Connecticut Medical Assistance Pharmacy Program Drug Utilization Review (DUR) Program DUR Board Meeting

March 2021 DUR Board Meeting Minutes Thursday, March 11, 2021 at 6:30 PM Virtual Meeting

ATTENDEES

Board Members Present: Ken Fisher, R.Ph. (Chair), Keith Lyke, R.Ph. (Co-chair), Carol Drufva R.Ph., Richard Gannon, Pharm.D., Ram Illindala, MD, Dennis Chapron, R.Ph., Damian Dos Santos, MD, Angela Boggs Pharm.D., Bhupesh Mangla, MD

Ex-Officio Non-Voting Member Present: Heather Kissinger, Pharm. D. (HID), Jason Gott, R.Ph. (DSS), Joseph Morasutti, Pharm.D. (Gainwell Technologies)

Guests: Rasheed Jandali (Johnson & Johnson), Adam Denman (Global Blood Therapeutics), Barry Scott (Takeda), Bryan Dillon (Otsuka), Erin Booth (Vertex), Joe Shaker (Sanofi Genzyme), Kristin Kollecas (Sanofi Genzyme), Susan Tillier (Leo), John Davis (Leo), Nicole Trask (Janssen), Gene Muise (Amgen), Donna Bischoff (Indivior), Patricia Mulcahy (Dexcom)

1. Introductory Business  Ken Fisher called the meeting to order at 6:37 p.m.

2. Previous Meeting Minutes  The December 2020 DUR meeting minutes were approved with the following change: o Page 1, under Ex-Officio Non-Voting Member Present, change “DXC” to “Gainwell Technologies”

3. Follow-Up from Previous Meeting  The Board reviewed section 3 titled “Follow-up from the December DUR Board Meeting.”  Follow-up 1, a request was made to know the thioridazine utilization during 4th quarter 2020.  Heather stated that 5 unique recipients filled 9 prescriptions for thioridazine during 4th quarter 2020.  Follow-up 2, a request was made to table the Ibrutinib/overutilization (hepatic impairment) and Istradefylline/overuse (hepatic impairment) criteria with the request to break the individual criteria into 2 separate alerts based on different levels of impairment.  Beginning with Ibrutinib, Heather recommended to approve as written due to the lack of ICD-10 codes for differentiating levels of hepatic impairment. The Ibrutinib criteria contained two different dosing recommendations for mild hepatic impairment (140 mg/day) and moderate hepatic impairment (70 mg/day).  The Board voted to approve as written due to the lack of ICD-10 codes to differentiate between mild and moderate hepatic impairment.  Heather presented two new criteria for the single Istradefylline/overuse (hepatic impairment) criteria stating it could be broken out more easily based on diagnoses used to define severity of moderate and severe hepatic impairment.  The Board voted to approve two separate criteria for Istradefylline/overuse (hepatic impairment): Istradefylline maximum dose in moderate hepatic impairment (defined by hepatic impairment without cirrhosis or hepatic failure) and Istradefylline should be avoided in patients with severe hepatic impairment (defined by a diagnosis of cirrhosis or hepatic failure). Connecticut Medical Assistance Pharmacy Program Drug Utilization Review (DUR) Program DUR Board Meeting

March 2021 DUR Board Meeting Minutes Thursday, March 11, 2021 at 6:30 PM Virtual Meeting

 The Board recommended to consistently apply this logic going forward for other medications when there is a recommendation for use in moderate versus severe hepatic impairment.  Follow-up 3, a request was made to run the top 50 prescribers/pharmacies report by prescribed quantity versus RX count.  Heather stated this information would be reviewed under agenda item #9.

4. Criteria Trend Summary  Heather discussed the criteria trend analyses tables included in the DUR Board meeting packet. The tables list the number of criteria exceptions found before and after DUR intervention letters are mailed. Criteria are suppressed for patients who are selected for intervention for 6 months after letters are mailed so that prescribers do not receive the same letter for the same patient month after month. In almost all cases the number of criteria exceptions noted 7 months after DUR letters were mailed was reduced as compared to the number of exceptions prior to letters being mailed.

5. Program Summary Review  The Board reviewed the program summary for 4th quarter 2020.  Heather stated that compared to the previous quarter prescription claims cost increased by approximately $15 million, the number of prescriptions increased by approximately 36,000, the number of unique recipients receiving a prescription increased by approximately 3,000 and the average paid per prescription increased by approximately $4.

6. Top 50 Medications by Utilization and by Total Cost  The Board reviewed the top 50 medications by utilization and by total cost for 4th quarter 2020.  Dennis questioned if there was criteria available for concurrent use of opioids and gabapentinoids and if there was an increased risk of respiratory depression with concomitant use.  Additionally, the Board requested to know the number of unique recipients identified by the criteria.  Heather stated she would follow-up with specific criteria that the DUR Board previously approved.  Rich stated that a previous study from the Canadian National Health System looked at the concurrent use of opioids and gabapentin which showed an increase in respiratory depression, although many patients enrolled in the study were also receiving benzodiazepines. Based on this and other recent information, hospitals have been removing gabapentin from post-operative order forms, however, short term use of gabapentin (tapering after one week) can be beneficial in certain patients. Additionally, gabapentin and pregabalin are now reported on the Monitoring Program (PDMP) site which can assist prescribers.  Angie stated that once providers prescribe gabapentin, the concurrent opioid dose should theoretically be decreased. Due diligence with concurrent therapy should be done but doesn’t always occur.  Rich stated that patients typically become comfortable with their regimens and doses and don’t always like to taper. This requires good follow-up by the prescriber.

7. Intervention Activity Report Connecticut Medical Assistance Pharmacy Program Drug Utilization Review (DUR) Program DUR Board Meeting

March 2021 DUR Board Meeting Minutes Thursday, March 11, 2021 at 6:30 PM Virtual Meeting

 Heather reviewed the Intervention Activity Report included in the DUR Board packet. It was stated that the Intervention Activity Report is a monthly summary of the distribution of letters mailed to prescribers, summarizing the targeted interventions reviewed during 4th quarter 2020.

In October 2020, 2,820 profiles were reviewed, and 2,339 letters were sent. The main intervention(s) reviewed for the adult population:  Underutilization of antipsychotics (796 letters)  Lock-in criteria (382 letters) The main intervention(s) reviewed for the pediatric population:  Pediatric psychotropic medication monitoring guidelines - stimulants (679 letters)

In November 2020, 2,815 profiles were reviewed, and 1,981 letters were sent. The main intervention(s) reviewed for the adult population were:  Overutilization of NSAIDs or butalbital in migraine, use of oral contraceptives in migraine (945 letters)  Lock-in criteria (247 letters) The main intervention(s) reviewed for the pediatric population were:  Risks associated with prolonged use of atypical antipsychotics in the pediatric population (480 letters)

In December 2020, 2,823 profiles were reviewed, and 1,628 letters were sent. The main intervention(s) reviewed for the adult population were:  Specialty mailer for chronic opioid use/no naloxone/increase risk of overdose (490 letters)  Overutilization of zolpidem (80 letters) o Dennis and Angie requested to know the specific criteria and dose that was targeted for zolpidem review. o Heather stated she would follow-up during the June DUR meeting.  Lock-in criteria (251 letters) The main intervention(s) reviewed for the pediatric population were:  Pediatric psychotropic medication monitoring guidelines - SSRIs (498 letters)

8. RetroDUR Criteria  The following criteria were approved as written by the DUR Board: 1. Bempedoic Acid/Ezetimibe / Overuse 2. Bempedoic Acid/Ezetimibe / Therapeutic Appropriateness 3. Bempedoic Acid/Ezetimibe / Therapeutic Appropriateness 4. Bempedoic Acid/Ezetimibe / Tendon Rupture 5. Bempedoic Acid/Ezetimibe / Simvastatin 40 & 80 mg 6. Bempedoic Acid/Ezetimibe / Pravastatin 80 mg 7. Bempedoic Acid/Ezetimibe / Cyclosporine 8. Bempedoic Acid/Ezetimibe / Fenofibrate Connecticut Medical Assistance Pharmacy Program Drug Utilization Review (DUR) Program DUR Board Meeting

March 2021 DUR Board Meeting Minutes Thursday, March 11, 2021 at 6:30 PM Virtual Meeting

9. Bempedoic Acid/Ezetimibe / Pregnancy / Pregnancy Negating 10. Bempedoic Acid/Ezetimibe / Therapeutic Appropriateness 11. Bempedoic Acid/Ezetimibe / Non-adherence 12. / Overuse 13. Upadacitinib / Therapeutic Appropriateness 15. Upadacitinib / Serious Infection (Black Box Warning) 16. Upadacitinib / Tuberculosis (Black Box Warning) 17. Upadacitinib / Thrombosis (Black Box Warning) 18. Upadacitinib / Malignancy 19. Upadacitinib / Gastrointestinal Perforation 20. Upadacitinib / Potent Immunosuppressants 21. Upadacitinib / Strong CYP3A4 Inhibitors 22. Upadacitinib / Strong CYP3A4 Inducers 23. Upadacitinib / Pregnancy / Pregnancy Negating 24. Upadacitinib / Lactation 25. Upadacitinib / Therapeutic Appropriateness 26. Upadacitinib / Non-adherence 27. Celecoxib Oral Solution / Overuse 28. Celecoxib Oral Solution / Overuse – Hepatic Impairment 29. Celecoxib Oral Solution / Therapeutic Appropriateness 30. Celecoxib Oral Solution / Severe Hepatic Impairment 31. Celecoxib Oral Solution / Severe Renal Impairment 32. Celecoxib Oral Solution / Therapeutic Appropriateness 33. Fluticasone-Umeclidinium-Vilanterol / Overutilization (Asthma) 34a. / Overuse 35. Encorafenib / Therapeutic Appropriateness - Pediatric 37. Encorafenib / Hemorrhage 38. Encorafenib / Uveitis 39. Encorafenib / QT Prolongation 40. Encorafenib / Moderate & Strong CYP3A4 Inhibitors 41. Encorafenib / Moderate & Strong CYP3A4 Inducers 42. Encorafenib / Sensitive CYP3A4 Substrates 43. Encorafenib / Drugs that Cause QT Prolongation 44. Encorafenib / Hormonal Contraceptives 45. Encorafenib / Pregnancy / Pregnancy Negating 46. Encorafenib / Lactation 47. Encorafenib / Therapeutic Appropriateness 48. Encorafenib / Non-adherence 49. Budesonide/Glycopyrrolate/Formoterol / Overutilization 50. Budesonide/Glycopyrrolate/Formoterol / Therapeutic Appropriateness 51. Budesonide/Glycopyrrolate/Formoterol / Therapeutic Appropriateness 52. Budesonide/Glycopyrrolate/Formoterol / Cardiovascular, Diabetes, Convulsive Disorders, & Thyrotoxicosis Connecticut Medical Assistance Pharmacy Program Drug Utilization Review (DUR) Program DUR Board Meeting

March 2021 DUR Board Meeting Minutes Thursday, March 11, 2021 at 6:30 PM Virtual Meeting

53. Budesonide/Glycopyrrolate/Formoterol / Adrenergic Drugs 55. Budesonide/Glycopyrrolate/Formoterol / Non-Potassium Sparing Diuretics 56. Budesonide/Glycopyrrolate/Formoterol / QT Prolonging Meds 57. Budesonide/Glycopyrrolate/Formoterol / Anticholinergics 58. Budesonide/Glycopyrrolate/Formoterol / Other LABAs 59. Budesonide/Glycopyrrolate/Formoterol / Strong CYP3A4 Inhibitors 60. Budesonide/Glycopyrrolate/Formoterol / Narrow Angle Glaucoma 61. Budesonide/Glycopyrrolate/Formoterol / Non-adherence 62. Budesonide/Glycopyrrolate/Formoterol / Nonselective Beta Blockers

 The following criteria were approved as amended by the DUR Board: 14. Upadacitinib / Therapeutic Appropriateness – Addition of hepatic failure to Util B 34. Encorafenib / Overuse – Addition of max dose of 450 mg 36. Encorafenib / Therapeutic Appropriateness – strike last sentence from alert message 54. Budesonide/Glycopyrrolate/Formoterol / Xanthine Derivatives & Steroids – remove reference to steroids from alert message and all steroids from Util B

 The following criteria were tabled until the March 2021 meeting by the DUR Board: 63. Carisoprodol / Opioid / Benzodiazepine / Therapeutic Appropriateness o Dennis questioned if there was clinical data to support risk of respiratory depression with concurrent use of opioids and carisoprodol. o Heather stated that carisoprodol potentiates GABA, similar to benzodiazepines. o Angie stated that clinical data exists to support the risk of opioids used concurrently with benzodiazepines so theoretically there is an enhanced risk when opioids are used concurrently with carisoprodol. o The Board reviewed letter type 500H associated with criteria 63. o Heather stated the RDUR system cannot insert 3 medications into an alert letter, therefore, if the Board voted to approve criteria 63 and associated letter type, the letter can only be sent to 2 prescribers and insert the alert message into the body of the letter, without listing the specific medications. o The Board requested to include information into letter type 500H regarding consideration of naloxone in patients receiving triple therapy with carisoprodol, opioids, and benzodiazepines. o Dennis requested a list of specific prescribers associated with patients receiving the triple therapy. o Heather stated she would follow-up during the June meeting. o Joe stated that the point of sale (POS) adjudication system flags concurrent therapy to let the pharmacy know prior to dispensing concurrent therapy. Additionally, prescribers are required by law to check the PDMP prior to prescribing a controlled substance. o Keith stated a new start of a controlled substance requires a check of the PDMP each time. o Angie stated that chronic use requires a check of the PDMP every three months. o The Board discussed the technical aspects of the PDMP system including reporting processes to the State and methods software companies have integrated into their systems for ease of access in order to check the PDMP. 64. Skeletal muscle relaxant / Opioid / Therapeutic Appropriateness Connecticut Medical Assistance Pharmacy Program Drug Utilization Review (DUR) Program DUR Board Meeting

March 2021 DUR Board Meeting Minutes Thursday, March 11, 2021 at 6:30 PM Virtual Meeting

o Dennis stated he had hesitations regarding the therapeutic appropriateness of any skeletal muscle relaxant (SMR) used with an opioid. While there is concern with carisoprodol used concurrently, he questioned whether use with other agents from the class was an issue. o Dennis commented that the age of a patient was a factor when weighing the severity of adverse effects associated with concurrent therapy. o Keith commented that Medicare plans don’t cover certain muscle relaxants due to their status on the Beers list. o Bhupesh commented that single agent cyclobenzaprine used short term is not necessarily an issue in younger patients but when addition of an opioid occurs this can become a problem. Over medicating is not always the answer. Referral to physical therapy or orthopedic practitioner for steroidal spinal injections may be a better option when you have a patient with unresolved back pain.

9. Top 50 Prescribers and Pharmacies of Controlled Substances  The Board reviewed the top 50 prescribers and pharmacies of controlled substances report for 4th quarter 2020  Heather stated the report was run by quantity dispensed, rather than prescription count, for the current quarter.

10. Quarterly Opioid Utilization Trends  The Board reviewed the Opioid Utilization Report for 4th quarter 2020. Overall, opioid utilization saw a decline from 1st to 2nd quarter 2020, however, when reviewing 3rd and 4th quarter utilization opioid use is trending back toward 1st quarter utilization amounts. Long acting opioids account for 0.24% of all Medicaid claims during 4th quarter and short acting opioids account for 2.48% of all Medicaid claims during 4th quarter.

11. Butalbital Discussion  In late November 2020, a lock-in (LI) request was received for a patient suspected to be overutilizing butalbital prescriptions. Their case was reviewed during the December cycle, the patient was found to be overutilizing butalbital- acetaminophen-codeine (non-scheduled), and overutilization letters were sent to 5 different prescribers. Non-scheduled butalbital products are not considered part of the LI criteria for CT, therefore, a LI letter was not sent.  During this same time, overutilization of butalbital was reviewed during the December RDUR cycle in tandem with the Migraine newsletter. 357 patients were reviewed for intervention and 304 were targeted for intervention. 23 patients were found to be overutilizing non-scheduled butalbital products.  The Board discussed the potential for adding non-scheduled butalbital medications to the LI criteria but requested additional information regarding abuse potential and risk of physical dependence.  Ken considered the risk of restricting a medication that was not considered a controlled substance by the Food and Drug Administration (FDA).  Heather stated she would follow-up during the June DUR meeting.

12. Quarterly Newsletter  The Board voted to approve the March newsletter with the following changes: Connecticut Medical Assistance Pharmacy Program Drug Utilization Review (DUR) Program DUR Board Meeting

March 2021 DUR Board Meeting Minutes Thursday, March 11, 2021 at 6:30 PM Virtual Meeting

o Page 3, under Cyclobenzaprine, change “Cyclobenzaprine has a half-life of 1-3 days and two case reports found the potential for cyclobenzaprine induced delirium in two octogenarians ” to “Cyclobenzaprine has a half-life of 1-3 days and two case reports found the potential for cyclobenzaprine induced protracted delirium in the very elderly.” o Page 3, under Tizanidine, change “Concurrent use with ciprofloxacin or fluvoxamine is contraindicated due to additive hypotension and motor impairment that can occur” to “Concurrent use with ciprofloxacin or fluvoxamine is contraindicated due to the potentiation of hypotension and bradycardia.” o Page 3, under Tizanidine, change “It is recommended to use caution with other central alpha 2 agonists” to “It is recommended to use with caution with other central alpha 2 agonists and to consider avoiding use in patients receiving multiple antihypertensives.”

New Business 2021 DUR meeting dates  Heather stated that the CMS annual report would be emailed to the members on May 13, one month prior to the June meeting, when the report is scheduled to be reviewed.  The remaining 2021 DUR Board meeting dates were confirmed as the following: o June 10th o September 9th o December 9th  The meeting was adjourned at 8:35 pm.