Indian Journal of Palliative Care
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  In this Article
    Abstract
    Gabapentin
    Pharmacology
    Cautions
    Undesirable effects
    Dose and use
    Stopping gabapentin
    Supply
    References
    Article Tables

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DRUG HIGHLIGHT
Year : 2003  |  Volume : 9  |  Issue : 2  |  Page : 71-74

Palliativedrugs.com therapeutic highlights: gabapentin


1 Emeritus Clinical Reader in Palliative Medicine, Oxford University, United Kingdom
2 Clinical Reader in Palliative Medicine and Medical Oncology, Nottingham University, United Kingdom
3 Senior Pharmacist palliativedrugs.com, Nottingham, United Kingdom
4 Senior Pharmacist, Christian Medical College, Vellore, India

Correspondence Address:
Andrew Wilcock
Hayward House, City Hospital Nottingham NG5 1PB
United Kingdom
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Source of Support: None, Conflict of Interest: None


Rights and PermissionsRights and Permissions

   Abstract 

This is the second in a series of highlights drawn from the www.palliativedrugs.com website. The website provides free access to the Palliative Care Formulary, a monthly newsletter and a bulletin board for advice to be given and received. With almost 10,000 professional members it is the largest palliative care resource of its kind.



How to cite this article:
Twycross R, Wilcock A, Charlesworth S, Thresiamma M P. Palliativedrugs.com therapeutic highlights: gabapentin. Indian J Palliat Care 2003;9:71-4

How to cite this URL:
Twycross R, Wilcock A, Charlesworth S, Thresiamma M P. Palliativedrugs.com therapeutic highlights: gabapentin. Indian J Palliat Care [serial online] 2003 [cited 2020 Oct 26];9:71-4. Available from: https://www.jpalliativecare.com/text.asp?2003/9/2/71/19879



   Gabapentin Top


Class: Anti-epileptic.

Indications: Adjunctive treatment for partial seizures with or without secondary generalisation; [1,2] neuropathic pain of any cause.[3-12]


   Pharmacology Top


Gabapentin is a chemical analogue of GABA but does not act as a GABA-receptor agonist. It binds to a specific site in the CNS, gabapentin-binding protein, and interacts with a2d calcium channels in the CNS.[13] It increases GABA synthesis and release but its exact mechanism of action is complex and not fully understood. Absorption is by a saturable mechanism and bio-availability is more than halved as the dose increases from 100mg to 1200mg. Antacids containing aluminium or magnesium reduce gabapentin bio-availability by 10-25%. It is not protein-bound and freely crosses the blood-brain barrier. It is excreted unchanged by the kidneys and cumulates in renal impairment. The halflife increases to 50h when creatinine clearance is <30ml/min and to over 5 days in anuria. Initial drowsiness or dizziness occurs in 50% of patients and generally resolves over 7-10 days of use.[12] Gabapentin has few drug interactions. Cimetidine impairs the renal excretion of gabapentin but not to a clinically important extent. It does not interact with anti-retroviral antibiotics. Gabapentin is increasingly used for neuropathic pain.[3-12] However, there is no evidence that it is more effective than older anti-epileptics.[14] Although in an open study in diabetic neuropathy, gabapentin provided better relief than amitriptyline,[15] in a randomised controlled trial no difference was detected.[16] In motor neurone disease (amyotrophic lateral sclerosis), gabapentin 800mg t.d.s slowed decrease in arm strength marginally (p>0.5) over a 6-month period.[17] It reduces spasticity and muscle spasm in multiple sclerosis.[18] There is a report of gabapentin abolishing opioid-related myoclonus.[19]

Bio-availability PO 100mg, 74%; 300mg, 60%; 600mg, 49%; 1200mg, 33%.

Onset of action 1-3h.

Time to peak plasma concentration 2-3h PO.

Plasma halflife 5-7h, increasing to 2-5 days in severe renal failure.

Duration of action probably 8-12h.


   Cautions Top


Renal impairment; psychotic illness; absence seizures; false positive readings for urinary protein with Ames N-Multistix SG; aluminium-and magnesium-containing compounds reduce bio-availability.


   Undesirable effects Top


For full list, see manufacturer's SPC.

Very common (>10%): drowsiness, dizziness.

Common (>1-10%): anxiety, amnesia, fatigue, tremor, nystagmus, diplopia, amblyopia, dysarthria, ataxia, myalgia, arthralgia, peripheral oedema, weight gain, dry mouth, dyspepsia, pharyngitis, diarrhoea.

Uncommon (0.1-1%): leucopenia, impotence, gynaecomastia.[20]


   Dose and use Top


Gabapentin should be given at least 2h after antacids containing aluminium or magnesium. For both neuropathic pain and epilepsy, a rapid upward titration is suggested in the SPC [Table - 1]. However, in order to reduce undesirable effects, a slower titration of the initial dose of gabapentin over several weeks is advisable in elderly patients, those with renal impairment (see below) or if receiving other CNS depressant drugs. [12,21] The dose is titrated to achieve greatest benefit without unacceptable undesirable effects. The maximum licensed doses for neuropathic pain and epilepsy are 1800mg/day and 2400mg/ day respectively, but up to 3600mg/day has been used for both indications. The dose of gabapentin should be adjusted in adults with renal impairment and those on haemodialysis [Table - 2].[21] As creatinine clearance declines with age, the maximum tolerated dose is likely to be lower in the elderly, e.g. 1200mg/day. If required the capsules can be opened and the contents mixed with water, fruit juice, apple sauce, etc.[22]


   Stopping gabapentin Top


To avoid precipitating seizures or pain, gabapentin should be withdrawn gradually over at least 1 week.


   Supply Top


Gabantin (Sun Pharma 044 2835 0815)

Capsules 300 mg, 400 mg

(100 mg prepared extemporaneously) 28 days @300mgtds=Rs.824/-

 
   References Top

1.Anonymous (1994) Gabapentin - a new antiepileptic drug. Drug and Therapeutics Bulletin. 32:29-30.  Back to cited text no. 1    
2.Chadwick D (1994) Gabapentin. Lancet. 343:89-91.  Back to cited text no. 2    
3.Caraceni A et al. (1999) Gabapentin as an adjuvant to opioid analgesia for neuropathic cancer pain. Journal of Pain and Symptom Management. 17:441-445.  Back to cited text no. 3    
4.Schachter S and Sauter M (1996) Treatment of central pain with gabapentin: case reports. Journal of Epilepsy. 9:223-225.  Back to cited text no. 4    
5.Backonja M et al. (1998) Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: a randomized controlled trial. Journal of the American Medical Association. 280:1831-1836.  Back to cited text no. 5    
6.Rowbotham M et al. (1998) Gabapentin for the treatment of postherpetic neuralgia: a randomised controlled trial. Journal of the American Medical Association. 280:1837-1842.  Back to cited text no. 6    
7.Rice ASC et al. (2001) Gabapentin in postherpetic neuralgia: a randomised, double blind, placebo-controlled study. Pain. 94:215-224.  Back to cited text no. 7    
8.Serpell MG et al. (2002) Gabapentin in neuropathic pain syndromes: a randomised, double-blind, placebo-controlled trial. Pain. 99:557-566.  Back to cited text no. 8    
9.Bone M et al. (2002) Gabapentin in post amputation phantom limb pain: a randomised, double-blind, placebo-controled, cross-over study. Regional Anaesthesia and Pain Medicine. 27:481-486.  Back to cited text no. 9    
10.Pandey CK et al. (2002) Gabapentin for the treatment of pain in guillain-barre syndrome: a double-blinded, placebo-controlled, crossover study. Anaesthesia and Analgesia. 95:1719-1723.  Back to cited text no. 10    
11.Pelham A et al. (2002) Gabapentin for coeliac plexus pain. Palliative Medicine. 16:355-356.  Back to cited text no. 11    
12.Backonja M and Glanzman RL (2003) Gabapentin dosing for neuropathic pain: Evidence from randomized, placebo controlled clinical trials. Clinical Therapeutics. 25:81-104.  Back to cited text no. 12    
13.Taylor C et al. (1998) A summary of mechanistic hypothesis of gabapentin pharmacology. Epilepsy and Research. 29:223-249.  Back to cited text no. 13    
14.Collins S et al. (2000) Antidepressants and anticonvulsants for diabetic neuropathy and postherpetic neuralgia: a quantitative systematic review. Journal of Pain and Symptom Management. 20:449-458.  Back to cited text no. 14    
15.Dallocchio C et al. (2000) Gabapentin vs. amitriptyline in painful diabetic neuropathy: an open-label pilot study. Journal of Pain and Symptom Management. 20:280-285.  Back to cited text no. 15    
16.Morello CM et al. (1999) Randomized double-blind study comparing the efficacy of gabapentin with amitriptyline on diabetic peripheral neuropathic pain. Archives of Internal Medicine. 159:1931-1937.  Back to cited text no. 16    
17.Miller R et al. (1996) Placebo-controlled trial of gabapentin in patients with amyotrophic lateral sclerosis. Western Amyotrophic Lateral Sclerosis Study Group. Neurology. 47:1383-1388.  Back to cited text no. 17    
18.Cutter NC et al. (2000) Gabapentin effect on spasticity in multiple sclerosis: a placebo controlled, randomized trial. Archives of Physical Medicine and Rehabilitation. 81:164-169.  Back to cited text no. 18    
19.Mercadante S et al. (2001) Gabapentin for opioid-related myoclonus in cancer patients. Support Care Cancer. 9:205-206.  Back to cited text no. 19    
20.Zylicz Z (2000) Painful gynecomastia: an unusual toxicity of gabapentin? Journal of Pain and Symptom Management. 20:2-3.  Back to cited text no. 20    
21.Dworkin RH et al. (2003) Advances in neuropathic pain. Archives of Neurology. 60:1524-1534.  Back to cited text no. 21    
22.Gidal B et al. (1998) Gabapentin absorption: effect of mixing with foods of varying macronutrient composition. Annals of Pharmacotherapy. 32:405-409.  Back to cited text no. 22    


    Tables

[Table - 1], [Table - 2]



 

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