Duphaston Drug Interactions

In vitro data show that the major metabolic pathway generating the main pharmacologically active metabolite 20α dihydrodydrogesterone (DHD) is catalyzed by aldo-keto reductase 1C (AKR 1C) in human cytosol. Next to the cytosolic metabolism there are metabolic transformations by cytochrome P450 isoenzymes (CYPs), nearly exclusively via CYP3A4, resulting in several minor metabolites. The main active metabolite DHD is substrate for metabolic transformation by CYP3A4.
Therefore, the metabolism of dydrogesterone and DHD may be increased by concomitant use of substances known to induce these CYP enzymes such as anticonvulsants (e.g. Phenobarbital, phenytoin, carbamazepine), anti-infectives (e.g. rifampicin, rifabutin, nevirapine, efavirenz) and herbal preparations containing e.g. St John's Wort (Hypericum perforatum), sage, or gingko biloba.
Ritonavir and nelfinavir, although known as strong cytochrome enzyme inhibitors, by contrast exhibit enzyme-inducing properties when used concomitantly with steroid hormones.
Clinically, increased metabolism of dydrogesterone may lead to a decreased effect and changes in the bleeding pattern.
In vitro studies have shown that dydrogesterone and DHD do not inhibit or induce CYP drug-metabolizing enzymes at clinically relevant concentrations.