SUMMARY OF PRODUCT CHARACTERISTICS, LABELLING AND PACKAGE LEAFLET
1
SUMMARY OF PRODUCT CHARACTERISTICS
2 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
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each film-coated tablet contains 2 mg of chlormadinone acetate and 0.03 mg of ethinyl estradiol.
Excipient with known effects: One coated tablet contains 75.27 mg lactose monohydrate.
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Film-coated tablet.
Tablets are biconvex, pink and rounded.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Hormonal contraception
The decision to prescribe
4.2 Posology and method of administration
Administration of the film-coated tablets
One film-coated tablet should be taken daily, at the same time (preferably at night) for 21 consecutive days, followed by a 7-day tablet-free period; withdrawal bleeding, similar to menstruation, should occur two to four days after the administration of the last tablet. The tablets should be resumed after the 7-day rest period, using the following blister of
The film-coated tablet should be removed from the blister, choosing the tablet marked with the correct day of the week, and swallowed whole with a little liquid, if necessary. The tablets should be taken daily, following the direction of the arrow.
Starting administration of the film-coated tablets
No previous administration of a hormonal contraceptive (during the last menstruation cycle): The first film-coated tablet should be taken on day one of the women’s natural cycle, i.e. on the first bleeding day of the next menstruation. If the first film-coated tablet is taken on the first day of
3 menstruation, contraception starts on the first day of administration and also continues during the seven-day medication-free interval.
The first film-coated tablet can also be taken on the 2nd-5th day of menstruation, irrespective of whether bleeding has ceased or not. In this case additional mechanical contraceptive measures must be taken during the first seven days of administration.
If menstruation had started more than five days earlier, then the woman should be instructed to wait until her next menstruation before starting to take
Change from another hormonal contraceptive to
Change from a 21 or 22-day hormonal contraceptive: All the tablets from the previous container should be finished. The first film-coated tablet of
Change from a combined daily hormonal contraceptive (28-day contraceptive): The administration of
Change from a progestogen-only pill ("POP"): The first
Change from a contraceptive hormone injection or implant: Administration of
Change from a vaginal ring or transdermal patch: The use of
After a miscarriage or an abortion in the first trimester After a miscarriage or an abortion in the first trimester administration of
After childbirth or after a miscarriage or abortion in the second trimester After childbirth women who do not breast-feed can start administration 21-28 days after delivery in which case no additional mechanical contraceptive measures are required.
If administration starts more than 28 days after childbirth, additional mechanical contraceptive measures are necessary during the first seven days.
If a woman has already had sexual intercourse, pregnancy must be ruled out or she must wait until her next menstruation before starting administration.
Lactation (see section 4.6)
4 After discontinuation of
Irregular administration of a tablet If the patient has forgotten to take a film-coated tablet but no more than 12 hours have passed since she did so, additional contraceptive measures are not required. She should continue to take the tablet as usual.
If more than 12 hours have passed since she forgot to take the tablet, the contraceptive effect of the medicinal product may have diminished. She should immediately take the missed film-coated tablet. The next film-coated tablet should be taken as usual. Another contraceptive method, such as a condom, should also be used during the following seven days. If within these seven days the pack finishes, start with the next pack as soon as the previous one is finished. In other words, no time interval should be left between packs (“seven-day rule”). The normal withdrawal bleed will probably not occur until the pack is finished; however, spotting often occurs during administration of the tablets. If the next menstrual period does not occur after taking the second pack, a pregnancy test should be performed.
Instructions in case of vomiting or diarrhoea
If vomiting occurs within 4 hours after administration of the tablets or severe diarrhoea develops, absorption may be incomplete and reliable contraception is no longer ensured. In this case the instructions in "Irregular tablet administration" (see above) should be followed.
4.3 Contraindications
Combined hormonal contraceptives (CHCs) should not be used in the following conditions: - initial or early signs of thrombosis, thrombophlebitis - loss of control of diabetes mellitus. - uncontrolled hypertension or significant rise in blood pressure (values consistently over 140/90 mm Hg) - hepatitis, jaundice, liver function disorders until liver values return to normal - generalised pruritus, cholestasis, especially during a previous pregnancy or oestrogen therapy - Dubin-Johnson syndrome, Rotor syndrome, alterations in bile flow - history or existence of benign or malignant liver tumours - severe epigastric pain, hepatomegaly or symptoms of intra-abdominal haemorrhage (see 4.8) - first case or repetition of porphyria (the three forms, particularly acquired porphyria) - presence or history of hormone-sensitive malignant tumours, such as of the breast or womb - severe lipid metabolism alterations - pancreatitis or a history of same, if associated with severe hypertriglyceridemia - first symptoms of migraine headaches or more frequent episodes of unusual severe headaches - acute sensory disturbances, such as visual or auditory disturbances - motor disturbances (particularly paresis) - increase in epileptic attacks - severe depression - otosclerosis deteriorating during previous pregnancies - amenorrhoea of unknown cause - endometrial hyperplasia - genital bleeding of unknown cause. - hypersensitivity to the active substances or to any of the excipients listed in section 6.1. - Presence or risk of venous thromboembolism (VTE) - Venous Thromboembolism – current VTE (on anticoagulants) or history of (e.g. deep venous thrombosis [DVT] or pulmonary embolism [PE])
5 - Known hereditary or acquired predisposition for venous thrombosis, such as APC-resistance (including Factor V Leiden), antithrombin-III-deficiency, protein C deficiency, protein S deficiency - Major surgery with prolonged immobilisation (see section 4.4) - 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) - Arterial thromboembolism – current arterial thrombosis, history of arterial thrombosis (e.g. myocardial infarction) or prodromal condition (e.g. angina pectoris) - Cerebrovascular disease – current stroke, history of stroke or prodromal condition (e.g. transient ischaemic attack, TIA) - Known hereditary or acquired predisposition for arterial thromboembolism, such as hyperhomocysteinaemia and antiphospholipidantibodies (anticardiolipin-antibodies, lupus anticoagulant) - History of migraine with focal neurological symptoms - A high risk of arterial thrombosis 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 - /…/ is contraindicated for concomitant use with the medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir, (see sections 4.4 and section 4.5).
4.4 Special warnings and precautions for use
Warnings
Smoking increases the risk of the severe cardiovascular adverse events of combined oral conraceptives (COC). The risk increases in heavy smokers and with age, particularly in women over 35. Women over 35 should use a different contraceptive method.
The administration of COC is associated with an increased risk of different serious diseases, such as myocardial infarction, thromboembolism, stroke or liver cancers. Other risk factors, such as hypertension, hyperlipidaemia, obesity and diabetes significantly increase the risk of morbidity and mortality.
If any of the conditions or risk factors mentioned below is present, the suitability of
Thromboembolism and other vascular diseases - The results of epidemiological studies indicate a relationship between the use of an oral contraceptive and an increased risk of arterial and venous thrombotic and thromboembolic diseases such as myocardial infarction, cerebral stroke, deep vein thrombosis and pulmonary embolism. These events are rare.
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
6 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 a period of one year. However, in any individual woman this number may be far higher, depending on her underlying risk factors (see below).
Epidemiological studies in women who use low dose combined oral contraceptives (<50 µg ethinylestradiol) have found that out of 10,000 women between about 6 and 12 will develop a VTE in one year.
Out of 10,000 women who use a levonorgestrel-containing CHC about 61 will develop a VTE in one year.
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 % cases.
It is not yet known how the risk with chlormadinone-containing CHCs compares with the risk with levonorgestrel-containing CHCs.
Extremely rarely, thrombosis has been reported to occur CHC users in other blood vessels, e.g. hepatic, mesenteric, renal, cerebral 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).
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 In these situations it is advisable to discontinue surgery to the legs or pelvis, neurosurgery, or use of the patch/pill/ring (in case of elective major trauma 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
Note: temporary immobilisation including air travel >4 hours can also be a risk factor for VTE,
1 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
7 particularly in women with other risk factors
Positive family history (venous If a hereditary predisposition is suspected, the thromboembolism ever in a sibling or parent woman should be referred to a specialist for especially at a relatively early age e.g. before 50) advice before deciding about any CHC use
Other medical conditions associated with VTE Cancer, system 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.
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).
Table: Risk factors for ATE
8 Risk factor Comment Increasing age Particularly above 35 years Smoking Women should be advised not to smoke if they wish to use 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 If a hereditary predisposition is suspected, the thromboembolism ever in a sibling or parent woman should be referred to a specialist for especially at relatively early age e.g. below 50) 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 Diabetes mellitus, hyperhomocysteinaemia, vascular events valvular heart disease and atrial fibrillation, dyslipoproteinaemia, 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).
Symptoms of 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 chocking; - sweating, nausea, vomiting or dizziness; - extreme weakness, anxiety, or shortness of breath; - rapid or irregular heartbeats.
The presence of one serious risk factor or multiple risk factors for venous or arterial disease, respectively, can also constitute a contra-indication. The possibility of anticoagulant therapy should also be taken into account. COC users should be specifically pointed out to contact their physician in case of possible symptoms of thrombosis. In case of suspected or confirmed thrombosis, COC use should be discontinued. Adequate alternative contraception should be initiated because of the teratogenicity of anticoagulant therapy (coumarins).
- Other medical conditions related to the circulation of the blood are diabetes mellitus, systemic lupus erythematosus, haemolytic uraemic syndrome, chronic inflammatory bowel disease (Crohn’s disease or ulcerative colitis) and sickle cell anaemia.
9
- When assessing the risk/benefit ratio, it should be taken into account that suitable treatment of these factors can reduce the risk of thrombosis.
- An increase in the frequency or severity of migraine during the use of combined oral contraceptives (which could be early signs of a cardiovascular event) may be reason for immediately discontinuing the use of the combined oral contraceptive.
Tumours Some epidemiological studies indicate that the prolonged use of oral contraceptives is a risk factor for the development of cervical cancer in women infected with the human papiloma virus (HPV). There is still some controversy, however, about the extent to which this outcome is influenced by other factors (such as the number of sexual partners or the use of barrier contraceptives) (see also “Medical examination”).
A meta-analysis of 54 epidemiological studies showed that the administration of oral contraceptives slightly increased the risk of breast cancer (RR = 1.24). This increased risk is transient and gradually disappears 10 years after stopping use. These studies do not refer to the causes. 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.
There have been rare reports of benign liver tumours, and even rarer cases of malignant tumours in women taking oral contraceptives. In isolated cases, these tumours have led to potentially fatal intra-abdominal haemorrhage. In the case of severe abdominal pain which does not spontaneously remit, hepatomegaly or signs of intra-abdominal haemorrhage, the possibility of a liver tumour should be considered, stopping the use of
Other medical conditions - A slight increase in blood pressure has been reported in many women taking oral contraceptives, but a clinically significant increase is rare. The relationship between the use of an oral contraceptive and clinical hypertension has not been confirmed. If the increase in blood pressure is clinically significant during the use of
- In women with a history of gestational herpes, there may be a recurrence during the use of COC.
- In women with a personal or family history of hypertriglyceridaemia, the risk of pancreatitis increases during the administration of COC. In cases of acute or chronic alterations of liver function, it may be necessary to interrupt the use of combined oral contraceptives until liver function values return to normal. In cases of a recurrence of cholestatic jaundice occurring during pregnancy or before the use of sex hormones, the use of combined oral contraceptives should be stopped.
- COC can affect peripheral resistance to insulin or glucose tolerance, so diabetic patients taking oral contraceptives should be closely monitored.
- Uncommonly, chloasma may appear, especially in women with a history of gestational chloasma. Women with a tendency to develop chloasma should avoid exposure to the sun and ultraviolet radiation during the use of oral contraceptives.
- In women with hereditary angioedema exogenous estrogens may induce or exacerbate symptoms of angioedema.
10 - Worsening of endogenous depression, of epilepsy, of Crohn’s disease and of ulcerative colitis has been reported during COC use.
- 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; gallstones; porphyria; systemic lupus erythematosus; haemolytic uraemic syndrome; Sydenham's chorea; herpes gestationis; otosclerosis-related hearing loss.
• This medicinal product contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
ALT elevations During clinical trials with patients treated for hepatitis C virus infections (HCV) with the medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin, transaminase (ALT) elevations higher than 5 times the upper limit of normal (ULN) occurred significantly more frequent in women using ethinylestradiol-containing medications such as combined hormonal contraceptives (CHCs) (see sections 4.3 and 4.5).
Precautions for use
The administration of oestrogens or oestrogen-progestogen combinations can have negative effects on certain diseases/conditions. Special medical supervision is required in the following cases:
- epilepsy - multiple sclerosis - tetany - migraine (see also 4.3) - asthma - heart or kidney failure - Sydenham’s chorea (St. Vitus Dance) - diabetes mellitus (also see 4.3) - liver disease (also see 4.3) - dyslipoproteinaemia (see also 4.3) - autoimmune diseases (including systemic lupus erythematosus) - obesity - hypertension (see also 4.3) - endometriosis - varicose veins - phlebitis (see also 4.3) - blood clotting alterations (see also 4.3) - mastopathy - uterine myoma - gestational herpes - depression (see also 4.3) - chronic inflammatory bowel disease (Crohn’s disease, ulcerative colitis; see also 4.8)
Medical examination/consultation Prior to the initiation or reinstitution of
11 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.
The medical examination includes measuring blood pressure, examination of the breasts, the abdomen and the external and internal genital organs, a cervical smear and appropriate lab tests.
Women should be advised that hormonal contraceptives do not protect against HIV infections (AIDS) and other sexually transmitted diseases.
Altered efficacy Missing a tablet (see “Irregular administration of a tablet“), vomiting or intestinal disorders, including diarrhoea, the long-term concomitant administration of certain medicinal products (see 4.5) or, very rarely, metabolic alterations, can affect contraceptive efficacy.
Impact on control of the cycle - Breakthrough bleeding and spotting All oral contraceptives can cause irregular vaginal bleeding (breakthrough bleeding and spotting), in particular during the first few cycles of administration. Medical assessment of irregular cycles is therefore required after an adjustment period of approximately three cycles. During the administration of
Intermenstrual bleeding could be an indication that contraceptive efficacy is diminished (see “Irregular administration of a tablet”, “Instructions in case of vomiting” and 4.5).
- Absence of withdrawal bleed Withdrawal bleeding occurs after 21 days of treatment. Occasionally, in particular during the first few months of administration, the withdrawal bleed may not occur. However, this does not necessarily indicate a diminished contraceptive effect. If bleeding does not occur after a cycle in which no tablets have been missed, the 7-day rest period has not been extended, no other concomitant medication has been taken and there has been no vomiting or diarrhoea, pregnancy is unlikely and the use of
4.5 Interaction with other medicinal products and other forms of interaction
The interactions of ethinyl estradiol, the oestrogen component of
The following medicinal products/active substances can reduce the serum concentration of ethinyl estradiol:
- all medicinal products which increase gastrointestinal motility (such as metoclopramide) or affect absorption (such as activated charcoal)
12 - active substances which induce hepatic microsomal enzymes, such as rifampicin, rifabutine, barbiturates, antiepileptic drugs (such as carbamazepine, phenytoin and topiramate), griseofulvin, barbexaclone, primidone, modafinil, some protease inhibitors (such as ritonavir) and St. John’s Wort (see 4.4)
When treatment with these medicinal products/active substances is given concomitantly with
If concomitant medicinal product administration runs beyond the end of the tablets in the COC blister pack, the next COC pack should be started without the usual tablet-free interval.
The following medicinal products/active substances can increase the serum concentration of ethinyl estradiol:
- active substances which inhibit the sulfonation of ethinyl estradiol in the intestinal wall, such as ascorbic acid or paracetamol - atorvastatin (increases the AUC of ethinyl estradiol by 20 %) - active substances which inhibit hepatic microsomal enzymes, such as imidazole-antimycotics (such as fluconazole), indinavir or troleandomycin.
Pharmacodynamic interactions Concomitant use with the medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir, with or without ribavirin may increase the risk of ALT elevations (see sections 4.3 and 4.4). Therefore, /…/-users must switch to an alternative method of contraception (e.g., progestagen- only contraception or non-hormonal methods) prior to starting therapy with this combination drug regimen. /…/ can be restarted 2 weeks following completion of treatment with this combination drug regimen.
Ethinyl estradiol can affect the metabolism of other substances:
- by inhibiting hepatic microsomal enzymes and therefore increasing the serum concentration of active substances such as diazepam (and other benzodiazepines metabolised by hydroxylation), cyclosporin, theophylline and prednisolone. - by inducing hepatic glucuronidation and thus reducing the serum concentration of, for example, clofibrate, paracetamol, morphine and lorazepam.
Insulin or oral antidiabetic requirements can be altered as a result of the effects on glucose tolerance (see 4.4).
This can also apply to recently taken medication. The summary of product characteristics of prescribed drugs should be reviewed for their possible interaction with
Laboratory tests Some laboratory tests can be affected during the administration of a COC, such as liver, adrenal and thyroid function tests, plasma concentrations of carrier proteins (such as SHBG, lipoproteins), carbohydrate metabolism parameters, clotting and fibrinolysis. The nature and magnitude of the effect partly depends on the nature and dose of the hormones used.
4.6 Fertility, pregnancy and lactation
13 evidence of teratogenic or foetotoxic effects when oestrogens were accidentally taken during pregnancy in combination with other progestogens in doses similar to those of
The increased risk of VTE during the postpartum period should be considered when re-starting
Lactation can be affected by oestrogens, as they can affect the quantity and composition of maternal milk. Small quantities of steroidal contraceptives and/or their metabolites can be excreted in maternal milk, which could affect the child. Therefore,
4.7 Effects on the ability to drive and use machines
There is no evidence that hormonal contraceptives have negative effects on the ability to drive or use machinery.
4.8 Undesirable effects
The most common (>20 %) undesirable effects were breakthrough bleeding, spotting, headache and mastodynia. The following undesirable effects were reported after the administration of chlormadinone acetate and ethinyl estradiol in a clinical study with 1,629 women.
Frequencies are defined as follows: Very common: ≥1/10 Common: ≥1/100 to < 1/10 Uncommon: ≥1/1000 to < 1/100 Rare: ≥1/10 000 to < 1/1000 Very rare: <1/10 000 Not known (cannot be estimated from the available data)
Immune system disorders Uncommon: drug hypersensitivity including allergic reactions
Psychiatric disorders Common: depression, excitability, nervousness
Nervous system disorders Common: dizziness, migraine (and/or worsening of same)
Eye disorders Common: visual alterations Rare: conjunctivitis, discomfort when wearing contact lenses
Ear and labyrinth disorders Rare: sudden hearing loss, tinnitus
Vascular disorders Rare: hypertension, hypotension, circulatory failure, varicose veins, venous thromboembolism (VTE), arterial thromboembolism (ATE)
Gastrointestinal disorders Very common: nausea Common: vomiting Uncommon: abdominal pain, abdominal distension, diarrhoea
14
Skin and subcutaneous tissue disorders Common: acne Uncommon: abnormal pigmentation, chloasma, hair loss, dry skin. Rare: urticaria, allergic skin reactions, eczema, erythema, pruritus, worsening of psoriasis, hirsutism Very rare: erythema nodosum
Musculoskeletal and connective tissue disorders Uncommon: back pain, muscular disorders
Reproductive system and breast disorders Very common: vaginal secretion, dysmenorrhoea, amenorrhoea Common: pain in the lower abdomen. Uncommon: galactorrhoea, fibroadenoma of the breast, genital candidiasis, ovarian cyst Rare: increased breast size, vulvovaginitis, menorrhagia, premenstrual syndrome.
General disorders and administration site conditions Common: tiredness, heaviness in the limbs, oedema, weight gain Uncommon: loss of libido, diaphoresis Rare: increased appetite
Investigations Common: increased blood pressure Uncommon: changes in blood lipids, including hypertriglyceridaemia
The following undesirable effects have also been reported after the use of oral contraceptives including 0.03 mg ethinylestradiol and 2 mg Chlormadinone acetate:
- An increased risk of arterial and venous thrombotic and thrombo-embolic events, including myocardial infarction, stroke, transient ischemic attacks, venous thrombosis and pulmonary embolism has been observed in women using CHCs, which are discussed in more detail in section 4.4. - An increased risk of biliary system alterations has been observed in some studies on the prolonged administration of combined hormonal contraceptives. - On rare occasions, after the administration of hormonal contraceptives, benign, or even more rarely, malignant liver tumours have been observed which have produced potentially fatal haemorrhage in the abdominal cavity (see 4.4). - Worsening of chronic inflammatory bowel disease (Crohn’s disease, ulcerative colitis; see also 4.4)
See 4.4 for other serious undesirable effects such as cervical or breast cancer.
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
There is no information concerning severe toxic effects in the case of overdose. The following symptoms may appear: nausea, vomiting and, in the case of young girls, vaginal bleeding. It may be necessary, but only on rare occasions, to control electrolytes, fluid balance and liver function.
15
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Systemic hormonal contraceptives; progestogens and estrogens, fixed combinations. ATC code: G03AA15.
The continuous administration of
The lowest daily dose of chlormadinone acetate for the total suppression of ovulation is 1.7 mg. The total endometrial transformation dose is 25 mg per cycle.
Chlormadinone acetate is an anti-androgenic progestogen. Its effect is based on its ability to displace androgens from their receptors.
Clinical efficacy and safety
In clinical trials investigating the administration of Chlormadinone acetate 2 mg + ethinylestradiol 0.03 mg for 2 years to 1,655 women, involving more than 22,000 menstrual cycles, there were 12 pregnancies. In 7 women, there were errors in the administration of the drug, concomitant diseases causing nausea or vomiting, or other concomitant medicinal products were administered which may have reduced the contraceptive efficacy of hormonal contraceptives.
Pearl index Number of Pearl index 95% confidence pregnancies interval Practical use 12 0.698 [0.389; 1.183] Theoretical use 5 0.291 [0.115; 0.650]
5.2 Pharmacokinetic properties
Chlormadinone acetate (CMA)
Absorption After oral administration, chlormadinone acetate is rapidly and almost completely absorbed. The systemic bioavailability of CMA is high, as it is not subject to first pass metabolism. Peak plasma concentrations are reached after 1-2 hours.
Distribution The fraction of CMA bound to human plasma proteins, largely albumin, is more than 95 %. However, CMA shows no binding affinity to SHBG (sex hormone-binding globulin) or CBG (corticosteroid-binding globulin). In the body, CMA is largely stored in fatty tissue.
Biotransformation Different processes of reduction and oxidation and conjugation with glucuronides and sulphate give rise to a large variety of metabolites. The principal metabolites in human plasma are 3- and 3-hydroxy-CMA, the half lives of which do not differ essentially from that of unmetabolised chlormadinone acetate. The 3-hydroxy metabolites show androgenic activity similar to that of CMA itself. In urine, the metabolites of CMA are predominantly conjugated. After enzyme hydrolysis, the principal metabolite is 2-hydroxy-CMA, besides the 3-hydroxy and dihydroxy metabolites.
16
Elimination CMA is eliminated from plasma with a half-life of approximately 34 hours (after a single dose) and 36-39 hours (after multiple doses). CMA and its metabolites are excreted both in urine and in faeces in approximately the same quantities after oral administration.
Ethinyl estradiol (EE)
Absorption EE is rapidly and almost completely absorbed after oral administration; peak plasma concentrations are reached after 1.5 hours. Due to presystemic conjugation and first pass metabolism in the liver, the absolute bioavailability is only approximately 40 % and subject to considerable interindividual variations (20-65 %).
Distribution The plasma concentrations of ethinyl estradiol reported in the literature vary considerably. Approximately 98 % of ethinyl estradiol is bound to plasma proteins, almost exclusively to albumin.
Biotransformation Like natural oestrogens, ethinyl estradiol is biotransformed by the P-450 cytochrome through hydroxylation of the aromatic ring. The principal metabolite is 2-hydroxy ethinyl estradiol, which is again metabolised to other metabolites and conjugated. Ethinyl estradiol undergoes presystemic conjugation both in the mucosa of the small intestine and in the liver. Largely glucuronides are found in urine, and sulphates in bile and plasma.
Elimination The mean plasma half-life of ethinyl estradiol is approximately 12-14 hours. Ethinyl estradiol is excreted in urine and faeces in a proportion of 2:3. The ethinyl estradiol sulphate excreted in bile after hydrolysis by intestinal bacteria is subject to enterohepatic circulation.
5.3 Preclinical safety data
The acute toxicity of oestrogens is low. Due to the considerable differences between animal species and humans, the results of animal experiments with oestrogens only have a limited predictive value for their use in humans. In experimental animals, relatively small doses of ethinyl estradiol, a synthetic oestrogen often used in oral contraceptives, had an embryolethal effect; urogenital tract abnormalities and feminisation of masculine foetuses have been observed. These effects are considered to be species-specific.
Chlormadinone acetate has shown embryolethal effects in rabbits, rats and mice. Teratogenicity was also observed at embryotoxic doses in rabbits and at the smallest dose (1 mg/kg/day) tested in mice. The significance of these findings for administration in humans is not clear. The preclinical data from conventional chronic toxicity, genotoxicity and carcinogenic potential studies showed no special risk for humans besides those described elsewhere in this summary of product characteristics.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Tablet core: Lactose monohydrate, Maize starch, Povidone K30, Magnesium stearate,
17 Film-coating: Hypromellose, Macrogol 6000, Talc, Titanium dioxide (E171), Red iron oxide (E172).
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years
6.4 Special precautions for storage
This medical product does not require any special storage conditions.
6.5 Nature and contents of the container
Blisters of transparent PVC coated with PVDC and aluminium.
It is available in calendar packs of 1, 3, 4 and 6 blisters, each one containing 21 tablets.
<[Applicable in DE and SK only:]> The blister packs may come with a blister holder.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7. MARKETING AUTHORISATION HOLDER
<[To be completed nationally]>
8. MARKETING AUTHORISATION NUMBER
<[To be completed nationally]>
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
<[To be completed nationally]>
10. DATE OF THE REVISION OF THE TEXT
MM/YYYY
18
LABELLING
19
PARTICULARS TO APPEAR ON THE OUTER PACKAGING:
Aluminium and PVC/PVDC film blister packaging. *
*: Information regarding the package sizes in the labelling of each Member State: The package sizes included in each labelling will be the approved for the reference product in the each relevant Member State
1. NAME OF THE MEDICINAL PRODUCT
Chlormadinone acetate/ethinylestradiol
2. STATEMENT OF ACTIVE SUBSTANCE(S)
Each film-coated tablet contains 2 mg of chlormadinone acetate and 0.03 mg of ethinylestradiol
3. LIST OF EXCIPIENTS
Contains lactose monohydrate. Please see leaflet for further information.
4. PHARMACEUTICAL FORM AND CONTENTS
1x21 film-coated tablets 3x21 film-coated tablets 4x21 film-coated tablets 6x21 film-coated tablets
5. METHOD AND ROUTE(S) OF ADMINISTRATION
Oral use Read the package leaflet before 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 {MM/YYYY}
20 9. SPECIAL STORAGE CONDITIONS
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
<[To be completed nationally]>
12. MARKETING AUTHORISATION NUMBER(S)
<[To be completed nationally]>
13. BATCH NUMBER
Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
<[To be completed nationally]>
16. INFORMATION IN BRAILLE
17. UNIQUE IDENTIFIER – 2D BARCODE
<2D barcode carrying the unique identifier included.>
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA
PC: SN: NN:
21
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS
Aluminium and PVC/PVDC film blister packaging.
1. NAME OF THE MEDICINAL PRODUCT
Chlormadinone acetate/ethinylestradiol
2. NAME OF THE MARKETING AUTHORISATION HOLDER
<[To be completed nationally]>
3. EXPIRY DATE
EXP {MM/YYYY}
4. BATCH NUMBER
Batch
5. OTHER
Oral use
22
MINIMUM PARTICULARS TO APPEAR ON BLISTER HOLDER*
*Applicable in DE and SK only
1. NAME OF THE MEDICINAL PRODUCT
Chlormadinone acetate/ethinylestradiol
2. NAME OF THE MARKETING AUTHORISATION HOLDER
<[To be completed nationally]>
3. EXPIRY DATE
4. BATCH NUMBER
5. OTHER
What to do if you forget to take
23
PACKAGE LEAFLET
24 Package leaflet: Information for the user
Chlormadinone acetate, ethinylestradiol
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 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 taking 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 or pharmacist. - This medicine has been prescribed for you only. Do not pass it on to other women. It may harm them. - If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.
What is in this leaflet 1. What
1. What
2. What you need to know before you take
General notes
Before you start using
Before you start taking
25 precautions, decide whether
Do not use
You should not use
26 - If you have (or have ever had) a type of migraine called ‘migraine with aura’ - If you have hepatitis C and are taking the medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir (see also in section “Other medicines and /…/”).
If one of these conditions occurs during administration of
You must also not take
Warnings and precautions
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 clot (thrombosis) section below.
For a description of symptoms of these serious side effects please go to “How to recognise a blood clot”
Tell your doctor if any of the following conditions apply to you. If the condition develops, or gets worse while you are using
BLOOD CLOTS Using a combined hormonal contraceptive (CHC) such as
Blood clots can develop - In veins (referred to as a ‘venous thrombosis’, a ‘venous thromboembolism’ or VTE) - In the arteries (referred to as an ‘arterial thrombosis’, ‘arterial thromboembolism’ or ATE)
27
Recovery from blood clots is not always complete. Rarely, there may be serious lasting effects, very rarely, they may be fatal.
It is important to remember that the overall risk of having a harmful blood clot due to
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 Deep vein thrombosis 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
• sudden unexplained breathlessness or rapid breathing; Pulmonary embolism • 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’). Symptoms most commonly occur in one eye: Retinal vein thrombosis • immediate loss of vision or (blood clot in the eye) • painless blurring of vision which can progress to loss of vision
• chest pain, discomfort, pressure, heaviness Heart attack • 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
• sudden weakness or numbness of the face, arm or leg, Stroke 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;
28 • 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. • swelling and slight blue discolouration of an extremity; Blood clots blocking other • severe pain in your stomach (acute abdomen) 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
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 blood clot in the leg or lung (DVT or PE) with
Risk of developing a blood clot in a year Women who are not using a combined hormonal About 2 out of 10,000 women pill/patch/ring and are not pregnant Women using a combined hormonal contraceptive pill About 5-7 out of 10,000 women containing levonorgestrel, norethisterone or norgestimate Women using
Factors that increase your risk of a blood clot in a vein
29 The risk of a blood clot with
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
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
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
Development of cancer Some studies indicate that one risk factor for the development of cervical cancer is the long-term use of hormonal contraceptives by women whose cervix is infected with a specific sexually transmitted virus (human papilloma virus).
30 However, the extent to which this result is influenced by other factors (such as differences in the number of sexual partners or in the use of barrier methods of contraception) is disputed.
Studies reported a slightly increased risk of breast cancer in women who are currently using COCs. During the course of 10 years after cessation of COC use this increased risk gradually returns to the age-related background risk. 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.
Very rarely, benign but still dangerous liver tumours can occur; these tumours can break up and cause life-threatening internal bleeding. Studies have indicated an increased risk for the development of cancer in the cells of the liver associated with the long-term use of oral contraceptives. However, this type of cancer is very rare. If you develop severe pains in your upper abdomen that do not go away on their own, you should consult your doctor.
Other diseases Many women taking oral contraceptives experienced a slight increase in blood pressure. Should your blood pressure increase considerably while you are taking
If you developed pemphigoid gestationis early on in a pregnancy, this disease can occur again while you are using an oral contraceptive.
If you have or members of your family have had a specific type of disorder affecting the level of fats in your blood (hypertriglyceridaemia), there is an increased risk of inflammation of the pancreas. If you develop acute or chronic liver function problems, your doctor may recommend that you stop taking
The use of oral contraceptives can affect the ability to break down glucose (glucose tolerance). If your glucose tolerance is reduced or if you have diabetes, your doctor should monitor you closely while you are taking
Occasionally, brownish skin blotches (chloasma) may appear, particularly if you have experienced these blotches during a previous pregnancy. If you have a tendency for chloasma, you should avoid direct exposure to the sun or ultraviolet light (e.g. sun beds).
In women with hereditary angioedema oral contraceptives may increase the symptoms.
Adverse effects on existing diseases You should be monitored especially carefully by your doctor - If you suffer from seizures (epilepsy) - If you suffer from multiple sclerosis - If you suffer from very severe muscle cramps (tetany) - If you suffer from migraines (see also section 2) - If you suffer from asthma - If you have impaired heart or kidney function (see also section 2) - If you suffer from St. Vitus’s dance (chorea minor) - If you are diabetic (see also section 2) - If you have a liver disease (see also section 2) - If you have a disorder of the lipid metabolism (see also section 2 ) - If you suffer from diseases of the immune system (including lupus erythematosus)
31 - If you are significantly overweight - If you suffer from high blood pressure (see also section 2) - If you have been diagnosed with benign excessive growth of the lining of the womb (endometriosis) (see also section 2) - If you suffer from varicose veins or phlebitis (see also section 2) - If you have blood clotting problems (see also section 2) - If you have been diagnosed with a benign tumour in the womb (myoma) - If you have a breast disease (mastopathy) - If you had a blistered rash (pemphigoid gestationis) during a previous pregnancy - If you suffer from bouts of depression (see also section 2) - If you suffer from a chronic inflammatory bowel disease (Crohn’s disease, ulcerative colitis).
Talk to your doctor if you have or have ever had one of the above diseases, or if one of these diseases occurs while you are taking
Effectiveness If you do not take the contraceptive regularly, experience vomiting or diarrhoea after taking the tablet (see section 3) or use certain other medicines at the same time (see section 2), the contraceptive effect of
Even if used correctly, oral contraceptives cannot provide 100 % protection against pregnancy.
Irregular bleeding Particularly in the first few months of taking oral contraceptives, irregular bleeding from the vagina (breakthrough bleeding/spotting) may occur. If such irregular bleeding continues to occur during 3 months, or recurs after previously regular cycles, please consult your doctor. Spotting may also be a sign that the contraceptive effect is reduced. In some cases, withdrawal bleeding may be absent after
Other medicines and
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription.
The contraceptive effect of
You should not take herbal medicines containing St. John’s wort together with
Inform your doctor if you are taking insulin or other medicines to lower your blood sugar. The dosage of these medicines may have to be changed.
32
When using oral contraceptives, the excretion of diazepam, ciclosporin, theophylline or prednisolone may be reduced with the result that the effect of these active substances may be greater and last longer. The effect of preparations containing clofibrate, paracetamol, morphine or lorazepam may be reduced if taken at the same time.
Please remember that the above details also apply if you have taken one of these active substances shortly before you start taking
Some laboratory tests on liver, adrenal and thyroid functions, certain blood proteins, carbohydrate metabolism and blood clotting may be affected by the administration of
Do not use /…/ if you have Hepatitis C and are taking the medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir as this may cause increases in liver function blood test results (increase in ALT liver enzyme). Your doctor will prescribe another type of contraceptive prior to start of the treatment with these medicinal products. /…/ can be restarted approximately 2 weeks after completion of this treatment. See section “Do not use /…/”.
You can take
Pregnancy and breast-feeding
If you are using
Driving and using machines
No special precautions are required.
This medicine contains lactose monohydrate (milk sugar). If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
3. How to take
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.
Method of administration
To be taken by mouth.
How and when to take
33
Press out the first tablet at the position on the cycle pack which is marked with the corresponding weekday (e.g. "Sun" for Sunday) and swallow it without chewing. You then take another tablet every day in the direction of the arrow, if possible at the same time of day, preferably in the evening. If possible, the interval between taking two tablets should always be 24 hours. The days printed on the cycle pack allow you to check every day whether you have already taken the tablet for that particular day.
Take one tablet daily for 21 consecutive days. Afterwards there is a break of seven days. Normally 2-4 days after taking the last tablet withdrawal bleeding similar to your menstrual period will start. After the seven-day break continue taking the tablets from the next cycle pack of
When can you start taking
If you have not taken any oral contraceptives before (during the last menstrual cycle)
Take your first tablet of
If your period has already started, take the first tablet on the 2nd - 5th day of your period, no matter whether or not bleeding has already stopped. However, in this case you must use additional mechanical contraceptive methods during the first seven days of administration (seven-day rule). If your period started more than five days previously, please wait until your next period and then start taking
If you have previously been using another oral contraceptive pill taken over 21 or 22 days
You should use up all of the tablets from the old pack as you usually do. On the day after you finish the old pack, start by taking the first film-coated tablet of
If you have previously been taking a daily combined oral contraceptive pill with a 28 pill cycle
After you have taken the last pill containing active ingredient from the old pack (after 21 or 22 days), start by taking the first film-coated tablet of
If you have taken an oral contraceptive containing only a progestogen (progestogen-only pill, "POP")
When an oral contraceptive is used which contains only a progestogen, withdrawal bleeding similar to menstrual period may be absent. Take the first
If you have had contraceptive hormone injections or a contraceptive implant before
Take the first tablet of
If you have previously been using a combined contraceptive vaginal ring or patch:
34 When changing from a combined contraceptive vaginal ring or patch, follow the advice of your doctor.
If you have had a miscarriage or abortion in the first three months of pregnancy
After a miscarriage or abortion you can start taking
If you have given birth or had a miscarriage in the 3rd - 6th month of pregnancy
If you are not breast-feeding, you can start taking
If, however, more than 28 days have passed since birth, you must use additional mechanical contraceptive methods for the first seven days.
If you have already had sexual intercourse, you must rule out pregnancy or wait until your next period before you start taking
Please remember that you should not take
How long can you take
You may take
What should you do in the event of vomiting or diarrhoea while taking
If vomiting or diarrhoea occurs within 4 hours after you have taken a tablet, you should continue
If you take more
There is no evidence that taking a large number of film-coated tablets at once will result in any signs of serious poisoning. Nausea, vomiting and (particularly in the case of young girls) light vaginal bleeding may occur. In this case, talk to a doctor.
If you forget to take
35 intercourse in the week before the oversight, you must realize that there is a risk of pregnancy. The same applies if you forgot one or more tablets and you do not have bleeding in the following 7 days tablet-free interval. In these cases, contact your doctor.
If you stop taking
If you stop taking
Spotting and breakthrough bleeding
All oral contraceptives can cause irregular bleeding (spotting and breakthrough bleeding), particularly during the first few months. Please consult your doctor if you are still experiencing irregular bleeding after 3 months or if irregular bleeding recurs after a previously regular cycle.
Bleeding between periods can also be a sign of a reduced contraceptive effect.
It is possible that some women using
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 and persistent, or have any change to your health that you think may be due to
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 take
The most common side effects (in more than 20 % of cases) reported in clinical trials with the combination Chlormadinone/ethinylestradiol were bleeding between periods and spotting, headaches and tenderness in the breasts.
The following side effects were reported after the combination Chlormadinone/ethinylestradiol was taken in a clinical study involving 1629 women.
Very common (may affect more than 1 in 10 people) - Nausea - Vaginal discharge, pain during periods, absence of periods
Common (may affect up to 1 in 10 people) - Depression, irritability, anxiety - Dizziness, migraines (and/or worsening migraines) - Impaired vision - Vomiting - Acne - Lower abdominal pain - Tiredness, heaviness in the legs, water retention, weight gain - Increased blood pressure
36
Uncommon (may affect up to 1 in 100 people) - Abdominal pain, bloating, diarrhoea - Pigmentation disorders, brownish skin blotches on the face, hair loss, dry skin - Back pain, muscle aches - Discharge from the breasts, benign changes to the connective tissue in the breast, vaginal fungal infections, ovarian cysts - Drug hypersensitivity including allergic reactions. - Reduced sex drive, tendency to sweat - Changes to blood fat levels including an elevated triglyceride content
Rare (may affect up to 1 in 1,000 people) - Inflammation of the conjunctivae, problems wearing contact lenses - Acute hearing loss, ringing in the ears - High blood pressure, low blood pressure, circulatory collapse, formation of varicose veins and venous thrombosis, harmful blood clots in a vein or artery for example: in a leg or foot (i.e. DVT); in a lung (i.e. PE); heart attack; stroke; mini-stroke or temporary stroke-like symptoms, known as transient ischaemic attack (TIA); 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) - Hives, allergic skin reactions, skin rash (eczema), inflammatory reddening of the skin, itching, worsening of existing psoriasis, increased body and facial hair - Breast enlargement, inflammation of the vagina, prolonged and/or increased menstrual bleeding, premenstrual syndrome (physical and psychological symptoms before the onset of menstrual bleeding) - Increased appetite
Very rare (may affect up to 1 in 10,000 people) - Erythema nodosum
In addition, combined oral contraceptives have been associated with increased risks for serious disorders and side effects: - Risk of blockages in the veins and arteries (see section 2) - Risk of bile ducts disorders (see section 2) - Risk of developing tumours (e.g. liver tumours, which in isolated cases led to life-threatening bleeding in the abdominal cavity, as well as cervical and breast cancer; see section 2) - Worsening of chronic inflammatory bowel disease (Crohn’s disease, ulcerative colitis).
Please read the information in section 2 carefully and if necessary consult with your doctor immediately.
Reporting of side effects If you get any side effects, talk to your doctor or pharmacist. 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
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the outer carton and the tablet strip (single-cycle pack) after “EXP”. The expiry date refers to the last day of that month.
37 This medicinal product does not require any special storage conditions.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.
6. Contents of the pack and other information
What
The active substances are ethinylestradiol and chlormadinone acetate.
One film-coated tablet contains 0.03 mg of ethinylestradiol and 2.0 mg of chlormadinone acetate.
The other ingredients are: Tablet core: lactose monohydrate, maize starch, povidone K 30, magnesium stearate (Ph. Eur.) Coating: hypromellose, macrogol 6000, talc, titanium dioxide (E 171) and iron (III) oxide (E 172)
What
<[Applicable in DE and SK only:]> The blister packs may come with a blister holder.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorization Holder <[To be completed nationally]>
Manufacturer <[To be completed nationally]>
This medicinal product is authorised in the Member States of the EEA under the following names:
Czech Republic:
This leaflet was last revised in {MM/YYYY}
38