Interactions : אינטראקציות

4.5 Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed.
The efficacy of estrogens and progestogens might be impaired:
• The metabolism of estrogens and progestogens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically P450 enzymes, such as anticonvulsants (e.g.
phenobarbital, carbamazepin, phenytoin) and anti-infectives (e.g. rifampicin, rifabutin, nevirapine, efavirenz).
• Ritonavir 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 estrogens and progestogens.
• Clinically, an increased metabolism of estrogens and progestogens may lead to decreased effect and changes in the uterine bleeding profile.
Effect of HRT with estrogens on other medicinal products

Hormone contraceptives containing estrogens have been shown to significantly decrease plasma concentrations of lamotrigine when co-administered due to induction of lamotrigine glucuronidation. This may reduce seizure control. Althoughthe potential interaction between hormone replacement therapy and lamotrigine has not been studied, it is expected that a similar interaction exists, which may lead to a reduction in seizure control among women taking both medicinal products together.

Pharmacodynamic interactions

During clinical trials with the HCV combination drug regimen ombitasvir/paritaprevir/ritonavir with and without dasabuvir, ALTelevations greater than 5 times the upper limit of normal (ULN) were significantly more frequent in women usingethinylestradiol-containing medicinal products such as CHCs.
Women using medicinal products containing estrogens otherthan ethinylestradiol, such as estradiol, had a rate of ALT elevation similar to those not receiving any estrogens; however,due to the limited number of women taking these other estrogens, caution is warranted for co-administration with thecombination drug regimen ombitasvir/paritaprevir/ritonavir with or without dasabuvir and also the regimen withglecaprevir/pibrentasvir (see section 4.4).