Azaspirodecanediones (anxiolytics).

Buspirone

Each tablet contains buspirone hydrochloride 5 mg or 10 mg.

Oral tablet.

Buspar is indicated for the short-term management of anxiety disorders and the relief of symptoms of anxiety with or without accompanying depression.

Dosage should be adjusted according to response for maximum effect. The recommended initial dose is 5 mg two to three times daily and this may be increased every two to three days. The usual therapeutic dose is 15 to 30 mg daily in divided doses with a maximum recommended dose of 45 mg daily in divided doses.

Renal and Hepatic Impairment:

Dosage should be reduced in renal or hepatic impairment.

Placebo-controlled trails, in which 334 patients were treated with buspirone for up to six weeks, have not shown buspirone at doses recommended for adult to be an effective treatment for generalised anxiety disorder in patients less than 18 years.

Plasma concentrations of buspirone and its active metabolite were higher in paediatric patients, compared to adults given equivalent doses.

Dosage should be adjusted according to response for maximum effect. The recommended initial dose is 5 mg two to three times daily and this may be increased as required. The usual therapeutic dose is 15 to 30 mg daily in divided doses with a maximum recommended dose of 45 mg daily in divided doses.

Buspar should not be used in patients hypersensitive to any of the ingredients in the formulation. Buspar should not be used in patients with epilepsy. Buspar should not be used in patients with severe renal impairment, defined as creatinine clearance of 20 ml/minute or below, or a plasma creatinine above 200 micromoles/litre. Buspar should not be used in patients with severe hepatic disease.

In controlled studies in healthy volunteers, Buspar in single doses up to 20 mg caused no significant impairment of cognitive or psychomotor functions, unlike the benzodiazepines, diazepam or lorazepam. In studies in healthy volunteers, Buspar did not potentiate the psychomotor impairment produced by alcohol, in contrast to a comparative benzodiazepine. However, no data are available on concomitant use of alcohol and Buspar at single doses greater than 20mg. It is prudent therefore to avoid alcohol while taking Buspar.

As Buspar does not exhibit cross-tolerance with benzodiazepines and other common sedative/hypnotic agents, it will not block the withdrawal syndrome often seen with cessation of therapy with these compounds. Before starting therapy with Buspar, it is advisable to withdraw patients gradually from prior chronic treatment with these agents.

In patients with a history of renal or hepatic impairment, Buspar should be used with caution.

This product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

The occurrence of elevated blood pressure in patients receiving both buspirone and monoamine oxidase inhibitors (phenelzine and tranylcypromine) has been reported. It is therefore recommended that Buspar should not be used concomitantly with a monoamine oxidase inhibitor (MAOI).

In vitro studies have shown that buspirone does not displace warfarin, digoxin, phenytoin or propranolol from plasma proteins.

In a study in normal volunteers, no interaction with amitriptyline was seen. A similar study with diazepam showed a slight increase in metabolite (nordiazepam) levels.

Buspirone has been shown “in vitro” to be metabolised by Cytochrome P450 3A4 (CYP3A4). This is consistent with the interaction observed between buspirone and substances that inhibit this isoenzyme, e.g. erythromycin, itraconazole, nefazodone, grapefruit juice, diltiazem and verapamil. In cases where Buspar is likely to be used with a potent inhibitor of CYP3A4 a lower dose of buspirone (e.g. 2.5mg b.i.d.) should be used.

Co-administration of rifampicin, a potent inducer of CYP3A4, with Buspar has been shown to considerably decrease the plasma concentration and pharmacodynamic effects of buspirone.

Buspar is generally well tolerated. If side-effects occur they are normally observed at the beginning of treatment and usually subside with continued use and/or decreased dosage.

In controlled trials, the only side-effects that occurred with significantly greater frequency with buspirone treatment than with placebo were dizziness, headache, nervousness, light-headedness, excitement and nausea. Tachycardia, palpitations, chest pain, drowsiness, confusion, seizures, dry mouth, fatigue and sweating/clamminess have also been reported rarely.

Bristol-Myers Squibb

(POM)

14 April 2009