gabapentin (Neurontin, Gralise)
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Introduction
Tradename: Neurontin.
Indications
- partial seizures
- panic disorder
- anxiety disorder
- attention deficit disorder
- neuropathic pain syndrome*
- post herpetic neuralgia (FDA approved)[7]
- diabetic neuropathy[7]*
- fibromyalgia[11]
- off-label use, effectiveness questionable[12]; number needed to treat = number needed to harm = 8; NNT = 6-7[20]
- marked increase in use for pain 2002-2015[19]
- alcohol & benzodiazepine withdrawal
- low back pain (marginally better than placebo)[17]
- migraine headache[5], prophylaxis[7]
- behavioral & psychological symptoms of dementia[6]
- hot flashes[7]
- essential tremor[14]
- restless legs syndrome[14]
- alcoholism, maintenance of abstinence[16]
- off label use to unexplained chronic cough[15]
* only weak evidence supports use of gabapentin for diabetic neuropathy; only pregabalin is FDA approved for this indication[23]
* minimal evidence supports use of gabapentin for nondiabetic neuropathic pain syndrome
Contraindications
- NOT useful for bipolar disorder, restless legs syndrome, muscle cramps, hiccups[7]
- ineffective for acute shingles, traumatic nerve injury, burn injury, sickle cell pain, complex regional pain syndrome[23]
- GRS11 cites falls in the elderly as a relative contraindication[25]
- perioperative gabapentinoids of minimal benefit for postoperative pain[27]
- time to resolution of postoperative pain is not shortened by gabapentin[21]
- perioperative gabapentin increases risk of delirium (RR=1.3), new antipsychotic use (RR=1.2), & pneumonia (RR=1.1) in elderly patients after major surgery[26]
Dosage
- start 300 mg PO QHS
- increase over a few days to 300-600 mg PO TID
- max 3.6 g/day
- therapeutic doses > 900 mg/day
- Pediatrics: Start 15 mg/kg/day, max 45 mg/kg/day.
Tabs: 100, 300, 400 mg.
* no dosage adjustment in liver failure[15] Dose adjustment in renal failure:
| creatinine clearance | dose |
|---|---|
| > 60 mL/min | 400 mg TID |
| 30-60 mL/min | 300 mg BID |
| 15-30 mL/min | 300 mg QD |
| < 15 mL/min | 300 mg QOD |
200-300 mg following each 4 hours of hemodialysis
Pharmacokinetics
- oral bioavailability is about 60%
- largely NOT bound to plasma proteins
- excreted unchanged in the urine
- elimination 1/2life is 5-7 hours
elimination via kidney
1/2life = 5-7 hours
protein binding = 0 %
elimination by hemodialysis = +
Adverse effects
- neurologic (common > 10%)
- systemic (less common 1-10%)
- pruritus, dyspepsia, dryness of throat/mouth, constipation, back pain, peripheral edema, myalgia, impotence, leukopenia, weight gain*, rhinitis, pharyngitis, cough, vasodilation
- 25 cases of suicide reported in patients on neurontin; no proof of link to neurontin[8]
- no evidence of cognitive impairment[10]
- respiratory depression in patients with COPD[24]
- low incidence of skin rash[15]
* common in elderly[10], otherwise well-tolerated in the elderly
Drug interactions
- antacids decrease bioavailability of gabapentin
- much of the increase in use 2002-2015 in patients also using benzodiazepines &/or opioids[19]
- prevalence of depression is 61% among patients coprescribed gabapentin + cyclobenzaprine[22]
- increased risk of respiratory depression in combination with opiates[24]
- drug interaction(s) anticonvulsants with anti-bacterial agents
- drug interaction(s) anticonvulsants with statins
- drug interaction(s) of gabapentin with opiates
Laboratory
Mechanism of action
- structurally related to GABA, but does not interact with GABA receptors
- binds to alpha-2 delta subunit of voltage-gated Ca+2 channel
- membrane stabilizer
- may affect hypothalamic thermoregulatory centers
More general terms
More specific terms
Additional terms
Component of
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 702
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ 5.0 5.1 Prescriber's Letter 8(6):34 2001
- ↑ 6.0 6.1 Miller L, Annals of Pharmacotherapy 35:427, 2001 (case report & literature review)
- ↑ 7.0 7.1 7.2 7.3 7.4 7.5 Prescriber's Letter 10(8):48 2003
- ↑ 8.0 8.1 Prescriber's Letter 11(10): 2004 Neurontin Use and the Risk of Suicide Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=201005&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Journal Watch 25(9):74, 2005 Salinsky MC, Storzbach D, Spencer DC, Oken BS, Landry T, Dodrill CB. Effects of topiramate and gabapentin on cognitive abilities in healthy volunteers. Neurology. 2005 Mar 8;64(5):792-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15753411
- ↑ 10.0 10.1 10.2 Journal Watch 25(15):118-19, 2005 Rowan AJ, Ramsay RE, Collins JF, Pryor F, Boardman KD, Uthman BM, Spitz M, Frederick T, Towne A, Carter GS, Marks W, Felicetta J, Tomyanovich ML; VA Cooperative Study 428 Group. New onset geriatric epilepsy: a randomized study of gabapentin, lamotrigine, and carbamazepine. Neurology. 2005 Jun 14;64(11):1868-73. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15955935
- ↑ 11.0 11.1 Arnold LM, Goldenberg DL, Stanford SB, Lalonde JK, Sandhu HS, Keck PE Jr, Welge JA, Bishop F, Stanford KE, Hess EV, Hudson JI. Gabapentin in the treatment of fibromyalgia: A randomized, double-blind, placebo-controlled, multicenter trial. Arthritis Rheum. 2007 Mar 28;56(4):1336-1344 [Epub ahead of print] PMID: https://www.ncbi.nlm.nih.gov/pubmed/17393438
- ↑ 12.0 12.1 Prescriber's Letter 17(5): 2010 Off-label Uses of Gabapentin: More Scrutiny Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260502&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Prescriber's Letter 18(11): 2011 Gralise (Extended-Release Gabapentin) Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=271109&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 14.0 14.1 14.2 Deprecated Reference
- ↑ 15.0 15.1 15.2 15.3 Medical Knowledge Self Assessment Program (MKSAP) 16, 17, 19. American College of Physicians, Philadelphia 2012, 2015, 2021
- ↑ 16.0 16.1 Mason BJ et al. Gabapentin treatment for alcohol dependence: A randomized clinical trial. JAMA Intern Med 2013 Nov 4 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24190578
- ↑ 17.0 17.1 Goodman CW, Brett AS. Gabapentin and pregabalin for pain - Is increased prescribing a cause for concern? N Engl J Med 2017 Aug 3; 377:411 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28767350 Free full text
- ↑ Shanthanna H, Gilron I, Rajarathinam M et al Benefits and safety of gabapentinoids in chronic low back pain: A systematic review and meta-analysis of randomized controlled trials. PLOS Medicine. August 15, 2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28809936 Free Article <Internet> http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002369
- ↑ 19.0 19.1 19.2 Johansen ME. Gabapentinoid use in the United States 2002 through 2015. JAMA Intern Med 2018 Jan 2; PMID: https://www.ncbi.nlm.nih.gov/pubmed/29297045 https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2666788
- ↑ 20.0 20.1 Moore A, Derry S, Wiffen P Gabapentin for Chronic Neuropathic Pain JAMA. 2018;319(8):818-819. February 27, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29486015 https://jamanetwork.com/journals/jama/article-abstract/2673524
Wallach JD, Ross JS. Gabapentin Approvals, Off-Label Use, and Lessons for Postmarketing Evaluation Efforts. JAMA. 2018;319(8):776-778. February 27, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29486013 https://jamanetwork.com/journals/jama/article-abstract/2673522 - ↑ 21.0 21.1 Hah J, Mackey SC, Schmidt P et al. Effect of perioperative gabapentin on postoperative pain resolution and opioid cessation in a mixed surgical cohort: A randomized clinical trial. JAMA Surg 2018 Apr 1; 153:303 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29238824 https://jamanetwork.com/journals/jamasurgery/fullarticle/2664958
- ↑ 22.0 22.1 Qato DM, Ozenberger K, Olfson M Prevalence of Prescription Medications With Depression as a Potential Adverse Effect Among Adults in the United States. JAMA. 2018;319(22):2289-2298 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29896627 https://jamanetwork.com/journals/jama/fullarticle/2684607
- ↑ 23.0 23.1 23.2 Goodman CW, Brett AS. A clinical overview of off-label use of gabapentinoid drugs. JAMA Intern Med 2019 Mar 25; PMID: https://www.ncbi.nlm.nih.gov/pubmed/30907944 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2728959
- ↑ 24.0 24.1 24.2 FDA Drug Safety Communication. Dec 19, 2019 FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR). When used with CNS depressants or in patients with lung problems https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-serious-breathing-problems-seizure-and-nerve-pain-medicines-gabapentin-neurontin
- ↑ 25.0 25.1 Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
- ↑ 26.0 26.1 George J Gabapentin After Surgery Ups Risks in Older Adults. Delirium, new antipsychotic use, and pneumonia more common. MedPage Today September 20, 2022 https://www.medpagetoday.com/neurology/painmanagement/100827
Park CM, Inouye SK, Marcantonio ER et al Perioperative Gabapentin Use and In-Hospital Adverse Clinical Events Among Older Adults After Major Surgery. JAMA Intern Med. Published online September 19, 2022. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36121671 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2796501
Bongiovanni T, Anderson TS, Marcum ZA. Perioperative Gabapentin Use in Older Adults. Revisiting Multimodal Pain Management. JAMA Intern Med. 2022;182(11):1127-1128. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36121647 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2796503 - ↑ 27.0 27.1 Verret M et al. Perioperative use of gabapentinoids for the management of postoperative acute pain: A systematic review and meta-analysis. Anesthesiology 2020 Aug; 133:265. PMID: https://www.ncbi.nlm.nih.gov/pubmed/32667154 https://anesthesiology.pubs.asahq.org/article.aspx?articleid=2766309
Kharasch ED et al. Perioperative gabapentinoids: Deflating the bubble. Anesthesiology 2020 Aug; 133:251. PMID: https://www.ncbi.nlm.nih.gov/pubmed/32667153 https://anesthesiology.pubs.asahq.org/article.aspx?articleid=2766307