Contrezin 0,03 mg, 3,0 mg Tablet

u2022 Oral contraception.

Posology
Combined oral contraceptives, when taken correctly, have a failure rate of approximately 1 % per year. The failure rate may increase when pills are missed or taken incorrectly.
Tablets must be taken in the order directed on the package, at about the same time every day, with some liquid if needed. One tablet is taken daily for 28 days. Each subsequent pack is started the day after the last intake of the previous pack.
A withdrawal bleed usually starts on day 2 to 3 after starting placebo tablets (white tablets in the last row) and may not be finished before the next pack is started.
How to start CONTREZIN:
a) No preceding hormonal contraceptive use (in the past month):
The first tablet must be taken on day 1 of the womanu2019s natural cycle (i.e. the first day of her menstrual bleeding). Starting on day 2 to 5 is allowed, but during the first cycle a barrier method is recommended in addition for the first 7 days of tablet-taking.
b) Changing from a combined hormonal contraceptive (combined oral contraceptive), vaginal ring or transdermal patch):
Start with CONTREZIN preferably on the day after the last active tablet of her previous combined oral contraceptive, but at the latest on the day following the usual tablet-free or inactive tablet interval of her previous combined oral contraceptive. In the event a vaginal ring or transdermal patch has been used, start using CONTREZIN preferably on the day of removal, but at the latest when the next application would have been due.
c) Changing from a progestogen-only method (minipill, injection, implant) or from a progestogen-releasing intrauterine system:
The patient may switch any day from the minipill, from an implant or the intrauterine system on the day of its removal and from an injectable when the next injection would be due, but should in all of these cases be advised to additionally use a barrier method for the first 7 days of tablet-taking.
d) Following first-trimester abortion:
The patient may start immediately. When doing so, she need not take additional contraceptive measures.
e) Following delivery or second-trimester abortion:
For breastfeeding women see u201dPregnancy and lactationu201d.
Women should be advised to start at day 21 to 28 after delivery or second-trimester abortion. When starting later, the woman should be advised to additionally use a barrier method for the first 7 days of tablet-taking. However, if intercourse has already occurred, pregnancy should be excluded before the actual start of CONTREZIN use or the woman must wait for her first menstrual period.
Management of missed tablets:
Placebo tablets from the last (4th) row of the blister can be disregarded. However, they should be discarded to avoid unintentionally prolonging the placebo tablet phase. The following advice only refers to missed active tablets:
If the user is less than 12 hours late in taking any active tablet, contraceptive protection is not reduced. The woman should take the tablet as soon as she remembers and should take further tablets at the usual time.
If she is more than 12 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:
1. Active tablet-taking must never be discontinued for longer than seven days.
2. 7 days of uninterrupted active tablet-taking are required to attain adequate suppression of the hypothalamic-pituitary-ovarian-axis.
Accordingly, the following advice can be given in daily practice:
Day 1 to 7:
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. In addition, a barrier method such as a condom should be used for the next 7 days. If intercourse took place in the preceding 7 days, the possibility of a pregnancy cannot be excluded. The more tablets that are missed and the closer they are to the inactive tablet phase, the higher the risk of a pregnancy.
Day 8 to 14:
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. 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 this is not the case, or if she missed more than 1 tablet, the woman should be advised to use extra precautions for 7 days.
Day 15 to 24:
The risk of reduced reliability is imminent because of the forthcoming inactive tablet phase. However, by adjusting the tablet-intake schedule, reduced contraceptive protection can still be prevented. If either of the following two options is adhered to, there is 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, the woman should be advised to 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 7 inactive tablets must be discarded. The next 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 active tablets-taking days.
2. The woman may also be advised to discontinue active tablet-taking from the current pack. She should then have a tablet-free interval of up to 7 days, including the days she missed tablets, and subsequently continue with the next pack, starting in the silver section with the tablets for the appropriate day of the week.
If the woman missed active tablets and subsequently has no withdrawal bleed in the inactive tablet phase, the possibility of a pregnancy should be considered.
Inactive tablet-taking
The white tablets are inactive tablets and missing these can be disregarded. However, they should be discarded to avoid unintentionally prolonging the inactive tablet phase.
Advice in case of gastrointestinal disturbances:
In case of gastrointestinal disturbances, absorption may not be complete and additional contraceptive measure should be taken. If vomiting occurs within 3 to 4 hours after active tablet-taking, the advice concerning missed tablets is applicable. If the woman does not want to change her normal tablet-taking schedule, she must take the extra tablet(s) needed from another pack.
How to delay a period:
To delay a period the woman should continue with another pack of CONTREZIN without taking the inactive tablets from her current pack. The extension can be carried on for as long as wished until the end of the active tablets in the second pack. During the extension the woman may experience breakthrough bleeding or spotting. Regular intake of CONTREZIN is then resumed after the inactive tablet phase.
Special populations:
Paediatric population
CONTREZIN is only indicated after menarche.
Elderly
CONTREZIN is not indicated after menopause.
Patients with hepatic impairment
CONTREZIN is contraindicated in women with severe hepatic diseases. See also sections 4.3 and 5.2.
Patients with renal impairment
CONTREZIN is contraindicated in women with severe renal insufficiency or acute renal failure. See also sections 4.3 and 5.2.
Method of administration
For oral use.

Combined oral contraceptives such as CONTREZIN should not be used in the presence of any of the conditions listed below. Should any of the conditions appear for the first-time during treatment with CONTREZIN , the product should be stopped immediately.
u2022 Hypersensitivity to drospirenone, ethinylestradiol or to any of the excipients listed in section 6.1.
u2022 Presence or risk of venous thromboembolism (VTE)
o Venous thromboembolism u2013 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)
u2022 Presence or risk of arterial thromboembolism (ATE)
o Arterial thromboembolism u2013 current arterial thromboembolism, history of arterial thromboembolism (e.g. myocardial infarction) or prodromal condition (e.g. angina pectoris)
o Cerebrovascular disease u2013 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 The presence of a severe or multiple risk factor(s) for arterial thromboembolism (see section 4.4) such as:
uf0a7 diabetes mellitus with vascular symptoms
uf0a7 severe hypertension
uf0a7 severe dyslipoproteinaemia
u2022 Severe hepatic disease as long as liver function values have not returned to normal.
u2022 Severe renal insufficiency or acute renal failure with a creatine clearance of < 30 mL/min.
u2022 Presence or history of liver tumours (benign or malignant).
u2022 Known or suspected sex-steroid influenced malignancies (e.g. of the genital organs or the breasts).
u2022 Undiagnosed vaginal bleeding.
u2022 Known or suspected pregnancy.
u2022 CONTREZIN is contraindicated for concomitant use with the medicines containing ombitasvir/ paritaprevir/ ritonavir and dasabuvir, or medicine containing glecaprevir/ pibrentasvir (see sections 4.4 and 4.5).

Warnings
If any of the conditions or risk factors mentioned below is present, the suitability of CONTREZIN 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 healthcare provider to determine whether the use of CONTREZIN should be discontinued.
In case of suspected or confirmed VTE or ATE, CONTREZIN use should be discontinued. In case anticoagulant therapy is started, adequate alternative contraception should be initiated because of the teratogenicity of anticoagulant therapy (coumarins).
Circulatory disorders
The risk of VTE is highest during the first year of use. This increased risk is present after initially starting CONTREZIN or restarting (following a 4 week or greater pill free interval) the same or a different combined oral contraceptive. This increased risk is mainly present during the first 3 months.
The overall risk for venous thromboembolism (VTE) in patients of low oestrogen dose combined oral contraceptives is two to threefold higher than for non-patients of combined oral contraceptives who are not pregnant.
Risk factors for VTE and ATE
The risk for venous and arterial thromboembolic complications in CONTREZIN patients may increase substantially in a woman with additional risk factors, particularly if there are multiple risk factors. CONTREZIN is contraindicated if a woman has multiple risk factors that put her at high risk of venous and 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 u2013 in this case her total risk of VTE/ ATE should be considered. If the balance of benefits and risks is negative CONTREZIN should not be prescribed (see section 4.3).
Risk factors for VTE and ATE include:
u2022 Obesity (body mass index over 30 kg/m 2 )
o Risk increases substantially as BMI rises. It is particularly important to consider if other risk factors also present
u2022 Prolonged immobilisation
o major surgery, any surgery to the legs or pelvis, neurosurgery, or major trauma. 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.
o Antithrombotic treatment should be considered if CONTREZIN has not been discontinued in advance.
o Note: temporary immobilisation including air travel > 4 hours can also be a risk factor for VTE, particularly in women with other risk factors
u2022 Family history
o Positive family history (venous thromboembolism ever in a sibling or parent especially at a relatively early age e.g. before 50)
o If a hereditary predisposition is suspected, the woman should be referred to a medical practitioner for advice before deciding about any CONTREZIN use
u2022 Other medical conditions associated with VTE
o Cancer, systemic lupus erythematosus, haemolytic uraemic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) and sickle cell disease
o Diabetes mellitus, hyperhomocysteinaemia, valvular heart disease and atrial fibrillation, dyslipoproteinaemia and systemic lupus erythematosus.
u2022 Increasing age
o Particularly above 35 years
u2022 Hypertension
u2022 Smoking
o Women should be advised not to smoke if they wish to use CONTREZIN . Women over 35 who continue to smoke should be strongly advised to use a different method of contraception
u2022 Migraine
o An increase in frequency or severity of migraine during CONTREZIN use (which may be prodromal of a cerebrovascular event) may be a reason for immediate discontinuation
The increased risk of thromboembolism in pregnancy, and particularly the 6-week period of the puerperium, must be considered (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 CONTREZIN . Symptoms of deep vein thrombosis (DVT) can include:
u2022 unilateral swelling of the leg and/or foot or along a vein in the leg.
u2022 pain or tenderness in the leg which may be felt only when standing or walking,
u2022 increased warmth in the affected leg; red or discoloured skin on the leg.
Symptoms of pulmonary embolism (PE) can include:
u2022 sudden onset of unexplained shortness of breath or rapid breathing.
u2022 sudden coughing which may be associated with haemoptysis.
u2022 sharp chest pain.
u2022 severe light headedness or dizziness.
u2022 rapid or irregular heartbeat.
Some of these symptoms (e.g. u201cshortness of breathu201d, u201ccoughingu201d) are non-specific and might be misinterpreted as more frequent or less severe events (e.g. respiratory tract infections). Other signs of vascular occlusion can include sudden pain, swelling and slight blue discolouration 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.
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 CONTREZIN . Symptoms of a cerebrovascular accident can include:
u2022 sudden numbness or weakness of the face, arm, or leg, especially on one side of the body.
u2022 sudden trouble walking, dizziness, loss of balance or coordination.
u2022 sudden confusion, trouble speaking or understanding.
u2022 sudden trouble seeing in one or both eyes.
u2022 sudden, severe, or prolonged headache with no known cause.
u2022 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:
u2022 pain, discomfort, pressure, heaviness, sensation of squeezing or fullness in the chest, arm, or below the breastbone.
u2022 discomfort radiating to the back, jaw, throat, arm, stomach.
u2022 feeling of being full, having indigestion or choking.
u2022 sweating, nausea, vomiting or dizziness.
u2022 extreme weakness, anxiety, or shortness of breath.
u2022 rapid or irregular heartbeats
Tumours:
The most important risk factor for cervical cancer is persistent human papilloma virus infection. Long-term use of CONTREZIN may further contribute to an increased risk of cervical cancer.
There is a slightly increased relative risk (RR= 1,24) of having breast cancer diagnosed in women who are currently using CONTREZIN . The excess risk gradually disappears during the course of the 10 years after cessation of CONTREZIN use.
Benign liver tumours and, even more rarely, malignant liver tumours have been reported in patients taking combined oral contraceptives (COCs). In isolated cases, these tumours have led to life-threatening intra-abdominal haemorrhages. 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 CONTREZIN . Malignancies may be life-threatening or may have a fatal outcome.
Other conditions
Women using CONTREZIN and concomitant medicines with the potential to increase serum potassium such as ACE-inhibitors, angiotensin II receptor antagonists, aldosterone antagonists, potassium-sparing diuretics or NSAIDs used for long term treatment should be tested for serum potassium during the first treatment cycle.
Women with hypertriglyceridaemia, or a family history thereof, may be at an increased risk of pancreatitis when using combined oral contraceptives such as CONTREZIN.
Small increases in blood pressure have been reported in many women taking COCs and clinically relevant increases may occur. If a sustained clinically significant hypertension develops during the use of CONTREZIN, then it is prudent for the medical practitioner to withdraw CONTREZIN and treat the hypertension.
The occurrence or deterioration of the following conditions have been reported with COCs use: jaundice and/or pruritus related to cholestasis, gallstone formation, porphyria; systemic lupus erythematosus, haemolytic uraemic syndrome; Sydenhamu2019s chorea; herpes gestationis; otosclerosis-related hearing loss.
In women with hereditary angioedema, exogenous oestrogens included in CONTREZIN may induce or exacerbate symptoms of angioedema.
Acute or chronic disturbances of liver function may necessitate the discontinuation of CONTREZIN until markers of liver function return to normal. Recurrence of cholestatic jaundice which first occurred during pregnancy or previous use of sex steroids necessitates the discontinuation of CONTREZIN . CONTREZIN may influence peripheral insulin resistance and glucose tolerance. Hence diabetic women should be carefully observed while taking CONTREZIN . Chloasma may occur, especially in women with a history of chloasma gravidarum. Women with a tendency to develop chloasma should avoid exposure to the sun or ultraviolet radiation whilst taking CONTREZIN .
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 healthcare provider in case of mood changes and depressive symptoms, including shortly after initiating treatment.
Worsening of epilepsy, of Crohn's disease and of ulcerative colitis has been reported during COCs use.
ALT elevations
During clinical trials with patients treated for hepatitis C virus infections (HCV) with the medicines 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 medicines such as CONTREZIN (see sections 4.3 and 4.5).

Interactions between CONTREZIN and other medicines may lead to breakthrough bleeding and/or contraceptive failure. The following interactions have been reported in the literature.
Hepatic metabolism:
Interactions can occur with medicines that induce microsomal enzymes, which can result in increased clearance of sex hormones (e.g. phenytoin, barbiturates, primidone, carbamazepine, rifampicin, and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin and products containing St Johnu2019s Wort). HIV protease (e.g. ritonavir) and non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine), and combinations of them, have been reported to potentially affect hepatic metabolism.
Enzyme inhibitors
Concomitant administration of strong CYP3A4 inhibitors can increase plasma concentrations of the oestrogen or the progestin or both. (e.g. ketoconazole, etoricoxib)
Other medicines
CONTREZIN may affect the metabolism of certain other medicines. Accordingly, plasma and tissue concentrations either increase (e.g. cyclosporine) or decrease (e.g. lamotrigine). Based on in vivo interaction studies in female patients using omeprazole, simvastatin or midazolam as marker substrate, an interaction of drospirenone at doses of 3 mg with the cytochrome P450 mediated metabolism of other medicines is unlikely. Clinical data suggests that ethinylestradiol is inhibiting the clearance of CYP1A2 substrates leading to a weak (e.g. theophylline) or moderate (e.g. tizanidine) increase in their plasma concentration.
Interference with enterohepatic circulation:
Enterohepatic circulation of oestrogens may decrease when certain antibiotic medicines are given, which may reduce ethinylestradiol concentrations (e.g. penicillins, tetracyclines). Women on treatment with any of these medicines should temporarily use a barrier method in addition to CONTREZIN or choose another method of contraception. With microsomal enzyme-inducing medicines, the barrier method should be used during the time of concomitant medicine administration and for 28 days after their discontinuation. Women on treatment with antibiotics (except rifampicin and griseofulvin) should use the barrier method until 7 days after discontinuation. If the period during which the barrier method is used runs beyond the end of the active tablets in the CONTREZIN pack, the inactive tablets should be omitted and the next pack of CONTREZIN should be started with the active tablets (i.e. without the usual inactive tablet interval).
Other interactions:
Concomitant use with the medicines 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, CONTREZIN -patients must switch to an alternative method of contraception (e.g., progestogen-only contraception or non-hormonal methods) prior to starting therapy with this combination regimen. CONTREZIN can be restarted 2 weeks following completion of treatment with this combination regimen.
In patients without renal insufficiency, the concomitant use of drospirenone and ACE-inhibitors or NSAIDs did not show a significant effect on serum potassium. Nevertheless, concomitant use of CONTREZIN with aldosterone antagonists or potassium-sparing diuretics has not been studied. In this case, serum potassium should be tested during the first treatment cycle.
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. Drospirenone causes an increase in plasma renin activity and plasma aldosterone induced by its mild antimineralocorticoid activity.

Women of Childbearing Potential
CONTREZIN is indicated for use by women of childbearing potential Refer to sections 4.1, 4.2, 4.3 and 4.4
Pregnancy
CONTREZIN is not indicated during pregnancy. If pregnancy occurs during treatment with CONTREZIN , further intake should be stopped.
Breastfeeding
The use of CONTREZIN is not recommended during breastfeeding. Small amounts of the contraceptive steroids and/or their metabolites may be excreted with the milk.
Fertility
CONTREZIN is a contraceptive. It is indicated for the prevention of pregnancy.

CONTREZIN can cause dizziness (see section 4.8) which may affect the ability to execute sound coordination and therefore influence the ability to drive and use machinery.

System Organ Class Frequent Less frequent Immune system disorders Asthma, hypersensitivity Psychiatric disorders Depressive mood Libido increased, libido decreased Nervous system disorders Headache
Ear and labyrinth Hypoacusis Vascular disorders Migraine Hypertension, hypotension, Venous thromboembolism (VTE), Arterial thromboembolism (ATE) Gastrointestinal disorders Nausea, abdominal pain vomiting, diarrhoea Skin and subcutaneous tissue disorders Acne, pruritus, eczema, alopecia, erythema nodosum, erythema multiforme, rash, urticaria Reproductive system and Menstrual disorders, breast enlargement, vaginitis,
breast disorders intermenstrual bleeding, breast pain, breast tenderness, leucorrhoea, vaginal moniliasis , unscheduled uterine bleeding, genital tract bleeding breast discharge General disorders and administration site conditions Increased weight fluid retention, body weight changes
The following side effects have been reported in women using CONTREZIN s, which are discussed under 4.4 Special warning and precautions for use:
- Venous thromboembolic disorders.
- Arterial thromboembolic disorders.
- Hypertension.
- Liver tumours.
- Occurrence or deterioration of conditions for which association with CONTREZIN use is not conclusive: Crohn's disease, ulcerative colitis, epilepsy, uterine myoma, porphyria, systemic lupus erythematosus, herpes gestationis, Sydenham's chorea, haemolytic uremic syndrome, cholestatic jaundice.
- Chloasma.
- Acute or chronic disturbances of liver function may necessitate the discontinuation of CONTREZIN use until markers of liver function return to normal.
- In women with hereditary angioedema exogenous oestrogens may induce or exacerbate symptoms of angioedema
The frequency of diagnosis of breast cancer is very slightly increased among CONTREZIN patients. As breast cancer is rare in women under 40 years of age the excess number is small in relation to the overall risk of breast cancer. Causation with CONTREZIN use is unknown. For further information, see sections 4.3 and 4.4.

Symptoms that may occur in case of taking an overdose of active tablets are nausea; vomiting; and, in young girls, slight vaginal bleeding. There are no antidotes and further treatment is symptomatic and supportive.