Gabapentin

Overview

Gabapentin is an anticonvulsant and neuropathic pain medicine first developed in the 1970s as a structural analogue of gamma-aminobutyric acid (GABA). Unlike GABA, it does not act directly on GABA receptors. Instead, its mechanism involves binding to the α2δ subunit of voltage-gated calcium channels in the brain and spinal cord. This reduces calcium influx into presynaptic neurons, which decreases release of excitatory neurotransmitters such as glutamate, norepinephrine, and substance P. By modulating these pathways, gabapentin dampens abnormal electrical activity and reduces the transmission of pain signals.

Gabapentin was approved for epilepsy but its role has expanded dramatically. Today, it is most often prescribed for neuropathic pain conditions (nerve-related pain), such as postherpetic neuralgia following shingles or painful diabetic neuropathy. It is also used in restless legs syndrome (RLS) and has numerous off-label uses, including anxiety disorders, hot flushes in menopause, migraine prevention, and alcohol withdrawal support. Its broad utility comes from its favourable safety profile compared to many older anticonvulsants and opioid analgesics.

Gabapentin is available in multiple forms: capsules, tablets, oral solutions, and extended-release tablets (e.g., Gralise, Horizant in the US). Absorption is saturable, meaning that as doses increase, a smaller proportion is absorbed. Peak blood levels usually occur 2–3 hours after dosing. Unlike many drugs, gabapentin is not metabolised by the liver and is eliminated unchanged in urine, making kidney function the key factor in clearance. This means that dose adjustments are essential in renal impairment, and dialysis can remove the drug effectively.

In the EU, gabapentin is widely available as a generic and is not a controlled substance. However, in the UK it was reclassified in 2019 as a controlled drug due to increasing misuse and association with opioid-related deaths. Similar concerns exist in the US where misuse potential has been reported, particularly in people with a history of substance use disorder. Despite this, when used appropriately under medical supervision, gabapentin remains a safe and effective therapy.

Interactions

Gabapentin has fewer pharmacokinetic interactions than many other antiepileptics, but clinically important interactions still exist.

• Opioids (morphine, oxycodone, tramadol): Increase sedation and risk of respiratory depression.
• Alcohol and sedatives (benzodiazepines, Z-drugs, antihistamines): Additive CNS depressant effects.
• Antacids containing aluminium or magnesium: Can reduce gabapentin absorption by up to 20%. Take gabapentin at least 2 hours after such antacids.
• Other antiepileptics: Few direct pharmacokinetic interactions, but additive sedative effects are possible.
• Herbal remedies and supplements: Products with sedative properties (e.g., valerian, kava) can amplify drowsiness. Always inform your clinician of all supplements taken.

Gabapentin does not interact significantly with the cytochrome P450 system, so interactions with many common drugs (statins, anticoagulants, antibiotics) are minimal.

Overdose / Missed Dose

Overdose: Large ingestions can cause double vision, slurred speech, severe drowsiness, lethargy, and in some cases coma. Seizures may occur. Management is supportive. Haemodialysis is effective in removing gabapentin, especially in renal failure.

Accidental double dose: Usually leads to drowsiness or dizziness. Advise the patient to avoid hazardous activities and seek medical advice if severe symptoms develop.

Missed dose: Take as soon as remembered unless it is nearly time for the next dose. If so, skip the missed dose and resume the regular schedule. Never take two doses together.

Patients and carers should be instructed to keep medicines in a safe place, follow the prescribed schedule closely, and consult a clinician if dosing errors occur.

Storage

• Store at room temperature (below 25°C) away from moisture and direct heat.
• Keep in original blister pack or tightly closed container until use.
• Oral solution must be refrigerated after opening and used within the time specified on the label.
• Do not use after the expiry date.
• Keep out of the reach of children. Ingesting large amounts can be harmful.
• Return unused or expired medication to a pharmacy for safe disposal.

When travelling, carry gabapentin in original packaging with the prescription label. Some countries regulate gabapentin as a controlled drug—check regulations before crossing borders.