Gabapentin and Pregabalin: Indications and Abuse

1. Supported in part by Arkansas Blue Cross and Blue Shield and the Office of the Arkansas Drug Director and in partnership with the Arkansas Academy of Family Physicians (AAFP), the Arkansas Medical Society (AMS), the Arkansas State Medical Board (ASMB), the Arkansas Department of Health (ADH) and its Division of Substance Misuse and Injury Prevention (Prescription Drug Monitoring Program—PDMP) Continuing Education Credit: TEXT: 501-406-0076 Event ID:32802-30782

2. Gabapentin and Pregabalin: Indications and Abuse Shona Ray-Griffith, MD Assistant Professor University of Arkansas for Medical Sciences

3. Disclosures • I receive clinical trial support from Neuronetics. • I have received clinical trial support from Sage Therapeutics. • Neither will be discussed today.

4. Objectives • Discuss pharmacology and FDA indications for gabapentin • Discuss pharmacology and FDA indications for pregabalin • Describe abuse of gabapentin and pregabalin

5. Poll Everywhere Text shonaraygrif105 to 22333

7. Fuentes AV, Pineda MD, Venkata KCN. “Comprehension of Top 200 Prescribed Drugs in the US as a Resource for Pharmacy Teaching, Training and Practice” Pharmacy (Basel) 2018;6(2):43

10. Pharmacology of Gabapentin • GABA analog • Does NOT bind to GABA receptor or affect GABA binding, synthesis, uptake, or degradation • Does exert a neuronal inhibitory effect by blocking presynaptic voltage-dependent calcium channels • Peak plasma concentration occurs 3 hours after oral ingestion • Renal elimination • Half-life of 5-7 hours

12. Uses of Gabapentin • Alcohol use disorder • Alcohol withdrawal • Chronic refractory cough • Hiccups • Chronic pruritus • Vasomotor symptoms a/w menopause • Social anxiety disorder* • Focal (partial) seizures • Postherpetic neuralgia • Fibromyalgia • Neuropathic pain • Restless legs syndrome • Postoperative pain

13. Guidelines for Neuropathic Pain • European Federation of Neurological Societies (EFNS) recommends gabapentin as first-line therapy for diabetic neuropathy, postherpetic neuralgia, and central neuropathic pain. • National Institute for Health and Care Excellence (NICE), Canadian Pain Society (CPS), and NeuPSIG (by the International Association for the Study of Pain) guidelines recommend gabapentin as first line therapy for all neuropathic pain.

14. 2014 Lawsuits

15. Pharmacology of Pregabalin • GABA analog • Does NOT bind to GABA receptor or affect GABA binding, synthesis, uptake, or degradation • Does exert a neuronal inhibitory effect by blocking presynaptic voltage-dependent calcium channels • inhibits excitatory neurotransmitter release, including glutamate, NE, serotonin, dopamine, substance P, and calcitonin gen-related peptide) • Antinociceptive and anticonvulsant activity • Peak plasma concentration occurs 3 hours after oral ingestion • Renal elimination • Half-life of 6.3 hours • Schedule V drug

17. Uses of Pregabalin • Chronic refractory cough • Generalized anxiety disorder • Chronic pruritus • Focal (partial) seizures • Social anxiety disorder • Vasomotor symptoms a/w menopause • Fibromyalgia • Neuropathic pain • Diabetic neuropathy • Postherpeticneuralgia • Spinal cord injury-associated neuropathic pain • Critically ill patients • Postoperative pain • Restless legs syndrome

20. Abuse of Gabapentin • Smith RV, Havens JR, Walsh SL. “Gabapentin misuse, abuse and diversion: A systematic review” Addiction 2016;111:1160-1174. • Gabapentin misuse ranged from 15-22% • Gabapentin abuse with a prescription ranged from 40-65% • Prescriptions from a provider are main source of diversion • Used in combination with benzodiazepines, opioids, and alcohol • Cutting agent for heroin • Use for 1) recreational, 2) self-harm, and 3) self-medication

21. Abuse/Dependence of Gabapentin • Mersfelder TL and Nichols WH. “Gabapentin: Abuse, Dependence, and Withdrawal” Annals of Pharmacotherapy 2016; 50(3):229-233 • Abuse and dependence: 8 case reports • All had history of substance use disorder • Potentiates the effects of opioids • Replace effects of cocaine or the withdrawal symptoms from cocaine use • Dosages of gabapentin ranged from 3600-7200mg/day with average of 3000mg/day • Symptoms: euphoria, relaxation, delirium, sedation, confusion, fatigue

22. Withdrawal of Gabapentin • Mersfelder TL and Nichols WH. “Gabapentin: Abuse, Dependence, and Withdrawal” Annals of Pharmacotherapy 2016; 50(3):229-233 • Withdrawal • Onset 24-48 hours after last use (doses of 500-8000mg daily) • Symptoms: agitation (>50%), confusion and disorientation (45%), diaphoresis (36%), GI symptoms (23%), tremor (18%), tachycardia (18%), HTN (18%), insomnia (14%) • Isolated reports of akathisia, catatonia, and seizures • Treatment: reinstate gabapentin

23. Gabapentin/Pregabalin Abuse • HakkinenM, Vuori E, Kalso E, Gergov M, Ojanpera I. “Profiles of pregabalin and gabapentin by postmortem toxicology” Forensic Science International 2014; 241:1-6. • 2010-2011: Toxicology reports on 13,766 cases out of 101,472 deaths (13.6%) • Pregabalin positive in 2.3% of toxicology investigated reports • Gabapentin positive in 0.31% of toxicology investigated reports • 91% of deceased pregabalin users and 88% of deceased gabapentin users were also positive for opioids • Users were significantly younger (under 30 years) • In all cases, other drugs were found.

24. Street Rx • Gabapentin • $1-2/pill for 300mg to 800mg pills • Pregablin • $20 for 75mg pill

26. Questions about the Topic Continuing Education Credit: TEXT: 501-406-0076 Event ID: 32802-30782

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