Buspirone

Buspirone is an Antianxiety Agent belonging to the Serotonin 5-HT1A receptor agonist class.

Buspirone is an anxiolytic agent used for short-term treatment of generalized anxiety and second-line treatment of depression.

Buspirone rapidly and almost completely absorbed from the GI tract. The bioavailability is about 1.5%-13%. The time to peak plasma concentration is within 40-90 min. The volume of distribution is about 5.3 L/kg. The Plasma protein binding is approximately 86%-95%, mainly to albumin. Buspirone extensively metabolised in the liver by CYP3A4 enzyme via oxidative dealkylation to 1-pyrimidinylpiperazine as active metabolite and via hydroxylation to inactive metabolites; undergoes extensive first-pass metabolism. The Excretion of Buspirone via urine (approx 29-63%, mainly as metabolites); faeces (approx. 18-38%). The Elimination half-life of Buspirone is about 2-3 hours.

Buspirone shows side effects like Headache, dizziness, lightheadedness, nausea, nervousness, and excitement.

Buspirone is available in the form of Oral tablets.

Buspirone is available in India, UK, Germany, Italy, France, Switzerland, and Malaysia.

Buspirone is a Serotonin 5-HT1A receptor agonist belonging to the class Antianxiety Agent.

The mechanism of action of buspirone is unknown. Buspirone has a high affinity for serotonin 5-HT_1A and 5-HT₂ receptors, without affecting benzodiazepine-GABA receptors. Buspirone has moderate affinity for dopamine D₂ receptors.

The Onset of action of Buspirone is not clinically established.

The Buspirone can remain in your body for around 18 hours.

Buspirone is available in the form of an Oral Tablet.

Buspirone comes as a tablet to take by mouth. It is usually taken twice daily and must be taken consistently, either always with food or always without food each time.

Buspirone is used to treat anxiety disorders or in the short-term treatment of symptoms of anxiety. Buspirone is in a class of medications called anxiolytics. It works by changing the amounts of certain natural substances in the brain.

Buspirone is an Antianxiety Agent belonging to the Serotonin 5-HT1A receptor agonist class.

Buspirone has high affinity for serotonin (5-HT_1A and 5-HT₂), moderate affinity for dopamine (D₂), and no affinity for GABA receptors.

Buspirone is approved for use in the following clinical indications

• Generalized anxiety disorder
• Shivering, targeted temperature management
• Unipolar depression, augmentation

• Generalized anxiety disorder

Oral: Initial: 10 to 15 mg/day in 2 to 3 divided doses; may increase every 2 to 3 days in increments of 5 mg/day to a maximum of 60 mg/day; usual dose: 20 to 30 mg/day in 2 to 3 divided doses.

• Shivering, targeted temperature management

Oral: 30 mg every 8 hours during the cooling phase of targeted temperature management.

• Unipolar depression, augmentation

Oral: Initial: 15 to 20 mg/day in 2 divided doses; may increase every 3 to 7 days in increments of 10 to 15 mg/day to a maximum of 60 mg/day in 2 divided doses.

Buspirone is available in various strengths as 5 mg, 7.5 mg, 10 mg, 15 mg, 30 mg.

Buspirone is available in the form of an Oral Tablet.

• Dosage Adjustment in Kidney Patient

CrCl ≥60 mL/minute: No dosage adjustment necessary.

CrCl <60 mL/minute: No specific dose adjustments can be recommended.

• Dosage Adjustment in Hepatic impairment Patient

Mild to moderate impairment: There are no dosage adjustments provided.

Severe impairment: Use not recommended.

Avoid grapefruit products, it may increase the plasma concentrations of the drug.

Buspirone is contraindicated in patients with

• Hypersensitivity
• Epilepsy.
• Concomitant use with MAOIs.
• Severe renal (CrCl <20 mL/min) or hepatic impairment.
• Lactation

• Sedative/hypnotic withdrawal: Buspirone does not exhibit cross-tolerance with benzodiazepines or other sedative/hypnotic agents. If substituting buspirone for any of these agents, gradually withdraw the drug(s) prior to initiating buspirone.

Avoid consumption of alcohol. Alcohol may cause additive CNS depressant effects.

It is not known whether Buspirone passes into breast milk or if it could harm a nursing baby.

Buspirone is not recommended for use in pregnant women as not enough studies are done to understand its safety and efficacy.

Avoid grapefruit products, it may increase the plasma concentrations of the drug.

• Common

Chest pain, Cold and clammy skin, diaphoresis, skin rash, Diarrhea, nausea, sore throat, Abnormal dreams, ataxia, confusion, drowsiness, excitement, headache, hostility, insomnia, nervousness, numbness, outbursts of anger, paresthesia, asthenia, musculoskeletal pain, myalgia, tremor, blurred vision, Tinnitus, Nasal congestion.

• Rare

Apathy, claustrophobia, cold intolerance, delayed ejaculation, depersonalization, dissociative reaction, dysphoria, euphoria, fear, glossopyrosis, hallucination, hyperacusis, involuntary muscle movements, malaise, psychosis (including exacerbation of psychosis, roaring sensation in head, seizure, slowed reaction time, slurred speech, stupor, suicidal ideation, vertigo.

• CYP3A4 Inducers (Strong): May decrease the serum concentration of Buspirone. Management: Consider alternatives to this combination. If coadministration of these agents is deemed necessary, monitor patients for reduced buspirone effects and increase buspirone doses as needed.

• CYP3A4 Inhibitors (Strong): May increase the serum concentration of Buspirone. Management: Limit the buspirone dose to 2.5 mg daily and monitor patients for increased buspirone effects/toxicities if combined with strong CYP3A4 inhibitors. Dose adjustments of buspirone or a strong CYP3A4 inhibitor should be based on clinical assessment.

• Erythromycin (Systemic): May increase the serum concentration of Buspirone. Management: Limit the buspirone dose to 2.5 mg twice daily and monitor for increased buspirone effects/toxicities if combined with erythromycin. Dose adjustments of buspirone or erythromycin should be based on clinical assessments.

• Fenfluramine: May enhance the serotonergic effect of Serotonergic Agents (Moderate Risk, Miscellaneous). This could result in serotonin syndrome.

• Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

• Grapefruit Juice: May increase the serum concentration of Buspirone. Management: Patients should avoid consuming large quantities of grapefruit juice during use of buspirone. If patients consume grapefruit juice during buspirone therapy, monitor for increased buspirone adverse effects.

• Lorcaserin: May enhance the serotonergic effect of Serotonergic Agents (Moderate Risk, Miscellaneous). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined.

• Oxitriptan: May enhance the serotonergic effect of Serotonergic Agents (Moderate Risk, Miscellaneous). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined.

• Resveratrol: May increase the serum concentration of Buspirone.

• Serotonergic Agents (High Risk): Buspirone may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined.

The common side effects of Buspirone include the following

• Common side effects

Headache, dizziness, lightheadedness, nausea, nervousness, and excitement.

• Rare side effects

Hives, difficulty breathing, swelling of your face, lips, tongue, or throat, lightheadedness, agitation, hallucinations, fever, sweating, shivering, fast heart rate, muscle stiffness, twitching, loss of coordination, nausea, vomiting, and diarrhea.

• Pregnancy

Pregnancy Category

Pregnancy Category B: No fertility impairment or fetal damage was observed in reproduction studies performed in rats and rabbits at buspirone doses of approximately 30 times the maximum recommended human dose. In humans, however, adequate, and well- controlled studies during pregnancy have not been performed. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

• Nursing Mothers

The extent of the excretion in human milk of buspirone or its metabolites is not known. In Tats, however, buspirone and its metabolites are excreted in milk. Buspirone administration to nursing women should be avoided if clinically possible.

• Pediatric Use

Safety and efficacy are not established for Pediatrics.

• Geriatric Use

In one study of 6632 patients who received buspirone for the treatment of anxiety, 605 patients were >65 years old and 41 were 275 years old; the safety and efficacy profiles for these 605 elderly patients (mean age = 70.8 years) were like those in the younger population (mean age = 43.3 years). Review of spontaneously reported adverse clinical events has not identified differences between elderly and younger patients, but greater sensitivity of some older patients cannot be ruled out.

Symptoms: Nausea, vomiting, dizziness, drowsiness, miosis, gastric distress, mild bradycardia, hypotension, extrapyramidal symptoms, and convulsions.

Management: Symptomatic and supportive treatment w/ immediate gastric lavage. May consider activated charcoal w/in 1 hour of ingestion of >5 mg/kg.

• Pharmacodynamic

Buspirone, an azaspirodecanedione, is an anxioselective drug w/ only a little sedative effect but w/o anticonvulsant and muscle relaxant properties. It has a high affinity for serotonin (5-HT_1A and 5-HT₂), moderate affinity for dopamine (D₂), and no affinity for GABA receptors.

• Pharmacokinetics

Absorption

Buspirone rapidly and almost completely absorbed from the GI tract. The bioavailability is about 1.5%-13%. The time to peak plasma concentration is within 40-90 min.

Distribution

The volume of distribution is about 5.3 L/kg. The Plasma protein binding is approximately 86%-95%, mainly to albumin.

Metabolism and Excretion

Buspirone extensively metabolized in the liver by CYP3A4 enzyme via oxidative dealkylation to 1-pyrimidinylpiperazine as active metabolite and via hydroxylation to inactive metabolites; undergoes extensive first-pass metabolism. The Excretion of Buspirone via urine (approx 29-63%, mainly as metabolites); faeces (approx. 18-38%). The Elimination half-life of Buspirone is about 2-3 hours.

• https://www.uptodate.com/contents/buspirone-drug-information#F143260
• https://www.rxlist.com/physical_symptoms_of_anxiety_panic_disorders/article.htm
• https://medlineplus.gov/druginfo/meds/a688005.html
• https://reference.medscape.com/drug/buspar-buspirone-342913#5
• https://go.drugbank.com/drugs/DB00490
• https://www.drugs.com/buspirone.html#dosage
• https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21-190_BuSpar_Prntlbl.pdf