Interactions : אינטראקציות

7. DRUG INTERACTIONS
Effects of PROVIGIL on CYP3A4/5 Substrates
The clearance of drugs that are substrates for CYP3A4/5 (e.g., steroidal contraceptives, cyclosporine, midazolam, and triazolam) may be increased by PROVIGIL via induction of metabolic enzymes, which results in lower systemic exposure. Dosage adjustment of these drugs should be considered when these drugs are used concomitantly with PROVIGIL [see Clinical Pharmacology (12.3)].
The effectiveness of steroidal contraceptives may be reduced when used with PROVIGIL and for two months after discontinuation of therapy. Alternative or concomitant methods of contraception are recommended for patients taking steroidal contraceptives (e.g., ethinyl estradiol) when treated concomitantly with PROVIGIL and for two months after discontinuation of PROVIGIL treatment.
Blood levels of cyclosporine may be reduced when used with PROVIGIL. Monitoring of circulating cyclosporine concentrations and appropriate dosage adjustment for cyclosporine should be considered when used concomitantly with PROVIGIL.

Effects of PROVIGIL on CYP2C19 Substrates
Elimination of drugs that are substrates for CYP2C19 (e.g., phenytoin, diazepam, propranolol, omeprazole, and clomipramine) may be prolonged by PROVIGIL via inhibition of metabolic enzymes, with resultant higher systemic exposure. In individuals deficient in the CYP2D6 enzyme, the levels of CYP2D6 substrates which have ancillary routes of elimination through CYP2C19, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, may be increased by co-administration of PROVIGIL.
Dose adjustments of these drugs and other drugs that are substrates for CYP2C19 may be necessary when used concomitantly with PROVIGIL [see Clinical Pharmacology (12.3)].

Warfarin
More frequent monitoring of prothrombin times/INR should be considered whenever PROVIGIL is coadministered with warfarin [see Clinical Pharmacology (12.3)].
Monoamine Oxidase (MAO) Inhibitors
Caution should be used when concomitantly administering MAO inhibitors and PROVIGIL.