Dienille Special Precautions

Warnings: If any of the conditions listed as follows is present, the benefits of combined oral contraceptive use must be weighed against the possible risks of each individual woman and discussed with her before she decides to start using it. The patient should be warned that in case of appearance, aggravation, or exacerbation of any of these conditions medical advice should be sought without delay. The consulting physician should be then decide whether Dienille's use must be discontinued.
Vascular diseases: Because of the possibility of severe health damage (see Adverse Reactions) persistence of risk factors (such as varicose veins, advanced stage phlebitis and thrombosis, existence of heart disease, obesity, blood clotting disorders) combined oral contraceptive use must be carefully weighed against the possible risks before the start of Dienille.
The use of any combined oral contraceptive (COC) carries an increased risk for venous thromboembolism (VTE) compared with no use. The excess risk of VTE is highest during the first year a woman ever uses a COC. This increased risk is less than the risk of VTE associated with pregnancy, which is estimated as 60 per 100 000 pregnancies. VTE may be fatal in 1-2% of the cases. It is known how Dienille influences the risk of VTE compared with other COCs.
Epidemiological studies have shown that the incidence of VTE in users of oral contraceptives with low oestrogen content (<50 μg ethinylestradiol) ranges from about 20 to 40 cases per 100,000 woman-years, but this risk estimate varies according to the progestogen. This compares with 5 to 10 cases per 100,000 woman-years for non-users.
Epidemiological studies have also associated the use of combined COCs with an increased risk for arterial (myocardial infarction, transient ischaemic attack) thromboembolism.
Incidence of VTE in users of oral contraceptives with 30 μg ethinylestradiol and levonorgestrel is up to 20 cases per 100 000 women-years. Studies show no data about different risks associated with the use of Dienogest/Ethinylestradiol compared to contraceptives containing levonorgestrel.
Thrombosis has very rarely been reported to occur in other veins or arteries, e.g. hepatic, mesenteric, renal, cerebral or retinal in combined oral contraceptive users. There is no consensus as to whether the occurrence of these events is associated with the use of combined oral contraceptives.
Symptoms of arterial or venous thrombosis are: unusual pains in or swelling of the leg(s); sudden severe pain in the chest, whether or not reaching to the left arm; sudden breathlessness; sudden coughing; any unusual severe, prolonged headache; sudden partial or complete loss of vision; diplopia; blurred speech or aphasia; vertigo; collapse with or without focal epilepsy; weakness or very marked numbness suddenly affecting one side or one part of the body; motor disturbances; 'acute' abdomen.
Women taking combined oral contraceptives have higher risk for venous thromboembolic complications in the presence of the following: increased age; a positive family history of venous thromboembolism (in a sibling or parent at a relatively early age). If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding about any combined oral contraceptive use; prolonged immobilization, major surgery, any surgery to the legs, or major trauma. In these situations it is advisable to discontinue combined oral contraceptive use (in the case of elective surgery at least four weeks in advance) and not to resume until two weeks after complete remobilization. If stopping the combined oral contraceptive use was not possible in the right time, care should be taken to thrombosis prophylaxis; obesity (body mass index >30 kg/m²).
There is no consensus about the possible role of varicose veins and superficial thrombophlebitis in the development or course of deep venous thrombosis.
Women taking combined oral contraceptives have higher risk for arterial thromboembolic complications in the presence of the following: increased age; dyslipoproteinaemia; hypertension; valvular heart disease; atrial fibrillation; migraine; a positive family history (arterial thromboembolism ever in a sibling or parent at relatively early age). If a hereditary 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); smoking: cigarette smoking increases the risk of serious cardiovascular adverse reactions (such as heart attack, stroke) to oral contraceptive use. With heavier smoking and increasing age the risk further increases.
Women over 35 who use oral contraceptives should be strongly advised not to smoke. If she does not give up smoking, other contraceptive methods should be employed, especially, if other risk factors are also present.
Presence of severe risk factor/factors leading to the development of venous or arterial disorders might contraindicate application of Dienille. Introduction of anti-coagulatory treatment should also be considered. Women taking combined oral contraceptives should be warned that if they experience probable signs of thrombosis medical advice should sought without delay. In case of suspected or diagnosed thrombosis taking of the COC should be terminated and alternative methods of contraception should be employed because of the teratogenic effect of anti-coagulants (coumarin derivatives).
It should also be noted that risk of thromboembolism is increased in the post-partum period (see Use in Pregnancy & Lactation).
Other medical conditions which have been associated with adverse vascular events include diabetes mellitus, systemic lupus erythematosus, haemolytic uraemic syndrome, and chronic inflammatory bowel diseases (Crohn's disease or ulcerative colitis).
An increase in frequency or severity of migraine during combined oral contraceptive use (which may be prodromal of a cerebrovascular event) may be a reason for immediate discontinuation of the combined oral contraceptive.
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 (such as sexual behavior, incidence of human papilloma-virus infection, etc).
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. The increased risk diminishes in 10 years after finishing combined oral contraceptives. For further information see Adverse Reactions.
Breast cancer belongs to the hormone-dependent tumors. Some conditions such as early menarche, late (after 52 years of age) menopause, being nullipara, anovulatoric cycles etc, have long been recognized as risk factors in the development of breast cancer. These risk factors raise the possibility of hormonal effects in the pathogenesis of breast cancer. Hormone receptors play a central role in the tumor biology of breast cancer. Some of them induce growth factors, such as transforming growth factor-alpha (TGF-alpha).
Estrogens and gestagens influence proliferation of breast cancer cells. Among others this is the tumor biological rationale for pharmaceutical treatment of receptor positive, postmenopausal breast cancer.
Several epidemiological studies investigating the connection between combined oral contraceptive use and breast cancer acknowledge that development of breast cancer in middle age women is related to the early start and extended application of combined oral contraceptives. However, this is only one factor among possible other factors.
Benignant or very rarely malignant hepatic tumors have been reported on rare occasions in long-term users of oral contraceptives. In isolated cases these tumors were sources of life-threatening abdominal bleedings. A hepatic tumor should be considered in the differential diagnosis when upper abdominal pain, enlarged liver or signs of intra-abdominal haemorrhage occurs.
Other conditions: If hypertriglyceridaemia is present in the patient's or family history, use of combined oral contraceptives can increase the risk of development of pancreatitis.
Although increase in the blood pressure is common in women taking combined oral contraceptives, clinical hypertension is a rare finding. However, if hypertension develops while taking combined oral contraceptives, treatment should be discontinued and blood pressure lowering measures initiated. After successful treatment of hypertension, application of combined oral contraceptives can be started again, if the consulting physician considers this safe.
If, during the use of a COC in pre-existing hypertension, constantly elevated blood pressure values or a significant increase in blood pressure do not respond adequately to antihypertensive treatment, the COC must be withdrawn.
Where considered appropriate, COC use may be resumed if normotensive values can be achieved with hypertensive therapy.
Although no causative relationship has been proven, the following diseases / conditions worsen upon combined oral contraceptive use and pregnancy: cholestatic jaundice and/or pruritus, gallstones, porphyria, systemic lupus erythematosus, haemolytic uraemic syndrome, Sydenham chorea, gestational herpes, impaired hearing caused by otosclerosis in the middle ear.
If active or chronic liver disease is present, application of combined oral contraceptives should be suspended until liver function tests have been found to be normal.
If jaundice due to pregnancy or due to the use of steroids occurs or cholestatic pruritus develops, use of hormonal contraceptives should be stopped.
Combined oral contraceptives may diminish glucose tolerance and increase the need for insulin in peripheral tissues, however, usually it is not necessary to change anti-diabetic treatment regime in women taking combined oral contraceptives. Nevertheless, their status should be closely monitored, especially when starting the pill.
Development of Crohn's disease and ulcerative colitis has been described in women taking combined oral contraceptives.
Chloasma 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 this preparation.
In women with hereditary angioedema exogenous estrogens may induce or exacerbate symptoms of angioedema.
Worsening of endogenous depression or epilepsy has been reported during COC use.
The use of oestrogens in girls may cause premature closure of the epiphyses resulting in decreased final adult height.
Progestin containing compounds may have aldosterone antagonist properties that can have an important impact on potassium level.
Medical examinations: Assessment of women prior to starting or re-starting Dienille should include a detailed personal (and family) medical history. Pregnancy should be excluded. Blood pressure should be measured and physical examination should be guided by this and by the sections Contraindications and Precautions. Women taking Dienille should be encouraged to read the patient information leaflet carefully and to follow the suggestions in it. The frequency and nature of these assessments should be based upon relevant guidelines and should be adapted to the individual woman.
Women should be warned that taking the pill does not protect them against HIV-infection (AIDS) or other sexually transmitted diseases.
Regular medical assessment is also important because some contraindications or risk factors can appear at first during COC use.
Reduced reliability: Reliability of combined oral contraceptives may be reduced under the following circumstances: if the patient does not take the film- coated tablets on a regular basis, vomiting or severe diarrhea occurs (see DOSAGE & ADMINISTRATION, or because of interaction with other medicinal products (see INTERACTIONS).
Change in bleeding pattern: Combined oral contraceptives may cause irregular (spotting or break-through) bleeding, especially in the first few months of treatment. Thus, the investigation of irregular bleeding should be shifted until hormonal equilibrium develops; usually this takes three cycles.
If irregular bleeding after regular cycles, or persistent bleeding is present, non-hormonal causes such as pregnancy and the presence of a malignant tumor should be excluded, this may indicate a diagnostic curettage as well.
Occasionally, withdrawal bleeding may not occur at all. If the film- coated tablets have been taken correctly (according to DOSAGE & ADMINISTRATION), pregnancy is very unlikely. If withdrawal bleeding fails to occur at the end of a second pack or if she did not follow the suggestions as previously mentioned, pregnancy must be ruled out before resuming with the next pack.
Metabolic interactions leading to an increased clearance of sexual steroids might elicit break-through bleeding or lead to a decreased contraceptive potential (see INTERACTIONS).
The herbal remedy St John's wort (Hypericum perforatum) should not be taken concomitantly with Dienille as this could potentially lead to a loss of contraceptive effect (see INTERACTIONS).
Dienille: This medicinal product contains lactose, glucose and soy lecithin. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption, or are allergic to peanut and soya should not take this medicine.
ALT elevations: During clinical trials with patients treated for hepatitis C virus infections (HCV) with the medicinal products containing ombitasvir / paritaprevir / ritonavir and dasabuvir with / without ribavirin, transaminase (ALT) elevations higher than 5 times the upper limit of normal (ULN) occurred significantly more frequent in women using ethinylestradiol-containing medications such as combined hormonal contraceptives (CHCs). Patients who are taking ethinylestradiol-containing medicinal products must switch to an alternative method of contraception (e.g. progestin only contraception or non-hormonal methods) prior to initiating ombitasvir / paritaprevir / ritonavir and dasabuvir therapy (See Contraindications and Interactions).
Effects on Ability to Drive and Use Machines: No effects on ability to drive and use machines have been observed.