Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
75 mg, 150 mg and 300 mg capsules
Approved indications: epilepsy, neuropathic pain
Australian Medicines Handbook section 16.1
Gamma-aminobutyric acid (GABA) is a neurotransmitter. Although pregabalin is an analogue of GABA, its therapeutic effect may be on other neural pathways. Pregabalin reduces the release of neurotransmitters by interfering with the calcium channels in nerve terminals. It has therefore been studied in neuropathic pain and as an adjunctive treatment for epilepsy.
Common examples of neuropathic pain are diabetic neuropathy and post-herpetic neuralgia. In a double-blind trial involving 146 patients with diabetic neuropathy pregabalin was more efficacious than placebo at reducing pain. After eight weeks of treatment the pain of the patients taking pregabalin had reduced by 2.5 points, on an 11 point scale, compared with a 0.8 decrease in the placebo group.1 In another eight-week double-blind trial, which included some Australian patients, pregabalin reduced the pain of herpetic neuralgia more than placebo did. Compared to placebo, mean pain scores were 1.2 points lower with pregabalin 150 mg/day and 1.57 points lower with 300 mg/day.2
Most patients with epilepsy can be managed with monotherapy, but some will need adjunctive treatment. Pregabalin has been studied as adjunctive treatment for patients with partial seizures, with or without secondary generalised seizures. An international study compared adding pregabalin with adding placebo to the treatment of 287 patients. After 12 weeks there was no decrease in seizure frequency in the placebo group, but a 20.6% reduction in the pregabalin 150 mg/day group and a 47.8% reduction in the 600 mg/day group. Approximately 44% of the patients taking the higher dose of pregabalin had at least a 50% reduction in seizure frequency.3
As pregabalin alters neurotransmission it can cause a variety of neurological adverse effects. In the neuropathic pain studies 28-36% of the patients taking 300 mg/day developed dizziness and 20-24% developed somnolence.12 Other common problems include ataxia, co-ordination problems, confusion and altered vision. Patients are therefore advised not to drive, until the effects of pregabalin are known. Other complaints include peripheral oedema, weight gain and dry mouth.
Most of a dose of pregabalin is excreted unchanged in the urine, with an elimination half-life of six hours. Lower doses are required if the patient has a reduced creatinine clearance.
While pregabalin has met the efficacy criteria for pain relief it is important to note that the response varies between patients. Only 32% of the patients with post-herpetic neuralgia will feel much improved, or very much improved with treatment. The response tends to be greater in patients with somnolence.
There is also a variation in the response of patients with epilepsy. Although seizure frequency will be at least halved in approximately 44% of patients given 600 mg/day, the responder rate with 150 mg/day is not significantly different from placebo (14% versus 6.2%). While 150 mg/day is an acceptable starting dose it may need to be gradually increased.3
Chronic pain and epilepsy are long-term problems so there need to be long-term studies of pregabalin to see if its benefits are maintained in the people who respond, and to see if any other adverse effects emerge. There is also a need to see how pregabalin compares with drugs, such as gabapentin, which have similar indications.
Notes on references
At the time the comment was prepared, information about this drug was available on the website of the Food and Drug Administration in the USA (www.fda.gov).
At the time the comment was prepared, a scientific discussion about this drug was available on the website of the European Agency for the Evaluation of Medicinal Products (www.emea.eu.int).
- LaMoreaux L. Pregabalin for the treatment of painful diabetic peripheral neuropathy: a double-blind, placebo-controlled trial. Pain 2004;110:628-38. .
- Sabatowski R, GÃ¡lvez R, Cherry DA, Jacquot F, Vincent E, Maisonobe P. The 1008-045 Study Group. Pregabalin reduces pain and improves sleep and mood disturbances in patients with post-herpetic neuralgia: results of a randomised, placebo-controlled clinical trial. Pain 2004;109:26-35. .
- Arroyo S, Anhut H, Kugler AR, Knapp LE, Garofalo EA. Pregabalin add-on treatment: a randomized, double-blind, placebo-controlled, dose-response study in adults with partial seizures. Epilepsia 2004;45:20-7. .