Buspirone Hydrochloride

Reversible MAOI; starting buspirone is contraindicated due to increased risk of serotonin syndrome.

Contraindicated due to increased risk of serotonin syndrome and/or elevated blood pressure. Use within 14 days before or after MAOI treatment is contraindicated.

Intravenous methylene blue (reversible MAOI); starting buspirone is contraindicated due to increased risk of serotonin syndrome.

Increased risk of serotonin syndrome and/or elevated blood pressure. Contraindicated within 14 days of stopping either drug.

Diltiazem increased buspirone AUC 5.5-fold and Cmax 4-fold; adverse events attributable to buspirone may be more likely during concomitant administration.

CYP3A4 inhibitor; 5-6 fold increase in buspirone concentrations with increased incidence of side effects; low dose buspirone recommended.

Verapamil increased buspirone AUC and Cmax 3.4-fold; adverse events attributable to buspirone may be more likely during concomitant administration.

No statistically significant differences in steady-state pharmacokinetic parameters observed when buspirone added to amitriptyline regimen.

Minor adverse clinical effects (dizziness, headache, nausea) observed; about 15% increases in nordiazepam concentrations.

Coadministration did not appear to prolong or intensify sedative effects, but use with caution due to CNS activity.

Concomitant administration resulted in increased serum haloperidol concentrations; clinical significance unclear.

CYP3A4 inhibitor that may increase buspirone concentrations; concomitant use should be approached with caution.

One report suggested concomitant use may cause 3-6 fold elevations in ALT; however, similar study found no interactive effect on hepatic transaminases.

Coadministration did not appear to prolong or intensify sedative effects, but use with caution due to CNS activity.

Diazepam: After addition of buspirone to the diazepam dose regimen, no statistically significant differences in the steady-state pharmacokinetic parameters (C max , AUC, and C min ) were observed for diazepam, but increases of about 15% were seen for nordiazepam, and minor adverse clinical effects (dizziness, headache, and nausea) were observed.

Itraconazole: In a study in healthy volunteers, coadministration of buspirone (10 mg as a single dose) with itraconazole (200 mg/day for 4 days) increased plasma buspirone concentrations (13 fold increase in C max and 19 fold increase in AUC).

Other inhibitors and inducers of CYP3A4: Substances that inhibit CYP3A4, such as ketoconazole or ritonavir, may inhibit buspirone metabolism and increase plasma concentrations of buspirone while substances that induce CYP3A4, such as dexamethasone or certain anticonvulsants (phenytoin, phenobarbital, carbamazepine), may increase the rate of buspirone metabolism.

Protein Binding In vitro , buspirone does not displace tightly bound drugs like phenytoin, propranolol, and warfarin from serum proteins. Therapeutic levels of aspirin, desipramine, diazepam, flurazepam, ibuprofen, propranolol, thioridazine, and tolbutamide had only a limited effect on the extent of binding of buspirone to plasma proteins (see CLINICAL PHARMACOLOGY ).

Other inhibitors and inducers of CYP3A4: Substances that inhibit CYP3A4, such as ketoconazole or ritonavir, may inhibit buspirone metabolism and increase plasma concentrations of buspirone while substances that induce CYP3A4, such as dexamethasone or certain anticonvulsants (phenytoin, phenobarbital, carbamazepine), may increase the rate of buspirone metabolism.

Therapeutic levels of aspirin, desipramine, diazepam, flurazepam, ibuprofen, propranolol, thioridazine, and tolbutamide had only a limited effect on the extent of binding of buspirone to plasma proteins (see CLINICAL PHARMACOLOGY ).