DrugsLevel 4 LocalisationS4TAB · FCTEML

Cyproterone Acetate/ Ethinylestradiol

Antiandrogen and oestrogenContraceptive

Indications

Registered South African indications:

Oral contraception in women who require anti-androgen therapy
Control of idiopathic hirsutism in women
Severe acne

Cautions

Contraindications

Registered South African contraindications

Hypersensitivity to the active substances or to any of its excipients
Pregnancy - known or suspected
After a recent evacuation of a hydatidiform mole until urine and plasma gonadotropin concentrations have returned to normal
Lactation
Known or suspected breast cancer
Concomitant use with another hormonal contraceptive
Patients with liver diseases or malignant or wasting diseases
History of arterial or venous thromboembolic disorders. This may include:
- Myocardial infarction
- Pulmonary embolism
- Venous thrombosis
- Stroke
Severe chronic depression
Sickle-cell anaemia
Depression not well controlled with treatment
A history of depression with the use of hormonal contraceptives
Oestrogen-dependent neoplasms
Functional ovarian cysts
The Dubin-Johnson or Rotor syndromes
Disorders of lipid metabolism
Markedly impaired liver function
Cerebrovascular insufficiency
Coronary artery disease
Thrombophlebitis
Deteriorating otosclerosis
History of pruritus during previous pregnancy
Undiagnosed vaginal bleeding
Herpes
Recurrent cholestatic jaundice
Porphyria
Patients with classical migraine
Relative contraindications (these patients would require medical supervision):
- Diabetes mellitus
- Tetany
- Hypertension
- Epilepsy
- Chorea
- Multiple sclerosis
- Renal dysfunction
- Asthma
- Mental depression
- Varicose veins
- Cardiac dysfunction
- Gallbladder disease
- Patients who wear contact lenses
- Obese patients, or other conditions influenced by fluid retention
- The risk benefits should be considered in patients with endometriosis and uterine fibroids
It is advised that the use of cyproterone acetate/ ethinylestradiol be discontinued if any of the following symptoms occur
- The onset of migraine or severe headache in a new patient or more frequent occurrence of unusually severe headaches
- When there is a gradual or sudden loss of vision or hearing or other sudden perceptual disorders
- At the first signs of thrombo-embolic disorders, e.g., pulmonary embolism, cerebrovascular insufficiency, thrombophlebitis, cerebral haemorrhage, retinal thrombosis, coronary or mesenteric thrombosis
- Surgery or prolonged bed rest as this may increase the risk of thromboembolic episodes. It is recommended that oral contraceptives be discontinued 4 to 6 weeks before major surgery
- Cyproterone acetate/ ethinylestradiol should be discontinued if persistent upper abdominal pain, hepatitis, or jaundice develops
- If blood pressure rises markedly, cyproterone acetate/ ethinylestradiol should be discontinued
- Onset of severe depression
- Severe upper abdominal pain or liver enlargement
- Pregnancy

Contraindications registered in other jurisdictions

Hypersensitivity to the active substances or to any of its excipients
Concomitant use with another hormonal contraceptive
Venous thrombosis present or in history (deep venous thrombosis, pulmonary embolism)
Arterial thrombosis present or in history (e.g. myocardial infarction) or prodromal conditions (e.g. angina pectoris and transient ischaemic attack)
Presence or history of cerebrovascular accident
Presence of severe or multiple risk factor(s) for venous or arterial thrombosis, such as:
- Diabetes mellitus with vascular symptoms
- Severe hypertension
- Severe dyslipoproteinaemia
Hereditary or acquired predisposition for venous or arterial thrombosis, such as activated protein C (APC) resistance, antithrombin-III-deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinaemia, and antiphospholipid-antibodies (anticardiolipin-antibodies, lupus anticoagulant)
History of migraine with focal neurological symptoms
Presence or history of severe hepatic disease e.g. active viral hepatitis and severe cirrhosis, as long as liver function values have not returned to normal
Presence or history of liver tumours (benign or malignant)
Current or history of breast cancer
Pregnancy - known or suspected
Breastfeeding
Meningioma or history of meningioma
Concomitant use with the medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir or medicinal products containing glecaprevir/pibrentasvir or sofosbuvir/velpatasvir/voxilaprevir
Cyproterone acetate/ ethinylestradiol is not for use in men

Should any of the conditions appear for the first time during their use, the product should be stopped immediately. Relevant national clinical guidance on combined oral contraceptives (COCs) should also be consulted

Cautions

Renal impairment
Hypertension
Current or history of depression
Obesity
Migraine
Cardiovascular disease
Chloasma
Systemic lupus erythematosus
Hemolytic uraemic syndrome
Chronic inflammatory bowel disease
Sickle cell disease
Persistent human papillomavirus infection
Hypertriglyceridaemia or a family history thereof
Family history of venous thromboembolism
Age over 35 years
Smoking
Hyperhomocysteinaemia
Valvular heart disease
Atrial fibrillation
Hereditary angioedema
Galactose intolerance
Lapp lactase deficiency
Fructose intolerance
Glucose-galactose malabsorption
Sucrase-isomaltase deficiency

Adult dosage

Forms avail. in SA and covered in this monograph: fct, tab

South African registered indications and dosages

Oral contraception in women who require anti-androgen therapy
Control of idiopathic hirsutism in women
Severe acne
- Especially androgen-dependent acne accompanied by inflammation, seborrhoea or the formation of nodes

Cyproterone Acetate/ Ethinylestradiol
2/0.035 (mg)

Oral (fct, tab): Initial: 1 tab, dly commenced on the first day of the menstrual cycle (the first day of menstrual bleeding). The first tablet should be taken from the specified section of the calendar pack, starting with the indicated day on the strip; Thereafter: 1 tab dly, taken at the same time, following the sequence of the arrows on the pack, until all tablets are consumed; Treatment duration: 21 days
THEN

Inactive tablets

Oral (fct, tab): 1 tab, dly following the sequence of the arrows on the pack; Treatment duration: 7 days

Before commencing with cyproterone acetate/ ethinylestradiol, a thorough gynaecological examination should be done, and the patient’s medical history carefully evaluated. Regular medical examinations are recommended during use. Pregnancy should be excluded

Disorders of the clotting system and family history of thrombo-embolic diseases, especially at a young age, should be excluded

Androgen-producing tumours or an adrenal enzyme defect should be ruled out before prescribing cyproterone acetate/ ethinylestradiol for the treatment of hirsutism

Additional contraceptive precautions should be taken for the first 14 days of the first cycle or if a tablet is accidentally missed. For more on missed doses see additional prescribing points

Spotting may occur but will usually stop spontaneously. The patient is advised to consult her doctor if prolonged and persistent bleeding occurs

The tablet should be taken roughly at the same time every day, not exceeding 24 hours, for maximum effectiveness. The tablet may be taken with a meal to reduce nausea

Subsequent cycles: A new pack should be started the very next day after completing the previous pack, once again following the order directed on the packaging. This method should be followed as long as the contraception is desired

Length of use: The length of use depends on the severity of the clinical picture. Treatment should generally be carried out over several months. It is recommended that cyproterone acetate/ ethinylestradiol be taken for at least another 3 to 4 cycles after the signs have subsided. The need to continue treatment should be evaluated periodically