Interactions : אינטראקציות

4.5   Interaction with other medicinal products and other forms of interaction

Note: the prescribing information of concomitant medications should be consulted to identify interactions.

Effects of other medicinal products on Primolut Nor

Interactions can occur with drugs that induce microsomal enzymes, which can result in increased clearance of sex hormones which may lead to changes in the uterine bleeding profile and/or reduction of the therapeutic effect.

Enzyme induction can already be observed after a few days of treatment. Maximal enzyme induction is generally seen within a few weeks. After the cessation of drug therapy enzyme induction may be sustained for about 4 weeks .

Substances increasing the clearance of sex hormones (diminished efficacy by enzyme- induction), e.g.:
Phenytoin, barbiturates, bosentan, primidone, carbamazepine, rifampicin and HIV medication ritonavir, nevirapine and efavirenz, and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin and products containing St. Johns wort (Hypericum perforatum).

Substances with variable effects on the clearance of sex hormones, e.g.: When co-administered with sex hormones, many HIV/HCV protease inhibitors and non- nucleoside reverse transcriptase inhibitors can increase or decrease plasma concentrations of estrogen or progestin. These changes may be clinically relevant in some cases.

Substances decreasing the clearance of sex hormones (enzyme inhibitors): The clinical relevance of potential interactions with enzyme inhibitors remains unknown.
Strong and moderate CYP3A4 inhibitors such as azole antifungals (e.g. itraconazole, voriconazole, fluconazole), verapamil, macrolides (e.g. clarithromycin, erythromycin), diltiazem and grapefruit juice can increase plasma concentrations of the estrogen or the progestin or both.

Etoricoxib doses of 60 to 120 mg/day have been shown to increase plasma concentrations of ethinylestradiol 1.4 to 1.6-fold, respectively when taken concomitantly with a combined hormonal medicinal product containing 0.035 mg ethinylestradiol.

Effects of Primolut Nor on other medicinal products
Progestogens may interfere with the metabolism of other drugs. Accordingly, plasma and tissue concentrations may either increase (e.g. ciclosporin) or decrease (e.g. lamotrigine).
Clinical data suggest that ethinylestradiol inhibits the clearance of CYP1A2 substrates, leading to a weak (e.g. theophylline) or moderate (e.g. tizanidine) increase in plasma concentration.

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). Primolut Nor can be restarted 2 weeks following completion of treatment with this combination drug regimen.

Other forms of interaction
The use of progestogens may influence the results of certain laboratory tests (e.g. tests for hepatic function, thyroid function and coagulation).