Zoely

/ MSD

One tablet is to be taken daily for 28 consecutive days. Each pack starts with 24 white active tablets, followed by 4 yellow placebo tablets. A subsequent pack is started immediately after finishing the previous pack, without a break in daily tablet intake and irrespective of presence or absence of withdrawal bleeding. Withdrawal bleeding usually starts on day 2-3 after intake of the last white tablet and may not have finished before the next pack is started.
Renal impairment: Although data in renal impaired patients are not available, renal impairment is unlikely to affect the elimination of nomegestrol acetate and estradiol.
Hepatic impairment: No clinical studies have been performed in patients with hepatic insufficiency. Since the metabolism of steroid hormones might be impaired in patients with severe hepatic disease, the use of Zoely in these women is not indicated as long as liver function values have not returned to normal.
For Method of administration, please refer to prescribing information.

Oral contraception.

Hypersensitivity, presence or history of venous thrombosis, arterial thrombosis or prodromal conditions, presence or history of cerebrovascular accident, history of migraine with focal neurological symptoms, the presence of a severe or multiple risk factor(s) for venous or arterial thrombosis, hereditary or acquired predisposition for venous or arterial thrombosis, pancreatitis or a history thereof if associated with severe hypertriglyceridemia, presence or history of severe hepatic disease as long as liver function values have not returned to normal, presence or history of liver tumors, known or suspected sex steroid-influenced malignancies, undiagnosed vaginal bleeding.

The use of any CHC (including Zoely) carries an increased risk of venous thromboembolism (VTE) compared with no use. The excess risk of VTE is highest during the first year a woman ever uses a combined oral contraceptive. Epidemiological studies have also associated the use of COCs with an increased risk for arterial thromboembolism (myocardial infarction, transient ischemic attack). The risk of arterial thromboembolic complications or of a cerebrovascular accident in COC users increases with age and smoking. Women over 35 years of age should be strongly advised not to smoke if they wish to use a COC). An increase in requency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event) may be a reason for immediate discontinuation. An increased risk of cervical cancer in long-term users of COCs (> 5 years) has been reported in some epidemiological studies, but there continues to be controversy about the extent to which this finding is attributable to the confounding effects of sexual behaviour and other factors such as human papilloma virus (HPV). No epidemiological data on the risk of cervical cancer in users of Zoely are available. A meta-analysis from 54 epidemiological studies reported that there is a slightly increased relative risk (RR = 1.24) of having breast cancer diagnosed in women who are currently using COCs. The excess risk gradually disappears during the course of the 10 years after cessation of COC use. Women with hypertriglyceridemia, or a family history thereof, may be at an increased risk of pancreatitis when using COCs. Although small increases in blood pressure have been reported in many women taking COCs, clinically relevant increases are rare. A relationship between COC use and clinical hypertension has not been established.  Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal.  Diabetic women should be carefully observed while taking a COC, especially in the first months of use.

Acne, abnormal withdrawal bleeding, decreased libido, depression/ depressed mood, mood altered, headache, migraine, nausea, metrorrhagia, menorrhagia, breast pain, pelvic pain, weight increased.
See prescribing information for full details.

Influence of other medicinal products on Zoely: Interactions between oral contraceptives and enzyme-inducing medicinal products may lead to breakthrough bleeding and/or contraceptive failure.
Hepatic metabolism: Interactions can occur with substances that induce CYP450 enzymes, resulting in reduced concentrations of sex hormones and decreased effectiveness of combined oral contraceptives, including Zoely. These substances are represented mostly with anticonvulsants (e.g. carbamazepine, topiramate, phenytoin, phenobarbital, primidone, oxcarbazepine, felbamate); anti-infective drugs (e.g. rifampicin, rifabutin, griseofulvin); St. John’s wort; bosentan and HIV or Hepatitis C virus (HCV) protease inhibitors (e.g. ritonavir, boceprevir, telaprevir) and non-nucleoside reverse transcriptase inhibitors (e.g. efavirenz).
Enzyme induction can occur after a few days of treatment. Maximal enzyme induction is generally observed within a few weeks. After drug therapy is discontinued, enzyme induction can last for about 28 days.
A barrier contraceptive method should also be used during the concomitant use of an enzyme inducer, and for 28 days after its discontinuation. In case of long-term treatment with hepatic enzyme-inducing substances another method of contraception should be considered.
If concomitant drug administration runs beyond the end of the active tablets in the current blister pack, the next blister pack should be started right away without the usual placebo tablet interval.
Concomitant administration of strong (e.g. ketoconazole, itraconazole, clarithromycin) or moderate (e.g. fluconazole, diltiazem, erythromycin) CYP3A4 inhibitors may increase the serum concentrations of oestrogens or progestogens.
Medicinal product interaction studies were not performed with Zoely, but two studies with rifampicin and ketoconazole, respectively, were performed with a higher dosed nomegestrol acetate-estradiol combination (nomegestrol acetate 3.75 mg + 1.5 mg estradiol) in post-menopausal women.
Concomitant use of rifampicin decreases the AUC0-∞ of nomegestrol acetate by 95 % and increases the AUC0-tlast of estradiol by 25 %. Concomitant use of ketoconazole (200 mg single dose) does not modify estradiol metabolism whereas increases in the peak concentration (85 %) and AUC0-∞ (115 %) of nomegestrol acetate were observed, which were of no clinical relevance. Similar conclusions are expected in women of childbearing potential.
Influence of Zoely on other medicinal products: Contraceptives containing ethinylestradiol may decrease the concentrations of lamotrigine by approximately 50%. Attention should be paid, notably when introducing a combined contraceptive, even with estradiol, in a well-equilibrated woman given lamotrigine.
Other interactions: During clinical trials with the HCV combination drug regimen ombitasvir/paritaprevir/ritonavir with and without dasabuvir, ALT elevations greater than 5 times the upper limit of normal (ULN) were significantly more frequent in women using ethinylestradiol-containing medications such as CHCs.
Women using medications containing oestrogens other than ethinylestradiol, such as estradiol, 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 drug regimen ombitasvir/paritaprevir/ritonavir with or without dasabuvir.

Pregnancy: Zoely is not indicated during pregnancy. If pregnancy occurs while taking Zoely, further intake should be stopped. Most epidemiological studies have revealed neither an increased risk of birth defects in infants born to women who used ethinylestradiol-containing COCs prior to pregnancy, nor a teratogenic effect when ethinylestradiol-containing COCs were taken inadvertently during early pregnancy.
Breast-feeding: Small amounts of the contraceptive steroids and/or their metabolites may be excreted with the breast milk, but there is no evidence that this adversely affects infant health.
See prescribing information for full details.

Multiple doses up to five times the daily dose of Zoely and single doses up to 40 times the daily dose of nomegestrol acetate alone have been used in women without safety concern. On the basis of general experience with combined oral contraceptives, symptoms that may occur are: nausea, vomiting and, in young girls, slight vaginal bleeding. There are no antidotes and further treatment should be symptomatic.