1. Name Of The Medicinal Product
BUSPAR TABLETS 5 MG.
BUSPAR TABLETS 10 MG.
2. Qualitative And Quantitative Composition
Each tablet contains buspirone hydrochloride 5 mg or 10 mg.
3. Pharmaceutical Form
Oral tablet.
4. Clinical Particulars
4.1 Therapeutic Indications
Buspar is indicated for the short-term management of anxiety disorders and the relief of symptoms of anxiety with or without accompanying depression.
4.2 Posology And Method Of Administration
Adults:
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.
Elderly:
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.
Renal and Hepatic Impairment:
Dosage should be reduced in renal or hepatic impairment.
Children:
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. (See 5.2, Pharmacokinetic Properties.)
4.3 Contraindications
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.
4.4 Special Warnings And Precautions For Use
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.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
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.
4.6 Pregnancy And Lactation
In some studies, administration of high doses of buspirone to pregnant animals produced effects on survival, birth and weaning weights, although there was no effect on foetal development. Since the relevance of this finding in humans has not been established, Buspar is contraindicated in pregnancy and in lactation.
4.7 Effects On Ability To Drive And Use Machines
Since early and transient adverse events may occur, patients should be cautioned not to drive or operate machines until they are certain that Buspar does not affect them adversely.
4.8 Undesirable Effects
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.
4.9 Overdose
There is no specific antidote to Buspar. Buspar is not removed by haemodialysis. The stomach should be emptied as quickly as possible. Treatment should be symptomatic and supportive. The ingestion of multiple agents should be suspected.
Death by deliberate or accidental overdose has not been observed. A dose of 375 mg per day in healthy volunteers produced no significant adverse effects. As maximum dose levels are reached symptoms most commonly observed are: nausea, vomiting, dizziness, drowsiness and miosis.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Buspar is an azaspirodecanedione. The exact mechanism of Buspar anxioselective action is not fully known. It does not act on benzodiazepine receptor sites and lacks sedative, anticonvulsant and muscle relaxant properties. From animal studies it is known to interact with serotonin, noradrenaline, acetylcholine and dopamine systems of the brain. Buspar enhances the activity of specific noradrenergic and dopaminergic pathways, whereas the activity of serotonin and acetylcholine are reduced.
5.2 Pharmacokinetic Properties
Buspar is rapidly absorbed when given orally. It is then subject to considerable first-pass metabolism. Peak plasma levels occur 60-90 minutes after dosing. Plasma concentration is linearly related to dose. Following multiple dosing steady state plasma concentrations are achieved within 2 days. Buspar is 95% protein bound. Buspar is eliminated primarily by liver metabolism. In pharmacokinetic studies mean plasma half-lives varied from 2 to 11 hours.
At steady state, the following doses of buspirone in children aged 6-12 years resulted in increases in Cmax (maximum concentration) and AUC (area under the curve), compared with adults, as shown in the table:
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Across the dose range studied, the Cmax and AUC of 1-PP (the active metabolite of buspirone, 1-pyrimidinylpiperazine) in children were approximately double those of adults.
5.3 Preclinical Safety Data
No further relevant information.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Lactose anhydrous, sodium carboxymethyl starch, microcrystalline cellulose, silicon dioxide colloidal, magnesium stearate.
6.2 Incompatibilities
None known.
6.3 Shelf Life
36 months.
6.4 Special Precautions For Storage
Do not store above 25°C
6.5 Nature And Contents Of Container
The tablets are packaged in blisters packs containing 90 tablets.
6.6 Special Precautions For Disposal And Other Handling
No specific instructions.
7. Marketing Authorisation Holder
Bristol-Myers Squibb Holdings Ltd
t/a Bristol-Myers Pharmaceuticals
Uxbridge Business Park
Sanderson Road
Uxbridge
Middlesex
UB8 1DH
8. Marketing Authorisation Number(S)
Buspar Tablets 5mg: PL 00125/0162
Buspar Tablets 10mg: PL 00125/0163
9. Date Of First Authorisation/Renewal Of The Authorisation
11.06.1987 / 16.05.2008
10. Date Of Revision Of The Text
16.05.2008
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