Diane-35 Special Precautions

Diane-35 consists of the progestogen cyproterone acetate and the oestrogen ethinylestradiol and is administered for 21 days of a monthly cycle. It has a composition similar to a combined oral contraceptive (COC).
Duration of administration: The time to symptomatic relief is at least three months. The treating physician should regularly check whether there is still a need for treatment (see Dosage & Administration).
If any of the disorders/risk factors mentioned below are present, the benefit of using Diane-35 should be weighed against the possible risks for the woman and discussed with her before she decides to use Diane-35. In the event of aggravation/exacerbation or first appearance of any of these disorders or risk factors, the woman should contact her physician. The physician should then decide whether the use of Diane-35 should be terminated.
Circulatory diseases: The use of Diane-35 carries an increased risk of venous thromboembolism (VTE) compared with non-use. The additional VTE risk is greatest during the first year of initial Diane-35 use by a woman or upon resumed use or a switch after a pill-free interval of at least one month. A venous thromboembolism can be fatal in 1-2% of cases.
Epidemiological studies have shown that the incidence of VTE in users of Diane-35 is 1.5 to 2 times higher than in users of combined oral contraceptives (COCs) containing levonorgestrel and may be similar to the risk for COCs containing desogestrel/gestodene/drospirenone.
The Diane-35 user group is likely to include patients who have a congenital increased cardiovascular risk, e.g. due to polycystic ovary syndrome.
Furthermore, epidemiological studies have associated the use of hormonal contraceptives with an increased risk for arterial (myocardial infarction, transient ischemic attack) thromboembolism.
In very rare cases, thrombosis has been reported to occur in other blood vessels among users of hormonal contraceptives, e.g. arteries and veins of the liver, mesentery, kidney, brain or retina.
The following may occur as symptoms of venous or arterial thrombosis or a cerebrovascular accident: unusual unilateral leg pain and/or swelling; sudden severe chest pain, regardless of whether it radiates to the left arm; sudden dyspnoea; sudden onset of cough; any unusual, severe, persistent headache; sudden partial or complete loss of vision; diplopia; slurred speech or aphasia; vertigo; collapse with or without a focal seizure; weakness or very significant numbness suddenly affecting one side or one part of the body; motor disorders; "acute" abdomen.
The risk of venous thromboembolic events rises with: Increasing age.
Smoking (the risk increases further with increasing tobacco consumption and age, especially in women over 35 years of age. Women over 35 years of age should be strongly advised not to smoke if they wish to use Diane-35).
A positive family history (i.e. venous thromboembolism in a sibling or parent at a relatively young age). If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before making a decision regarding the use of a hormonal contraceptive.
Prolonged bed confinement, major surgery, leg surgery or severe trauma. In these situations, it is recommended that use be terminated (in case of elective surgery, at least four weeks in advance) and not resumed until two weeks after full mobility has been regained. If the use of Diane-35 has not been terminated in advance, therapy with an antithrombotic agent should be considered.
Obesity (body mass index over 30 kg/m²).
The risk of arterial thromboembolic complications or cerebrovascular accident rises with: Increasing age.
Smoking (the risk rises further with increasing tobacco consumption and age, especially in women over 35 years of age. Women over 35 years of age should be strongly advised not to smoke if they wish to use Diane-35).
Dyslipoproteinaemia.
Obesity (body mass index over 30 kg/m²).
Hypertension.
Migraine.
Valvular heart disease.
Atrial fibrillation.
A positive family history (arterial thrombosis in a sibling or parent at a relatively young age). If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before making a decision regarding the use of a hormonal contraceptive.
Other diseases that have been associated with adverse circulatory events, including diabetes mellitus, systemic lupus erythematosus, haemolytic-uraemic syndrome, chronic inflammatory bowel disease (e.g. Crohn's disease or ulcerative colitis) and sickle cell anaemia.
The increased risk of thromboembolism in the puerperium must be considered (for information on Pregnancy and lactation, see Use in Pregnancy & Lactation).
An increase in the frequency or severity of migraine whilst using Diane-35 (which may be prodromal for a cerebrovascular event) can be a reason for immediate discontinuation of Diane-35.
Women using Diane-35 should be specifically instructed to contact their physician if possible symptoms of thrombosis occur. Diane-35 must be discontinued if thrombosis is suspected or confirmed. Due to the teratogenicity of anticoagulants (coumarins), appropriate methods of contraception should be used.
Tumors: Some epidemiological studies have indicated that long-term use of combined oral contraceptives may contribute to an increased risk of cervical cancer. There continues to be controversy about the extent to which this is attributable to sexual behaviour and other factors, such as infection with human papillomavirus (HPV).
A meta-analysis from 54 epidemiological studies reported that there is a slightly increased relative risk (RR = 1.24) of having breast cancer in women who are currently using combined oral contraceptives. The excess risk gradually disappears during the course of the 10 years after cessation of COC use. Because breast cancer is rare in women under 40 years of 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. These studies do not provide evidence for causation. 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 breast cancers diagnosed in ever-users tend to be less advanced clinically than the cancers diagnosed in never-users.
In rare cases, benign liver tumors, and even more rarely, malignant liver tumors have been reported, possibly leading to life-threatening intra-abdominal hemorrhages, after the use of hormonal substances, such as those contained in Diane-35. If non-specific upper abdominal complaints, liver enlargement or signs of intra-abdominal hemorrhage occur, a liver tumor should be included in the differential diagnosis.
Reduced efficacy: The contraceptive efficacy of Diane-35 may be reduced in the event of e.g. missed tablets (Dosage & Administration), gastrointestinal disturbances (Dosage & Administration) or certain concomitant medication (Interactions).
Diane-35 contains 31 mg lactose per tablet. Patients with rare genetic galactose or fructose intolerance, lactase deficiency, glucose-galactose malabsorption or sucrase-isomaltase deficiency should not take Diane-35.
There is some epidemiological evidence that the incidence of venous thromboembolism is higher in users of this product when compared to users of combined oral contraceptives with low oestrogen content (<50 mcg ethinylestradiol).
Effects on ability to drive or use machines: No observed effects.