Evra Drug Interactions

Changes in contraceptive effectiveness associated with coadministration of other drugs: If a woman on hormonal contraceptives takes a drug or herbal product that induces enzymes, including CYP3A4, that metabolize contraceptive hormones, the patient should be counseled to use additional contraception or a different method of contraception. Drugs or herbal products that induce such enzymes may decrease the plasma concentrations of contraceptive hormones, and may decrease the effectiveness of hormonal contraceptives or increase breakthrough bleeding. Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include: some anti-epileptics (e.g. carbamazepine, eslicarbazepine acetate, felbamate, oxcarbazepine, phenytoin, rufinamide, topiramate); (fos)aprepitant; barbiturates; bosentan; griseofulvin; some (combinations of) HIV protease inhibitors (e.g. nelfinavir, ritonavir, ritonavir-boosted protease inhibitors); modafinil; some non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine); rifampin and rifabutin; St. John's wort.
Management: Enzyme induction may be observed after a few days of treatment. Maximal enzyme induction is generally seen in about 10 days but may then be sustained for at least 4 weeks after the cessation of medicinal product therapy.
Short-term: A woman on short-term treatment with medicinal products that induce hepatic drug metabolizing enzymes or individual active substances that induce these enzymes should temporarily use a barrier method in addition to EVRA, i.e. during the time of concomitant medicinal product administration and for 28 days after their discontinuation.
Long-term: In women on long-term treatment with enzyme-inducing active substances, another reliable, non-hormonal, method of contraception is recommended.
Increase in plasma hormone levels associated with coadministered drugs: Some drugs and grapefruit juice may increase the plasma levels of ethinyl estradiol if coadministered. Examples include: acetaminophen, ascorbic acid, CYP3A4 inhibitors (including itraconazole, ketoconazole, voriconazole, fluconazole, and grapefruit juice), etoricoxib, some HIV protease inhibitors (e.g. atazanavir, indinavir), HMG-CoA reductase inhibitors (including atorvastatin and rosuvastatin), some non-nucleoside reverse transcriptase inhibitors (e.g. etravirine).
Changes in plasma levels of coadministered drugs: Data from oral combination hormonal contraceptives indicate that they may also affect the pharmacokinetics of some other drugs if used concomitantly.
Examples of drugs whose plasma levels may be increased (due to CYP inhibition) include: cyclosporine, omeprazole, prednisolone, selegiline, theophylline, tizanidine, voriconazole.
Examples of drugs whose plasma levels may be decreased (due to induction of glucuronidation) include: acetaminophen, clofibric acid, lamotrigine (see as follows), morphine, salicylic acid, temazepam.
Lamotrigine: Combined hormonal contraceptives have been shown to significantly decrease plasma concentrations of lamotrigine when coadministered likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary.
Contraindicated co-administration: Concomitant use with the medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir, with or without ribavirin may increase the risk of ALT elevations (see Contraindications and Precautions). Therefore, 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. EVRA can be restarted 2 weeks following completion of treatment with this combination drug regimen.
Physicians are advised to consult the labeling of concurrently-used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations and the possible need to adjust dosages.
Laboratory tests: Certain endocrine and liver function tests and blood components may be affected by hormonal contraceptives: Increased prothrombin and factors VII, VIII, IX, and X; decreased anti-thrombin III; decreased protein S; increased norepinephrine (noradrenaline)-induced platelet aggregability.
Increased thyroid binding globulin (TBG) leading to increased circulating total thyroid hormone, as measured by protein-bound iodine (PBI), T4 by column or by radioimmunoassay. Free T3 resin uptake is decreased, reflecting the elevated TBG, free T4 concentration is unaltered.
Other binding proteins may be elevated in serum.
Sex hormone-binding globulins (SHBG) are increased and result in elevated levels of total circulating endogenous sex steroids. However, the free or biologically active levels of sex steroids either decrease or remain the same.
High-density lipoprotein (HDL-C), total cholesterol (Total-C), low-density lipoprotein (LDL-C) and triglycerides may all increase slightly with EVRA, while LDL-C/HDL-C ratio may remain unchanged.
Glucose tolerance may be decreased.
Serum folate levels may be depressed by hormonal contraceptive therapy. This has potential to be of clinical significance if a woman becomes pregnant shortly after discontinuing hormonal contraceptives. All women are now advised to take supplemental folic acid peri-conceptionally.