Regulon Drug Interactions

Note: The prescribing information of concomitant medications 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, or glecaprevir/pibrentasvir may increase the risk of ALT elevations (see Contraindications and Precautions). Therefore, Regulon users must switch to an alternative method of contraception (e.g., progestogen-only contraception or non-hormonal methods) prior to starting therapy with this combination drug regimen. Regulon can be restarted 2 weeks following completion of treatment with this combination drug regimen.
Pharmacokinetic interactions: Effects of other medicinal products on Regulon: Interactions can occur with drugs that induce microsomal enzymes, especially cytochrome P450 isoenzymes (CYP), which can result in increased clearance of sex hormones and which may lead to breakthrough bleeding and/or oral contraceptive failure.
Management: 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.
Short-term treatment: Women on treatment with enzyme inducing drugs should temporarily use a barrier method or another method of contraception in addition to the COC. The barrier method must be used during the whole time of the concomitant drug therapy and for 28 days after its discontinuation.
If the drug therapy runs beyond the end of the tablets in the COC pack, the next COC pack should be started right after the previous one without the usual tablet-free interval.
Long-term treatment: In women on long-term treatment with 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 COCs (diminished efficacy of COCs by enzyme-induction), e.g.: Barbiturates, bosentan, carbamazepine, phenytoin, primidone, rifampicin, and certain HIV protease inhibitors (e.g. ritonavir) and non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine, efavirenz) and possibly also felbamate, griseofulvin, oxcarbazepine, topiramate, rifabutin and products containing the herbal remedy St. John's Wort (Hypericum perforatum).
Substances with variable effects on the clearance of COCs: When co-administered with COCs, many combinations of HIV protease inhibitors (e.g. nelfinavir) and non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine) and/or combinations with HCV inhibitors (e.g. boceprevir, telaprevir) 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/HCV 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.
Substances decreasing the clearance of COCs (enzyme inhibitors) 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 progestins, including etonogestrel.
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.
Effects of Regulon on other medicinal products: Oral contraceptives may interfere with the metabolism of other active substances. Accordingly, plasma and tissue concentrations may be affected.
Ciclosporin: Oral contraceptives may inhibit the metabolism of ciclosporin in the liver resulting in increased incidence of adverse events.
Lamotrigine: Combined oral contraceptives have been shown to induce the metabolism of lamotrigine which may result in subtherapeutic plasma levels of lamotrigine.
Clinical data suggests that ethinylestradiol is inhibiting the clearance of CYP1A2 substrates leading to a weak (e.g. theophylline) or moderate (e.g. tizanidine) increase in their plasma concentration.
Tizanidine: Oral contraceptives may enhance the blood pressure lowering effect of tizanidine due to inhibition of the metabolism of tizanidine via CYP1A2. Caution should be exercised when prescribing tizanidine to users of oral contraceptives due to the narrow therapeutic window of tizanidine.
Levothyroxine: Oestrogen therapy may lead to a reduction of free thyroxine and increase of TSH in hypothyroid women treated with levothyroxine. The combination may be used with dose adjustment.
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.