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Medication Safety Issues
Sound-alike/look-alike issues:
BusPIRone may be confused with buPROPion
Pronunciation
(byoo SPYE rone)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Management of generalized anxiety disorder (GAD)
Use: Unlabeled/Investigational
Management of aggression in mental retardation and secondary mental disorders; major depression; potential augmenting agent for antidepressants; premenstrual syndrome
Pregnancy Risk Factor
B
Pregnancy Considerations
No impairment of fertility or fetotoxic effects were noted in animal studies with doses 30 times maximum recommended human dose. There are no adequate and well-controlled studies in pregnant women.
Lactation
Excretion in breast milk unknown/not recommended
Contraindications
Hypersensitivity to buspirone or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• Cognitive/motor impairment: Low potential for cognitive or motor impairment; until effects on patient known, patients should be warned to use caution when performing tasks which require mental alertness (eg, operating machinery or driving).
• Restlessness syndrome: Has been reported in small number of patients; may be attributable to buspirone's antagonism of central dopamine receptors. Monitor for signs of any dopamine-related movement disorders (eg, dystonia, akathisia, pseudo-parkinsonism)
Disease-related concerns:
• Hepatic impairment: Use in patients with severe hepatic impairment is not recommended.
• Renal impairment: Use in patients with severe renal impairment is not recommended.
Concurrent drug therapy issues:
• MAO inhibitors: Use with MAO inhibitors may result in hypertensive reactions; concurrent use is not recommended.
Special populations:
• Pediatrics: Safety and efficacy of buspirone have not been established in children <6 years of age. No long-term safety/efficacy data available in children.
Other warnings/precautions:
• 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.
Adverse Reactions
>10%: Central nervous system: Dizziness (12%)
1% to 10%:
Cardiovascular: Chest pain (>1%)
Central nervous system: Drowsiness (10%), headache (6%), nervousness (5%), lightheadedness (3%), anger/hostility (2%), confusion (2%), excitement (2%), dream disturbance (?1%)
Dermatologic: Rash (1%)
Gastrointestinal: Nausea (8%), diarrhea (2%)
Neuromuscular & skeletal: Numbness (2%), weakness (2%), musculoskeletal pain (1%), paresthesia (1%), incoordination (1%), tremor (1%)
Ocular: Blurred vision (2%)
Otic: Tinnitus (?1%)
Respiratory: Nasal congestion (?1%), sore throat (?1%)
Miscellaneous: Diaphoresis (1%)
<1%, postmarketing, and/or case reports (limited to important or life-threatening): Akathisia, allergic reaction, angioedema, anorexia, bradycardia, bruising, cardiomyopathy, cogwheel rigidity, conjunctivitis, CVA, dyskinesia, dyspnea, dystonia, edema, enuresis, eosinophilia, epistaxis, EPS, galactorrhea, hallucination, heart failure, hyper-/hypotension, hyperventilation, irritable colon, leukopenia, menstrual irregularity, MI, muscle spasms, parkinsonism, personality disorders, PID, psychosis, rectal bleeding, restless leg syndrome, seizure, serotonin syndrome, suicidal ideation, syncope, thrombocytopenia, thyroid abnormality, transaminase increases, visual disturbances (tunnel vision)
Metabolism/Transport Effects
Substrate of CYP2D6 (minor), 3A4 (major)
Drug Interactions
Antidepressants (Serotonin Reuptake Inhibitor/Antagonist): BusPIRone may enhance the serotonergic effect of Antidepressants (Serotonin Reuptake Inhibitor/Antagonist). This may cause serotonin syndrome. Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of BusPIRone. Risk D: Consider therapy modification
Calcium Channel Blockers (Nondihydropyridine): May decrease the metabolism of BusPIRone. Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Grapefruit Juice: May decrease the metabolism of BusPIRone. Risk D: Consider therapy modification
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Macrolide Antibiotics: May decrease the metabolism of BusPIRone. Exceptions: Azithromycin; Dirithromycin [Off Market]; Spiramycin. Risk D: Consider therapy modification
MAO Inhibitors: BusPIRone may enhance the adverse/toxic effect of MAO Inhibitors. Elevated blood pressure has been reported. Risk X: Avoid combination
Rifamycin Derivatives: May increase the metabolism of BusPIRone. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: BusPIRone may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Selective Serotonin Reuptake Inhibitors may decrease the metabolism of BusPIRone. Risk C: Monitor therapy
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
Ethanol/Nutrition/Herb Interactions
Ethanol: Ethanol (may increase CNS depression).
Food: Food may decrease the absorption of buspirone, but it may also decrease the first-pass metabolism, thereby increasing the bioavailability of buspirone. Grapefruit juice may cause increased buspirone concentrations; avoid intake of large quantities of grapefruit juice.
Herb/Nutraceutical: St John's wort may decrease buspirone levels or increase CNS depression. Avoid valerian, gotu kola, kava kava (may increase CNS depression).
Storage
Store at USP controlled room temperature of 25°C (77°F). Protect from light.
Mechanism of Action
The mechanism of action of buspirone is unknown. Buspirone has a high affinity for serotonin 5-HT1A and 5-HT2 receptors, without affecting benzodiazepine-GABA receptors. Buspirone has moderate affinity for dopamine D2 receptors.
Pharmacodynamics/Kinetics
Absorption: Rapid
Distribution: Vd: 5.3 L/kg
Protein binding: 86% to 95%
Metabolism: Hepatic oxidation, primarily via CYP3A4; extensive first-pass effect
Bioavailability: ~4%
Half-life elimination: 2-3 hours
Time to peak, serum: 40-90 minutes
Excretion: Urine: 29% to 63% (<0.1% dose excreted unchanged); feces: 18% to 38%
Dosage
Oral:
Generalized anxiety disorder:
Children ?6 years and Adolescents: Initial: 5 mg daily; increase in increments of 5 mg/day at weekly intervals as needed, to a maximum dose of 60 mg/day divided into 2-3 doses
Adults: 15 mg/day (7.5 mg twice daily); may increase in increments of 5 mg/day every 2-3 days to a maximum of 60 mg/day; target dose for most people is 20-30 mg/day (10-15 mg twice daily)
Elderly: Initial: 5 mg twice daily, increase by 5 mg/day every 2-3 days as needed up to 20-30 mg/day; maximum daily dose: 60 mg/day.
Dosing adjustment in renal impairment: Patients with impaired renal function demonstrated increased plasma levels and a prolonged half-life of buspirone. Use in patients with severe renal impairment not recommended.
Dosing adjustment in hepatic impairment: Patients with impaired hepatic function demonstrated increased plasma levels and a prolonged half-life of buspirone. Use in patients with severe hepatic impairment not recommended.
Monitoring Parameters
Mental status, symptoms of anxiety
Patient Education
Take only as directed; do not increase dose or take more often than prescribed. May take 2-3 weeks to see full effect; do not discontinue this medicine without consulting prescriber. Avoid large quantities of grapefruit juice. Do not use alcohol or other prescription or OTC medications (especially pain medications, sedatives, antihistamines, or hypnotics) without consulting prescriber. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. You may experience drowsiness, lightheadedness, impaired coordination, dizziness, or blurred vision (use caution when driving or engaging in tasks requiring alertness until response to drug is known); or upset stomach, nausea (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help). Report persistent vomiting; chest pain or rapid heartbeat; persistent CNS effects (eg, confusion, restlessness, anxiety, insomnia, excitation, headache, dizziness, fatigue, impaired coordination); or worsening of condition. Breast-feeding precaution: Breast-feeding is not recommended.
Geriatric Considerations
Because buspirone is less sedating than other anxiolytics, it may be a useful agent in geriatric patients when an anxiolytic is indicated.
Additional Information
Has shown little potential for abuse; needs continuous use. Because of slow onset, not appropriate for “as needed” (prn) use or for brief, situational anxiety. Ineffective for treatment of benzodiazepine or ethanol withdrawal.
Anesthesia and Critical Care Concerns/Other Considerations
Takes 2-3 weeks for full effect. Because of slow onset, not appropriate for “as needed” (prn) use or for brief, situational anxiety; not effective for severe anxiety; does not show cross-tolerance with benzodiazepines or other sedatives; less sedating than other anxiolytics; has shown little potential for abuse; needs continuous use; ineffective for benzodiazepine or ethanol withdrawal
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Child/Adolescent Considerations
Anxiety disorders: One pilot study of 15 children, 6-14 years of age (mean: 10 years), with mixed anxiety disorders, used initial doses of 5 mg/day; doses were individualized with increases in increments of 5 mg/day weekly as needed, to a maximum dose of 20 mg/day divided into 2 doses (mean dose required: 18.6 mg/day). Some authors (Carrey, 1996 and Kutcher, 1992), based on their clinical experience, recommend higher doses. Open-label study in 25 prepubertal inpatients (mean age: 8 years) with anxiety symptoms and moderately-aggressive behavior utilized a mean optimal dose of 28 mg/day (Pfeffer, 1997). Dosages ranging from 15-45 mg/day were utilized in children 6-17 years of age with pervasive developmental disorders (Buitelaar, 1998). The safety and efficacy of buspirone were evaluated in two placebo-controlled 6-week trials involving a total of 559 pediatric patients (6-17 years of age) with generalized anxiety disorder (GAD). Doses studied were 7.5-30 mg twice daily (15-60 mg/day). There were no significant differences between buspirone and placebo with regard to the symptoms of GAD following doses recommended for the treatment of GAD in adults (Bristol-Myers Squibb, BuSpar® package labeling, July 2001).
Buitelaar JK, van der Gaag RJ, and van der Hoeven J, “Buspirone in the Management of Anxiety and Irritability in Children With Pervasive Developmental Disorders: Results of an Open-Label Study,” J Clin Psychiatry, 1998, 59(2):56-9.
Carrey NJ, Wiggins DM, and Milin RP, “Pharmacological Treatment of Psychiatric Disorders in Children and Adolescents,” Drugs, 1996, 51(5):750-9.
Kutcher SP, Reiter S, Gardner DM, et al, “The Pharmacotherapy of Anxiety Disorders in Children and Adolescents,” Psychiatr Clin North Am, 1992, 15(1):41-67.
Pfeffer CR, Jiang H, and Domeshek LJ, “Buspirone Treatment of Psychiatrically Hospitalized Prepubertal Children With Symptoms of Anxiety and Moderately Severe Aggression,” J Child Adolesc Psychopharmacol, 1997, 7(3):145-55.
Mental Health: Comment
Buspirone is an azaspirodecanedione (nonbenzodiazepine) anxiolytic and is not GABA-ergic. It is extensively metabolized primarily by oxidation producing several hydroxylated derivatives and a pharmacologically-active metabolite, 1-pyrimidinyl piperazine (1-PP). 1-PP has about 20% the activity of buspirone. Buspirone decreases anxiety without causing sedation or having anticonvulsant or muscle relaxant properties. Initial therapeutic effect is usually seen as a decrease in irritability and worry. Buspirone is as effective as the benzodiazepines in relieving anxiety, but has a slow onset of action. It is important to wait 3-4 weeks before assessing the response to buspirone.
The advantages of buspirone include a low abuse potential (no reinforcing value in substance abusers and tended to cause dysphoria at doses >40 mg/day), causes no impairment of psychomotor activity, is not associated with dependence and can be abruptly discontinued, produces minimal sedation, and does not potentiate the effects of alcohol. May be useful for those who become disinhibited on benzodiazepines, those with a history of benzodiazepines/substance abuse, and those with a medical history in whom the use of a benzodiazepines may be risky.
The disadvantages of buspirone include a lag time for onset of anxiolytic effect similar to antidepressants, the requirement for multiple daily dosing, an inability to use as a PRN medication, a lack of cross tolerance with benzodiazepines, an inability to prevent withdrawal from benzodiazepines or alcohol, the requirement for adherent patients, and the potential for patients with previous exposure to benzodiazepines to be less likely to respond.
Nursing: Physical Assessment/Monitoring
Assess other medications patient may be taking for effectiveness and interactions. Monitor therapeutic effectiveness and adverse reactions at beginning of therapy and periodically with long-term use. Assess knowledge/teach patient appropriate use, interventions to reduce side effects, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as hydrochloride: 5 mg, 7.5 mg, 10 mg, 15 mg, 30 mg
BuSpar®: 5 mg, 10 mg, 15 mg, 30 mg
Pricing: U.S. (www.drugstore.com)
Tablets (BuSpar)
5 mg (60): $67.99
10 mg (60): $109.99
15 mg (60): $169.97
30 mg (30): $147.73
Tablets (BusPIRone HCl)
5 mg (30): $14.00
7.5 mg (60): $45.99
10 mg (90): $19.00
15 mg (90): $69.31
30 mg (30): $50.99
References
Buitelaar JK, van der Gaag RJ, and van der Hoeven J, “Buspirone in the Management of Anxiety and Irritability in Children With Pervasive Developmental Disorders: Results of an Open-Label Study,” J Clin Psychiatry, 1998, 59(2):56-9.
Carrey NJ, Wiggins DM, and Milin RP, “Pharmacological Treatment of Psychiatric Disorders in Children and Adolescents,” Drugs, 1996, 51(5):750-9.
Fanciullacci M, Sicuteri R, Alessandri M, et al, “Buspirone, But Not Sumatriptan, Induces Miosis in Humans: Relevance for a Serotoninergic Pupil Control,” Clin Pharmacol Ther, 1995, 57(3):349-55.
Gammans RE, Mayol RF, and LaBudde JA, “Metabolism and Disposition of Buspirone,” Am J Med, 1986, 80(3B):41-51.
Gammans RE, Westrick ML, Shea JP, et al, “Pharmacokinetics of Buspirone in Elderly Subjects,” J Clin Pharmacol, 1989, 29(1):72-8.
Goetz CM, Krenzelok EP, Lopez G, et al, “Buspirone Toxicity: A Prospective Study,” Vet Hum Toxicol, 1989, 31:371.
Green WH, Child and Adolescent Clinical Psychopharmacology, 3rd ed, Philadelphia, PA: Lippincott Williams & Wilkins, 2001.
Hanna GL, Feibusch EL, and Albright KJ, “Buspirone Treatment of Anxiety, Associated With Pharyngeal Dysphagia in a Four-Year Old,” J Child Adolesc Psychopharmacol, 1997, 7(2):137-43.
Jann MW, “Buspirone: An Update on a Unique Anxiolytic Agent,” Pharmacotherapy, 1988, 8(2):100-16.
Kivisto KT, Lamberg TS, and Kantola T, “Plasma Buspirone Concentrations Are Greatly Increased by Erythromycin and Itraconazole,” Clin Pharmacol Ther, 1997, 62(3):348-54.
Kunik ME, Yudofsky SC, Silver JM, et al, “Pharmacologic Approach to Management of Agitation Associated With Dementia,” J Clin Psychiatry, 1994, 55(Suppl 2):13-7.
Kutcher SP, Reiter S, Gardner DM, et al, “The Pharmacotherapy of Anxiety Disorders in Children and Adolescents,” Psychiatr Clin North Am, 1992, 15(1):41-67.
Lejoyeux M, et al, “Serotonin Syndrome: Incidence, Symptoms, and Treatment,” CNS Drugs, 1994, 2:132-43.
McIvor RJ and Sinanan K, “Buspirone-Induced Mania,” Br J Psychiatry, 1991, 158:136-7.
Norden MJ, “Buspirone Treatment of Sexual Dysfunction Associated With Selective Serotonin Reuptake Inhibitors,” Depression, 1994, 2:109-12.
Pfeffer CR, Jiang H, and Domeshek LJ, “Buspirone Treatment of Psychiatrically Hospitalized Prepubertal Children With Symptoms of Anxiety and Moderately Severe Aggression,” J Child Adolesc Psychopharmacol, 1997, 7(3):145-55.
Preskorn SH, “Recent Pharmacologic Advances in Antidepressant Therapy for the Elderly,” Am J Med, 1993, 94(5A):2S-12S.
Schweizer E and Rickels K, “New and Emerging Clinical Uses for Buspirone,” J Clin Psychiatry Monograph, 1994, 12(1):46-54.
Simeon JG, Knott VJ, DuBois C, et al, “Buspirone Therapy of Mixed Anxiety Disorders in Childhood and Adolescence: A Pilot Study,” J Child Adolesc Psychopharmacol, 1994, 4(3):159-70.
Soni P and Weintraub AL, “Buspirone-Associated Mental Status Changes,” J Am Acad Child Adolesc Psychiatry, 1992, 31(6):1098-9.
Sussman N, “The Usage of Buspirone in Psychiatry,” J Clin Psychiatry Monograph, 1994, 12(1):3-19.
Tiller JW, Burrows GD, and O'Sullivan BT, “Buspirone Overdose,” Med J Aust, 1989, 150(1):54-5.
Weis KJ, “Management of Anxiety and Depression Syndromes in Elderly,” J Clin Psychiatry, 1994, 55(Suppl 2):5-12.
International Brand Names
Lexi-Comp.com
Last full review/revision August 2008
Content last modified August 2008
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