| The following information is principally based on studies in patients who used oral contraceptives with higher concentrations of estrogens and progestogens than those in common use today. The effect of long-term use of the oral contraceptives with lower concentrations of both estrogens and progestogens remains to be determined. The efficacy of any contraceptive method, except sterilisation, depends upon the reliability with which it is used. Correct and consistent use of such methods can result in lower failure rates. Thrombo-embolism An increased risk of thromboembolic disease (VTE) associated with the use of oral contraceptives is well established but is smaller than that associated with pregnancy, which has been estimated at 60 cases per 100,000 pregnancies. 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 or norethisterone (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 per year. The incidence in users of second generation pills is about 15 per 100,000 women per year of use. The incidence in 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 risk of venous thromboembolism is highest during the first year a combined oral contraceptive is taken. This increased risk applies to the first time ever combined oral contraceptive use is begun rather than each time a woman starts a new type of combined oral contraceptive. The level of all 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 suitability of combined oral contraceptives for patients with any of these risk factors should be discussed with the patient before a final decision is taken.The physician should be alert to the earliest manifestations of these disorders (thrombophlebitis, cerebrovascular disorders, pulmonary embolism and retinal thrombosis). Should any of these occur or be suspected, Loestrin should be discontinued immediately.Cigarette smoking increases the risk of serious cardiovascular side effects from oral contraceptive use. This risk increases with age and with heavy smoking (15 or more cigarettes a day) and is quite marked in women over 35 years of age. Women who use oral contraceptives should be strongly advised not to smoke.Hepatic tumours Benign hepatic tumours have been associated with oral contraceptive usage. Malignant hepatic tumours have also been reported on rare occasions in long term users of oral contraceptives. A hepatic tumour should be considered in the differential diagnosis when upper abdominal pain, enlarged liver or signs of intra-abdominal haemorrhage occur.Ovarian, endometrial, cervical and breast cancer Numerous 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 combined oral contraceptives offer substantial protection against both ovarian and endometrial cancer.An increased risk of cervical cancer in long term users of combined oral contraceptives has been reported in some studies, but there continues to be controversy about the extent to which this is attributable to the confounding effects of sexual behaviour and other factors.A 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 in those women who have 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 ten 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).Estimated cumulative numbers of breast cancers per 10,000 women diagnosed in 5 years of use and up to 10 years after stopping COCs, compared with numbers of breast cancers diagnosed in 10,000 women who had never used COCs Reasons for stopping Loestrin immediately 1) Occurrence of migraine in patients who have never previously suffered from it. Any unusually frequent or severe headaches.
2) Any kind of visual disturbance e.g. proptosis or diplopia and migraine.
3) Suspicion of thrombosis or infarction.
4) Combined oral contraceptives should be stopped at least six weeks before elective surgery and during and following prolonged immobilisation e.g. after accidents, etc.
5) Loestrin should be discontinued if the patient becomes jaundiced or has a significant rise in blood pressure.
6) Patients with a history of depression should be carefully observed and the drug discontinued if the depression recurs to a serious degree.
7) Since the safety of Loestrin in pregnancy has not been demonstrated, it is recommended that for any patient who has missed a period, the absence of pregnancy should be established before continuing the contraceptive regimen.
8) Clear exacerbation of conditions known to be capable of deteriorating during oral contraception or pregnancy.
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 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. In case of undiagnosed, persistent or recurrent abnormal vaginal bleeding, appropriate diagnostic measures should be conducted to rule out malignancy. Women with a strong family history of breast cancer or who have breast nodules should be monitored with particular care.Estrogen-progestogen preparations should be used with caution in patients with a history of hypertension and some women experience an increase in blood pressure following the administration of contraceptive steroids. Pregnancy should be excluded before starting treatment. Because these agents may cause some degree of fluid retention, patients with conditions which might be influenced by this such as epilepsy, migraine, asthma, and cardiac or renal dysfunction should be carefully monitored.A decrease in glucose tolerance has been observed in a significant percentage of patients on oral contraceptives. The mechanism of this decrease is obscure. For this reason, pre-diabetic and diabetic patients should be carefully observed whilst receiving Loestrin.Under the influence of estrogen-progestogen preparations, pre-existing uterine fibroleiomyomata may increase in size. Loestrin may mask the onset of the climacteric.The following conditions also require careful consideration: multiple sclerosis, porphyria, tetany, disturbed liver function, gallstones, cardiovascular disease, renal disease, chloasma or any disease that is prone to worsen during pregnancy. The deterioration or first appearance of any of these conditions may indicate that the oral contraceptive should be stopped. Contact lens wearers who develop visual changes or changes to lens tolerance should be assessed by an optometrist.Interference with laboratory tests The following laboratory results may be altered by the use of oral contraceptives: hepatic function (increased sulpho-bromophthalein retention and other tests); thyroid function (increased thyroid binding globulin (TBG) leading to increased circulating total thyroid hormone as measured by protein-bound iodine (PBI), T4 by column or by radioimmunoassay. Free T3 resin uptake is decreased, reflecting the elevated TBG. Free T4 concentration is unaltered); haematological tests (increased prothrombin and factors VII, VIII, IX and X, decreased antithrombin 3 and increased adrenaline induced platelet aggregation); measurement of pregnanediol excretion (reduced). Other binding proteins may be elevated in the serum, sex-binding globulins are increased, triglycerides may be increased and serum folate levels may be depressed. Therefore, if such tests are abnormal in a patient taking Loestrin, it is recommended that they be repeated after Loestrin has been withdrawn for two months. The pathologist should be advised of the administration of Loestrin when relevant specimens are submitted. Any influence of prolonged administration of Loestrin on pituitary, ovarian, adrenal, hepatic and uterine functions is unknown at present. | |