Đăng xuất
In vitro drug metabolism studies show that dutasteride is metabolised by human cytochrome P450 isoenzyme CYP3A4. Therefore, blood concentrations of dutasteride may increase in the presence of inhibitors of CYP3A4.
Phase II data showed a decrease in clearance of dutasteride when co-administered with the CYP3A4 inhibitors verapamil (37%) and diltiazem (44%). In contrast, no decrease in clearance was seen when amlodipine, another calcium channel antagonist, was co-administered with dutasteride. A decrease in clearance and subsequent increase in exposure to dutasteride, in the presence of CYP3A4 inhibitors, is unlikely to be clinically significant due to the wide margin of safety (up to 10 times the recommended dose has been given to patients for up to six months), therefore no dose adjustment is necessary.
In vitro, dutasteride is not metabolised by human cytochrome P450 isoenzymes CYP1A2, CYP2A6, CYP2E1, CYP2C8, CYP2C9, CYP2C19, CYP2B6 and CYP2D6.
Dutasteride neither inhibits human cytochrome P450 drug-metabolizing enzymes in vitro nor induces cytochrome P450 isoenzymes CYP1A, CYP2B, and CYP3A in rats and dogs in vivo.
In vitro studies demonstrate that dutasteride does not displace warfarin, diazepam, acenocoumarol, phenprocoumon or phenytoin from plasma protein, nor do these model compounds displace dutasteride. Compounds that have been tested for drug interactions in man include tamsulosin, terazosin, warfarin, digoxin, and cholestyramine, and no clinically significant pharmacokinetic or pharmacodynamic interactions have been observed.
Although specific interaction studies were not performed with other compounds, approximately 90% of the subjects in large Phase III studies receiving dutasteride were taking other medications concomitantly. No clinically significant adverse interactions were observed in clinical trials when dutasteride was co-administered with anti-hyperlipidemics, angiotensin converting enzyme (ACE) inhibitors, beta-adrenergic blocking agents, calcium channel blockers, corticosteroids, diuretics, nonsteroidal anti-inflammatory drugs (NSAIDs), phosphodiesterase Type V inhibitors, and quinolone antibiotics.
