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Oral contraceptives are contra-indicated in patients with recurrent cholestatic jaundice, or markedly impaired liver function, hormone-dependent neoplasms, thrombophlebitis, or thromboembolic disorders, or a history thereof, severe migraine, cerebrovascular insufficiency, coronary-artery disease, and undiagnosed abnormal vaginal bleeding. Medication should be discontinued immediately if migraine becomes focal or there is a loss of vision, or if there is an onset of unexplained chest pain. |
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Known or suspected carcinoma of the breast. |
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Known or suspected oestrogen-dependent neoplasia. |
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Benign or malignant liver tumour which developed during the use of oral contraceptives or other oestrogen containing products, or a history thereof. |
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Combined oral contraceptives should be avoided in known or suspected pregnancy. |
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Severe disturbances of liver function; a history of idiopathic jaundice of pregnancy or severe pruritis of pregnancy; Dubin-Johnson syndrome; Rotor syndrome. |
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Disturbances of lipometabolism. |
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A history of herpes of pregnancy. |
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Severe diabetes with vascular changes. |
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Otosclerosis with deterioration during pregnancies. |
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Relative contra-indications include a history of diabetes mellitus, epilepsy, asthma, hypertension, depression, porphyria, or states in which fluid retention occur. |
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For Contraception: |
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To achieve maximum contraceptive effectiveness, MINULETTE must be taken as directed and at intervals not exceeding 24 hours. Patients should be instructed to take the tablets at the same time every day, preferably after the evening meal or at bedtime. On the first day of the menstrual cycle, i.e. the first day of bleeding, the patient will take the first tablet marked with the appropriate day of the week from those in the red area of the package. Thereafter, one tablet is taken daily following the arrows on the package, until all 28 tablets have been taken. Withdrawal bleeding should usually occur within 2 to 4 days after the last active tablet is taken. During this first cycle, a mechanical method of contraception should be supplemented until 14 tablets have been taken. If the tablets are begun after Day 5, it must be considered that ovulation and conception may have occurred before the tablets were started. |
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The next and all subsequent courses of MINULETTE will begin on the day after the last package was completed, even if withdrawal bleeding has not occurred or is still in progress. Each course of MINULETTE is thus begun on the same day of the week as the first course, with a tablet from the red area of the package. |
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The patient who is changing from another oral contraceptive product will begin MINULETTE on day 1 of the next menstrual period. If more than seven days elapse before MINULETTE is begun, pregnancy must first be excluded. During the first MINULETTE cycle, a mechanical, i.e. barrier, method of contraception should be used until 14 consecutive daily tablets have been taken. |
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If transient spotting or breakthrough bleeding occurs, the patient is instructed to continue the regimen since such bleeding is usually without significance. If the bleeding is persistent or prolonged, the patient is advised to consult her physician. |
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MINULETTE can be prescribed postpartum or postabortum as soon as the first normal menstrual period following a normal biphasic cycle occurs. If a further pregnancy is contra-indicated for medical reasons, medication with MINULETTE must be initiated by the 12th (but not the 7th) day postpartum, or immediately postabortum or by the 5th day postabortum at the latest. |
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The most serious adverse reactions associated with the use of oral contraceptives are indicated under “Warnings”and “Precautions”. The following side-effects were reported in clinical trials of MINULETTE: | |
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Vomiting |
Nervousness | |
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Spotting |
Depressive moods | |
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Breakthrough bleeding |
Change in libido | |
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Dysmenorrhoea |
Varicose complaints | |
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Breast tension |
Oedema | |
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The following side-effects have been reported less frequently: | |
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Chloasma |
Galactorrhoea | |
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Gastritis |
Mastopathy | |
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Abdominal complaints |
Paraesthesia | |
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Alopecia |
Insomnia | |
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Vaginal discharge |
Flush | |
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Aggressive behaviour |
Tiredness | |
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Increased appetite | |
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Androgenic symptoms | |
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Amenorrhoea, hypomenorrhoea, | |
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and metrorrhagia | |
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The following have been reported in users of oral contraceptives and should be considered potential side-effects of MINULETTE : | |
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Change in cervical erosion or cervical secretion; | |
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Intolerance to contact lenses. | |
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The following adverse reactions have been reported in users of oral contraceptives, but the association has been neither confirmed nor refuted: | |
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Chorea |
Porphyria |
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Hirsutism | |
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The incidence of diseases of the circulatory system in women using combined oral contraceptives is significantly greater than those of controls, and the mortality is slightly increased. Coronary thrombosis, cerebrovascular accidents and venous thrombosis, are more likely to occur in women aged 35 years or over, particularly if they have used the contraceptive for longer than five years, if they smoke, if they are obese or if they are hypertensive. Additional risk factors are diabetes, hypercholesterolaemia and familial hyperlipoproteinaemia. | |
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However, the risk of mortality due to oral contraceptives in women under 35 who are in the high risk group is in general far less than the risk of mortality due to pregnancy. | |
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Hypertension may occur in association with the use of oral contraceptives. Regular blood pressure checks, including a pretreatment level, are advisable. | |
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Prolonged amenorrhoea following the use of oral contraceptives may occur. The incidence is in the order of 1 % of users. Caution should be advised where oligomenorrhoea or amenorrhoea have occurred in the past. | |
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Mood changes, mass gain, skin pigmentation, vaginal candidiasis, gall bladder disease, gastro-intestinal irritation and fluid retention may occur. | |
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Case reports have been published of benign hepatic tumours in women on oral contraceptives for a prolonged time, but a causal relationship has not been established. The preparation should be discontinued it persistent upper abdominal pain develops. | |
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Interactions with other medicines and efficacy: | |
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Oral contraceptive failure may occur with concomitant antibiotic therapy. For maximal protection, additional non-hormonal contraception should be recommended for the duration of antibiotic: therapy and for seven days afterwards. Those on long term antibiotic therapy need only take extra precautions for the first two weeks of antibiotic therapy. | |
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Spotting and breakthrough bleeding are possible signs of diminished contraceptive effectiveness. | |
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Induction of the microsomal liver enzyme system may occur and thus accelerate the oxidative degeneration of, among other things, sex hormones. Of particular clinical relevance are potent enzyme inducers such as barbiturates, hydantoins, phenylbutazone, and rifampicin, since both cycle disturbances (increased rate of intermenstrual bleeding and amenorrhoea) and individual pregnancies have been recorded under their concurrent use. | |
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Reports have also been made of reduced substance levels under the simultaneous use of certain antibiotics (e.g., ampicillin). | |
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An interaction should be considered in particular when intermenstrual bleeding suddenly occurs under oral ovulation inhibitors. An additional, non-hormonal method of contraception (with the exception of the rhythm and temperature methods) is recommended, if the greatest possible protection against pregnancy must be ensured in such cases. An alternative method of contraception should be considered if enzyme-inducing preparations must be administered for a protracted period of time. The efficacy of the contraceptive pill may be decreased when it is administered concomitantly with other medicines such as anti-epileptic agents, rifampicin, phenylbutazone and ampicillin. Patients should be carefully monitored for a decreased response to these drugs. | |
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Combination oral contraceptives have been reported to antagonize the effectiveness of oral anticoagulants, antihypertensive agents, anticonvulsants, and hypoglycaemic agents. Oral contraceptives may interfere with the oxidative metabolism of diazepam and chlordiazepoxide, resulting in plasma accumulation of the parent compound. Patients receiving these benzodiazepines on a long term basis should be monitored for increased sedative effects. The effects of benzodiazepines on oral contraceptive metabolism have not been determined. | |
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Oestrogen therapy may decrease the antidepressant response to tricyclic antidepressants and increase their incidence of toxic side-effects. | |
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Oestrogens may enhance the effects of glucocorticoids. | |
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Effects on laboratory tests: | |
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Oestrogen-containing preparations can effect many laboratory tests. Some examples are: | |
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Increased prothrombin and Factors VII, VIII, IX and X; decreased anti-thrombin 3; increased norepinephrine induced platelet aggregability; | |
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Increased thyroid-binding globulin (TBG) leading to increased circulating total-thyroid hormone, as measured by protein-bound iodine (PBI), T4 by radio immunoassay. Free T3 resin uptake is decreased, reflecting the elevated TBG; free T4 concentration is unaltered. | |
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Reduced response to metyrapone test. | |
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The results of these tests should not be regarded as reliable until oral contraceptive use has been discontinued for 1 to 2 months. Abnormal tests should then be repeated. | |
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Oral contraceptives may produce false positive results when neutrophil alkaline phosphate activity is evaluated for the early diagnosis of pregnancy. | |
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Surgery is more likely to be associated with an increased incidence of thrombotic side-effects. Adequate precaution should be taken. | |
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A thorough history and physical examination should be performed before prescribing oral contraceptives and periodically during their administration. Special attention should be given to blood pressure, breasts, abdomen and pelvic organs. |
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Oral contraceptives may cause depressive moods. Patients with a history of mental depression should be carefully observed and the drug discontinued if depression recurs to a serious degree. |
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These agents may cause a degree of fluid retention. Women with cardiac or renal dysfunction, or asthma, require careful observation since these conditions may be exacerbated by the fluid retention, which may occur in oral contraceptive users. |
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Users of oral contraceptives may have disturbances in normal tryptophan metabolism which may result in a relative pyridoxine deficiency. The clinical significance of this is yet to be determined. |
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Serum folate levels may be depressed by oral contraceptive use. Women who become pregnant shortly after discontinuing these drugs may have a greater chance of developing folate deficiency and its complications. |
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Laboratory tests: |
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Papanicolaou smears should be performed before prescribing these drugs and periodically during their administration. Baseline and periodic blood glucose determinations should be performed in patients predisposed to diabetes mellitus. UNDER NO CIRCUMSTANCES SHOULD THE ORAL CONTRACEPTIVE TABLETS BE STOPPED WITHOUT HAVING ADOPTED A SATISFACTORY ALTERNATIVE METHOD OF CONTRACEPTION. |
MINULETTE® tablets