Zoely

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS

 



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions.

1. NAME OF THE MEDICINAL PRODUCT

Zoely 2.5 mg/1.5 mg film-coated tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

White active film-coated tablets: Each film-coated tablet contains 2.5 mg nomegestrol acetate and 
1.5 mg estradiol (as hemihydrate).
Yellow placebo film-coated tablets: The tablet does not contain active substances.

Excipients with known effect
Each white active film-coated tablet contains 57.71 mg of lactose monohydrate.
Each yellow placebo film-coated tablet contains 61.76 mg of lactose monohydrate.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Film-coated tablet (tablet).
Active film-coated tablets: white, round and coded ‘ne’ on both sides.
Placebo film-coated tablets: yellow, round and coded ‘p’ on both sides.

4. CLINICAL PARTICULARS

4.1 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.

 



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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).

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 natural cycle (i.e. the first day of her menstrual 
bleeding). When doing so, no additional contraceptive measures are necessary.

Changing from a combined hormonal contraceptive (combined oral contraceptive (COC), vaginal 
ring or transdermal patch)
The woman should start with Zoely preferably on the day after the last active tablet (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 tablet-taking.

Following first-trimester abortion
The woman may start immediately. When doing so, no additional contraceptive measures are necessary.

Following delivery or second-trimester abortion
Women should be advised to start 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.

 



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If she 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 user 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 user 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 user 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 user is unlikely to have a withdrawal bleed 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 bleed in the placebo tablet phase, the 
possibility of a pregnancy should be considered.

Please note: If the user 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.

Yellow placebo tablets missed

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 

 



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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 bleed and may experience 
breakthrough-bleeding and spotting during the subsequent pack (just as when delaying a period).

4.3 Contraindications

Combined hormonal contraceptives (CHCs) must not be used in the following conditions. As no 
epidemiological data are yet available with 17β-estradiol containing CHCs, the contraindications for 
ethinylestradiol containing CHCs are considered applicable to the use of Zoely. 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 

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 arterial thromboembolism, history of arterial 
thromboembolism (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).

 



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 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

Warnings
If any of the conditions or risk factors mentioned below is present, the suitability of Zoely should be 
discussed with the woman.

In the event of aggravation, or first appearance of any of these conditions or risk factors, the woman 
should be advised to contact her doctor to determine whether the use of Zoely should be discontinued. 
All data presented below are based upon epidemiological data obtained with CHCs containing 
ethinylestradiol. Zoely contains 17β-estradiol. As no epidemiological data are yet available with 
estradiol containing-CHCs, the warnings are considered applicable to the use of Zoely.

Risk of venous thromboembolism (VTE)
 The use of any combined hormonal contraceptive (CHC) increases the risk of venous 

thromboembolism (VTE) compared with no use. Products that contain levonorgestrel,
norgestimate or norethisterone are associated with the lowest risk of VTE. It is not yet 
known how the risk with Zoely compares with these lower risk products. The decision to 
use any product other than one known to have the lowest VTE risk should be taken only 
after a discussion with the woman to ensure she understands the risk of VTE with CHCs, 
how her current risk factors influence this risk, and that her VTE risk is highest in the 
first ever year of use. There is also some evidence that the risk is increased when a CHC is 
re-started after a break in use of 4 weeks or more.

 In women who do not use a CHC and are not pregnant about 2 out of 10,000 will develop a 
VTE over the period of one year. However, in any individual woman, the risk may be far 
higher, depending on her underlying risk factors (see below).

 Epidemiological studies in women who use low dose (< 50 µg ethinylestradiol) combined 
hormonal contraceptives have found that out of 10,000 women between 6 and 12 will develop a 
VTE in one year.

 It is estimated that out of 10,000 women who use a levonorgestrel-containing CHC about 61 will 
develop a VTE in one year.

 It is not yet known how the risk of VTE with CHCs that contain nomegestrol acetate in 
combination with estradiol compares with the risk with low dose levonorgestrel-containing 
CHCs.

 The number of VTEs per year with low dose CHCs is fewer than the number expected in 
women during pregnancy or in the postpartum period.

 VTE may be fatal in 1-2 % of cases.
 Extremely rarely, thrombosis has been reported to occur in CHC users in other blood vessels, 

e.g. hepatic, mesenteric, renal, or retinal veins and arteries.

Risk factors for VTE
The risk for venous thromboembolic complications in CHC users may increase substantially in a 
woman with additional risk factors, particularly if there are multiple risk factors (see table).

Zoely is contraindicated if a woman has multiple risk factors that put her at high risk of venous 
thrombosis (see section 4.3). If a woman has more than one risk factor, it is possible that the increase 
in risk is greater than the sum of the individual factors – in this case her total risk of VTE should be 
considered. If the balance of benefits and risks is considered to be negative, a CHC should not be
prescribed (see section 4.3).

                                                     
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Mid-point of range of 5-7 per 10,000 WY, based on a relative risk for CHCs containing levonorgestrel versus non-use of approximately 2.3 to 3.6

 



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Table: Risk factors for VTE
Risk factor Comment

Obesity (body mass index over 30 kg/m²) Risk increases substantially as BMI rises.

Particularly important to consider if other risk 
factors also present.

Prolonged immobilisation, major surgery, any 
surgery to the legs or pelvis, neurosurgery, or 
major trauma

Note: Temporary immobilisation including air 
travel > 4 hours can also be a risk factor for VTE, 
particularly in women with other risk factors.

In these situations it is advisable to discontinue 
use of the pill (in the case of elective surgery at 
least four weeks in advance) and not resume until 
two weeks after complete remobilisation. Another
method of contraception should be used to avoid 
unintentional pregnancy.

Antithrombotic treatment should be considered if 
Zoely has not been discontinued in advance.

Positive family history (venous thromboembolism 
ever in a sibling or parent especially at a 
relatively early age, e.g., before 50)

If a hereditary predisposition is suspected, the 
woman should be referred to a specialist for 
advice before deciding about any CHC use.

Other medical conditions associated with VTE Cancer, systemic lupus erythematosus, 
haemolytic uraemic syndrome, chronic 
inflammatory bowel disease (Crohn's disease or 
ulcerative colitis) and sickle cell disease

Increasing age Particularly above 35 years

 There is no consensus about the possible role of varicose veins and superficial thrombophlebitis 
in the onset or progression of venous thrombosis.

 The increased risk of thromboembolism in pregnancy, and particularly the 6-week period of the 
puerperium, must be considered (for information on "Pregnancy and lactation" see section 4.6).

Symptoms of VTE (deep vein thrombosis and pulmonary embolism)
In the event of symptoms women should be advised to seek urgent medical attention and to inform the 
healthcare professional that she is taking a CHC.
Symptoms of deep vein thrombosis (DVT) can include:

- unilateral swelling of the leg and/or foot or along a vein in the leg;
- pain or tenderness in the leg which may be felt only when standing or walking;
- increased warmth in the affected leg; red or discoloured skin on the leg.

Symptoms of pulmonary embolism (PE) can include:
- sudden onset of unexplained shortness of breath or rapid breathing;
- sudden coughing which may be associated with haemoptysis;
- sharp chest pain;
- severe light headedness or dizziness;
- rapid or irregular heartbeat.

Some of these symptoms (e.g. “shortness of breath”, “coughing”) are non-specific and might be 
misinterpreted as more common or less severe events (e.g. respiratory tract infections).
Other signs of vascular occlusion can include: sudden pain, swelling and slight blue discoloration of 
an extremity.
If the occlusion occurs in the eye symptoms can range from painless blurring of vision which can 
progress to loss of vision. Sometimes loss of vision can occur almost immediately.

 



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Risk of arterial thromboembolism (ATE)
Epidemiological studies have associated the use of CHCs with an increased risk for arterial 
thromboembolism (myocardial infarction) or for cerebrovascular accident (e.g., transient ischaemic 
attack, stroke). Arterial thromboembolic events may be fatal.

Risk factors for ATE
The risk of arterial thromboembolic complications or of a cerebrovascular accident in CHC users 
increases in women with risk factors (see table). Zoely is contraindicated if a woman has one serious 
or multiple risk factors for ATE that puts her at high risk of arterial thrombosis (see section 4.3). If a 
woman has more than one risk factor, it is possible that the increase in risk is greater than the sum of 
the individual factors – in this case her total risk should be considered. If the balance of benefits and 
risks is considered to be negative a CHC should not be prescribed (see section 4.3).

Table: Risk factors for ATE
Risk factor Comment
Increasing age Particularly above 35 years

Smoking Women should be advised not to smoke if they 
wish to use a CHC. Women over 35 who continue 
to smoke should be strongly advised to use a 
different method of contraception.

Hypertension

Obesity (body mass index over 30 kg/m2) Risk increases substantially as BMI increases.

Particularly important in women with
additional risk factors

Positive family history (arterial thromboembolism 
ever in a sibling or parent especially at relatively 
early age, e.g., below 50)

If a hereditary predisposition is suspected, the 
woman should be referred to a specialist for 
advice before deciding about any CHC use.

Migraine An increase in frequency or severity of migraine 
during CHC use (which may be prodromal of a 
cerebrovascular event) may be a reason for 
immediate discontinuation.

Other medical conditions associated with
adverse vascular events

Diabetes mellitus, hyperhomocysteinaemia,
valvular heart disease and atrial fibrillation,
dyslipoproteinaemia and systemic lupus
erythematosus

Symptoms of ATE
In the event of symptoms women should be advised to seek urgent medical attention and to inform the 
healthcare professional that she is taking a CHC.
Symptoms of a cerebrovascular accident can include:

- sudden numbness or weakness of the face, arm or leg, especially on one side of the body;
- sudden trouble walking, dizziness, loss of balance or coordination;
- sudden confusion, trouble speaking or understanding;
- sudden trouble seeing in one or both eyes;
- sudden, severe or prolonged headache with no known cause;
- loss of consciousness or fainting with or without seizure.

Temporary symptoms suggest the event is a transient ischaemic attack (TIA).

 



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Symptoms of a myocardial infarction (MI) can include:
- pain, discomfort, pressure, heaviness, sensation of squeezing or fullness in the chest, arm, or

below the breastbone;
- discomfort radiating to the back, jaw, throat, arm, stomach;
- feeling of being full, having indigestion or choking;
- sweating, nausea, vomiting or dizziness;
- extreme weakness, anxiety, or shortness of breath;
- rapid or irregular heartbeats.

Tumours
 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.

 With the use of the higher-dosed COCs (50 g ethinylestradiol) the risk of endometrial and 
ovarian cancer is reduced. Whether this also applies to 17β-estradiol-containing COCs remains 
to be confirmed.

 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. Because breast cancer is rare in women under 40 years of age, the excess number of 
breast cancer diagnoses in current and recent COC users is small in relation to the overall risk of 
breast cancer. The breast cancers diagnosed in ever-users tend to be less advanced clinically 
than the cancers diagnosed in never-users. The observed pattern of increased risk may be due to 
an earlier diagnosis of breast cancer in COC users, the biological effects of COCs or a 
combination of both.

 In rare cases, benign liver tumours, and even more rarely, malignant liver tumours have been 
reported in users of COCs. In isolated cases, these tumours have led to life-threatening 
intra-abdominal haemorrhages. Therefore, a hepatic tumour should be considered in the 
differential diagnosis when severe upper abdominal pain, liver enlargement or signs of 
intra-abdominal haemorrhage occur in women taking COCs.

Meningioma
The occurrence of meningioma (single and multiple) has been reported with prolonged use (several 
years) of nomegestrol monotherapy at doses of 3.75 mg or 5 mg daily and higher. If a meningioma is 
diagnosed in a patient treated with Zoely, treatment should be stopped (see section 4.3).

Hepatitis C
 During clinical trials with the Hepatitis C virus (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. See section 4.5.

Other conditions
 Women with hypertriglyceridaemia, 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. However, if a sustained clinically significant hypertension develops 
during the use of a COC, then it is prudent for the physician to suspend the intake of the tablets 
and treat the hypertension. Where considered appropriate, COC use may be resumed if 
normotensive values can be achieved with antihypertensive therapy.

 



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 The following conditions have been reported to occur or deteriorate with both pregnancy and 
COC use, but the evidence of an association with COC use is inconclusive: jaundice and/or 
pruritus related to cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; 
haemolytic uraemic syndrome; Sydenham’s chorea; herpes gestationis; otosclerosis-related 
hearing loss.

 In women with hereditary angioedema, exogenous oestrogens may induce or exacerbate 
symptoms of angioedema.

 Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use 
until markers of liver function return to normal. Recurrence of cholestatic jaundice which occurred 
first during pregnancy or previous use of sex steroids necessitates the discontinuation of COCs.

 Although COCs may have an effect on peripheral insulin resistance and glucose tolerance, there 
is no evidence for a need to alter the therapeutic regimen in diabetics using low-dose COCs 
(containing  0.05 mg ethinylestradiol). However, diabetic women should be carefully observed 
while taking a COC, especially in the first months of use.

 Crohn’s disease, ulcerative colitis, and worsening of depression have been associated with COC 
use.

 Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. 
Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation 
whilst taking COCs.

 Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or 
glucose-galactose malabsorption should not take this medicinal product.

 Depressed mood and depression are well-known undesirable effects of hormonal contraceptive 
use (see section 4.8). Depression can be serious and is a well-known risk factor for suicidal 
behaviour and suicide. Women should be advised to contact their physician in case of mood 
changes and depressive symptoms, including shortly after initiating the treatment.

Medical examination/consultation
Prior to the initiation or reinstitution of Zoely use a complete medical history (including family 
history) should be taken and pregnancy must be ruled out. Blood pressure should be measured and a 
physical examination should be performed, guided by the contraindications (see section 4.3) and 
warnings (see section 4.4). It is important to draw a woman’s attention to the information on venous 
and arterial thrombosis, including the risk of Zoely compared with other CHCs, the symptoms of VTE 
and ATE, the known risk factors and what to do in the event of a suspected thrombosis.

The woman should also be instructed to carefully read the user leaflet and to adhere to the advice 
given. The frequency and nature of examinations should be based on established practice guidelines 
and be adapted to the individual woman.

Women should be advised that hormonal contraceptives do not protect against HIV infections (AIDS) 
and other sexually transmitted diseases.

Reduced efficacy
The efficacy of COCs may be reduced in the event of e.g., missed tablets (see section 4.2), 
gastro-intestinal disturbances during active tablet-taking (see section 4.2) or use of concomitant 
medicinal products that decrease the plasma concentrations of nomegestrol acetate and/or estradiol 
(see section 4.5).

Cycle control
With all COCs, irregular bleeding (spotting or breakthrough bleeding) may occur, especially during 
the first months of use. Therefore, the evaluation of any irregular bleeding is only meaningful after an 
adaptation interval of about 3 cycles. The percentage of women using Zoely experiencing intracyclic 
bleeding after this adaptation period ranged from 15-20 %.

If bleeding irregularities persist or occur after previously regular cycles, then non-hormonal causes 
should be considered and adequate diagnostic measures are indicated to exclude malignancy or 
pregnancy. These may include curettage.

 



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The duration of the withdrawal bleeding in women using Zoely is on average 3-4 days. Users of Zoely 
may also miss their withdrawal bleeding although not being pregnant. During clinical trials, absence of 
withdrawal bleeding ranged over the cycles 1-12 from 18 % to 32 %. In such cases, absence of 
withdrawal bleeding was not associated with a higher occurrence of breakthrough bleeding/spotting in 
the subsequent cycles. 4.6 % of the women did not have a withdrawal bleeding in the first three cycles 
of use and the occurrences of absence of withdrawal bleeding in the later cycles of use were high in 
this subgroup, ranging from 76 % to 87 % of women. 28 % of the women experienced absence of 
withdrawal bleeding in at least one of the cycles 2, 3 and 4, associated with higher occurrences of 
absence of withdrawal bleeding in the later cycles of use, ranging from 51 % to 62 %.

If absence of withdrawal bleeding occurs and Zoely has been taken according to the instructions as 
described in section 4.2, it is unlikely that the woman is pregnant. However, pregnancy must be ruled 
out before Zoely use is continued, if Zoely has not been taken as directed or if two consecutive 
withdrawal bleedings are missed.

Paediatric population
It is unknown whether the amount of estradiol in Zoely is sufficient to maintain adequate levels of 
estradiol in adolescents, especially for bone mass accrual (see section 5.2).

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.

4.5 Interaction with other medicinal products and other forms of interaction

Interactions
Note: The prescribing information of concomitant medications 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.

 



12

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.

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.

Breastfeeding 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 breast-
feeding mother has completely weaned her child and an alternative contraceptive method should be 
proposed to women wishing to breastfeed.

 



13

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.

Tabulated list of adverse reactions
Possibly related adverse reactions that have been reported in clinical trials or during postmarketing use 
with Zoely are listed in the table below.

All adverse reactions are listed by system organ class and frequency; 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).

System organ class
Adverse reaction in MedDRA Term1

Very common Common Uncommon Rare
Metabolism and 
nutrition disorders

increased 
appetite, fluid 
retention

decreased 
appetite

Psychiatric disorders decreased libido, 
depression/ 
depressed mood, 
mood altered

increased libido

Nervous system 
disorders

headache, 
migraine

cerebrovascular 
accident,
transient 
ischaemic attack, 
disturbance in 
attention

Eye disorders contact lens 
intolerance/dry 
eye

Vascular disorders hot flush venous 
thromboembolism

Gastrointestinal 
disorders

nausea abdominal 
distension

dry mouth

Hepatobiliary 
disorders

cholelithiasis, 
cholecystitis

Skin and subcutaneous 
tissue disorders

acne hyperhydrosis, 
alopecia, 
pruritus, dry 
skin, seborrhea

chloasma, 
hypertrichosis

Musculoskeletal and 
connective tissue 
disorders

sensation of 
heaviness

 



14

System organ class
Adverse reaction in MedDRA Term1

Very common Common Uncommon Rare
Reproductive system 
and breast disorders

abnormal 
withdrawal 
bleeding

metrorrhagia, 
menorrhagia, 
breast pain, 
pelvic pain

hypomenorrhoea, 
breast swelling, 
galactorrhoea, 
uterine spasm, 
premenstrual 
syndrome, breast 
mass, 
dyspareunia, 
vulvovaginal 
dryness

vaginal odour, 
vulvovaginal 
discomfort

General disorders and 
administration site 
conditions

irritability, 
oedema

hunger

Investigations weight increased hepatic enzyme 
increased

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 Appendix V.

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 PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Sex hormones and modulators of the genital system, progestogens and 
oestrogens, 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.

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


15

The oestrogen contained in Zoely is 17β-estradiol, a natural oestrogen identical to the endogenous 
human 17β-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 randomized, 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 μg (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 randomized, 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 

 



16

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.

 



17

Special populations

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.

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.

5.3 Preclinical safety data

Repeat 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 PARTICULARS

6.1 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)
Poly(vinyl alcohol) (E1203)
Titanium dioxide (E171)
Macrogol 3350
Talc (E553b)

Tablet coating (yellow placebo film-coated tablets)
Poly(vinyl alcohol) (E1203)
Titanium dioxide (E171)
Macrogol 3350
Talc (E553b)
Iron oxide yellow (E172)
Iron oxide black (E172)

 



18

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 film-coated tablets and 4 yellow 
film-coated 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 tablet 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: 21 April 2016

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency: http://www.ema.europa.eu.

 



19

ANNEX II

A. MANUFACTURERS RESPONSIBLE FOR BATCH 
RELEASE

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 
THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT

 



20

A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturers responsible for batch release

Delpharm Lille S.A.S.
Parc d’Activités Roubaix-Est
22 Rue de Toufflers
CS 50070
59452 LYS-LEZ-LANNOY
France

Teva Operations Poland Sp. z o.o.
ul. Mogilska 80
31-546 Krakow
Poland

N.V. Organon
Kloosterstraat 6
5349 AB Oss
The Netherlands

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch.

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to medical prescription.

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION

 Periodic safety update reports (PSURs)

The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal.

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT

 Risk management plan (RMP)

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities 
and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation 
and any agreed subsequent updates of the RMP.

An updated RMP should be submitted:
 At the request of the European Medicines Agency;

 



21

 Whenever the risk management system is modified, especially as the result of new information 
being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached.

 Obligation to conduct post-authorisation measures

The MAH shall complete, within the stated timeframe, the below measures:

Description Due date
Non-interventional post-authorisation safety study (PASS):
A prospective observational study to assess in particular the risk of Venous 
thromboembolic events (VTE) and ATE in nomegestrol/estradiol users compared 
with the VTE risk in users of combined oral contraceptives containing 
levonorgestrel.
Submission of final study report

30 April 2021

 



22

ANNEX III

LABELLING AND PACKAGE LEAFLET

 



23

A. LABELLING

 



24

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON

1. NAME OF THE MEDICINAL PRODUCT

Zoely 2.5 mg/1.5 mg film-coated tablets
nomegestrol acetate/estradiol

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each white active tablet contains 2.5 mg nomegestrol acetate and 1.5 mg estradiol (as hemihydrate).

3. LIST OF EXCIPIENTS

Contains lactose monohydrate

See leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

28 film-coated tablets
84 film-coated tablets
168 film-coated tablets
364 film-coated tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

 



25

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Theramex Ireland Limited
3rd Floor, Kilmore House,
Park Lane, Spencer Dock,
Dublin 1
D01 YE64
Ireland

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/11/690/001 28 film-coated tablets
EU/1/11/690/002 84 film-coated tablets
EU/1/11/690/003 168 film-coated tablets
EU/1/11/690/004 364 film-coated tablets

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

zoely

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN

 



26

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER

1. NAME OF THE MEDICINAL PRODUCT

Zoely 2.5 mg/1.5 mg tablets
nomegestrol acetate/estradiol

2. NAME OF THE MARKETING AUTHORISATION HOLDER

Theramex Ireland Limited

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER

[Box for placing day label stating:] Place day label here
[Day numbering for each individual tablet:] Start,2, ….28
[Arrows indicating the sequence of the tablets:] 

 



27

DAY LABEL SHEET INCLUDING STICKERS PROVIDED WITH THE LEAFLET

Day label sheet
Choose the day label that begins with your starting day.
Place the label on the blister over the words ‘Place day label here’.

SUN MON TUE WED THU FRI SAT
MON TUE WED THU FRI SAT SUN
TUE WED THU FRI SAT SUN MON
WED THU FRI SAT SUN MON TUE
THU FRI SAT SUN MON TUE WED
FRI SAT SUN MON TUE WED THU
SAT SUN MON TUE WED THU FRI

[Second day label sheet for box of 3 blisters stating, twice:]

SUN MON TUE WED THU FRI SAT
MON TUE WED THU FRI SAT SUN
TUE WED THU FRI SAT SUN MON
WED THU FRI SAT SUN MON TUE
THU FRI SAT SUN MON TUE WED
FRI SAT SUN MON TUE WED THU
SAT SUN MON TUE WED THU FRI

[In front of day labels intended for second blister:] Blister 2
[In front of day labels intended for third blister:] Blister 3

 



28

B. PACKAGE LEAFLET

 



29

Package leaflet: Information for the user

Zoely 2.5 mg/1.5 mg film-coated tablets
nomegestrol acetate/estradiol

This medicine is subject to additional monitoring. This will allow quick identification of new 
safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects.

Important things to know about combined hormonal contraceptives (CHCs):
 They are one of the most reliable reversible methods of contraception if used correctly.
 They slightly increase the risk of having a blood clot in the veins and arteries, especially in the 

first year or when restarting a combined hormonal contraceptive following a break of 4 or more 
weeks.

 Please be alert and see your doctor if you think you may have symptoms of a blood clot (see 
section 2 “Blood clots”).

Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor, pharmacist or nurse.
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them.
- If you get any side effects talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Zoely is and what it is used for
2. What you need to know before you use Zoely
3. How to use Zoely
4. Possible side effects
5. How to store Zoely
6. Contents of the pack and other information

1. What Zoely is and what it is used for

Zoely is a contraceptive pill that is used to prevent pregnancy.

 All 24 white film-coated tablets are active tablets that contain a small amount of two different 
female hormones. These are nomegestrol acetate (a progestogen) and estradiol (an oestrogen).

 The 4 yellow tablets are inactive tablets that do not contain hormones and are called placebo 
tablets.

 Contraceptive pills that contain two different hormones, like Zoely, are called ‘combined pills’.
 Estradiol, the oestrogen in Zoely, is identical to the hormone produced by your ovaries during a 

menstrual cycle.
 Nomegestrol acetate, the progestogen in Zoely, is derived from the hormone progesterone. 

Progesterone is produced by your ovaries during a menstrual cycle.

2. What you need to know before you use Zoely

General notes

Before you start using Zoely you should read the information on blood clots (thrombosis) in section 2.
It is particularly important to read the symptoms of a blood clot – see section 2 “Blood clots”.

 



30

Before you can begin taking Zoely, your doctor will ask you some questions about your personal 
health history and that of your close relatives. The doctor will also measure your blood pressure and, 
depending upon your personal situation, may also carry out some other tests.

In this leaflet, several situations are described where you should stop taking the pill, or where the 
reliability of the pill may be decreased. In such situations you should not have sexual intercourse or 
you should take extra non-hormonal contraceptive precautions, e.g., use a condom or another barrier 
method. Do not use rhythm or temperature methods. These methods can be unreliable because the pill 
alters the usual changes in temperature and cervical mucus that occur during the menstrual cycle.

Zoely, like other hormonal contraceptives, does not protect against HIV infection (AIDS) or any 
other sexually transmitted disease.

Do not use Zoely
You must not use Zoely if you have any of the conditions listed below. If you do have any of the 
conditions listed below, you must tell your doctor. Your doctor will discuss with you what other form 
of birth control would be more appropriate.

 if you have (or have ever had) a blood clot in a blood vessel of your legs (deep vein thrombosis,
DVT), your lungs (pulmonary embolus, PE) or other organs;

 if you know you have a disorder affecting your blood clotting - for instance, protein C 
deficiency, protein S deficiency, antithrombin – III deficiency, Factor V Leiden or 
antiphospholipid antibodies;

 if you need an operation or if you are off your feet for a long time (see section ‘Blood clots);
 if you have ever had a heart attack or a stroke;
 if you have (or have ever had) angina pectoris (a condition that causes severe chest pain and

may be a first sign of a heart attack) or transient ischaemic attack (TIA – temporary stroke
symptoms);

 if you have any of the following diseases that may increase your risk of a clot in the arteries:
– severe diabetes with blood vessel damage
– very high blood pressure
– a very high level of fat in the blood (cholesterol or triglycerides);
– a condition known as hyperhomocysteinaemia

 if you have (or have ever had) a type of migraine called ‘migraine with aura’;
 if you have (had) inflammation of the pancreas (pancreatitis) associated with high levels of fat 

in your blood;
 if you have (had) severe liver disease and your liver is not yet working normally;
 if you have (had) a benign or malignant tumour in the liver;
 if you have (had), or if you may have, cancer of the breast or the genital organs;
 in case of presence or history of meningioma (generally benign tumour of the tissue located 

between the brain and the skull). In case of doubt, contact your doctor.
 if you have any unexplained bleeding from the vagina;
 if you are allergic to estradiol or nomegestrol acetate, or any of the other ingredients of this 

medicine (listed in section 6).

If any of these conditions appear for the first time while using Zoely, stop taking it at once and tell 
your doctor. In the meantime, use a non-hormonal contraceptive. See also ‘General Notes’ in section 2 
above.

 



31

When to take special care with Zoely

When should you contact your doctor?

Seek urgent medical attention

 if you notice possible signs of a blood clot that may mean you are suffering from a blood clot in 
the leg (i.e., deep vein thrombosis), a blood clot in the lung (i.e., pulmonary embolism), a heart 
attack or a stroke (see “Blood clots” section below).

For a description of the symptoms of these serious side effects please go to “How to recognise a blood 
clot”.
 if you notice any changes in your own health, especially involving any of the items mentioned 

in this leaflet (see also in section 2 ‘Do not use Zoely’; do not forget about the changes in the 
health of your immediate family);

 if you feel a lump in your breast;
 if you experience symptoms of angioedema such as swollen face, tongue and/or throat and/or 

difficulty swallowing or hives together with difficulty breathing;
 if you are going to use other medicines (see also in section 2 ‘Other medicines and Zoely’);
 if you are to be immobilised or are to have surgery (tell your doctor at least four weeks in 

advance);
 if you have unusual, heavy vaginal bleeding;
 if you forgot one or more tablets in the first week of the blister pack and had unprotected 

intercourse in the seven days before (see also in section 3 ‘If you forget to take Zoely’);
 if you have severe diarrhoea or experience severe vomiting;
 if you miss periods and suspect you may be pregnant (do not start the next blister pack until 

your doctor tells you, see also in section 3 ‘If you have missed one or more periods’).

Tell your doctor if any of the following conditions apply to you.
If the condition develops, or gets worse while you are using Zoely, you should also tell your doctor.
 if you have hereditary angioedema. Consult your doctor immediately if you experience 

symptoms of angioedema such as swollen face, tongue and/or throat and/or difficulty 
swallowing or hives, together with difficulty breathing. Products containing oestrogens may 
induce or worsen symptoms of angioedema;

 if a close relative has or has ever had breast cancer;
 if you have epilepsy (see in section 2 ‘Other medicines and Zoely’);
 if you have liver disease (for instance jaundice) or gallbladder disease (for instance gallstones);
 if you have diabetes;
 if you have depression;
 if you have Crohn’s disease or ulcerative colitis (chronic inflammatory bowel disease);
 if you have systemic lupus erythematosus (SLE - a disease affecting your natural defence 

system);
 if you have haemolytic uraemic syndrome (HUS - a disorder of blood clotting causing failure of 

the kidneys);
 if you have sickle cell anaemia (an inherited disease of the red blood cells);
 if you have elevated levels of fat in the blood (hypertriglyceridaemia) or a positive family 

history for this condition. Hypertriglyceridaemia has been associated with an increased risk of 
developing pancreatitis (inflammation of the pancreas);

 if you need an operation or if you are off your feet for a long time (see in section 2 ‘Blood
clots).

 if you have just given birth you are at an increased risk of blood clots. You should ask your 
doctor how soon after delivery you can start taking Zoely.

 if you have an inflammation in the veins under the skin (superficial thrombophlebitis);
 if you have varicose veins.
 if you have a condition that occurred for the first time or worsened during pregnancy or

previous use of sex hormones (e.g. hearing loss, porphyria [a disease of the blood], herpes 

 



32

gestationis [skin rash with vesicles during pregnancy], Sydenham’s chorea [a disease of the 
nerves in which sudden movements of the body occur] (see in section 2 ‘When should you 
contact your doctor’);

 if you have (or have ever had) chloasma [yellowish-brown pigment patches, so called 
‘pregnancy patches’, particularly on the face]. If so, avoid too much exposure to the sun or 
ultraviolet light;

BLOOD CLOTS

Using a combined hormonal contraceptive such as Zoely increases your risk of developing a blood 
clot compared with not using one. In rare cases a blood clot can block blood vessels and cause serious 
problems.

Blood clots can develop
 in veins (referred to as ‘venous thrombosis’, ‘venous thromboembolism’ or VTE)
 in the arteries (referred to as an ‘arterial thrombosis’, ‘arterial thromboembolism’ or ATE).
Recovery from blood clots is not always complete. Rarely, there may be serious lasting effects or, very 
rarely, they may be fatal.

It is important to remember that the overall risk of a harmful blood clot due to Zoely is small.

HOW TO RECOGNISE A BLOOD CLOT

Seek urgent medical attention if you notice any of the following signs or symptoms.

Are you experiencing any of these signs? What are you possibly 
suffering from?

 swelling of one leg or along a vein in the leg or foot especially when 
accompanied by:

 pain or tenderness in the leg which may be felt only when 
standing or walking

 increased warmth in the affected leg
 change in colour of the skin on the leg e.g. turning pale, red or 

blue

Deep vein thrombosis

 sudden unexplained breathlessness or rapid breathing;
 sudden cough without an obvious cause, which may bring up blood;
 sharp chest pain which may increase with deep breathing;
 severe light headedness or dizziness;
 rapid or irregular heartbeat;
 severe pain in your stomach;

If you are unsure, talk to a doctor as some of these symptoms such as 
coughing or being short of breath may be mistaken for a milder condition 
such as a respiratory tract infection (e.g., a ‘common cold’).

Pulmonary embolism

Symptoms most commonly occur in one eye:
 immediate loss of vision or
 painless blurring of vision which can progress to loss of vision

Retinal vein thrombosis
(blood clot in the eye)

 



33

 chest pain, discomfort, pressure, heaviness
 sensation of squeezing or fullness in the chest, arm or below the 

breastbone;
 fullness, indigestion or choking feeling;
 upper body discomfort radiating to the back, jaw, throat, arm and 

stomach;
 sweating, nausea, vomiting or dizziness;
 extreme weakness, anxiety, or shortness of breath;
 rapid or irregular heartbeats

Heart attack

 sudden weakness or numbness of the face, arm or leg, especially on 
one side of the body;

 sudden confusion, trouble speaking or understanding;
 sudden trouble seeing in one or both eyes;
 sudden trouble walking, dizziness, loss of balance or coordination;
 sudden, severe or prolonged headache with no known cause;
 loss of consciousness or fainting with or without seizure.

Sometimes the symptoms of stroke can be brief with an almost immediate 
and full recovery, but you should still seek urgent medical attention as you 
may be at risk of another stroke.

Stroke

 swelling and slight blue discolouration of an extremity;
 severe pain in your stomach (acute abdomen).

Blood clots blocking 
other blood vessels

BLOOD CLOTS IN A VEIN

What can happen if a blood clot forms in a vein?
 The use of combined hormonal contraceptives has been connected with an increase in the risk of 

blood clots in the vein (venous thrombosis). However, these side effects are rare. Most 
frequently, they occur in the first year of use of a combined hormonal contraceptive.

 If a blood clot forms in a vein in the leg or foot it can cause a deep vein thrombosis (DVT).
 If a blood clot travels from the leg and lodges in the lung it can cause a pulmonary embolism.
 Very rarely a clot may form in a vein in another organ such as the eye (retinal vein thrombosis).

When is the risk of developing a blood clot in a vein highest?
The risk of developing a blood clot in a vein is highest during the first year of taking a combined 
hormonal contraceptive for the first time. The risk may also be higher if you restart taking a combined 
hormonal contraceptive (the same product or a different product) after a break of 4 weeks or more.

After the first year, the risk gets smaller but is always slightly higher than if you were not using a 
combined hormonal contraceptive.

When you stop Zoely your risk of a blood clot returns to normal within a few weeks.

What is the risk of developing a blood clot?
The risk depends on your natural risk of VTE and the type of combined hormonal contraceptive you 
are taking.

The overall risk of a blood clot in the leg or lung (DVT or PE) with Zoely is small.
 Out of 10,000 women who are not using any combined hormonal contraceptive and are not 

pregnant, about 2 will develop a blood clot in a year.
 Out of 10,000 women who are using a combined hormonal contraceptive that contains 

levonorgestrel, norethisterone, or norgestimate, about 5-7 will develop a blood clot in a year.

 



34

 It is not yet known how the risk of a blood clot with Zoely compares to the risk with a combined 
hormonal contraceptive that contains levonorgestrel.

 The risk of having a blood clot will vary according to your personal medical history (see 
“Factors that increase your risk of a blood clot” below).

Risk of developing a blood clot 
in a year

Women who are not using a combined hormonal pill and are not 
pregnant

About 2 out of 10,000 women

Women using a combined hormonal contraceptive pill containing 
levonorgestrel, norethisterone or norgestimate

About 5-7 out of 10,000 women

Women using Zoely Not yet known

Factors that increase your risk of a blood clot in a vein
The risk of a blood clot with Zoely is small but some conditions will increase the risk. Your risk is 
higher:
 if you are very overweight (body mass index or BMI over 30 kg/m2);
 if one of your immediate family has had a blood clot in the leg, lung or other organ at a young 

age (e.g., below the age of about 50). In this case you could have a hereditary blood clotting 
disorder;

 if you need to have an operation, or if you are off your feet for a long time because of an injury 
or illness, or you have your leg in a cast. The use of Zoely may need to be stopped several 
weeks before surgery or while you are less mobile. If you need to stop Zoely ask your doctor 
when you can start using it again.

 as you get older (particularly above about 35 years);
 if you gave birth less than a few weeks ago

The risk of developing a blood clot increases the more conditions you have.
Air travel (> 4 hours) may temporarily increase your risk of a blood clot, particularly if you have some 
of the other factors listed.
It is important to tell your doctor if any of these conditions apply to you, even if you are unsure. Your 
doctor may decide that Zoely needs to be stopped.
If any of the above conditions change while you are using Zoely, for example a close family member 
experiences a thrombosis for no known reason or you gain a lot of weight, tell your doctor.

BLOOD CLOTS IN AN ARTERY

What can happen if a blood clot forms in an artery?
Like a blood clot in a vein, a clot in an artery can cause serious problems. For example, it can cause a 
heart attack or a stroke.

Factors that increase your risk of a blood clot in an artery

It is important to note that the risk of a heart attack or stroke from using Zoely is very small but can 
increase:

 with increasing age (beyond about 35 years);
 if you smoke. When using a combined hormonal contraceptive like Zoely you are advised to 

stop smoking. If you are unable to stop smoking and are older than 35 your doctor may advise 
you to use a different type of contraceptive;

 if you are overweight;
 if you have high blood pressure;
 if a member of your immediate family has had a heart attack or stroke at a young age (less than 

about 50). In this case you could also have a higher risk of having a heart attack or stroke;

 



35

 if you, or someone in your immediate family, have a high level of fat in the blood (cholesterol
or triglycerides);

 if you get migraines, especially migraines with aura;
 if you have a problem with your heart (valve disorder, disturbance of the rhythm called atrial

fibrillation)
 if you have diabetes.

If you have more than one of these conditions or if any of them are particularly severe, the risk of 
developing a blood clot may be increased even more.
If any of the above conditions change while you are using Zoely, for example, you start smoking, a 
close family member experiences a thrombosis for no known reason or you gain a lot of weight, tell 
your doctor.

Cancer
Breast cancer has been found slightly more often in women using combined pills, but it is not known 
whether this is caused by the combined pills. For example, it may be that tumours are found more in 
women on combined pills because they are examined by the doctor more often. After stopping the 
combined pill, the increased risk gradually reduces.
It is important to check your breasts regularly and you should contact your doctor if you feel any 
lump. You should also tell your doctor if a close relative has, or ever had breast cancer (see section 2
“When to take special care with Zoely”).

In rare cases, benign (noncancerous) liver tumours, and in even fewer cases malignant (cancerous) 
liver tumours have been reported in pill users. Contact your doctor if you have unusual severe 
abdominal pain.

Cervical cancer is caused by an infection with the human papilloma virus (HPV). It has been reported 
to occur more often in women using the pill for more than 5 years. It is unknown if this finding is due 
to the use of hormonal contraceptives or to other factors, such as difference in sexual behaviour.

Meningiomas
Cases of meningioma (generally benign tumours of the brain) have been reported with prolonged use 
(several years) of nomegestrol monotherapy (without estradiol) at higher doses of 3.75 and 5 mg and
more (see section ‘Do not use Zoely’). If a meningioma is diagnosed, treatment with Zoely should be 
stopped.

Psychiatric disorders
Some women using hormonal contraceptives including Zoely have reported depression or depressed 
mood. Depression can be serious and may sometimes lead to suicidal thoughts. If you experience 
mood changes and depressive symptoms contact your doctor for further medical advice as soon as 
possible.

Laboratory tests
If you are having any blood or urinary test, tell your doctor that you are using Zoely as it may affect 
the results of some tests.

Children and adolescents
No data on efficacy and safety are available in adolescents below 18 years.

Other medicines and Zoely
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines, including medicines obtained without a prescription and herbal medicines.
Also tell any other doctor or dentist who prescribes another medicine (or the dispensing pharmacist) 
that you use Zoely.
 There are medicines that can make Zoely less effective in preventing pregnancy, or can cause 

unexpected bleeding. These include medicines used to treat:

 



36

– epilepsy (e.g. primidone, phenytoin, phenobarbital, carbamazepine, oxcarbazepine, 
topiramate, felbamate);

– tuberculosis (e.g. rifampicin);
– HIV infections (e.g. rifabutin, ritonavir, efavirenz);
– Hepatitis C virus (HCV) infection (e.g. boceprevir, telaprevir);
– other infectious diseases (e.g. griseofulvin);
– high blood pressure in the blood vessels in the lungs (bosentan).

 The herbal product St. John’s wort may also stop Zoely from working properly. If you want to 
use herbal products containing St. John’s wort while you are already using Zoely you should 
consult your doctor first.

 If you are taking medicines or herbal products that might make Zoely less effective, a barrier 
contraceptive method should also be used. Since the effect of another medicine on Zoely may 
last up to 28 days after stopping the medicine, it is necessary to use the additional barrier 
contraceptive method for that long.

 Some medicines can increase the levels of the active substances of Zoely in the blood. The 
effectiveness of the pill is maintained, but tell your doctor if you are using anti-fungal medicines 
containing ketoconazole.

 Zoely may also interfere with the working of other medicines – such as the anti-epileptic 
lamotrigine.

 The Hepatitis C virus (HCV) combination drug regimen ombitasvir/paritaprevir/ritonavir with or
without dasabuvir may cause increases in liver function blood test results (increase in ALT liver 
enzyme) in women using CHCs containing ethinylestradiol. Zoely contains estradiol instead of 
ethinylestradiol. It is not known whether an increase in ALT liver enzyme can occur when using 
Zoely with this HCV combination drug regimen. Your doctor will advise you.

Pregnancy and breast-feeding
Zoely must not be used by women who are pregnant, or who think they may be pregnant. If you get 
pregnant while using Zoely you should stop using Zoely and contact your doctor.
If you want to stop Zoely because you want to get pregnant, see in section 3 ‘If you stop taking Zoely’.

Zoely is not usually recommended for use during breast-feeding. If you wish to use the pill while 
breast-feeding, please seek the advice of your doctor.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines
Zoely has no or negligible effect on your ability to drive and use machines.

Zoely contains lactose
Zoely contains lactose. If you have been told by your doctor that you have an intolerance to some 
sugars, contact your doctor before taking this medicine.

3. How to use Zoely

When and how to take the tablets
The Zoely blister contains 28 tablets: 24 white tablets with the active substances (number 1-24) and 
4 yellow tablets without active substances (number 25-28).

Each time you start a new blister of Zoely, take the number 1 white active tablet in the left-hand top 
corner (see ‘Start’). Choose from the 7 stickers with day indicators the one in the grey column that 
begins with your starting day. For example, if you start on a Wednesday, use the day label sticker that 
starts with ‘WED’. Stick it on the blister, just above the row of white active tablets where it reads 
‘Place day label here’. This allows you to check whether you took your daily tablet.
Take one tablet each day at about the same time, with some water if necessary.
Follow the direction of the arrows on the blister, so use the white active tablets first and then the 
yellow placebo tablets.

 



37

Your period will start during the 4 days that you use the yellow placebo tablets (so-called withdrawal 
bleeding). Usually it will start 2-3 days after the last white active tablet and may not have finished 
before the next blister is started.
Start taking your next blister immediately after the last yellow tablet, even if your period hasn’t 
finished. This means that you will always start a new blister on the same day of the week, and also that 
you have your period on roughly the same days each month.
Some users may not have their period every month during the intake of the yellow tablets. If you have 
taken Zoely every day according to these directions, it is unlikely that you are pregnant (see also 
section 3 ‘If you have missed one or more periods’).

Starting your first pack of Zoely

When no hormonal contraceptive has been used in the past month
Start taking Zoely on the first day of your cycle (i.e. the first day of your menstrual bleeding). Zoely 
will work immediately. You do not need to use an additional contraceptive method.

When changing from another combined hormonal contraceptive (combined pill, vaginal ring, or 
transdermal patch)
You can start taking Zoely the day after you have taken the last tablet from your present pill blister 
(this means no tablet-free break). If your present pill blister also contains inactive (placebo) tablets you 
can start Zoely on the day after taking the last active tablet (if you are not sure which this is, ask your 
doctor or pharmacist). You can also start later, but never later than the day following the tablet-free 
break of your present pill (or the day after the last inactive tablet of your present pill). In case you use 
a vaginal ring or transdermal patch, it is best to start using Zoely on the day you remove the ring or 
patch. You can also start, at the latest, on the day you would have started using the next ring or patch.
If you follow these instructions, it is not necessary to use an additional contraceptive method.

When changing from a progestogen-only pill (minipill)
You can stop taking the minipill any day and start taking Zoely the next day. But if you are having 
intercourse, make sure you also use a barrier method of contraception for the first 7 days that you are 
taking Zoely.

When changing from a progestogen-only injectable, implant or a hormone-medicated intrauterine 
system (IUS)
Start using Zoely when your next injection is due or on the day that your implant or IUS is removed. 
But if you are having intercourse, make sure you also use a barrier method of contraception for the 
first 7 days that you are taking Zoely.

After having a baby
You can start Zoely between 21 and 28 days after having a baby. If you start later than day 28, you 
should also use a barrier method of contraception during the first 7 days of Zoely use. If, after having a 
baby, you have had sexual intercourse before starting Zoely, be sure that you are not pregnant or wait 
until the next menstrual period. If you want to start Zoely after having a baby and are breast-feeding, 
see also section 2 ‘Pregnancy and Breast-feeding’.
Ask your doctor what to do if you are not sure when to start.

After a miscarriage or an abortion
Follow the advice of your doctor.

If you take more Zoely than you should
There have been no reports of serious harmful effects from taking too many Zoely tablets at one time. 
If you have taken several tablets at a time, you may have nausea, vomiting or vaginal bleeding. If you 
discover that a child has taken Zoely, ask your doctor for advice.

 



38

If you forget to take Zoely

The following advice only refers to missed white active tablets.
 if you are less than 24 hours late in taking a tablet, the reliability of the pill is maintained. Take 

the tablet as soon as you remember and take the next tablets at the usual time.
 if you are 24 or more hours late in taking any tablet, the reliability of the pill may be reduced. 

The more consecutive tablets you have missed, the higher the risk that the contraceptive 
efficacy is decreased. There is a particularly high risk of becoming pregnant if you miss white
active tablets at the beginning or at the end of the blister. Therefore you should follow the rules 
given below.

Day 1-7 of white active tablet intake (see picture and schedule)
Take the last white active missed tablet as soon as you remember (even if this means taking two 
tablets at the same time) and take the next tablet at the usual time. However, use a barrier method such 
as a condom as an extra precaution until you have taken your tablets correctly for 7 days in a row.
If you had sexual intercourse in the week before missing the tablets, there is a possibility of becoming 
or being pregnant. So contact your doctor immediately.

Day 8-17 of white active tablet intake (see picture and schedule)
Take the last missed tablet as soon as you remember (even if this means taking two tablets at the same 
time) and take the next tablets at the usual time. If you have taken your tablets correctly in the 7 days 
prior to the missed tablet, the protection against pregnancy is not reduced, and you do not need to use 
extra precautions. However, if you have missed more than 1 tablet, use a barrier method such as a 
condom as an extra precaution until you have taken your tablets correctly for 7 days in a row.

Day 18-24 of white active tablet intake (see picture and schedule)
There is a particularly high risk of becoming pregnant if you miss white active tablets close to the 
yellow placebo tablet interval. By adjusting your intake schedule this higher risk can be prevented.

The following two options can be followed. You do not need to use extra precautions if you have 
taken your tablets correctly in the 7 days prior to the missed tablet. If this is not the case, you should 
follow the first of these two options and use a barrier method such as a condom as an extra precaution 
until you have taken your tablets correctly for 7 days in a row.
Option 1)
Take the last missed white active tablet as soon as you remember (even if this means taking two 
tablets at the same time) and take the next tablets at the usual time. Start the next blister as soon as the 
white active tablets in the current blister are finished, so skip the yellow placebo tablets. You may 
not have your period until you take the yellow placebo tablets at the end of the second blister, but you 
may have spotting (drops or flecks of blood) or breakthrough bleeding while taking the white active 
tablets.
Option 2)
Stop taking the white active tablets and start taking the yellow placebo tablets for a maximum of 3 
days so that the total number of placebo plus missed white active tablets is not more than 4. At the end 
of the placebo tablet interval, start the next blister.

If you cannot remember how many white active tablets you have missed, follow the first option, use a 
barrier method such as a condom as an extra precaution until you have taken your tablets correctly for 
7 days in a row, and contact your doctor (as you may not have been protected from being pregnant).
If you have forgotten to take white active tablets in a blister, and you do not have the expected 
monthly period while taking the yellow placebo tablets from the same blister, you may be pregnant. 
Consult your doctor before you start with the next blister.

Yellow placebo tablets missed
The last 4 yellow tablets of the fourth row are placebo tablets which do not contain active substances. 
If you forgot to take one of these tablets the reliability of Zoely is maintained. Throw away the yellow 
placebo tablet(s) you missed and continue taking the next tablets at the usual time.

 



39

Picture

Schedule: if you are 24 or more hours late taking white tablets

If you vomit or have severe diarrhoea
If you vomit within 3-4 hours of taking a white active tablet, or you have severe diarrhoea, the active 
ingredients of your Zoely tablet may not have been completely absorbed into your body. The situation 
is similar to if you forget a white active tablet. After vomiting or diarrhoea, you must take another 
white active tablet from a reserve blister as soon as possible. If possible take it within 24 hours of 
when you normally take your pill. Take the next tablet at the usual time. If this is not possible or 24 or 
more hours have passed, you should follow the advice given under "If you forget to take Zoely". If 
you have severe diarrhoea, please tell your doctor.
The yellow tablets are placebo tablets which do not contain active substances. If you vomit or have 
severe diarrhoea within 3-4 hours of taking a yellow tablet, the reliability of Zoely is maintained.

If you want to delay your period
You can delay your period by not taking the yellow placebo tablets and going straight to a new blister 
of Zoely. You may experience light or menstruation-like bleeding while using this second blister. 
When you wish your period to begin during the second blister, stop taking the white active tablets and 
start taking the yellow placebo tablets. After finishing the 4 yellow placebo tablets from the second 
blister, start with the next (third) blister.

 



40

If you want to change the starting day of your period
If you take the tablets according to the instructions, then your period will begin during the placebo 
days. If you have to change this day, reduce the number of placebo days – when you take the yellow 
placebo tablets – (but never increase them – 4 is the maximum). For example, if you start taking the 
placebo tablets on Friday, and you want to change this to a Tuesday (3 days earlier) you must start a 
new blister 3 days earlier than usual. You may not have any bleeding during the shortened period of 
yellow placebo tablet intake. While using the next blister you may have some spotting (drops or flecks 
of blood) or breakthrough bleeding on white active tablet-taking days.
If you are not sure what to do, consult your doctor.

If you have unexpected bleeding
With all combined pills, for the first few months, you can have some irregular vaginal bleeding 
(spotting or breakthrough bleeding) between your periods. You may need to use sanitary protection, 
but keep taking your tablets as usual. Irregular vaginal bleeding usually stops once your body has 
adjusted to the pill (usually after about 3 months). If bleeding continues, becomes heavy or starts 
again, contact your doctor.

If you have missed one or more periods
Clinical trials with Zoely have shown that you may occasionally miss your regular monthly period 
after Day 24.
 If you have taken all the tablets correctly, and you have not vomited or had severe diarrhoea, or 

used other medicines, then it is very unlikely that you are pregnant. Keep taking Zoely as usual. 
See also in section 3 ‘If you vomit or have severe diarrhoea’ or in section 2 ‘Other medicines 
and Zoely’.

 If you have not taken all the tablets correctly, or if your expected period does not happen twice 
in a row, you may be pregnant. Contact your doctor immediately. Do not start the next blister of 
Zoely until your doctor has checked that you are not pregnant.

If you stop taking Zoely
You can stop taking Zoely at any time. If you do not want to become pregnant, first ask your doctor 
about other methods of birth control.
If you stop taking Zoely because you want to get pregnant, you are recommended to wait until you 
have had a natural period before trying to conceive. This will help you to determine when the baby 
will be due.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you get any side effect, particularly if severe or persistent, or have any change to your health that 
you think may be due to Zoely, please talk to your doctor.

An increased risk of blood clots in your veins (venous thromboembolism (VTE)) or blood clots in 
your arteries (arterial thromboembolism (ATE)) is present for all women taking combined hormonal 
contraceptives. For more detailed information on the different risks from taking combined hormonal 
contraceptives, please see section 2, “What you need to know before you use Zoely”.
The following side effects have been linked with the use of Zoely:

Very common (may affect more than 1 in 10 people):
 acne
 changes to menstrual periods (e.g. absence or irregularity)

Common (may affect up to 1 in 10 people):
 decreased interest in sex; depression/depressed mood; mood changes
 headache or migraine

 



41

 feeling sick (nausea)
 heavy menstrual periods; breast pain; pelvic pain
 weight gain

Uncommon (may affect up to 1 in 100 people):
 increased appetite; fluid retention (oedema)
 hot flush
 swollen abdomen
 increased sweating; hair loss; itching; dry skin; oily skin
 heaviness in limbs
 regular but scanty periods; larger breasts; breast lump; milk production while not pregnant; 

premenstrual syndrome; pain during intercourse; dryness in the vagina or vulva; spasm of the 
uterus

 irritability
 increased liver enzymes

Rare (may affect up to 1 in 1,000 people):
 harmful blood clots in a vein or artery, for example:

o in a leg or foot (i.e., DVT)
o in a lung (i.e., PE)
o heart attack
o stroke
o mini-stroke or temporary stroke-like symptoms known as a transient ischaemic attack 

(TIA)
o blood clots in the liver, stomach/intestine, kidneys or eye.

The chance of having a blood clot may be higher if you have any other conditions that increase this 
risk. (See section 2 for more information on the conditions that increase risk for blood clots and the 
symptoms of a blood clot.)
 decreased appetite
 increased interest in sex
 disturbance in attention
 dry eye; contact lens intolerance
 dry mouth
 golden brown pigment patches, mostly in the face; excessive hair growth
 vaginal smell; discomfort in the vagina or vulva
 hunger
 disease of the gallbladder

Allergic (hypersensitive) reactions have been reported in users of Zoely, but the frequency cannot be 
estimated from the available data.

Further information on the possible side effect changes to menstrual periods (e.g. absence or irregular) 
during the use of Zoely is described in section 3 ‘When and how to take the tablets’, ‘If you have 
unexpected bleeding’ and ‘If you have missed one or more periods’).

Reporting of side effects
If you get any side effects talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet.
You can also report side effects directly via the national reporting system listed in Appendix V. By 
reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Zoely

Keep this medicine out of the sight and reach of children.

 

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42

Do not use this medicine after the expiry date which is stated on the blister and carton after EXP. The 
expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Combined pills (including Zoely tablets) no longer required should not be disposed via wastewater or 
the municipal sewage system. The hormonal active ingredients in the tablet may have harmful effects 
if they reach the aquatic environment. Return them to a pharmacy or dispose them in another safe way 
according to local requirements. These measures will help to protect the environment.

6. Contents of the pack and other information

What Zoely contains
- The active substances are: nomegestrol acetate and estradiol

White active film-coated tablets: Each tablet contains 2.5 mg nomegestrol acetate and 1.5 mg 
estradiol (as hemihydrate).
Yellow placebo film-coated tablets: The tablet does not contain active substances.

- The other ingredients are:
Tablet core (white active and yellow placebo film-coated tablets):
Lactose monohydrate (see section 2 ‘Zoely contains lactose’), microcrystalline cellulose (E460), 
crospovidone (E1201), talc (E553b), magnesium stearate (E572) and colloidal anhydrous silica 
Tablet coat (white active film-coated tablets):
Poly(vinyl alcohol) (E1203), titanium dioxide (E171), macrogol 3350 and talc (E553b)
Tablet coat (yellow placebo film-coated tablets):
Poly(vinyl alcohol) (E1203), titanium dioxide (E171), macrogol 3350, talc (E553b), iron oxide 
yellow (E172) and iron oxide black (E172)

What Zoely looks like and contents of the pack
The active film-coated tablets (tablets) are white and round. They are coded ‘ne’ on both sides.
The placebo film-coated tablets are yellow and round. They are coded ‘p’ on both sides.
Zoely comes in blisters of 28 film-coated tablets (24 white active film-coated tablets and 4 yellow 
placebo film-coated tablets) packed in a ply carton. Pack sizes: 28, 84, 168 and 364 film-coated 
tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Theramex Ireland Limited
3rd Floor, Kilmore House,
Park Lane, Spencer Dock,
Dublin 1
D01 YE64
Ireland

Manufacturer
Delpharm Lille S.A.S.
Parc d’Activités Roubaix-Est
22 Rue de Toufflers
CS 50070
59452 LYS-LEZ-LANNOY
France

Teva Operations Poland Sp. z o.o.
ul. Mogilska 80
31-546 Krakow

 



43

Poland

N.V. Organon
Kloosterstraat 6
5349 AB Oss
The Netherlands

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

This leaflet was last revised in.

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET