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BusPIRone

Pronunciation

(byoo SPYE rone)

Index Terms

BuSpar
Buspirone Hydrochloride

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as hydrochloride:

Generic: 5 mg, 7.5 mg, 10 mg, 15 mg, 30 mg

Pharmacologic Category

Antianxiety Agent, Miscellaneous

Pharmacology

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.

Absorption

Rapid and complete; bioavailability is limited by extensive first-pass effect; only ~1% of the oral dose reaches the systemic circulation unchanged.

Distribution

V_d: 5.3 L/kg (Gammans 1986)

Metabolism

Hepatic oxidation, primarily via CYP3A4 to several metabolites including an active metabolite, 1-pyrimidinylpiperazine (1-PP; exhibits about 25% of the activity of buspirone); extensive first-pass effect

Excretion

Urine: 29% to 63% (primarily as metabolites); feces: 18% to 38%

Onset of Action

DELETE

Time to Peak

Serum: 40 to 90 minutes

Half-Life Elimination

2 to 3 hours; increased with renal or hepatic impairment

Protein Binding

~86%

Special Populations: Renal Function Impairment

AUC increased 4-fold.

Special Populations: Hepatic Function Impairment

AUC increased 13-fold.

Use: Labeled Indications

Anxiety: Management of anxiety disorders or the short-term relief of the symptoms of anxiety.

Off Label Uses

Augmentation agent for antidepressants

Data from a randomized controlled trial in patients with nonpsychotic major depressive disorder without remission despite treatment with a selective serotonin reuptake inhibitor (ie, citalopram) who were randomized to either sustained-release bupropion or buspirone as an augmentation strategy supports the use of add-on buspirone for the treatment of this condition ^{[Trivedi 2006]}.

Based on the American Psychiatric Association (APA) practice guideline for the treatment of patients with major depressive disorder, buspirone (added to citalopram) is an effective augmentation strategy for this condition.

Contraindications

Hypersensitivity to buspirone or any component of the formulation; concomitant use of MAOIs intended to treat depression or within 14 days of discontinuing MAOIs intended to treat depression; concomitant use of MAOIs within 14 days of discontinuing buspirone; initiation of buspirone in patients receiving reversible MAOIs (eg, linezolid, IV methylene blue).

Dosing: Adult

Note: Periodically assess the usefulness of the drug for the individual patient.

Anxiety: Oral: Initial: 7.5 mg twice daily; may increase every 2 to 3 days in increments of 2.5 mg twice daily to a maximum of 30 mg twice daily; usual dose: 20 to 30 mg/day (in divided doses).

Augmentation agent for antidepressants (off-label use): Oral: Initial: 7.5 mg twice daily; may increase weekly in increments of 7.5 mg twice daily to a maximum of 30 mg twice daily (Trivedi, 2006).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer’s labeling; use with caution (these patients demonstrated increased plasma levels and a prolonged half-life of buspirone).

Severe impairment: Use not recommended.

Dosing: Hepatic Impairment

Severe impairment: Use not recommended.

Administration

Administer with or without food, but must be consistent.

Dietary Considerations

Avoid large quantities of grapefruit juice.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). Protect from light.

Drug Interactions

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Analgesics (Opioid): CNS Depressants may enhance the CNS depressant effect of Analgesics (Opioid). Management: Avoid concomitant use of opioid analgesics and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Antidepressants (Serotonin Reuptake Inhibitor/Antagonist): BusPIRone may enhance the serotonergic effect of Antidepressants (Serotonin Reuptake Inhibitor/Antagonist). Management: The combination of a serotonin reuptake inhibitor,antagonist and buspirone should be undertaken with great caution. When combined treatment is clinically indicated, monitor closely for signs of serotonin toxicity/serotonin syndrome. Consider therapy modification

Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of BusPIRone. Isavuconazonium considerations are addressed in separate monographs. Exceptions: Isavuconazonium Sulfate. Consider therapy modification

Antipsychotic Agents: Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification

Calcium Channel Blockers (Nondihydropyridine): May decrease the metabolism of BusPIRone. Exceptions: Bepridil. Consider therapy modification

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dapoxetine: May enhance the adverse/toxic effect of Serotonin Modulators. Avoid combination

Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Grapefruit Juice: May increase the serum concentration of BusPIRone. Management: Monitor for increased therapeutic effects of buspirone if increased quantities of grapefruit juice are consumed. Periodic, small portions of grapefruit juice are likely of little concern, but large quantities should be avoided. Consider therapy modification

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Ioflupane I 123: BusPIRone may diminish the diagnostic effect of Ioflupane I 123. Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Macrolide Antibiotics: May decrease the metabolism of BusPIRone. Exceptions: Azithromycin (Systemic); Fidaxomicin; Roxithromycin; Spiramycin. Consider therapy modification

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

MAO Inhibitors: BusPIRone may enhance the adverse/toxic effect of MAO Inhibitors. Specifically, blood pressure elevations been reported. Avoid combination

Metaxalone: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Methotrimeprazine: May enhance the CNS depressant effect of CNS Depressants. CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

Methylene Blue: BusPIRone may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Avoid combination

Methylphenidate: May enhance the adverse/toxic effect of Serotonin Modulators. Specifically, the risk of serotonin syndrome or serotonin toxicity may be increased. Monitor therapy

Metoclopramide: Serotonin Modulators may enhance the adverse/toxic effect of Metoclopramide. This may be manifest as symptoms consistent with serotonin syndrome or neuroleptic malignant syndrome. Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

Resveratrol: May increase the serum concentration of BusPIRone. Monitor therapy

Rifamycin Derivatives: May decrease the serum concentration of BusPIRone. Management: The degree to which rifampin alters buspirone concentrations warrants the consideration of an alternative to buspirone that is not metabolized by CYP3A4. If these agents are used together, buspirone dose adjustments may be needed. Consider therapy modification

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

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. Management: The combination of a selective serotonin reuptake inhibitor and buspirone should be undertaken with great caution. When combined treatment is clinically indicated, monitor closely for signs of serotonin toxicity/serotonin syndrome. Consider therapy modification

Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

St John's Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Yohimbine: May diminish the therapeutic effect of Antianxiety Agents. Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Test Interactions

The presence of buspirone may result in a false positive on a urinary assay for metanephrine/catecholamine; discontinue buspirone ≥48 hours prior to collection of urine sample for catecholamines.

Adverse Reactions

>10%: Central nervous system: Dizziness (3% to 12%)

1% to 10%:

Cardiovascular: Chest pain (≥1%)

Central nervous system: Drowsiness (10%), headache (6%), nervousness (5%), confusion (2%), excitement (2%), numbness (2%), outbursts of anger (2%), abnormal dreams (≥1%), ataxia (1%) paresthesia (1%)

Dermatologic: Diaphoresis (1%), skin rash (1%)

Gastrointestinal: Nausea (8%), diarrhea (2%), sore throat (≥1%)

Neuromuscular & skeletal: Weakness (2%), musculoskeletal pain (1%), tremor (1%)

Ophthalmic: Blurred vision (2%)

Otic: Tinnitus (≥1%)

Respiratory: Nasal congestion (≥1%)

<1% (Limited to important or life-threatening): Alcohol abuse, alopecia, amenorrhea, angioedema, anorexia, bradycardia, bruise, cardiac failure, cardiomyopathy, cerebrovascular accident, claustrophobia, cogwheel rigidity, conjunctivitis, dyskinesia, dystonia, edema, eosinophilia, epistaxis, extrapyramidal reaction, galactorrhea, hallucination, hemorrhagic diathesis, hypersensitivity reaction, hypertension, hyperventilation, hypotension, increased intraocular pressure, increased serum ALT, increased serum AST, increased serum transaminases, irritable bowel syndrome, leukopenia, memory impairment, menstrual disease, myocardial infarction, parkinsonian-like syndrome, pelvic inflammatory disease, personality disorder, photophobia, psychosis, rectal hemorrhage, restless leg syndrome, seizure, serotonin syndrome, slowed reaction time, slurred speech, suicidal ideation, syncope, thrombocytopenia, thyroid disease, urinary incontinence, visual disturbance (tunnel vision)

Warnings/Precautions

Concerns related to adverse effects:

• Akathisia: Akathisia, or restlessness, has been reported in small number of patients; may be a result of central dopamine receptor antagonism. Monitor for signs of any dopamine-related movement disorders (eg, dystonia, akathisia, pseudo-parkinsonism, tardive dyskinesia).

• CNS depression: May rarely cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

• Serotonin syndrome: Potentially life-threatening serotonin syndrome has occurred with serotonergic agents, including buspirone, particularly when used in combination with other serotonergic agents (eg, triptans, TCAs, fentanyl, lithium, tramadol, buspirone, St John’s wort, tryptophan) or agents that impair metabolism of serotonin (eg, MAOIs intended to treat psychiatric disorders, other MAOIs [ie, linezolid and IV methylene blue]). Monitor patients closely for signs of serotonin syndrome, such as mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile blood pressure, diaphoresis, flushing, hyperthermia); neuromuscular changes (eg, tremor, rigidity, myoclonus); GI symptoms (eg, nausea, vomiting, diarrhea); and/or seizures. Discontinue treatment (and any concomitant serotonergic agent) immediately if signs/symptoms arise.

Disease-related concerns:

• Hepatic impairment: Use caution in patients with hepatic impairment; use in severe hepatic impairment is not recommended.

• Renal impairment: Use caution in patients with renal impairment; use in severe renal impairment is not recommended.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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.

Monitoring Parameters

Mental status, symptoms of anxiety, signs/symptoms of serotonin syndrome.

Pregnancy Risk Factor

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience fatigue, dizziness, anxiety, headache, or nausea. Have patient report immediately to prescriber signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, abnormal heartbeat, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea), agitation, abnormal movements, twitching, change in balance, difficulty speaking, or difficulty swallowing (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.