Interactions : אינטראקציות

4.5    Interaction with other medicinal products and other forms of interaction

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

Effects of other medicinal products on NuvaRing
Interactions can occur with drugs or herbal products that induce microsomal enzymes which can result in increased clearance of sex hormones and which may lead to breakthrough bleeding and/or contraceptive failure.

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

Short-term treatment
Women on treatment with enzyme-inducing drugs or herbal products should temporarily use a barrier method or another method of contraception in addition to NuvaRing. Note: NuvaRing should not be used with a diaphragm, cervical cap, or female condom. The barrier method must be used during the whole time of the concomitant drug therapy and for 28 days after its discontinuation.
If concomitant drug administration runs beyond the 3 weeks of a ring-cycle, the next ring should be inserted immediately, without having the usual ring-free interval.

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

The following interactions have been reported in the literature.

Substances increasing the clearance of combined hormonal contraceptives Interactions can occur with medicinal or herbal products that induce microsomal enzymes, specifically cytochrome P450 enzymes (CYP), which can result in increased clearance reducing plasma concentrations of sex hormones and may decrease the effectiveness of combined hormonal contraceptives, including NuvaRing. These products include phenytoin, phenobarbital, primidone, bosentan, carbamazepine, rifampicin, and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin, some HIV protease inhibitors (e.g. ritonavir) and non-nucleoside reverse transcriptase inhibitors (e.g. efavirenz), and products containing the herbal remedy St. John’s wort.

Substances with variable effects on the clearance of combined hormonal contraceptives When co-administered with hormonal contraceptives, many combinations of HIV protease inhibitors (e.g. nelfinavir) and non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine), and/or combinations with HCV medicinal products (e.g. boceprevir, telaprevir), can increase or decrease plasma concentrations of progestagens, including etonogestrel, or estrogen. The net effect of these changes may be clinically relevant in some cases.

Substances decreasing the clearance of combined hormonal contraceptives The clinical relevance of potential interactions with enzyme inhibitors remains unknown.
Concomitant administration of strong (e.g. ketoconazole, itraconazole, clarithromycin) or moderate (e.g. fluconazole, diltiazem, erythromycin) CYP3A4 inhibitors may increase the serum concentrations of estrogens or progestogens, including etonogestrel.

There have been reports of ring breakage during concomitant use of intravaginal preparations, including antimycotic, antibiotic and lubricant products (see section 4.4, ‘Broken Rings’). Based on pharmacokinetic data, vaginally administered antimycotics and spermicides are unlikely to affect the contraceptive efficacy and safety of NuvaRing.

Hormonal contraceptives may interfere with the metabolism of other drugs. Accordingly, plasma and tissue concentrations may either increase (e.g., ciclosporin) or decrease (e.g. lamotrigine).

Pharmacodynamic interactions
Concomitant use with medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir, with or without ribavirin, or glecaprevir/pibrentasvir may increase the risk of ALT elevations (see sections 4.3 and 4.4). Therefore, NuvaRing 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. NuvaRing can be restarted 2 weeks following completion of treatment with this combination drug regimen.

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 sex hormone binding globulin), lipid / lipoprotein fractions, parameters of carbohydrate metabolism and parameters of coagulation and fibrinolysis.
Changes generally remain within the normal laboratory range.

Interaction with tampons

Pharmacokinetic data show that the use of tampons has no effect on the systemic absorption of the hormones released by NuvaRing. On rare occasions NuvaRing might be expelled while removing a tampon (see advice for ‘What to do if the ring was temporarily outside the vagina’ in section 4.2).