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5mg Tablets: Buspirone hydrochloride 5mg in a round, flat, bevel-edged, scored, white or almost white tablet with a diameter of 7mm, embossed BU 5 on one face.
10mg Tablets: Buspirone hydrochloride 10mg in a round, flat, bevel-edged, scored, white or almost white tablet with a diameter of 9mm, embossed BU 10 on one face.
Buspirone is an azaspirondecandione, a non-benzodiazepine anxiolytic. Buspirone's mechanism of action is very complex and, so far, it is not totally elucidated. Several different neuropharmacologic processes can be involved. Buspirone has an affinity for 5-HT1A -receptors, moderate affinity for DA2-receptors, and weak affinity for 5-HT2-receptors but no affinity for the benzodiazepine receptor complex in vitro.
Buspirone selectively blocks presynaptic dopamine receptors. Buspirone increases the firing rate of midbrain dopaminergic nerves. In the locus ceruleus buspirone increases the spontaneous firing of noradrenergic nerves.
The mechanism of action is very complex, but current investigations suggest that buspirone's main neuropharmacologic effects are mediated by the serotonin-1A receptors.
Buspirone is one of the many anxiolytics. Its advantages compared to benzodiazepines are that buspirone is less sedative, tolerance and abuse are not problems with buspirone and buspirone does not produce withdrawal symptoms like benzodiazepines do.
Absorption and Bioavailability: Buspirone is rapidly and almost completely absorbed after oral administration (Tmax: 0.89 hours ± 0.15). Peak plasma concentrations of the medicine averaged 1.13 ± 0.15ng/mL following a single oral dose of 10mg in a study in healthy adults. The mean bioavailability of the oral compared to the intravenous dose is 3.9% ± 4.3, depending on the extensive first pass metabolism of buspirone.
Distribution: After a single intravenous administration the volume of distribution was 433 litres ± 231 (5.3L/kg ± 2.61) and the mean systemic clearance was 1.70L/kg/hour ± 0.62. The elimination half-life for oral medicine was 2.1 hours ± 1.2.
Buspirone is highly serum protein bound (95%), mainly to human serum albumin and α1-acid glycoprotein. Food decreases the first-pass metabolism altering the bioavailability of buspirone.
Metabolism and Excretion: Buspirone is extensively metabolised in the liver. Metabolic sites in the liver are saturated by buspirone so that higher doses yield more unchanged buspirone.
This conclusion is consistent with the finding of a significant increase in unchanged buspirone elimination half-life (34%) during steady state as compared to that of a single dose. These results suggest that the pharmacokinetics of buspirone are non-linear after multiple dosing; in particular, dose increases and repeated dosing may lead to somewhat greater blood levels of unchanged buspirone than would be predicted from single dose studies.
About 29-63% of a single oral dose is excreted in urine and 18-38% in faeces within 24 hours, mainly as metabolites. Only less than 0.1% of the parent medicine is excreted unchanged in the urine. With current assay methods, however, only 25% of the medicine and its metabolites can be detected. The rest is still unidentified metabolites.
Effect of Age and Disease on Pharmacokinetics: The pharmacokinetics of buspirone in healthy men and women over 65 years of age were compared with those in men and women aged 21 to 39 years. Buspirone pharmacokinetics were evaluated after a single 15mg dose and after 15mg every eight hours for five days. No statistically significant differences between any age or sex group were found.
The pharmacokinetics in hepatic cirrhosis and in conditions where hepatic function is impaired is associated with decreased clearance of buspirone. Therefore, appropriate caution should be exercised when administering buspirone to patients with decreased hepatic function.
In mild or moderate renal failure the pharmacokinetics of buspirone and its active metabolite 1-PP are similar compared with normal renal function.
For anuric patients higher concentrations of the 1-PP metabolite are attained while they are undergoing haemo-dialysis. Hence the dosage of the medicine should be reduced by 25-50% in anuric patients.
Effect of Food: Plasma buspirone levels may be roughly three times greater when the tablets are taken with food as compared to administration without food.
Anxiety disorders. Short term relief of the symptoms of anxiety.
Adults: Initial dose is 15mg daily (5mg three times a day). The dose may then be increased 5mg per day, as needed, at intervals of 2 to 3 days. The daily dose should not exceed 60mg. Usually if patients do not respond at a total daily dose of 40mg it is unlikely that increasing the dose will be of any benefit.
Children: Buspirone is not recommended for children under 18 years of age.
BIRON is contraindicated in:
Dose adjustments are needed when treating patients with severe renal or hepatic disorders.
Buspirone does not usually impair psychomotor and cognitive function, but some patients may experience sedation.
Buspirone does not prevent possible symptoms of withdrawal after abrupt cessation of benzodiazepine use. Buspirone may potentiate the effects of alcohol or other CNS depressants.
Although buspirone has only minimal sedative effect, patients should be cautioned about driving a vehicle or operating machinery until it is reasonably certain that buspirone does not affect these functions adversely.
Concomitant use with monoamine oxidase inhibitors is not recommended.
Use During Pregnancy and Breast-Feeding: Use during pregnancy and breast-feeding is not recommended. Although in animal studies there is no likelihood of foetal damage, adequate human studies are not available. No problems with human breast-fed infants have been reported. Studies with rats, however, indicate that buspirone is excreted in breast milk.
Cardiovascular: Non-specific chest pain.
Central Nervous System: Dream disturbances
EENT: Tinnitus, sore throat, nasal congestion
Cardiovascular: Hypertension, hypotension, syncope
CNS: Depersonalisation, dysphoria, noise intolerance, euphoria, akathisia, fearfulness, loss of interest, dissociative reaction, hallucinations, suicidal ideation, seizures.
EENT: Redness and itching of the eyes, altered taste, altered smell, conjunctivitis.
Gastrointestinal: Flatulence, anorexia, increased appetite, salivation, irritable colon, rectal bleeding.
Genitourinary: Urinary hesitancy, menstrual irregularity and spotting, dysuria.
Musculoskeletal: Muscle cramps, muscle spasms, stiff muscles, arthralgias.
Neurological: Involuntary movements, slowed reaction time.
Respiratory: Hyperventilation, shortness of breath.
Sexual Function: Decreased or increased libido.
Skin: Oedema, pruritis, flushing, easy bruising, hair loss, dry skin.
Cardiovascular: Congestive heart failure, cardiomyopathy, bradycardia.
CNS: Cold intolerance, stupor, slurred speech, psychosis.
EENT: Inner ear abnormality, eye pain, photo-phobia, pressure on eyes.
Endocrine: Galactorrhoea, thyroid abnormality.
Gastrointestinal: Burning of the tongue.
Genitourinary: Amenorrhoea, enuresis, nocturia.
Neurological: Muscle weakness.
Rare: Epistaxis.
Sexual Function: Delayed ejaculation, impotence.
Skin: Acne, thinning of nails.
Buspirone is highly bound to serum proteins and may displace other medicines. A slight increase (9%) has been noticed with digoxin. No significant changes in amitriptyline pharmacokinetics can be detected when administered with buspirone in healthy volunteers. Similarly, the pharmacokinetics of diazepam has been shown to remain the same with buspirone, whereas buspirone possibly increased Cmax and AUC of nordiazepam by approximately 20%.
No significant interactions were reported between buspirone and cimetidine, flurazepam, and triazolam. Buspirone increases serum haloperidol concentration. Raised blood pressure has been noticed in patients taking both buspirone and MAO-inhibitors.
Data from the controlled clinical trials with over 700 patients suggests safe co-administration of buspirone and analgesics, antihistamines, sedative-hypnotics, contraceptives, and antihypertensives. Diazepam, but not clorazepate, together with buspirone resulted in increased sedation.
The concomitant use of CYP3A inhibitors increases buspirone bioavailability, e.g. itraconazole to 19-fold, erythromycin and diltiazem to 6-fold, verapamil to 3 fold. The concomitant use of these drugs with buspirone should be avoided or buspirone dose reduced accordingly.
Potent CYP enzyme inducers may decrease the bioavailability of buspirone. Rifampicin has decreased buspirone bioavailability to 10% from control values.
There is no specific antidote for buspirone. Treatment of buspirone overdose consists of symptomatic and supportive measures, immediate gastric lavage, monitoring of respiration, pulse and blood pressure.
Protect from light and moisture. Store below 30°C. Keep out of reach of children.
Prescription Medicine.
100 tablets.
The active ingredient of BIRON, buspirone hydrochloride is 8-(4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl)-8-azaspiro-(4,5)-decane-7,9-dione hydrochloride. Its molecular formula and weight are C21H31N5O2.HCl and 421.97 respectively.
Other ingredients of the tablets are: microcrystalline cellulose, sodium starch glycolate, talc, magnesium stearate and colloidal anhydrous silica.
Douglas Pharmaceuticals Ltd
P.O. Box 45-027
AUCKLAND 8
Ph: (09) 835-0660
Fax: (09) 835-0665
27 August 2001