Nextstellis Drug Interactions

Note: The prescribing information of concomitant medicinal products should be consulted to identify potential interactions.
Pharmacokinetic interactions: Effects of other medicinal products on Nextstellis: Interactions can occur with medicinal products that induce microsomal enzymes, resulting in increased clearance of sex hormones, 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 observed within a few weeks. After the cessation of medicinal product therapy, enzyme induction may be sustained for about 4 weeks.
Short-term treatment: Women on treatment with enzyme-inducing medicinal products should temporarily use a barrier method or another method of contraception in addition to the CHC. The barrier method must be used during the whole time of the concomitant medicinal product therapy and for 28 days after its discontinuation. If the medicinal product therapy runs beyond the end of the pink active tablets in the CHC pack, the white placebo tablets must be discarded and the next CHC pack should be started right away.
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.
Medicinal products increasing the clearance of CHCs (enzyme-induction), e.g.: barbiturates, bosentan, carbamazepine, phenytoin, primidone, rifampicin and HIV medicinal products (e.g. ritonavir, nevirapine and efavirenz) and possibly also felbamate, griseofulvin, oxcarbazepine, topiramate and products containing the herbal St. John's wort (Hypericum perforatum).
Medicinal products 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 oestrogens and progestogens. The effect of these changes may be clinically relevant in some cases.
Therefore, the prescribing information of concomitant HIV/HCV medicinal products should be consulted to identify potential interactions and any related recommendations. In case of any doubt, an additional barrier method of contraception should be used by women on protease inhibitor or non-nucleoside reverse transcriptase inhibitor therapy.
Medicinal products decreasing the clearance of CHCs (enzyme inhibitors): The clinical relevance of potential interactions with enzyme inhibitors remains unknown. Concomitant administration of strong CYP3A4 inhibitors can increase plasma concentrations of oestrogens or progestogens or both.
Potential interactions with drospirenone: In a multiple dose study with a drospirenone (3 mg/day)/ethinylestradiol (0.02 mg/day) combination, co-administration of the strong CYP3A4 inhibitor ketoconazole for 10 days increased the area under the curve during a 24-hour period (AUC(0-24 h)) of drospirenone (and ethinylestradiol) 2.7-fold (and 1.4-fold, respectively).
Potential interactions with estetrol: Estetrol is predominantly glucuronised by UDP-glucuronosyltransferase (UGT) 2B7 enzyme (see PHARMACOLOGY: 'Pharmacokinetics' under Actions). No clinically relevant interaction was observed with estetrol and the strong UGT inhibitor valproic acid.
Effects of Nextstellis on other medicinal products: Oral contraceptives may affect the metabolism of certain other active substances. Accordingly, plasma and tissue concentrations may either increase (e.g., ciclosporin) or decrease (e.g., lamotrigine).
Based on in vitro inhibition studies and in vivo interaction studies in female volunteers using omeprazole, simvastatin and midazolam as marker substrate, an interaction of drospirenone at doses of 3 mg with the metabolism of other active substances is unlikely.
Based on in vitro inhibition studies, an interaction of estetrol contained in Nextstellis with the metabolism of other active substances is unlikely.
Pharmacodynamic interactions: Concomitant use with the HCV medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir, with or without ribavirin, may increase the risk of ALT elevations in women using ethinylestradiol containing medicinal products such as CHCs (see Precautions). Women using medicinal products containing oestrogens other than ethinylestradiol, had a rate of ALT elevation similar to those not receiving any oestrogens; however, due to the limited number of women taking these other oestrogens, caution is warranted for co-administration with the combination therapeutic regimen ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin.
In patients without renal impairment, the concomitant use of drospirenone and angiotensin converting enzyme (ACE)-inhibitors or non-steroidal anti-inflammatory drugs (NSAIDs) did not show a significant effect on serum potassium. Nevertheless, concomitant use of Nextstellis with aldosterone antagonists or potassium-sparing diuretics has not been studied. In this case, serum potassium should be tested during the first treatment cycle. See also Precautions.
Paediatric population: Interaction studies have only been performed in adults.