Buspar drug interactions precautions
Psychotropic Agents
MAO inhibitors: It is recommended that BuSpar not be used concomitantly with MAO inhibitors.
Amitriptyline: After addition of Buspar to the amitriptyline dose regimen, no statistically significant differences in the steady-state pharmacokinetic parameters (Cmax, AUC, and Cmin) of amitriptyline or its metabolite nortriptyline were observed.
Diazepam: After addition of Buspar to the diazepam dose regimen, no statistically significant differences in the steady-state pharmacokinetic parameters (Cmax, AUC, and Cmin) were observed for diazepam, but increases of about 15% were seen for nordiazepam, and minor adverse clinical effects (dizziness, headache, and nausea) were observed.
Haloperidol: In a study in normal volunteers, concomitant administration of Buspar and haloperidol resulted in increased serum haloperidol concentrations. The clinical significance of this finding is not clear.
Trazodone: There is one report suggesting that the concomitant use of Desyrel® (trazodone hydrochloride) and Buspar may have caused 3- to 6-fold elevations on SGPT (ALT) in a few patients. In a similar study attempting to replicate this finding, no interactive effect on hepatic transaminases was identified.
Triazolam/Flurazepam: Coadministration of Buspar with either triazolam or flurazepam did not appear to prolong or intensify the sedative effects of either benzodiazepine.
Other Psychotropics: Because the effects of concomitant administration of Buspar with most other psychotropic drugs have not been studied, the concomitant use of Buspar with other CNS-active drugs should be approached with caution.
Inhibitors and Inducers of Cytochrome P450 3A4 (CYP3A4)
Buspar has been shown in vitro to be metabolized by CYP3A4. This finding is consistent with the in vivo interactions observed between Buspar and the following:
Diltiazem and Verapamil: In a study of nine healthy volunteers, coadministration of Buspar (10 mg as a single dose) with verapamil (80 mg t.i.d.) or diltiazem (60 mg t.i.d.) increased plasma Buspar concentrations (verapamil increased AUC and Cmax of Buspar 3.4-fold while diltiazem increased AUC and Cmax 5.5-fold and 4-fold, respectively.) Adverse events attributable to Buspar may be more likely during concomitant administration with either diltiazem or verapamil. Subsequent dose adjustment may be necessary and should be based on clinical assessment.
Erythromycin: In a study in healthy volunteers, coadministration of Buspar (10 mg as a single dose) with erythromycin (1.5 g/day for 4 days) increased plasma Buspar concentrations (5-fold increase in Cmax and 6-fold increase in AUC). These pharmacokinetic interactions were accompanied by an increased incidence of side effects attributable to Buspar. If the two drugs are to be used in combination, a low dose of Buspar (eg, 2.5 mg b.i.d.) is recommended. Subsequent dose adjustment of either drug should be based on clinical assessment.
Grapefruit Juice: In a study in healthy volunteers, coadministration of Buspar (10 mg as a single dose) with grapefruit juice (200 mL double-strength t.i.d. for 2 days) increased plasma Buspar concentrations (4.3-fold increase in Cmax; 9.2-fold increase in AUC). Patients receiving Buspar should be advised to avoid drinking such large amounts of grapefruit juice.
Itraconazole: In a study in healthy volunteers, coadministration of Buspar (10 mg as a single dose) with itraconazole (200 mg/day for 4 days) increased plasma Buspar concentrations (13-fold increase in Cmax and 19-fold increase in AUC). These pharmacokinetic interactions were accompanied by an increased incidence of side effects attributable to Buspar. If the two drugs are to be used in combination, a low dose of Buspar (eg, 2.5 mg q.d.) is recommended. Subsequent dose adjustment of either drug should be based on clinical assessment.
Nefazodone: In a study of steady-state pharmacokinetics in healthy volunteers, coadministration of Buspar (2.5 or 5 mg b.i.d.) with nefazodone (250 mg b.i.d.) resulted in marked increases in plasma Buspar concentrations (increases up to 20-fold in Cmax and up to 50-fold in AUC) and statistically significant decreases (about 50%) in plasma concentrations of the Buspar metabolite 1-PP. With 5 mg b.i.d. doses of Buspar, slight increases in AUC were observed for nefazodone (23%) and its metabolites hydroxynefazodone (HO-NEF) (17%) and meta-chlorophenylpiperazine (9%). Slight increases in Cmax were observed for nefazodone (8%) and its metabolite HO-NEF (11%). Subjects receiving Buspar 5 mg b.i.d. and nefazodone 250 mg b.i.d experienced lightheadedness, asthenia, dizziness, and somnolence, adverse events also observed with either drug alone. If the two drugs are to be used in combination, a low dose of Buspar (eg, 2.5 mg q.d.) is recommended. Subsequent dose adjustment of either drug should be based on clinical assessment.
Rifampin: In a study in healthy volunteers, coadministration of Buspar (30 mg as a single dose) with rifampin (600 mg/day for 5 days) decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of Buspar. If the two drugs are to be used in combination, the dosage of Buspar may need adjusting to maintain anxiolytic effect.
Other Inhibitors and Inducers of CYP3A4: Substances that inhibit CYP3A4, such as ketoconazole or ritonavir, may inhibit Buspar metabolism and increase plasma concentrations of Buspar while substances that induce CYP3A4, such as dexamethasone or certain anticonvulsants (phenytoin, phenobarbital, carbamazepine), may increase the rate of Buspar metabolism. If a patient has been titrated to a stable dosage on Buspar, a dose adjustment of Buspar may be necessary to avoid adverse events attributable to Buspar or diminished anxiolytic activity. Consequently, when administered with a potent inhibitor of CYP3A4, a low dose of Buspar used cautiously is recommended. When used in combination with a potent inducer of CYP3A4 the dosage of Buspar may need adjusting to maintain anxiolytic effect.
Other Drugs
Cimetidine: Coadministration of Buspar with cimetidine was found to increase Cmax (40%) and Tmax (2-fold), but had minimal effects on the AUC of Buspar.
Protein Binding
In vitro, Buspar does not displace tightly bound drugs like phenytoin, propranolol, and warfarin from serum proteins. However, there has been one report of prolonged prothrombin time when Buspar was added to the regimen of a patient treated with warfarin. The patient was also chronically receiving phenytoin, phenobarbital, digoxin, and Synthroid®. In vitro, Buspar may displace less firmly bound drugs like digoxin. The clinical significance of this property is unknown.
Therapeutic levels of aspirin, desipramine, diazepam, flurazepam, ibuprofen, propranolol, thioridazine, and tolbutamide had only a limited effect on the extent of binding of Buspar to plasma proteins.
Synthroid® is the registered trademark of Abbott Laboratories.
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