Buspirone
Buspirax®
Category
Antianxiety
(USPDI)
Mechanism of action / Pharmacokinetics
The exact mechanism of action of buspirone has not been determined. Invitro , buspirone has a high affinity for serotonin (5-HT1A) receptors. Buspirone acts as partial agonist at post synaptic 5-HT receptors. Buspirone has moderate affinity for brain D2-dopamine receptors and appears to act as presynaptic dopamine agonist. It also increases norepinephrine metabolism in the locus ceruleus. It has no significant affinity for benzodiazepine receptors and dose not affect GABA bindings.
(USPDI,Facts)
Pharmacokinetics properties
Absorption Rapidly & completely absorbed from the GI with extensive first-pass metabolism
Bioavailability Approximately 4%
Distribution 5.3 ± 2.6 L/kg
Protein binding 95% ; 70 % to albumin and 30% to alpha1-acid glycoprotein
Biotransformation Hepatic
Half-life Elimination about 2 to 3 hours following single oral dose
Onset of action 4 weeks to reach max. effect
Peak plasma concentration 1 to 6 ng/ml following single oral dose of 20 mg
Elimination Renal: (29-63)%
Fecal: (18-38)%
Dialysis Decreased or had no effect on buspirone clearance
(USPDI)
Indications
Antianxiety
Contraindication
Buspirone is contraindicated in patients hypersensitivity to buspirone HCl.
(Facts,PDR)
Warnings and precautions
- Buspirone dose not exhibit cross-tolerance with benzodiazepines or other common sedatives or hypnotics and will not block symptoms of their withdrawal , they should therefore, be gradually withdrawn before starting treatment with buspirone.
- Do not use in patients with severe hepatic or renal impairment.
- Buspirone should not be used in patients with epilepsy or a history of such disorders.
- Buspirone may impair the patient’s ability to drive or operate machinery.
- Physicians should carefully evaluate patients for a history of drug abuse and follow such patients closely, observing them for signs of buspirone misuse or abuse.
(PDR,Facts)
pregnancy
Category B
Use during pregnancy only if clearly needed.
(Facts)
Breast - Feeding
The extent of the excretion in brest milk of buspirone or its metabolites is not known. Avoid administration to nursing women, if possible.
(Facts)
Drug Interaction
- Coadministration of buspirone with erythromycin, clarithromycin, itraconazole, ketoconazole, cimetidine, diltiazem, verapamil, fluvoxamine and nefazodone increased plasma buspirone concentrations.
- The sedative effects of buspirone may be enhanced if taken with alcohol or CNS depressant.
- Coadministration of buspirone with haloperidol and rifampicin may result in increased serum haloperidol and rifampicin concentrations.
- There have been reports of elevated blood pressure when buspirone was added to a regimen including an MAOI. Therefore, do not use concomitantly.
- If buspirone is to be used in combination with a potent inhibitor of CYP3A4, a low dose of buspirone(eg,2.5 mg bid)is recommended.
- Concomitant use of trazodone and buspirone may have caused
3- to 6- fold elevations on SGPT (ALT) in a few patients.
- Parkinson-like symptoms developed in a patient taking a drug
regimen that included buspirone, indinavir and ritonavir.
- For a report of potentially fatal gastro intestinal bleeding and marked hyperglycaemia after use of buspirone with clozapine.
- After addition of buspirone to the amitriptyline and diazepam dose regimen, no statistically significant difference in the steady state pharmacokinetic parameters were observed for amitriptyline or its metabolite nortriptyline and for diazepam, but increases of about 15% were seen for nordiazepam, and minor adverse clinical
effects (dizziness, headache and nausea) were observed.
- Coadministration of buspirone with either triazolam or flurazepam didn’t appear to prolong or intensify the sedative effect of either benzodiazepine.
- Therapeutic levels of aspirin, desipramine, diazepam, flurazepam, ibuprofen, propranolol, thioridazine and tolbutamide had only a limited effect on the extent of binding buspirone to plasma proteins.
(USPDI,PDR,Martindale,Facts)
Adverse reaction
Dizziness; drowsiness; insomnia; nervousness; lightheadedness; decreased concentration; excitement; anger/hostility; confusion; depression; tachycardia; palpitation; blurred vision; nausea; dry mouth; abdominal/gastric distress; diarrhea; constipation; vomiting; musculoskeletal aches/pain;
numbness; paresthesia; incoordination; tremor; skin rash; headache; fatigue;weakness; sweating/clamminess; chest pain; tinnitus; sore throat; nasal congestion; seizures; syncope; hypotension; hypertension; cerebrovascular accident; CHF; MI; cardiomyopathy; brady cardia; dream disturbances;depersonalization;
dysphoria; noise intolerance; euphoria; akathisia; fearfulness; loss of interest; disassociative reaction; hallucinations; suicidal ideation; feeling of claustrophobia; cold intolerance; stupor and slurred speech; psychosis; edema; pruritus; flushing; easy bruising; hair loss; dry skin; facial edema; blisters; acne; thinning of nails; galactorrhea; thyroid abnormality; flatulence; anorexia; increased; appetite; salivation; irritable colon; rectal bleeding; burning of tongue; urinary frequancy; urinary hesitancy; menstural irregularity; spotting and dysuria; amenorrhea; pelvic inflammatory disease; enuresis; nocturia; muscle cramps/spasms; rigid/stiff muscles; arthralgias; hyperventilation; shortness of breath; chestcongestion; epistaxis; weight gain; fever; roaring sensation in the head; weight loss; malaise; alcohol abuse; bleeding disturbance; loss of voice; hiccoughs; decreased or increased libido; delayed ejaculation; impotence; involuntary movements; slowed reaction time; muscle weakness; redness and itching of the eyes; altered taste/smell; cojunctivitis; inner ear abnormality; eye pain; photophobia; pressure on eyes.
(Facts -PDR-Martindale)
Overdosage
In clinical pharmacology trials, doses as high as 375mg/day were administered to healthy male volunteers. As this dose was approached, the following symptoms were observed; nausea; vomiting; dizziness; drowsiness; miosis and gastric distress.
No deaths have been reported.
(PDR)
Dosage and Administration
Usual adult and geriatric dose:
Antianxiety agent-oral , initally 5mg two or three times a day , or 7.5mg two times a day , the dosage being increased by 5mg per day at two-to three-day intervals until the desired response is obtained. the usual therapeutic dosage is 20 to 30 mg a day , and usual adult prescribing limits are 60 mg per day.
usual pediatric dose:
safety and efficacy have not been established in children under 18 years of age.
(USPDI)
Storage
Store below 30 and away from heat & direct light.
(USPDI)
How Supplied
Buspirax is available as 5,10 mg , flat and white tablets.
There are blisters of 5×10 in a box of 50’s for Buspirax 10mg and blisters of 5×20 in a box of 100’s for Buspirax 5mg.
Reference
1- PDR 2006 2-USPDI 2006 3-USPDI 2004
4- Martindale 2007 5- Drug Facts 2008