- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6. Pregnancy and lactation.
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
Changing from a combined Every Day pill (28 day tablets):Femodette should be started after taking the last active tablet from the Every Day Pill pack. The first Femodette tablet is taken the next day. Additional contraceptive precautions are not then required.
Changing from a progestogen-only pill (POP):The first tablet of Femodette should be taken on the first day of bleeding, even if a POP has already been taken on that day. Additional contraceptive precautions are not then required. The remaining progestogen-only pills should be discarded.Post-partum and post-abortum use: After pregnancy, oral contraception can be started 21 days after a vaginal delivery, provided that the patient is fully ambulant and there are no puerperal complications. Additional contraceptive precautions will be required for the first 7 days of pill taking. Since the first post-partum ovulation may precede the first bleeding, another method of contraception should be used in the interval between childbirth and the first course of tablets. After a first-trimester abortion, oral contraception may be started immediately in which case no additional contraceptive precautions are required.
Special circumstances requiring additional contraceptionIncorrect administration: A single delayed tablet should be taken as soon as possible, and if this can be done within 12 hours of the correct time, contraceptive protection is maintained. With longer delays, additional contraception is needed. Only the most recently delayed tablet should be taken, earlier missed tablets being omitted, and additional non-hormonal methods of contraception (except the rhythm and temperature methods) should be used for the next 7 days, while the next 7 tablets are being taken. Additionally, therefore, if tablet(s) have been missed during the last 7 days of a pack, there should be no break before the next pack is started. In this situation, a withdrawal bleed should not be expected until the end of the second pack. Some breakthrough bleeding may occur on pill taking days but this is not clinically significant. If the patient does not have a withdrawal bleed during the tablet-free interval following the end of the second pack, the possibility of pregnancy must be ruled out before starting the next pack.Gastro-intestinal upset: Vomiting or diarrhoea may reduce the efficacy of oral contraceptives by preventing full absorption. If vomiting or diarrhoea occurs within 4 hours of taking Femodette tablet-taking from the current pack should be continued. Additional non-hormonal methods of contraception (except the rhythm or temperature methods) should be used during the gastro-intestinal upset and for 7 days following the upset. If these 7 days overrun the end of a pack, the next pack should be started without a break. In this situation, a withdrawal bleed should not be expected until the end of the second pack. If the patient does not have a withdrawal bleed during the tablet-free interval following the end of the second pack, the possibility of pregnancy must be ruled out before starting the next pack. Other methods of contraception should be considered if the gastro-intestinal disorder is likely to be prolonged.Children: Not applicable.Elderly: Not applicable.
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 supervisionThe 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:
|• 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.|
Hepatic enzyme inducersDrugs which induce hepatic enzymes (especially cytochrome P450 3A4) increase the metabolism of contraceptive steroids and hence may result in breakthrough bleeding and pregnancy. The following have been shown to have clinically important interactions with COCs:
Antiretroviral agents• ritonavir;• nelfinavir;• nevirapine.
Anticonvulsants• barbiturates (including phenobarbitone);• primidone;• phenytoin;• carbamazepine;• oxcarbazepine;• topiramate.
Antibiotics/antifungals• griseofulvin;• rifampacin.
Herbal remedies• St John's wort (Hypericum perforatum)
Managing interactions with hepatic enzyme inducersSince interactions of enzyme inducers, including the antibiotics rifampicin and griseofulvin, with oral contraceptives may lead to breakthrough bleeding and/or contraceptive failure the following precautions are recommended:Women on short term treatment with any of these drugs should temporarily use a barrier method in addition to the COC or choose another method of contraception. With microsomal enzyme-inducing drugs, such as rifampicin and griseofulvin, the barrier method should be used during the time of concomitant drug administration and for 28 days after their discontinuation. For women receiving long-term therapy with hepatic enzyme inducers, another method of contraception should be used.
Non-enzyme inducing antibioticsSome clinical reports suggest that enterohepatic circulation of oestrogens may decrease when certain antibiotic agents are given, which may reduce ethinylestradiol concentrations (e.g. penicillins, tetracyclines).
Managing interactions with non-enzyme inducing antibioticsSince interactions of some antibiotics with oral contraceptives may lead to breakthrough bleeding and/or contraceptive failure the following precautions are recommended:Women on short term treatment with antibiotics (except rifampicin and griseofulvin) should temporarily use a barrier method in addition to the COC or choose another method of contraception. If the barrier method is chosen it should be used until 7 days after discontinuation of the antibiotics. If these 7 days overrun the end of a pack, the next pack should be started without a break. In this situation, a withdrawal bleed should not be expected until the end of the second pack. If the patient does not have a withdrawal bleed during the tablet-free interval following the end of the second pack, the possibility of pregnancy must be ruled out before resuming with the next pack.
Effects on other drugsOral contraceptives may affect the metabolism of certain other drugs. Accordingly, plasma and tissue concentrations may either increase (e.g. cyclosporin) or decrease (e.g. lamotrigine).Note: The prescribing information of concomitant medications should be consulted to identify potential interactions.• Laboratory testsThe use of oral contraceptives may influence the results of certain laboratory tests including biochemical parameters of liver, thyroid, adrenal and renal function, plasma levels of carrier proteins and lipid/lipoprotein fractions, parameters of carbohydrate metabolism and parameters of coagulation and fibrinolysis. Laboratory staff should therefore be informed about oral contraceptive use when laboratory tests are requested.
|System Organ Class||Adverse events reported in clinical trials||Adverse events reported post marketing|
|Common(≥1/100)||Uncommon (≥ 1/1000, <1/100)||Rare (< 1/1000)|
|Eye disorders||contact lens intolerance|
|Gastrointestinal disorders||nausea, abdominal pain||vomiting, diarrhea|
|Immune system disorders||hypersensitivity||exacerbation of hereditary angioedema|
|Investigations||weight increased||weight decreased|
|Metabolism and nutrition disorders||fluid retention||Hypertriglyceridemia, changes in glucose tolerance or effect on peripheral insulin resistance|
|Nervous system disorders||headache||migraine|
|Hepatobiliary disorders||liver function disturbances|
|Psychiatric disorders||depressed mood, mood altered||libido decreased||libido increased|
|Reproductive system and breast disorders||breast pain, breast tenderness||breast hypertrophy||vaginal discharge, breast discharge||reduced menstrual flow, spotting, breakthrough bleeding and missed withdrawal bleeding, post pill amenorrhoea|
|Skin and subcutaneous tissue disorders||rash, urticaria||erythema nodosum, erythema multiforme||chloasma,|
Conditions reported to deteriorate with pregnancy or previous COC use• Jaundice and/or pruritus related to cholestasis; gallstone formation; systemic lupus erythematosus; exacerbation of chorea, herpes gestationis; otosclerosis-related hearing loss; Crohn's disease, ulcerative colitis, sickle cell anaemia; renal dysfunction; hereditary angioedema; porphyria; cervical cancer.
Primary containers:The blister packs consist of hard tempered aluminium foil of thickness 20µm and transparent PVC film of thickness 250µm.Presentation:Blister calendar pack contaiing 21 tablets.
Bayer House, Strawberry Hill, Newbury, Berkshire, RG14 1JA
+44 (0)1635 563 393
+44 (0)1635 563 000