Interactions : אינטראקציות

4.5   Interaction with other medicinal products and other forms of interaction

Interactions
Note: The prescribing information of concomitant medicinal products should be consulted to identify potential interactions.

Influence of other medicinal products on Zoely
Interactions between oral contraceptives and enzyme-inducing medicinal products may lead to breakthrough bleeding and/or contraceptive failure.

Hepatic metabolism: Interactions can occur with substances that induce CYP450 enzymes, resulting in reduced concentrations of sex hormones and decreased effectiveness of combined oral contraceptives, including Zoely. These substances are represented mostly with anticonvulsants (e.g. carbamazepine, topiramate, phenytoin, phenobarbital, primidone, oxcarbazepine, felbamate); anti-infective drugs (e.g. rifampicin, rifabutin, griseofulvin); St.
John’s wort; bosentan and HIV or Hepatitis C virus (HCV) protease inhibitors (e.g. ritonavir, boceprevir, telaprevir) and non-nucleoside reverse transcriptase inhibitors (e.g. efavirenz).

Enzyme induction can occur after a few days of treatment. Maximal enzyme induction is generally observed within a few weeks. After drug therapy is discontinued, enzyme induction can last for about 28 days.

A barrier contraceptive method should also be used during the concomitant use of an enzyme inducer, and for 28 days after its discontinuation. In case of long-term treatment with hepatic enzyme-inducing substances another method of contraception should be considered.

If concomitant drug administration runs beyond the end of the active tablets in the current blister pack, the next blister pack should be started right away without the usual placebo tablet interval.

Concomitant administration of strong (e.g. ketoconazole, itraconazole, clarithromycin) or moderate (e.g. fluconazole, diltiazem, erythromycin) CYP3A4 inhibitors may increase the serum concentrations of oestrogens or progestogens.

Medicinal product interaction studies were not performed with Zoely, but two studies with rifampicin and ketoconazole, respectively, were performed with a higher dosed nomegestrol acetate-estradiol combination (nomegestrol acetate 3.75 mg + 1.5 mg estradiol) in post- menopausal women. Concomitant use of rifampicin decreases the AUC0-∞ of nomegestrol acetate by 95 % and increases the AUC0-tlast of estradiol by 25 %. Concomitant use of ketoconazole (200 mg single dose) does not modify estradiol metabolism whereas increases in the peak concentration (85 %) and AUC0-∞ (115 %) of nomegestrol acetate were observed, which were of no clinical relevance. Similar conclusions are expected in women of childbearing potential.

Influence of Zoely on other medicinal products
Contraceptives containing ethinylestradiol may decrease the concentrations of lamotrigine by approximately 50%. Attention should be paid, notably when introducing a combined contraceptive, even with estradiol, in a well-equilibrated woman given lamotrigine.

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