Coadministration with another strong CYP3A4 inhibitor increased the buspirone AUC by 19-fold with an increased incidence of buspirone-related adverse effects. Barbiturates: (Moderate) Monitor for reduced anxiolytic effect of buspirone. In vivo interaction studies with these drugs have not been performed. 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. This may explain why benzodiazepines cause drowsiness while buspirone does not. Meclizine: (Moderate) The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation. (Moderate) The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs. Buspirone is a sensitive substrate of CYP3A4. Duloxetine: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as buspirone and serotonin norepinephrine reuptake inhibitors (SNRIs). Buspirone is a sensitive CYP3A4 substrate. 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. Droperidol: (Major) CNS depressants have additive effects with droperidol. In vitro, buspirone is a CYP3A4 substrate. Cyclobenzaprine: (Moderate) Concomitant use of skeletal muscle relaxants with buspirone can result in additive CNS depression. Several other anti-retroviral protease inhibitors also inhibit CYP3A4, and these may interact with buspirone in a similar manner. Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of dihydrocodeine, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. The infant should be monitored regularly, and if sedation, nausea, reduced suckling, or other signs of toxicity are observed, either breast-feeding or the benzodiazepine should be discontinued. . Dosage adjustments of either or both medications may be necessary. Predictions regarding this interaction can be made based on the metabolic pathways of these drugs. Elagolix: (Moderate) Monitor for decreased efficacy of buspirone if elagolix is added to a patient on a stable dosage of buspirone; a dose increase of buspirone may be needed to maintain anxiolytic activity. The infant's neurological exam and electroencephalography were normal. Buspirone (flexible dosage, 20-60 mg/day) or placebo was added to the SSRI for 4 weeks; the mean daily dose of buspirone at endpoint was 48.5 mg (SD = 1.0). The maximum daily dosage should not exceed 60 mg per day. Buspirone increases firing in the locus ceruleus, an area of brain where norepinephrine cell bodies are found in high concentration. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical treatment should be initiated. Chlorzoxazone: (Moderate) Concomitant use of skeletal muscle relaxants with buspirone can result in additive CNS depression. Generalized anxiety disorder:Oral: Initial: 10 to 15 mg/day in 2 to 3 divided doses; may increase every 2 to 3 days in increments of 5 mg/day to a maximum of 60 mg/day; usual dose: 20 to 30 mg/day in 2 to 3 divided doses (Chessick 2006; Sramek 1999). Coadministration may result in elevated buspirone plasma concentrations. Dose adjustment of either drug should be based on clinical assessment. In addition, buspirone is a primary CYP3A4 substrate and concurrent use with an inhibitor of CYP3A4, such as fluvoxamine, may decrease systemic clearance of buspirone leading to increased or prolonged effects. Therefore, before starting therapy with buspirone, withdraw patients gradually from the benzodiazepine. The combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. Triazolam: (Moderate) It is common for patients to overlap anxiety treatment when switching from benzodiazepines to buspirone. Ribociclib; Letrozole: (Moderate) A low dose of buspirone used cautiously is recommended when coadministered with ribociclib. If hydrocodone is used with buspirone, the dose of one or both drugs should be reduced. Chlorpheniramine: (Moderate) The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation. Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. If buspirone is to be administered concurrently with significant CYP3A4 inhibitors, a low dose of buspirone is recommended initially. Theoretically, apraclonidine might potentiate the effects of CNS depressant drugs such as the anxiolytics, sedatives, and hypnotics, including barbiturates or benzodiazepines. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. The maximum daily dosage should not exceed 60 mg per day. If concurrent use is necessary, monitor for the emergence of serotonin syndrome and inform patients of the increased risk. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs. In vivo interaction studies with these drugs have not been performed. If a patient has been titrated to a stable dosage of buspirone, a dose adjustment of buspirone may be necessary to avoid adverse events attributable to buspirone. In a non-interventional observational cohort study, buspirone accounted for 16 of the 831 pregnancies in which women had taken a newly marketed drug during their first trimester. Trifluoperazine: (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as buspirone. Specific criteria for anxiolytics must be met, including 1) limiting use to indications specified in the OBRA guidelines (e.g., generalized anxiety disorder, panic disorder) which meet the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for the indication, and 2) evidence exists that other possible reasons for the individual's distress have been considered, and 3) use results in maintenance or improvement in mental, physical, and psychosocial well-being as reflected on the Minimum Data Set (MDS) or other assessment tool. 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. The extent of excretion of buspirone and its metabolites into human milk is not known, and the manufacturer recommends that buspirone administration during breast-feeding should be avoided if possible. 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