Interactions : אינטראקציות

4.5 Interaction with other medicinal products and other forms of interaction
Note: The prescribing information of concomitant medicinal products should be consulted to identify potential interactions.

Pharmacodynamic interactions
Concomitant use with the medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir, with or without ribavirin may increase the risk of ALT elevations (see sections 4.3 and 4.4). Therefore, EVRA-users must switch to an alternative method of contraception (e.g., progestagen-only contraception or non-hormonal methods) prior to starting therapy with this combination drug regimen. EVRA can be restarted 2 weeks following completion of treatment with this combination drug regimen.

Effects of other medicinal products on EVRA
Interactions can occur with drugs that induce microsomal enzymes which can result in increased clearance of sex hormones and which may lead to breakthrough bleeding and/or contraceptive failure. The following interactions have been reported in the literature.

Substances increasing the clearance of CHCs (diminished efficacy of CHCs by enzyme- induction),e.g.:
Barbiturates, bosentan, carbamazepine, phenytoin, primidone, rifampicin, modafinil and HIV medications ritonavir, nevirapine and efavirenz; and possibly also felbamate, griseofulvin, oxcarbazepine, topiramate and products containing the herbal remedy St. John's Wort (hypericum perforatum).


Management
Enzyme induction may be observed after a few days of treatment. Maximal enzyme induction is generally seen in about 10 days but may then be sustained for at least 4 weeks after the cessation of medicinal product therapy.

Short-term
A woman on short-term treatment with medicinal products that induce hepatic drug metabolising enzymes or individual active substances that induce these enzymes should temporarily use a barrier method in addition to EVRA, i.e. during the time of concomitant medicinal product administration and for 28 days after their discontinuation.

If concomitant medicinal product administration extends beyond the end of the three-week patch period, the next transdermal patch should be applied without the usual transdermal patch-free interval.

Long-term
In women on long-term treatment with enzyme-inducing active substances, another reliable, non-hormonal, method of contraception is recommended.

Substances with variable effects on the clearance of CHCs
When co-administered with CHCs, many combinations of HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors, including combinations with HCV inhibitors can increase or decrease plasma concentrations of estrogen or progestins. The net effect of these changes may be clinically relevant in some cases.

Therefore, the prescribing information of concomitant HIV medications should be consulted to identify potential interactions and any related recommendations. In case of any doubt, an additional barrier contraceptive method should be used by women on protease inhibitor or non-nucleoside reverse transcriptase inhibitor therapy.

Inhibition of ethinyl estradiol metabolism
Etoricoxib has been shown to increase plasma levels of ethinyl estradiol (50 to 60%) when taken concomitantly with an oral triphasic hormonal contraceptive. It is thought that etoricoxib increases ethinyl estradiol levels because it inhibits sulfotransferase activity thereby inhibiting ethinyl estradiol metabolism.

Effect of EVRA on other medicinal products
Hormonal contraceptives may affect the metabolism of certain other active substances.
Accordingly, plasma and tissue concentrations may increase (e.g. ciclosporin). Dosage adjustment of the concomitant medicinal product may be necessary.

Lamotrigine: Combined hormonal contraceptives have been shown to significantly decrease plasma concentrations of lamotrigine when coadministered likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary.

Laboratory tests
The use of contraceptive steroids may influence the results of certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and renal function, plasma levels of (carrier) proteins, e.g. corticosteroid-binding globulin and lipid/lipoprotein fractions, parameters of carbohydrate metabolism and parameters of coagulation and fibrinolysis.
Changes generally remain within the normal laboratory range.