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  • CLASSES

    Anxiolytics, Non-Benzodiazepines

    DEA CLASS

    Rx

    DESCRIPTION

    Oral anxiolytic pharmacologically distinct from other anxiolytics
    Used for adults with generalized anxiety disorder; efficacy in pediatric patients is uncertain
    Not effective for the acute relief of anxiety due to a delayed onset of effect

    COMMON BRAND NAMES

    BuSpar

    HOW SUPPLIED

    BuSpar/Buspirone/Buspirone Hydrochloride Oral Tab: 5mg, 7.5mg, 10mg, 15mg, 30mg

    DOSAGE & INDICATIONS

    For the treatment of generalized anxiety disorder (GAD) or for the short-term relief of the symptoms of anxiety.
    Oral dosage
    Adults

    7.5 mg PO twice daily initially, then increase as needed by 5 mg/day every 2 to 3 days. Usual maintenance dose: 15 to 30 mg/day administered in 2 to 3 divided doses. Max: 60 mg/day PO.

    Geriatric Adults

    5 mg PO twice daily initially, then increase as needed by 5 mg/day every 2 to 3 days. Usual maintenance dose: 15 to 30 mg/day administered in 2 to 3 divided doses. Max: 60 mg/day. According to the federal Omnibus Budget Reconciliation Act (OBRA), tapering attempts or documentation of medical necessity are required in residents of long-term care facilities receiving an anxiolytic.

    MAXIMUM DOSAGE

    Adults

    60 mg/day PO.

    Geriatric

    60 mg/day PO.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    Infants

    Not indicated.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Buspirone is not recommended for use in patients with severe hepatic impairment.

    Renal Impairment

    CrCl less than 30 mL/minute: Buspirone is not recommended for use in patients with severe renal impairment or renal failure.
     
    Intermittent hemodialysis
    Buspirone is not recommended in patients with renal failure.

    ADMINISTRATION

    Oral Administration

    Buspirone should be taken in a consistent manner with regard to food, either always with or always without food.

    STORAGE

    Generic:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    BuSpar:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Buspirone is contraindicated in patients with a known hypersensitivity to buspirone.
     
    Buspirone may interfere with the urinary metanephrine/catecholamine assay. It has been mistakenly read as metanephrine during routine assay testing for pheochromocytoma, resulting in a false positive laboratory result. Buspirone hydrochloride should therefore be discontinued for at least 48 hours prior to undergoing a urine collection for catecholamines.

    MAOI therapy

    The use of monoamine oxidase inhibitor therapy (MAOI therapy) intended to treat depression with buspirone or within 14 days of stopping treatment with buspirone is contraindicated because of an increased risk of serotonin syndrome and/or elevated blood pressure. The use of buspirone within 14 days of stopping an MAOI intended to treat depression is also contraindicated. Starting buspirone in a patient who is being treated with reversible MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome. Use other serotonergic medications with caution in patients taking buspirone due to a potential increase in serotonin syndrome risk. If serotonin syndrome occurs, discontinue serotonergic agents and institute appropriate treatment.

    Benzodiazepine dependence

    Buspirone has a slow onset of action; buspirone does not exhibit cross-tolerance with benzodiazepines and other common sedative/hypnotic drugs. Buspirone will not block the withdrawal syndrome often seen with cessation of therapy in those with benzodiazepine dependence. Therefore, before starting therapy with buspirone, it is advisable to withdraw patients gradually from the benzodiazepine or other prior CNS depressant treatment. Patients who are being converted from a benzodiazepine to buspirone therapy may need to overlap buspirone initiation with the downward titration of the benzodiazepine or other treatment. Rebound or withdrawal symptoms may occur over varying time periods, depending in part on the type of drug, and its effective half-life of elimination.

    Akathisia

    Because buspirone can bind to central dopamine receptors, a question has been raised about its potential to cause acute and chronic changes in dopamine-mediated neurological function (e.g., dystonia, pseudo-parkinsonism, akathisia, and tardive dyskinesia). Clinical experience in controlled trials has failed to identify any significant antipsychotic-like activity; however, a syndrome of restlessness, appearing shortly after initiation of treatment, has been reported in some small fraction of buspirone-treated patients. The syndrome may be explained in several ways. For example, buspirone may increase central noradrenergic activity; alternatively, the effect may be attributable to dopaminergic effects (i.e., represent akathisia).

    Renal failure, renal impairment

    Buspirone is metabolized by the liver and excreted by the kidneys. A pharmacokinetic study in patients with impaired renal function demonstrated increased plasma levels and a prolonged half-life of buspirone. Therefore, the administration of buspirone to patients with severe renal impairment or with renal failure is not recommended.

    Hepatic disease

    Buspirone is metabolized by the liver and excreted by the kidneys. A pharmacokinetic study in patients with impaired hepatic function demonstrated increased plasma levels and a lengthened half-life of buspirone. Therefore, the administration of buspirone to patients with severe hepatic disease is not recommended.

    Driving or operating machinery, ethanol ingestion

    Studies indicate that buspirone is less sedating than other anxiolytics and that it does not produce significant functional impairment. However, its CNS effects in any individual patient may not be predictable. Therefore, patients should be cautioned about driving or operating machinery until they are reasonably certain that buspirone treatment does not affect them adversely. While formal studies of the interaction of the drug with alcohol indicate that buspirone does not increase alcohol-induced impairment in motor and mental performance, it is prudent to avoid ethanol ingestion while taking buspirone.

    Geriatric

    The safety and efficacy profiles of buspirone in geriatric patients are similar to those in younger adults; however, greater sensitivity of some older patients cannot be ruled out; a lower initial dosage is recommended in geriatric patients. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). When buspirone is being used to manage behavior, stabilize mood, or treat a psychiatric disorder, the facility should attempt periodic tapering of the medication or provide documentation of medical necessity in accordance with OBRA guidelines.

    Pregnancy

    Well-controlled studies in pregnant women have not been performed with buspirone; therefore, buspirone should be used during pregnancy only when clearly needed. In a non-interventional observational cohort study, buspirone accounted for 16 of the 831 pregnancies in which women had taken a newly marketed drug during their first trimester. Overall, birth defects were noted in 14 of 557 newborns (2.5%). The 16 buspirone outcomes included 2 elective abortions, 1 intrauterine death, 12 normal term babies, and 1 newborn with cystic fibrosis. Teratogenic effects were not observed in animal studies when using approximately 30 times the maximum recommended human dose (MRHD); however, animal reproduction studies are not always predictive of human response. The effects of buspirone during labor and delivery are unknown.

    Breast-feeding

    Buspirone should be avoided during breast-feeding if clinically possible; the extent of excretion of buspirone and its active metabolite into human milk is not known. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. Buspirone and its metabolites are excreted in the milk of lactating rats. There is often a lack of information regarding anxiolytic use during breast-feeding. Due to individual variability in the response to anxiolytics, it may be prudent to continue the existing regimen with caution if ongoing treatment is deemed necessary during breast-feeding. A pooled analysis found that maternal use of paroxetine usually produced undetectable or low drug concentrations in infant serum; this agent may be an option when initiating therapy for generalized anxiety disorder (GAD) in a breast-feeding mother. For acute anxiety requiring a benzodiazepine, short-acting agents such as oxazepam or lorazepam are preferred. The infant should be monitored regularly, and if sedation, nausea, reduced suckling, or other signs of toxicity are observed, either breast-feeding or the benzodiazepine should be discontinued. 

    Children, infants

    Buspirone is not approved by the FDA for any indication in infants, children, or adolescents. Buspirone has been used clinically in children and adolescents 6 years of age and older for the treatment of anxiety. However, efficacy in pediatric patients is uncertain; two placebo-controlled 6-week trials for generalized anxiety disorder (GAD) in pediatric patients 6 to 17 years of age reported no significant differences in efficacy between buspirone and placebo with regard to the symptoms of GAD following doses recommended for the treatment of GAD in adults. No unexpected safety findings were associated with buspirone in these trials. There are no long-term safety or efficacy data in pediatric patients.

    ADVERSE REACTIONS

    Severe

    suicidal ideation / Delayed / 0.1-1.0
    seizures / Delayed / 0.1-1.0
    GI bleeding / Delayed / 0.1-1.0
    cardiomyopathy / Delayed / 0-0.1
    stroke / Early / 0-0.1
    bradycardia / Rapid / 0-0.1
    myocardial infarction / Delayed / 0-0.1
    heart failure / Delayed / 0-0.1
    serotonin syndrome / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    visual impairment / Early / Incidence not known

    Moderate

    hostility / Early / 2.0-2.0
    confusion / Early / 2.0-2.0
    excitability / Early / 2.0-2.0
    blurred vision / Early / 2.0-2.0
    euphoria / Early / 0.1-1.0
    hallucinations / Early / 0.1-1.0
    involuntary movements / Delayed / 0.1-1.0
    dysphoria / Early / 0.1-1.0
    akathisia / Delayed / 0.1-1.0
    edema / Delayed / 0.1-1.0
    hematoma / Early / 0.1-1.0
    elevated hepatic enzymes / Delayed / 0.1-1.0
    dyspnea / Early / 0.1-1.0
    hypertension / Early / 0.1-1.0
    hypotension / Rapid / 0.1-1.0
    conjunctivitis / Delayed / 0.1-1.0
    dysuria / Early / 0.1-1.0
    dysarthria / Delayed / 0-0.1
    psychosis / Early / 0-0.1
    myasthenia / Delayed / 0-0.1
    eosinophilia / Delayed / 0-0.1
    thrombocytopenia / Delayed / 0-0.1
    leukopenia / Delayed / 0-0.1
    bleeding / Early / 0-0.1
    photophobia / Early / 0-0.1
    galactorrhea / Delayed / 0-0.1
    ejaculation dysfunction / Delayed / 0-0.1
    impotence (erectile dysfunction) / Delayed / 0-0.1
    chest pain (unspecified) / Early / 1.0
    dystonic reaction / Delayed / Incidence not known
    ataxia / Delayed / Incidence not known
    pseudoparkinsonism / Delayed / Incidence not known
    urinary retention / Early / Incidence not known

    Mild

    dizziness / Early / 12.0-12.0
    drowsiness / Early / 10.0-10.0
    nausea / Early / 8.0-8.0
    headache / Early / 6.0-6.0
    diarrhea / Early / 2.0-2.0
    tremor / Early / 1.0-1.0
    abnormal dreams / Early / 1.0-1.0
    paresthesias / Delayed / 1.0-1.0
    arthralgia / Delayed / 0.1-1.0
    myalgia / Early / 1.0-1.0
    musculoskeletal pain / Early / 1.0-1.0
    muscle cramps / Delayed / 0.1-1.0
    hyperhidrosis / Delayed / 1.0-1.0
    pruritus / Rapid / 0.1-1.0
    alopecia / Delayed / 0.1-1.0
    flushing / Rapid / 0.1-1.0
    xerosis / Delayed / 0.1-1.0
    rash / Early / 1.0-1.0
    weight gain / Delayed / 0.1-1.0
    weight loss / Delayed / 0.1-1.0
    anorexia / Delayed / 0.1-1.0
    hypersalivation / Early / 0.1-1.0
    flatulence / Early / 0.1-1.0
    appetite stimulation / Delayed / 0.1-1.0
    hyperventilation / Early / 0.1-1.0
    fever / Early / 0.1-1.0
    syncope / Early / 0.1-1.0
    dysgeusia / Early / 0.1-1.0
    ocular pruritus / Rapid / 0.1-1.0
    parosmia / Delayed / 0.1-1.0
    increased urinary frequency / Early / 0.1-1.0
    libido decrease / Delayed / 0.1-1.0
    menstrual irregularity / Delayed / 0.1-1.0
    libido increase / Delayed / 0.1-1.0
    malaise / Early / 0.1-1.0
    acne vulgaris / Delayed / 0-0.1
    epistaxis / Delayed / 0-0.1
    hiccups / Early / 0-0.1
    ocular pain / Early / 0-0.1
    amenorrhea / Delayed / 0-0.1
    nocturia / Early / 0-0.1
    nasal congestion / Early / 1.0
    tinnitus / Delayed / 1.0
    restlessness / Early / Incidence not known
    emotional lability / Early / Incidence not known
    insomnia / Early / Incidence not known
    restless legs syndrome (RLS) / Delayed / Incidence not known
    vertigo / Early / Incidence not known
    ecchymosis / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    weakness / Early / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Aspirin, ASA; Caffeine: (Minor) In vitro studies showed that therapeutic levels of aspirin, ASA increased the plasma concentrations of free buspirone by 23% through plasma protein binding displacement. In vivo interaction studies with these drugs have not been performed.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of dihydrocodeine, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Acetaminophen; Chlorpheniramine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Acetaminophen; Codeine: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of codeine, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs.
    Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Acetaminophen; Diphenhydramine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other central nervous system depressants, such as buspirone, can potentiate the effects of hydrocodone and may lead to additive CNS or respiratory depression. If hydrocodone is used with buspirone, the dose of one or both drugs should be reduced.
    Acetaminophen; Oxycodone: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of oxycodone, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs.
    Acetaminophen; Pamabrom; Pyrilamine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Acetaminophen; Pentazocine: (Moderate) Concomitant use of pentazocine with other CNS depressants can potentiate respiratory depression, CNS depression, and sedation. Pentazocine should be used cautiously in any patient receiving these agents, which may include buspirone.
    Acetaminophen; Propoxyphene: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of propoxyphene, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs.
    Acrivastine; Pseudoephedrine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Aldesleukin, IL-2: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
    Alfentanil: (Moderate) If concomitant use of alfentanil and buspirone is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Alprazolam: (Moderate) It is common for patients to overlap anxiety treatment when switching from benzodiazepines to buspirone. Buspirone has a slow onset of action and the drug will not block the withdrawal syndrome often seen with cessation of benzodiazepine therapy in those with benzodiazepine dependence. Therefore, before starting therapy with buspirone, withdraw patients gradually from the benzodiazepine. Alternatively, conversion to buspirone therapy may require treatment overlap to allow for the downward titration of the benzodiazepine while buspirone takes effect. It should be noted that the combination of buspirone and benzodiazepines can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent.
    Amiodarone: (Moderate) CYP3A4 inhibitors, such as amiodarone,may decrease systemic clearance of buspirone leading to increased or prolonged effects. If this combination is used, a low dose of buspirone, such as 2.5 mg PO twice daily, is recommended initially. Subsequent dosage adjustments should be based on clinical response.
    Amitriptyline: (Moderate) Coadministration of buspirone with tricyclic antidepressants (TCAs) may increase the risk of serotonin syndrome. Both types of medications have serotonergic properties. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Amobarbital: (Moderate) Monitor for reduced anxiolytic effect of buspirone. Potent inducers of CYP3A4, such as the barbiturates, may increase the rate of buspirone metabolism. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect. There is also a risk of additive CNS depression (drowsiness) when buspirone is given concomitantly with barbiturates. In a study in healthy volunteers, co-administration of buspirone with a potent CYP3A4 inducer decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone.
    Amoxapine: (Moderate) CNS depressants should be combined cautiously with amoxapine because they could cause additive depressant effects and possible respiratory depression or hypotension. This combination is considered to be safe as long as patients are monitored for excessive adverse effects from either agent.
    Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Concomitant administration of clarithromycin with buspirone may result in increases in buspirone AUC; the mechanism is probably reduced buspirone metabolism via CYP3A4. A low dose of buspirone is recommended if administered with significant CYP3A4 inhibitors. Subsequent dose adjustments should be based on clinical assessment.
    Amphetamines: (Moderate) Coadministration of buspirone with amphetamines may increase the risk of serotonin syndrome. At high doses, amphetamines can increase serotonin release and act as serotonin agonists. Buspirone has some serotonergic properties. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Amprenavir: (Moderate) When buspirone is administered with an inhibitor of CYP3A4 like amprenavir, a lower dose of buspirone is recommended. Dose adjustment of either drug should be based on clinical assessment.
    Apalutamide: (Moderate) Monitor for decreased efficacy of buspirone if apalutamide is added to a patient on a stable dosage of buspirone; a dose increase of buspirone may be needed to maintain anxiolytic activity. Buspirone is a sensitive CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the AUC of buspirone by 89.6%.
    Apraclonidine: (Minor) No specific drug interactions were identified with systemic agents and apraclonidine during clinical trials. Theoretically, apraclonidine might potentiate the effects of CNS depressant drugs such as the anxiolytics, sedatives, and hypnotics, including barbiturates or benzodiazepines.
    Aprepitant, Fosaprepitant: (Moderate) Use caution if buspirone and aprepitant, fosaprepitant are used concurrently and monitor for an increase in buspirone-related adverse effects for several days after administration of a multi-day aprepitant regimen. In vitro, buspirone is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of buspirone. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
    Aripiprazole: (Moderate) The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Asenapine: (Moderate) The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Aspirin, ASA: (Minor) In vitro studies showed that therapeutic levels of aspirin, ASA increased the plasma concentrations of free buspirone by 23% through plasma protein binding displacement. In vivo interaction studies with these drugs have not been performed.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Monitor for reduced anxiolytic effect of buspirone. Potent inducers of CYP3A4, such as the barbiturates, may increase the rate of buspirone metabolism. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect. There is also a risk of additive CNS depression (drowsiness) when buspirone is given concomitantly with barbiturates. In a study in healthy volunteers, co-administration of buspirone with a potent CYP3A4 inducer decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone. (Minor) In vitro studies showed that therapeutic levels of aspirin, ASA increased the plasma concentrations of free buspirone by 23% through plasma protein binding displacement. In vivo interaction studies with these drugs have not been performed.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of codeine, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs. (Moderate) Monitor for reduced anxiolytic effect of buspirone. Potent inducers of CYP3A4, such as the barbiturates, may increase the rate of buspirone metabolism. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect. There is also a risk of additive CNS depression (drowsiness) when buspirone is given concomitantly with barbiturates. In a study in healthy volunteers, co-administration of buspirone with a potent CYP3A4 inducer decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone. (Minor) In vitro studies showed that therapeutic levels of aspirin, ASA increased the plasma concentrations of free buspirone by 23% through plasma protein binding displacement. In vivo interaction studies with these drugs have not been performed.
    Aspirin, ASA; Caffeine: (Minor) In vitro studies showed that therapeutic levels of aspirin, ASA increased the plasma concentrations of free buspirone by 23% through plasma protein binding displacement. In vivo interaction studies with these drugs have not been performed.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of dihydrocodeine, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs. (Minor) In vitro studies showed that therapeutic levels of aspirin, ASA increased the plasma concentrations of free buspirone by 23% through plasma protein binding displacement. In vivo interaction studies with these drugs have not been performed.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Concomitant use of skeletal muscle relaxants with buspirone can result in additive CNS depression. Dosage adjustments of either or both medications may be necessary. (Minor) In vitro studies showed that therapeutic levels of aspirin, ASA increased the plasma concentrations of free buspirone by 23% through plasma protein binding displacement. In vivo interaction studies with these drugs have not been performed.
    Aspirin, ASA; Carisoprodol: (Moderate) Concomitant use of skeletal muscle relaxants with buspirone can result in additive CNS depression. Dosage adjustments of either or both medications may be necessary. (Minor) In vitro studies showed that therapeutic levels of aspirin, ASA increased the plasma concentrations of free buspirone by 23% through plasma protein binding displacement. In vivo interaction studies with these drugs have not been performed.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of codeine, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs. (Moderate) Concomitant use of skeletal muscle relaxants with buspirone can result in additive CNS depression. Dosage adjustments of either or both medications may be necessary. (Minor) In vitro studies showed that therapeutic levels of aspirin, ASA increased the plasma concentrations of free buspirone by 23% through plasma protein binding displacement. In vivo interaction studies with these drugs have not been performed.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Minor) In vitro studies showed that therapeutic levels of aspirin, ASA increased the plasma concentrations of free buspirone by 23% through plasma protein binding displacement. In vivo interaction studies with these drugs have not been performed.
    Aspirin, ASA; Dipyridamole: (Minor) In vitro studies showed that therapeutic levels of aspirin, ASA increased the plasma concentrations of free buspirone by 23% through plasma protein binding displacement. In vivo interaction studies with these drugs have not been performed.
    Aspirin, ASA; Omeprazole: (Minor) In vitro studies showed that therapeutic levels of aspirin, ASA increased the plasma concentrations of free buspirone by 23% through plasma protein binding displacement. In vivo interaction studies with these drugs have not been performed.
    Aspirin, ASA; Oxycodone: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of oxycodone, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs. (Minor) In vitro studies showed that therapeutic levels of aspirin, ASA increased the plasma concentrations of free buspirone by 23% through plasma protein binding displacement. In vivo interaction studies with these drugs have not been performed.
    Aspirin, ASA; Pravastatin: (Minor) In vitro studies showed that therapeutic levels of aspirin, ASA increased the plasma concentrations of free buspirone by 23% through plasma protein binding displacement. In vivo interaction studies with these drugs have not been performed.
    Atazanavir: (Moderate) When buspirone is administered with an inhibitor of CYP3A4 like atazanavir, a lower dose of buspirone is recommended. Dose adjustment of either drug should be based on clinical assessment.
    Atazanavir; Cobicistat: (Moderate) A low dose of buspirone used cautiously is recommended when coadministered with cobicistat. If a patient has been titrated to a stable dosage of buspirone, a dose adjustment of buspirone may be necessary to avoid adverse events attributable to buspirone. Administering cobicistat with buspirone may increase buspirone concentration and risk for adverse events. Buspirone is a sensitive substrate of CYP3A4. Cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the buspirone AUC by 19-fold with an increased incidence of buspirone-related adverse effects. (Moderate) When buspirone is administered with an inhibitor of CYP3A4 like atazanavir, a lower dose of buspirone is recommended. Dose adjustment of either drug should be based on clinical assessment.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Theoretically, concurrent use of methylene blue and buspirone may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and buspirone increases central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Atropine; Difenoxin: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of diphenoxylate/difenoxin, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs.
    atypical antipsychotic: (Moderate) The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Azelastine: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including buspirone.
    Azelastine; Fluticasone: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including buspirone.
    Baclofen: (Moderate) Concomitant use of skeletal muscle relaxants with buspirone can result in additive CNS depression. Dosage adjustments of either or both medications may be necessary.
    Barbiturates: (Moderate) Monitor for reduced anxiolytic effect of buspirone. Potent inducers of CYP3A4, such as the barbiturates, may increase the rate of buspirone metabolism. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect. There is also a risk of additive CNS depression (drowsiness) when buspirone is given concomitantly with barbiturates. In a study in healthy volunteers, co-administration of buspirone with a potent CYP3A4 inducer decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Monitor for reduced anxiolytic effect of buspirone. Potent inducers of CYP3A4, such as the barbiturates, may increase the rate of buspirone metabolism. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect. There is also a risk of additive CNS depression (drowsiness) when buspirone is given concomitantly with barbiturates. In a study in healthy volunteers, co-administration of buspirone with a potent CYP3A4 inducer decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone.
    Belladonna; Opium: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of opium, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Theoretically, concurrent use of methylene blue and buspirone may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and buspirone increases central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Berotralstat: (Moderate) Monitor for an increase in buspirone-related adverse reactions if coadministration with berotralstat is necessary; the effect may be more pronounced if the patient has been titrated to a stable dose of buspirone and berotralstat is added or removed from therapy. Buspirone is a sensitive CYP3A4 substrate and berotralstat is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors increased buspirone exposure by 3.4 to 6-fold and was accompanied by increased buspirone-related adverse reactions.
    Boceprevir: (Moderate) Close clinical monitoring is advised when administering buspirone with boceprevir due to an increased potential for buspirone-related adverse events. If buspirone dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of buspirone. Buspirone is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated buspirone plasma concentrations.
    Brexpiprazole: (Moderate) The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Brompheniramine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including buspirone. (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other central nervous system depressants, such as buspirone, can potentiate the effects of hydrocodone and may lead to additive CNS or respiratory depression. If hydrocodone is used with buspirone, the dose of one or both drugs should be reduced. (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other central nervous system depressants, such as buspirone, can potentiate the effects of hydrocodone and may lead to additive CNS or respiratory depression. If hydrocodone is used with buspirone, the dose of one or both drugs should be reduced. (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Brompheniramine; Phenylephrine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Brompheniramine; Pseudoephedrine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Buprenorphine: (Moderate) If concurrent use of buspirone and buprenorphine is necessary, consider a dose reduction of one or both drugs because of the potential for additive pharmacological effects. Sedation, coma, or respiratory depression may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
    Buprenorphine; Naloxone: (Moderate) If concurrent use of buspirone and buprenorphine is necessary, consider a dose reduction of one or both drugs because of the potential for additive pharmacological effects. Sedation, coma, or respiratory depression may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
    Butabarbital: (Moderate) Monitor for reduced anxiolytic effect of buspirone. Potent inducers of CYP3A4, such as the barbiturates, may increase the rate of buspirone metabolism. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect. There is also a risk of additive CNS depression (drowsiness) when buspirone is given concomitantly with barbiturates. In a study in healthy volunteers, co-administration of buspirone with a potent CYP3A4 inducer decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone.
    Butalbital; Acetaminophen: (Moderate) Monitor for reduced anxiolytic effect of buspirone. Potent inducers of CYP3A4, such as the barbiturates, may increase the rate of buspirone metabolism. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect. There is also a risk of additive CNS depression (drowsiness) when buspirone is given concomitantly with barbiturates. In a study in healthy volunteers, co-administration of buspirone with a potent CYP3A4 inducer decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone.
    Butalbital; Acetaminophen; Caffeine: (Moderate) Monitor for reduced anxiolytic effect of buspirone. Potent inducers of CYP3A4, such as the barbiturates, may increase the rate of buspirone metabolism. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect. There is also a risk of additive CNS depression (drowsiness) when buspirone is given concomitantly with barbiturates. In a study in healthy volunteers, co-administration of buspirone with a potent CYP3A4 inducer decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of codeine, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs. (Moderate) Monitor for reduced anxiolytic effect of buspirone. Potent inducers of CYP3A4, such as the barbiturates, may increase the rate of buspirone metabolism. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect. There is also a risk of additive CNS depression (drowsiness) when buspirone is given concomitantly with barbiturates. In a study in healthy volunteers, co-administration of buspirone with a potent CYP3A4 inducer decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone.
    Butorphanol: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as buspirone, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
    Calcium, Magnesium, Potassium, Sodium Oxybates: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs.
    Capsaicin; Metaxalone: (Moderate) Concomitant use of skeletal muscle relaxants with buspirone can result in additive CNS depression. Dosage adjustments of either or both medications may be necessary.
    Carbamazepine: (Moderate) Substances that are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4, like carbamazepine, may increase the rate of buspirone metabolism.
    Carbetapentane; Chlorpheniramine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including buspirone. (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including buspirone. (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including buspirone. (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Carbetapentane; Guaifenesin: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including buspirone.
    Carbetapentane; Guaifenesin; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including buspirone.
    Carbetapentane; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including buspirone.
    Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including buspirone. (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Carbetapentane; Pseudoephedrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including buspirone.
    Carbetapentane; Pyrilamine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including buspirone. (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Carbinoxamine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with other central nervous system depressants, such as buspirone, can potentiate the effects of hydrocodone and may lead to additive CNS or respiratory depression. If hydrocodone is used with buspirone, the dose of one or both drugs should be reduced. (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other central nervous system depressants, such as buspirone, can potentiate the effects of hydrocodone and may lead to additive CNS or respiratory depression. If hydrocodone is used with buspirone, the dose of one or both drugs should be reduced. (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Carbinoxamine; Phenylephrine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Carbinoxamine; Pseudoephedrine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Cariprazine: (Moderate) The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Carisoprodol: (Moderate) Concomitant use of skeletal muscle relaxants with buspirone can result in additive CNS depression. Dosage adjustments of either or both medications may be necessary.
    Celecoxib; Tramadol: (Moderate) Tramadol can cause additive CNS depression when used with other agents that are CNS depressants including buspirone.
    Cenobamate: (Moderate) If cenobamate is added to a patient receiving a stable buspirone dose, a dose increase of buspirone may be needed to maintain anxiolytic activity. Buspirone is a sensitive CYP3A4 substrate and cenobamate is a moderate CYP3A4 inducer. CYP3A4 inducers may increase the rate of buspirone metabolism.
    Ceritinib: (Moderate) A low dose of buspirone used cautiously is recommended when coadministered with ceritinib. If a patient has been titrated to a stable dosage of buspirone, a dose adjustment of buspirone may be necessary to avoid adverse events attributable to buspirone. Administering ceritinib with buspirone may increase buspirone concentration and risk for adverse events. Buspirone is a sensitive substrate of CYP3A4. Ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the buspirone AUC by 19-fold with an increased incidence of buspirone-related adverse effects.
    Cetirizine: (Moderate) Additive drowsiness may occur if cetirizine/levocetirizine is administered with other drugs that depress the CNS, including buspirone.
    Cetirizine; Pseudoephedrine: (Moderate) Additive drowsiness may occur if cetirizine/levocetirizine is administered with other drugs that depress the CNS, including buspirone.
    Chlophedianol; Dexbrompheniramine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Chloral Hydrate: (Moderate) The combination of buspirone and other CNS depressants can increase the risk for sedation.
    Chlorcyclizine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Chlordiazepoxide: (Moderate) It is common for patients to overlap anxiety treatment when switching from benzodiazepines to buspirone. Buspirone has a slow onset of action and the drug will not block the withdrawal syndrome often seen with cessation of benzodiazepine therapy in those with benzodiazepine dependence. Therefore, before starting therapy with buspirone, withdraw patients gradually from the benzodiazepine. Alternatively, conversion to buspirone therapy may require treatment overlap to allow for the downward titration of the benzodiazepine while buspirone takes effect. It should be noted that the combination of buspirone and benzodiazepines can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent.
    Chlordiazepoxide; Amitriptyline: (Moderate) Coadministration of buspirone with tricyclic antidepressants (TCAs) may increase the risk of serotonin syndrome. Both types of medications have serotonergic properties. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be initiated. (Moderate) It is common for patients to overlap anxiety treatment when switching from benzodiazepines to buspirone. Buspirone has a slow onset of action and the drug will not block the withdrawal syndrome often seen with cessation of benzodiazepine therapy in those with benzodiazepine dependence. Therefore, before starting therapy with buspirone, withdraw patients gradually from the benzodiazepine. Alternatively, conversion to buspirone therapy may require treatment overlap to allow for the downward titration of the benzodiazepine while buspirone takes effect. It should be noted that the combination of buspirone and benzodiazepines can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent.
    Chlordiazepoxide; Clidinium: (Moderate) It is common for patients to overlap anxiety treatment when switching from benzodiazepines to buspirone. Buspirone has a slow onset of action and the drug will not block the withdrawal syndrome often seen with cessation of benzodiazepine therapy in those with benzodiazepine dependence. Therefore, before starting therapy with buspirone, withdraw patients gradually from the benzodiazepine. Alternatively, conversion to buspirone therapy may require treatment overlap to allow for the downward titration of the benzodiazepine while buspirone takes effect. It should be noted that the combination of buspirone and benzodiazepines can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent.
    Chlorpheniramine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Chlorpheniramine; Codeine: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of codeine, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs. (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Chlorpheniramine; Dextromethorphan: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of dihydrocodeine, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs. (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of dihydrocodeine, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs. (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other central nervous system depressants, such as buspirone, can potentiate the effects of hydrocodone and may lead to additive CNS or respiratory depression. If hydrocodone is used with buspirone, the dose of one or both drugs should be reduced. (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other central nervous system depressants, such as buspirone, can potentiate the effects of hydrocodone and may lead to additive CNS or respiratory depression. If hydrocodone is used with buspirone, the dose of one or both drugs should be reduced. (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with other central nervous system depressants, such as buspirone, can potentiate the effects of hydrocodone and may lead to additive CNS or respiratory depression. If hydrocodone is used with buspirone, the dose of one or both drugs should be reduced. (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other central nervous system depressants, such as buspirone, can potentiate the effects of hydrocodone and may lead to additive CNS or respiratory depression. If hydrocodone is used with buspirone, the dose of one or both drugs should be reduced. (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Chlorpheniramine; Phenylephrine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Chlorpheniramine; Pseudoephedrine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Chlorpromazine: (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as buspirone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Chlorzoxazone: (Moderate) Concomitant use of skeletal muscle relaxants with buspirone can result in additive CNS depression. Dosage adjustments of either or both medications may be necessary.
    Cimetidine: (Moderate) CYP3A4 inhibitors, such as cimetidine, may decrease systemic clearance of buspirone leading to increased or prolonged effects. If buspirone is to be administered concurrently with significant CYP3A4 inhibitors, a low dose of buspirone is recommended initially.
    Ciprofloxacin: (Moderate) Close clinical monitoring is recommended if buspirone is administered with ciprofloxacin; buspirone dose reductions may be required. The plasma concentrations of buspirone may be elevated when administered concurrently with ciprofloxacin. Predictions regarding this interaction can be made based on the metabolic pathways of these drugs. Ciprofloxacin is an inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of buspirone. These drugs used in combination may result in elevated buspirone plasma concentrations, causing an increased risk for buspirone-related adverse events.
    Citalopram: (Moderate) Coadministration of buspirone with citalopram may increase the risk of serotonin syndrome. Buspirone has some serotonergic properties. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Clarithromycin: (Moderate) Concomitant administration of clarithromycin with buspirone may result in increases in buspirone AUC; the mechanism is probably reduced buspirone metabolism via CYP3A4. A low dose of buspirone is recommended if administered with significant CYP3A4 inhibitors. Subsequent dose adjustments should be based on clinical assessment.
    Clemastine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Clobazam: (Moderate) Concomitant administration of clobazam with other CNS depressant drugs including anxiolytics, sedatives, and hypnotics, can potentiate the CNS effects (i.e., increased sedation or respiratory depression) of either agent.
    Clomipramine: (Moderate) Coadministration of buspirone with tricyclic antidepressants (TCAs) may increase the risk of serotonin syndrome. Both types of medications have serotonergic properties. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Clonazepam: (Moderate) It is common for patients to overlap anxiety treatment when switching from benzodiazepines to buspirone. Buspirone has a slow onset of action and the drug will not block the withdrawal syndrome often seen with cessation of benzodiazepine therapy in those with benzodiazepine dependence. Therefore, before starting therapy with buspirone, withdraw patients gradually from the benzodiazepine. Alternatively, conversion to buspirone therapy may require treatment overlap to allow for the downward titration of the benzodiazepine while buspirone takes effect. It should be noted that the combination of buspirone and benzodiazepines can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent.
    Clorazepate: (Moderate) It is common for patients to overlap anxiety treatment when switching from benzodiazepines to buspirone. Buspirone has a slow onset of action and the drug will not block the withdrawal syndrome often seen with cessation of benzodiazepine therapy in those with benzodiazepine dependence. Therefore, before starting therapy with buspirone, withdraw patients gradually from the benzodiazepine. Alternatively, conversion to buspirone therapy may require treatment overlap to allow for the downward titration of the benzodiazepine while buspirone takes effect. It should be noted that the combination of buspirone and benzodiazepines can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent.
    Clozapine: (Moderate) The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Cobicistat: (Moderate) A low dose of buspirone used cautiously is recommended when coadministered with cobicistat. If a patient has been titrated to a stable dosage of buspirone, a dose adjustment of buspirone may be necessary to avoid adverse events attributable to buspirone. Administering cobicistat with buspirone may increase buspirone concentration and risk for adverse events. Buspirone is a sensitive substrate of CYP3A4. Cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the buspirone AUC by 19-fold with an increased incidence of buspirone-related adverse effects.
    Codeine: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of codeine, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs.
    Codeine; Guaifenesin: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of codeine, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs.
    Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of codeine, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs.
    Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of codeine, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs. (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as buspirone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Codeine; Promethazine: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of codeine, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs. (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as buspirone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Conivaptan: (Moderate) Monitor for an increase in buspirone-related adverse reactions if coadministration with conivaptan is necessary; the effect may be more pronounced if the patient has been titrated to a stable dose of buspirone and conivaptan is added or removed from therapy. Buspirone is a sensitive CYP3A substrate and conivaptan is a moderate CYP3A inhibitor. Coadministration with other moderate CYP3A inhibitors increased buspirone exposure by 3.4 to 6-fold and was accompanied by increased buspirone-related adverse reactions.
    Crizotinib: (Moderate) Monitor for an increase in buspirone-related adverse reactions if coadministration with crizotinib is necessary; the effect may be more pronounced if the patient has been titrated to a stable dose of buspirone and crizotinib is added or removed from therapy. Buspirone is a sensitive CYP3A4 substrate and crizotinib is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased buspirone exposure by 3.4 to 6-fold and was accompanied by increased buspirone-related adverse reactions.
    Cyclizine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Cyclobenzaprine: (Moderate) Concomitant use of skeletal muscle relaxants with buspirone can result in additive CNS depression. Dosage adjustments of either or both medications may be necessary.
    Cyproheptadine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Dabrafenib: (Major) The concomitant use of dabrafenib and buspirone may lead to decreased buspirone concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of buspirone efficacy. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect. Dabrafenib is a moderate CYP3A4 inducer and buspirone is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
    Danazol: (Minor) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of buspirone, a CYP3A4 substrate.
    Dantrolene: (Moderate) Concomitant use of skeletal muscle relaxants with buspirone can result in additive CNS depression. Dosage adjustments of either or both medications may be necessary.
    Darunavir: (Moderate) The plasma concentrations of buspirone may be elevated when administered concurrently with darunavir. Close clinical monitoring is recommended during coadministration; buspirone dose reductions may be required. Predictions regarding this interaction can be made based on the metabolic pathways of these drugs. Darunavir is an inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of buspirone. These drugs used in combination may result in elevated buspirone plasma concentrations, causing an increased risk for buspirone-related adverse events.
    Darunavir; Cobicistat: (Moderate) A low dose of buspirone used cautiously is recommended when coadministered with cobicistat. If a patient has been titrated to a stable dosage of buspirone, a dose adjustment of buspirone may be necessary to avoid adverse events attributable to buspirone. Administering cobicistat with buspirone may increase buspirone concentration and risk for adverse events. Buspirone is a sensitive substrate of CYP3A4. Cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the buspirone AUC by 19-fold with an increased incidence of buspirone-related adverse effects. (Moderate) The plasma concentrations of buspirone may be elevated when administered concurrently with darunavir. Close clinical monitoring is recommended during coadministration; buspirone dose reductions may be required. Predictions regarding this interaction can be made based on the metabolic pathways of these drugs. Darunavir is an inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of buspirone. These drugs used in combination may result in elevated buspirone plasma concentrations, causing an increased risk for buspirone-related adverse events.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) A low dose of buspirone used cautiously is recommended when coadministered with cobicistat. If a patient has been titrated to a stable dosage of buspirone, a dose adjustment of buspirone may be necessary to avoid adverse events attributable to buspirone. Administering cobicistat with buspirone may increase buspirone concentration and risk for adverse events. Buspirone is a sensitive substrate of CYP3A4. Cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the buspirone AUC by 19-fold with an increased incidence of buspirone-related adverse effects. (Moderate) The plasma concentrations of buspirone may be elevated when administered concurrently with darunavir. Close clinical monitoring is recommended during coadministration; buspirone dose reductions may be required. Predictions regarding this interaction can be made based on the metabolic pathways of these drugs. Darunavir is an inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of buspirone. These drugs used in combination may result in elevated buspirone plasma concentrations, causing an increased risk for buspirone-related adverse events.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) When buspirone is administered with a potent inhibitor of CYP3A4 like ritonavir, a low dose of buspirone used cautiously is recommended. Some patients receiving drugs that are potent inhibitors of CYP3A4 with buspirone have reported lightheadedness, asthenia, dizziness, and drowsiness. If the two drugs are to be used in combination, a low dose of buspirone (e.g., 2.5 mg PO twice daily) is recommended. Subsequent dose adjustment of either drug should be based on clinical assessment. Several other anti-retroviral protease inhibitors also inhibit CYP3A4, and these may interact with buspirone in a similar manner.
    Delavirdine: (Moderate) CYP3A4 inhibitors, such as delaviridine, may decrease systemic clearance of buspirone leading to increased or prolonged effects. If buspirone is to be administered concurrently with significant CYP3A4 inhibitors, a low dose of buspirone (i.e., 2.5 mg PO twice daily) is recommended initially. Subsequent dosage adjustments should be based on clinical response.
    Desipramine: (Moderate) Coadministration of buspirone with tricyclic antidepressants (TCAs) may increase the risk of serotonin syndrome. Both types of medications have serotonergic properties. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Desvenlafaxine: (Moderate) Coadministration of buspirone with serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk of serotonin syndrome. Both types of medications have serotonergic properties. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Dexamethasone: (Moderate) Potent inducers of hepatic cytochrome P450 3A4, such as dexamethasone, may increase the rate of buspirone metabolism.
    Dexbrompheniramine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Dexbrompheniramine; Pseudoephedrine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Dexchlorpheniramine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Diazepam: (Moderate) It is common for patients to overlap anxiety treatment when switching from benzodiazepines to buspirone. Buspirone has a slow onset of action and the drug will not block the withdrawal syndrome often seen with cessation of benzodiazepine therapy in those with benzodiazepine dependence. Therefore, before starting therapy with buspirone, withdraw patients gradually from the benzodiazepine. Alternatively, conversion to buspirone therapy may require treatment overlap to allow for the downward titration of the benzodiazepine while buspirone takes effect. It should be noted that the combination of buspirone and benzodiazepines can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent.
    Dicyclomine: (Moderate) Dicyclomine can cause drowsiness, so it should be used cautiously in patients receiving CNS depressants like buspirone.
    Digoxin: (Minor) Buspirone can displace digoxin from plasma proteins, but the clinical significance of this effect has yet to be determined.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of dihydrocodeine, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs.
    Diltiazem: (Moderate) Coadministration of buspirone with diltiazem substantially increases the plasma concentration of buspirone. During coadministration with diltiazem, close monitoring is suggested, with adjustment of buspirone dosage if needed.
    Dimenhydrinate: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Diphenhydramine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with other central nervous system depressants, such as buspirone, can potentiate the effects of hydrocodone and may lead to additive CNS or respiratory depression. If hydrocodone is used with buspirone, the dose of one or both drugs should be reduced. (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Diphenhydramine; Ibuprofen: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Diphenhydramine; Naproxen: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Diphenhydramine; Phenylephrine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Diphenoxylate; Atropine: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of diphenoxylate/difenoxin, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs.
    Doxepin: (Moderate) Coadministration of buspirone with tricyclic antidepressants (TCAs) may increase the risk of serotonin syndrome. Both types of medications have serotonergic properties. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Doxylamine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Doxylamine; Pyridoxine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Dronabinol: (Moderate) Use caution if coadministration of dronabinol with buspirone is necessary, and monitor for additive dizziness, confusion, somnolence, and other CNS effects.
    Dronedarone: (Moderate) Dronedarone is metabolized by and is an inhibitor of CYP3A. Buspirone is a substrate for CYP3A4. The concomitant administration of dronedarone and CYP3A substrates may result in increased exposure of the substrate and should, therefore, be undertaken with caution.
    Droperidol: (Major) CNS depressants have additive effects with droperidol. Following administration of droperidol, lower doses of the other CNS depressant should be used.
    Duloxetine: (Moderate) Coadministration of buspirone with serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk of serotonin syndrome. Both types of medications have serotonergic properties. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Duvelisib: (Moderate) Monitor for an increase in buspirone-related adverse reactions if coadministration with duvelisib is necessary; the effect may be more pronounced if the patient has been titrated to a stable dose of buspirone and duvelisib is added or removed from therapy. Buspirone is a sensitive CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors increased buspirone exposure by 3.4 to 6-fold and was accompanied by increased buspirone-related adverse reactions.
    Efavirenz: (Moderate) Substances that are inducers of hepatic cytochrome P450 isoenzyme CYP3A4, such as efavirenz, may increase the rate of buspirone metabolism. In a study of healthy volunteers, co-administration of buspirone with rifampin decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect.
    Efavirenz; Emtricitabine; Tenofovir: (Moderate) Substances that are inducers of hepatic cytochrome P450 isoenzyme CYP3A4, such as efavirenz, may increase the rate of buspirone metabolism. In a study of healthy volunteers, co-administration of buspirone with rifampin decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Substances that are inducers of hepatic cytochrome P450 isoenzyme CYP3A4, such as efavirenz, may increase the rate of buspirone metabolism. In a study of healthy volunteers, co-administration of buspirone with rifampin decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect.
    Elagolix: (Moderate) Monitor for decreased efficacy of buspirone if elagolix is added to a patient on a stable dosage of buspirone; a dose increase of buspirone may be needed to maintain anxiolytic activity. Buspirone is a sensitive CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer.
    Elagolix; Estradiol; Norethindrone acetate: (Moderate) Monitor for decreased efficacy of buspirone if elagolix is added to a patient on a stable dosage of buspirone; a dose increase of buspirone may be needed to maintain anxiolytic activity. Buspirone is a sensitive CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer.
    Elbasvir; Grazoprevir: (Moderate) Administering buspirone with elbasvir; grazoprevir may result in elevated buspirone plasma concentrations. Buspirone is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) A low dose of buspirone used cautiously is recommended when coadministered with cobicistat. If a patient has been titrated to a stable dosage of buspirone, a dose adjustment of buspirone may be necessary to avoid adverse events attributable to buspirone. Administering cobicistat with buspirone may increase buspirone concentration and risk for adverse events. Buspirone is a sensitive substrate of CYP3A4. Cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the buspirone AUC by 19-fold with an increased incidence of buspirone-related adverse effects.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) A low dose of buspirone used cautiously is recommended when coadministered with cobicistat. If a patient has been titrated to a stable dosage of buspirone, a dose adjustment of buspirone may be necessary to avoid adverse events attributable to buspirone. Administering cobicistat with buspirone may increase buspirone concentration and risk for adverse events. Buspirone is a sensitive substrate of CYP3A4. Cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the buspirone AUC by 19-fold with an increased incidence of buspirone-related adverse effects.
    Encorafenib: (Moderate) Coadministration of encorafenib with buspirone may result in increased toxicity or decreased efficacy of buspirone. Buspirone is a sensitive CYP3A4 substrate. In vitro studies with encorafenib showed time-dependent inhibition of CYP3A4 and induction of CYP3A4. The clinical relevance of the in vivo effect of encorafenib on CYP3A4 is not established.
    Enzalutamide: (Moderate) Monitor for decreased efficacy of buspirone if enzalutamide is added to a patient on a stable dosage of buspirone; a dose increase of buspirone may be needed to maintain anxiolytic activity. Buspirone is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the AUC of buspirone by 89.6%.
    Erythromycin: (Moderate) Concomitant administration of erythromycin with buspirone may result in significant increases in buspirone AUC; the mechanism is probably reduced buspirone metabolism via CYP3A4. If the two drugs are to be used in combination, a low dose of buspirone is recommended. Subsequent dose adjustment of either drug should be based on clinical assessment.
    Erythromycin; Sulfisoxazole: (Moderate) Concomitant administration of erythromycin with buspirone may result in significant increases in buspirone AUC; the mechanism is probably reduced buspirone metabolism via CYP3A4. If the two drugs are to be used in combination, a low dose of buspirone is recommended. Subsequent dose adjustment of either drug should be based on clinical assessment.
    Escitalopram: (Moderate) Coadministration of buspirone with escitalopram may increase the risk of serotonin syndrome. Buspirone has some serotonergic properties. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Estazolam: (Moderate) It is common for patients to overlap anxiety treatment when switching from benzodiazepines to buspirone. Buspirone has a slow onset of action and the drug will not block the withdrawal syndrome often seen with cessation of benzodiazepine therapy in those with benzodiazepine dependence. Therefore, before starting therapy with buspirone, withdraw patients gradually from the benzodiazepine. Alternatively, conversion to buspirone therapy may require treatment overlap to allow for the downward titration of the benzodiazepine while buspirone takes effect. It should be noted that the combination of buspirone and benzodiazepines can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent.
    Eszopiclone: (Moderate) The combination of buspirone and other CNS depressants can increase the risk for sedation.
    Ethotoin: (Moderate) Hydantoins are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4 and may increase the rate of buspirone metabolism. In a study of healthy volunteers, co-administration of buspirone with rifampin decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone. An in vitro study indicated that buspirone did not displace highly protein-bound drugs such as phenytoin. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect. In addition, CNS depressants like the barbiturates may also enhance drowsiness or CNS depression.
    Fedratinib: (Moderate) Monitor for an increase in buspirone-related adverse reactions if coadministration with fedratinib is necessary; the effect may be more pronounced if the patient has been titrated to a stable dose of buspirone and fedratinib is added or removed from therapy. Buspirone is a sensitive CYP3A4 substrate and fedratinib is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors increased buspirone exposure by 3.4 to 6-fold and was accompanied by increased buspirone-related adverse reactions.
    Fenfluramine: (Moderate) Use fenfluramine and buspirone with caution due to an increased risk of serotonin syndrome. Monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Fentanyl: (Major) Concomitant use of fentanyl with other CNS depressants, such as buspirone, can potentiate the effects of fentanyl on respiration, CNS depression, sedation, and hypotension.
    Fluoxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering buspirone and fluoxetine. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Fluphenazine: (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as buspirone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Flurazepam: (Moderate) It is common for patients to overlap anxiety treatment when switching from benzodiazepines to buspirone. Buspirone has a slow onset of action and the drug will not block the withdrawal syndrome often seen with cessation of benzodiazepine therapy in those with benzodiazepine dependence. Therefore, before starting therapy with buspirone, withdraw patients gradually from the benzodiazepine. Alternatively, conversion to buspirone therapy may require treatment overlap to allow for the downward titration of the benzodiazepine while buspirone takes effect. It should be noted that the combination of buspirone and benzodiazepines can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent.
    Fluvoxamine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering buspirone and fluvoxamine. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Food: (Major) Buspirone should be taken consistently with or without food because food decreases the presystemic clearance of buspirone.
    Fosamprenavir: (Moderate) When buspirone is administered with an inhibitor of CYP3A4 like fosamprenavir, a lower dose of buspirone is recommended. Dose adjustment of either drug should be based on clinical assessment.
    Fosphenytoin: (Moderate) Hydantoins are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4 and may increase the rate of buspirone metabolism. In a study of healthy volunteers, co-administration of buspirone with rifampin decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone. An in vitro study indicated that buspirone did not displace highly protein-bound drugs such as phenytoin. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect. In addition, CNS depressants like the barbiturates may also enhance drowsiness or CNS depression.
    General anesthetics: (Moderate) General anesthetics potentiate the effects of CNS depressants.
    Grapefruit juice: (Major) Patients receiving buspirone should be advised to avoid drinking large amounts of grapefruit juice. In a study in healthy volunteers, coadministration of buspirone (10 mg single dose) with grapefruit juice (200 mL double-strength three times daily for 2 days) increased plasma buspirone concentrations significantly (4.3-fold increase in Cmax; 9.2-fold increase in AUC). Subjective drowsiness and other side effects of buspirone, like dizziness, nausea, headache, nervousness, or restlessness. may be increased with grapefruit juice ingestion.
    Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other central nervous system depressants, such as buspirone, can potentiate the effects of hydrocodone and may lead to additive CNS or respiratory depression. If hydrocodone is used with buspirone, the dose of one or both drugs should be reduced.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other central nervous system depressants, such as buspirone, can potentiate the effects of hydrocodone and may lead to additive CNS or respiratory depression. If hydrocodone is used with buspirone, the dose of one or both drugs should be reduced.
    Haloperidol: (Moderate) Monitor for adverse effects, such as excess sedation and QT prolongation, during coadministration of buspirone and haloperidol. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and buspirone. Elevated haloperidol concentrations may increase the risk of adverse effects, including QT prolongation.
    Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other central nervous system depressants, such as buspirone, can potentiate the effects of hydrocodone and may lead to additive CNS or respiratory depression. If hydrocodone is used with buspirone, the dose of one or both drugs should be reduced.
    Hydantoins: (Moderate) Hydantoins are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4 and may increase the rate of buspirone metabolism. In a study of healthy volunteers, co-administration of buspirone with rifampin decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone. An in vitro study indicated that buspirone did not displace highly protein-bound drugs such as phenytoin. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect. In addition, CNS depressants like the barbiturates may also enhance drowsiness or CNS depression.
    Hydrocodone: (Moderate) Concomitant use of hydrocodone with other central nervous system depressants, such as buspirone, can potentiate the effects of hydrocodone and may lead to additive CNS or respiratory depression. If hydrocodone is used with buspirone, the dose of one or both drugs should be reduced.
    Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with other central nervous system depressants, such as buspirone, can potentiate the effects of hydrocodone and may lead to additive CNS or respiratory depression. If hydrocodone is used with buspirone, the dose of one or both drugs should be reduced.
    Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with other central nervous system depressants, such as buspirone, can potentiate the effects of hydrocodone and may lead to additive CNS or respiratory depression. If hydrocodone is used with buspirone, the dose of one or both drugs should be reduced.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Concomitant use of hydrocodone with other central nervous system depressants, such as buspirone, can potentiate the effects of hydrocodone and may lead to additive CNS or respiratory depression. If hydrocodone is used with buspirone, the dose of one or both drugs should be reduced.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other central nervous system depressants, such as buspirone, can potentiate the effects of hydrocodone and may lead to additive CNS or respiratory depression. If hydrocodone is used with buspirone, the dose of one or both drugs should be reduced.
    Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other central nervous system depressants, such as buspirone, can potentiate the effects of hydrocodone and may lead to additive CNS or respiratory depression. If hydrocodone is used with buspirone, the dose of one or both drugs should be reduced.
    Hydromorphone: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of hydromorphone, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs.
    Hydroxyzine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Theoretically, concurrent use of methylene blue and buspirone may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and buspirone increases central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Ibuprofen; Oxycodone: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of oxycodone, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs.
    Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with buspirone, a CYP3A substrate, as buspirone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Iloperidone: (Moderate) The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Imatinib: (Moderate) CYP3A4 inhibitors, such as imatinib, may decrease systemic clearance of buspirone leading to increased or prolonged effects. If buspirone is to be administered concurrently with significant CYP3A4 inhibitors, a low dose of buspirone is recommended initially.
    Imipramine: (Moderate) Coadministration of buspirone with tricyclic antidepressants (TCAs) may increase the risk of serotonin syndrome. Both types of medications have serotonergic properties. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Indinavir: (Moderate) When buspirone is administered with an inhibitor of CYP3A4 like indinavir, a lower dose of buspirone is recommended. Dose adjustment of either drug should be based on clinical assessment.
    Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with buspirone may result in increased serum concentrations of buspirone. Buspirone is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
    Isocarboxazid: (Contraindicated) Concomitant use of monoamine oxidase inhibitors (MAOIs) and buspirone is contraindicated because several cases of elevated blood pressure have been reported in patients taking MAO inhibitors who were then given buspirone; serotonin syndrome may also occur. A 10-day interval after discontinuing isocarboxazid is recommended before initiating buspirone treatment. At least 14 days should elapse between the discontinuation of phenelzine and initiating buspirone, At least a 7-day interval should elapse after discontinuing tranylcypromine before initiating buspirone treatment. Monitor for serotonin-related effects during therapy transitions.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Substances that are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4, such as rifampin, may increase the rate of buspirone metabolism. In a study of healthy volunteers, co-administration of buspirone with rifampin decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone. An in vitro study indicated that buspirone did not displace highly protein-bound drugs such as phenytoin. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect.
    Isoniazid, INH; Rifampin: (Major) Substances that are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4, such as rifampin, may increase the rate of buspirone metabolism. In a study of healthy volunteers, co-administration of buspirone with rifampin decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone. An in vitro study indicated that buspirone did not displace highly protein-bound drugs such as phenytoin. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect.
    Itraconazole: (Major) A low dose of buspirone is recommended (e.g., 2.5 mg daily) if used in combination with itraconazole. Subsequent dose adjustment of either drug should be based on clinical assessment. Buspirone is a sensitive CYP3A4 substrate; itraconazole is a strong CYP3A4 inhibitor. In a study in healthy volunteers, coadministration of buspirone with itraconazole increased the AUC and Cmax of buspirone by 19-fold and 13-fold, respectively. These pharmacokinetic interactions were accompanied by an increased incidence of side effects attributable to buspirone.
    Ivosidenib: (Moderate) Monitor for loss of efficacy of buspirone during coadministration of ivosidenib; a buspirone dose adjustment may be necessary. Buspirone is a sensitive substrate of CYP3A4; ivosidenib induces CYP3A4 and may lead to decreased buspirone concentrations.
    Ketoconazole: (Moderate) Pharmacokinetic data suggest that concomitant administration of ketoconazole and buspirone results in significant (up to 19-fold) increases in buspirone AUC; the mechanism is probably reduced buspirone metabolism via CYP3A4. However, a wide interindividual variability in the extent of the interaction has been noted. Some patients receiving these drugs with buspirone concurrently have reported lightheadedness, asthenia, dizziness, and drowsiness. If the two drugs are to be used in combination, a low dose of buspirone (e.g., 2.5 mg PO twice daily) is recommended.
    Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Concomitant administration of clarithromycin with buspirone may result in increases in buspirone AUC; the mechanism is probably reduced buspirone metabolism via CYP3A4. A low dose of buspirone is recommended if administered with significant CYP3A4 inhibitors. Subsequent dose adjustments should be based on clinical assessment.
    Lasmiditan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and buspirone. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Lefamulin: (Moderate) Monitor for an increase in buspirone-related adverse reactions if coadministration with oral lefamulin is necessary; the effect may be more pronounced if the patient has been titrated to a stable dose of buspirone and oral lefamulin is added or removed from therapy. Buspirone is a sensitive CYP3A4 substrate and oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin. Coadministration with other moderate CYP3A4 inhibitors increased buspirone exposure by 3.4 to 6-fold and was accompanied by increased buspirone-related adverse reactions.
    Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of buspirone; monitor for potential reduction in efficacy. Buspirone is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of buspirone; monitor for potential reduction in efficacy. Buspirone is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    Letermovir: (Moderate) Administering letermovir with buspirone may increase buspirone concentration and risk for adverse events. The magnitude of this interaction may be increased in patients who are also receiving cyclosporine. If a patient has been titrated to a stable dosage of buspirone, a dose adjustment of buspirone may be necessary to avoid adverse events attributable to buspirone. Consequently, when administered with both letermovir and cyclosporine, a low dose of buspirone used cautiously is recommended. Buspirone is a sensitive substrate of CYP3A4. Letermovir is a moderate CYP3A4 inhibitor. The combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.
    Levocetirizine: (Moderate) Additive drowsiness may occur if cetirizine/levocetirizine is administered with other drugs that depress the CNS, including buspirone.
    Levoketoconazole: (Moderate) Pharmacokinetic data suggest that concomitant administration of ketoconazole and buspirone results in significant (up to 19-fold) increases in buspirone AUC; the mechanism is probably reduced buspirone metabolism via CYP3A4. However, a wide interindividual variability in the extent of the interaction has been noted. Some patients receiving these drugs with buspirone concurrently have reported lightheadedness, asthenia, dizziness, and drowsiness. If the two drugs are to be used in combination, a low dose of buspirone (e.g., 2.5 mg PO twice daily) is recommended.
    Levomethadyl: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of levomethadyl, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs.
    Levomilnacipran: (Moderate) Coadministration of buspirone with serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk of serotonin syndrome. Both types of medications have serotonergic properties. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Levorphanol: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of levorphanol, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs.
    Linezolid: (Contraindicated) Due to an increased risk of serotonin syndrome, treatment initiation with buspirone is contraindicated in patients currently receiving linezolid, an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. If urgent psychiatric treatment is required, interventions other than buspirone (e.g., alternative medication, hospitalization) should be considered. In patients receiving buspirone and requiring urgent treatment with linezolid, buspirone should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. Buspirone may be re-initiated 24 hours after the last dose of linezolid.
    Lithium: (Moderate) Coadministration of buspirone with lithium may increase the risk of serotonin syndrome. Both medications have central serotonergic properties. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. If serotonin syndrome is suspected, all serotonergic agents should be discontinued and appropriate medical treatment should be implemented.
    Lonafarnib: (Moderate) A low dose of buspirone used cautiously is recommended when coadministered with lonafarnib. If a patient has been titrated to a stable dosage of buspirone, a dose adjustment of buspirone may be necessary to avoid adverse events attributable to buspirone. Administering lonafarnib with buspirone may increase buspirone concentration and risk for adverse events. Buspirone is a sensitive substrate of CYP3A4; lonafarnib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the buspirone AUC by 19-fold with an increased incidence of buspirone-related adverse effects.
    Lopinavir; Ritonavir: (Major) When buspirone is administered with a potent inhibitor of CYP3A4 like ritonavir, a low dose of buspirone used cautiously is recommended. Some patients receiving drugs that are potent inhibitors of CYP3A4 with buspirone have reported lightheadedness, asthenia, dizziness, and drowsiness. If the two drugs are to be used in combination, a low dose of buspirone (e.g., 2.5 mg PO twice daily) is recommended. Subsequent dose adjustment of either drug should be based on clinical assessment. Several other anti-retroviral protease inhibitors also inhibit CYP3A4, and these may interact with buspirone in a similar manner.
    Lorazepam: (Moderate) It is common for patients to overlap anxiety treatment when switching from benzodiazepines to buspirone. Buspirone has a slow onset of action and the drug will not block the withdrawal syndrome often seen with cessation of benzodiazepine therapy in those with benzodiazepine dependence. Therefore, before starting therapy with buspirone, withdraw patients gradually from the benzodiazepine. Alternatively, conversion to buspirone therapy may require treatment overlap to allow for the downward titration of the benzodiazepine while buspirone takes effect. It should be noted that the combination of buspirone and benzodiazepines can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent.
    Lorlatinib: (Moderate) Monitor for decreased efficacy of buspirone if lorlatinib is added to a patient on a stable dosage of buspirone; a dose increase of buspirone may be needed to maintain anxiolytic activity. Buspirone is a sensitive CYP3A4 substrate and lorlatinib is a moderate CYP3A4 inducer.
    Loxapine: (Moderate) The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for sedation.
    Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may reduce the efficacy of buspirone by decreasing its systemic exposure. A buspirone dosage adjustment may be necessary to maintain anxiolytic activity. Lumacaftor is a strong CYP3A inducer. Buspirone has been shown in vitro to be metabolized via CYP3A4; this finding is consistent with in vivo interactions observed. When coadministered with rifampin, another strong CYP3A inducer, buspirone Cmax and AUC decreased by 84% and 90%, respectively.
    Lumateperone: (Moderate) The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Lurasidone: (Moderate) The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Maprotiline: (Moderate) CNS depressants should be combined cautiously with maprotiline because they could cause additive depressant effects and possible respiratory depression or hypotension.
    Meclizine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Meperidine: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of meperidine, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs.
    Meperidine; Promethazine: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of meperidine, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs. (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as buspirone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Mephobarbital: (Moderate) Monitor for reduced anxiolytic effect of buspirone. Potent inducers of CYP3A4, such as the barbiturates, may increase the rate of buspirone metabolism. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect. There is also a risk of additive CNS depression (drowsiness) when buspirone is given concomitantly with barbiturates. In a study in healthy volunteers, co-administration of buspirone with a potent CYP3A4 inducer decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone.
    Meprobamate: (Moderate) The combination of buspirone and other CNS depressants can increase the risk for sedation.
    Mesoridazine: (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as buspirone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Metaxalone: (Moderate) Concomitant use of skeletal muscle relaxants with buspirone can result in additive CNS depression. Dosage adjustments of either or both medications may be necessary.
    Methadone: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of methadone, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Theoretically, concurrent use of methylene blue and buspirone may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and buspirone increases central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Methohexital: (Moderate) Monitor for reduced anxiolytic effect of buspirone. Potent inducers of CYP3A4, such as the barbiturates, may increase the rate of buspirone metabolism. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect. There is also a risk of additive CNS depression (drowsiness) when buspirone is given concomitantly with barbiturates. In a study in healthy volunteers, co-administration of buspirone with a potent CYP3A4 inducer decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone.
    Methscopolamine: (Moderate) CNS depression can be increased when methscopolamine is combined with other CNS depressants such as any anxiolytics, sedatives, and hypnotics.
    Methylene Blue: (Moderate) Theoretically, concurrent use of methylene blue and buspirone may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and buspirone increases central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Metoclopramide: (Minor) Combined use of metoclopramide and other CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase possible sedation.
    Midazolam: (Moderate) It is common for patients to overlap anxiety treatment when switching from benzodiazepines to buspirone. Buspirone has a slow onset of action and the drug will not block the withdrawal syndrome often seen with cessation of benzodiazepine therapy in those with benzodiazepine dependence. Therefore, before starting therapy with buspirone, withdraw patients gradually from the benzodiazepine. Alternatively, conversion to buspirone therapy may require treatment overlap to allow for the downward titration of the benzodiazepine while buspirone takes effect. It should be noted that the combination of buspirone and benzodiazepines can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent.
    Mifepristone: (Moderate) Strong CYP3A4 inhibitors, such as mifepristone, may decrease systemic clearance of buspirone leading to increased concentrations or prolonged effects. If buspirone is to be administered concurrently with significant CYP3A4 inhibitors, a low dose of buspirone (i.e., 2.5 mg PO twice daily) is recommended initially. Subsequent dosage adjustments should be based on clinical response.
    Milnacipran: (Moderate) Coadministration of buspirone with serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk of serotonin syndrome. Both types of medications have serotonergic properties. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Mirtazapine: (Moderate) The use of mirtazapine with buspirone may increase the risk for serotonin syndrome. Both medications have serotonergic effects. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome.
    Mitotane: (Major) Use caution if mitotane and buspirone are used concomitantly, and monitor for decreased efficacy of buspirone and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and buspirone is a CYP3A4 substrate in vitro; coadministration may result in decreased plasma concentrations of buspirone. Coadministration with another strong CYP3A inducer, rifampin, decreased the buspirone Cmax by 83.7% and AUC by 89.6%.
    Molindone: (Moderate) The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for sedation.
    Monoamine oxidase inhibitors: (Contraindicated) Concomitant use of monoamine oxidase inhibitors (MAOIs) and buspirone is contraindicated because several cases of elevated blood pressure have been reported in patients taking MAO inhibitors who were then given buspirone; serotonin syndrome may also occur. A 10-day interval after discontinuing isocarboxazid is recommended before initiating buspirone treatment. At least 14 days should elapse between the discontinuation of phenelzine and initiating buspirone, At least a 7-day interval should elapse after discontinuing tranylcypromine before initiating buspirone treatment. Monitor for serotonin-related effects during therapy transitions.
    Morphine: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of morphine, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of morphine and buspirone is imperative, reduce the dose of one or both drugs.
    Morphine; Naltrexone: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of morphine, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of morphine and buspirone is imperative, reduce the dose of one or both drugs.
    Nabilone: (Moderate) Concomitant use of nabilone with other CNS depressants can potentiate the effects of nabilone on respiratory depression.
    Nalbuphine: (Moderate) Concomitant use of nalbuphine with other CNS depressants, such as buspirone, can potentiate the effects of nalbuphine on respiratory depression, CNS depression, and sedation.
    Nefazodone: (Major) The administration of nefazodone with buspirone has resulted in marked increases in plasma buspirone concentrations most likely due to CYP3A4 inhibition by nefazodone. Some patients receiving both drugs concurrently have reported lightheadedness, asthenia, dizziness, and drowsiness. If buspirone is to be administered concurrently with nefazodone, a low dose of buspirone, such as 2.5 mg PO twice daily, is recommended. Subsequent dosage adjustments should be based on clinical response.
    Nelfinavir: (Moderate) When buspirone is administered with an inhibitor of CYP3A4 like nelfinavir, a lower dose of buspirone is recommended. Dose adjustment of either drug should be based on clinical assessment.
    Nicardipine: (Minor) Nicardipine is an inhibitor of CYP3A4 isoenzymes. Co-administration with nicardipine may lead to an increase in serum levels of drugs that are CYP3A4 substrates including buspirone.
    Nilotinib: (Moderate) Concomitant use of nilotinib, a moderate CYP3A4 inhibitor, and buspirone, a CYP3A4 substrate, may result in increased buspirone levels. A buspirone dose reduction may be necessary if these drugs are used together.
    Nirmatrelvir; Ritonavir: (Major) When buspirone is administered with a potent inhibitor of CYP3A4 like ritonavir, a low dose of buspirone used cautiously is recommended. Some patients receiving drugs that are potent inhibitors of CYP3A4 with buspirone have reported lightheadedness, asthenia, dizziness, and drowsiness. If the two drugs are to be used in combination, a low dose of buspirone (e.g., 2.5 mg PO twice daily) is recommended. Subsequent dose adjustment of either drug should be based on clinical assessment. Several other anti-retroviral protease inhibitors also inhibit CYP3A4, and these may interact with buspirone in a similar manner.
    Nortriptyline: (Moderate) Coadministration of buspirone with tricyclic antidepressants (TCAs) may increase the risk of serotonin syndrome. Both types of medications have serotonergic properties. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Olanzapine: (Moderate) The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Olanzapine; Fluoxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering buspirone and fluoxetine. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, serotonergic drugs should be discontinued and appropriate medical treatment should be initiated. (Moderate) The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Olanzapine; Samidorphan: (Moderate) The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Oliceridine: (Moderate) If concomitant use of oliceridine and buspirone is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) When buspirone is administered with a potent inhibitor of CYP3A4 like ritonavir, a low dose of buspirone used cautiously is recommended. Some patients receiving drugs that are potent inhibitors of CYP3A4 with buspirone have reported lightheadedness, asthenia, dizziness, and drowsiness. If the two drugs are to be used in combination, a low dose of buspirone (e.g., 2.5 mg PO twice daily) is recommended. Subsequent dose adjustment of either drug should be based on clinical assessment. Several other anti-retroviral protease inhibitors also inhibit CYP3A4, and these may interact with buspirone in a similar manner.
    Oritavancin: (Moderate) Buspirone is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of buspirone may be reduced if these drugs are administered concurrently.
    Orphenadrine: (Moderate) Concomitant use of skeletal muscle relaxants with buspirone can result in additive CNS depression. Dosage adjustments of either or both medications may be necessary.
    Oxazepam: (Moderate) It is common for patients to overlap anxiety treatment when switching from benzodiazepines to buspirone. Buspirone has a slow onset of action and the drug will not block the withdrawal syndrome often seen with cessation of benzodiazepine therapy in those with benzodiazepine dependence. Therefore, before starting therapy with buspirone, withdraw patients gradually from the benzodiazepine. Alternatively, conversion to buspirone therapy may require treatment overlap to allow for the downward titration of the benzodiazepine while buspirone takes effect. It should be noted that the combination of buspirone and benzodiazepines can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent.
    Oxybutynin: (Moderate) Additive CNS depression may occur when oxybutynin is used concomitantly with other CNS-depressant drugs, including anxiolytics, sedatives, and hypnotics.
    Oxycodone: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of oxycodone, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs.
    Oxymorphone: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of oxymorphone, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs.
    Ozanimod: (Major) Coadministration of ozanimod with buspirone is not recommended due to the potential for hypertensive crisis. If coadministration is necessary, closely monitor patients for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Buspirone may increase blood pressure by increasing serotonin concentrations.
    Palbociclib: (Moderate) Monitor for an increase in buspirone-related adverse reactions if coadministration with palbociclib is necessary. If palbociclib is added to a patient stabilized on buspirone, a buspirone dose adjustment may be necessary to avoid adverse events. Palbociclib is a weak time-dependent inhibitor of CYP3A while buspirone is a sensitive CYP3A4 substrate.
    Paliperidone: (Moderate) The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Papaverine: (Moderate) Concurrent use of papaverine with potent CNS depressants such as buspirone could lead to enhanced sedation.
    Paroxetine: (Moderate) Coadministration of buspirone and paroxetine may increase the risk of serotonin syndrome. Serotonin syndrome has been reported with both drugs when taken alone, but especially when coadministered with other serotonergic agents. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Pazopanib: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and buspirone, a CYP3A4 substrate, may cause an increase in systemic concentrations of buspirone. Use caution when administering these drugs concomitantly.
    Pentazocine: (Moderate) Concomitant use of pentazocine with other CNS depressants can potentiate respiratory depression, CNS depression, and sedation. Pentazocine should be used cautiously in any patient receiving these agents, which may include buspirone.
    Pentazocine; Naloxone: (Moderate) Concomitant use of pentazocine with other CNS depressants can potentiate respiratory depression, CNS depression, and sedation. Pentazocine should be used cautiously in any patient receiving these agents, which may include buspirone.
    Pentobarbital: (Moderate) Monitor for reduced anxiolytic effect of buspirone. Potent inducers of CYP3A4, such as the barbiturates, may increase the rate of buspirone metabolism. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect. There is also a risk of additive CNS depression (drowsiness) when buspirone is given concomitantly with barbiturates. In a study in healthy volunteers, co-administration of buspirone with a potent CYP3A4 inducer decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone.
    Perampanel: (Moderate) Co-administration of perampanel with CNS depressants, including ethanol, may increase CNS depression. The combination of perampanel (particularly at high doses) with ethanol has led to decreased mental alertness and ability to perform complex tasks (such as driving), as well as increased levels of anger, confusion, and depression; similar reactions should be expected with concomitant use of other CNS depressants, such as buspirone.
    Perphenazine: (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as buspirone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Perphenazine; Amitriptyline: (Moderate) Coadministration of buspirone with tricyclic antidepressants (TCAs) may increase the risk of serotonin syndrome. Both types of medications have serotonergic properties. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be initiated. (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as buspirone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Pexidartinib: (Moderate) Monitor for decreased efficacy of buspirone if pexidartinib is added to a patient on a stable dosage of buspirone; a dose increase of buspirone may be needed to maintain anxiolytic activity. Buspirone is a sensitive CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Phenelzine: (Contraindicated) Concomitant use of monoamine oxidase inhibitors (MAOIs) and buspirone is contraindicated because several cases of elevated blood pressure have been reported in patients taking MAO inhibitors who were then given buspirone; serotonin syndrome may also occur. A 10-day interval after discontinuing isocarboxazid is recommended before initiating buspirone treatment. At least 14 days should elapse between the discontinuation of phenelzine and initiating buspirone, At least a 7-day interval should elapse after discontinuing tranylcypromine before initiating buspirone treatment. Monitor for serotonin-related effects during therapy transitions.
    Phenobarbital: (Moderate) Monitor for reduced anxiolytic effect of buspirone. Potent inducers of CYP3A4, such as the barbiturates, may increase the rate of buspirone metabolism. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect. There is also a risk of additive CNS depression (drowsiness) when buspirone is given concomitantly with barbiturates. In a study in healthy volunteers, co-administration of buspirone with a potent CYP3A4 inducer decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Monitor for reduced anxiolytic effect of buspirone. Potent inducers of CYP3A4, such as the barbiturates, may increase the rate of buspirone metabolism. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect. There is also a risk of additive CNS depression (drowsiness) when buspirone is given concomitantly with barbiturates. In a study in healthy volunteers, co-administration of buspirone with a potent CYP3A4 inducer decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone.
    Phenothiazines: (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as buspirone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Phentermine; Topiramate: (Major) Although not specifically studied, coadministration of CNS depressant drugs with topiramate may potentiate CNS depression such as dizziness or cognitive adverse reactions, or other centrally mediated effects of these agents. Monitor for increased CNS effects if coadministering.
    Phenytoin: (Moderate) Hydantoins are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4 and may increase the rate of buspirone metabolism. In a study of healthy volunteers, co-administration of buspirone with rifampin decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone. An in vitro study indicated that buspirone did not displace highly protein-bound drugs such as phenytoin. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect. In addition, CNS depressants like the barbiturates may also enhance drowsiness or CNS depression.
    Pimozide: (Moderate) The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for sedation.
    Posaconazole: (Moderate) Posaconazole and buspirone should be coadministered with caution due to an increased potential for buspirone-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of buspirone. These drugs used in combination may result in elevated buspirone plasma concentrations, causing an increased risk for buspirone-related adverse events.
    Pregabalin: (Moderate) Concomitant administration of pregabalin with CNS depressant drugs, including buspirone, can potentiate the CNS effects of either agent.
    Primidone: (Moderate) Monitor for reduced anxiolytic effect of buspirone. Potent inducers of CYP3A4, such as the barbiturates, may increase the rate of buspirone metabolism. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect. There is also a risk of additive CNS depression (drowsiness) when buspirone is given concomitantly with barbiturates. In a study in healthy volunteers, co-administration of buspirone with a potent CYP3A4 inducer decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone.
    Procarbazine: (Contraindicated) Simultaneous use of buspirone with drugs that possess monoamine oxidase inhibitor activity, such as procarbazine, can increase blood pressure, so it is recommended that this combination be avoided. When switching drug therapy, there should be a 14-day delay after discontinuing a drug with MAOI-like actions before initiating a serotonergic drug like buspirone treatment.
    Prochlorperazine: (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as buspirone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Promethazine: (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as buspirone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Promethazine; Dextromethorphan: (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as buspirone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Promethazine; Phenylephrine: (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as buspirone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Propoxyphene: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of propoxyphene, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs.
    Protriptyline: (Moderate) Coadministration of buspirone with tricyclic antidepressants (TCAs) may increase the risk of serotonin syndrome. Both types of medications have serotonergic properties. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Pseudoephedrine; Triprolidine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Pyrilamine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Quazepam: (Moderate) It is common for patients to overlap anxiety treatment when switching from benzodiazepines to buspirone. Buspirone has a slow onset of action and the drug will not block the withdrawal syndrome often seen with cessation of benzodiazepine therapy in those with benzodiazepine dependence. Therefore, before starting therapy with buspirone, withdraw patients gradually from the benzodiazepine. Alternatively, conversion to buspirone therapy may require treatment overlap to allow for the downward titration of the benzodiazepine while buspirone takes effect. It should be noted that the combination of buspirone and benzodiazepines can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent.
    Quetiapine: (Moderate) The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Ramelteon: (Moderate) Due to pharmacodynamic additive effects, also use caution when combining ramelteon with buspirone.
    Ranolazine: (Moderate) Although data are not available, CYP3A4 inhibitors, such as ranolazine, may decrease systemic clearance of buspirone leading to increased or prolonged effects. If buspirone is to be administered concurrently with significant CYP3A4 inhibitors, a low dose of buspirone (i.e., 2.5 mg PO twice daily) is recommended initially. Subsequent dosage adjustments should be based on clinical response.
    Rasagiline: (Major) Monitor blood pressure for hypertension during concomitant use of rasagiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor) and buspirone. If a hypertensive crisis occurs, rasagiline should be discontinued immediately and therapy to lower blood pressure should be instituted immediately. Concomitant use of non-selective MAOIs and buspirone is contraindicated because several cases of elevated blood pressure have been reported when the drugs were used together or in succession.
    Remifentanil: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of remifentnil, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use is imperative, reduce the dose of one or both drugs if clinically indicated.
    Ribociclib: (Moderate) A low dose of buspirone used cautiously is recommended when coadministered with ribociclib. If a patient has been titrated to a stable dosage of buspirone, a dose adjustment of buspirone may be necessary to avoid adverse events attributable to buspirone. Administering ribociclib with buspirone may increase buspirone concentration and risk for adverse events. Buspirone is a sensitive substrate of CYP3A4. Ribociclib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the buspirone AUC by 19-fold with an increased incidence of buspirone-related adverse effects.
    Ribociclib; Letrozole: (Moderate) A low dose of buspirone used cautiously is recommended when coadministered with ribociclib. If a patient has been titrated to a stable dosage of buspirone, a dose adjustment of buspirone may be necessary to avoid adverse events attributable to buspirone. Administering ribociclib with buspirone may increase buspirone concentration and risk for adverse events. Buspirone is a sensitive substrate of CYP3A4. Ribociclib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the buspirone AUC by 19-fold with an increased incidence of buspirone-related adverse effects.
    Rifampin: (Major) Substances that are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4, such as rifampin, may increase the rate of buspirone metabolism. In a study of healthy volunteers, co-administration of buspirone with rifampin decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone. An in vitro study indicated that buspirone did not displace highly protein-bound drugs such as phenytoin. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect.
    Rifapentine: (Moderate) Monitor for decreased efficacy of buspirone if rifapentine is added to a patient on a stable dosage of buspirone; a dose increase of buspirone may be needed to maintain anxiolytic activity. Buspirone is a sensitive CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased buspirone exposure by 89.6%.
    Risperidone: (Moderate) The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Ritonavir: (Major) When buspirone is administered with a potent inhibitor of CYP3A4 like ritonavir, a low dose of buspirone used cautiously is recommended. Some patients receiving drugs that are potent inhibitors of CYP3A4 with buspirone have reported lightheadedness, asthenia, dizziness, and drowsiness. If the two drugs are to be used in combination, a low dose of buspirone (e.g., 2.5 mg PO twice daily) is recommended. Subsequent dose adjustment of either drug should be based on clinical assessment. Several other anti-retroviral protease inhibitors also inhibit CYP3A4, and these may interact with buspirone in a similar manner.
    Ropinirole: (Moderate) The combination of buspirone and other CNS depressants, such as ropinirole, can increase the risk for sedation.
    Rotigotine: (Major) Concomitant use of rotigotine with other CNS depressants, such as buspirone, can potentiate the sedation effects of rotigotine.
    Saquinavir: (Moderate) When buspirone is administered with an inhibitor of CYP3A4 like saquinavir, a lower dose of buspirone is recommended. Dose adjustment of either drug should be based on clinical assessment.
    Secobarbital: (Moderate) Monitor for reduced anxiolytic effect of buspirone. Potent inducers of CYP3A4, such as the barbiturates, may increase the rate of buspirone metabolism. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect. There is also a risk of additive CNS depression (drowsiness) when buspirone is given concomitantly with barbiturates. In a study in healthy volunteers, co-administration of buspirone with a potent CYP3A4 inducer decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone.
    Sedating H1-blockers: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Selegiline: (Contraindicated) Concomitant use of transdermal selegiline with buspirone or within 14 days after discontinuation of treatment with either agent is contraindicated due to the risk of serotonin syndrome. For selegiline oral formulations, monitor blood pressure for hypertension during concomitant use of buspirone. If a hypertensive crisis occurs, selegiline should be discontinued immediately and therapy to lower blood pressure should be instituted immediately.
    Serotonin norepinephrine reuptake inhibitors: (Moderate) Coadministration of buspirone with serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk of serotonin syndrome. Both types of medications have serotonergic properties. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Serotonin-Receptor Agonists: (Moderate) Buspirone should be used cautiously with serotonin-receptor agonists. Pharmacologically, buspirone is a serotonin agonist, and using in conjunction with other serotonin agonists could result in serotonin syndrome, which can be serious and consists of symptoms such as mental status changes, diaphoresis, tremor, myoclonus, hyperreflexia, and fever. Patients receiving serotonin-agonists and buspirone should be informed of the signs and symptoms of serotonin syndrome.
    Sertraline: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering buspirone and sertraline. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Sibutramine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sibutramine with drugs that have serotonergic properties, such as buspirone. Sibutramine is a serotonin, norepinephrine, and dopamine reuptake inhibitor. Additive effects on serotonin and dopamine are possible in combination with buspirone. CNS effects, such as sedation, may be possible. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving this combination should be monitored for the emergence of serotonin syndrome.
    Simeprevir: (Moderate) Simeprevir, a mild intestinal CYP3A4 inhibitor, may increase the side effects of buspirone, which is a CYP3A4 substrate. Monitor patients for adverse effects of buspirone.
    Skeletal Muscle Relaxants: (Moderate) Concomitant use of skeletal muscle relaxants with buspirone can result in additive CNS depression. Dosage adjustments of either or both medications may be necessary.
    Sodium Oxybate: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs.
    Sotorasib: (Moderate) Monitor for decreased efficacy of buspirone if sotorasib is added to a patient on a stable dosage of buspirone; a dose increase of buspirone may be needed to maintain anxiolytic activity. Buspirone is a sensitive CYP3A4 substrate and sotorasib is a moderate CYP3A4 inducer.
    Sufentanil: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of sufentanil, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use is imperative, reduce the dose of one or both drugs if clinically indicated.
    Tapentadol: (Moderate) Additive CNS depressive effects are expected if tapentadol is used in conjunction with other CNS depressants including anxiolytics, sedatives, and hypnotics. When such combined therapy is contemplated, a dose reduction of one or both agents should be considered.
    Tedizolid: (Minor) Caution is warranted with the concurrent use of tedizolid and buspirone due to the theoretical risk of serious CNS reactions, such as serotonin sydrome. Animal studies did not predict serontoneric effects with tedizolid. However, tedizolid is an antibiotic that is a weak reversible, non-selective MAO inhibitor and monoamine oxidase type A deaminates serotonin; therefore, coadministration theoretically could lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Several cases of elevated blood pressure have been reported in patients in whom buspirone was added to a non-selective traditional MAO-inhibitor regimen.
    Telaprevir: (Moderate) Close clinical monitoring is advised when administering buspirone with telaprevir due to an increased potential for buspirone-related adverse events. If buspirone dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of buspirone. Buspirone is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated buspirone plasma concentrations.
    Telithromycin: (Moderate) Concentrations of buspirone may be increased with concomitant use of telithromycin. Buspirone is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Telotristat Ethyl: (Moderate) Use caution if coadministration of telotristat ethyl and buspirone is necessary, as the systemic exposure of buspirone may be decreased resulting in reduced efficacy. If these drugs are used together, monitor patients for suboptimal efficacy of buspirone; consider increasing the dose of buspirone if necessary. Buspirone is a CYP3A4 substrate. The mean Cmax and AUC of another sensitive CYP3A4 substrate was decreased by 25% and 48%, respectively, when coadministered with telotristat ethyl; the mechanism of this interaction appears to be that telotristat ethyl increases the glucuronidation of the CYP3A4 substrate.
    Temazepam: (Moderate) It is common for patients to overlap anxiety treatment when switching from benzodiazepines to buspirone. Buspirone has a slow onset of action and the drug will not block the withdrawal syndrome often seen with cessation of benzodiazepine therapy in those with benzodiazepine dependence. Therefore, before starting therapy with buspirone, withdraw patients gradually from the benzodiazepine. Alternatively, conversion to buspirone therapy may require treatment overlap to allow for the downward titration of the benzodiazepine while buspirone takes effect. It should be noted that the combination of buspirone and benzodiazepines can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent.
    Tetrabenazine: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as buspirone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Thalidomide: (Major) Avoid the concomitant use of thalidomide with anxiolytics, sedatives, and hypnotics due to the potential for additive sedative effects.
    Thiethylperazine: (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as buspirone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Thiopental: (Moderate) Monitor for reduced anxiolytic effect of buspirone. Potent inducers of CYP3A4, such as the barbiturates, may increase the rate of buspirone metabolism. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect. There is also a risk of additive CNS depression (drowsiness) when buspirone is given concomitantly with barbiturates. In a study in healthy volunteers, co-administration of buspirone with a potent CYP3A4 inducer decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone.
    Thioridazine: (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as buspirone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Thiothixene: (Moderate) The combination of buspirone and CNS depressants like thiothixene can increase the risk for sedation.
    Tipranavir: (Moderate) When buspirone is administered with an inhibitor of CYP3A4 like tipranavir, a lower dose of buspirone is recommended. Dose adjustment of either drug should be based on clinical assessment.
    Tizanidine: (Moderate) Concurrent use of tizanidine and CNS depressants like buspirone can cause additive CNS depression.
    Topiramate: (Major) Although not specifically studied, coadministration of CNS depressant drugs with topiramate may potentiate CNS depression such as dizziness or cognitive adverse reactions, or other centrally mediated effects of these agents. Monitor for increased CNS effects if coadministering.
    Tramadol: (Moderate) Tramadol can cause additive CNS depression when used with other agents that are CNS depressants including buspirone.
    Tramadol; Acetaminophen: (Moderate) Tramadol can cause additive CNS depression when used with other agents that are CNS depressants including buspirone.
    Trandolapril; Verapamil: (Moderate) Coadministration of buspirone with verapamil substantially increases the plasma concentrations of buspirone by about three-fold. The mechanism is probably related to the inhibition of CYP3A4 by verapamil. Buspirone dose adjustment may be necessary and should be based on clinical assessment.
    Tranylcypromine: (Contraindicated) Concomitant use of monoamine oxidase inhibitors (MAOIs) and buspirone is contraindicated because several cases of elevated blood pressure have been reported in patients taking MAO inhibitors who were then given buspirone; serotonin syndrome may also occur. A 10-day interval after discontinuing isocarboxazid is recommended before initiating buspirone treatment. At least 14 days should elapse between the discontinuation of phenelzine and initiating buspirone, At least a 7-day interval should elapse after discontinuing tranylcypromine before initiating buspirone treatment. Monitor for serotonin-related effects during therapy transitions.
    Trazodone: (Moderate) Coadministration of trazodone and buspirone may increase the risk of serotonin syndrome. Serotonin syndrome has been reported with both drugs when taken alone, but especially when coadministered with other serotonergic agents. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Triazolam: (Moderate) It is common for patients to overlap anxiety treatment when switching from benzodiazepines to buspirone. Buspirone has a slow onset of action and the drug will not block the withdrawal syndrome often seen with cessation of benzodiazepine therapy in those with benzodiazepine dependence. Therefore, before starting therapy with buspirone, withdraw patients gradually from the benzodiazepine. Alternatively, conversion to buspirone therapy may require treatment overlap to allow for the downward titration of the benzodiazepine while buspirone takes effect. It should be noted that the combination of buspirone and benzodiazepines can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent.
    Tricyclic antidepressants: (Moderate) Coadministration of buspirone with tricyclic antidepressants (TCAs) may increase the risk of serotonin syndrome. Both types of medications have serotonergic properties. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Trifluoperazine: (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as buspirone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Trihexyphenidyl: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of trihexyphenidyl.
    Trimethobenzamide: (Moderate) The concurrent use of trimethobenzamide with other medications that cause CNS depression, like buspirone, may potentiate the effects of either trimethobenzamide or buspirone.
    Trimipramine: (Moderate) Coadministration of buspirone with tricyclic antidepressants (TCAs) may increase the risk of serotonin syndrome. Both types of medications have serotonergic properties. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Triprolidine: (Moderate) The combination of buspirone and other CNS depressants, such as the sedating H1-blockers (sedating antihistamines), may increase the risk for sedation.
    Tucatinib: (Moderate) A low dose of buspirone used cautiously is recommended when coadministered with tucatinib. If a patient has been titrated to a stable dosage of buspirone, a dose adjustment of buspirone may be necessary to avoid adverse events attributable to buspirone. Administering tucatinib with buspirone may increase buspirone concentration and risk for adverse events. Buspirone is a sensitive substrate of CYP3A4; tucatinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the buspirone AUC by 19-fold with an increased incidence of buspirone-related adverse effects.
    Vemurafenib: (Moderate) Vemurafenib is an inducer of CYP3A4 and decreased plasma concentrations of drugs metabolized by this enzyme, such as buspirone, could be expected with concurrent use. Use caution, and monitor therapeutic effects of buspirone when coadministered with vemurafenib.
    Venlafaxine: (Moderate) Coadministration of buspirone with serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk of serotonin syndrome. Both types of medications have serotonergic properties. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Verapamil: (Moderate) Coadministration of buspirone with verapamil substantially increases the plasma concentrations of buspirone by about three-fold. The mechanism is probably related to the inhibition of CYP3A4 by verapamil. Buspirone dose adjustment may be necessary and should be based on clinical assessment.
    Vigabatrin: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with buspirone.
    Vilazodone: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering vilazodone with other drugs that have serotonergic properties such as buspirone. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Patients receiving vilazodone and buspirone should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. Vilazodone and buspirone should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.
    Viloxazine: (Moderate) Monitor for an increase in buspirone-related adverse effects if concomitant use of viloxazine is necessary. Concomitant use may increase buspirone exposure; viloxazine is a weak CYP3A inhibitor and buspirone is a CYP3A substrate.
    Voriconazole: (Moderate) A low dose of buspirone used cautiously is recommended when coadministered with voriconazole. If a patient has been titrated to a stable dosage of buspirone, a dose adjustment of buspirone may be necessary to avoid adverse events attributable to buspirone. Administering voriconazole with buspirone may increase buspirone concentration and risk for adverse events. Buspirone is a sensitive substrate of CYP3A4. Voriconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the buspirone AUC by 19-fold with an increased incidence of buspirone-related adverse effects.
    Vortioxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering vortioxetine with other drugs that have serotonergic properties such as buspirone. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome is suspected, vortioxetine and concurrent serotonergic agents should be discontinued.
    Voxelotor: (Moderate) Monitor for an increase in buspirone-related adverse reactions if coadministration with voxelotor is necessary; the effect may be more pronounced if the patient has been titrated to a stable dose of buspirone and voxelotor is added or removed from therapy. Buspirone is a sensitive CYP3A substrate and voxelotor is a moderate CYP3A inhibitor. Coadministration with other moderate CYP3A inhibitors increased buspirone exposure by 3.4 to 6-fold and was accompanied by increased buspirone-related adverse reactions.
    Zafirlukast: (Moderate) In vitro data indicate that zafirlukast inhibits the CYP2C9 and CYP3A4 isoenzymes at concentrations close to the clinically achieved total plasma concentrations. Until more clinical data are available, zafirlukast should be used cautiously in patients stabilized on drugs metabolized by CYP3A4, such as buspirone.
    Zaleplon: (Moderate) The combination of buspirone and other CNS depressants, such as sedative hypnotics including zaleplon, may increase the risk for drowsiness or sedation. Because the effects of the use of buspirone with most other psychotropic drugs have not been studied, the concomitant use of buspirone with other CNS-active drugs should be approached with caution.
    Ziconotide: (Moderate) CNS depressant medications, such as buspirone, may increase drowsiness, dizziness, and confusion that are associated with ziconotide. Dosage adjustments may be necessary if ziconotide is used with buspirone.
    Zileuton: (Moderate) CYP3A4 inhibitors, such as zileuton, may decrease systemic clearance of buspirone leading to increased or prolonged effects. If buspirone is to be administered concurrently with significant CYP3A4 inhibitors, a low dose of buspirone (i.e., 2.5 mg PO twice daily) is recommended initially. Subsequent dosage adjustments should be based on clinical response.
    Ziprasidone: (Moderate) The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Zolpidem: (Moderate) The combination of buspirone and other CNS depressants can increase the risk for sedation.

    PREGNANCY AND LACTATION

    Pregnancy

    Well-controlled studies in pregnant women have not been performed with buspirone; therefore, buspirone should be used during pregnancy only when clearly needed. In a non-interventional observational cohort study, buspirone accounted for 16 of the 831 pregnancies in which women had taken a newly marketed drug during their first trimester. Overall, birth defects were noted in 14 of 557 newborns (2.5%). The 16 buspirone outcomes included 2 elective abortions, 1 intrauterine death, 12 normal term babies, and 1 newborn with cystic fibrosis. Teratogenic effects were not observed in animal studies when using approximately 30 times the maximum recommended human dose (MRHD); however, animal reproduction studies are not always predictive of human response. The effects of buspirone during labor and delivery are unknown.

    Buspirone should be avoided during breast-feeding if clinically possible; the extent of excretion of buspirone and its active metabolite into human milk is not known. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. Buspirone and its metabolites are excreted in the milk of lactating rats. There is often a lack of information regarding anxiolytic use during breast-feeding. Due to individual variability in the response to anxiolytics, it may be prudent to continue the existing regimen with caution if ongoing treatment is deemed necessary during breast-feeding. A pooled analysis found that maternal use of paroxetine usually produced undetectable or low drug concentrations in infant serum; this agent may be an option when initiating therapy for generalized anxiety disorder (GAD) in a breast-feeding mother. For acute anxiety requiring a benzodiazepine, short-acting agents such as oxazepam or lorazepam are preferred. The infant should be monitored regularly, and if sedation, nausea, reduced suckling, or other signs of toxicity are observed, either breast-feeding or the benzodiazepine should be discontinued. 

    MECHANISM OF ACTION

    The mechanism of action of buspirone is not clearly understood since anxiety may be mediated by more than one neuropathway. In general, buspirone suppresses serotonergic activity while enhancing noradrenergic and dopaminergic cell firing. Buspirone does not inhibit monoamine oxidase. Buspirone does not have any significant activity at benzodiazepine receptors, nor does it affect GABA receptors, however buspirone has some inhibitory actions on GABAergic pathways. In vitro, buspirone exhibits highest affinity for serotonin (5-HT) type 1A receptors, moderate affinity for dopamine type 2 (DA2) receptors, and weak affinity for serotonin type 2 (5-HT2) receptors. Type 1A serotonin receptors are found in high quantities in the dorsal raphe and the hippocampus. Buspirone binding to type 1A serotonin receptors occurs on presynaptic neurons in the dorsal raphe and on postsynaptic neurons in the hippocampus. Animal studies reveal that buspirone inhibits the firing rate of 5-HT-containing neurons in the dorsal raphe. The dominant action of buspirone is partial agonism or mixed agonism/antagonism at 5-HT type 1A receptors.
     
    Buspirone also binds at dopamine type 2 (DA2) receptors, displaying properties of both a dopamine agonist and an antagonist. Buspirone blocks presynaptic dopamine receptors, however, effects on postsynaptic receptors are conflicting. Affinity for dopamine receptors differentiates buspirone from gepirone, a related investigational agent which does not interact with dopamine receptors.
     
    Buspirone increases firing in the locus ceruleus, an area of brain where norepinephrine cell bodies are found in high concentration. Benzodiazepines, in contrast, decrease firing in the locus ceruleus. This may explain why benzodiazepines cause drowsiness while buspirone does not.
     
    The net result of buspirone actions at serotonin and dopamine receptors and related secondary messengers is inhibition of the synthesis and release of serotonin, however, since anxiety is thought to be mediated via multiple CNS pathways, the effects on serotonin do not totally explain the anxiolytic action of buspirone. Clinically, buspirone relieves the symptoms associated with generalized anxiety disorder such as motor tension (restlessness, twitching, and muscle tension); autonomic hyperactivity (sweating, palpitations, and tachycardia); and vigilance and scanning.
     
    The immunosuppressive action of buspirone appears to be distinct from its anxiolytic action. Buspirone has no muscle relaxant activity, anticonvulsant activity, and does not lead to dependence after chronic administration.

    PHARMACOKINETICS

    Buspirone is administered orally. Buspirone undergoes extensive first-pass metabolism, leaving only 1% of unchanged drug in plasma. Approximately 86% of buspirone is bound to plasma proteins. Buspirone is oxidized in the liver primarily by CYP3A4. Animal models indicate that the major active metabolite, 1-PP, has one-fourth of the activity of buspirone. In addition, blood samples from humans chronically exposed to buspirone hydrochloride do not exhibit high levels of 1-PP. Other hydroxylated metabolites are inactive. The average elimination half-life of buspirone is about 2 to 3 hours in healthy adults. In a single-dose study, 29% to 63% of a buspirone dose was excreted in the urine within 24 hours, primarily as metabolites. Fecal excretion accounted for 18% to 38% of the dose.
     
    Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP3A4
    Buspirone is metabolized primarily by CYP3A4. When administered with a potent inhibitor of CYP3A4, a low dose of buspirone and caution are recommended. Low doses of buspirone, as well as subsequent dose adjustments, may be required during coadministration of moderate CYP3A4 inhibitors. When used in combination with a potent inducer of CYP3A4, an increased dose of buspirone may be needed to maintain the anxiolytic effect.

    Oral Route

    After oral administration, buspirone is rapidly absorbed. Extensive first-pass metabolism results in plasma concentrations of buspirone that are low and variable between individuals. Because buspirone exhibits non-linear pharmacokinetics, dose increases and repeated dosing may lead to somewhat higher blood levels of unchanged buspirone than would be predicted from results of single-dose studies. When given with food, the AUC and Cmax of buspirone increase by roughly 84% and 116%, respectively; however, the total amount of buspirone does not change. Therefore, food may decrease the pre-systemic clearance of buspirone. For this reason, buspirone should be taken in a consistent manner with regard to the timing of dosing; either always with or always without food.