Gabapentin
Gabapentin is an oral gabapentinoid used in adults and children for partial-onset seizures and in adults for post-herpetic neuralgia. It is also widely used off-label for various neuropathic pain conditions and restless legs syndrome.
- Chemical formula
- C9H17NO2
- CAS number
- 60142-96-3
- ATC code
- N03AX12
- Molecular weight
- 171.24 g/mol
- Drug class
- Gabapentinoid (alpha-2-delta ligand)
- Also known as
- CI-945, Gabapentina
What is it?
Gabapentin was approved as an antiepileptic in 1993 and for post-herpetic neuralgia in 2002. It is supplied as oral capsules, tablets, oral solution and gabapentin enacarbil extended-release tablets. Gabapentin is dispensed only on prescription and is classified as a controlled substance in some jurisdictions because of misuse concerns. Multiple authorised generics are widely available worldwide.
Mechanism of action
Gabapentin is a structural analogue of gamma-aminobutyric acid (GABA) but does not bind GABA receptors. It binds the alpha-2-delta auxiliary subunit of voltage-gated calcium channels in the central nervous system, reducing presynaptic calcium influx and the release of excitatory neurotransmitters such as glutamate, noradrenaline and substance P. The result is anticonvulsant and analgesic effects, particularly in neuropathic pain pathways.
Pharmacokinetics
Oral gabapentin has saturable absorption via the L-amino acid transporter, so bioavailability decreases with increasing dose (approximately 60% at 300mg three times daily, but lower at higher doses). This non-linear pharmacokinetics distinguishes it from pregabalin. Plasma protein binding is negligible. Gabapentin is excreted unchanged in urine, with a plasma half-life of approximately 5 to 7 hours. Renal impairment requires substantial dose reduction.
Indications
Gabapentin is approved in adults and children aged 3 years and older as adjunctive therapy for partial-onset seizures, and in adults for post-herpetic neuralgia. Gabapentin enacarbil extended-release is also approved for restless legs syndrome and post-herpetic neuralgia in some markets. According to international guidelines, gabapentin is also widely used off-label for diabetic peripheral neuropathy and other neuropathic pain syndromes.
Safety profile
Common adverse effects include drowsiness, dizziness, ataxia, peripheral oedema and weight gain. Gabapentin combined with opioids increases the risk of respiratory depression. Misuse and dependence have been reported, particularly in patients with substance use disorders. According to the prescribing information, withdrawal symptoms can occur after abrupt discontinuation, so the medication should be tapered gradually. Renal impairment requires substantial dose reduction.
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Frequently asked questions
How is gabapentin different from pregabalin? ▾
Both bind the alpha-2-delta calcium channel subunit and are used in similar indications, but pregabalin has linear pharmacokinetics and higher bioavailability than gabapentin, which has saturable absorption at higher doses. As a result, pregabalin reaches effective plasma levels more reliably and at lower doses, although clinical efficacy in neuropathic pain at adequate doses is broadly comparable. According to international guidelines, the choice is made by the prescriber.
Why must gabapentin be titrated? ▾
Gabapentin requires gradual titration to minimise side effects, particularly drowsiness, dizziness and ataxia, which are most prominent during initiation. According to the prescribing information, typical titration starts at 300mg on day 1, 300mg twice daily on day 2, 300mg three times daily on day 3, and increased further as needed. Therapeutic doses are usually 1800-3600mg per day in divided doses. Sudden discontinuation should be avoided.
Why must the dose be reduced in kidney disease? ▾
Gabapentin is excreted unchanged in urine, so renal impairment substantially increases plasma concentrations and the risk of adverse effects, including sedation, ataxia and cognitive impairment. According to the prescribing information, the dose is reduced based on creatinine clearance, including in patients on dialysis where supplemental doses are given after sessions. Renal function should be assessed before treatment and periodically thereafter.
Is gabapentin a controlled substance? ▾
Gabapentin has been associated with misuse and physical dependence, particularly in patients with substance use disorders or in combination with opioids. It is classified as a controlled substance in some jurisdictions including some U.S. states, but not at the federal level. According to regulatory communications, prescribers should screen for substance use history and monitor for misuse, particularly at higher doses or in combination with opioids.
What are the main contraindications for gabapentin? ▾
Gabapentin is contraindicated in known hypersensitivity to gabapentin or its excipients. Caution is required in renal impairment (with mandatory dose adjustment), in concurrent CNS depressants including opioids, in older adults, and during pregnancy and breastfeeding. According to the prescribing information, the medical history must be reviewed by a clinician before any prescription, particularly in patients with chronic kidney disease or substance use history.
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