Gabapentin

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Contents 1 More Specific Terms 2 Introduction 3 Indications 4 Contraindications 5 Dosage 6 Pharmacokinetics 7 Adverse-effects 8 Drug-interactions 9 Mechanism-of-action 10 More General Terms 11 Additional Terms 12 Internet Database 13 References

More Specific Terms

• gabapentin enacarbil (Horizant)

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

• alcohol & benzodiazepine withdrawal
• low back pain
• migraine headache [5], prophylaxis [7]
• behavioral & psychological symptoms of dementia [6]
• hot flashes [7]

Contraindications

• NOT useful for bipolar disorder, restless legs syndrome, muscle cramps, hiccups [7]
  

• pregnancy category = c
• safety in lactation = ?

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. 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%)

• dizziness, somnolence, ataxia, nystagmus, diplopia, amblyopia, nervousness, depression, dysarthria, amnesia, nystagmus, tremor, twitching, psychosis

• systemic (less common 1-10%)

• pruritis, 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]

• * common in elderly [10]
  

• drug adverse effects of anticonvulsants

Drug-interactions

• antacids decrease bioavailability of gabapentin

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

• anticonvulsant

Additional Terms

• pregabalin (Lyrica,'son of gabapentin')
• voltage-dependent Ca+2 channel alpha-2/delta

Internet Database

PubChem: 3446

References

1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
2. Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 702
3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
4. Kaiser Permanente Northern California Regional Drug Formulary, 1998
5. Prescriber's Letter 8(6):34 2001
6. Miller L, Annals of Pharmacotherapy 35:427, 2001 (case report & literature review)
7. Prescriber's Letter 10(8):48 2003
8. Prescriber's Letter 11(10): 2004 Neurontin Use and the Risk of Suicide Detail-Document#: [1] (subscription needed) [2]
9. 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: [3]
10. 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: [4]
11. 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: [5]
12. Prescriber's Letter 17(5): 2010 Off-label Uses of Gabapentin: More Scrutiny Detail-Document#: [6] (subscription needed) [7]
13. Prescriber's Letter 18(11): 2011 Gralise (Extended-Release Gabapentin) Detail-Document#: [8] (subscription needed) [9]

gabapentin (Neurontin, Gralise)