buspirone hydrochloride
BuSpar

Available forms
Available by prescription only
Tablets: 5 mg, 10 mg, 15 mg

Indications and dosages
 Management of anxiety disorders. Adults: Initially, 5 mg P.O. t.i.d. Dosage may be increased at 3-day intervals. Usual maintenance dose is 20 to 30 mg daily in divided doses. Don’t exceed 60 mg daily.

Pharmacodynamics
Anxiolytic action: Buspirone is an azaspirodecanedione derivative with anxiolytic activity. It suppresses conflict and aggressive behavior and inhibits conditioned avoidance responses. Its precise mechanism of action hasn’t been determined, but it appears to depend on simultaneous effects on several neurotransmitters and receptor sites: decreasing serotonin neuronal activity, increasing norepinephrine metabolism, and exerting a partial action as a presynaptic dopamine antagonist. Studies suggest an indirect effect on benzodiazepine gamma-aminobutyric acid (GABA)-chloride receptor complex or GABA receptors, or on other neurotransmitter systems.
 Buspirone isn’t pharmacologically related to benzodiazepines, barbiturates, or other sedatives and anxiolytics. It has a nontraditional clinical profile and is uniquely anxiolytic. It has no anticonvulsant or muscle relaxant activity and doesn’t appear to cause physical dependence or significant sedation.

Pharmacokinetics
Absorption: Absorbed rapidly and completely after oral administration, but extensive first-pass metabolism limits absolute bioavailability to 1% to 13% of the oral dose. Food slows absorption but increases the amount of unchanged drug in systemic circulation.
Distribution: 95% protein-bound; it doesn’t displace other highly protein-bound drugs such as warfarin.
Metabolism: Metabolized in the liver by hydroxylation and oxidation, resulting in at least one pharmacologically active metabolite, 1, pyrimidinylpiperazine (1-PP).
Excretion: 29% to 63% is excreted in urine in 24 hours, primarily as metabolites; 18% to 38% is excreted in feces.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug or within 14 days of taking an MAO inhibitor. Use cautiously in patients with renal or hepatic impairment.

Interactions
Drug-drug. CNS depressants: Increase sedation. Avoid use together.
Digoxin: Buspirone may displace digoxin from serum-binding sites. Monitor digoxin levels.
Haloperidol: Increases serum haloperidol levels. Decrease haloperidol dosage.
MAO inhibitors: Elevate blood pressure. Avoid use together.
Drug-food. Grapefruit juice: Elevates buspirone levels and increases pharmacologic and adverse effects. Tell patient to take drug with liquid other than grapefruit juice.
Drug-lifestyle. Alcohol use: Increases sedation. Discourage alcohol use.

Adverse reactions
CNS: dizziness, drowsiness, nervousness, insomnia, headache, light-headedness, fatigue, numbness.
EENT: blurred vision.
GI: dry mouth, nausea, diarrhea, abdominal distress.

Effects on lab test results
None reported.

Overdose and treatment
Signs and symptoms of overdose include severe dizziness, drowsiness, unusual constriction of pupils, and stomach upset, including nausea and vomiting.
 Treatment of overdose is symptomatic and supportive; empty stomach with immediate gastric lavage. Monitor respiration, pulse, and blood pressure. No specific antidote is known. Effect of dialysis is unknown.

Special considerations
• Buspirone has been used investigationally to treat nonmelancholic depression and parkinsonian syndrome.
• Patients previously given benzodiazepines may not show good clinical response to this agent.
• Monitor hepatic and renal function. Hepatic and renal impairment impedes metabolism and excretion of drug and may lead to toxic accumulation; dose reduction may be necessary.
• Although buspirone doesn’t appear to cause tolerance or physical or psychological dependence, it’s possible that a patient prone to drug abuse may experience these effects.
• Buspirone doesn’t block the withdrawal syndrome linked to benzodiazepines or other common sedative and hypnotic agents; therefore, these agents should be withdrawn gradually before replacement with buspirone therapy.
• Store tablets in tight, light-resistant containers at temperatures less than 86° F (30° C).
Breast-feeding patients
• It’s unknown whether buspirone and its metabolites appear in breast milk. Avoid using buspirone in breast-feeding women.

Patient education
• Advise patient to take drug exactly as prescribed; explain that therapeutic effect may not occur for 2 weeks or more. Warn patient not to double a missed dose; a missed dose should be taken as soon as possible unless it’s almost time for next dose.
• Caution patient to avoid hazardous tasks that require alertness until effects of drug are known. The effects of alcohol and other CNS depressants, such as antihistamines, sedatives, tranquilizers, sleeping aids, prescription pain medication, barbiturates, seizure medicine, muscle relaxants, anesthetics, and medicines for colds, coughs, hay fever, or allergies, may be enhanced by additive sedation and drowsiness caused by buspirone.
• Tell patient to store drug away from heat and light and out of the reach of children.
• Explain importance of regular follow-up visits to check progress. Urge patient to report adverse reactions immediately.
• Inform patient that results may not be seen in 3 to 4 weeks; however, an improvement may be noted within 7 to 10 days.
• Instruct patient to take drug with liquid other than grapefruit juice.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use