Gabapentin is an antiepileptic used as monotherapy or adjunctive therapy in the treatment of partial seizures with or without secondary generalisation. It is not generally considered effective for absence seizures. Although gabapentin is an analogue of gamma-aminobutyric acid (GABA), it is neither a GABA agonist nor antagonist and its mechanism of action is unknown. Gabapentin is also used in the treatment of neuropathic pain.
In the UK, the initial oral dose of gabapentin for the treatment of epilepsy is 300 mg on the first day of treatment, 300 mg twice daily on the second day, and 300 mg three times daily on the third day; thereafter the dose may be increased in increments of 300 mg every 2 to 3 days until effective antiepileptic control is achieved, which is usually within the range of 0.9 to 3.6 g daily. Higher doses up to amaximum of 4.8 g daily have been reported to be well tolerated. Similar doses are used in the United States of America. The total daily dose should be taken in three equally divided doses and the maximum dosage interval should not exceed 12 hours.
For details of doses in children, see below.
In the treatment of neuropathic pain, doses should be titrated to a usual maximum of 1.8 g daily in three divided doses, in a similar manner to that recommended above for the treatment of epilepsy. Higher doses have sometimes been given.
As with other antiepileptics, withdrawal of gabapentin therapy or transition to or from another type of antiepileptic therapy should be made gradually to avoid precipitating an increase in the frequency of seizures. Licensed product information recommends reducing the dose gradually over at least 7 days. For a discussion on whether or not to withdraw antiepileptic therapy in seizure-free patients.
Dosage of gabapentin should be reduced in patients with renal impairment (see below).
Gabapentin enacarbil (XP-13512) has been investigated as a prodrug of gabapentin.
Administration in children. In the UK, for the treatment of partial seizures with or without secondary generalisation, gabapentin is licensed for use as adjunctive therapy in children aged 6 years and over and as monotherapy in those aged 12 years and over. As adjunctive therapy, gabapentin may be given in an initial oral dose of 10 to 15 mg/kg daily, titrated over a period of about 3 days until effective antiepileptic control is achieved, which is usually within the range 25 to 35 mg/kg daily. Higher doses up to a maximum of 50 mg/kg daily have been reported to be well tolerated. Although not licensed for use in younger children, the BNFC suggests that similar initial doses may be used in those aged 2 to 12 years; maintenance doses of 10 to 20 mg/kg 3 times daily (up to 900 mg daily for children weighing 36 kg or under, or 1.2 g daily for those over 36 kg) are also recommended. Older children may be given the usual adult dosage regimen (see above) titrated to a maximum of 2.4 g daily. When used as monotherapy, the usual adult dosage regimen is given. In the USA, gabapentin is licensed for adjunctive use in children aged 3 years and over. Initial doses are as for the UK; the maintenance dose for children aged 3 to 4 years is 40 mg/kg daily, and for those aged 5 years and over is 25 to 35 mg/kg daily. Children aged 12 years and over may be given the usual adult dosage regimen (see above).
The total daily dose should be taken in 3 equally divided doses and the maximum dosage interval should not exceed 12 hours. For a pharmacokinetic study suggesting that initial doses in younger children should be proportionately higher than in older ones, see above.
Administration in renal impairment. Reduced doses of gabapentin are recommended for patients with renal impairment or those undergoing haemodialysis. Licensed UK product information recommends the following maintenance doses based on creatinine clearance (CC) and given as 3 divided doses:
- CC 50 to 79 mL/minute: 600 to 1800 mg daily
- CC 30 to 49 mL/minute: 300 to 900 mg daily
- CC 15 to 29 mL/minute: 300 mg on alternate days to 600 mg daily
- CC less than 15 mL/minute: 300 mg on alternate days to 300 mg daily
For those undergoing haemodialysis who have never received gabapentin, the recommended loading dose is 300 to 400 mg followed by 200 to 300 mg after each 4 hours of haemodialysis. On dialysis-free days no doses of gabapentin should be given (see also Overdosage, above).
Ciguatera poisoning. Gabapentin has relieved some of the neurological symptoms associated with ciguatera poisoning (see Mannitol).
Epilepsy. Gabapentin is used in epilepsy as adjunctive therapy for partial seizures with or without secondary generalisation in patients refractory to standard antiepileptics. In double-blind placebo-controlled studies in such patients seizure frequency was reduced when gabapentin was added to treatment. Long-term efficacy has been encouraging, and its lack of potential for interactions with other antiepileptics is considered to make it particularly suitable for adjunctive treatment. Dosage is adjusted against clinical response rather than by monitoring blood concentrations. Gabapentin is also used as monotherapy in partial epilepsy; its efficacy as adjunctive treatment in generalised seizures remains to be determined. Gabapentin has been found to be effective as adjunctive therapy in children with refractory partial seizures.
Headache. Benefit has been reported from the use of gabapentin in the prophylaxis of migraine. Gabapentin may also be effective in the management of cluster headache, and has been tried in the prophylaxis of chronic daily headache.
Hiccup. Gabapentin has been tried in the treatment of hiccups.
Hot flushes. Gabapentin appears to be of benefit in the management of hot flushes associated with treatment of breast cancer; a study involving 420 women with breast cancer experiencing hot flushes (excluding women on active chemotherapy, but most of whom were receiving adjuvant endocrine therapy), found that a dose of 900 mg daily in three divided doses for 8 weeks was effective, although a dose of 300 mg daily was not. There is also evidence of benefit from gabapentin in the same dose (900 mg daily) in women experiencing hot flushes as a symptom of the menopause. Another randomised placebo-controlled study found gabapentin 2.4 g daily to be as effective as conjugated oestrogens 625 micrograms daily in the treatment of hot flushes in postmenopausal women.
Lesch-Nyhan syndrome. The severe self-mutilation that occurs in patients with Lesch-Nyhan syndrome has been reported to improve in those given antiepileptics such as gabapentin.
Motor neurone disease. Interest has been shown in gabapentin as a potential therapy for amyotrophic lateral sclerosis (see Motor Neurone Disease) because it may inhibit glutamate formation. Results from an early study demonstrated a trend towards a beneficial effect; however, a randomised trial failed to confirm any benefit from gabapentin on disease progression or symptoms.
Multiple sclerosis. Gabapentin has been found to control pain, spasm, and spasticity in patients with multiple sclerosis. It may also be of benefit in acquired nystagmus secondary to multiple sclerosis.
Neuropathic pain. Antiepileptics are among the drugs used to manage neuropathic pain, which is often insensitive to opioid analgesics (see Choice of Analgesic). Although carbamazepine appears to be the usual choice, gabapentin is also given in the treatment of neuropathic pain, including central pain, complex regional pain syndrome, post-herpetic neuralgia, trigeminal neuralgia, and painful diabetic neuropathy.
Parkinsonism. While some overall ratings of Parkinson’s disease appeared to be improved by gabapentin in a double-blind study involving 19 patients with advanced parkinsonism, improvements in individual signs and symptoms were not significant. It was also reported that 5 of 6 other patients with progressive supranuclear palsy had experienced worsening of their disease when given gabapentin. Another study in 15 patients with motor complications failed to find any clinically significant benefit from gabapentin therapy.
Postoperative pain. There is growing interest in the use of analgesic adjuvants including antiepileptics such as gabapentin to modulate opioid dosage and efficacy for postoperative pain. A systematic review considered that evidence of benefit for gabapentin in acute pain was lacking, and noted that more effective analgesics for this indication were available. However, a later systematic review found that peri operative use of gabapentin effectively reduced opioid consumption and postoperative pain; further studies were considered warranted. It has been suggested that perioperative use of gabapentin may have other benefits, including pre-operative anxiolysis, attenuation of the haemodynamic response to intubation, and reduction in postoperative nausea and vomiting.
Psychiatric disorders. Gabapentin has psychotropic properties and has been tried in the management of several psychiatric disorders, including as an adjunct in the treatment of resistant depression and in the treatment of post-traumatic stress disorder. Although early open studies found that gabapentin may be of benefit in patients with bipolar disorder randomised controlled trials have so far failed to confirm this effect. Gabapentin is under investigation for the treatment of social anxiety disorder (see under Phobic Disorders).
Restless legs syndrome. The aetiology of restless legs syndrome (see Sleep-associated Movement Disorders) is obscure and treatment has been largely empirical. Two small randomised double-blind crossover studies found 6 weeks of treatment with gabapentin to produce improvement in symptoms; in patients undergoing haemodialysis the effects were seen with a dose of 300 mg after each of the 3 dialysis sessions per week, although in patients with idiopathic disease the mean effective dose was 1.855 g daily.
A prodrug of gabapentin, gabapentin enacarbil, is reported to be under investigation for the treatment of restless legs syndrome.
Soft-tissue rheumatism. Gabapentin may be of benefit in some patients with fibromyalgia. In a randomised controlled study treatment with oral gabapentin 1.2 to 2.4 g daily in 75 patients produced a greater improvement in mean pain score over 12 weeks than placebo in 75 controls. Sleep problems were also improved, but there was no difference between the groups in a depression rating scale. The drug was generally well tolerated.
Stiff-man syndrome. Gabapentin may improve the symptoms of stiff-man syndrome (see under Muscle Spasm in Uses of Diazepam) in patients unable to tolerate benzodiazepine therapy.
Tremor. A beta blocker is often the first drug used in patients with essential tremor who require regular treatment; however, gabapentin has also been tried with some success.
International Brand Drug Names
The information about drugs (tablets, pills, capsules, creams, solution, nasal spray, inhaler) around the world.
The United States Pharmacopeia 31, 2008: Gabapentin Capsules; Gabapentin Tablets.
Argentina: Abaglin; Alidial; Logistic; Neurontin; Ultraneural;
Australia: Gabaran; Gantin; Neurontin; Nupentin; Pendine;
Austria: Gabarex; Gabatal; Neurontin;
Brazil: Gabaneurin; Neurontin; Progresse;
Chile: Dineurin; Gabex; Gabictal; Neugabin; Normatol; Ritmenal;
Czech Republic: Apo-Gab; Gabagamma; Gabalept; Gabanox; Gabator; Gabenta; Neurontin; Nurabax;
Finland: Gabrion; Geabatan; Neuril; Neurontin;
Germany: Gabagamma; GabaLich; Gabax; Neurontin;
Greece: Gabantin; Gabental; Neurontin; Pentin;
Hong Kong: Neurontin;
Hungary: Gordius; Neurontin;
Indonesia: Epiven; Gabexal; Ganin; Nepatic; Neurontin;
Ireland: Gabture; Neurontin; Neurostil;
Mexico: Bapex; Gabantin; Gapridol; Neurontin; Nopatic;
Netherlands or Holland: Neurontin;
New Zealand: Neurontin; Nupentin;
Poland: Gabax; Neurontin;
Portugal: Gabamox; Neurontin;
Russia: Gapentek (Гапентек); Neurontin (Нейронтин); Tebantin (Тебантин);
South Africa: Epleptin; Neurontin;
Spain: Equipax; Gabamerck; Gabatur; Neurontin; Oxaquin;
UK or Britain: Neurontin;
US or USA: Gabarone; Neurontin;
Selections from the book: “Martindale: The Complete Drug Reference. Thirty-sixth edition”. Pharmaceutical Press. 2009