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The metabolism of oestrogens and progestagens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes, such as anticonvulsants (e.g. phenobarbital, phenytoin, carbamazepine) and anti-infectives (e.g. rifampicin, rifabutin, nevirapine, efavirenz).
Ritonavir, telaprevir and nelfinavir, although known as strong inhibitors, by contrast exhibit inducing properties when used concomitantly with steroid hormones. Herbal preparations containing St John's Wort (Hypericum perforatum) may induce the metabolism of oestrogens and progestagens.
Clinically, an increased metabolism of oestrogens and progestagens may lead to decreased effect and changes in the uterine bleeding profile.
Pharmacodynamic interactions: In clinical studies when there was co-administration of contraceptives containing ethinyl oestradiol with certain active substance combinations used in the treatment of HCV infections (ombitasvir/paritaprevir/ritonavir with or without dasabuvir; glecaprevir/pibrentasvir), ALT elevation occurred significantly more frequently than in patients who were treated exclusively with the antiviral active substances (including cases of an increase of up to five times the upper level of normal). Conversely, on use of other oestrogens (particularly oestradiol and oestradiol valerate) the incidence of elevation of transaminases was not higher than in patients not receiving oestrogen therapy. However, due to the limited number of women who were taking other oestrogen-containing medicinal products of this kind with one of the named active substance combinations, caution is advised on principle.
Drugs that inhibit the activity of hepatic microsomal drug metabolising enzymes, e.g. ketoconazole, may increase circulating levels of the active substances in Trisequens.
Concomitant administration of cyclosporine may cause increased blood levels of cyclosporine, creatinine and transaminases due to decreased metabolism of cyclosporine in the liver.
