Interactions : אינטראקציות

4.5     Interaction with other medicinal products and other forms of interaction

Interactions between ethinylestradiol or gestodene and other substances may lead to decreased or increased plasma and tissue concentrations of ethinylestradiol or gestodene.

Decreased ethinylestradiol serum concentrations may cause an increased incidence of breakthrough bleeding and menstrual irregularities and may possibly reduce efficacy of the COC.

Concomitant use not recommended:

Enzyme inducing agents such as: anticonvulsants (phenobarbital, phenytoin, primidone, carbamazepine, topiramate, felbamate); rifabutin; rifampicine; griseofulvine, and possibly St. John’s Wort. Reduction in the efficacy of contraception through increased hepatic metabolism during treatment and for one cycle following treatment discontinuation. Preference should be given to a nonhormonal contraceptive method.
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When co-administered with COCs 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. Please see the corresponding SmPC of each HIV or HCV protease inhibitors and nonnucleoside reverse transcriptase inhibitors for specific recommendation.

Strong and moderate CYP3A4 inhibitors such as azole antifungals (e.g. itraconazole, voriconazole, fluconazole), macrolides (e.g. clarithromycin, erythromycin), verapamil, 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 contraceptive containing 0.035 mg ethinylestradiol.
The clinical relevance of potential interactions with enzyme inhibitors remains unknown.

Modafinil: risk of a decreased contraceptive efficacy during treatment and for one cycle following treatment discontinuation.

Flunarizine: risk of galactorrhea due to increased sensitivity of mammary tissue to prolactin through the action of flunarizine.

Troleandomycin may increase the risk for intrahepatic cholestasis during co-administration with COCs.

Effects of COCs on other medicinal products:

Oral contraceptives may affect the metabolism of certain other drugs. Accordingly, plasma and tissue concentrations may either increase (e.g. cyclosporin) or decrease (e.g. lamotrigine).

Clinical data suggests that ethinylestradiol is inhibiting the clearance of CYP1A2 substrates leading to a weak (e.g., theophylline) or to moderate (e.g., tizanidine) increase in their plasma concentration.

The labelling of concomitant medications should be consulted to identify potential interactions.

Pharmacodynamic interactions
During clinical trials with patients treated for hepatitis C virus infections (HCV) with medicinal products containing ombitasvir/paritaprevir/ritonavir, dasabuvir with or without ribavirin, transaminase (ALT) elevations higher than 5 times the upper limit of normal (ULN) occurred significantly more frequently in women using ethinylestradiol-containing medications such as combined hormonal contraceptives (CHCs). Additionally, also in patients treated with glecaprevir/pibrentasvir or sofosbuvir/velpatasvir/voxilaprevir, ALT elevations were observed in women using ethinylestradiol-containing medications such as CHCs (see section 4.3).

Therefore, Minesse users must switch to an alternative method of contraception (e.g., progestagen- only contraception or non-hormonal methods) prior to starting therapy with these combination drug regimens. Minesse can be restarted 2 weeks following completion of treatment with these combination drug regimens