed medications is improved, but this could possibly result in safety issues for beneficiaries who are not adhering to their medication regimen and/or unnecessary costs (the direct costs of medications and costs attributed to adverse effects from poor adherence. She reviewed the current list of drugs with the LR alert on, as well as the timing of all overrides in 2016, and the top 20 drugs by total LR alert refill overrides in 2016.  Dr. Stebbins asked how this list was determined and Ms. Fingado stated that she believed it was an attempt to focus on medications used to treat chronic disease states. Dr. Stebbins noted that direct-acting oral anticoagulants are missing from this list and should be considered. Dr. Stebbins motioned to turn on the late refill (LR) alert for direct-acting oral anticoagulants. The motion was seconded and carried.

AYE: McBride, Mowers, Stafford, Stebbins, Wong NAY: None ABSTAIN: None ABSENT: Albertson, Finley

ACTION ITEM: The DUR Board recommendation to turn on the late refill (LR) alert for direct- acting oral anticoagulants will be submitted to DHCS.

 Ms. Fingado reported that some states use a text message instead of the formal alert process for LR alert, avoiding the cost associated with adjudicating prospective DUR alerts. However, at this time, the current prospective DUR system in California does not allow for this.  Ms. Fingado proposed conducting an academic detailing pilot program for late refills, where the physician could be contacted when a patient receives a medication that has a late refill overridden. The Board suggested direct-acting oral anticoagulants and beta- blockers could be a good start. Dr. Stebbins suggested the inclusion criteria for the pilot program could be a direct-acting oral anticoagulant or beta-blocker paid claim filled three or more days late.  Pauline asked if any of the managed health care plans had suggestions for how to handle late refills. Dr. Uzoh stated that soft edits are reviewed quarterly with the pharmacy benefit managers to identify the top alerts that are addressed with pharmacies via fax blasts.  Dr. Stafford wondered if LR alerts may be related to pill splitting and Dr. Stebbins stated that pill splitting is technically illegal. Dr. Stebbins noted that providers are probably unaware of late refills or prescriptions that have not been filled. Johanna Liu, PharmD (Santa Clara Family Health Plan) stated an intervention targeting pharmacies would not 7

be the best use of resources and that the documentation would be too difficult. Dr. Liu agreed that any late refill intervention should be targeting providers or patients.  Dr. Stebbins motioned to develop and complete an academic detailing pilot project regarding the late refill (LR) alert for beta-blockers, CLONIDINE, and CLOPIDOGREL. The motion was seconded and carried.

AYE: McBride, Mowers, Stafford, Stebbins, Wong NAY: None ABSTAIN: None ABSENT: Albertson, Finley

ACTION ITEM: The DUR Board recommendation to develop and complete an academic detailing pilot project regarding the late refill (LR) alert for beta-blockers, CLONIDINE, and CLOPIDOGREL will be submitted to DHCS.

iv. Update: Additive Toxicity (AT) Alert  Ms. Fingado reviewed the AT alert decisions made for the 32 drugs that were discussed after the February 21, 2017 Board meeting. While the current AT alert does not have to do with sedation, she stated that the new approach is to address additive toxicity from the perspective of sedation.  Dr. Finley asked whether from a legal standpoint we should just be consistent with FDA guidelines. Ms. Fingado stated that the FDA guidelines do not include SSRIs or SNRIs.  Dr. Wong asked if the AT alert could be determined by dose. He suggested turning off the alert for low doses. Ms. Fingado stated that the AT alert is either on or off, and could not be adjusted for dosage at this time. She emphasized that the additive toxicity (AT) alert is only generated starting with the fourth different concomitant medication that has the AT alert on (and beyond), so one or two other sedating drugs and a low dose of another would not be enough to trigger the alert.  Dr. Finley and Dr. Wong agreed that of the SSRIs, FLUVOXAMINE, PAROXETINE, and VILAZODONE are the most sedating and proposed these drugs should have the AT alert on. Dr. Stafford proposed removing the AT alert for duloxetine and as the FDA doesn’t have any SNRIs on their list of sedating drugs, he felt the class of SNRIs drugs could have the AT alert off. Dr. Mowers agreed and summarized the final decisions: o Of the SSRI’s only FLUVOXAMINE, PAROXETINE, and VILAZODONE should have the AT alert on (either kept on or turned on in test mode) o All SNRIs should have the AT alert turned off o The rest of the lists (tricyclics and other drugs) are accepted as presented.  There was a motion to accept these changes. There was no further discussion. The motion was seconded and carried.

AYE: Albertson, Finley, McBride, Mowers, Stafford, Stebbins, Wong NAY: None ABSTAIN: None ABSENT: None

ACTION ITEM: The DUR Board recommendation to turn the additive toxicity (AT) alert on in test mode for VILAZODONE, PROTRIPTYLINE, BREXIPIPRAZOLE, BUTALBITAL, LEVORPHANOL, MIDAZOLAM, NEFAZODONE, and SODIUM OXYBATE will be submitted to DHCS.

ACTION ITEM: The DUR Board recommendation to turn off the additive toxicity (AT) alert for CITALOPRAM, ESCITALOPRAM, FLUOXETINE, SERTRALINE, VORTIOXETINE, DESVENLAFAXINE, DULOXETINE, LEVOMILNACIPRAN, and BUPROPRION will be submitted to DHCS.

8

g. Review of DUR Educational Outreach to Providers was presented by Amanda Fingado

i. Proposal: Early Refill  Ms. Fingado reported that in accordance with California Board of Pharmacy requirements and federal rules, the Medi-Cal fee-for-service prospective DUR includes an alert for overutilization, also known as an early refill (ER) alert. This alert is generated if the most recent prescription for an identical product and beneficiary has greater than 25% of the days’ supply remaining. Currently, the ER alert is turned on for every drug.  Between October 1, 2015, and September 30, 2016 a total of 1,302,881 ER alerts were generated by pharmacy claims processed in the Medi-Cal fee-for- service program. Of these, a total of 397,848 (30.5%) were overridden by providers at the point-of-service, allowing for a paid claim. While the vast majority of pharmacies use the ER alert sparingly, the top 100 pharmacies by total ER overrides were responsible for 29.4% of the ER overrides and only 18.4% of paid pharmacy claims.  Ms. Fingado proposed sending letters to the top 100 pharmacies by total number of ER alert overrides in the Medi-Cal fee-for-service population.  The objectives of this pilot study involving DUR educational outreach to pharmacies would be to: 1) assess the feasibility and acceptability of DUR educational outreach letters to pharmacies; and 2) to decrease the total volume of early refill overrides by pharmacies.  The primary outcome variable will be the percentage decrease in the number of ER alert overrides among all pharmacies who received the mailing, assessed one year after the DUR mailing. This percentage will be compared with the percentage decrease in the number of ER alert overrides among all pharmacies not receiving the DUR mailing.  There was no further discussion. A motion was made – and seconded – to accept this proposal. The motion was carried.

AYE: McBride, Mowers, Stafford, Stebbins, Wong NAY: None ABSTAIN: None ABSENT: Albertson, Finley

ACTION ITEM: The DUR Board recommendation to conduct an educational outreach to pharmacies regarding early refill will be submitted to DHCS.

ii. Proposal: Fluoroquinolones  Ms. Fingado stated that the FDA now recommends that fluoroquinolones should not be prescribed to patients who have other treatment options for acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, and uncomplicated urinary tract infections, as the risks outweigh the benefits.  Ms. Fingado reported that a recent evaluation in the Medi-Cal fee-for-service population found that approximately two-thirds (n = 33,483; 68%) of fluoroquinolone use during a one-year period appeared to be potentially inappropriate based on the new FDA recommendations.  Ms. Fingado proposed sending letters to the top 100 prescribers of fluoroquinolones in the Medi-Cal fee-for-service population.  The objectives of this study would be to: 1) inform providers of the FDA- approved safety labeling changes for fluoroquinolones; and 2) decrease the number of Medi-Cal patients receiving treatment with fluoroquinolones for acute bacterial exacerbation of chronic bronchitis, acute sinusitis, and uncomplicated UTI.  The primary outcome variable will be the percentage decrease in the number of paid claims for fluoroquinolone among prescribers who received the mailing, assessed one year after the DUR mailing.  There was no further discussion. A motion was made – and seconded – to

9

accept this proposal. The motion was carried.

AYE: McBride, Mowers, Stafford, Stebbins, Wong NAY: None ABSTAIN: None ABSENT: Albertson, Finley

ACTION ITEM: The DUR Board recommendation to conduct an educational outreach to providers regarding fluoroquinolone prescribing will be submitted to DHCS.

h. Retrospective DUR presented by Dr. Shalini Lynch (UCSF):

i. Review of Retrospective DUR Criteria: Over-the-Counter (OTC) Medications  Dr. Lynch reported that outpatient prescription drug coverage for the Medi-Cal fee-for-service program includes all federally required drug classes and optional drug classes like vitamins and over-the-counter (OTC) medications, when prescribed by a physician. Dr. Lynch stated that while several OTC medications frequently rank among the top drugs by total number of utilizing beneficiaries, utilization patterns for these drugs have not yet been reviewed as a class to evaluate potential drug problems.  Dr. Lynch presented utilization data for all OTC medications in the Medi-Cal fee-for-service program with dates of service between January 1, 2016 and December 31, 2016. She reported on the top 10 drugs by utilizing beneficiaries and within the following age groups: 0-2 years of age, 3-12 years of age, 13-18 years of age, 40-64 years of age, and over 65 years of age. For each drug, the most frequent day supply per claim and the most frequent quantity per claim were reported, in addition to total utilizing beneficiaries, total paid claims, and total reimbursement paid to pharmacies. FERROUS SULFATE, LORATIDINE, and CLOTRIMAZOLE appeared in the top 10 drugs across all age groups.  Ms. Chan stated that a recent study was conducted by DHCS that included a questionnaire for consumer use of low-dose aspirin. She offered to find out if someone involved with the study could present to the Board at a future meeting.  The Board agreed that periodic review of the use of over-the-counter medications was important and that an educational outreach to providers related to the use of OTC medications could be valuable.  There was no further discussion. A motion was made – and seconded – to accept this proposal. The motion was carried.

AYE: McBride, Mowers, Stafford, Stebbins, Wong NAY: None ABSTAIN: None ABSENT: Albertson, Finley

ACTION ITEM: The DUR Board recommendation to develop a proposal for educational outreach to providers regarding the use of over-the-counter (OTC) medications will be submitted to DHCS. i. Review of DUR Publications presented by Dr. Shalini Lynch (UCSF)

i. DUR Alert (April, 2017): Adult Immunizations  Dr. Lynch presented a summary of the DUR educational alert entitled, “Medi- Cal Expands Access to Adult Immunizations in Pharmacies.”  Dr. Lynch reported that the Medi-Cal fee-for-service list of contract drugs now includes all ACIP-recommended adult immunizations as a pharmacy benefit. Medi-Cal managed care plans will have to offer these adult immunizations on their pharmacy formulary as well. In addition, the Presumptive Eligibility for Pregnant Women (PE4PW) program has also been expanded to offer a full range of influenza vaccines, in addition to Tdap. 10

 Dr. Lynch also shared that new pharmacy regulations require that pharmacists notify providers and submit vaccination information to the California Immunization Registry (CAIR). ii. DUR Bulletin (April, 2017): Proton Pump Inhibitors  Dr. Lynch presented a summary of the DUR educational bulletin entitled, “Improving the Quality of Care: Overutilization of Proton Pump Inhibitors.” The bulletin had the following three learning objectives: o Review the appropriate indications for short-term and long-term use of proton pump inhibitors (PPIs) o Describe potential adverse effects associated with use of PPIs o Summarize best practices for responsible prescribing of PPIs  Dr. Lynch provided some background information on PPIs, which are typically used to reduce gastric acid and are one of the most commonly prescribed medications in the United States. She reported that the FDA has issued several safety alerts for PPIs. Adverse effects may include increased risk of both acute and chronic kidney disease, hypomagnesemia, Clostridium difficile infection, osteoporotic fractures, and dementia.  Dr. Lynch described the results of a review of the Medi-Cal fee-for-service data that showed a total of 23,921 continuously-eligible beneficiaries had least one paid pharmacy claim for a PPI between November 1, 2015 and October 31, 2016. A total of 68% of these beneficiaries had 3 or less paid claims for PPIs and 61% had a PPI treatment duration of 90 days or less. Long-term users made up 13% of the study population. Long-term use of PPIs was determined when paid claims for PPIs total greater than 300 treatment days during the measurement year.  Dr. Lynch reported that there was no difference between those beneficiaries with or without an appropriate indication for use of PPIs in the concomitant use of medications that may increase the risk of adverse events with long-term or high-dose PPI therapy. In addition, she reported that beneficiaries with potentially appropriate indications for use of PPI therapy were more likely to have concomitant use of H2-receptor inhibitors, metoclopramide, and antacids.  Dr. Lynch stated that clinical recommendations included the following: o Prescribe PPIs only for clearly documented indications and reevaluate indications at transitions of care o Exercise caution in the elderly and patients with other risk factors for C. difficile infection or bone fractures o Recommend antacids or H2-blockers as needed for breakthrough symptoms after PPI discontinuation o Encourage non-pharmacologic/lifestyle management as first-line for GERD symptoms o For patients requiring long-term PPI therapy, obtain baseline magnesium level and follow recommended monitoring guidelines iii. Discussion/Recommendations for Future Educational Bulletins  Dr. Lynch highlighted the future topics for provider letters, educational bulletins and alerts, and prospective and retrospective DUR reviews.  Dr. Stafford requested prioritizing a retrospective DUR review using the parameters from the following 2016 adult core set measures: Opioids at High Dosage (OHD). Ms. Fingado agreed to prepare this review for presentation at one of the next two DUR Board meetings.  Dr. Mowers requested adding a proposal for educational outreach to providers regarding high use of triptan medications.  There was no further discussion. A motion was made – and seconded – to accept this proposal. The motion was carried.

11

AYE: McBride, Mowers, Stafford, Stebbins, Wong NAY: None ABSTAIN: None ABSENT: Albertson, Finley

ACTION ITEM: The DUR Board recommendation to develop a proposal for educational outreach to providers regarding high use of triptan medications will be submitted to DHCS. j. Pharmacy Update i. Medicaid DUR State Comparison FFY 2015 – Ms. Chan described how California compares with the rest of state Medicaid agencies, including a summary of best practices from other states that can be applied to California’s DUR program during FFY 2017 and FFY 2018. Areas for improvement identified included the following:  Prospective DUR: o Initiate follow up actions with individual pharmacy providers who routinely override prospective alerts. o Evaluate early refills policy by therapeutic class and consider setting specific limitations by each class of drugs. o Excluding carved out drugs and counting the top 10 drugs by paid claims from the FFS population only, may offer additional and important insights to FFS drug utilization.  Fraud, Waste, and Abuse Detection o Invite Audit & Investigational Branch (IB) to present a summary of the lock-in program at future DUR board meeting. o Review the CDC publication entitled, “Integrating and Expanding Prescription Drug Monitoring Program Data: Lessons from Nine States.” o Point-of-Service (POS) edits to limit the quantity of short- and long- acting opioids to a maximum of a 30-day supply (with a refill allowable at day 25). o Implement a follow-up action plan to our work on buprenorphine. o Coordinate with State-wide Opioid Workgroup to determine morphine equivalent daily dose (MEDD) cutoff and develop an algorithm to calculate MEDD. o Explore the feasibility to have Prospective DUR edits in place to monitor opioids being used concurrently with buprenorphine. o Medi-Cal DUR joined a CMS-led affinity group to address antipsychotic drug use in children. The affinity group has been extended to FFY 2018.  Managed Care Organizations (MCOs) o Implement the new Medicaid Managed Care regulations relevant to the Medi-Cal DUR program. ii. Pharmacy Policy Change: Meperidine – Ms. Chan confirmed that as of May 1, 2017, all meperidine formulations require an approved Treatment Authorization Request (TAR). iii. Pharmacy Policy Change: Opioid Quantity Limits – Ms. Chan stated that effective July 1, 2017, all short- and long-acting opioids will be limited to a 30-day supply and refills will be limited to every 25 days, with a maximum of three refills. iv. MMWR: Initial Prescription Opioids and Long Term Opioid Use – Ms. Chan reported that a study reported in the March 17, 2017, edition of the Morbidity and Mortality Weekly Report found that opioid-naïve, cancer-free adults who received a prescription for an opioid, the likelihood of chronic opioid use increased with each additional day of medication supplied, starting with the third day. The highest likelihood of continued opioid use at 1 and 3 years occurred in patients who started on either long-acting opioids or tramadol. v. FDA Drug Safety Communications: Codeine & Tramadol – Ms. Chan described a recent FDA Drug Safety Communication describing new FDA restrictions and warnings regarding codeine (contraindicated for cough or pain in children < 12 years of age) and tramadol (contraindicated for pain in children < 18 years of age). 12

The FDA Drug Safety Communication also recommended against use of these drugs by women who are breastfeeding. vi. DHCS Quality Improvement Strategy 2017 – Ms. Chan reported that the DHCS Quality Strategy Report is released annually, and includes progress and status of quality improvement projects. The report is organized by divisions and programs, and by the seven priorities established by DHCS. Ms. Chan stated that the DUR program plans to submit a project for continuous tracking and trending under Priority 7: Eliminate Health Disparities. vii. Academic Detailing Conference/Resources – Ms. Chan reminded the Board that the 2017 Academic Detailing Conference will be held on October 12, 2017 at DHCS. She also stated that resources from the 2016 Academic Detailing Conference have been added to the DUR website.

5) PUBLIC  None. COMMENTS 6) CONSENT  The next Board meeting will be held from 9:30 a.m. to 12:30 p.m. on September 19, 2017, AGENDA at DHCS in Training Rooms A + B on 1500 Capitol Avenue, Sacramento, CA 95814.

7) ADJOURNMENT  The meeting was adjourned at 12:29 p.m.

Action Items Ownership

Incorporate Dr. Wong’s edits into the minutes and post to the DUR website. Amanda The DUR Board recommendation to approve and submit the FFY 2016 DUR Annual Report to Pauline/Amanda CMS will be submitted to DHCS. The DUR Board recommendation to turn off the ingredient duplication (ID) alert for quetiapine Hannah/Pauline will be submitted to DHCS. The DUR Board recommendation to review the top 20 drugs by volume of ingredient duplication (ID) alerts in 2016 (excluding ACETAMINOPHEN, ALBUTEROL, GABAPENTIN, Amanda and QUETIAPINE) will be submitted to DHCS. The DUR Board recommendation to turn on the late refill (LR) alert for direct-acting oral Hannah/Pauline anticoagulants will be submitted to DHCS. The DUR Board recommendation to develop and complete an academic detailing pilot project Amanda/Hannah/ regarding the late refill (LR) alert for beta-blockers, clonidine, and clopidogrel will be submitted Shal/Pauline to DHCS. The DUR Board recommendation to turn the additive toxicity (AT) alert on in test mode for VILAZODONE, PROTRIPTYLINE, BREXIPIPRAZOLE, BUTALBITAL, LEVORPHANOL, Hannah/Pauline MIDAZOLAM, NEFAZODONE, and SODIUM OXYBATE will be submitted to DHCS. The DUR Board recommendation to turn off the additive toxicity (AT) alert for CITALOPRAM, ESCITALOPRAM, FLUOXETINE, SERTRALINE, VORTIOXETINE, DESVENLAFAXINE, Hannah/Pauline DULOXETINE, LEVOMILNACIPRAN, and BUPROPRION will be submitted to DHCS. The DUR Board recommendation to conduct an educational outreach to pharmacies regarding Amanda early refill will be submitted to DHCS. The DUR Board recommendation to conduct an educational outreach to providers regarding Amanda fluoroquinolone prescribing will be submitted to DHCS. The DUR Board recommendation to develop a proposal for educational outreach to providers Amanda regarding the use of over-the-counter (OTC) medications will be submitted to DHCS. The DUR Board recommendation to develop a proposal for educational outreach to providers Amanda regarding high use of triptan medications will be submitted to DHCS.

13

CMS Covered Outpatient Drug Final Rule-DUR Requirements and Medi-Cal Global DUR Board

Paul Nguyen, Pharm.D ., MBA Dorothy C. Uzoh, Pharm.D., BCPS., BCPP DHCS Pharmacy Policy Branch September 19, 2017

1 Background

• CMS released final rule in February, 2016 – Proposed rule was published February 2, 2012

• Final Rule effective April 1, 2016

• Drug Use Review (DUR) Requirements effective July 1, 2017

09/19/17 2

Final Rule Provisions

§438.3(s) - Requirements for MCOs, PIHPs, or PAHPs that provide covered outpatient drugs

(4) The MCO, PIHP or PAHP must operate a drug utilization review program that complies with the requirements described in section 1927(g) of the Act and 42 CFR part 456, subpart K, as if such requirement applied to the MCO, PIHP, or PAHP instead of the State.

(5) The MCO, PIHP or PAHP must provide a detailed description of its drug utilization review program activities to the State on an annual basis.

09/19/17 3 CMS Requirements

Section 1927 (g) (3) (D) of the Social Security Act (the Act) requires each State to submit an annual report on the operation of its Medicaid Drug Utilization Review (DUR) program.

Report should include information about the DUR activities of the Managed Care Organizations ( MCOs) effective FFY 2017. (New Requirement)

Generated based on the feedback received from MCOs about their activities.

09/19/17 4 Information Provided

In the words of CMS, states are to provide information such as: • Descriptions of the nature and scope of the prospective and retrospective DUR programs • Summaries of the interventions used in retrospective DUR and an assessment of the education program • Descriptions of the DUR Board activities • Assessments of the DUR program’s impact on quality of care as well as any cost savings generated by the program.

09/19/17 5 Drug Utilization Review (DUR) Program Requirements, §438.3(s)

(4) The MCO, PIHP or PAHP must operate a drug utilization review program that complies with the requirements described in section 1927(g) of the Act and 42 CFR part 456, subpart K, as if such requirement applied to the MCO, PIHP, or PAHP instead of the State.

09/19/17 6 DUR Program Requirements - 1

• Section 438.3(s)(4) requires managed care plans that provide coverage of covered outpatient drugs to also operate a DUR program that complies with the requirements at 1927(g) of the Act. • The managed care plans does not have to adopt the same DUR activities that the state’s FFS program enacts. • Section 1927(g)(1)(A) of the Act requires that the state’s DUR program assures that prescriptions are: – appropriate; – medically necessary; and – not likely to result in adverse medical results.

8/25/2017 7 DUR Program Requirements - 2

• The DUR program shall be designed to educate physicians and pharmacists to identify and reduce the frequency of patterns of fraud, abuse, gross overuse, or inappropriate or medically unnecessary care. • 42 CFR 456, Subpart K further defines the DUR program in three sections: – Prospective DUR – Retrospective DUR and – An Educational Program • DUR helps to ensure appropriate prescribing of medications and improves the quality of care of the beneficiary. • MCO contracts beginning July 1, 2017, and thereafter includes language on the above DUR requirements.

09/19/17 8 How to meet requirements

MCOs are now required to participate by either an individual or an entity on the State DUR Board. Their activities to include: • Implementation of a prospective DUR process, which includes DUR, edit program to detect drug interactions, ingredient duplications, drug-disease contradictions, drug abuse/misuse, etc., and alert dispensing pharmacy. • Implementation of a retrospective DUR process via drug claims data, which identifies range & type of drugs taken by members and general drug utilization patters of the plan to identify fraud, abuse, under or over utilization. • Provision of provider education programs and materials developed by Medi-Cal DUR team to their providers via established mechanisms.

09/19/17 9 Drug Utilization Review (DUR) Program Requirements, §438.3(s)

(5) The MCO, PIHP or PAHP must provide a detailed description of its drug utilization review program activities to the State on an annual basis.

09/19/17 10 Annual Report to the State

• Section 438.3(s)(5) requires managed care plans to provide a detailed description of its DUR program activities to the state on an annual basis.

• The purpose of the DUR Annual report is to ensure that managed care plans (MCOs, PIHPs and PAHPs) meet the parameters of section 1927(g) of the Act.

• MCO contracts beginning July 1, 2017, and thereafter includes language on their DUR annual reporting requirements.

8/25/2017 11 Next Steps

Details of Next Steps for DHCS : • An All Plan Letter (APL 17-008) was sent by DHCS to all the MCPs enumerating these requirements and DHCS mandate by CMS to monitor and approve the MCPs’ Medi-Cal DUR program activities, and ensure that they are compliant with Section 1927(g) of the SSA.

• For practical reasons, it became necessary that the MCOs utilize the established Medi-Cal State DUR Board (DUR Board) and educational components of the Medi-Cal DUR program.

• MCPs will maintain their current proprietary claims processing procedures and protocols and MCPs will individually administer the systematic components related to the prospective and retrospective DUR processes.

09/19/17 12

DUR Program Requirements

As is the case with the Fee-For-Service (FFS) program, MCPs are not required to implement all DUR Board recommended actions, nor are they required to mirror the Medi-Cal DUR activities.

Effective Date:

Effective July 1, 2017, in collaboration with DHCS’ FFS Program for covered outpatient drugs, MCPs shall participate in a global Medi-Cal DUR program.

09/19/17 13 Meeting Annual Report Requirements • MCOs must provide a detailed description of its DUR program activities to DHCS on an annual basis, which allows DHCS to compile and submit a single, annual Medi-Cal DUR report. • MCOs must include in the report methods of meeting the requirements of prospective, retrospective and educational activities performed. • MCOs must provide the rationale for not adopting the recommendations made by State DUR board during the reporting period. • DHCS will submit a combined report, reflecting the information submitted by each MCP, to the Secretary of Health and Human Services on an annual basis. 09/19/17 14 Composition of the Global DUR Board - 1

• The membership of the DUR Board must be made up of at least 1/3 but no more than 51 percent licensed and actively practicing physicians and at least 1/3 licensed and actively practicing pharmacists. • MCPs must actively participate, either individually, or by means of an entity selected to represent multiple MCPs (e.g. California Association of Health Plans, Local Health Plans of California), in activities involved with the DUR Board. • Participation may include select MCP representatives volunteering to serve as DUR Board members.

09/19/17 15 Composition of the Global DUR Board - 2

• The current Fee-For-Service DUR has 7 members; 4 pharmacists and 3 physicians. • The Global DUR Board is capped at 15 members. • The Goal is to add additional members who will represent the MCOs. • These new members will be appointed by DHCS Director, Jennifer Kent.

09/19/17 16 Composition of the Global DUR Board - 3

• Consideration for membership will be given to Plan size, geographical location, etc. This is to make it fair. • Considerations will also be given to the different Managed Care models. • Duration of terms and frequency of rotation is at the discretion of the Director.

09/19/17 17 Resources

• CMS-R-153, which describes the new requirements of states to include the activities of MCOs, including the revised annual survey

• All Plan Letter (APL)17-008

09/19/17 18

Questions?

09/19/17 19

MEDI-CAL DRUG USE REVIEW BOARD BYLAWS Sections:

1. Mission Statement 2. Authority 3. Membership 4. Term of Office 5. Officers 6. Meetings 7. Program Description 8. Annual Report 9. DUR Board Documents 10. Public Participation 11. Conflict of Interest Statement 12. Revision and Compliance

1. Mission Statement The mission of the Medi-Cal DUR Board is to facilitate the appropriate and cost effective delivery of health of the Medi-Cal beneficiaries.

2. Authority The Drug Use Review (DUR) board is authorized pursuant to Section 1927(g)(3) [42 U.S.C. 1396r-8] of the Social Security Act, also known as section 4401 of the Omnibus Budget Reconciliation Act of 1990 (OBRA 90). On May 6, 2016, the Centers for Medicare and Medicaid Services (CMS) released final rulemaking CMS-2390-F, which requires the Managed Care Plans (MCPs) to operate a DUR program that complies with the requirements of Section 1927(g) of the Social Security Act (SSA) and Title 42, CFR part 456, subpart K.1

1 Title 42, CFR, Section 438.3(s)(4) Medi-Cal Drug Use Review Board By-Laws Page 1

The complexities of the federal DUR requirements necessitate that MCPs utilize the established Medi-Cal State DUR Board (DUR Board) and educational components of the Medi-Cal DUR program. However, MCPs will maintain their current proprietary claims processing procedures and protocols and the MCPs will individually administer the systematic components related to the prospective and retrospective DUR processes. As is the case with the Fee-For-Service (FFS) program, MCPs are not required to implement all DUR Board recommended actions, nor are they required to mirror the Medi-Cal DUR activities. Effective July 1, 2017, in collaboration with DHCS’ FFS program for covered outpatient drugs, MCPs shall participate in a global Medi-Cal DUR program.

The Board shall serve in an advisory capacity to the Department of Health Care Services (Department), the California state Medicaid agency (Medi-Cal) to assure that its DUR program is operational and fulfills the requirement of the Act.

3. Membership The Board shall consist of at least one-third but not more than 51 percent physician members and at least one-third pharmacist members. The Director of the Department shall determine the size and composition of the Board, including the types of members considered appropriate to contribute their expertise to the DUR program. The size and composition of the board may be expanded to include representation from managed care health plans.

Board members must be actively practicing and licensed in California. Board members shall be health care professionals who have recognized knowledge and expertise in one or more of the following areas: the clinically appropriate prescribing of outpatient drugs; the clinically appropriate dispensing of outpatient drugs; drug use review, evaluation and intervention; and medical quality assurance.

4. Term of Office The term of office shall be at the pleasure of the Department’s Director. Appointment to the DUR Board is the sole responsibility of the Director upon recommendation from the

Medi-Cal Drug Use Review Board By-Laws Page 2

Chief of Medi-Cal Pharmacy Policy. The length of appointment and the conditions of replacement shall take into account the ongoing nature of the Board’s deliberations and shall provide for at least three overlapping appointments. Rotation off the Board will be activated based on the discretion of the Department, and related to the availability of approved Board members for replacement. Should any Board member be unable to fulfill his/her appointment term, that member should provide written notice to the Chair prior to resignation. While the board meetings may be accessed by the public via teleconference, board members shall attend in person to count for attendance and to vote. If a Board member is unable to attend three or more consecutive meetings, these absences shall be considered a voluntary vacancy on the Board and the Chair shall request a resignation.

5. Officers Officers shall consist of a Chair and Vice-Chair/Chair-Elect, who shall be elected every year during the third quarter meeting of the Board. The Chair shall preside over Board meetings. The Vice-Chair shall preside over Board meetings in the Chair's absence. The Vice-Chair shall serve as the Chair-elect and succeed the Chair upon completion of his/her term. Prior to serving as Chair or Vice Chair, Officers should have served on the Board at least one year and may be reelected at the Board's discretion. The term of the chair is one year. The term of the vice-chair is one year.

6. Meetings Meetings shall be held at least quarterly at a time and place determined by the Department. All meetings will operate under the restrictions of the Bagley Keene Open Meetings Act, set forth in Government Code sections 11120-11132. The Board shall meet in open public session, but can meet in executive session to review confidential information. Information reviewed by the Board that identifies an individual Medi-Cal recipient or provider shall be considered confidential and shall not be disclosed. Robert's Rules of Order shall be used to conduct meetings. A simple majority of members shall constitute a quorum and a simple majority is all that’s needed for a motion to pass. If a specific issue requires immediate action and a Board meeting will not occur in a timely

Medi-Cal Drug Use Review Board By-Laws Page 3

fashion, Board members may be contacted and asked to vote electronically. Upon approval of an item under consideration, it may be acted on immediately.

Meeting minutes will be taken as a basic form of proof that a meeting took place as well as a historical documentation of where, when, and why the meeting was held. Minutes should contain location, date, time, list of attendees and key points of discussion. Meeting minutes are public documents and are available to the public upon request.

To aid the proper capture of the meeting minutes, the meeting may be recorded. The recording is a public record and is available for 30 days to the public upon request. Any person attending a board meeting may also record the proceeding via audio, video, or still camera unless such actions constitute or would constitute a persistent disruption of the proceedings (Government Cod § 11124.1).

7. Program Description The program shall focus on medication therapies with the broad goals of improving patient outcomes, increasing the quality of prescribing practices, reducing healthcare costs, and improving beneficiary, prescriber, and pharmacist satisfaction. Towards these goals, the program shall implement strategies that identify and reduce adverse events, fraud, misuse, overutilization, underutilization, and inappropriate/ineffective care associated with specific drugs or groups of drugs. Strategies for improving prescribing may include education, data reports, audits, alerts, incentives, decision-making tools, and outreach aimed at beneficiaries, prescribers, and pharmacists.

There are three key functions of the DUR program: A. Prospective DUR B. Retrospective DUR C. Medication interventions designed to educate health care providers, pharmacists and beneficiaries

Medi-Cal Drug Use Review Board By-Laws Page 4

For both Prospective DUR and Retrospective DUR, the program shall assess data on drug use against predetermined standards, consistent with the following:

(i) compendia which shall consist of the following:

(I) American Hospital Formulary Service Drug Information;

(II) United States Pharmacopeia-Drug Information (or its successor publications); and

(III) the DRUGDEX Information System; and

(ii) the peer-reviewed medical literature.

(iii) Evidence-based practice guidelines as developed by the Medi-Cal Drug Advisory Committee (MCDAC) and disease-specific health improvement programs developed by the State.

A. Prospective DUR Prospective DUR is performed electronically at the time a drug is dispensed to a patient. This review is designed to identify potential problems such as drug-drug interactions, therapeutic duplication, inappropriate dosage, or duration of therapy. When a pharmacist is alerted to a potential problem, he or she is expected to use professional judgment to determine an appropriate intervention. Retrospective DUR examines drug use after the drug has been dispensed. The principal aim of retrospective DUR is to discern patterns of inappropriate or suboptimal drug use and engage in interventions to providers to prevent future unfavorable or undesirable outcomes.

The DUR Board is responsible to the Department for the following specific Prospective DUR activities: 1. The DUR Board shall, on an ongoing basis, serve in an advisory capacity to assess prospective alert data against explicit predetermined standards (currently using First Data Bank as the source for these standards) including but not limited to monitoring for therapeutic appropriateness, overutilization and underutilization, appropriate use of generic products, therapeutic duplication, drug-disease

Medi-Cal Drug Use Review Board By-Laws Page 5

contraindications, drug-drug interactions, incorrect drug dosage or duration of drug treatment, and clinical abuse/misuse and, as necessary, recommend remedial strategies, in order to improve the quality of care and to conserve program funds or personal expenditures. 2. Noting that standards of care and practices change with time, the DUR Board shall serve in an advisory capacity in the development and implementation of an evidence-based methodology for determining standards to identify, classify, target, and act upon those drug interactions that pose the greatest risk for drug-induced illness. 3. After determining what alerts are important, the Board shall serve in an advisory capacity to determine electronic messaging, focusing on the following principles: i. Clarity: the “what” ii. Understandability: the “why” iii. Actionable iv. Interoperability v. Standardized vi. Non-redundant

B. Retrospective DUR 1. Retrospective DUR is a two-part system: The first component is the ongoing periodic examination of claims data and other records to identify patterns of Medi- Cal fraud, abuse, gross overuse, or inappropriate and unnecessary care among physicians, pharmacists and Medi-Cal recipients associated with specific drugs or groups of drugs. The purpose of this component is to reduce the frequency of misuse and overuse of Medi-Cal drug benefits. 2. The second component of retrospective DUR is an ongoing periodic examination of claims data and other records to assess the clinical appropriateness of prescribing and dispensing of select Medi-Cal covered drugs. This includes monitoring for therapeutic appropriateness, overutilization and underutilization, therapeutic duplication, drug-disease contraindications, drug-drug interactions,

Medi-Cal Drug Use Review Board By-Laws Page 6

incorrect drug dosage or duration of drug treatment, clinical abuse/misuse and variations from best practice guidelines.

The DUR Board is responsible to the Department for identifying common drug therapy problems to educate providers and improve prescribing and dispensing practices. The Board also shall serve in an advisory capacity to recommend types of intensified recipient- or provider-specific interventions that shall most effectively improve the quality of drug therapy.

C. Medication interventions designed to educate health care providers and pharmacists, targeted toward therapy problems or individuals identified in the course of retrospective drug use reviews. Intervention programs shall include, in appropriate instances, at least: 1. Information dissemination sufficient to ensure the ready availability to physicians and pharmacists in the State of information concerning its duties, powers, and basis for its standards; 2. Written, oral, or electronic reminders containing patient-specific or drug-specific (or both) information and suggested changes in prescribing or dispensing practices, communicated in a manner designed to ensure the privacy of patient- related information; 3. Use of face-to-face discussions between health care professionals who are experts in rational drug therapy and selected prescribers and pharmacists who have been targeted for educational intervention, including discussion of optimal prescribing, dispensing, or pharmacy care practices, and follow-up face-to-face discussions; and 4. Intensified review or monitoring of selected prescribers or dispensers.

The Board shall re-evaluate interventions after an appropriate period of time to determine if the intervention improved the quality of drug therapy, to evaluate the success of the interventions and make modifications as necessary.

Medi-Cal Drug Use Review Board By-Laws Page 7

Additional functions of the DUR board to include:

D. The DUR Board will provide input to the Medi-Cal Drug Advisory Committee regarding the Medi-Cal formulary based on the analysis of the retrospective and prospective DUR programs and patient outcomes and when fraud, overuse have been identified. Similarly, the Board may provide input to the managed care Pharmacy & Therapeutic Committee or equivalent, based on the analysis of the retrospective DUR programs and outcomes that overlaps both FFS and managed care beneficiaries.

E. The Board periodically evaluates and recommends modification, addition or elimination of prospective and retrospective DUR criteria and standards.

F. The Board periodically evaluates and recommends modification, addition or elimination of existing prospective and retrospective DUR reports.

8. Annual Report The DUR board shall prepare a report in accordance to the questionnaire and template provided by the Centers for Medicaid and Medicare Services (CMS) on an annual basis which may include a description of the activities of the Board, including the nature and scope of the prospective and retrospective drug use review programs, a summary of the interventions used, an assessment of the impact of these educational interventions on quality of care, and an estimate of the cost savings generated as a result of such program. The board shall make every effort to review and approve the annual report on a timely basis, to allow sufficient time for the Department to submit the annual report within the timeline specified by CMS.

9. DUR Board Documents All meeting minutes and other official records of the DUR board shall be kept on file at the Department and/or fiscal intermediary offices for a period of three years and shall be open to public inspection.

Medi-Cal Drug Use Review Board By-Laws Page 8

10. Public Participation The public may attend all Board meetings, with the exception of Executive Sessions called to discuss confidential information. The Board may make and enforce reasonable rules regarding the conduct of persons attending its meetings. Opportunities shall be provided for individuals or representatives of groups to make comments to the Board. Requests to appear before the Board shall be made in writing and shall include the subject matter and name and affiliation of the speaker. Presentations are limited to five minutes unless the Board grants an extension.

11. Conflict of Interest Statement A conflict of interest shall exist for a board member when a matter under consideration by the Board directly affects a personal, professional or monetary interest of a Board member. A member shall disclose any conflict of interest preceding consideration of substantive matters or at the point when it becomes apparent to the member that a conflict exists. Minutes of the meeting shall reflect the conflict and abstention from voting for that member.

12. Revision and Compliance In the event specific topics require detailed elaboration, the board will create a supplementary addendum to the bylaws so as to include this information. The bylaws shall be reviewed as necessary to assure compliance with Section 1927(g)(3) [42 U.S.C. 1396r-8] of the Social Security Act, also known as section 4401 of the Omnibus Budget Reconciliation Act of 1990 (OBRA 90). Revisions shall be made as necessary and after approval by the Department Director. The bylaws shall be signed and dated to indicate the time of last review.

The bylaws shall go into effect on the ______day of the month ______, in year ______. Approved: ______. Chair, Medi-Cal DUR Board

Medi-Cal Drug Use Review Board By-Laws Page 9

QUARTERLY SUMMARY DRUG USE REVIEW (DUR) UTILIZATION REVIEW REPORT PERIOD: 2nd QUARTER 2017 (APRIL - JUNE 2017)

Executive Summary

The DUR quarterly report provides information on both prospective and retrospective drug utilization for the Medi-Cal Fee-for-Service (FFS) program. For this quarterly report, the prospective and retrospective data cover the second quarter of 2017 (2017 Q2). All tables can be found in Appendix A and definitions of selected terms can be found in Appendix B.

Prospective DUR As shown in Table 1.1, in 2017 Q2 overall drug claims decreased by 6% and total DUR alerts decreased by less than 1% in comparison to the prior quarter (2017 Q1). Similarly, in comparison to the prior-year quarter (2016 Q2), overall drug claims decreased by 9% and total DUR alerts decreased by 14%.

A comparison between 2017 Q2 and 2017 Q1 showed very little change among the top 10 drugs for each of the 12 prospective DUR alerts (Tables 2.1-2.12), except for the Drug-Age (PA) alert. ACETAMINOPHEN WITH CODEINE entered the top 10 for the first time (ranked #1) in total number of adjudicated PA alerts, with 158 adjudicated alerts during 2017 Q2. This increase is the result of First Databank (FDB) raising the minimum age for these drugs from 2 years of age to 12 years of age for all codeine/codeine containing and tramadol/tramadol containing products based upon recommendations by the Food and Drug Administration (FDA). The FDA had published a Drug Safety Communication on April 20, 2017, restricting the use of codeine and tramadol medicines in children less than 12 years of age due to the risk of serious side effects, including slowed or difficult breathing and death.

Retrospective DUR A comparison of 2017 Q2 to the prior-year quarter showed an 11% decrease in total utilizing beneficiaries and a 14% decrease in total paid claims (Table 3). When overall utilization from 2017 Q1 was compared to the prior quarter there was also a decrease in total utilizing beneficiaries (decrease of 5%) and total paid claims (decrease of 4%) However, the total reimbursement paid to pharmacies increased by 5% in comparison to the prior quarter.

In 2017 Q2, the 0-12 year age group posted double-digit across-the-board percentage decreases in total utilizing beneficiaries and total paid claims in comparison to both the prior quarter (Table 4) and the prior-year quarter.

As shown in Table 5, there were two drug therapeutic categories that posted across-the-board increases in total paid claims and percent of utilizing beneficiaries with a paid claim in comparison to both the prior quarter and the prior-year quarter: ANTIPSYCHOTIC,ATYPICAL,DOPAMINE,SEROTONIN ANTAGNST and ANTIPSYCHOTICS, ATYP, D2 PARTIAL AGONIST/5HT MIXED.

Similar findings can be seen in Table 6, where the following three drugs posted across-the-board increases in total paid claims and percent of utilizing beneficiaries with a paid claim in comparison to both the prior quarter and the prior-year quarter: QUETIAPINE FUMARATE, OLANZAPINE, and LURASIDONE.

DUR Quarterly Report – Version 1.0: July 25, 2017 1 2017 Q2 (APRIL 2017 – JUNE 2017) Appendix A: Prospective and Retrospective DUR Tables

Tables 1.1-1.2. Summary of Prospective DUR Alert Transactions. Table 1.1 provides summary level data (by volume) on pharmacy claims and DUR alert activities, including data and percent change from the prior quarter. Alerts are generated after adjudication of drug claims which exceed or otherwise fall outside of certain prescribed parameters. Please see Appendix B for definitions of terms used in this DUR report.

Table 1.1: Summary of Alert Transactions Current Quarter Prior Quarter % Change Prior-Year % Change 2017 Q2 2017 Q1 from Quarter from (Apr – Jun (Jan – Mar Prior 2016 Q2 Prior-Year Category 2017) 2017) Quarter (Apr – Jun 2016) Quarter Drug Claims 8,042,813 8,553,712 -6.0% 8,833,238 -8.9% DUR Drug Claims 3,906,086 4,052,003 -3.6% 4,548,064 -14.1% Total Alerts 957,660 959,197 -0.2% 1,098,094 -12.8% Total Alert Overrides 572,597 572,898 -0.1% 638,792 -10.4% Total Alert Cancels 135 134 0.7% 292 -53.8%

Note: Drug claims receiving multiple alerts can be adjudicated by pharmacists by responding to only one conflict code, followed by an intervention code and outcome code. The remaining alerts on the claim cannot be tracked as they are overridden by the pharmacist’s response to a single alert. For example, a single claim can generate up to eight different alerts, but the pharmacist can override all eight alerts by choosing to override only one alert. In addition, the number of cancelled alerts may be underrepresented due to the system’s inability to capture claims that were not adjudicated.

Table 1.2 provides a summary of the number of drug claims and alerts generated for each therapeutic problem type (sorted by alert frequency). Total alerts not adjudicated may be overrepresented, as claims with multiple alerts that have been adjudicated under one alert will show up as not adjudicated for the remaining alerts.

Table 1.2: Summary of Alert Transactions by Therapeutic Problem Type – 2017 Q2 Total % Total Alerts Alerts Alert % Alert Total Not Not Total Over- Over- Alert % Alert Adjud- Adjud- Therapeutic Problem Type Alerts rides rides Cancels Cancels icated icated Early Refill (ER) 289,703 93,642 32.3% 71 0.0% 195,990 67.7% Ingredient Duplication (ID) 218,202 153,614 70.4% 18 0.0% 64,570 29.6% Therapeutic Duplication (TD) 185,801 135,247 72.8% 20 0.0% 50,534 27.2% Late Refill (LR) 119,997 91,529 76.3% 12 0.0% 28,456 23.7% Total High Dose (HD) 50,707 30,925 61.0% 7 0.0% 19,775 39.0% Additive Toxicity (AT) 33,674 26,893 79.9% 4 0.0% 6,777 20.1% Total Low Dose (LD) 24,585 16,073 65.4% 3 0.0% 8,509 34.6% Drug-Pregnancy (PG) 22,239 15,265 68.6% 0 0.0% 6,974 31.4% Drug-Drug (DD) 9,803 7,326 74.7% 0 0.0% 2,477 25.3% Drug-Disease (MC) 2,450 1,752 71.5% 0 0.0% 698 28.5% Drug-Allergy (DA) 207 130 62.8% 0 0.0% 77 37.2% Drug-Age (PA) 292 201 68.8% 0 0.0% 91 31.2%

DUR Quarterly Report – Version 1.0: July 25, 2017 2 2017 Q2 (APRIL 2017 – JUNE 2017) Tables 2.1-2.12. Prospective DUR Alert Transactions by Therapeutic Problem Type. Each of the following tables provides greater detail of each of the 12 DUR alerts with the top 10 drugs generating each respective alert. For each of the top 10 drugs, data are provided for the total number of adjudicated alerts, alert overrides, alert cancels, paid claims, and the percentage of paid claims with alert overrides. Tables are listed in order of DUR alert priority, which is determined by the DUR Board.

Table 2.1: Top 10 Drugs by Therapeutic Problem Type – Drug-Allergy (DA) – 2017 Q2 % of Paid Total Total Claims Adjudicated Total Alert Total Alert Paid with Alert Rank Drug Generic Name/Ingredient Name Alerts Overrides Cancels Claims Overrides 1 PHENYTOIN SODIUM EXTENDED 80 80 0 2,203 3.6% 2 PHENYTOIN 56 56 0 845 6.6% 3 OXYCODONE HCL/ACETAMINOPHEN 8 8 0 6,421 0.1% 4 AMOXICILLIN/POTASSIUM CLAV 6 6 0 11,152 0.1% 5 OXYCODONE HCL 6 6 0 4,445 0.1% 6 AMOXICILLIN 4 4 0 39,735 0.0% 7 IBUPROFEN 2 2 0 83,542 0.0% 8 QUETIAPINE FUMARATE 2 2 0 141,445 0.0% 9 AMPICILLIN TRIHYDRATE 1 1 0 683 0.1% 10 ASPIRIN 1 1 0 64,250 0.0%

Table 2.2: Top 10 Drugs by Therapeutic Problem Type – Drug-Pregnancy (PG) – 2017 Q2 % of Paid Total Total Claims Adjudicated Total Alert Total Alert Paid with Alert Rank Drug Generic Name/Ingredient Name Alerts Overrides Cancels Claims Overrides 1 IBUPROFEN 13,521 13,521 0 83,542 16.2% 2 NORETHINDRONE 2,355 2,355 0 7,648 30.8% 3 SULFAMETHOXAZOLE/TRIMETHOPRIM 466 466 0 18,031 2.6% 4 METHYLERGONOVINE MALEATE 330 330 0 203 162.6% 5 NAPROXEN 274 274 0 12,956 2.1% 6 MISOPROSTOL 267 267 0 673 39.7% 7 DOXYCYCLINE HYCLATE 219 219 0 4,951 4.4% 8 LORAZEPAM 168 168 0 10,419 1.6% 9 LISINOPRIL 114 114 0 33,088 0.3% 10 METHIMAZOLE 113 113 0 1,436 7.9%

Table 2.3: Top 10 Drugs by Therapeutic Problem Type – Drug-Disease (MC) – 2017 Q2 % of Paid Total Total Claims Adjudicated Total Alert Total Alert Paid with Alert Rank Drug Generic Name/Ingredient Name Alerts Overrides Cancels Claims Overrides 1 POTASSIUM CHLORIDE 442 441 1 3,736 11.8% 2 METFORMIN HCL 395 395 0 41,225 1.0% 3 HALOPERIDOL 364 364 0 21,009 1.7% 4 METOPROLOL SUCCINATE 65 65 0 5,308 1.2% 5 METOPROLOL TARTRATE 60 60 0 8,126 0.7% 6 CARBAMAZEPINE 59 59 0 3,491 1.7% 7 HALOPERIDOL DECANOATE 59 59 0 3,996 1.5% 8 PROPRANOLOL HCL 45 45 0 4,200 1.1% 9 ATENOLOL 44 44 0 6,245 0.7% 10 TRIFLUOPERAZINE HCL 41 41 0 1,008 4.1%

DUR Quarterly Report – Version 1.0: July 25, 2017 3 2017 Q2 (APRIL 2017 – JUNE 2017) Table 2.4: Top 10 Drugs by Therapeutic Problem Type – Drug-Drug Interaction (DD) – 2017 Q2 % of Paid Total Total Claims Adjudicated Total Alert Total Alert Paid with Alert Rank Drug Generic Name/Ingredient Name Alerts Overrides Cancels Claims Overrides 1 ELVITEG/COB/EMTRI/TENOF ALAFEN 709 709 0 12,174 5.8% 2 GEMFIBROZIL 560 560 0 2,701 20.7% 3 DARUNAVIR ETHANOLATE 502 502 0 5,746 8.7% 4 SIMVASTATIN 409 409 0 11,915 3.4% 5 ATORVASTATIN CALCIUM 331 331 0 25,922 1.3% 6 METOCLOPRAMIDE HCL 296 296 0 5,199 5.7% 7 AMLODIPINE BESYLATE 243 243 0 21,482 1.1% 8 DARUNAVIR/COBICISTAT 224 224 0 5,222 4.3% 9 ETRAVIRINE 181 181 0 1,223 14.8% 10 ZIPRASIDONE HCL 158 158 0 19,180 0.8%

Table 2.5: Top 10 Drugs by Therapeutic Problem Type – Therapeutic Duplication (TD) – 2017 Q2 % of Paid Total Total Claims Adjudicated Total Alert Total Alert Paid with Alert Rank Drug Generic Name/Ingredient Name Alerts Overrides Cancels Claims Overrides 1 QUETIAPINE FUMARATE 25,446 25,445 1 141,445 18.0% 2 OLANZAPINE 16,453 16,453 0 76,461 21.5% 3 RISPERIDONE 15,248 15,245 3 86,027 17.7% 4 LURASIDONE HCL 10,400 10,396 4 38,867 26.7% 5 CLOZAPINE 6,474 6,473 1 20,081 32.2% 6 PALIPERIDONE PALMITATE 5,865 5,865 0 16,354 35.9% 7 TRAZODONE HCL 4,793 4,793 0 10,661 45.0% 8 ZIPRASIDONE HCL 4,711 4,711 0 19,180 24.6% 9 ALBUTEROL SULFATE 4,186 4,186 0 46,830 8.9% 10 PREDNISONE 3,621 3,621 0 18,387 19.7%

Table 2.6: Top 10 Drugs by Therapeutic Problem Type – Overutilization (ER) – 2017 Q2 % of Paid Total Total Claims Adjudicated Total Alert Total Alert Paid with Alert Rank Drug Generic Name/Ingredient Name Alerts Overrides Cancels Claims Overrides 1 QUETIAPINE FUMARATE 9,721 9,715 6 141,445 6.9% 2 ARIPIPRAZOLE 7,247 7,243 4 103,868 7.0% 3 RISPERIDONE 5,177 5,177 0 86,027 6.0% 4 OLANZAPINE 4,946 4,943 3 76,461 6.5% 5 BENZTROPINE MESYLATE 4,494 4,491 3 56,445 8.0% 6 LURASIDONE HCL 3,191 3,189 2 38,867 8.2% 7 LITHIUM CARBONATE 2,870 2,869 1 30,859 9.3% 8 ASPIRIN 2,092 2,087 5 64,250 3.2% 9 METFORMIN HCL 1,907 1,907 0 41,225 4.6% 10 HALOPERIDOL 1,650 1,650 0 21,009 7.9%

DUR Quarterly Report – Version 1.0: July 25, 2017 4 2017 Q2 (APRIL 2017 – JUNE 2017) Table 2.7: Top 10 Drugs by Therapeutic Problem Type – Underutilization (LR) – 2017 Q2 % of Paid Total Total Claims Adjudicated Total Alert Total Alert Paid with Alert Rank Drug Generic Name/Ingredient Name Alerts Overrides Cancels Claims Overrides 1 QUETIAPINE FUMARATE 17,371 17,369 2 141,445 12.3% 2 ARIPIPRAZOLE 17,358 17,355 3 103,868 16.7% 3 RISPERIDONE 10,280 10,279 1 86,027 11.9% 4 OLANZAPINE 8,302 8,302 0 76,461 10.9% 5 BENZTROPINE MESYLATE 7,114 7,113 1 56,445 12.6% 6 LURASIDONE HCL 5,665 5,664 1 38,867 14.6% 7 LITHIUM CARBONATE 4,712 4,712 0 30,859 15.3% 8 LEVOTHYROXINE SODIUM 2,981 2,981 0 26,283 11.3% 9 ATORVASTATIN CALCIUM 2,735 2,734 1 25,922 10.5% 10 HALOPERIDOL 2,484 2,484 0 21,009 11.8%

Table 2.8: Top 10 Drugs by Therapeutic Problem Type – Additive Toxicity (AT) – 2017 Q2 % of Paid Total Total Claims Adjudicated Total Alert Total Alert Paid with Alert Rank Drug Generic Name/Ingredient Name Alerts Overrides Cancels Claims Overrides 1 ARIPIPRAZOLE 1,696 1,695 1 103,868 1.6% 2 LITHIUM CARBONATE 1,509 1,509 0 30,859 4.9% 3 QUETIAPINE FUMARATE 1,495 1,495 0 141,445 1.1% 4 CLONAZEPAM 1,158 1,158 0 7,719 15.0% 5 HALOPERIDOL 1,009 1,009 0 21,009 4.8% 6 OLANZAPINE 903 903 0 76,461 1.2% 7 ZOLPIDEM TARTRATE 613 613 0 4,082 15.0% 8 TRAZODONE HCL 573 573 0 10,661 5.4% 9 RISPERIDONE 549 549 0 86,027 0.6% 10 CHLORPROMAZINE HCL 501 501 0 6,125 8.2%

Table 2.9: Top 10 Drugs by Therapeutic Problem Type – Ingredient Duplication (ID) – 2017 Q2 % of Paid Total Total Claims Adjudicated Total Alert Total Alert Paid with Alert Rank Drug Generic Name/Ingredient Name Alerts Overrides Cancels Claims Overrides 1 QUETIAPINE FUMARATE 30,871 30,868 3 141,445 21.8% 2 OLANZAPINE 15,082 15,080 2 76,461 19.7% 3 ARIPIPRAZOLE 13,484 13,482 2 103,868 13.0% 4 RISPERIDONE 11,702 11,700 2 86,027 13.6% 5 CLOZAPINE 6,789 6,789 0 20,081 33.8% 6 LURASIDONE HCL 5,912 5,912 0 38,867 15.2% 7 ALBUTEROL SULFATE 5,711 5,710 1 46,830 12.2% 8 ZIPRASIDONE HCL 4,009 4,009 0 19,180 20.9% 9 HALOPERIDOL 3,606 3,605 1 21,009 17.2% 10 LEVOTHYROXINE SODIUM 2,872 2,871 1 26,283 10.9%

DUR Quarterly Report – Version 1.0: July 25, 2017 5 2017 Q2 (APRIL 2017 – JUNE 2017) Table 2.10: Top 10 Drugs by Therapeutic Problem Type – Drug-Age (PA) – 2017 Q2 % of Paid Total Total Claims Adjudicated Total Alert Total Alert Paid with Alert Rank Drug Generic Name/Ingredient Name Alerts Overrides Cancels Claims Overrides 1 ACETAMINOPHEN WITH CODEINE 158 158 0 10,396 1.5% 2 AMITRIPTYLINE HCL 31 31 0 3,448 0.9% 3 DOXEPIN HCL 9 9 0 384 2.3% 4 ACETAMINOPHEN 5 5 0 20,284 0.0% 5 HYDROCODONE/ACETAMINOPHEN 5 5 0 37,845 0.0% 6 LATANOPROST 5 5 0 304 1.6% 7 SIROLIMUS 5 5 0 877 0.6% 8 ARIPIPRAZOLE 4 4 0 103,868 0.0% 9 BUDESONIDE 4 4 0 4,367 0.1% 10 DEXMETHYLPHENIDATE HCL 4 4 0 3,568 0.1%

Table 2.11: Top 10 Drugs by Therapeutic Problem Type – High Dose (HD) – 2017 Q2 % of Paid Total Total Claims Adjudicated Total Alert Total Alert Paid with Alert Rank Drug Generic Name/Ingredient Name Alerts Overrides Cancels Claims Overrides 1 OLANZAPINE 8,395 8,395 0 76,461 11.0% 2 RISPERIDONE 2,429 2,429 0 86,027 2.8% 3 QUETIAPINE FUMARATE 2,288 2,287 1 141,445 1.6% 4 HYDROCODONE/ACETAMINOPHEN 1,789 1,789 0 37,845 4.7% 5 AMOXICILLIN/POTASSIUM CLAV 1,529 1,529 0 11,152 13.7% 6 GABAPENTIN 1,363 1,363 0 22,691 6.0% 7 IBUPROFEN 1,153 1,152 1 83,542 1.4% 8 ARIPIPRAZOLE 926 926 0 103,868 0.9% 9 AMOXICILLIN 824 824 0 39,735 2.1% 10 FAMOTIDINE 686 685 1 13,920 4.9%

Table 2.12: Top 10 Drugs by Therapeutic Problem Type – Low Dose (LD) – 2017 Q2 % of Paid Total Total Claims Adjudicated Total Alert Total Alert Paid with Alert Rank Drug Generic Name/Ingredient Name Alerts Overrides Cancels Claims Overrides 1 LITHIUM CARBONATE 5,226 5,225 1 30,859 16.9% 2 GABAPENTIN 1,635 1,635 0 22,691 7.2% 3 DIVALPROEX SODIUM 994 992 2 11,993 8.3% 4 AZITHROMYCIN 735 735 0 23,004 3.2% 5 AMOXICILLIN 612 612 0 39,735 1.5% 6 ERYTHROMYCIN ETHYLSUCCINATE 521 521 0 1,898 27.4% 7 AMOXICILLIN/POTASSIUM CLAV 495 495 0 11,152 4.4% 8 ALBUTEROL SULFATE 466 466 0 46,830 1.0% 9 BUPROPION HCL 370 370 0 6,336 5.8% 10 ACYCLOVIR 348 348 0 7,930 4.4%

DUR Quarterly Report – Version 1.0: July 25, 2017 6 2017 Q2 (APRIL 2017 – JUNE 2017) Table 3. Summary of Medi-Cal FFS Pharmacy / Drug Utilization Measures. This table shows pharmacy utilization for the Medi-Cal FFS population, including the percent change from the prior quarter and prior-year quarter. Please note that all retrospective data tables exclude claims from beneficiaries in the Family Planning, Access, Care, and Treatment (Family PACT) program and the California Children's Services/Genetically Handicapped Persons Program (CCS/GHPP) because they have different guidelines concerning access to prescription drugs than other Medi-Cal FFS beneficiaries.

Table 3: Pharmacy Utilization Measures for the Medi-Cal FFS Population % Change Current Prior Prior-Year % Change from Quarter Quarter Quarter from Prior Prior-Year Category 2017 Q2 2017 Q1 2016 Q2 Quarter Quarter Total Eligible FFS Beneficiaries 2,319,092 2,361,077 2,697,522 -1.8% -14.0% Total Utilizing FFS Beneficiaries 726,694 767,587 818,051 -5.3% -11.2% Total Paid Rx Claims 2,457,112 2,569,845 2,853,608 -4.4% -13.9% Average Paid Rx Claims 1.06 1.09 1.06 -2.8% 0.0% per Eligible FFS Beneficiary Average Paid Rx Claims 3.38 3.35 3.49 0.9% -3.1% per Utilizing FFS Beneficiary Total Reimbursement Paid ($) to $616,092,117 $585,531,625 $629,661,657 5.2% -2.2% Pharmacies Average Reimbursement Paid ($) $265.66 $247.99 $233.42 7.1% 13.8% per Eligible FFS Beneficiary Average Reimbursement Paid ($) $847.80 $762.82 $769.71 11.1% 10.1% per Utilizing FFS Beneficiary Average Reimbursement Paid ($) $250.74 $227.85 $220.65 10.0% 13.6% per Paid Rx Claim

Table 4. Pharmacy Utilization by Age Group in the Medi-Cal FFS Population. This table presents pharmacy utilization data broken out by age group, including the percent change from the prior quarter and prior-year quarter.

Table 4: Pharmacy Utilization by Age Group in the Medi-Cal FFS Population Current % Change Current Quarter % Change Total Paid Quarter % Change Total % Change Total Age 2017 Q2 Total Paid Claims from 2017 Q2 Utilizing Utilizing Group Total Paid Claims from Prior-Year Total Utilizing Beneficiaries from Beneficiaries from (years) Claims Prior Quarter Quarter Beneficiaries Prior Quarter Prior-Year Quarter 0 – 12 207,317 -18.9% -20.0% 87,357 -17.8% -20.4% 13 – 18 112,599 -8.3% -18.4% 34,997 -8.4% -18.7% 19 – 39 773,879 -0.9% -10.3% 248,638 -1.0% -8.4% 40 – 64 1,130,183 -2.3% -11.9% 276,520 -2.5% -6.4% 65+ 219,394 -6.5% -25.2% 73,593 -8.8% -19.0% Total* 2,457,112 -4.4% -13.9% 726,694 -5.3% -11.2%

* Unknowns represent less than 1% of total

DUR Quarterly Report – Version 1.0: July 25, 2017 7 2017 Q2 (APRIL 2017 – JUNE 2017) Table 5. Top 20 Drug Therapeutic Categories in the Medi-Cal FFS Population. This table presents utilization of the top 20 drug therapeutic categories, by percentage of utilizing beneficiaries with a paid claim. The current quarter is compared to the prior quarter and prior-year quarter in order to illustrate changes in utilization and reimbursement dollars paid to pharmacies for these top utilized drugs. The prior-year quarter ranking of the drug therapeutic category is listed for reference.

Table 5: Top 20 Drug Therapeutic Categories by Percentage of Utilizing Beneficiaries with a Paid Claim

% Change Utilizing % % Change Benefici- % Change Utilizing aries Change Total Current % Benefici- with a Current Total Paid Quarter Utilizing aries with Paid Quarter Paid Claims 2017 Q2 Benefici- a Paid Claim 2017 Q2 Claims from Total aries Claim from Last Total from Prior- Utilizing with a from Prior- Year Paid Prior Year Benefici- Paid Prior Year Rank Rank Drug Therapeutic Category Description Claims Quarter Quarter aries Claim Quarter Quarter ANTIPSYCHOTIC,ATYPICAL, 1 1 408,430 1.3% 1.2% 141,508 19.5% 1.4% 2.6% DOPAMINE,SEROTONIN ANTAGNST NSAIDS, CYCLOOXYGENASE 2 2 101,685 -9.0% -19.4% 87,367 12.0% -0.6% -1.2% INHIBITOR - TYPE ANALGESICS 3 3 PENICILLINS 55,015 -17.8% -15.4% 49,920 6.9% -1.0% -0.4% ANTIPSYCHOTICS, ATYP, D2 PARTIAL 4 6 107,144 2.3% 1.3% 46,966 6.5% 0.5% 0.8% AGONIST/5HT MIXED NARCOTIC ANALGESIC AND NON- 5 4 53,813 -0.8% -24.0% 42,948 5.9% 0.3% -0.9% SALICYLATE ANALGESIC 6 5 PLATELET AGGREGATION INHIBITORS 63,732 -2.8% -16.9% 42,361 5.8% 0.1% -0.3% 7 9 ANTIHISTAMINES - 2ND GENERATION 50,407 5.4% -10.0% 34,259 4.7% 0.4% 0.1% 8 7 LAXATIVES AND CATHARTICS 47,345 -0.5% -19.7% 31,743 4.4% 0.2% -0.4% 9 8 IRON REPLACEMENT 40,977 -1.3% -17.2% 31,281 4.3% 0.1% -0.3% 10 10 ANTICONVULSANTS 78,066 0.2% -17.7% 31,182 4.3% 0.3% -0.1% BETA-ADRENERGIC AGENTS, 11 13 42,357 -18.2% -10.1% 31,148 4.3% -0.9% 0.2% INHALED, SHORT ACTING ANTIHYPERLIPIDEMIC - HMG COA 12 12 43,327 -1.7% -19.6% 28,333 3.9% 0.1% -0.3% REDUCTASE INHIBITORS ANTIHYPERTENSIVES, ACE 13 11 42,607 -2.5% -20.4% 28,211 3.9% 0.1% -0.3% INHIBITORS ANTIHYPERGLYCEMIC, BIGUANIDE 14 14 38,967 -0.9% -14.2% 26,103 3.6% 0.1% -0.1% TYPE ANTIPARKINSONISM 15 19 61,496 0.3% -4.1% 24,683 3.4% 0.2% 0.3% DRUGS,ANTICHOLINERGIC 16 17 CEPHALOSPORINS - 1ST GENERATION 24,588 1.7% -15.0% 23,184 3.2% 0.2% -0.1% 17 15 PRENATAL VITAMIN PREPARATIONS 26,326 -3.3% -21.0% 23,136 3.2% 0.0% -0.4% TOPICAL ANTI-INFLAMMATORY 18 16 25,947 -1.8% -26.4% 21,550 3.0% 0.1% -0.5% STEROIDAL SELECTIVE SEROTONIN REUPTAKE 19 20 38,049 2.1% -17.1% 21,238 2.9% 0.2% -0.1% INHIBITOR (SSRIS) 20 18 ANTIHISTAMINES - 1ST GENERATION 29,350 0.9% -20.0% 21,178 2.9% 0.2% -0.2%

DUR Quarterly Report – Version 1.0: July 25, 2017 8 2017 Q2 (APRIL 2017 – JUNE 2017) Table 6. Top 20 Drugs in the Medi-Cal FFS Population. This table presents utilization of the top 20 drugs, by percentage of utilizing beneficiaries with a paid claim. The current quarter is compared to the prior quarter and prior-year quarter in order to illustrate changes in utilization for these drugs. The prior-year quarter ranking of each drug is listed for reference.

Utilization of drugs for Medi-Cal fee-for-service beneficiaries also includes carved-out drugs utilized by beneficiaries in Medi-Cal managed care plans. Carved-out drugs are listed below in bolded and italicized print.

Table 6: Top 20 Drugs by Percentage of Utilizing Beneficiaries with a Paid Claim

% Change % Change Current of Utilizing of Utilizing Current % Change Quarter Benefici- Benefici- Quarter % Change Total Paid 2017 Q2 % Utilizing aries with a aries with a 2017 Q2 Total Paid Claims Total Benefici- Paid Claim Paid Claim Last Total Claims from Utilizing aries with from from Year Paid from Prior Prior-Year Benefici- a Paid Prior Prior-Year Rank Rank Drug Description Claims Quarter Quarter aries Claim Quarter Quarter 1 1 IBUPROFEN 82,781 -11.0% -19.4% 73,537 10.1% -0.7% -1.0% 2 2 QUETIAPINE FUMARATE 140,913 1.0% 2.0% 55,314 7.6% 0.5% 1.1% 3 4 ARIPIPRAZOLE 103,313 2.0% -0.7% 45,550 6.3% 0.5% 0.7% 4 3 ASPIRIN 62,897 -3.2% -19.3% 42,552 5.9% 0.1% -0.4% 5 5 AMOXICILLIN 39,069 -20.2% -17.2% 36,110 5.0% -0.9% -0.4% 6 10 RISPERIDONE 85,085 -0.1% -3.5% 35,027 4.8% 0.3% 0.4% 7 7 LORATADINE 49,734 5.0% -10.1% 33,919 4.7% 0.4% 0.1% 8 11 ALBUTEROL SULFATE 43,254 -19.8% -10.0% 32,010 4.4% -1.0% 0.2% 9 9 FERROUS SULFATE 40,943 -1.3% -15.1% 31,262 4.3% 0.1% -0.2% HYDROCODONE/ 10 6 37,178 0.9% -22.0% 30,611 4.2% 0.3% -0.5% ACETAMINOPHEN 11 8 DOCUSATE SODIUM 44,436 -0.8% -18.6% 30,332 4.2% 0.2% -0.4% 12 13 OLANZAPINE 76,193 1.9% 4.2% 29,837 4.1% 0.3% 0.7% 13 12 METFORMIN HCL 38,967 -0.9% -14.2% 26,103 3.6% 0.1% 0.0% 14 14 CEPHALEXIN 24,557 1.9% -14.8% 23,167 3.2% 0.2% -0.1% 15 17 BENZTROPINE MESYLATE 56,260 0.2% -3.3% 22,713 3.1% 0.2% 0.3% 16 15 LISINOPRIL 31,925 -1.7% -16.6% 21,382 2.9% 0.1% -0.1% 17 16 ACETAMINOPHEN 19,605 -23.5% -22.6% 18,417 2.5% -0.6% -0.4% 18 19 AZITHROMYCIN 18,032 -32.9% -16.2% 16,931 2.3% -1.0% -0.1% 19 20 ATORVASTATIN CALCIUM 25,635 0.7% -6.0% 16,829 2.3% 0.1% 0.2% 20 23 LURASIDONE HCL 38,783 4.1% 9.1% 16,813 2.3% 0.2% 0.4%

DUR Quarterly Report – Version 1.0: July 25, 2017 9 2017 Q2 (APRIL 2017 – JUNE 2017) APPENDIX B: Definition of terms.

Adjudicate: To pay or deny drug claims after evaluating the claim for coverage requirements

Average Reimbursement ($): A measure of the mean value of the reimbursement in dollars; the sum of the reimbursement divided by the number measured (in dollars).

Beneficiary: A person who has been determined eligible for Medi-Cal, as according to the California Code of Regulations 50024

Eligible FFS beneficiary: A Medi-Cal FFS beneficiary that qualifies for drug benefits

Quarter: One fourth, ¼, 25% or .25 of a year measured in months.

Reimbursement: The reimbursement paid to Medi-Cal pharmacy providers for legend and nonlegend drugs dispensed to Medi-Cal Fee-for-Service (FFS) beneficiaries. Reimbursement is determined in accordance with CA Welfare and Institutions Code Section 14105.45(b)(1).

Drug therapeutic category: Drug therapeutic categories are grouping of drugs at various hierarchy levels and characteristics that may be similar in chemical structure, pharmacological effect, clinical use, indications, and/or other characteristics of drug products.

Utilizing FFS beneficiary: A Medi-Cal beneficiary with at least one FFS prescription filled during the measurement period

DUR Quarterly Report – Version 1.0: July 25, 2017 10 2017 Q2 (APRIL 2017 – JUNE 2017)

PHYSICIAN-ADMINISTERED DRUGS: 1st QUARTER 2017

Utilization of physician-administered drugs during the first quarter of 2017 (January – March 2017) is presented below, stratified by category. In order to show changes in utilization over time, Table 1 shows the comparison to the prior quarter (2016 Q4) and Table 2 shows the comparison to the prior- year quarter (2016 Q1).

Table 1: 2017 Q1 Physician-Administered Drugs: Change from 2016 Q4 (one quarter) % Total % Change Total % Change Total Paid Change Category Utilizing from Reimbursement from Claims from Beneficiaries 2016 Q4 Dollars Paid 2016 Q4 2016 Q4 PHYSICIAN ADMINISTERED DRUG - NDC NOT REQUIRED (vaccines, 18,993 -33.4% 28,982 -29.6% $841,363 -22.9% hyaluronate) PHYSICIAN ADMINISTERED DRUG 267,144 -3.9% 605,980 -3.5% $66,796,248 4.7% - NDC REQUIRED MISCELLANEOUS PRODUCT - REPORTING REQUIRED (supplies, 102,382 -6.0% 214,167 -2.3% $2,457,355 -33.3% immune globulin, IV solutions) TOTAL 388,519 -6.5% 849,129 -4.4% $70,094,967 2.3%

Table 2: 2017 Q1 Physician-Administered Drugs: Change from 2016 Q1 (one year) % Total % Change Total % Change Total Paid Change Category Utilizing from Reimbursement from Claims from Beneficiaries 2016 Q1 Dollars Paid 2016 Q1 2016 Q1 PHYSICIAN ADMINISTERED DRUG - NDC NOT REQUIRED (vaccines, 18,993 -7.3% 28,982 -9.0% $841,363 0.4% hyaluronate) PHYSICIAN ADMINISTERED DRUG 267,144 -10.5% 605,980 -14.1% $66,796,248 -12.2% - NDC REQUIRED MISCELLANEOUS PRODUCT - REPORTING REQUIRED (supplies, 102,382 -24.6% 214,167 -23.2% $2,457,355 -22.4% immune globulin, IV solutions) TOTAL 388,519 -14.6% 849,129 -16.5% $70,094,967 -12.5%

The following three tables show the top 20 physician-administered drugs by total utilizing beneficiaries (Table 3), total reimbursement dollars paid (Table 4), and reimbursement paid per utilizing beneficiary (Table 5). Each table has the comparison to the prior quarter and the prior-year quarter, for reference. In addition, the prior-year ranking is given to show changes in utilization of a drug over time.

Version 1.0: Last updated August 16, 2017 Page 1 of 4

Table 3: Top 20 Physician-Administered Drugs by Total Utilizing Beneficiaries

2017 Q1 % Change % Change 2017 Q1 2017 Q1 Last Total Total Utilizing Total Utilizing Total Total Year HCPCS Utilizing Beneficiaries Beneficiaries Reimbursement Paid Rank Rank Code Drug Description Beneficiaries from 2016 Q4 from 2016 Q1 Dollars Paid Claims MEDROXYPROGES- 1 1 J3490 40,082 -2.9% -11.3% $2,661,102 40,975 TERONE ACETATE 2 2 J3490 LEVONORGESTREL 28,485 6.6% -9.6% $642,880 29,714 LEVONORGESTREL 3 5 S4993 21,335 1.7% -7.5% $2,597,792 21,774 -ETHIN ESTRADIOL ONDANSETRON 4 4 J2405 18,866 -14.6% -19.1% $104,661 22,705 HCL/PF KETOROLAC 5 6 J1885 16,820 -10.2% -15.0% $102,060 18,410 TROMETHAMINE ULIPRISTAL 6 3 J3490 15,028 -24.0% -38.3% $417,778 15,780 ACETATE 0.9 % SODIUM 7 7 X7700 14,476 -8.4% -6.9% $357,858 23,642 CHLORIDE 8 14 Q0144 AZITHROMYCIN 11,480 1.8% 23.0% $44,061 11,943 9 9 Z7610 ACETAMINOPHEN 11,427 8.1% -5.2% $95,041 13,218 10 12 J7307 ETONOGESTREL 11,247 4.2% 9.7% $8,122,875 11,275 CEFTRIAXONE 11 11 J0696 10,639 -0.8% -8.9% $62,638 11,589 SODIUM NORGESTIMATE- 12 10 S4993 ETHINYL 9,910 8.8% -15.7% $1,120,314 10,131 ESTRADIOL MORPHINE 13 8 J2270 9,462 -19.5% -26.2% $65,775 11,188 SULFATE 14 13 Z7610 IBUPROFEN 8,435 1.9% -15.0% $66,141 8,797 DEXAMETHASONE 15 16 J1100 7,690 1.6% -13.4% $52,026 9,678 SOD PHOSPHATE HYDROCODONE/ 16 18 Z7610 6,862 -6.0% -12.4% $74,926 7,527 ACETAMINOPHEN 17 19 S0191 MISOPROSTOL 6,430 4.4% -6.3% $10,911 6,490 FENTANYL 18 17 J3010 6,270 -6.9% -21.5% $32,100 6,873 CITRATE/PF 19 23 S0190 MIFEPRISTONE 6,068 2.4% -6.9% $408,908 6,094 HYDROMORPHONE 20 15 J1170 5,781 -25.0% -35.6% $47,491 7,644 HCL

Version 1.0: Last updated August 16, 2017 Page 2 of 4

Table 4: Top 20 Physician-Administered Drugs by Total Reimbursement Dollars Paid % Change 2017 Q1 Total % Change Total Reimburse- Total 2017 Q1 2017 Q1 Last Reimburse- ment Reimburse- Total Total Year HCPCS ment Dollars from ment Dollars Utilizing Paid Rank Rank Code Drug Description Dollars Paid 2016 Q4 from 2016 Q1 Beneficiaries Claims 1 1 J7307 ETONOGESTREL $8,122,875 9.9% 10.3% 11,247 11,275 COAGULATION FACTOR 2 2 J7189 VIIA,RECOMB $4,766,927 198.5% -14.3% 42 180 (NOVOSEVEN®) 3 N/A J7298 LEVONORGESTREL1 $3,011,087 12.9% N/A 4,204 4,205 ASPARAGINASE (ERWINIA 4 4 J9019 $2,767,855 89.9% -12.2% 33 268 CHRYSAN) MEDROXYPROGESTERONE 5 5 J3490 $2,661,102 -8.2% -10.6% 40,082 40,975 ACETATE 6 7 J9355 TRASTUZUMAB $2,617,629 -0.5% -0.3% 290 915 LEVONORGESTREL-ETHIN 7 6 S4993 $2,597,792 3.2% -7.2% 21,335 21,774 ESTRADIOL 8 9 J7300 COPPER $2,538,797 14.6% 11.1% 3,800 3,822 EPOETIN ALFA (100 UNITS 9 12 Q4081 $2,351,294 5.4% 8.1% 2,069 44,727 ESRD) 10 13 J1745 INFLIXIMAB $2,347,563 5.5% 15.2% 498 1,010 11 8 90378 PALIVIZUMAB $1,920,325 96.1% -22.9% 408 1,000 12 11 J2505 PEGFILGRASTIM $1,831,961 -5.6% -16.8% 278 555 NORELGESTROMIN/ETHIN. 13 14 J7304 $1,413,146 1.6% -21.6% 4,254 4,322 ESTRADIOL 14 15 J1300 ECULIZUMAB $1,385,627 -8.6% -5.5% 19 112 15 19 J9306 PERTUZUMAB $1,357,615 4.4% 19.0% 126 909 16 25 J7301 LEVONORGESTREL $1,205,332 22.0% 55.7% 1,804 1,807 17 16 J9035 BEVACIZUMAB $1,165,364 2.6% -19.3% 178 488 ANTIHEMOPH.FVIII,FULL LENGTH (INCLUDES -45.8% -49.6% 18 10 J7192 ADVATE®, HELIXATE®, $1,145,732 54 164 AND KOGENATE®) NORGESTIMATE-ETHINYL 19 17 S4993 $1,120,314 8.5% -17.5% 9,910 10,131 ESTRADIOL 20 21 J9266 PEGASPARGASE $882,584 -11.8% -16.3% 103 152 1Effective for dates of service on or after October 1, 2016, HCPCS codes J7297 (levonorgestrel-releasing intrauterine contraceptive system, 52 mg, 3 year duration) and J7298 (levonorgestrel-releasing intrauterine contraceptive system, 52 mg, 5 year duration) are benefits. Further, effective for dates of service on or after October 1, 2016, HCPCS code J7302 (levonorgestrel-releasing intrauterine contraceptive system, 52 mg) is no longer reimbursable.

Version 1.0: Last updated August 16, 2017 Page 3 of 4

Table 5: Top 20 Physician-Administered Drugs by Reimbursement Paid per Utilizing Beneficiary % Change % Change 2017 Q1 Reimburse- Reimburse- Reimburse- ment Dollars ment Dollars ment Paid per Paid per 2017 Q1 Last Dollars Paid Utilizing Utilizing 2017 Q1 Total Year HCPCS per Utilizing Beneficiary Beneficiary Total Paid Utilizing Rank Rank Code Drug Description Beneficiary from 2016 Q4 from 2016 Q1 Claims Beneficiaries 1 1 J1322 ELOSULFASE ALFA $236,196 128.7% 57.5% 37 < 10 FACTOR XIII A- 2 3 J7181 SUBUNIT,RECOMB $137,361 -18.9% 18.3% < 10 < 10 (TRETTEN®) 3 5 J1458 GALSULFASE $114,673 2.2% 9.0% 51 < 10 COAGULATION FACTOR 4 2 J7189 VIIA,RECOMB $113,498 162.9% -4.1% 180 42 (NOVOSEVEN®) ANTIHEMOPH.FVIII,B- 5 11 J7185 $97,060 156.5% 39.2% < 10 < 10 DOMAIN DEL (XYNTHA®) FACTOR IX RECOM,ALBUMIN 6 N/A J7202 $91,841 N/A N/A < 10 < 10 FUSION (IDELVION®)1 ASPARAGINASE (ERWINIA 7 8 J9019 $83,874 32.3% 9.1% 268 33 CHRYSAN) 8 9 J1300 ECULIZUMAB $72,928 20.2% 4.4% 112 19 9 6 J1743 IDURSULFASE $69,126 -26.3% -24.4% 97 10 FACTOR IX REC, FC FUSION 10 4 J7201 $68,673 -40.4% -40.6% 11 < 10 PROTN (ALPROLIX®) FACTOR IX HUMAN 11 24 J7195 $62,978 104.0% 136.6% < 10 < 10 RECOMBINANT (BENEFIX®) FACTOR IX RECOM,ALBUMIN 12 N/A J7199 $49,411 -60.7% N/A < 10 < 10 FUSION (IDELVION®)1 13 N/A J9039 BLINATUMOMAB2 $46,490 66.8% N/A 18 < 10 14 19 J3385 VELAGLUCERASE ALFA $46,249 19.9% 18.4% < 10 < 10 ANTIHEMO.FVIII,FULL 15 N/A C9137 LENGTH PEG $42,688 -1.8% N/A < 10 < 10 (ADYNOVATE®)3 16 13 J0221 ALGLUCOSIDASE ALFA $39,793 -20.2% -30.7% 10 < 10 17 18 J1786 IMIGLUCERASE $39,471 -4.2% -4.0% 23 < 10 ANTIHEMOPH.FVIII REC,FC 18 N/A J7205 $36,886 -25.7% N/A 43 12 FUSION (ELOCTATE®) 19 23 J9042 BRENTUXIMAB VEDOTIN $35,036 99.1% 21.2% 48 10 VINCRISTINE SULFATE 20 N/A J9371 5 $26,679 327.1% 57.5% < 10 < 10 LIPOSOMAL

1Code J7202 was effective January 1, 2017, however code J7199 was still accepted for this drug for part of 2017 Q1. 2Code J9039 was effective October 1, 2016. 3Code J7207 was effective January 1, 2017, however code C9137 was still accepted for this drug for part of 2017 Q1. 4Code J7205 was effective October 1, 2016, replacing code Q9975. 5Code J9371 did not have any utilizing beneficiaries in 2016 Q1.

Version 1.0: Last updated August 16, 2017 Page 4 of 4

PROSPECTIVE DUR REVIEW

DATE OF REVIEW: August 15, 2017

FIRST DATABANK DRUG THERAPEUTIC CATEGORIES:  ANALGESICS NARCOTIC, ANESTHETIC ADJUNCT AGENTS  ANALGESICS, NARCOTICS  ANTIHYPERGLYCEMIC, BIGUANIDE TYPE  ANTIHYPERGLYCEMIC-SGLT2 INHIBITOR-BIGUANIDE COMBS.  ANTIHYPERLIPIDEMIC - HMG COA REDUCTASE INHIBITORS  ANTINEOPLASTIC - ALKYLATING AGENTS  ANTINEOPLASTIC - ANTIMETABOLITES  ANTINEOPLASTIC EGF RECEPTOR BLOCKER MCLON ANTIBODY  ANTIPSYCHOTICS, ATYP, D2 PARTIAL AGONIST/5HT MIXED  ANTIVIRALS, HIV-SPECIFIC, CCR5 CO-RECEPTOR ANTAG.  GENERAL ANESTHETICS,INJECTABLE  LINCOSAMIDES  NARCOTIC ANALGESIC,NON-SALICYLATE,XANTHINE COMB  NON-NARC ANTITUSS-1ST ANTIHIST-DECONG-ANALG-EXPECT  SMOKING DETERRENT AGENTS (GANGLIONIC STIM,OTHERS)  TOPICAL LOCAL ANESTHETICS

DRUG PROBLEM TYPES: Drug-Allergy (DA), Drug-Pregnancy (PG), Drug-Disease (MC), Therapeutic Duplication (TD), Underutilization (LR), Additive Toxicity (AT), Ingredient Duplication (ID), Drug-Age (PA), High Dose (HD), Low Dose (LD)

BACKGROUND: Each week new Generic Code Number (GCN) sequence numbers are added. Prospective DUR alerts for Overutilization (ER) and Severity Level 1 Drug-Drug Interactions (DD) are automatically turned on for all new GCNs.

ISSUES: New GCNs are reviewed and cross-referenced to the Medi-Cal target drug list for prospective DUR. If a GCN matches a drug on the Medi-Cal target drug list, the prospective DUR alert profile for the existing GCN is used to set the alert profile for the new GCN. A list of new GCNs with alerts turned on other than ER and DD is provided to the DUR Board for review at each DUR Board meeting.

PROPOSED INTERVENTION RECOMMENDATION TO THE DUR BOARD:  Review list of GCNs with prospective DUR alerts turned on between April 1, 2017 and June 30, 2017 (Table 1).  Any DUR Board recommendations for additions, deletions, and/or changes will be submitted to DHCS for review. Status of recommendations will be reported to the DUR Board at DUR Board meetings, as needed.

Version 1.0: Last updated August 15, 2017 1 Table 1. New GCNs for Existing DUR Target Drugs: Q2 2017 (4/1/17 – 6/30/17).

Date GCN Drug Description Additional Alerts Turned On 077246 MORPHINE SULFATE IN 0.9 % NACL DA, MC, TD, AT, ID, HD, LD 076940 4/5/2017 076941 EMPAGLIFLOZIN/METFORMIN HCL MC, TD, HD, LD 076942 076943 4/19/2017 040237 SIMVASTATIN PG, MC, TD, LR, ID, PA, HD 4/26/2017 077292 ACETAMINOPHEN/CAFF/DIHYDROCOD ID, HD 077313 FENTANYL/BUPIVACAINE/NS/PF DA, MC, TD, AT, ID, HD, LD 077330 5/3/2017 066744 THIOTEPA 077140 NICOTINE POLACRILEX PG 5/10/2017 077331 DOCETAXEL 067940 FENTANYL CITRATE/PF DA, MC, TD, AT, ID, HD, LD 077355 MIDAZOLAM HCL IN 0.9 % NACL 046707 TRASTUZUMAB 5/17/2017 077379 PG 077381 RIBOCICLIB SUCCINATE/LETROZOLE 077382 074968 074969 MORPHINE SULFATE 074970 DA, MC, TD, AT, ID, HD, LD 5/25/2017 074971 077377 FENTANYL CITRATE/PF 077380 DOXYLAM/PE/DM/ACETAMINOPHEN/GG ID, HD 077325 5/31/2017 077326 CLINDAMYCIN IN 0.9 % SOD CHLOR HD, LD 077327 077337 METHOTREXATE PG 6/7/2017 077407 METFORMIN/BLOOD SUGAR DIAGNOST MC, TD, HD, LD 6/14/2017 077464 ARIPIPRAZOLE LAUROXIL MC, TD, LR, AT, ID, HD 6/28/2017 076850 MARAVIROC MC

Version 1.0: Last updated August 15, 2017 2

PROSPECTIVE DUR REVIEW

DATE OF REVIEW: August 15, 2017

FIRST DATABANK DRUG THERAPEUTIC CATEGORIES:  ANTIVIRALS, HIV-SPEC, NUCLEOSIDE-NUCLEOTIDE ANALOG  ANTIVIRALS, HIV-SPECIFIC, NUCLEOSIDE ANALOG, RTI  ARTV NUCLEOSIDE,NUCLEOTIDE,NON-NUCLEOSIDE RTI COMB  ARV COMB-NRTI,NUCLEOTIDE RTI, INTEGRASE INHIBITORS

DRUG PROBLEM TYPE: Ingredient Duplication (ID)

BACKGROUND: The ingredient duplication alert occurs when a claim is submitted for a drug that contains a systemically-absorbed drug that chemically duplicates a drug currently in the patient’s active paid claims medication history. A review of the ID alert was presented at the DUR Board meeting on May 16, 2017. This review revealed that the ID alert for quetiapine was responsible for the overall top drug/alert combination, by volume of alerts. At this meeting, a motion was passed where the DUR Board recommended a similar review of the following drugs that were among the top 20 drugs by volume of ingredient duplication (ID) alerts in 2016:

• ARIPIPRAZOLE • LITHIUM • BENZTROPINE • LURASIDONE • CHLORPROMAZINE • NORETHINDRONE-E.ESTRADIOL-IRON • CLOZAPINE • OLANZAPINE • DIVALPROEX • PALIPERIDONE • EMTRICITABINE • RISPERIDONE • HALOPERIDOL • SERTRALINE • LEVOTHYROXINE • ZIPRASIDONE

ISSUES: At the DUR Board meeting on February 18, 2014, the DUR Board motioned to add all HIV antiretroviral therapies with active ingredients available as both single and combination antiretroviral therapy formulations to the Target Drug List for Prospective DUR and to turn on the Ingredient Duplication (ID) alert for these drugs. The DUR Board action was influenced by evidence-based clinical guidelines for antiretroviral therapy that include fixed-dosage recommendations, including increased risks of adverse events and/or detrimental impact on clinical outcomes due to HIV antiretroviral active ingredient duplication. In addition, it was discussed that due to the high cost of some of these drugs, this class of drugs is at risk for possible drug diversion. Emtricitabine was one of the drugs in which the ID alert was turned on in 2014, and in 2016 it was one of the top 20 drugs by volume of ingredient ID alerts (rank: 20th).

REVIEW OF CURRENT MEDI-CAL FEE-FOR-SERVICE (FFS) CRITERIA: All ingredient (ID) alerts for emtricitabine with dates of service between January 1, 2016 and December 31, 2016 were reviewed. A review of the breakdown of ID alerts by formulation and dose is shown in Table 1.

Version 1.0: Last updated April 11, 2017. 1 Table 1. Drugs Generating Ingredient Duplication (ID) Alerts for Emtricitabine between July 1, 2016, and June 30, 2017

Total ID Alerts Drug n (%) emtricitabine/tenofovir alafenamide 2,683 (38%) elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide 1,904 (27%) emtricitabine/rilpivirine/tenofovir alafenamide 1,244 (18%) emtricitabine/tenofovir disoproxil 513 (7%) efavirenz/emtricitab/tenofovir disoproxil 239 (3%) emtricitabine/rilpivirine/tenofovir disoproxil 227 (3%) elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil 219 (3%) emtricitabine 52 (1%) TOTAL 7,081

The majority of the claims for emtricitabine had ID alerts generated due to different combinations of emtricibine and almost all of the claims for emtricitabine generated an ID alert for only emtricitabine. However, there were 311 claims (4%) that generated multiple ID alerts for additional HIV antiretroviral medication ingredients.

The most common ID alert (n = 5,523; 78%) was for beneficiaries switching from a regimen containing tenofovir disoproxil fumarate to the exact same regimen containing tenofovir alafenamide. While concomitant use of multiple drugs containing emtricitabine is contraindicated, switching to a tenofovir alafenamide-containing regimen from one containing tenofovir disoproxil fumarate may be recommended due to recent reports of improved bone density and renal function associated with the switch.

PROPOSED INTERVENTION RECOMMENDATION TO THE DUR BOARD:  Discuss the ingredient duplication (ID) alert data for emtricitabine, including the merits of reviewing these data again in a year to see if beneficiaries have stabilized after switching to a tenofovir alafenamide-containing regimen over the past year.  Consider using both Medi-Cal fee-for-service and managed care data to evaluate the following six measures used by Medicare to identify questionable prescribing patterns of HIV antiretroviral medications: o Claims history has no indication of HIV . No recorded diagnosis of HIV . No recorded laboratory tests used to monitor the use of HIV drugs . No additional medical services obtained from the HIV drug prescribers o Excessive doses of an HIV drug (at least two times the daily recommended dose of an active ingredient) o Excessive supply of an HIV drug (more than 480 days’ supply) o High number of pharmacies (received HIV drugs from six or more pharmacies) o High number of prescribers (received HIV drugs from six or more prescribers) o Contraindicated combination of HIV drugs for more than 60 days in one year  Any DUR Board recommendations for additions, deletions, and/or changes will be submitted to DHCS for review. Status of recommendations will be reported to the DUR Board at DUR Board meetings, as needed.

Version 1.0: Last updated April 11, 2017. 2

SUMMARY REPORT: UPDATES TO PROSPECTIVE DUR

DATE OF REVIEW: August 15, 2017

FIRST DATABANK DRUG THERAPEUTIC CATEGORIES:  Reviewed all drugs

DRUG PROBLEM TYPES: Reviewed all drug problem types

BACKGROUND: Once a claim is deemed reimbursable through the Medi-Cal fee-for-service (FFS) program, DUR processing begins. Following the criteria established by DHCS and the DUR Board, drugs are compared to the patient’s medical and pharmacy claims history file for select drug therapy problems. DUR alert messages are returned to the pharmacist for all problems detected by this review.

ISSUES: The main issues with the current prospective DUR documentation in the Medi-Cal fee- for-service program are as follows:  Minor discrepancies continue to exist between what is posted in the Medi-Cal DUR Manual under “DUR: Prospective Drug Use Review - Section 20” and the programming in the current prospective DUR system.  Alert-specific lists within Section 20 of the DUR Manual, when available, are difficult to navigate.  GCN profiles for certain drugs are often found to be inconsistent within the same drug.  The Medi-Cal DUR Manual section entitled, “DUR Appendix C: Criteria and Standards Summary - Section 35” is currently in a word document that cannot be searched or modified easily, and it also contains minor discrepancies when compared to Section 20 and/or the alert-specific lists.  Maintenance of the Medi-Cal DUR Manual is labor-intensive due to challenges in the way the manual is organized. For example, a change in alert status for a drug currently must be updated in up to four different sections across two separate documents.

PROPOSED INTERVENTION RECOMMENDATION TO THE DUR BOARD:  Discuss the following proposed changes to the DUR Manual: o Retire unused sections of the DUR Manual, including “Drug Use Review Manual Table of Contents”, “DUR: Introduction – Section 10”, “DUR Appendix A: Duplicate Therapy Section 25”, and “DUR Appendix B: Sample DUR Alerts.” o Modify “DUR: Prospective Drug Use Review - Section 20” to provide only a brief summary of the program, similar to “DUR: Retrospective Drug Use Review – Section 15.” o Replace “DUR Appendix C: Criteria and Standards Summary - Section 35” with a modifiable, comprehensive Excel spreadsheet that can be downloaded from the DUR website under the tab “Alert Criteria”. This document, known as the Prospective DUR Alert Master File contains a complete and accurate list of every drug and the alerts that are on for that drug.

Version 1.0: Last updated August 15, 2017 1 T = Alert is ON in test mode only Y = Alert is ON Aspirin Asenapine Aripiprazole Apixaban Androstenedione Anastrozole Ampicillin Amoxicillin Amobarbital Amlodipine Amitriptyline Amiodarone Aminophylline Aminoglutethimide Amikacin Ambrisentan Amantadine Altretamine Alprazolam Alitretinoin Aliskiren Alirocumab Alfentanil Alendronate Albuterol Albendazole Afatinib Acyclovir Acitretin Acetohydroxamic Acid Acetaminophen Acarbose Abiraterone Abarelix Abacavir DRUG DA Y Y Y Drug-Allergy PG Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Pregnancy MC Y Y Y Y Y Y Drug-Disease DD Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Drug TD Y Y Y Y Y Y Y Y Y Therapeutic Duplication ER Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Early Refill LR Y Y Y Y Y Y Late Refill AT Y Y T T T Y Additive Toxicity Last Updated: 8/22/2017 ID Y Y Y Y Y Y Y Y Y Y Ingredient Duplication PA Y Drug-Age HD Y Y Y Y Y Y Y Y Y Y Y Y Y High Dose LD Y Y Y Y Y Y Y Y Y Y Y Y Low Dose T = Alert is ON in test mode only Y = Alert is ON Candesartan Candesartan Cabozantinib Cabazitaxel Butorphanol Butalbital Butabarbital Busulfan Buspirone Bupropion/Naltrexone Bupropion Buprenorphine Brexipiprazole Brentuximab Bosutinib Bosentan Bortezomib Bleomycin Bicalutamide Bexarotene Benztropine Benzphetamine Bendamustine Benazepril Belinostat Baclofen Azithromycin Azilsartan Azathioprine Azacitidine Axitinib Auranofin Atropine Atorvastatin Atenolol Atazanavir DRUG DA Y Y Y Drug-Allergy PG Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Pregnancy MC Y Y Y Y Drug-Disease DD Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Drug TD Y Y Y Y Y Y Y Therapeutic Duplication ER Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Early Refill LR Y Y Y Y Y Y Y Late Refill AT Y T T T T T T Additive Toxicity Last Updated: 8/22/2017 ID Y Y Y Y Y Y Y Y Ingredient Duplication PA Y Drug-Age HD Y Y Y Y Y Y Y Y Y High Dose LD Y Y Y Y Y Y Y Y Y Low Dose T = Alert is ON in test mode only Y = Alert is ON Clomipramine Clomiphene Clofarabine Clobazam Clindamycin Clarithromycin Cladribine Citalopram Cisplatin Ciprofloxacin Cimetidine Gonadotropins Chorionic Chlorzoxazone Chlorpromazine Chlorotrianisene Chlorothiazide Chlordiazepoxide Chloramphenicol Chlorambucil Chenodiol Cetrorelix Ceritinib Cephalexin Celecoxib Cefixime Cefadroxil Cefaclor Carmustine Carisoprodol Cariprazine Carfilzomib Carboplatin Carbamazepine Captopril Capecitabine DRUG DA Y Drug-Allergy PG Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Pregnancy MC Y Y Y Y Y Y Drug-Disease DD Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Drug TD Y Y Y Y Y Y Y Y Therapeutic Duplication ER Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Early Refill LR Y Y Y Y Y Y Y Late Refill AT Y Y Y T T T T Additive Toxicity Last Updated: 8/22/2017 ID Y Y Y Y Y Y Y Y Ingredient Duplication PA Y Drug-Age HD Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y High Dose LD Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Low Dose T = Alert is ON in test mode only Y = Alert is ON Dienestrol Dicumarol Dicloxacillin Diclofenac Diazepam Dexrazoxane Desvenlafaxine Desipramine Denosumab Demeclocycline Demecarium Degarelix Deferiprone Decitabine Daunorubicin Dasatinib Dasabuvir Darunavir Dantrolene Danazol Dactinomycin Dabigatran Cytarabine Cyclophosphamide Cyclobenzaprine Cromolyn Crizotinib Conjugated Estrogen Codeine Cobicistat Clozapine Clorazepate Clopidogrel Clonidine Clonazepam DRUG DA Y Y Y Y Drug-Allergy PG Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Pregnancy MC Y Y Y Y Y Drug-Disease DD Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Drug TD Y Y Y Y Y Y Y Y Therapeutic Duplication ER Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Early Refill LR Y Y Y Y Y Y Y Late Refill AT Y Y Y Y T T T T Additive Toxicity Last Updated: 8/22/2017 ID Y Y Y Y Y Y Y Y Y Y Y Y Ingredient Duplication PA Y Y Y Drug-Age HD Y Y Y Y Y Y Y Y Y Y Y High Dose LD Y Y Y Y Y Y Y Y Y Y Y Low Dose T = Alert is ON in test mode only Y = Alert is ON Estazolam Escitalopram Erythromycin Erlotinib Eribulin Ergotamine Ergonovine Eprosartan Beta Epoetin Alfa Epoetin Epirubicin Enzalutamide Enalapril Emricitabine Elvitegravir Efavirenz Edoxaban Dutasteride Duloxetine Droperidol Dronedarone Doxycycline Doxorubicin Doxepin Dolutegravir Docetaxel Diphenoxylate Diltiazem Dihydroergotamine Dihydrocodeine Digoxin Diflunisal Difenoxin Diethylstilbestrol Dienogest DRUG DA Y Y Y Y Y Drug-Allergy PG Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Pregnancy MC Y Y Y Y Y Y Drug-Disease DD Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Drug TD Y Y Y Y Y Y Y Y Y Y Y Therapeutic Duplication ER Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Early Refill LR Y Y Y Y Y Y Y Y Y Y Late Refill AT Y T T Additive Toxicity Last Updated: 8/22/2017 ID Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Ingredient Duplication PA Y Y Drug-Age HD Y Y Y Y Y Y Y Y Y Y Y Y Y High Dose LD Y Y Y Y Y Y Y Y Y Y Y Y Y Low Dose T = Alert is ON in test mode only Y = Alert is ON Follitropins Fluvoxamine Fluvastatin Flutamide Flurbiprofen Flurazepam Fluphenazine Fluoxymesterone Fluoxetine Fluorouracil Fludarabine Fluconazole Floxuridine Finasteride Fentanyl Fenoprofen Famotidine Exemestane Evolocumab Everolimus Etretinate Etoposide Etonogestrel Etodolac Ethynodiol Ethotoin Estradiol Ethinyl Ethacrynate Etanercept Eszopiclone Estropipate Estrone Estriol Estramustine Estradiol DRUG DA Y Y Drug-Allergy PG Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Pregnancy MC Y Y Y Y Y Y Y Y Drug-Disease DD Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Drug TD Y Y Y Y Y Y Y Y Y Y Y Therapeutic Duplication ER Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Early Refill LR Y Y Y Y Y Late Refill AT Y Y Y Y T Additive Toxicity Last Updated: 8/22/2017 ID Y Y Y Y Y Y Y Y Y Y Ingredient Duplication PA Y Drug-Age HD Y Y Y Y Y Y Y Y Y Y Y Y High Dose LD Y Y Y Y Y Y Y Y Y Y Y Y Low Dose T = Alert is ON in test mode only Y = Alert is ON Irinotecan Irinotecan Irbesartan Ipratropium Ipilimumab Indomethacin Indium-111 Imipramine Imatinib Iloperidone Ifosfamide Idelalisib Idarubicin Ibuprofen Ibrutinib Hydroxyurea Hydromorphone Hydrocodone Hydrochlorothiazide Histrelin Haloperidol Griseofulvin Goserelin Glyburide Glipizide Gentamicin Gemtuzumab Gemfibrozil Gemcitabine Gefitinib Ganirelix Gabapentin Furosemide Fulvestrant Fosphenytoin Fosinopril DRUG DA Y Y Y Y Y Drug-Allergy PG Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Pregnancy MC Y Y Y Y Y Y Drug-Disease DD Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Drug TD Y Y Y Y Y Y Y Y Y Therapeutic Duplication ER Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Early Refill LR Y Y Y Y Y Y Y Y Late Refill AT Y Y Y T T Additive Toxicity Last Updated: 8/22/2017 ID Y Y Y Y Y Y Y Y Y Y Ingredient Duplication PA Y Drug-Age HD Y Y Y Y Y Y Y Y Y Y Y High Dose LD Y Y Y Y Y Y Y Y Y Y Y Low Dose T = Alert is ON in test mode only Y = Alert is ON Mechlorethamine Maraviroc Macitentan Lutropin Lurasidone Loxapine Lovastatin Losartan Lorcaserin Lorazepam Lopinavir Lomustine Lomitapide Lithium Lisinopril Liraglutide Levothyroxine Levorphanol Levomilnacipran Levofloxacin Leuprolide Letrozole Lenalidomide Leflunomide Lapatinib Lansoprazole Lamivudine Ketorolac Ketoprofen Kanamycin Ixabepilone Isotretinoin Isosorbide Isoniazid Isoflurophate DRUG DA Y Y Drug-Allergy PG Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Pregnancy MC Y Y Y Y Y Y Drug-Disease DD Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Drug TD Y Y Y Y Y Y Y Y Y Therapeutic Duplication ER Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Early Refill LR Y Y Y Y Y Y Late Refill AT Y Y Y T T Additive Toxicity Last Updated: 8/22/2017 ID Y Y Y Y Y Y Y Y Y Y Y Y Ingredient Duplication PA Y Drug-Age HD Y Y Y Y Y Y Y Y Y Y Y High Dose LD Y Y Y Y Y Y Y Y Y Y Y Low Dose T = Alert is ON in test mode only Y = Alert is ON Moexipril Mitoxantrone Mitotane Mitomycin Misoprostol Mirtazapine Mipomersen Minocycline Mifepristone Midazolam Metronidazole Metoprolol Metoclopramide Methysergide Methylphenidate Methylergonovine Methotrexate Methocarbamol Methimazole Methadone Metformin Metaxalone Metaproterenol Mesoridazine Mercaptopurine Meprobamate Mephobarbital Meperidine Menotropins Melphalan Meloxicam Megestrol Mefenamic Acid Medroxyprogesterone Meclofenamate DRUG DA Y Y Drug-Allergy PG Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Pregnancy MC Y Y Y Y Drug-Disease DD Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Drug TD Y Y Y Y Y Y Y Therapeutic Duplication ER Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Early Refill LR Y Y Y Y Late Refill AT Y Y T T T T T Additive Toxicity Last Updated: 8/22/2017 ID Y Y Y Y Y Ingredient Duplication PA Drug-Age HD Y Y Y Y Y Y Y Y Y High Dose LD Y Y Y Y Y Y Y Y Y Low Dose T = Alert is ON in test mode only Y = Alert is ON Oxazepam Oxaprozin Oxandrolone Oxaliplatin Ospemifene Orphenadrine Orlistat Contraceptives Oral Omeprazole Ombitasvir Omacetaxine Olmesartan Olaparib Olanzapine Nortriptyline Norethindrone Nizatidine Nivolumab Nitroglycerin Nitrofurantoin Nintedanib Nilotinib Nifedipine Nicotine Neomycin Nelarabine Nefazodone Naproxen Nandrolone Naltrexone/Bupropion Nafarelin Nabumetone Mycophenolate Morphine Molindone DRUG DA Y Y Drug-Allergy PG Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Pregnancy MC Y Y Y Y Y Y Y Y Y Drug-Disease DD Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Drug TD Y Y Y Y Y Y Y Y Y Y Y Therapeutic Duplication ER Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Early Refill LR Y Y Y Y Y Y Late Refill AT Y Y Y Y T T T Additive Toxicity Last Updated: 8/22/2017 ID Y Y Y Y Y Y Y Y Y Y Y Y Ingredient Duplication PA Drug-Age HD Y Y Y Y Y Y Y Y Y Y Y Y High Dose LD Y Y Y Y Y Y Y Y Y Y Y Y Low Dose T = Alert is ON in test mode only Y = Alert is ON Pomalidomide Plicamycin Plerixafor Pitavastatin Pioglitazone Pimozide Pimavanserin Phenytoin Phentermine Phenol Phenobarbital Phendimetrazine Phenacemide Pertuzumab Perphenazine Perindopril Pentostatin Pentobarbital Pentazocine Penicillins Penicillamine Pemetrexed Pembrolizumab Pazopanib Paroxetine Paritaprevir Panobinostat Pamidronate Paliperidone Palbociclib Paclitaxel Oxytocin Oxymorphone Oxymetholone Oxycodone DRUG DA Y Y Y Y Y Drug-Allergy PG Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Pregnancy MC Y Y Y Y Y Y Y Drug-Disease DD Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Drug TD Y Y Y Y Y Y Y Y Y Therapeutic Duplication ER Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Early Refill LR Y Y Y Y Y Y Y Y Late Refill AT Y Y Y Y Y Y Y T T T Additive Toxicity Last Updated: 8/22/2017 ID Y Y Y Y Y Y Y Y Y Ingredient Duplication PA Drug-Age HD Y Y Y Y Y Y Y Y Y Y High Dose LD Y Y Y Y Y Y Y Y Y Y Low Dose T = Alert is ON in test mode only Y = Alert is ON Rosiglitazone Romidepsin Rivaroxaban Ritonavir Risperidone Riociguat Rilpivirine Ribavirin Remifentanil Regorafenib Ramipril Ramelteon Raloxifene Quinine Quinestrol Quinapril Quetiapine Quazepam Protriptyline Propylthiouracil Propranolol Promethazine Progesterone Prochlorperazine Procarbazine Primidone Primaquine Prednisone Prednisolone Prazepam Pravastatin Pralatrexate Potassium Iodide Potassium Chloride Ponatinib DRUG DA Y Drug-Allergy PG Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Pregnancy MC Y Y Y Y Y Y Drug-Disease DD Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Drug TD Y Y Y Y Y Y Y Therapeutic Duplication ER Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Early Refill LR Y Y Y Y Y Y Late Refill AT Y Y T T T T Additive Toxicity Last Updated: 8/22/2017 ID Y Y Y Y Y Y Y Ingredient Duplication PA Y Drug-Age HD Y Y Y Y Y Y Y Y Y High Dose LD Y Y Y Y Y Y Y Y Y Low Dose T = Alert is ON in test mode only Y = Alert is ON Thalidomide Tetracycline Testosterone Tesamorelin Teriflunomide Tenofovir Teniposide Temsirolimus Temozolomide Temazepam Telmisartan Tazarotene Tapentadol Tamoxifen Suvorexant Sunitinib Sulindac Sulfisoxazole Sulfanilamide Sulfamethoxazole Sulfadiazine Sufentanil Strontium-89 Streptozocin Streptomycin Stanozolol Spironolactone Sorafenib Somatropin Sodium Oxybate Simvastatin Sertraline Secobarbital Samarium Sm Lexidronam 153 Rosuvastatin DRUG DA Y Y Y Y Drug-Allergy PG Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Pregnancy MC Y Y Y Y Y Drug-Disease DD Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Drug TD Y Y Y Y Y Y Y Y Therapeutic Duplication ER Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Early Refill LR Y Y Y Y Y Late Refill AT Y T T T T T Additive Toxicity Last Updated: 8/22/2017 ID Y Y Y Y Y Y Y Y Y Ingredient Duplication PA Y Y Y Drug-Age HD Y Y Y Y Y Y Y Y High Dose LD Y Y Y Y Y Y Y Y Low Dose T = Alert is ON in test mode only Y = Alert is ON Venlafaxine Vemurafenib Vandetanib Valsartan Valrubicin Acid Valproic Urofollitropin Ulipristal Triptorelin Trimetrexate Trimethoprim Trimethadione Triflupromazine Trifluoperazine Triazolam Tretinoin Trazodone Trastuzumab Trandolapril Trametinib Tramadol Tositumomab Toremifene Topotecan Topiramate Tolmetin Tobramycin Tizanidine Tigecycline Thyroid Thiothixene Thiotepa Thioridazine Thioguanine Theophylline DRUG DA Y Y Y Drug-Allergy PG Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Pregnancy MC Y Y Y Y Y Y Y Drug-Disease DD Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Drug TD Y Y Y Y Y Y Y Y Y Y Therapeutic Duplication ER Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Early Refill LR Y Y Y Y Y Y Y Late Refill AT Y Y Y Y Y Y Y Y T Additive Toxicity Last Updated: 8/22/2017 ID Y Y Y Y Y Y Y Y Y Y Y Y Ingredient Duplication PA Drug-Age HD Y Y Y Y Y Y Y Y Y Y Y Y High Dose LD Y Y Y Y Y Y Y Y Y Y Y Y Low Dose T = Alert is ON in test mode only Y = Alert is ON Zolpidem Zolpidem Acid Zoledronic Ziprasidone Zidovudine Zaleplon Warfarin Vortioxetine Vorinostat Voriconazole Vismodegib Vinorelbine Vincristine Vinblastine Vilazodone Verapamil DRUG DA Drug-Allergy PG Y Y Y Y Y Y Y Y Drug-Pregnancy MC Y Y Drug-Disease DD Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Drug-Drug TD Y Y Y Y Y Therapeutic Duplication ER Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Early Refill LR Y Y Y Y Late Refill AT Y Y Y T Additive Toxicity Last Updated: 8/22/2017 ID Y Y Y Y Y Y Ingredient Duplication PA Y Drug-Age HD Y Y Y Y Y High Dose LD Y Y Y Y Y Low Dose

DUR EDUCATIONAL OUTREACH TO PHARMACIES EARLY REFILL LETTER

DATE OF MAILING: June 9, 2017 DATE OF UPDATE: August 15, 2017

BACKGROUND The objective of Medi-Cal prospective drug use review (DUR) is to assist pharmacists in screening select drugs for certain clinically important potential drug therapy problems before the prescription is dispensed to the patient, thereby enhancing the clinical quality and cost effective use of those drugs. In accordance with California Board of Pharmacy requirements and federal rules, Medi-Cal prospective DUR includes an alert for overutilization, also known as an early refill (ER) alert. This alert is generated if the most recent previous prescription for an identical product for the same Medi-Cal fee-for-service beneficiary has greater than 25% of the days’ supply remaining. Currently, the ER alert is turned on for every drug.

Early refill alerts are intended to protect patients from adverse events associated with using a prescribed medication beyond the recommended dose. While the Medi-Cal DUR program recognizes that a legitimate need for an early refill may exist in some situations, early refills can also indicate drug overutilization or an increased potential for fraud, abuse, and diversion. Serious consequences of overutilization can include drug overdose, additive toxicity, and increased side effects. Finally, overutilization of certain drugs may serve as an indication of uncontrolled disease.

Between October 1, 2015, and September 30, 2016 a total of 1,302,881 ER alerts were generated by pharmacy claims processed in the Medi-Cal fee-for-service program. Of these, a total of 397,848 (30.5%) were overridden by providers at the point-of-service, resulting in a paid claim. A review of the ER alert data by pharmacy showed that the vast majority of pharmacies use the ER alert sparingly. Out of 5,342 pharmacies with a paid claim for a Medi-Cal fee-for-service beneficiary during FFY 2015, the top 100 pharmacies by total ER overrides were responsible for 29.4% of the ER overrides and only 18.4% of paid pharmacy claims.

OBJECTIVES  To assess the feasibility and acceptability of DUR educational outreach letters to pharmacies  To decrease the total volume of early refill overrides by pharmacies

Version 1.0: Last modified August 15, 2017 1

METHODS The top 100 pharmacies by total number of ER alert overrides in the Medi-Cal fee-for- service program during calendar year 2016 were sent a letter than contained information about early refills.

The mailing also included the following:  Pharmacy ranking by number of ER alert overrides (overall ER overrides and overrides of scheduled medications)  Pharmacy response survey

Timeframe of mailing following approval of packet by DHCS:  Early Refill Pharmacy Letters (n=100) o May 24, 2017: packet submitted to Publications o June 1, 2017: final, edited packet approved by DHCS o June 8, 2017: packet sent to printer o June 9, 2017: packet mailed to providers

OUTCOMES  Direct costs associated with mailing: o A total of 100 letters were mailed for a total estimated direct cost of $49.96 o Each letter was estimated to have a direct cost of $0.9991, which equals the cost of one envelope and postage for one envelope (return envelopes were inadvertently left out of the mailing).  Rate of undeliverable letters (within 90 days): o There was one letter returned as undeliverable, which was subsequently resent with the correct address information, for an undeliverable rate of 0%.  Pharmacy response rate (within 90 days): o Even without the return envelope a total of 29 pharmacies still responded, either by telephone, by mail, or both, for a response rate of 29%.

As stated in the original proposal, the primary outcome variable will be the percentage decrease in the number of ER alert overrides among all pharmacies who received the mailing, assessed one year after the DUR mailing (paid claims between July 1, 2017, and June 30, 2018). This percentage will be compared with the percentage decrease in the number of ER alert overrides among all pharmacies not receiving the DUR mailing.

Version 1.0: Last modified August 15, 2017 2

DUR EDUCATIONAL OUTREACH TO PROVIDERS FLUOROQUINOLONE LETTER

DATE OF MAILING: August 2, 2017 DATE OF UPDATE: August 15, 2017

BACKGROUND Fluoroquinolones, including ciprofloxacin, ofloxacin, gemifloxacin, levofloxacin, and moxifloxacin, are broad-spectrum antibiotics that interfere with the growth of bacteria via inhibition of certain enzymes needed for bacterial replication. Fluoroquinolones are FDA- approved to treat various bacterial infections and are the only oral antibiotics that can be reliably used to treat infections caused by gram-negative bacilli.

Despite the many FDA-approved indications for use of fluoroquinolones, the Centers for Disease Control and Prevention, the Infectious Diseases Society of America, and the American Thoracic Society all recommend fluoroquinolones not be used as first-line therapy in community settings when other treatment options are available. Fluoroquinolones should be initiated only after other antibiotic classes have been tried and failed, or in such cases with a demonstrated drug resistance.

On July 26, 2016, the FDA approved safety labeling changes for fluoroquinolones, including an updated Boxed Warning, due to potential serious adverse effects, including tendinitis, tendon rupture, peripheral neuropathy, confusion, and hallucinations. The FDA recommends that fluoroquinolones should not be prescribed to patients who have other treatment options for acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, and uncomplicated urinary tract infections, as the risks outweigh the benefits.

A recent study in the Medi-Cal fee-for-service population found that of the 50,843 beneficiaries with at least one paid claim for a fluoroquinolone during a one-year period (between December 1, 2015, and November 30, 2016), approximately two-thirds (68%) of fluoroquinolone use appeared to be potentially inappropriate based on the new FDA recommendations. During the seven days preceding the paid claim for a fluoroquinolone, a total of 5,102 beneficiaries (10%) had a primary or secondary diagnosis of acute bacterial exacerbation of chronic bronchitis, a total of 9,165 beneficiaries (19%) had a primary or secondary diagnosis of acute sinusitis, and 19,306 beneficiaries (39%) had a primary or secondary diagnosis of an uncomplicated UTI. For reference, uncomplicated UTI was the most frequent diagnosis given preceding a paid claim for a fluoroquinolone, followed by septicemia.

Version 1.0: Last modified August 15, 2017 1

OBJECTIVES  To inform providers of the FDA-approved safety labeling changes for fluoroquinolones  To decrease the number of Medi-Cal patients receiving treatment with fluoroquinolones for acute bacterial exacerbation of chronic bronchitis, acute sinusitis, and uncomplicated UTI

METHODS The top 100 prescribers (by total number of paid claims prescribed) of fluoroquinolones in the Medi-Cal fee-for-service program between January 1, 2017 and June 30, 2017 were sent a letter with information about the FDA recommendations for fluoroquinolone use.

The mailing also included the following:  Medi-Cal DUR article on fluoroquinolones  Provider response survey for each provider

Timeframe of mailing following approval of packet by DHCS:  Top Fluoroquinolone Prescriber Letters (n=100) o July 25, 2017: packet submitted to Publications o July 31, 2017: final, edited packet approved by DHCS o August 2, 2017: packet sent to printer o August 2, 2017: packet mailed to providers

OUTCOMES  Direct costs associated with mailing: o A total of 100 letters were mailed for a total estimated direct cost of $99.91 o Each letter was estimated to have a direct cost of $0.9991, which equals the cost of two envelopes and postage for two envelopes, as a self-addressed stamped envelope was included with each letter  Rate of undeliverable letters (within 90 days): o TBD  Provider response rate (within 90 days): o TBD

As stated in the original proposal, the primary outcome variable will be the percentage decrease in the number of paid claims for fluoroquinolone among prescribers who received the mailing, assessed one year after the DUR mailing (paid claims between January 1, 2018, and June 30, 2018).

Version 1.0: Last modified August 15, 2017 2

DUR EDUCATIONAL OUTREACH TO PROVIDERS UPDATE: METABOLIC TESTING IN CHILDREN AND ADOLESCENTS LETTER - 2016

DATE OF MAILING: November 11, 2016 and January 30, 2017 DATE OF UPDATE: October 26, 2016, February 17, 2017, May 17, 2017, and August 15, 2017

BACKGROUND Effective October 1, 2014, any use of antipsychotics for Medi-Cal beneficiaries 0 – 17 years of age requires an approved Treatment Authorization Request (TAR). A report on the impact of this policy was presented to the DUR Board at the September 20, 2016 DUR Board meeting. At that meeting, the DUR Board recommended DUR educational outreach to providers regarding metabolic monitoring for children and adolescents using antipsychotic medications, using methods similar to the mailing conducted in August 2015.

OBJECTIVES  To improve metabolic monitoring rates among children and adolescents in the Medi- Cal fee-for-service population with ≥ 4 paid claims for an antipsychotic medication between January 1, 2015 and September 30, 2016

METHODS The study population identified when writing the policy impact report was used to identify Medi-Cal fee-for-service (FFS) beneficiaries in need of metabolic testing. This initial study population was comprised of a total of 2,272 children and adolescents who met the following criteria:  Between 1 and 17 years of age (between January 1, 2015 and December 31, 2015)  Had at least two paid claims for an antipsychotic medication between January 1, 2015 and December 31, 2015  Did not have a paid claim for either a HbA1C/glucose or LDL-C/cholesterol test between January 1, 2015 and December 31, 2015

For the mailing, eligibility criteria was re-reviewed for each of these beneficiaries to ensure they remained continuously enrolled in the Medi-Cal fee-for-service program between January 1, 2016 (the day after the original data pull for the DUR educational bulletin) and September 30, 2016.

Version 3: Last modified August 15, 2017 1

Further inclusion/exclusion criteria for beneficiaries to be included in the study population:  Beneficiaries < 18 years of age through November 30, 2016  Beneficiaries with ≥ 2 paid claims for an antipsychotic medication between January 1, 2016 and September 30, 2016 (≥ 4 paid claims total between January 1, 2015 and September 30, 2016)  Beneficiaries currently taking an antipsychotic medication (a paid claim with a days supply extending past July 31, 2016)  Did not have a paid claim for either an HbA1C/glucose or LDL-C/cholesterol test between January 1, 2015 and September 30, 2016  Patient/prescriber combinations were excluded if they were already mailed letters in 2015 and a patient survey was received by the DUR program

A total of 588 beneficiaries from the original cohort of 2,272 met the above inclusion/ exclusion criteria. There were two cases where a beneficiary had two prescribers prescribing different medications concurrently so both prescribers were included in the mailing. Twenty- four patient/prescriber combinations were excluded from this mailing as they had already received a letter in the 2015 mailing and had returned surveys on file. A total of 361 prescribers were identified for educational outreach letters.

Prescribers were mailed a letter with a summary of clinical recommendations. The mailing included the following:  List of patients (name and date of birth) from the study population linked to this prescriber  Medi-Cal DUR article on appropriate antipsychotic medication use among children and adolescents  Provider response survey(s); one survey per patient

Timeframe of mailing following approval of packet by DHCS:  Prescriber Letters (n=361) o October 25, 2016: packet submitted to Publications o October 31, 2016: final, edited packet approved by DHCS o November 11, 2016: packets printed o November 11, 2016: packet mailed to providers

Version 3: Last modified August 15, 2017 2

OUTCOMES  Direct costs associated with mailing: o A total of 361 letters were mailed for a total estimated direct cost of $360.67 o Each letter was estimated to have a direct cost of $0.9991, which equals the cost of two envelopes and postage for two envelopes, as a self-addressed stamped envelope was included with each letter  Rate of undeliverable letters (within 90 days): o A total of 68 prescribers (out of 361 unique prescribers) had their letters returned to sender as undeliverable, for a preliminary undeliverable rate of 19%. o A total of 67 undeliverable letters were re-sent to different addresses on January 30, 2017, and 5 of these were also returned as undeliverable. o The final undeliverable rate includes those prescribers with both mailings returned as undeliverable (n = 5) and those prescribers who had the first mailing returned undeliverable and did not have an additional address for the remailing (n = 4), for a final undeliverable rate of 2%.  Provider response rate (within 90 days): o A total of 114 prescribers (out of 361 unique prescribers) returned 206 patient surveys, for a provider response rate of 32%. o If undeliverable letters are removed from the denominator, the response rate stays at 32% (114 out of 352 unique prescribers) o The 206 patient surveys received represent 35% of patient profiles in this mailing (a total of 588 patients).

Survey responses (n=206)  A total of 180 surveys (87%) indicated that the patient was currently under their care, with the majority choosing one of the two following responses (respondents could check more than one option): o “I have reviewed the information and will order metabolic testing” (n=123; 60%) o “I have reviewed the information and will continue without change” (n=48; 23%)  A total of 26 surveys (13%) indicated that the patient was not currently under their care, with the following responses: o “but has previously been a patient of mine” o “however, I did prescribe medication while covering for other MD or in the ER” o “and has never been a patient of mine”  A total of 95 patient surveys (46%) contained written comments from providers. o The majority of comments discussed lab testing recently completed or ordered

Primary Outcome Variable  Out of the 588 patients in the mailing, a total of 481 (82%) continue to be eligible in the Medi-Cal fee-for-service program. The letters for 10 of these beneficiaries were returned as undeliverable, leaving a total of 471 beneficiaries as the denominator. o 92 of these beneficiaries (20%) had at least one laboratory monitoring test done within 90 days of the mailing . 66 beneficiaries (14%) had both laboratory monitoring tests completed Version 3: Last modified August 15, 2017 3

Secondary Outcome Variable  Out of the 471 beneficiaries evaluated for the primary outcome variable, a total of 104 of these beneficiaries (22%) have not had at least two paid claims for an antipsychotic medication since the mailing (dates of service November 1, 2016 through April 30, 2017). Data are stratified by lab monitoring status in Table 1.

Table 1. Continued use of antipsychotic medications among children and adolescents, stratified by lab monitoring within 6 months of the mailing (dates of service November 1, 2016 through April 30, 2017).

≤ 1 paid claim for ≥ 2 paid claims for antipsychotic antipsychotics Had at least one 13 (3%) 79 (17%) lab test (n=92) Did not have either 91 (19%) 288 (61%) lab test (n=379) Total (n=471) 104 (22%) 367 (78%)

DISCUSSION The 61% rate of those children and adolescents who received at least two paid claims for an antipsychotic and did not complete at least one laboratory monitoring test in that same timeframe (Table 1) is almost identical to the 60% rate found in the original metabolic monitoring mailing, which was mailed in August 2015. The original mailing excluded many providers who did not have updated addresses in the Medi-Cal Provider Master File (PMF), so it is notable that the rate did not change once we expanded the mailing to those not listed in the PMF.

In addition, the provider response rate went up slightly in the current mailing (from 28% to 31%) and the rate of undeliverable letters went down considerably, from 30% to 19% (preliminary) and 2% (final). The undeliverable rate improved as the mailing protocol was changed to allow use of NPI addresses and also to allow a one-time re-mailing when a letter was returned as undeliverable, if an updated address could be determined (NPI search, telephone calls to offices, etc.).

Version 3: Last modified August 15, 2017 4

Medi-Cal DUR Educational Outreach to Providers: Academic Detailing Pilot Project

Background: The objective of Medi-Cal prospective drug use review (DUR) is to assist pharmacists in screening select drugs for certain clinically important potential drug therapy problems before the prescription is dispensed to the patient, thereby enhancing the clinical quality and cost effective use of those drugs. In accordance with California Board of Pharmacy requirements and federal rules, Medi-Cal prospective DUR includes an alert for underutilization, also known as an late refill (ER) or refill-too- late. This alert is generated when a sub-therapeutic pattern of prescription drug use is detected when patients fail to renew prescriptions for selected maintenance drugs before more than 125% of the days’ supply of the previous prescription has been used. Currently, the LR alert is turned on for the following drugs:

Alendronate Clonazepam Fluvastatin Molindone Rosuvastatin Amitriptyline Clonidine Fluvoxamine Naltrexone/Bupropion Sertraline Amlodipine Clopidogrel Furosemide Nifedipine Simvastatin Apixaban Clozapine Gabapentin Nitroglycerin Somatropin Aripiprazole Dabigatran Gemfibrozil Nortriptyline Testosterone Asenapine Desipramine Glipizide Olanzapine Thioridazine Atenolol Desvenlafaxine Glyburide Paliperidone Thiothixene Atorvastatin Digoxin Haloperidol Paroxetine Thyroid Benazepril Diltiazem Iloperidone Perphenazine Trifluoperazine Benztropine Doxepin Imipramine Phenobarbital Triflupromazine Bupropion Droperidol Levomilnacipran Phenytoin Valproic Acid Bupropion/Naltrexone Duloxetine Levothyroxine Pimavanserin Venlafaxine Buspirone Edoxaban Lithium Pimozide Verapamil Captopril Enalapril Lovastatin Pioglitazone Vilazodone Carbamazepine Epoetin Alfa Loxapine Pravastatin Vortioxetine Cariprazine Epoetin Beta Lurasidone Propranolol Ziprasidone Celecoxib Escitalopram Megestrol Quetiapine Chlorpromazine Etanercept Mesoridazine Risperidone Citalopram Fluoxetine Metoprolol Rivaroxaban Clomipramine Fluphenazine Mirtazapine Rosiglitazone

Late Refill Alerts in the Medi-Cal Fee-for-Service (FFS) Population: Between January 1, 2016, and December 31, 2016 a total of 469,956 LR alerts were generated by pharmacy claims processed in the Medi-Cal fee-for-service program. Of these, a total of 400,566 (85.2%) were overridden by providers at the point-of-service, resulting in a paid claim. A review of the LR alert data by the length of time the prescription was late found that of the claims with LR alert overrides, 51.3% were within the first seven days of generating the LR alert. As shown in Table 1, the timing of LR alert overrides for medications went up to the 11th-week after the 125% cutoff for generating the LR alert. Using the example listed above, the refill that was due for dispensing on January 31, 2017, would end up being filled at the end of April, 11 weeks after the 8-day buffer allowed before the claim generated the LR alert.

Version 1.0: Last modified August 15, 2017. 1 of 4

Table 1. Status of all Late Refill (LR) Alert Overrides during 2016. Status of Alert Weeks past the Total Adjudicated Not Adjudicated 125% cutoff Alerts Overridden Cancelled Abandoned Duplicate 1 205,401 40 11,141 23,615 240,197 2 101,664 15 5,765 11,792 119,236 3 72,585 18 4,411 8,425 85,439 4 10,647 1 781 1,254 12,683 5 2,854 0 211 335 3,400 6 2,223 0 193 279 2,695 7 1,849 0 154 203 2,206 8 1,321 0 123 162 1,606 9 1,267 0 116 156 1,539 10 668 0 73 91 832 11 87 0 12 24 123 Total 400,566 74 22,980 46,336 469,956

The top 20 drugs by total LR alert overrides during this time period are shown in Table 2, along with the total number of paid claims for each drug during FFY 2016.

Based on DUR Board recommendations at the May 16, 2017, DUR Board meeting, the LR alert was turned on for all direct oral anticoagulants (DOACs), effective June 30, 2017. The DUR Board also recommended developing an academic detailing pilot project and focusing on LR alerts generated by beta-adrenergic blockers, clonidine, clopidogrel, and DOACs. Once the LR alerts were turned on for the DOACs, a review of all LR alerts for these drugs was conducted for all overridden LR alerts for all drugs recommended for inclusion in the academic detailing pilot project. LR alerts that were 3 or more days beyond the allowed window were followed between July 1, 2017, and August 11, 2017. Results are shown in Table 2.

Table 2. Summary of Late Refill Alerts ≥ 3 Days Late, by Drug and Week (during the Six-Week Period between July 1, 2017, and August 11, 2017). WEEK DRUG TOTAL 1 2 3 4 5 6 APIXABAN < 10 < 10 < 10 < 10 < 10 < 10 < 10 ATENOLOL 32 27 26 25 29 39 178 CLONIDINE 51 47 56 63 45 57 319 CLOPIDOGREL 12 < 10 18 10 18 < 10 72 DABIGATRAN < 10 < 10 < 10 < 10 < 10 < 10 < 10 METOPROLOL 55 51 51 67 68 46 338 PROPRANOLOL 26 24 32 27 19 17 145 RIVAROXABAN < 10 < 10 12 11 < 10 12 51 TOTAL 178 166 195 207 188 181 1115

Version 1.0: Last modified August 15, 2017. 2 of 4

Beta-adrenergic blockers made up over half (59%) of the LR alerts during this time period. One area for the DUR Board to discuss is whether these additional beta-adrenergic blockers should have the LR alert turned on (the LR alert is currently off for all GCNs):

 ACEBUTOLOL  CARVEDILOL  NEBIVOLOL  BETAXOLOL  LABETALOL  PINDOLOL  BISOPROLOL  NADOLOL  SOTALOL

Objectives:  To assess the feasibility and acceptability of DUR educational outreach to providers using academic detailing via telephone.  To learn more about late refill overrides.

Methods: Weekly reports of individual LR alerts for selected medications for the previous week (Sunday through Friday) will be generated each Monday morning. The report will include the following information for each LR alert:  Prescribing provider name and contact information  Overriding pharmacy name and contact information  Beneficiary name, sex, date of birth  Date of override  Medication details: drug name, strength, formulation, quantity, days’ supply, previous fill information

Monday was selected as alert data are uploaded over the weekend and would be complete for the prior week on Monday morning.

A pharmacist with training in academic detailing methods will contact each prescribing provider by telephone on behalf of the DUR program, in order to let them know the LR alert was generated and overridden at the pharmacy. A survey will be sent to each provider after the call, which will include questions about the late refill alert intervention.

The pilot project is anticipated to last for four weeks and a summary of the project will be presented at a future DUR Board meeting.

Outcomes: The primary outcome variable will be the percentage of prescribers who the pharmacist is able to contact. In addition, response rates will be calculated, and response data and comments will be presented in aggregate in a report to DHCS and the DUR Board.

Academic Detailing Talking Points.  In accordance with California Board of Pharmacy requirements and federal rules, Medi-Cal prospective DUR includes an alert for underutilization, also known as a late refill (LR) alert.  The LR alert is generated when patients fail to renew prescriptions for selected drugs before more than 125% of the days’ supply of the previous prescription has been used.  You are receiving this call because the Medi-Cal prospective DUR system shows that a pharmacy generated a late refill override for one of your patients.  Your patient [NAME, DOB] tried to fill a claim [NUMBER OF DAYS] late for [DRUG] on [DATE].

Version 1.0: Last modified August 15, 2017. 3 of 4

 While it does take a couple of weeks to fully process the paid claim, an overridden LR alert almost always results in a paid claim.  We wanted to let you know in case you needed to talk with your patient regarding the importance of adhering to the prescribed medication regimen, especially for [DRUG].  The success of the Medi-Cal DUR program is enhanced by the two-way exchange of information. Therefore, we would appreciate hearing your thoughts regarding this information.  Potential follow-up questions: o Did you find this information about the late refill of [DRUG] to be useful? o Had you already been contacted about this late refill from the pharmacy? o Do you normally get contacted from pharmacies regarding late refills? o Would you like us to contact you again for similar late refill issues? o Is there any drug in particular that you have safety concerns about? o Are there any similar topics for which you would like to be contacted? o Do you have any questions for me about the Medi-Cal DUR Program?

Version 1.0: Last modified August 15, 2017. 4 of 4 Update: DUR Publications

Shal Lynch, PharmD, CGP Health Sciences Associate Clinical Professor Department of Clinical Pharmacy School of Pharmacy

September 19, 2017 DUR Publications

May 2017: DUR Educational Alert . Drug Safety Communication: Risks of Codeine and Tramadol Use in Children

August 2017: DUR Educational Bulletin . Clinical Review: Drug-Induced QT Interval Prolongation

2 Update: DUR Publications 9/19/2017 May 2017: DUR Educational Alert (1)

Drug Safety Communication: Risks of Codeine and Tramadol Use in Children

. On April 20, 2017, the FDA announced they are restricting the use of codeine and tramadol medicines in children. They are also recommending against the use of codeine and tramadol medicines in breastfeeding mothers due to possible harm to their infants. . Over-the-counter (OTC) or other FDA-approved prescription medicines should be considered for pain management in children <12 years of age and in adolescents <18 years of age. . Cough is often secondary to infection and usually will get better on its own, so treatment may not be necessary. . OTC cough and cold medications should not be used in children <2 years of age.

3 Update: DUR Publications 9/19/2017 August 2017: DUR Educational Bulletin (1)

Clinical Review: Drug-Induced QT Interval Prolongation

. Learning Objectives • Review medications with known risk for causing torsades de pointes (TdP) • Describe the risk factors for drug-induced QT interval prolongation, including TdP. • Summarize best practices for responsible prescribing of QT- prolonging drugs.

4 Update: DUR Publications 9/19/2017 August 2017: DUR Educational Bulletin (2)

Clinical Review: Drug-Induced QT Interval Prolongation

. Background • Changes in the electrical activity that control contraction of the cells of the heart muscle can lead to a condition in which there is an abnormally long QT interval on the ECG, that may result in TdP, a rare, but potentially fatal, ventricular arrhythmia. • QT prolongation is relatively rare, but is a top reason the FDA has removed drugs from the US market. • Arizona Center for Education and Research on Therapeutics (AZCERT) developed a standardized process to identify and categorize drugs according to their ability to cause QT prolongation and TdP.

5 Update: DUR Publications 9/19/2017 August 2017: DUR Educational Bulletin (3)

Clinical Review: Drug-Induced QT Interval Prolongation Table: Antipsychotic Medications and TdP Risk TdP Risk CredibleMeds Definition Antipsychotic Category chlorpromazine* First- Prolong the QT interval and are associated with haloperidol* Known Generation TdP when used as directed. pimozide (Typical) thioridazine* Antipsychotic perphenazine* aripiprazole* Prolong the QT interval, but insufficient evidence to asenapine* clozapine* Possible indicate these drugs, when used as directed, are Iioperidone* Second- associated with TdP. paliperidone Generation pimavanserin (Atypical) risperidone* Antipsychotic Drugs are associated with TdP, but only under olanzapine* Conditional conditions or circumstances of their use or quetiapine* because the drug facilitates induction of TdP ziprasidone*

6 Update: DUR Publications 9/19/2017 August 2017: DUR Educational Bulletin (4)

Clinical Review: Drug-Induced QT Interval Prolongation

. Other Medications with known TdP Risk:

• Anesthetics, general: propofol, • Antiemetics: droperidol, ondansetron sevoflurane • Antifungals: fluconazole, pentamidine • Antiarrhythmics: amiodarone, • Antimalarial: chloroquine disopyramide, dofetilide, dronedarone, • Antinausea: domperidone flecainide, ibutilide, procainamide, • Antineoplastic agent: oxaliplatin quinidine, sotalol • Cholinesterase inhibitor: donepezil • Antibiotics: azithromycin, ciprofloxacin, • Local anesthetic: cocaine clarithromycin, erythromycin, • Opioid agonist: methadone levofloxacin, moxifloxacin, • Phosphodiesterase 3 inhibitors: • Anticancers: arsenic trioxide, anagrelide, cilostazol vandetanib • Vasodilator: papaverine (intra-coronary) • Antidepressants: citalopram, escitalopram

7 Update: DUR Publications 9/19/2017 August 2017: DUR Educational Bulletin (5)

Clinical Review: Drug-Induced QT Interval Prolongation

. Methods • Retrospective cohort study • Inclusion criteria: ‒ Between 18 and 64 years of age ‒ Continuously eligible with exclusive coverage in the Medi-Cal fee-for-service program ‒ Diagnosis of schizophrenia and/or bipolar disorder during either the measurement year (between April 1, 2016, and March 31, 2017) or the year prior • A total of 68,533 beneficiries met inclusion criteria

8 Update: DUR Publications 9/19/2017 August 2017: DUR Educational Bulletin (6)

Clinical Review: Drug-Induced QT Interval Prolongation

. Antipsychotic medication use stratified into five categories: • Known TdP Risk: 8% (n = 5,654) • Possible TdP Risk: 38% (n = 26,025) • Conditional TdP Risk: 24% (n = 16,746) • Other (at least one paid claim for an antipsychotic medication not yet classified as having TdP risk): 4% (n = 3,014) • None (no paid claims for any antipsychotic medication during the measurement year): 25% (n = 17,094)

9 Update: DUR Publications 9/19/2017

August 2017: DUR Educational Bulletin (7)

Clinical Review: Drug-Induced QT Interval Prolongation

. Clinical characteristics

Known Possible Conditional Percentage with ≥ 1 paid claim for non-antipsychotic 49.4% 42.1% 44.9% medications with known TdP risk Percentage with ≥ 12 paid claims for non- 19.2% 22.0% 22.5% antipsychotic medications with known TdP risk Percentage with ≥ 1 medical conditions that may 11.9% 10.0% 9.9% cause QT prolongation Percentage with  1 paid claim for an ECG 10.1% 7.9% 8.8% Percentage with any potential adverse cardiac event 1.6% 1.5% 1.6%

10 Update: DUR Publications 9/19/2017 August 2017: DUR Educational Bulletin (9)

Clinical Review: Drug-Induced QT Interval Prolongation

. Utilization of non-antipsychotic known TdP risk medications and prevalence of medical conditions that may lead to QT prolongation

Total non-antipsychotic Total paid claims for non- Total medical conditions Study population known TdP risk antipsychotic known TdP that may lead to QT n = 68,533 medications risk medications prolongation Sex  Female (n = 34,180) 1.5 ± 2.1 p < 0.001 9.9 ± 9.1 p < 0.001 0.2 ± 0.2 n.s.  Male (n = 34,353) 1.2 ± 1.7 8.8 ± 9.4 0.2 ± 0.1 Age Group  18 - 49 years of age (n = 47,008) 1.4 ± 1.9 n.s. 8.5 ± 8.2 p < 0.001 0.1 ± 0.1 p < 0.001  50 - 64 years of age (n = 21,525) 1.4 ± 2.4 10.2 ± 9.4 0.6 ± 0.3 Race/Ethnicity  White/Caucasian, non-Hispanic(n = 27,781) 1.5 ± 2.2 p < 0.001 9.5 ± 9.1 p < 0.001 0.2 ± 0.1 p < 0.01  All other races/ethnicities (n = 40,752) 1.2 ± 1.4 9.1 ± 9.0 0.1 ± 0.2 California Region of Residence  Los Angeles County (n = 17,904) 1.4 ± 2.1 n.s. 9.4 ± 9.1 n.s. 0.2 ± 0.1 n.s.  All other regions/counties (n = 50,629) 1.4 ± 2.0 9.3 ± 9.3 0.2 ± 0.2

11 Update: DUR Publications 9/19/2017 August 2017: DUR Educational Bulletin (11)

Clinical Review: Drug-Induced QT Interval Prolongation

. Clinical Recommendations: • Risk for QT interval prolongation should be assessed for every patient before beginning a QT-prolonging medication. • QT-prolonging medications should be avoided in elderly patients, patients with pre-existing heart disease, history of ventricular arrhythmias, or with metabolic abnormalities such as hypokalemia, except for cases in which the benefits of treatment clearly outweigh the risks. • Cytochrome P450 inhibitors should be avoided in patients taking QT-prolonging medications.

12 Update: DUR Publications 9/19/2017 August 2017: DUR Educational Bulletin (12)

Clinical Review: Drug-Induced QT Interval Prolongation

. Clinical Recommendations (cont.): • Discuss risks of QT-prolonging medications with patients and the symptoms in which patients should seek emergency treatment. • Pay careful attention to potential electrolyte loss in patients at high risk for QT interval prolongation. • Regular electrolyte and ECG monitoring is recommended for patients at high risk for QT interval prolongation and those taking additional concomitant QT-prolonging medications. • Where congenital LQTS is suspected, ECG screening is recommended for all of the patient’s first-degree relatives.

13 Update: DUR Publications 9/19/2017 Future Topics: Bulletins

DUR Educational Bulletins:

. Describe recent FDA labeling changes for opioids and other CNS depressants, including an evaluation of high-risk drug use in the Medi-Cal population (in progress) . Provide treatment guidelines for managing pain in population with co-morbid mental health conditions, including those with a documented history of substance abuse . Nicotine replacement therapy – to be timed with implementation of pharmacist furnishing of NRT . Annual vaccine bulletin, including any updates on current guidelines (ongoing, published each September)

14 Update: DUR Publications 9/19/2017 Future Topics: Alerts/Educational Outreach

DUR Educational Alerts:

. FDA drug safety communications (ongoing)

DUR Educational Outreach to Medi-Cal Providers/Pharmacies:

. Academic Detailing Pilot: Late Refill . Provider Letter: High Use of Triptan Medications . Provider Letter: OTC

15 Update: DUR Publications 5/16/2017

Future Topics: Alerts/Prospective Reviews

Prospective DUR Reviews:

. Top DUR alerts by volume (ongoing) . Top 20 drugs by volume of ingredient duplication (ID) alerts in 2016 (ongoing) . Quarterly review of new GCNs (ongoing, quarterly) . Updated therapeutic duplication alert, once implemented . Review of test data: additive toxicity alert (for presentation in February 2018) . Topics from today’s meeting: Discrepancy clean-up (ongoing)

16 Update: DUR Publications 5/16/2017 Future Topics: Retrospective Reviews

Retrospective DUR Reviews:

. Hormonal contraceptives, specifically in the pharmacy setting . Assessment of opioid use and mortality, linking death index information with medical/pharmacy claims data (stratified by gender) . Annual review of drugs added to the Medi-Cal List of Contract Drugs (ongoing, presented each November) . 2016 Adult Core Set Measures: • Diabetes Screening for People With Schizophrenia or Bipolar Disorder Who Are Using Antipsychotic Medications (SSD) • Use of Opioids at High Dosage (OHD) . Topic from today’s meeting: 2017 Child Core Set Measures

17 Update: DUR Publications 9/19/2017

Topics

• Pharmacy Policy: – Codeine and Tramadol restrictions – Opioid Quantity Limits – Sumatriptan succinate tablets removed restriction • DHCS $90M Grant to Fight Opioid Crisis • Academic Detailing Conference, October 12, 2017 • Child Core Set – CMS Report • Adult Core Set – CMS Report • CMS Annual Report FFY 2018 Questionnaire

Medi-Cal DUR Board Meeting 09-19-17

Codeine & Tramadol

• Pharmacy Policy: – Codeine and tramadol are contraindicated in use to treat cough or pain for children <12 years of age – Tramadol is contraindicated in children <18 years to treat pain after surgery to remove the tonsils and/or adenoids – Warning (recommends against) use of codeine and tramadol in adolescents 12-18 years of age who are obese, has obstructive sleep apnea or sever lung disease, with increased risk of serious breathing problems

Medi-Cal DUR Board Meeting 09-19-17 Opioid Quantity Limits

• Pharmacy Policy Change: Effective July 1, 2017 – Opioids quantity limit – Includes first prescriptions • Continuous update to address – Short acting opioids – Long acting opioids

Medi-Cal DUR Board Meeting 09-19-17 Sumatriptan Succinate Tablets

• Policy change effective October 1, 2017 • New policy to remove restrictions on the number of prescriptions within a twelve month period.

Medi-Cal DUR Board Meeting 09-19-17 DHCS $90M Opioid Grant

• In April 2017, DHCS announced expanding services to fight opioid crisis with new $90M grant from SAMHSA • Opioid 90M Grant • Large portion of grant to support MAT, using buprenorphine • Opioid misuse prevention • Wider distribution of naloxone • Coordination with local coalitions to reduce opioid abuse

Medi-Cal DUR Board Meeting 09-19-17

The Toll of Drug Abuse

• 2013 Drug Overdose Death by CA Counties and other states: Source: Opioid 90M Grant Location 2013 Drug Overdose death per 100,000 Lake County 46.3 Plumas County 41.1 Lassen County 31.5 West Virginia 30.7 Sierra County 30.6 Humboldt County 30 Trinity County 29

Medi-Cal DUR Board Meeting 09-19-17 The Toll of Drug Abuse -2

• 2013 Drug Overdose Death by CA Counties and other states:

Location 2013 Drug Overdose death per 100,000 Del Norte County 28 Shasta County 28 Mariposa County 27.6 Nevada County 26.9 Kentucky 23.2 Rhode Island 22.9 California 11.6

Medi-Cal DUR Board Meeting 09-19-17 ED Visits for Opioid Poisoning

• Highest CA rates by county: (Source: OSHPD)

County Number Rate (per 100,000) population Plumas 61 61.7

Humboldt 316 46.3

Lake 137 42.2

Shasta 375 42.0

Trinity 27 39.1 Santa Cruz 459 34.2

Medi-Cal DUR Board Meeting 09-19-17 ED Visits for Opioid Poisoning-2

• Highest CA rates by county: (Source: OSHPD)

County Number Rate (per 100,000 Population) Tehama 101 34.2

Del Norte 45 31.5

Mendocino 137 31.4

Tuolumne 85 30.9

Mariposa 28 30.8 San Francisco 1,238 30.0

Medi-Cal DUR Board Meeting 09-19-17 Academic Detailing

• Webpage: – Academic detailing

• 2017 Conference Date: October 12, 2017 – Pre-meeting survey – Speakers – Topics – Best Practices – Assistance from DHCS’s Strategic Planning & Workforce Development Branch

Medi-Cal DUR Board Meeting 09-19-17

Child Core Set

• DHCS Quality Measures and Reporting – Pediatric Dashboard • Quality of Care for Child in Medicaid: Findings from the 2015 Child Core Set – Child Core Set 2015 CMS Report

Medi-Cal DUR Board Meeting 09-19-17 Adult Core Set

• Quality of Care for Adults in Medicaid: Findings from the 2015 Adult Core Set • Adult Core Set 2015 CMS Report

Medi-Cal DUR Board Meeting 09-19-17 CMS DUR Annual Report FFY 2018

Process Timeline

CMS CMS DUR States provide convened ADURS CMS finalizes Annual Report input and edits conference Subcommittee questionnaire Questionnaire to ADURS submits input & submission call with and edits FFY 2018 ADURS Subcommittee rules (process Draft August 2018 and due date) July 2017 August 2018

Medi-Cal DUR Board Meeting 09-19-17 Questions?

Email:

[email protected]

Medi-Cal DUR Board Meeting 09-19-17