Gabapentin and Pregabalin

Gabapentin and pregabalin can be given as adjunctive therapy in partial epilepsy with or without secondary generalisation. They are also licensed for the treatment of neuropathic pain.

The mode of action of gabapentin is unknown. Gabapentin is not metabolised, exhibits no protein binding and does not induce hepatic enzymes.

Indications

• Gabapentin is licensed for use as add-on therapy for the treatment of partial seizures with or without secondary generalisation not satisfactorily controlled with other antiepileptics. It is of no use in other seizure types.
• Gabapentin is also indicated as a treatment for neuropathic pain.

Cautions

• Avoid sudden withdrawal (may cause anxiety, insomnia, nausea, pain and sweating. Taper off over at least 1 week).
• History of psychotic illness
• Elderly (may need to reduce dose)
• Renal impairment (reduce the dose)
• Diabetes mellitus, false positive readings with some urinary protein tests
• Pregnancy (but benefit of treatment outweighs risk to the fetus) and breast-feeding (present in milk and manufacturer advises avoid)

Important interactions

• Its potential for drug interaction is small and, to date, no clinically significant interaction with other drugs has been reported.

Common problems

• Gabapentin is usually well tolerated
• Side effects of gabapentin are mainly related to the central nervous system and these include drowsiness, dizziness, diplopia, ataxia and headaches.
• It may occasionally worsen seizures, particularly myoclonic seizures.
• Gabapentin treatment has not been associated with any serious idiosyncratic reaction to date.

Other side-effects

Other reported adverse effects include:

• Diarrhoea, dry mouth, dyspepsia, nausea and vomiting
• Peripheral oedema
• Weight gain
• Arthralgia, rash
• Leucopenia
• Allergic reactions, including urticaria, angioedema, and Stevens-Johnson Syndrome

Initiation

• The initial dose is 300-400 mg/day and the titration rate consists of weekly dose increases up to 1800-2400 mg/day in the first instance.
• The optimal dose remains to be established: the maximum recommended dose is currently 3600 mg/day but the efficacy of higher doses is presently being investigated.
• In view of its short elimination half-life a three times daily dosage is recommended.

Monitoring

• There is no need to measure its plasma concentration as a guide to dosing.
• Dose and blood levels of have been correlated with decreased seizure frequency and the current target range is 12-120 mcmol/L.
• Evidence suggests that there is good correlation between plasma and saliva concentrations.

Indications

• Adjunctive therapy for partial seizures with or without secondary generalisation
• Peripheral neuropathic pain

Contraindications

• Breast-feeding

Cautions

• Avoid abrupt withdrawal (taper-off over at least 1 week)
• Renal impairment (reduce the dose)
• Pregnancy (toxicity has been shown in animal studies

Common problems

• Dry mouth
• Constipation, vomiting, flatulence
• Oedema
• Dizziness, drowsiness, attention disturbance, disturbances in muscle control and movement, memory impairment, speech disorder, paraesthesia
• Euphoria, confusion, fatigue, appetite changes, weight gain
• Changes in sexual function
• Visual disturbances, including blurred vision, diplopia, eye strain and eye irritation