| There is a general opinion, based on statistical evidence, that users of combined oral contraceptives (ie oestrogen plus progestogen) experience more often than non-users various disorders of the circulation of blood, including strokes (blood clots in, and haemorrhages from, the blood vessels of the brain), heart attacks (coronary thromboses) and blood clots obstructing the arteries of the lungs (pulmonary emboli). There may not be a full recovery from such disorders and it should be realised that in a few cases they may be fatal.To date no association between these disorders and progestogen-only oral contraceptives (such as Micronor Oral Contraceptive Tablets) has been shown. However there is a risk that the users of such progestogen only oral contraceptives will (like users of the combined oral contraceptive) be exposed to an increased risk of suffering from these disorders.Assessment 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 contra-indications (Section 4.3) and warnings 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.Exclude likelihood of pregnancy before starting treatment.In case of undiagnosed, persistent or recurrent abnormal vaginal bleeding, appropriate measures should be conducted to rule out malignancy.Oral contraceptives DO NOT protect against HIV infections (AIDS) or any other sexually transmitted disease.Because of a possible increased risk of post surgery thrombo-embolic complications in oral contraceptive users, therapy should be discontinued six weeks prior to elective surgery.When Micronor is administered during the post-partum period, the increased risk of thrombo-embolic disease associated with the post-partum period must be considered. Conditions requiring supervision The theoretical or proven risks usually outweigh the advantages of using POPs in the conditions listed below. Consequently the decision to prescribe the POP must be made with specialist clinical judgement and in consultation with the individual patient.• A history of breast cancer with no evidence of disease in the last 5 years• Severe decompensated cirrhosis• Liver tumours (benign and malignant)• Acute or chronic hepatocellular disease with abnormal liver function• Systemic Lupus Erythematosus (SLE) with antiphospholipid antibodies• Current or history of ischaemic heart disease• History of cerebrovascular accidents, including transient ischaemic attacks• PorhyriaThe worsening or first appearance of any of these conditions may indicate that Micronor should be discontinued.Ectopic pregnancy The incidence of ectopic pregnancies for progestogen-only oral contraceptive users is 5 per 1000 woman-years, which is higher than for women using other contraceptive methods but similar to the incidence for women not using any contraception. Up to 10% of pregnancies reported in clinical studies of progestogen-only oral contraceptive users are extrauterine. Although symptoms of ectopic pregnancy should be watched for, a history of ectopic pregnancy need not be considered a contraindication to use of this contraceptive method. Vaginal bleeding and abdominal pain are typical symptoms of an ectopic pregnancy. Women reporting these symptoms should be evaluated.Carcinomas Numerous epidemiological studies have been performed on the incidence of breast, endometrial, ovarian and cervical cancer in women using oral contraceptives. Breast cancer A meta-analysis from 54 epidemiological studies reported that there is a slightly increased relative risk of having breast cancer diagnosed in women who are currently using oral contraceptives (OCs). The observed pattern of increased risk may be due to an earlier diagnosis of breast cancer in OC users, the biological effects of OCs or a combination of both. The additional breast cancers diagnosed in current users of OCs or in women who have used OCs in the last 10 years are more likely to be localised to the breast than those in women who have never used OCs.Breast cancer is rare among women under 40 years of age whether or not they take OCs. Whilst the background risk increases with age, the excess number of breast cancer diagnoses in current and recent progesterone-only pill (POP) users is small in relation to the overall risk of breast cancer, possibly of similar magnitude to that associated with combined OCs. However, for POPs, the evidence is based on much smaller populations of users and so is less conclusive than that for combined OCs.The most important risk factor for breast cancer in POP users is the age women discontinue the POP; 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 POP use, such that by 10 years there appears to be no excess.The evidence suggests that compared with never-users, among 10,000 women who use POPs for up to five years but stop by age 20, there would be much less than one extra case of breast cancer diagnosed up to 10 years afterwards. For those stopping by age 30 after 5 years use of the POP, there would be an estimated 2-3 extra cases (additional to the 44 cases of breast cancer per 10,000 women in this age group never exposed to oral contraceptives). For those stopping by age 40 after 5 years use, there would be an estimated 10 extra cases diagnosed up to 10 years afterwards (additional to the 160 cases of breast cancer per 10,000 never-exposed women in this age group).It is important to inform patients that users of all contraceptive pills appear to have a small increase in the risk of being diagnosed with breast cancer, compared with non-users of oral contraceptives, but that this has to be weighed against the known benefits.Cervical cancer Some studies suggest that oral contraceptive use has been associated with an increase in the risk of cervical intraepithelial neoplasia in some populations of women. However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behaviour and other factors. There is insufficient data to determine whether the use of POPs increases the risk of developing cervical intraepithelial neoplasia.Hepatic neoplasia Malignant hepatic tumours have been reported on rare occasions in long-term users of oral contraceptives. Benign hepatic tumours have also been associated with oral contraceptive use. A hepatic tumour should be considered in the differential diagnosis when upper abdominal pain, enlarged liver or signs of intra-abdominal haemorrhage occur.Carbohydrate and lipid metabolism Carbohydrate changes in healthy individuals from clinical studies are mixed. Most studies show no effect, but in some studies there is a suggestion of slight deterioration in glucose tolerance and elevation in plasma insulin concentration. From the limited data on POPs in diabetic women, no increase in insulin dose was required.Delayed follicular atresia/ovarian cysts If follicular development occurs, atresia of the follicle is sometimes delayed, and the follicle may continue to grow beyond the size it would attain in a normal cycle. Generally these enlarged follicles disappear spontaneously. Often they are asymptomatic; in some cases they are associated with mild abdominal pain. Rarely they may twist or rupture, requiring surgical intervention.Bleeding irregularities Irregular menstrual patterns are common among women using progestogen-only oral contraceptives. If genital bleeding is suggestive of infection, malignancy or other abnormal conditions, such non-pharmacologic causes should be ruled out. If prolonged amenorrhea occurs, the possibility of pregnancy should be evaluated.Headache The onset or exacerbation of migraine or development of headache with a new pattern, which is recurrent, persistent or severe, requires discontinuation of oral contraceptives and evaluation of the cause should be considered.Other conditions and warnings In the following conditions the benefit of oral contraception generally outweighs the theoretical or known risk. However, they may need to be considered before prescribing to individual patients or continuing treatment if they arise:• Multiple risk factors for cardiovascular disease (including older age, smoking, diabetes, hypertension and obesity)• Vascular disease (including coronary heart disease with angina, peripheral vascular disease with intermittent claudication, hypertensive retinopathy)• History of venous thrombo-embolism (VTE) or current VTE• Major surgery with prolonged immobilisation• Known thrombogenic mutations (such as Factor V Leiden, Prothrombin mutation, Protein S, Protein C and Antithrombin deficiencies• Migraine with or without focal aura at any age or a past history ( 5 years ago). The onset or exacerbation of migraine or development of headache with a new pattern which is recurrent, persistent or severe requires evaluation of the cause• Carriers of known gene mutations associated with breast cancer (e.g. BRCA1)• Diabetes with or without vascular involvement (although all patients with diabetes are at increased risk of arterial disease)• Known hyperlipidaemias. However, routine screening of women with is not considered appropriate• Gall bladder disease • History of cholestasis related to past COC use• Benign liver tumour (focal nodular hyperplasia)• Inflammatory bowel disease (including Crohn's disease and ulcerative colitis)• Raynaud's disease secondary with Systemic Lupus Erythematosus (SLE) if lupus anticoagulant is present.Laboratory tests Certain endocrine and liver function tests and blood components may be affected by progestogen-only oral contraceptive use:• Sex hormone-binding globulin (SHBG) concentrations may be decreased• Thyroxine concentrations may be decreased, due to a decrease in thyroid binding globulin (TBG).Excipients The tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. | |
