1. Name Of The Medicinal Product
BUSPIRONE 10mg TABLETS
2. Qualitative And Quantitative Composition
Each dosage form contains 10mg buspirone hydrochloride.
For excipients, see 6.1
3. Pharmaceutical Form
Tablet.
White, uncoated, flat bevelled edge with A10 on one side and a score line on the other.
4. Clinical Particulars
4.1 Therapeutic Indications
Buspirone is indicated for the treatment of short-term management of anxiety disorders and the relief of symptoms of anxiety with or without accompanying symptoms of depression.
4.2 Posology And Method Of Administration
Posology
The dosage should be individualised for each patient.
Adults (including the elderly): the usual starting dosage is 5mg given two to three times per day. The dosage may be increased every 2-3 days. The usual therapeutic dosage is 15 to 30mg daily in divided doses. The maximum recommended dose is 45mg daily in divided doses.
Renal and Hepatic Impairment
Dosage should be reduced in renal or hepatic impairment
Children:
Placebo-controlled trials, in which 334 patients were treated with buspirone for up to six weeks, have not shown buspirone at doses recommended for adults 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.)
Method of Administration
For oral administration.
4.3 Contraindications
Buspirone is contraindicated in the following groups of patients.
• patients with known hypersensitivity to buspirone hydrochloride or any ingredient in the tablet.
• patients with epilepsy.
• patients with severe renal or hepatic impairment. Severe renal impairment can be defined as a creatinine clearance of 20ml/min or below, or a plasma creatinine above 200µmol/l.
4.4 Special Warnings And Precautions For Use
Buspirone should be used with care in the following situations.
• Patients with rare hereditary problems of galactose intolerance, the lapp lactase deficiency or glucose – galactose malabsorption should not take this medicine.
• patients with a history of renal or hepatic impairment.
• alcohol use should be avoided, although buspirone has not been reported to potentiate the psychomotor impairment produced by alcohol. No data are available on concomitant use of alcohol and single doses of buspirone greater than 20mg
• buspirone 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 agents. Patients should be gradually withdrawn from these agents before initiating buspirone treatment.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
• Antidepressants - the occurrence of elevated blood pressure in patients receiving buspirone and monoamine oxidase inhibitors (phenelzine and tranylcypromine) has been reported. Buspirone should not be used concomitantly with a MAOI. In healthy volunteers no interaction with the tricyclic antidepressant amitriptyline was seen.
• Baclofen, lofexidine, nabilone, antihistamines may enhance any sedative effect.
• Cytochrome P450 3A4 (CYP3A4) inhibitors – e.g. erythromycin, itraconazole, nefazodone, grapefruit juice, diltiazem and verapamil. In cases where buspirone 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.
• Haloperidol – buspirone can increase the plasma concentration of haloperidol
• Rifampicin – coadministration of rifampicin, a potent inducer of CYP3A4, with buspirone has been shown to considerably decrease the plasma concentration and pharmacodynamic effects of buspirone.
Buspirone should be used with caution in combination with serotonergic drugs (including MAOIs, L-tryptophan, triptans, tramadol, linezolid, SSRIs, lithium and St. John's Wort) as there are isolated reports of serotonin syndrome occurring in patients on concomitant SSRI therapy. If this condition is suspected, treatment with buspirone should be immediately discontinued and supportive symptomatic treatment should be initiated.
In vitro studies have shown that buspirone does not displace warfarin, digoxin, phenytoin, or propranolol from plasma proteins.
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, buspirone is contraindicated in pregnancy and in lactation.
4.7 Effects On Ability To Drive And Use Machines
Single doses of buspirone up to 20mg have been shown not to cause significant impairment of cognitive or psychomotor functions, unlike diazepam or lorazepam. However, as dizziness and drowsiness have been reported as adverse effects of treatment patients should make sure they are unaffected before driving or operating machinery.
4.8 Undesirable Effects
• Nervous system Disorders: dizziness, headache, nervousness, light-headedness, excitement, paraesthesiae, sleep disturbances are amongst the most frequent adverse effects reported others are drowsiness, confusion, seizure and dry mouth.
• Ear and Labyrinth Disorders: tinnitus.
• Cardiac Disorders: chest pain, tachycardia, palpitations
• Respiratory Disorders: nasal congestion
• Gastrointestinal Disorders: nausea, sore throat.
• Skin and Subcutaneous tissue Disorders: sweating/clamminess.
• Body as a whole-General Disorders: fatigue.
4.9 Overdose
Features:
Symptoms include nausea, vomiting, headache, dizziness, drowsiness, tinnitus and restlessness. Mild bradycardia and hypotension have been reported.
Extrapyramidal symptoms have been reported after therapeutic doses. Rarely convulsions may occur.
Management:
Treatment should by symptomatic and supportive. The benefit of gastric decontamination is uncertain. Consider activated charcoal if the patient presents within 1 hour of ingestion of more than 5mg/kg provided they are not too drowsy.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
ATC code NO5B E01
Buspirone is an azaspirodecanedione. The exact mechanism of Buspirone 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 (norepinephrine), acetylcholine and dopamine systems of the brain. Buspirone enhances the activity of specific noradrenergic and dopaminergic pathways, whereas the activity of serotonin and acetylcholine are reduced.
5.2 Pharmacokinetic Properties
Absorption: Buspirone hydrochloride is rapidly absorbed from the gastrointestinal tract reaching peak plasma concentrations within 40 to 90 minutes after administration by mouth. Systemic bioavailability is low because of extensive first-pass metabolism.
Distribution: Buspirone is about 95% bound to plasma proteins.
Metabolism: Metabolism in the liver is extensive via the cytochrome P450 isoenzyme CYP3A4. The elimination half-life of buspirone is usually about 2 to 4 hours but half-lives of up to 11 hours have been reported.
Elimination: Buspirone is excreted mainly as metabolites in the urine, and also the faeces.
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 in adults.
5.3 Preclinical Safety Data
There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Lactose monohydrate,
Magnesium stearate,
Purified talc,
Polyvidone K-25,
Potato starch.
6.2 Incompatibilities
Not applicable.
6.3 Shelf Life
Three years.
6.4 Special Precautions For Storage
Do not store above 25°C.
Store in the original container.
6.5 Nature And Contents Of Container
The product is supplied in blister packs in cartons:
a) Carton: Printed carton manufactured from white folding box board.
b) Blister pack: manufactured from 250µm white rigid PVC and surface printed 20µm hard temper aluminium foil with 5-7g/M² PVC compatible heat seal lacquer on the reverse side.
Blister pack sizes: 20, 21, 28, 30, 56, 60, 84, 90, 100, 112, 126
6.6 Special Precautions For Disposal And Other Handling
There are no special instructions for use/handling.
7. Marketing Authorisation Holder
Actavis UK Limited
(Trading styles: Actavis)
Whiddon Valley
BARNSTAPLE
N Devon EX32 8NS
8. Marketing Authorisation Number(S)
PL 0142/0456
9. Date Of First Authorisation/Renewal Of The Authorisation
24 July 2002/
23 January 2009
10. Date Of Revision Of The Text
23/01/2009
11 DOSIMETRY
(IF APPLICABLE)
12 INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS
(IF APPLICABLE)
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