|Medical ExaminationAssessment of women prior to starting oral contraceptives (and at regular intervals thereafter) should include a personal and family medical history of each woman. Physical examination should be guided by this and by the contraindications (section 4.3) and warnings (section 4.4) for this product. The frequency and nature of these assessments should be based upon relevant guidelines and should be adapted to the individual woman, but should include measurement of blood pressure and, if judged appropriate by the clinician, breast, abdominal and pelvic examination including cervical cytology. Undiagnosed vaginal bleeding that is suspicious for underlying conditions should be investigated.Exclude the likelihood of pregnancy before starting treatment.|
Warnings:Women should be advised that oral contraceptives do not protect against HIV infections (AIDS) and other sexually transmitted diseases.
Conditions which require strict medical supervision The decision to prescribe the COC must be made using clinical judgement and in consultation with the woman. Exacerbation or first appearance of any of these conditions may indicate that use of the oral contraceptive should be discontinued: • Diabetes mellitus with mild vascular disease or mild nephropathy, retinopathy or neuropathy• Hypertension that is adequately controlled, i.e. systolic >140 to159 mm Hg or diastolic > 90 to 94mmHg (see also Section 4.4 'Reasons for stopping oral contraception immediately') • porphyria• obesity• migraine• cardiovascular diseases
Reasons for stopping oral contraception immediately:When stopping oral contraception non-hormonal contraception should be used to ensure contraceptive protection is maintained.1. Occurrence for the first time, or exacerbation, of migrainous headaches or unusually frequent or unusually severe headaches2. Sudden disturbances of vision, of hearing or other perceptual disorders3. First signs of thrombosis or blood clots (e.g. unusual pains in or swelling of the leg(s), stabbing pains on breathing or coughing for no apparent reason). Feeling of pain and tightness in the chest4. Six weeks before an elective major operation (e.g. abdominal, orthopaedic), any surgery to the legs, medical treatment for varicose veins or prolonged immobilisation, e.g. after accidents or surgery. Do not restart until 2 weeks after full ambulation. In case of emergency surgery, thrombotic prophylaxis is usually indicated e.g. subcutaneous heparin5. Onset of jaundice, hepatitis, itching of the whole body6. Significant rise in blood pressure 7. Severe upper abdominal pain or liver enlargement8. Clear exacerbation of conditions known to be capable of deteriorating during oral contraception or pregnancy (see section 4.4 'Conditions which deteriorate in pregnancy or during previous COC use' under 'Other conditions')
Circulatory Disorders • Venous thromboembolismSome epidemiological studies have suggested an association between the use of combined oral contraceptives (COCs) and an increased risk of arterial and venous thrombotic and thromboembolic diseases such as myocardial infarction, stroke, deep venous thrombosis and pulmonary embolism. These events occur rarely. Full recovery from such disorders does not always occur, and it should be realised that in a few cases they are fatal.The use of any combined oral contraceptive carries an increased risk of venous thromboembolism (VTE) compared with no use. The excess risk of VTE is highest during the first year a woman ever uses a combined oral contraceptive. This increased risk is less than the risk of VTE associated with pregnancy which is estimated as 60 cases per 100 000 pregnancies. Venous thromboembolism is fatal in 1-2% of cases.Some epidemiological studies have reported a greater risk of VTE for women using combined oral contraceptives containing desogestrel or gestodene (the so-called third generation pills) than for women using pills containing levonorgestrel (the so-called second generation pills).The spontaneous incidence of VTE in healthy non-pregnant women (not taking any oral contraceptive) is about 5 cases per 100,000 women per year. The incidence in users of second generation pills is about 15 per 100,000 women per year of use. The incidence in users of third generation pills is about 25 cases per 100,000 women per year of use; this excess incidence has not been satisfactorily explained by bias or confounding. The level of all of these risks of VTE increases with age and is likely to be further increased in women with other known risk factors for VTE such as obesity.The risk of VTE increases with:• age; • obesity (body mass index over 30 kg/m2); • a personal or family history (i.e. venous thromboembolism ever in a sibling or parent at a relatively early age). If a hereditary or acquired predisposition is suspected, the woman should be referred to a specialist for advice before deciding about any COC use (see section 4.4 for further information on biochemical factors under 'Other factors affecting circulatory events'); • prolonged immobilisation, major surgery, any surgery to the legs, or major trauma. In these situations it is advisable to discontinue COC use (in the case of elective surgery at least six weeks in advance) and not to resume until two weeks after complete remobilisation. There is no consensus about the possible role of varicose veins and superficial thrombophlebitis in venous thromboembolism.The increased risk of thromboembolism in the puerperium must be considered (for information on Pregnancy and Lactation see Section 4.6).Common signs/symptoms of VTE include:• severe pain in the calf of one leg; swelling of the lower leg• sudden breathlessness, chest pain.• Arterial thromboembolic-related conditionsThe use of a combined oral contraceptive may also increase the risk of conditions such as stroke and myocardial infarction which are secondary to arterial thromboembolic events. Other risk factors for arterial thromboembolism include:• age• smoking (with heavier smoking and increasing age the risk further increases, especially in women over 35 years of age)• a positive family history (i.e., venous or arterial thromboembolism ever in a sibling or parent at a relatively early age). If a hereditary or acquired predisposition is suspected, the woman should be referred to a specialist for advice before deciding about any COC use• obesity (body mass index over 30 kg/m2)• dyslipoproteinaemia• hypertension• valvular heart disease• atrial fibrillation• migraine. An increase in frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event) may be a reason for immediate discontinuation of the COC Common signs/symptoms associated with arterial thromboembolism include:• sudden severe pain in the chest, whether or not reaching to the left arm; • any unusual severe, prolonged headache, especially if it occurs for the first time or gets progressively worse, or is associated with any of the following symptoms: • sudden partial or complete loss of vision or diplopia;• aphasia;• vertigo;• collapse with or without focal epilepsy;• weakness or very marked numbness suddenly affecting one side or one part of the body.• Other factors affecting circulatory events Other medical conditions which have been associated with adverse circulatory events include diabetes mellitus, systemic lupus erythematosus, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) sickle cell disease.Biochemical factors that may be indicative of hereditary or acquired predisposition for venous or arterial thrombosis include Activated Protein C (APC) resistance, hyperhomocysteinaemia, antithrombin-III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).When considering risk/benefit, the physician should take into account that adequate treatment of a condition may reduce the associated risk of thrombosis and that the risk associated with pregnancy is higher than that associated with COC use.TumoursNumerous epidemiological studies have been reported on the risks of ovarian, endometrial, cervical and breast cancer in women using combined oral contraceptives. The evidence is clear that high dose combined oral contraceptives offer substantial protection against both ovarian and endometrial cancer. However, it is not clear whether low dose COCs confer protective effects to the same level.• Breast cancerA 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 combined oral contraceptives (COCs). 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. The additional breast cancers diagnosed in current users of COCs or in women who have used COCs in the last ten years are more likely to be localised to the breast than those in women who never used COCs.Breast cancer is rare among women under 40 years of age whether or not they take COCs. Whilst this background risk increases with 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 (see bar chart).The most important risk factor for breast cancer in COC users is the age women discontinue the COC; the older the age at stopping, the more breast cancers are diagnosed. Duration of use is less important and the excess risk gradually disappears during the course of the 10 years after stopping COC use such that by 10 years there appears to be no excess.The possible increase in risk of breast cancer should be discussed with the user and weighed against the benefits of COCs taking into account the evidence that they offer substantial protection against the risk of developing certain other cancers (e.g. ovarian and endometrial cancer).• Cervical CancerThe most important risk factor for cervical cancer is persistent HPV infection. Some epidemiological studies have indicated that long-term use of COCs may further contribute to this increased risk but there continues to be controversy about the extent to which this finding is attributable to confounding effects, e.g., cervical screening and sexual behaviour including use of barrier contraceptives.• Liver CancerIn rare cases benign and, in even rarer cases, malignant liver tumours leading in isolated cases to life-threatening intraabdominal haemorrhage have been observed after the use of hormonal substances such as those contained in Femodette. If severe upper abdominal complaints, liver enlargement or signs of intra-abdominal haemorrhage occur, the possibility of a liver tumour should be included in the differential diagnosis.
Other conditionsThe possibility cannot be ruled out that certain chronic diseases may occasionally deteriorate during the use of combined oral contraceptives • Known hyperlipidaemiasWomen with hypertriglyceridemia, or a family history thereof, may be at an increased risk of pancreatitis when using COCs.Women with hyperlipidaemias are at an increased risk of arterial disease (see section 4.4 'Circulatory disorders'). However routine screening of women on COCs is not appropriate.• Blood pressureHypertension is a risk factor for stroke and myocardial infarction (see section 4.4 'Arterial thromboembolic-related conditions'). Although small increases in blood pressure have been reported in many women taking COCs, clinically relevant increases are rare. However, if sustained hypertension develops during the use of a COC, antihypertensive treatment should normally be instigated at a level of 160/100 mm Hg in uncomplicated patients or at 140/90 mm Hg in those with target organ damage, established cardiovascular disease, diabetes or with increased cardiovascular risk factors. Decisions about the continued use of the COC should be made at lower BP levels, and alternative contraception may be advised.• Conditions which deteriorate in pregnancy or during previous COC useThe following conditions have been reported to occur or deteriorate with both pregnancy and COC use. Consideration should be given to stopping Femodette if any of the following occur during use:
• Disturbances of liver functionAcute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal.• Diabetes (without vascular involvement)Insulin-dependent diabetics without vascular disease can use COCs. However it should be remembered that all diabetics are at an increased risk of arterial disease and this should be considered when prescribing COCs. Diabetics with existing vascular disease are contraindicated from using COCs (see section 4.3 Contraindications).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 COCs.• ChloasmaChloasma 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.• Menstrual ChangesReduction of menstrual flow: This is not abnormal and it is to be expected in some patients. Indeed, it may be beneficial where heavy periods were previously experienced.Missed menstruation: Occasionally, withdrawal bleeding may not occur at all. If the tablets have been taken correctly, pregnancy is very unlikely. If withdrawal bleeding fails to occur at the end of a second pack, the possibility of pregnancy must be ruled out before resuming with the next pack.Intermenstrual bleeding: 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 three cycles. 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. This may include curettage.Some women may experience amenorrhoea or oligomenorrhoea after discontinuation of oral contraceptives, especially when these conditions existed prior to use. Women should be informed of this possibility.• Lactose and Sucrose IntoleranceEach tablet of this medicinal product contains 37.155 mg lactose and 19.660 mg sucrose per tablet. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, fructose intolerance or glucose-galactose malabsorption or sucrase-isomaltase should not take this medicine.
| ||• jaundice and/or pruritus related to cholestasis • COCs may increase the risk of gallstone formation and may worsen existing disease • systemic lupus erythematosus • herpes gestationis • otosclerosis-related hearing loss • sickle cell• anaemia• renal dysfunction• hereditary angioedema • any other condition an individual woman has experienced worsening of during pregnancy or previous use of COCs.