nt iridectomy.
5.4 Potential Thioridazine Interaction
The effect of fluvoxamine (25 mg immediate-release tablets given twice daily for one week) on thioridazine steady-state concentrations was eva luated in 10 male inpatients with schizophrenia. Concentrations of thioridazine and its two active metabolites, mesoridazine and sulforidazine, increased 3-fold following coadministration of fluvoxamine.
Thioridazine administration produces a dose-related prolongation of the QTc interval, which is associated with serious ventricular arrhythmias, such as torsades de pointes-type arrhythmias, and sudden death. It is likely that this experience underestimates the degree of risk that might occur with higher doses of thioridazine. Moreover, the effect of fluvoxamine may be even more pronounced when it is administered at higher doses.
Therefore, LUVOX CR Capsules should not be coadministered with thioridazine (see CONTRAINDICATIONS [4]).
5.5 Potential Tizanidine Interaction
Fluvoxamine is a potent inhibitor of CYP1A2, and tizanidine is a CYP1A2 substrate. The effect of immediate-release fluvoxamine maleate tablets (100 mg daily for four days) on the pharmacokinetics and pharmacodynamics of a single dose of tizanidine has been studied in 10 healthy male subjects. Tizanidine Cmax was increased approximately 12-fold (range 5-fold to 32-fold), elimination half-life was increased by almost 3-fold, and AUC increased 33-fold (range 14-fold to 103-fold). The mean maximal effect on blood pressure was a 35 mm Hg decrease in systolic blood pressure, a 20 mm Hg decrease in diastolic blood pressure, and a 4 beat/min decrease in heart rate. Drowsiness was significantly increased, and performance on the psychomotor task was significantly impaired. LUVOX CR Capsules and tizanidine should not be used together (see CONTRAINDICATIONS [4]).
5.6 Potential Pimozide Interaction
Pimozide is metabolized by the CYP3A4 isozyme and it has been demonstrated that ketoconazole, a potent inhibitor of CYP3A4, blocks the metabolism of this drug, resulting in increased plasma concentrations of parent drug. An increased plasma concentration of pimozide causes QT prolongation and has been associated with torsades de pointes-type ventricular tachycardia, sometimes fatal. As noted below, a substantial pharmacokinetic interaction has been observed for fluvoxamine in combination with alprazolam, a drug that is known to be metabolized by the CYP3A4 isozyme. Although it has not been definitively demonstrated that fluvoxamine is a potent CYP3A4 inhibitor, it is likely to be, given the substantial interaction of fluvoxamine with alprazolam. Consequently, it is recommended that fluvoxamine not be used in combination with pimozide (see CONTRAINDICATIONS [4]).
5.7 Potential Alosetron Interaction
In a pharmacokinetic study, 40 healthy female subjects received fluvoxamine in escalating doses from 50 to 200 mg/day for 16 days with coadministration of alosetron 1 mg on the last day. Fluvoxamine increased mean alosetron plasma concentrations (AUC) approximately 6-fold and prolonged the half-life by approximately 3-fold. Consequently, it is recommended that LUVOX CR Capsules not be used in combination with alosetron (see CONTRAINDICATIONS [4] and Lotronex® (alosetron) package insert).
5.8 Potential Ramelteon Interaction |
