Texas Medicaid

Gabapentinoid Drug Use Evaluation

Educational RetroDUR Initial Study Mailing Follow – up /Restudy

Executive Summary

To determine opportunities for improving the safety and efficacy of drug therapy Purpose: for patients prescribed gabapentinoids.

Gabapentinoids (e.g., pregabalin and gabapentin) are widely used in neurology, psychiatry, and primary healthcare but are increasingly being reported as possessing a potential for misuse.1 The U.S. Food and Drug Administration has Why Issue was Selected: found that the number of patients dispensed gabapentinoids concurrently with opioid analgesics has recently increased, with more than one-half of patients concurrently dispensed both a gabapentinoid and an opioid analgesic.2 Gabapentinoids are central nervous system (CNS) depressants and increase the risk for respiratory depression, coma, and death when combined with opioids.3,6

Performance Indicators Exceptions

(<18 Years) FFS (<18 Years) MCO

1. Gabapentinoid and opioid use (0) 3 (0) 3268 concomitantly

2. Multiple prescribers of

gabapentinoids and (0) 1810  Opioids (0) 2 Program Specific (0) 7955  CNS depressants (0) 6 Information:

3. Gabapentinoid use with:  CNS Depressants (0) 15 (6) 12847  1st generation antihistamines (0) 1 (0) 134

4. Gabapentinoid use in patients (0) 18 (4) 6,662 with respiratory impairment

5. Use of a gabapentinoid without (4) 264 (603) 13,925 an approved indication

Types of Intervention: Cover letter and individual patient profiles.

Main Outcome Measures: Re-measure of performance indicators.

 Reduce the use of gabapentinoids in individuals with: - An unapproved indication Anticipated Results: - Respiratory depression - Concomitant use of other CNS depressants - Concomitant use of opioids

Performance Indicator #1: Gabapentinoid and Opioid Use Concomitantly

Why has this indicator been Gabapentinoids are CNS depressants and increase the risk for respiratory selected? depression, coma, and death when combined with opioids.3,6

How will the patients be

selected?

Candidates (denominator): Patients on a gabapentinoid in the last 90 days. *Does not include patients with seizure, cancer, hospice, limb amputation, and quadriplegia or paraplegia. Exception criteria Candidates that have 60 days or more of overlapping therapy with an opioid in the past 90 days. *Does not include medication assisted treatment (MAT) drugs (numerator): used in the outpatient setting. Performance Indicator #2: Gabapentinoid Use Concomitantly with Central Nervous System Depressants

Why has this indicator been Gabapentinoids are CNS depressants and increase the risk for respiratory selected? depression, coma, and death when combined with other CNS depressants.3,6

How will the patients be

selected?

Candidates (denominator): Patients on a gabapentinoid in the last 90 days. *Does not include patients with seizure, cancer, hospice, limb amputation, and quadriplegic or paraplegic. Candidates that have 60 days or more of overlapping therapy with a CNS Exception criteria depressant (excluding opioids) in the past 90 days. *CNS depressants include (numerator): barbiturates, benzodiazepines, muscle relaxants, antidepressants, antipsychotics, first generation antihistamines, sedative hypnotics.

Performance Indicator #3: Multiple Prescribers, Coordination of Care

Concurrent therapy with opioids or CNS depressants and gabapentinoids from Why has this indicator been multiple prescribers is an opportunity to promote coordination of care and selected? minimize risk of adverse events secondary to respiratory depression, and should be closely monitored.

selected?

Candidates (denominator): Patients on a gabapentinoid in the last 90 days. *Does not include patients with seizure, cancer, hospice, limb amputation, and quadriplegia or paraplegia.

Candidates on an opioid or CNS depressant with 60 days or more of overlap who are receiving the medications from more than one prescriber.*Does not Exception criteria include MAT drugs used in the outpatient setting. CNS depressants include (numerator): barbiturates, benzodiazepines, muscle relaxants, antidepressants, antipsychotics, first generation antihistamines, and sedative hypnotics.

Performance Indicator #4: Gabapentinoid Use with Respiratory Impairment

Why has this indicator been Gabapentinoids are CNS depressants that have an additive respiratory selected? depression effect on those that already have underlying respiratory impairment.6

How will the patients be

selected?

Candidates (denominator): Patients on a gabapentinoid in the last 90 days. *Does not include patients with seizure, cancer, hospice, limb amputation, and quadriplegic or paraplegic.

Candidates who have a diagnosis of respiratory impairment in the last 2 years. Exception criteria *Respiratory impairment includes asthma, chronic obstructive pulmonary (numerator): disease (COPD), sleep apnea, cystic fibrosis, chronic bronchitis, and emphysema.

Performance Indicator #5: Use of a Gabapentinoid without an Approved Indication.

Why has this indicator been To ensure that gabapentinoids are being used for an approved indication.5 selected?

How will the patients be

selected?

Gabapentin 1. Neuropathic pain Exception criteria 2. Seizures 3. Restless legs syndrome (numerator): 4. ALS-amyotrophic lateral sclerosis 5. Fibromyalgia 6. Migraine

Pregabalin 1. Spinal cord injury

References: 1. Schifano F. Misuse and Abuse of Pregabalin and Gabapentin: Cause for Concern? CNS Drugs. 2014; 28(6):491-496. 2. Throckmorton DC, Woodcock J. Combined Gabapentinoid and Opioid Use: The Consequences of Shifting Prescribing Trends. Ann Intern Med. 2018; 169:727–728. doi: 10.7326/M18-2175. Accessed 4/13/2020. 3. Smith RV, Havens JR, and Walsh SL. Gabapentin Misuse, Abuse, and Diversion: a Systematic Review. Addiction. 2016 Jul; 111(7):1160-1174. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5573873/. Accessed 4/13/2020. 4. Drugs. Abuse and Misuse of Pregabalin and Gabapentin. 2017 Mar; 77(4):403-426. doi: 10.1007/s40265-017-0700-x. Accessed 4/13/2020. 5. Gabapentin and Pregabalin. Micromedex Solutions. Truven Health Analytics, Inc. Ann Arbor, MI. Available at: http://www.micromedexsolutions.com. Accessed 4/13/2020 6. U.S Food and Drug Administration. FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR). Available at: https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about- serious-breathing-problems-seizure-and-nerve-pain-medicines-gabapentin-neurontin. Accessed 4/13/2020.

Created: 10/2019 Revised: 4/2020 Template Name: Rules: 44314,44315,44316,44317

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RE: Caring for Patients Using Gabapentinoids

Dear Dr. <>:

Thank you for providing quality care for Texas Fee-For-Service (FFS) Medicaid patients. The content of this letter has been approved by the Texas Drug Utilization Review (DUR) Board, whose function is to promote safe and cost-effective drug therapy and provide opportunities for continuous improvement of care.

This letter was selected to encourage prudent use of gabapentinoid medications in the Texas Medicaid FFS program based on guidance from the US Food and Drug Administration and additional concerns with gabapentinoid misuse and abuse.1-4

 Guidance is available at: https://www.fda.gov/news-events/fda-brief/fda-brief-fda-requires-new-warnings- gabapentinoids-about-risk-respiratory-depression

Claims data indicate that in the Texas Fee-For-Service (FFS) Medicaid program there are approximately 514 individuals being treated with gabapentinoid medications. There were 968 claims for gabapentinoid medications in a recent 90 day period.

Total Texas Medicaid FFS Specific Data Number of Patients with Gabapentinoid Indicator Summary Opportunities* <18 Years >18 Years  Gabapentinoid and opioid use concomitantly 0 3  Multiple prescribers of gabapentinoids and 0 -Opioids 2

-CNS depressants 0 6

 Gabapentinoid use with: 0 15 -CNS Depressants 0 6 -1st generation antihistamines  Gabapentinoid use in patients with respiratory impairment 0 18  Use of a gabapentinoid without an approved indication 4 264 *Based on data through 5/29/2020

P.O. Box 13247 • Austin, Texas 78711-3247 • 512-424-6500 • hhs.texas.gov

The enclosed patient profiles reflect one or more of the above issues and are provided as a medical record reminder for when your patients return for their next appointments.

We acknowledge that there may be clinical variables influencing an individual patient’s management that are not apparent in claims data. However, we believe the issues identified may assist you in caring for your patient(s). It is possible that your license number may have been inadvertently assigned to the claim as an error at the pharmacy during the billing process. Also, some prescribed medications as well as some recommended laboratory monitoring or physical examinations may not appear on the patient’s profile because they may have been privately purchased or were not billable to Medicaid Services. We thank you for reviewing this information and caring for Texas Medicaid patients, and we welcome the opportunity to discuss any comments or concerns you may have about our quality management program. Please feel free to call our office at 1-866-923-7208 with questions or concerns. If your mailing address is incorrect, it must be updated through the Texas Medical Board online at http://www.tmb.state.tx.us/page/change-address.

Sincerely,

Medicaid Drug Use Review Board Vendor Drug Program H-630

Gabapentinoid Indicator Summary Gabapentinoid and Opioid Use Concomitantly  Gabapentinoids include gabapentin (marketed as Neurontin®, Gralise®, and generics), gabapentin enacarbil (marketed as Horizant®), and pregabalin (marketed as Lyrica®, Lyrica® CR, and generics).4,5  Gabapentinoids are CNS depressants and increase the risk for respiratory depression, coma, and death when combined with opioids.1,4  This combination is particularly dangerous to the elderly and should be avoided, per the Beers Criteria®.6 Gabapentinoid Use Concomitantly with Central Nervous System Depressants  Gabapentinoids are CNS depressants and increase the risk for respiratory depression, coma, and death when combined with other CNS depressants.4  CNS depressants include opioids, anti-anxiety medications, antidepressants, sedating antipsychotics, antihistamines, and sedative hypnotics. 4 Multiple Prescribers, Coordination of Care  Concurrent therapy with opioids or CNS depressants and gabapentinoids from multiple prescribers is an opportunity to promote coordination of care and minimize the risk of adverse events secondary to respiratory depression.  If concurrent therapy is prescribed, it is important to start with low doses and carefully titrate with close monitoring. Patient education on the potential for CNS and respiratory depression and possible symptoms (e.g. confusion, unusual dizziness, lethargy, shallow breathing, bluish-colored skin/lips, etc.) should also be provided.4 Gabapentinoid Use with Respiratory Impairment  Gabapentinoids are CNS depressants that have an additive respiratory depression effect on those that already have underlying respiratory impairment.4  Elderly patients are at higher risk of respiratory depression and death due to reduced lung function.4-6 Use of a Gabapentinoid without an Approved Indication  Encourage the use of gabapentinoids for approved indications or indications with a significant amount of supporting data.5  Despite having limited FDA-approved indications for use, gabapentin was the 6th most commonly prescribed medication in the United States in 2018 and accounted for over 67 million prescriptions.7  Off-label use lacking strong clinical supporting evidence can expose patients to unnecessary risks.4,8,9

References: 1. Throckmorton DC, Woodcock J. Combined Gabapentinoid and Opioid Use: The Consequences of Shifting Prescribing Trends. Ann Intern Med. 2018; 169:727–728. doi: 10.7326/M18-2175. Accessed 6/4/2020. 2. Smith RV, Havens JR, and Walsh SL. Gabapentin Misuse, Abuse, and Diversion: a Systematic Review. Addiction. 2016 Jul; 111(7):1160-1174. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5573873/. Accessed 6/4/2020. 3. Drugs. Abuse and Misuse of Pregabalin and Gabapentin. 2017 Mar; 77(4):403-426. doi: 10.1007/s40265- 017-0700-x. Accessed 6/4/2020. 4. U.S Food and Drug Administration. FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR). Available at: https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-serious-breathing-problems- seizure-and-nerve-pain-medicines-gabapentin-neurontin. Accessed 6/4/2020. 5. Gabapentin and Pregabalin. Micromedex Solutions. Truven Health Analytics, Inc. Ann Arbor, MI. Available at: http://www.micromedexsolutions.com. Accessed 6/4/2020.

6. American Geriatrics Society. 2019 Updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2019;67(4):674-694. Available at: https://www.aafp.org/afp/2019/1201/p672.pdf. Accessed 6/5/2020. 7. Medicine use and spending in the U.S. — a review of 2018 and outlook to 2023. Parsippany, NJ: IQVIA Institute for Human Data Science, 2019. Available at: https://www.iqvia.com/insights/the-iqvia- institute/reports/medicine-use-and-spending-in-the-us-a-review-of-2018-and-outlook-to-2023. Accessed 6/5/2020. 8. Goodman CW, Brett AS. Gabapentin and pregabalin for pain—is increased prescribing a cause for concern? N Engl J Med. 2017; 377(5): 411-414. Available at: https://www.nejm.org/doi/10.1056/NEJMp1704633. Accessed 6/5/2020. 9. Goodman CW, Brett AS. Gabapentinoids for pain: potential unintended consequences. Am Fam Physician. 2019;100(11):672-675. Available at: https://www.aafp.org/afp/2019/1201/p672.html. Accessed 6/5/2020.

Off-Label Use of a Gabapentinoid: According to submitted pharmacy and medical claims, it appears that your patient is receiving a gabapentinoid (i.e., gabapentin, pregabalin) for a diagnosis other than approved indications. Off-label gabapentinoid use has been linked to higher rates of misuse and abuse. Please review your patient’s history and determine if alternative therapy is appropriate.

Gabapentinoid with a History of Substance Abuse: According to submitted pharmacy and medical claims, it appears that your patient is receiving a gabapentinoid (i.e., gabapentin, pregabalin) and has a history of substance abuse. Studies have shown that patients with a history of substance abuse are at higher risk of abusing a gabapentinoid. Please review your patient’s history and determine if alternative therapy is appropriate.

Concurrent Therapy with Gabapentinoids and Opioids-Multiple Prescribers: According to submitted pharmacy and medical claims, it appears that your patient is receiving a gabapentinoid (i.e., gabapentin, pregabalin) concurrently with an opioid from different prescribers. The use of this drug combination has been associated with adverse drug events including CNS depression and a statistically significant increase in the odds of opioid-related death. Please review your patient’s history and determine if alternative therapy is appropriate.

Concurrent Therapy with Gabapentinoids and Opioids: According to submitted pharmacy and medical claims, it appears that your patient is receiving a gabapentinoid (i.e., gabapentin, pregabalin) concurrently with an opioid. The use of this drug combination has been associated with adverse drug events including CNS depression and a statistically significant increase in the odds of opioid-related death. Please review your patient’s history and determine if alternative therapy is appropriate.

Gabapentinoid High Dose: According to submitted pharmacy and medical claims, it appears that your patient is receiving a gabapentinoid (i.e., gabapentin, pregabalin) at a dose higher than the recommended by the labeling. The maximum daily dose for gabapentin is 3,600mg and 660mg for pregabalin. Please review your patient’s history and determine if an alternative dose is appropriate.