Zoely - summary of medicine characteristics

1. NAME OF THE MEDICINAL PRODUCT

Zoely 2.5 mg/1.5 mg film-coated tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each white active tablet contains 2.5 mg nomegestrol acetate and 1.5 mg estradiol (as hemihydrate). Each yellow placebo tablet does not contain active substances.

Excipients with known effect

Each white active tablet contains 57.7 mg of lactose monohydrate.

Each yellow placebo tablet contains 61.8 mg of lactose monohydrate.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Film-coated tablet (tablet).

The active tablet is white, round and coded ‘ne’ on both sides.

The placebo tablet is yellow, round and coded ‘p’ on both sides.

4. CLINICAL PARTICULARS4.1 Therapeutic indications

Oral contraception.

The decision to prescribe Zoely should take into consideration the individual woman’s current risk factors, particularly those for venous thromboembolism (VTE), and how the risk of VTE with Zoely compares with other combined hormonal contraceptives (CHCs) (see sections 4.3 and 4.4).

4.2 Posology and method of administration

Posology

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. See ‘Cycle control’ in section 4.4.

Special populations

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 (see section 4.3).

Paediatric population

Safety and efficacy have not been established in adolescents under 18 years of age. There is no relevant use of Zoely in children and pre-menarchal adolescents.

Method of administration

Oral use.

How to take Zoely

Tablets must be taken every day at about the same time without regard to meals. Tablets should be taken with some liquid as needed, and in the order as directed on the blister. Stickers marked with the 7 days of the week are provided. The woman should choose the sticker that starts with the day she begins taking the tablets and stick it on the blister.

How to start Zoely

No preceding hormonal contraceptive use (in the past month)

Tablet-taking has to start on day 1 of the woman’s menstrual cycle (i.e. the first day of her menstrual bleeding). When doing so, no additional contraceptive measures are necessary.

Changing from a CHC (combined oral contraceptive (COC), vaginal ring or transdermal patch) The woman should start with Zoely preferably on the day after the last active tablet-taking (the last tablet containing the active substances) of her previous COC, but at the latest on the day following the usual tablet-free or placebo tablet interval of her previous COC. In case a vaginal ring or transdermal patch has been used, the woman should start using Zoely preferably on the day of removal, but at the latest when the next application would have been due.

Changing from a progestogen-only-method (minipill, implant, injectable) or from a hormone-medicated intra uterine system (IUS)

The woman may switch any day from the minipill and Zoely should be started on the next day. An implant or IUS may be removed any day, and Zoely should be started on the day of its removal. When changing from an injectable, Zoely should be started on the day when the next injection would have been due. In all of these cases, the woman should be advised to additionally use a barrier method until she has completed 7 days of uninterrupted white active table-taking.

Following first-trimester abortion

The woman may start the tablet-taking immediately. When doing so, no additional contraceptive measures are necessary.

Following delivery or second-trimester abortion

The woman should be advised to start the tablet-taking between day 21 and 28 after delivery or second-trimester abortion. When starting later, the woman should be advised to additionally use a barrier method until she has completed 7 days of uninterrupted white active tablet-taking. However, if intercourse has already occurred, pregnancy should be excluded before the actual start of COC use or the woman has to wait for her first menstrual period.

For breast-feeding women see section 4.6.

Management of missed tablets

The following advice only refers to missed white active tablets :

If the woman is less than 24 hours late in taking any active tablet, contraceptive protection is not reduced. The woman should take the tablet as soon as she remembers and should take further tablets at the usual time.

If the woman is 24 or more hours late in taking any active tablet, contraceptive protection may be reduced. The management of missed tablets can be guided by the following two basic rules:

• • 7 days of uninterrupted white active tablet-taking are required to attain adequate suppression of

the hypothalamic-pituitary-ovarian-axis.

• • The more white active tablets are missed and the closer the missed tablets are to the 4 yellow placebo tablets, the higher the risk of a pregnancy.

Day 1–7

The woman should take the last missed white tablet as soon as she remembers, even if this means taking two tablets at the same time. She then continues to take tablets at her usual time. In addition, a barrier method such as a condom should be used until she has completed 7 days of uninterrupted white tablet-taking. If intercourse took place in the preceding 7 days, the possibility of a pregnancy should be considered.

Day 8–17

The woman should take the last missed white tablet as soon as she remembers, even if this means taking two tablets at the same time. She then continues to take tablets at her usual time. Provided that the woman has taken her tablets correctly in the 7 days preceding the first missed tablet, there is no need to use extra contraceptive precautions. However, if she has missed more than 1 tablet, the woman should be advised to use extra precautions until she has completed 7 days of uninterrupted white tablet-taking.

Day 18–24

The risk of reduced reliability is imminent because of the forthcoming yellow placebo tablet phase. However, by adjusting the tablet-intake schedule, reduced contraceptive protection can still be prevented. By adhering to either of the following two options, there is therefore no need to use extra contraceptive precautions, provided that in the 7 days preceding the first missed tablet the woman has taken all tablets correctly. If this is not the case, she should follow the first of these two options and use extra precautions for the next 7 days as well.

• 1. The woman should take the last missed tablet as soon as she remembers, even if this means taking two tablets at the same time. She then continues to take tablets at her usual time until the active tablets are used up. The 4 placebo tablets from the last row must be discarded. The next blister pack must be started right away. The woman is unlikely to have a withdrawal bleeding until the end of the active tablets section of the second pack, but she may experience spotting or breakthrough bleeding on tablet-taking days.

• 2. The woman may also be advised to discontinue active tablet-taking from the current blister pack. She should then take placebo tablets from the last row for a maximum of 3 days such that the total number of placebo plus missed white active tablets is not more than 4, and subsequently continue with the next blister pack.

If the woman missed tablets and subsequently has no withdrawal bleeding in the placebo tablet phase, the possibility of a pregnancy should be considered.

Please note: If the woman is not sure about the number or colour of tablets missed and what advice to follow, a barrier method should be used until she has completed 7 days of uninterrupted white active tablet-taking.

The following advice only refers to missed yellow placebo tablets:

Contraceptive protection is not reduced. Yellow tablets from the last (4th) row of the blister can be disregarded. However, the missed tablets should be discarded to avoid unintentionally prolonging the placebo tablet phase.

Advice in case of gastro-intestinal disturbances

In case of severe gastro-intestinal disturbance (e.g., vomiting or diarrhoea), absorption of the active substances may not be complete and additional contraceptive measures should be taken.

If vomiting occurs within 3–4 hours after white tablet-taking, the tablet should be considered as missed and a new tablet should be taken as soon as possible. The new tablet should be taken within 24 hours of the usual time of tablet-taking if possible. The next tablet should then be taken at the usual time. If 24 or more hours have passed since last tablet intake, the advice concerning missed tablets, as given in section 4.2 „Management of missed tablets“, is applicable. If the woman does not want to change her normal tablet-taking schedule, she has to take the extra white tablet(s) from another pack.

How to shift periods or how to delay a period

To delay a period the woman should continue with another blister pack of Zoely without taking the yellow placebo tablets from her current pack. The extension can be carried on for as long as wished until the end of the white active tablets in the second pack. Regular intake of Zoely is then resumed after the yellow placebo tablets have been taken of the second pack. During the extension the woman may experience breakthrough-bleeding or spotting.

To shift her periods to another day of the week than the woman is used to with her current scheme, she can be advised to shorten her forthcoming yellow placebo tablet phase with a maximum of 4 days. The shorter the interval, the higher the risk that she does not have a withdrawal bleeding and may experience breakthrough-bleeding and spotting during the subsequent pack (just as when delaying a period).

4.3 Contraindications

CHCs must not be used in the following conditions. Should any of the conditions appear for the first time during Zoely use, the medicinal product should be stopped immediately.

• • Presence or risk of venous thromboembolism (VTE)

o Venous thromboembolism – current VTE (on anticoagulants) or history of (e.g. deep venous thrombosis [DVT] or pulmonary embolism [PE]).

o Known hereditary or acquired predisposition for venous thromboembolism, such as activated protein C (APC)-resistance (including Factor V Leiden), antithrombin-III-deficiency, protein C deficiency, protein S deficiency.

o Major surgery with prolonged immobilisation (see section 4.4).

o A high risk of venous thromboembolism due to the presence of multiple risk factors (see section 4.4).

• • Presence or risk of arterial thromboembolism (ATE)

o Arterial thromboembolism – current ATE, history of ATE (e.g. myocardial infarction) or prodromal condition (e.g. angina pectoris).

o Cerebrovascular disease – current stroke, history of stroke or prodromal condition (e.g. transient ischaemic attack [TIA]).

o Known hereditary or acquired predisposition for arterial thromboembolism, such as hyperhomocyste­inaemia and antiphospholipid-antibodies (anticardiolipin-antibodies, lupus anticoagulant).

o History of migraine with focal neurological symptoms.

o A high risk of arterial thromboembolism due to multiple risk factors (see section 4.4) or to the presence of one serious risk factor such as:

• • diabetes mellitus with vascular symptoms;
• • severe hypertension;
• • severe dyslipoprotei­naemia.
• • Pancreatitis or a history thereof if associated with severe hypertriglyce­ridaemia.
• • Presence or history of severe hepatic disease as long as liver function values have not returned to normal.
• • Presence or history of liver tumours (benign or malignant).
• • Known or suspected sex steroid-influenced malignancies (e.g., of the genital organs or the

breasts).

• • Presence or history of meningioma.
• • Undiagnosed vaginal bleeding.
• • Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

4.5 Interaction with other medicinal products and other forms of interaction

Interactions

Note: The prescribing information of concomitant medicinal products should be consulted to identify potential interactions.

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 AUCo-vof 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 AUCo-v(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 medicinal products such as CHCs. Women using medicinal products 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 and also the regimen with glecaprevir/pi­brentasvir (see section 4.4).

4.6 Fertility, pregnancy and lactation

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.

Clinical data on a limited number of exposed pregnancies indicate no adverse effect of Zoely on the foetus or neonate.

In animal studies, reproductive toxicity has been observed with the nomegestrol acetate / estradiol combination (see preclinical safety data in section 5.3).

The increased risk of VTE during the postpartum period should be considered when re-starting Zoely (see section 4.2 and 4.4).

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.

Breast-feeding may be influenced by COCs as they may reduce the quantity and change the composition of breast milk. Therefore, the use of COCs should not be recommended until the breastfeeding mother has completely weaned her child and an alternative method of contraception should be proposed to women wishing to breastfeed.

Fertility

Zoely is indicated for the prevention of pregnancy. For information on return to fertility, see section 5.1.

4.7 Effects on ability to drive and use machines

Zoely has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

Summary of the safety profile

Six multi-centre clinical trials of up to one-year duration were used to evaluate safety of Zoely. In total 3,434 women, aged 18–50, were enrolled and completed 33,828 cycles.

Most commonly reported adverse reactions in these clinical trials were acne (15.4%) and withdrawal bleeding irregular (9.8%).

An increased risk for venous and arterial thromboembolism, causative of serious adverse events has been observed with the use of CHCs (see section 4.4)

Tabulated list of adverse reactions

Possibly related adverse reactions that have been reported in clinical trials or during post-marketing use with Zoely are listed in the table below.

Adverse reactions are listed according to the MedDRA system organ class and ranked under frequency groupings using the following convention: very common (> 1/10), common (> 1/100 to < 1/10), uncommon (> 1/1,000 to < 1/100) and rare (> 1/10,000 to < 1/1,000).

Table: List of adverse reactions

1The most appropriate MedDRA term to describe a certain adverse reaction is listed. Synonyms or related conditions are not listed, but should be taken into account as well.

In addition to the above-mentioned adverse reactions, hypersensitivity reactions have been reported in Zoely users (frequency unknown).

Description of selected adverse reactions

An increased risk of arterial and venous thrombotic and thromboembolic events, including myocardial infarction, stroke, transient ischaemic attacks, venous thrombosis and pulmonary embolism has been observed in women using CHCs, which are discussed in more detail in section 4.4.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in

4.9 Overdose

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.

5. PHARMACOLOGICAL PROPERTIES5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Sex hormones and modulators of the genital system, progestogens and estrogens, fixed combinations, ATC code: G03AA14.

Mechanism of action

Nomegestrol acetate is a highly selective progestogen derived from the naturally occurring steroid hormone, progesterone. Nomegestrol acetate has a strong affinity for the human progesterone receptor and has an anti-gonadotropic activity, a progesterone receptor-mediated anti-oestrogenic activity, a moderate anti-androgenic activity, and is devoid of any oestrogenic, androgenic, glucocorticoid or mineralocorticoid activity.

The oestrogen contained in Zoely is 17p-estradiol, an oestrogen identical to the endogenous human 17P-estradiol.

The contraceptive effect of Zoely is based on the interaction of various factors, the most important of which are seen as the inhibition of ovulation and the changes in the cervical secretion.

Clinical efficacy and safety

In two randomised, open-label, comparative efficacy-safety trials, more than 3,200 women have been treated for up to 13 consecutive cycles with Zoely and more than 1,000 women with drospirenone 3 mg – ethinylestradiol 30 ^g (21/7 regimen).

In the Zoely group, acne was reported by 15.4 % of the women (versus 7.9 % in the comparator group), weight increased was reported by 8.6 % of the women (versus 5.7 % in the comparator group), and abnormal withdrawal bleeding (predominantly absence of withdrawal bleeding) was reported by 10.5 % of the women (versus 0.5 % in the comparator group).

In the clinical trial performed with Zoely in the European Union the following Pearl Indices for the age class 18–35 years were calculated:

Method failure: 0.40 (upper limit 95 % confidence interval 1.03).

Method and user failure: 0.38 (upper limit 95 % confidence interval 0.97).

In the clinical trial performed with Zoely in the United States the following Pearl Indices for the age class 18–35 years were calculated:

Method failure: 1.22 (upper limit 95 % confidence interval 2.18).

Method and user failure: 1.16 (upper limit 95 % confidence interval 2.08).

In a randomised, open label trial, 32 women were treated for 6 cycles with Zoely.

After discontinuation of Zoely, return to ovulation in the first 28 days after last tablet intake was observed in 79 % of the women.

Endometrial histology was investigated in a subgroup of women (n=32) in one clinical study after 13 cycles of treatment. There were no abnormal results.

Paediatric population

No data on efficacy and safety are available in adolescents below 18 years. Available pharmacokinetic data are described in section 5.2.

5.2 Pharmacokinetic properties

Nomegestrol acetate

Absorption

Orally administered nomegestrol acetate is rapidly absorbed.

Maximum plasma concentrations of nomegestrol acetate of about 7 ng/mL are reached at 2 h after single administration. The absolute bioavailability of nomegestrol acetate after a single dose is 63 %. No clinically relevant effect of food was observed on the bioavailability of nomegestrol acetate.

Distribution

Nomegestrol acetate is extensively bound to albumin (97–98 %), but does not bind to sex hormone binding globulin (SHBG) or corticoid binding globulin (CBG). The apparent volume of distribution of nomegestrol acetate at steady-state is 1,645 ± 576 L.

Biotransformation

Nomegestrol acetate is metabolized into several inactive hydroxylated metabolites by liver cytochrome P450 enzymes, mainly CYP3A4 and CYP3A5 with possible contribution of CYP2C19 and CYP2C8. Nomegestrol acetate and its hydroxylated metabolites undergo extensive phase 2 metabolism to form glucuronide- and sulphate conjugates. The apparent clearance at steady state is 26 L/h.

Elimination

The elimination half-life (t1/2) is 46 h (ranging from 28–83 h) at steady state. The elimination half-life of metabolites was not determined.

Nomegestrol acetate is excreted via urine and faeces. Approximately 80 % of the dose is excreted in urine and faeces within 4 days. Excretion of nomegestrol acetate was nearly complete after 10 days and amounts excreted were higher in faeces than in urine.

Linearity

Dose-linearity was observed in the range 0.625–5 mg (assessed in fertile and post-menopausal women).

Steady-state conditions

The pharmacokinetics of nomegestrol acetate are not influenced by SHBG.

Steady-state is achieved after 5 days. Maximum plasma concentrations of nomegestrol acetate of about 12 ng/mL are reached 1.5 h after dosing. Average steady state plasma concentrations are 4 ng/mL.

Drug drug interactions

Nomegestrol acetate causes in vitro no notable induction or inhibition of any cytochrome P450 enzymes and has no clinically relevant interaction with the P-gp transporter.

Estradiol

Absorption

Estradiol is subject to a substantial first-pass effect after oral administration. The absolute bioavailability is about 1 %. No clinically relevant effect of food was observed on the bioavailability of estradiol.

Distribution

The distribution of exogenous and endogenous estradiol is similar. Oestrogens are widely distributed in the body and are generally found in higher concentrations in the sex hormone target organs.

Estradiol circulates in the blood bound to SHBG (37 %) and to albumin (61 %), while only approximately 1–2 % is unbound.

Biotransformation

Oral exogenous estradiol is extensively metabolized. The metabolism of exogenous and endogenous estradiol is similar. Estradiol is rapidly transformed in the gut and the liver in several metabolites, mainly estrone, which are subsequently conjugated and undergo entero-hepatic circulation. There is a dynamic equilibrium between estradiol, estrone and estrone-Sulfate due to various enzymatic activities including estradiol-dehydrogenases, sulfotransferases and aryl sulfatases. Oxidation of estrone and estradiol involves cytochrome P450 enzymes, mainly CYP1A2, CYP1A2 (extra hepatic), CYP3A4, CYP3A5, and CYP1B1 and CYP2C9.

Elimination

Estradiol is rapidly cleared from the circulation. Due to metabolism and enterohepatic circulation, a large circulating pool of oestrogen sulfates and glucuronides is present. This results in a highly variable baseline-corrected elimination half-life of estradiol, which is calculated to be 3.6 ± 1.5 h, after intravenous administration.

Steady-state conditions

Maximum serum concentrations of estradiol are about 90 pg/mL and are reached 6 h after dosing. Average serum concentrations are 50 pg/mL and these estradiol levels correspond with the early and late phase of a woman’s menstru­al cycle.

Special populations

Effect of renal impairment

No studies were performed to evaluate the effect of renal disease on the pharmacokinetics of Zoely.

Effect of hepatic impairment

No studies were conducted to evaluate the effect of hepatic disease on the pharmacokinetics of Zoely. However, steroid hormones may be poorly metabolized in women with impaired liver function.

Ethnic groups

No formal studies were performed to assess pharmacokinetics in ethnic groups.

Paediatric population

The pharmacokinetics of nomegestrol acetate (primary objective) after single oral dosing of Zoely in healthy postmenarcheal female adolescents and adult subjects were similar. However, after single oral dosing, for the estradiol component (secondary objective), the exposure was 36 % lower in adolescents versus adult subjects. The clinical relevance of this result is unknown.

5.3 Preclinical safety data

Repeated dose toxicity studies with estradiol, nomegestrol acetate or combination have indicated expected oestrogenic and gestagen effects.

Reproductive toxicity studies performed with the combination have shown foetotoxicity which is consistent with estradiol exposure.

Genotoxicity and carcinogenicity studies were not conducted with the combination. Nomegestrol acetate is not genotoxic.

However, it must be borne in mind that sex steroids can promote the growth of certain hormone-dependent tissues and tumours.

6. PHARMACEUTICAL PARTICULARS6.1 List of excipients

Tablet core (white active and yellow placebo film-coated tablets)

Lactose monohydrate

Microcrystalline cellulose (E460)

Crospovidone (E1201)

Talc (E553b)

Magnesium stearate (E572)

Colloidal anhydrous silica

Tablet coat (white active film-coated tablets)

Polyvinyl alcohol (E1203)

Titanium dioxide (E171)

Macrogol 3350

Talc (E553b)

Tablet coating (yellow placebo film-coated tablets)

Polyvinyl alcohol (E1203)

Titanium dioxide (E171)

Macrogol 3350

Talc (E553b)

Yellow iron oxide (E172)

Black iron oxide (E172)

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

PVC/aluminium blister containing 28 film-coated tablets (24 white active tablets and 4 yellow placebo tablets).

Pack sizes: 28, 84, 168 and 364 film-coated tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

COC tablets (including Zoely tablets) no longer required should not be disposed via wastewater or the municipal sewage system. The hormonal active compounds in the tablets may have harmful effects if reaching the aquatic environment. The tablets should be returned to a pharmacy or disposed of in another safe way according to local requirements. These measures will help to protect the environment.

7. MARKETING AUTHORISATION HOLDER

Theramex Ireland Limited

3rd Floor, Kilmore House,

Park Lane, Spencer Dock,

Dublin 1

D01 YE64

Ireland

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/11/690/001

EU/1/11/690/002

EU/1/11/690/003

EU/1/11/690/004

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 27 July 2011

Date of latest renewal: 10 May 2021