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  • CLASSES

    Anxiolytics, Non-Benzodiazepines

    DEA CLASS

    Rx

    DESCRIPTION

    Oral anxiolytic drug distinct from the benzodiazepines; slow onset of anxiolytic effect so not used for acute episodes; does not cause sedation or psychomotor impairment.

    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 other anxiety disorders or for the short-term relief of the symptoms of anxiety.
    NOTE: Patients who are converted from a benzodiazepine to buspirone may need to overlap buspirone initiation with the downward titration of the benzodiazepine. The onset of anxiolytic effect of buspirone may take 2 weeks; maximal effects occur at 3—6 weeks.
    NOTE: There is no body of evidence available that addresses the appropriate duration of treatment for GAD. However, in a study of long-term use, patients were treated with buspirone for 1 year without ill effect. Periodically reassess the usefulness of the drug for the individual patient.
    Oral dosage
    Adults

    Initially, 7.5 mg PO twice daily, then increase as needed by 5 mg/day every 2—3 days. Usual maintenance dose is 15—30 mg/day administered in 2—3 divided doses. Dosage should not exceed 60 mg/day.

    Geriatric

    Initially, 5 mg PO twice daily, then increase as needed by 5 mg/day every 2—3 days. Usual maintenance dose is 15—30 mg/day PO administered in 2—3 divided doses. Dosage should not exceed 60 mg/day. The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of anxiolytics in residents of long-term care facilities (LTCFs). Although there are no daily dose thresholds for buspirone, the lowest possible effective dose should be administered. In addition, the facility should attempt periodic tapering of the medication or provide documentation of medical necessity in accordance with OBRA guidelines.

    Children >= 6 years† and Adolescents†

    Limited data are available. Initially, 2.5—5 mg PO twice daily depending on the child's age, then increased as needed by no more than 5 mg/day every 7 days. Usual average maintenance dose is 15—30 mg/day PO, given in 2—3 divided doses. The safety and effectiveness of buspirone in 559 pediatric patients 6—17 years of age were evaluated in 2 placebo-controlled 6-week trials for generalized anxiety disorder (GAD). There were no significant differences between buspirone and placebo with regard to the symptoms of GAD following doses recommended for the treatment of GAD in adults. Safety and effectiveness were not established.

    For the treatment of autistic disorder†.
    Oral dosage
    Adults

    Data are limited, but buspirone may be useful in autistic patients with coexisting anxiety. Doses of 5 to 15 mg PO 3 times per day after gradual titration have been recommended. Dosage should not exceed 60 mg/day PO.

    Children and Adolescents 5 years and older

    Data are limited. 0.2 mg/kg/day to 0.6 mg/kg/day PO (Usual range: 15 mg/day to 45 mg/day PO); start at lower dosage and follow gradual titration. Dosage should not exceed 60 mg/day.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    60 mg/day PO.

    Elderly

    60 mg/day PO.

    Adolescents

    Safety and efficacy have not been established; 60 mg/day PO has been suggested.

    Children

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Modify based on degree of hepatic impairment. It may be prudent to reduce dosage by 25—50% and adjust based on patient clinical response and tolerance. The manufacturer recommends against use in patients with severe hepatic dysfunction.

    Renal Impairment

    CrCl > 70 mL/min: No dosage adjustment appears necessary.
    CrCl 11—70 mL/min: Modify dosage based on degree of renal impairment. It may be prudent to reduce initial dosage by 25—50% and adjust based on patient clinical response and tolerance.
    CrCl <= 10 mL/min: The manufacturer recommends against use in severe renal dysfunction.
     
    Intermittent hemodialysis
    The manufacturer recommends against use in severe renal dysfunction. The dialyzability of buspirone has not been determined.

    ADMINISTRATION

    Oral Administration

    Food may increase the bioavailability of buspirone. To ensure consistency of response to this drug, patients should take buspirone in a consistent manner with regard to the timing of dosing; either always with or always without food.

    STORAGE

    Generic:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    BuSpar:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Buspirone is contraindicated in patients with a known hypersensitivity to buspirone.
     
    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 neuroleptic-like activity; however, a syndrome of restlessness, appearing shortly after initiation of treatment, has been reported in some small fraction of buspirone-treated patients.

    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-active 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. The onset of anxiolytic effect of buspirone may take 2 weeks; maximal effects occur at 3—6 weeks.

    Renal disease, renal failure, renal impairment

    Caution should be used when administering buspirone to patients with renal disease that leads to renal impairment because the drug and its metabolites are eliminated mainly through the kidneys; decreased renal function or renal failure could result in decreased excretion and possible accumulation of the drug and its metabolites.

    Hepatic disease

    Caution should be used when administering buspirone to patients with hepatic disease because the drug is metabolized by the liver. Decreased hepatic function results in decreased clearance of the drug and a longer half-life; administration to those with severe hepatic disease is not recommended.

    Children, infants, neonates

    Safe and effective use in neonates, infants, children, and adolescents < 18 years old has not been established. The safety and effectiveness of buspirone in 559 pediatric patients of 6—17 years of age were evaluated in two placebo-controlled 6-week trials for generalized anxiety disorder (GAD). Safety and effectiveness were not established in these children at doses recommended for use in adults. No unexpected safety findings were associated with buspirone in these trials. There are no long-term safety or efficacy data in children.

    Geriatric

    There were no effects of age on the pharmacokinetics of buspirone. The safety and efficacy profiles of buspirone in 605 anxious, geriatric patients (mean age = 70.8 years) were similar to those in a younger adult population. The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of anxiolytics in residents of long-term care facilities. Specific criteria for use must be met, and the facility should attempt to periodically taper the medication as outlined in the OBRA guidelines, unless a taper is clinically contraindicated. Monitoring should consist of a review for continued need at least quarterly, and documentation of the rationale for continuation is required.

    Driving or operating machinery, ethanol intoxication

    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 concomitant ethanol intoxication while taking buspirone.

    Pregnancy

    Buspirone is classified as FDA pregnancy risk category B. No fertility impairment or fetal damage was observed in reproduction studies performed in rats and rabbits at doses of approximately 30 times the maximum recommended human dose. However, well-controlled pregnancy studies in humans have not been performed, and animal reproduction studies are not always predictive of human response. In one case report, a woman took buspirone (45 mg/day), fluoxetine (20 mg/day), and carbamazepine (600 mg/day) throughout pregnancy and for 3 weeks postpartum. She reported seizure-like activity in the infant at 3 weeks, 4 months, and 5.5 months of age. While both fluoxetine and carbamazepine were present in the breast milk and infant serum samples, buspirone was undetectable. The infant's neurological exam and electroencephalography were normal. The authors were unable to determine the cause of the seizure-like activity. In a 1998 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. Because the available data are too limited to be conclusive, buspirone should be used during pregnancy only if clearly needed. The effects of buspirone during labor and delivery are unknown.

    Breast-feeding

    According to the manufacturer, the extent of excretion of buspirone and its metabolites into human milk is not known, and buspirone administration during breast-feeding should be avoided if possible. Buspirone and its metabolites are excreted in the milk of lactating rats. In one case report, a woman took buspirone (45 mg/day), fluoxetine (20 mg/day), and carbamazepine (600 mg/day) throughout pregnancy and for 3 weeks postpartum. She reported seizure-like activity in the infant at 3 weeks, 4 months, and 5.5 months of age. While both fluoxetine and carbamazepine were present in the breast milk and infant serum samples, buspirone was undetectable. The infant's neurological exam and electroencephalography were normal. The authors were unable to determine the cause of the seizure-like activity. Although the American Academy of Pediatrics (AAP) does not specifically address the use of buspirone during breast-feeding, the AAP cautions that psychotropic medications affect neurotransmitter function in the developing central nervous system, and therefore, the accurate prediction of long-term adverse effects may not be possible. Due to individual variability in the response to buspirone and other anxiolytics, it may be prudent to continue the existing regimen if ongoing treatment is deemed necessary during breast-feeding. However, because a pooled analysis found that maternal use of paroxetine usually produced undetectable or low drug concentrations in infant serum, this agent may be preferred when initiating therapy for generalized anxiety disorder in a breast-feeding mother. A short-acting benzodiazepine such as lorazepam may be beneficial when immediate relief of anxiety symptoms is required, although the AAP classifies many benzodiazepines as drugs for which the effects on a nursing infant are unknown but may be of concern, particularly with prolonged exposure. If any benzodiazepine is used by a breast-feeding mother, the infant should be monitored for adverse effects, such as sedation. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    ADVERSE REACTIONS

    Severe

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

    Moderate

    excitability / Early / 2.0-2.0
    hostility / Early / 2.0-2.0
    confusion / Early / 2.0-2.0
    blurred vision / Early / 2.0-2.0
    dysphoria / Early / 0.1-1.0
    involuntary movements / Delayed / 0.1-1.0
    akathisia / Delayed / 0.1-1.0
    euphoria / Early / 0.1-1.0
    hallucinations / Early / 0.1-1.0
    hematoma / Early / 0.1-1.0
    edema / Delayed / 0.1-1.0
    elevated hepatic enzymes / Delayed / 0.1-1.0
    dyspnea / Early / 0.1-1.0
    hypotension / Rapid / 0.1-1.0
    hypertension / Early / 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
    bleeding / Early / 0-0.1
    leukopenia / Delayed / 0-0.1
    thrombocytopenia / Delayed / 0-0.1
    eosinophilia / Delayed / 0-0.1
    photophobia / Early / 0-0.1
    ejaculation dysfunction / Delayed / 0-0.1
    impotence (erectile dysfunction) / Delayed / 0-0.1
    chest pain (unspecified) / Early / 1.0
    ataxia / Delayed / Incidence not known
    pseudoparkinsonism / Delayed / Incidence not known
    dystonic reaction / Delayed / Incidence not known
    galactorrhea / 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
    paresthesias / Delayed / 1.0-1.0
    myalgia / Early / 1.0-1.0
    muscle cramps / Delayed / 0.1-1.0
    musculoskeletal pain / Early / 1.0-1.0
    arthralgia / Delayed / 0.1-1.0
    flushing / Rapid / 0.1-1.0
    xerosis / Delayed / 0.1-1.0
    pruritus / Rapid / 0.1-1.0
    alopecia / Delayed / 0.1-1.0
    hyperhidrosis / Delayed / 1.0-1.0
    rash (unspecified) / Early / 1.0-1.0
    weight gain / Delayed / 0.1-1.0
    hypersalivation / Early / 0.1-1.0
    flatulence / Early / 0.1-1.0
    anorexia / Delayed / 0.1-1.0
    weight loss / Delayed / 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
    parosmia / Delayed / 0.1-1.0
    ocular pruritus / Rapid / 0.1-1.0
    menstrual irregularity / Delayed / 0.1-1.0
    libido increase / Delayed / 0.1-1.0
    libido decrease / Delayed / 0.1-1.0
    increased urinary frequency / Early / 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
    insomnia / Early / Incidence not known
    vertigo / Early / Incidence not known
    restless legs syndrome (RLS) / Delayed / Incidence not known
    emotional lability / Early / Incidence not known
    restlessness / Early / Incidence not known
    ecchymosis / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    weakness / Early / Incidence not known
    fatigue / Early / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Aspirin, ASA; Caffeine: 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; Butalbital: Substances that are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4, such as 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 when buspirone is given concomitantly with barbiturates.
    Acetaminophen; Butalbital; Caffeine: Substances that are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4, such as 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 when buspirone is given concomitantly with barbiturates.
    Acetaminophen; Butalbital; Caffeine; Codeine: Substances that are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4, such as 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 when buspirone is given concomitantly with barbiturates. 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; Caffeine; Dihydrocodeine: 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: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Acetaminophen; Codeine: 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: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Acetaminophen; Diphenhydramine: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Acetaminophen; Hydrocodone: 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: 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; Pentazocine: 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: 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.
    Acetaminophen; Tramadol: Tramadol can cause additive CNS depression when used with other agents that are CNS depressants including buspirone.
    Acrivastine; Pseudoephedrine: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Aldesleukin, IL-2: 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: The combination of buspirone and other CNS depressants, such as alfentanil, can increase the risk for sedation.
    Alprazolam: 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: 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: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tricyclic antidepressants (TCAs) with other drugs that have serotonergic properties such as buspirone. Buspirone increases the sensitivity of postsynaptic serotonin receptors and TCAs inhibit the reuptake of serotonin. 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, tricyclic antidepressants and concurrent serotonergic agents should be discontinued.
    Amitriptyline; Chlordiazepoxide: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tricyclic antidepressants (TCAs) with other drugs that have serotonergic properties such as buspirone. Buspirone increases the sensitivity of postsynaptic serotonin receptors and TCAs inhibit the reuptake of serotonin. 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, tricyclic antidepressants and concurrent serotonergic agents should be discontinued. 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.
    Amobarbital: Substances that are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4, such as 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 when buspirone is given concomitantly with barbiturates.
    Amoxapine: 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; Lansoprazole: 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.
    Amoxicillin; Clarithromycin; Omeprazole: 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.
    Amprenavir: 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.
    Apomorphine: Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants could result in additive depressant effects.
    Apraclonidine: 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: 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: The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Asenapine: The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Aspirin, ASA: 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: Substances that are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4, such as 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 when buspirone is given concomitantly with barbiturates. 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: Substances that are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4, such as 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 when buspirone is given concomitantly with barbiturates. 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. 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: 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. 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: Concomitant use of skeletal muscle relaxants with buspirone can result in additive CNS depression. Dosage adjustments of either or both medications may be necessary. 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: 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. Concomitant use of skeletal muscle relaxants with buspirone can result in additive CNS depression. Dosage adjustments of either or both medications may be necessary. 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: 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: 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: 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. 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: 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: 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: The plasma concentrations of buspirone may be elevated when administered concurrently with cobicistat. 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. Cobicistat 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. 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: 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: 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.
    Atropine; Diphenoxylate: 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.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: Substances that are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4, such as 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 when buspirone is given concomitantly with barbiturates.
    atypical antipsychotic: The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Azelastine: An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including buspirone.
    Azelastine; Fluticasone: An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including buspirone.
    Baclofen: 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: Substances that are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4, such as 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 when buspirone is given concomitantly with barbiturates.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: Substances that are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4, such as 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 when buspirone is given concomitantly with barbiturates.
    Belladonna; Opium: 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: 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.
    Boceprevir: 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: The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Brompheniramine: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Brompheniramine; Carbetapentane; Phenylephrine: 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. The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Brompheniramine; Dextromethorphan; Guaifenesin: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Brompheniramine; Guaifenesin; Hydrocodone: 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. The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Brompheniramine; Hydrocodone; Pseudoephedrine: 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. The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Brompheniramine; Pseudoephedrine: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Buprenorphine: 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: 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: Substances that are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4, such as 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 when buspirone is given concomitantly with barbiturates.
    Butorphanol: Concomitant use of butorphanol with other CNS depressants, such as buspirone, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
    Capsaicin; Metaxalone: 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: Substances that are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4, like carbamazepine, may increase the rate of buspirone metabolism.
    Carbetapentane; Chlorpheniramine: 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. The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Carbetapentane; Chlorpheniramine; Phenylephrine: 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. The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Carbetapentane; Diphenhydramine; Phenylephrine: 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. The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Carbetapentane; Guaifenesin: 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: 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: 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: 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. The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Carbetapentane; Pseudoephedrine: 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: 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. The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Carbinoxamine: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Carbinoxamine; Hydrocodone; Phenylephrine: 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. The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: 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. The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Carbinoxamine; Phenylephrine: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Carbinoxamine; Pseudoephedrine: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Cariprazine: The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Carisoprodol: Concomitant use of skeletal muscle relaxants with buspirone can result in additive CNS depression. Dosage adjustments of either or both medications may be necessary.
    Cetirizine: Additive drowsiness may occur if cetirizine/levocetirizine is administered with other drugs that depress the CNS, including buspirone.
    Cetirizine; Pseudoephedrine: Additive drowsiness may occur if cetirizine/levocetirizine is administered with other drugs that depress the CNS, including buspirone.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Chloral Hydrate: The combination of buspirone and other CNS depressants can increase the risk for sedation.
    Chlorcyclizine: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Chlordiazepoxide: 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: 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: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Chlorpheniramine; Codeine: 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. The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Chlorpheniramine; Dextromethorphan: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: 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. The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: 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. The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: 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. The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Chlorpheniramine; Hydrocodone: 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. The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Chlorpheniramine; Hydrocodone; Phenylephrine: 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. The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: 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. The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Chlorpheniramine; Phenylephrine: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Chlorpheniramine; Pseudoephedrine: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Chlorpromazine: 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: 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: 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.
    Clarithromycin: 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: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Clobazam: 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: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tricyclic antidepressants (TCAs) with other drugs that have serotonergic properties such as buspirone. Buspirone increases the sensitivity of postsynaptic serotonin receptors and TCAs inhibit the reuptake of serotonin. 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, tricyclic antidepressants and concurrent serotonergic agents should be discontinued.
    Clonazepam: 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: 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: The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Cobicistat: The plasma concentrations of buspirone may be elevated when administered concurrently with cobicistat. 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. Cobicistat 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.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: The plasma concentrations of buspirone may be elevated when administered concurrently with cobicistat. 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. Cobicistat 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.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: The plasma concentrations of buspirone may be elevated when administered concurrently with cobicistat. 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. Cobicistat 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.
    Codeine: 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: 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: Because promethazine causes pronounced sedation, an enhanced CNS depressant effect or additive drowsiness may occur when it is combined with other CNS depressants like buspirone. 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; Promethazine: Because promethazine causes pronounced sedation, an enhanced CNS depressant effect or additive drowsiness may occur when it is combined with other CNS depressants like buspirone. 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.
    COMT inhibitors: COMT inhibitors should be given cautiously with other agents that cause CNS depression, including buspirone, due to the possibility of additive sedation.
    Crizotinib: Concomitant use of crizotinib and buspirone may result in increased buspirone concentrations. Crizotinib is a CYP3A4 and P-glycoprotein (PGP) inhibitor, while buspirone is a CYP3A4 substrate. Monitor patients for toxicity with coadministration.
    Cyclizine: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Cyclobenzaprine: 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: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Dalfopristin; Quinupristin: CYP3A4 inhibitors, such as dalfopristin; quinapristin, 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.
    Danazol: Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of buspirone, a CYP3A4 substrate.
    Dantrolene: 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: 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: The plasma concentrations of buspirone may be elevated when administered concurrently with cobicistat. 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. Cobicistat 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. 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: 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.
    Dasatinib: Dasatinib inhibits CYP3A4. Therefore, caution is warranted when drugs that are metabolized by this enzyme, such as buspirone, are administered concurrently with dasatinib as increased adverse reactions may occur.
    Delavirdine: 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: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tricyclic antidepressants (TCAs) with other drugs that have serotonergic properties such as buspirone. Buspirone increases the sensitivity of postsynaptic serotonin receptors and TCAs inhibit the reuptake of serotonin. 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, tricyclic antidepressants and concurrent serotonergic agents should be discontinued.
    Desvenlafaxine: Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering serotonin norepinephrine reuptake inhibitors (SNRIs) 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. Patients receiving these combinations should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
    Dexamethasone: Potent inducers of hepatic cytochrome P450 3A4, such as dexamethasone, may increase the rate of buspirone metabolism.
    Dexchlorpheniramine: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Dexmedetomidine: Co-administration of dexmedetomidine with benzodiazepines is likely to lead to an enhancement of CNS depression.
    Dextromethorphan; Diphenhydramine; Phenylephrine: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Dextromethorphan; Promethazine: Because promethazine causes pronounced sedation, an enhanced CNS depressant effect or additive drowsiness may occur when it is combined with other CNS depressants like buspirone.
    Diazepam: 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: Dicyclomine can cause drowsiness, so it should be used cautiously in patients receiving CNS depressants like buspirone.
    Digoxin: Buspirone can displace digoxin from plasma proteins, but the clinical significance of this effect has yet to be determined.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: 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: 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: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Diphenhydramine: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Diphenhydramine; Hydrocodone; Phenylephrine: 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. The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Diphenhydramine; Ibuprofen: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Diphenhydramine; Phenylephrine: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Doxepin: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tricyclic antidepressants (TCAs) with other drugs that have serotonergic properties such as buspirone. Buspirone increases the sensitivity of postsynaptic serotonin receptors and TCAs inhibit the reuptake of serotonin. 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, tricyclic antidepressants and concurrent serotonergic agents should be discontinued.
    Doxylamine: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Doxylamine; Pyridoxine: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Dronabinol, THC: Use caution if coadministration of dronabinol with buspirone is necessary, and monitor for additive dizziness, confusion, somnolence, and other CNS effects.
    Dronedarone: 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: CNS depressants have additive effects with droperidol. Following administration of droperidol, lower doses of the other CNS depressant should be used.
    Duloxetine: Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering serotonin norepinephrine reuptake inhibitors (SNRIs) 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. Patients receiving these combinations should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
    Efavirenz: 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: 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.
    Elbasvir; Grazoprevir: 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.
    Erythromycin: 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: 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.
    Estazolam: 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: The combination of buspirone and other CNS depressants can increase the risk for sedation.
    Ethanol: Alcohol is associated with CNS depression. The combined use of alcohol and CNS depressants can lead to additive CNS depression, which could be dangerous in tasks requiring mental alertness and fatal in overdose. Alcohol taken with other CNS depressants can lead to additive respiratory depression, hypotension, profound sedation, or coma. Consider the patient's use of alcohol or illicit drugs when prescribing CNS depressant medications. In many cases, the patient should receive a lower dose of the CNS depressant initially if the patient is not likely to be compliant with avoiding alcohol.
    Ethotoin: 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.
    Fentanyl: 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; Olanzapine: The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Fluphenazine: 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: 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.
    Food: Buspirone should be taken consistently with or without food because food decreases the presystemic clearance of buspirone.
    Fosamprenavir: 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: 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: General anesthetics potentiate the effects of CNS depressants.
    Grapefruit juice: Grapefruit juice has been reported to significantly increase buspirone peak concentrations and AUC, probably through the inhibition of gut-wall CYP3A4 isoenzyme metabolism. There may be great variation in the significance of this effect among individuals. Subjective drowsiness and other side effects of buspirone may be increased with grapefruit juice ingestion. Patients receiving buspirone should be advised to avoid drinking large amounts of grapefruit juice.
    Guaifenesin; Hydrocodone: 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: 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: The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for sedation. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and CYP3A4 substrates such as buspirone. Elevated haloperidol concentrations may increase the risk of adverse effects, including QT prolongation. Until more data are available, it is advisable to closely monitor for adverse events when buspirone is coadministered with haloperidol.
    Homatropine; Hydrocodone: 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: 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: 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: 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: 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: 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: 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: 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: 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: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: 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: 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: 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: The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Imatinib, STI-571: 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: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tricyclic antidepressants (TCAs) with other drugs that have serotonergic properties such as buspirone. Buspirone increases the sensitivity of postsynaptic serotonin receptors and TCAs inhibit the reuptake of serotonin. 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, tricyclic antidepressants and concurrent serotonergic agents should be discontinued.
    Indinavir: 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: 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: Concomitant use of 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 HCL. A 10-day interval after discontinuing isocarboxazid is recommended before initiating buspirone treatment.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: 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: 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: Due to itraconazole-induced inhibition of cytochrome P450 3A4, increased serum concentrations of buspirone are possible when these agents are coadministered.
    Ivacaftor: Use caution when administering ivacaftor and buspirone concurrently. Ivacaftor is an inhibitor of CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as buspirone, can increase buspirone exposure leading to increased or prolonged therapeutic effects and adverse events.
    Kava Kava, Piper methysticum: Any substance that acts on the CNS may interact with kava kava. These interactions are probably pharmacodynamic in nature. Patients should probably avoid concomitant administration.
    Ketoconazole: 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.
    Lesinurad: 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.
    Levocetirizine: Additive drowsiness may occur if cetirizine/levocetirizine is administered with other drugs that depress the CNS, including buspirone.
    Levomethadyl: 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: Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering serotonin norepinephrine reuptake inhibitors (SNRIs) 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. Patients receiving these combinations should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
    Levorphanol: 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: Linezolid should generally not be administered to patients taking serotonergic agents, such as buspirone, due to the potential for serious CNS reactions, such as serotonin syndrome. Serotonin syndrome has been reported when linezolid has been administerd with certain serotonergic agents. In theory, serotonin syndome could occur with the concomitant use of buspirone; however, the FDA states that it is unclear if concomitant use of linezolid and agents with lesser degrees of serotonergic activity would pose a comparable risk. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. 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.
    Lithium: Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including anxiolytics, sedatives, and hypnotics.
    Lopinavir; Ritonavir: 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. When buspirone is administered with an inhibitor of CYP3A4 like lopinavir, a lower dose of buspirone is recommended. Dose adjustment of either drug should be based on clinical assessment.
    Lorazepam: 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.
    Loxapine: The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for sedation.
    Luliconazole: Theoretically, luliconazole may increase the side effects of buspirone, which is a CYP3A4 substrate. Monitor patients for adverse effects of buspirone, such as CNS reactions. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
    Lumacaftor; Ivacaftor: 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.
    Lumacaftor; Ivacaftor: Use caution when administering ivacaftor and buspirone concurrently. Ivacaftor is an inhibitor of CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as buspirone, can increase buspirone exposure leading to increased or prolonged therapeutic effects and adverse events.
    Lurasidone: The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Maprotiline: CNS depressants should be combined cautiously with maprotiline because they could cause additive depressant effects and possible respiratory depression or hypotension.
    Meclizine: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Meperidine: 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: Because promethazine causes pronounced sedation, an enhanced CNS depressant effect or additive drowsiness may occur when it is combined with other CNS depressants like buspirone. 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.
    Mephobarbital: Substances that are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4, such as 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 when buspirone is given concomitantly with barbiturates.
    Meprobamate: The combination of buspirone and other CNS depressants can increase the risk for sedation.
    Mesoridazine: 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: 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: 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: 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: Substances that are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4, such as 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 when buspirone is given concomitantly with barbiturates.
    Methscopolamine: CNS depression can be increased when methscopolamine is combined with other CNS depressants such as any anxiolytics, sedatives, and hypnotics.
    Methylene Blue: 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: Combined use of metoclopramide and other CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase possible sedation.
    Midazolam: 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, RU-486: CYP3A4 inhibitors, such as mifepristone, 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.
    Milnacipran: Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering serotonin norepinephrine reuptake inhibitors (SNRIs) 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. Patients receiving these combinations should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
    Mirtazapine: Although unlikely to occur with use of mirtazapine alone, there have been rare case reports of serotonin syndrome with the drug. Coadministration of buspirone, which potentiates the actions of serotonin, may result in serotonin syndrome.
    Mitotane: 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: The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for sedation.
    Monoamine oxidase inhibitors: Concomitant use of 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 HCL. A 10-day interval after discontinuing isocarboxazid is recommended before initiating buspirone treatment.
    Morphine: 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 codeine and buspirone is imperative, reduce the dose of one or both drugs.
    Morphine; Naltrexone: 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 codeine and buspirone is imperative, reduce the dose of one or both drugs.
    Nabilone: Concomitant use of nabilone with other CNS depressants can potentiate the effects of nabilone on respiratory depression.
    Nalbuphine: 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: 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: 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: 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: 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.
    Nortriptyline: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tricyclic antidepressants (TCAs) with other drugs that have serotonergic properties such as buspirone. Buspirone increases the sensitivity of postsynaptic serotonin receptors and TCAs inhibit the reuptake of serotonin. 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, tricyclic antidepressants and concurrent serotonergic agents should be discontinued.
    Olanzapine: The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Ombitasvir; Paritaprevir; Ritonavir: 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: 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: 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: 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: Additive CNS depression may occur when oxybutynin is used concomitantly with other CNS-depressant drugs, including anxiolytics, sedatives, and hypnotics.
    Oxycodone: 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: 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.
    Paliperidone: The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Papaverine: Concurrent use of papaverine with potent CNS depressants such as buspirone could lead to enhanced sedation.
    Pazopanib: 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: 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: 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: Substances that are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4, such as 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 when buspirone is given concomitantly with barbiturates.
    Perampanel: 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: 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: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tricyclic antidepressants (TCAs) with other drugs that have serotonergic properties such as buspirone. Buspirone increases the sensitivity of postsynaptic serotonin receptors and TCAs inhibit the reuptake of serotonin. 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, tricyclic antidepressants and concurrent serotonergic agents should be discontinued. 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.
    Phenelzine: Concomitant use of 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 HCL. A 10-day interval after discontinuing isocarboxazid is recommended before initiating buspirone treatment.
    Phenobarbital: Substances that are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4, such as 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 when buspirone is given concomitantly with barbiturates.
    Phenothiazines: 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: 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.
    Phenylephrine; Promethazine: Because promethazine causes pronounced sedation, an enhanced CNS depressant effect or additive drowsiness may occur when it is combined with other CNS depressants like buspirone.
    Phenytoin: 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.
    Pimavanserin: The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Pimozide: The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for sedation.
    Posaconazole: 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.
    Pramipexole: The combination of buspirone and other CNS depressants, such as pramipexole, can increase the risk for sedation.
    Pregabalin: Concomitant administration of pregabalin with CNS depressant drugs, including buspirone, can potentiate the CNS effects of either agent.
    Primidone: Substances that are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4, such as 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 when buspirone is given concomitantly with barbiturates.
    Procarbazine: 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: 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: Because promethazine causes pronounced sedation, an enhanced CNS depressant effect or additive drowsiness may occur when it is combined with other CNS depressants like buspirone.
    Propoxyphene: 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: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tricyclic antidepressants (TCAs) with other drugs that have serotonergic properties such as buspirone. Buspirone increases the sensitivity of postsynaptic serotonin receptors and TCAs inhibit the reuptake of serotonin. 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, tricyclic antidepressants and concurrent serotonergic agents should be discontinued.
    Quazepam: 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: The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Ramelteon: Due to pharmacodynamic additive effects, also use caution when combining ramelteon with buspirone.
    Ranolazine: 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: In theory, there is the potential for a pharmacodynamic interaction between rasagiline and buspirone since both enhance dopaminergic activity. Concomitant use of MAOIs and buspirone is contraindicated by the manufacturer of buspirone because several cases of elevated blood pressure have been reported in patients taking MAO inhibitors who were then given buspirone HCl.
    Remifentanil: 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 of codeine and buspirone is imperative, reduce the dose of one or both drugs.
    Rifampin: 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.
    Risperidone: The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Ritonavir: 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: The combination of buspirone and other CNS depressants, such as ropinirole, can increase the risk for sedation.
    Rotigotine: Concomitant use of rotigotine with other CNS depressants, such as buspirone, can potentiate the sedation effects of rotigotine.
    Saquinavir: 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: Substances that are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4, such as 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 when buspirone is given concomitantly with barbiturates.
    Sedating H1-blockers: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Selective serotonin reuptake inhibitors: Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) 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. The addition of fluoxetine to a regimen consisting of buspirone and trazodone was reported to result in an increase in anxiety-type symptoms in one patient. Another patient developed a grand mal seizure while receiving the combination of buspirone and fluoxetine. CYP3A4 inhibitors such as fluvoxamine 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. Patients receiving these combinations should be monitored for the emergence of serotonin syndrome, neuroleptic malignant syndrome-like reactions, or other adverse effects.
    Selegiline, Transdermal: Concomitant use of 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 HCL. A 10-day interval after discontinuing isocarboxazid is recommended before initiating buspirone treatment.
    Selegiline: Concomitant use of 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 HCL. A 10-day interval after discontinuing isocarboxazid is recommended before initiating buspirone treatment.
    Serotonin norepinephrine reuptake inhibitors: Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering serotonin norepinephrine reuptake inhibitors (SNRIs) 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. Patients receiving these combinations should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
    Serotonin-Receptor Agonists: 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.
    Sibutramine: Sibutramine is a serotonin reuptake inhibitor. Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering sibutramine with 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. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
    Simeprevir: 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: 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: Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs.
    Streptogramins: CYP3A4 inhibitors, such as dalfopristin; quinapristin, 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.
    Sufentanil: 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 of codeine and buspirone is imperative, reduce the dose of one or both drugs.
    Tapentadol: 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: 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: 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: 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.
    Temazepam: 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: 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: Avoid the concomitant use of thalidomide with anxiolytics, sedatives, and hypnotics due to the potential for additive sedative effects.
    Thiethylperazine: 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: Substances that are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4, such as 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 when buspirone is given concomitantly with barbiturates.
    Thioridazine: 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: The combination of buspirone and CNS depressants like thiothixene can increase the risk for sedation.
    Tipranavir: 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: Concurrent use of tizanidine and CNS depressants like buspirone can cause additive CNS depression.
    Topiramate: 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: Tramadol can cause additive CNS depression when used with other agents that are CNS depressants including buspirone.
    Trandolapril; Verapamil: 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: Concomitant use of 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 HCL. A 10-day interval after discontinuing isocarboxazid is recommended before initiating buspirone treatment.
    Trazodone: Due to the risk of serotonin syndrome, concurrent use of trazodone and other serotonergic medications, such as buspirone, should be avoided if possible. If concomitant use is clinically warranted, patients should be informed of the increased risk of serotonin syndrome, particularly during treatment initiation and during dose increases. 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. Treatment with trazodone and any concomitant serotonergic agents should be discontinued immediately if signs and symptoms of serotonin syndrome occur, and supportive symptomatic treatment should be initiated. Myoclonus, which responded to a serotonin antagonist, was reported in a patient taking trazodone with buspirone and a dopamine antagonist.
    Triazolam: 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: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tricyclic antidepressants (TCAs) with other drugs that have serotonergic properties such as buspirone. Buspirone increases the sensitivity of postsynaptic serotonin receptors and TCAs inhibit the reuptake of serotonin. 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, tricyclic antidepressants and concurrent serotonergic agents should be discontinued.
    Trifluoperazine: 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: CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of trihexyphenidyl.
    Trimethobenzamide: The concurrent use of trimethobenzamide with other medications that cause CNS depression, like buspirone, may potentiate the effects of either trimethobenzamide or buspirone.
    Trimipramine: Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tricyclic antidepressants (TCAs) with other drugs that have serotonergic properties such as buspirone. Buspirone increases the sensitivity of postsynaptic serotonin receptors and TCAs inhibit the reuptake of serotonin. 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, tricyclic antidepressants and concurrent serotonergic agents should be discontinued.
    Triprolidine: The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Vemurafenib: 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: Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering serotonin norepinephrine reuptake inhibitors (SNRIs) 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. Patients receiving these combinations should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
    Verapamil: 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: 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: Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering vilazodone 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. Patients receiving this combination should be monitored closely for toxicity.
    Voriconazole: Voriconazole is an inhibitor of CYP3A4 isoenzyme. Buspirone is a substrate for CYP3A4, and when combined with voriconazole, may theoretically have reduced metabolism, and therefore higher serum concentrations resulting in toxicity.
    Vortioxetine: 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.
    Zafirlukast: 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: The combination of buspirone and other CNS depressants can increase the risk for sedation.
    Ziconotide: 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: 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: The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Zolpidem: The combination of buspirone and other CNS depressants can increase the risk for sedation.

    PREGNANCY AND LACTATION

    Pregnancy

    Buspirone is classified as FDA pregnancy risk category B. No fertility impairment or fetal damage was observed in reproduction studies performed in rats and rabbits at doses of approximately 30 times the maximum recommended human dose. However, well-controlled pregnancy studies in humans have not been performed, and animal reproduction studies are not always predictive of human response. In one case report, a woman took buspirone (45 mg/day), fluoxetine (20 mg/day), and carbamazepine (600 mg/day) throughout pregnancy and for 3 weeks postpartum. She reported seizure-like activity in the infant at 3 weeks, 4 months, and 5.5 months of age. While both fluoxetine and carbamazepine were present in the breast milk and infant serum samples, buspirone was undetectable. The infant's neurological exam and electroencephalography were normal. The authors were unable to determine the cause of the seizure-like activity. In a 1998 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. Because the available data are too limited to be conclusive, buspirone should be used during pregnancy only if clearly needed. The effects of buspirone during labor and delivery are unknown.

    According to the manufacturer, the extent of excretion of buspirone and its metabolites into human milk is not known, and buspirone administration during breast-feeding should be avoided if possible. Buspirone and its metabolites are excreted in the milk of lactating rats. In one case report, a woman took buspirone (45 mg/day), fluoxetine (20 mg/day), and carbamazepine (600 mg/day) throughout pregnancy and for 3 weeks postpartum. She reported seizure-like activity in the infant at 3 weeks, 4 months, and 5.5 months of age. While both fluoxetine and carbamazepine were present in the breast milk and infant serum samples, buspirone was undetectable. The infant's neurological exam and electroencephalography were normal. The authors were unable to determine the cause of the seizure-like activity. Although the American Academy of Pediatrics (AAP) does not specifically address the use of buspirone during breast-feeding, the AAP cautions that psychotropic medications affect neurotransmitter function in the developing central nervous system, and therefore, the accurate prediction of long-term adverse effects may not be possible. Due to individual variability in the response to buspirone and other anxiolytics, it may be prudent to continue the existing regimen if ongoing treatment is deemed necessary during breast-feeding. However, because a pooled analysis found that maternal use of paroxetine usually produced undetectable or low drug concentrations in infant serum, this agent may be preferred when initiating therapy for generalized anxiety disorder in a breast-feeding mother. A short-acting benzodiazepine such as lorazepam may be beneficial when immediate relief of anxiety symptoms is required, although the AAP classifies many benzodiazepines as drugs for which the effects on a nursing infant are unknown but may be of concern, particularly with prolonged exposure. If any benzodiazepine is used by a breast-feeding mother, the infant should be monitored for adverse effects, such as sedation. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    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. The onset of anxiolytic effect can take 3—6 weeks. Distribution of buspirone in the human body has not been fully elucidated. An in vitro binding study indicated that approximately 86% of buspirone is bound to plasma proteins. Buspirone and its metabolites are found in breast milk. Metabolism of buspirone occurs in the liver primarily by oxidation, which in vitro has been shown to be mediated by cytochrome P450 3A4 (CYP3A4). Buspirone has a major active metabolite, 1-PP, whose anxiolytic effect in humans has not been established. There are other hydroxylated, inactive derivatives. In a single-dose study, 29—63% of a buspirone dose was excreted in the urine within 24 hours, primarily as metabolites; fecal excretion accounted for 18—38% of the dose. The average elimination half-life of buspirone is roughly 2—4 hours in healthy adults.
     
    Affected cytochrome P450 isoenzymes: CYP3A4

    Oral Route

    After oral administration, buspirone is rapidly and almost completely absorbed, but only about 4% of a dose reaches systemic circulation because of extensive first-pass metabolism in the liver. When given with food, the AUC and Cmax of buspirone increase by roughly 84% and 116%, respectively; 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.