Side Effects of Diane-35 (Cyproterone Acetate and Ethinyl Estradiol)
Diane-35 has significant cardiovascular risks including thromboembolism and should only be used for its approved indications of acne and hirsutism when other treatments have failed, not as a first-line contraceptive. 1
Common Side Effects
- Cardiovascular effects: Edema, varicose vein aggravation, increased risk of arterial thromboembolism, cerebral thrombosis, hypertension, and myocardial infarction 1, 2
- Central nervous system effects: Depression, migraine, headaches, mood changes, and nervousness 1
- Skin effects: Chloasma, melasma, allergic rash, and erythema nodosum 1
- Endocrine effects: Amenorrhea, breakthrough bleeding, breast pain/tenderness, breast changes, fluid retention, and infertility 1
- Gastrointestinal effects: Abdominal bloating, abdominal cramps, nausea, weight changes (increase or decrease), vomiting, and appetite changes 1, 2
- Genitourinary effects: Cervical ectropion, cervical secretion changes, vaginal candidiasis, and vaginitis 1
Serious Side Effects
Thromboembolic Complications
- Deep vein thrombosis and pulmonary embolism are significant risks 1, 3
- Venous thromboembolism risk is particularly concerning and has led to regulatory actions in some countries 3, 4
- Thromboembolism may not always be recognized at an early stage by users 3
Other Serious Adverse Effects
- Hepatic effects: Cholestatic jaundice, liver dysfunction 1
- Blood effects: Decreased folate levels, exacerbation of porphyria 1
- Anaphylaxis and exacerbation of systemic lupus erythematosus 1
Contraindications
Diane-35 is contraindicated in patients with:
- Active or history of arterial thromboembolic disease (stroke or myocardial infarction) 1
- Breast cancer or other estrogen/progestin-sensitive cancers 1
- Cerebrovascular disease or coronary artery disease 1
- Deep vein thrombosis, thromboembolic disease, or pulmonary embolism (current or history) 1
- Headaches with focal neurologic symptoms or migraine with aura (or without aura if ≥35 years) 1
- Hepatic dysfunction, hepatic tumors (benign or malignant) 1
- Hypercoagulopathies 1
- Uncontrolled hypertension 1
- Pregnancy (Pregnancy category X) 1
- Smoking if ≥35 years of age 1
- Undiagnosed uterine bleeding 1
- Thrombogenic valvular or rhythm diseases 1
Drug Interactions
Diane-35 has numerous drug interactions, including:
- Many antibiotics (cephalosporins, chloramphenicol, macrolides, penicillins, tetracyclines, sulfas) 1
- Anticonvulsants (barbiturates, carbamazepine, phenytoin, primidone, topiramate) 1
- HIV protease inhibitors (amprenavir, nelfinavir, ritonavir) 1
- Herbal supplements (St. John's wort) 1
- Other medications: aprepitant, bexarotene, bosentan, modafinil, rifampin 1
Special Considerations
Efficacy for Acne and Hirsutism
- Diane-35 is effective for treating acne and hirsutism 5, 6, 7
- In one study, 82.8% of patients with facial acne showed good or very good response after six cycles 7
- When combined with finasteride, it may be more effective for hirsutism treatment than Diane-35 alone 5
Monitoring Requirements
- Baseline monitoring: Pregnancy status, blood pressure 1
- Ongoing monitoring: Blood pressure, general health status changes 1
Risk-Benefit Assessment
Despite concerns about venous thromboembolism risk, some researchers argue that the benefits of Diane-35 for treating hyperandrogenism symptoms are clear and that the thromboembolism risks are comparable to third-generation combined oral contraceptives 6. However, regulatory authorities in some countries have taken action due to safety concerns, particularly regarding its widespread use as a contraceptive rather than for its approved indications 4.