Danazol

Registered South African indications:

• Endometriosis
• Severe breast pain and nodularity
• Prophylaxis of hereditary angioneurotic oedema

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Breastfeeding
• Severe renal impairment
• Severe hepatic impairment
• Impaired cardiac function
• Porphyria
• Active thrombosis or thromboembolic disease and a history of such events
• Androgen dependent tumour
• Abnormal genital bleeding that has not been fully investigated
• Concomitant administration with simvastatin

Cautions

• Mild to moderate renal impairment
• Mild to moderate hepatic impairment
• Elderly
• Hypertension 
• Cardiovascular disease 
• Any state which may be exacerbated by fluid retention
• Diabetes mellitus
• Polycythaemia
• Epilepsy
• Lipoprotein disorder
• History of thrombosis
• Marked or persistent androgenic reaction to previous gonadal steroid therapy
• Migraine
• Known or suspected malignant disease
• Prolonged use
• Galactose intolerance
• Lapp lactase deficiency 
• Glucose-galactose malabsorption

Forms avail. in SA and covered in this monograph: cap

Endometriosis
-Mild

• Oral (cap): 200-400mg/day, in 2 divided doses; Max: 800mg/24hrs; Treatment duration: 3-9 months

-Moderate to severe

• Oral (cap): 800mg/day, in 2 divided doses; Max: 800mg/24hrs; Treatment duration: 3-9 months

Initiate treatment on 1st day of menstrual cycle or after pregnancy has been excluding

Fibrocystic breast disease
Severe breast pain and nodularity

• Oral (cap): 100mg, 12hrly; Treatment duration: 3 months

Prophylaxis of hereditary angioneurotic oedema
- males and females

• Oral (cap): Initial: 400mg, dly; Maintenance: Once attack free for 2 months reduce to lowest effective dose

Not established for use in children

Pregnancy

• Contraindicated
• There is epidemiological and toxicological evidence of hazard in human pregnancy. Danazol is known to be associated with the risk of virilisation to the female foetus if administered during human pregnancy. Danazol should not be used during pregnancy. Women of childbearing age should be advised to use an effective, non-hormonal, method of contraception. If the patient conceives during therapy, danazol should be stopped

Breastfeeding

• Contraindicated
• Danazol has the theoretical potential for androgenic effects in breastfed infants and therefore either danazol therapy or breastfeeding should be discontinued

Renal Impairment

• Caution; dose adjustment recommended

Hepatic Impairment

• Mild (Child-Pugh Class A): Caution; no dose adjustment recommended
• Moderate (Child-Pugh Class B): Reduce the daily recommended dose by 50% (based on clinical response) 9
• Severe (Child-Pugh Class C): Contraindicated

Elderly

• Not indicated for use in geriatric patients

Porphyria Information

• Probably porphyrinogenic (PRP)

Drugs in Sport

• Prohibited - At all times

Central Nervous System Disorders

• Emotional lability
• Anxiety
• Depressed mood
• Nervousness 
• Change in libido
• Dizziness
• Headache
• Vertigo
• Benign intracranial hypertension
• Aggravation of epilepsy 
• Carpal tunnel syndrome
• Migraine
• Fatigue

Cardiovascular Disorders

• Hypertension
• Palpitation 
• Tachycardia
• Thrombotic events
• Myocardial infarction
• Flushing
• Exacerbation of hypertension

Respiratory Disorders

• Pleuritic pain
• Interstitial pneumonitis

Gastrointestinal Disorders

• Nausea
• Epigastric pain

Hepatobiliary Disorders

• Hepatobiliary disorders
• Increase in serum transaminase levels 
• Cholestatic jaundice
• Benign hepatic adenomata 
• Pancreatitis
• Peliosis hepatis 
• Malignant hepatic tumour 
• Hepatocellular injury
• Hepatic failure
• Jaundice hepatocellular
• Hepatocellular focal nodular hyperplasia

Genitourinary Disorders

• Haematuria 

Endocrine and Metabolic Disorders

• Acne
• Increased weight 
• Increased appetite
• Seborrhoea
• Hirsutism
• Hair loss
• Voice change
• Hypertrophy of the clitoris
• Fluid retention
• Spotting
• Alteration of the timing of menstrual cycle 
• Amenorrhoea
• Flushing
• Vaginal dryness
• Vaginal irritation 
• Reduction in breast size
• Amenorrhoea 
• Reduction in spermatogenesis
• Diabetes mellitus 
• Symptomatic hypoglycaemia in non-diabetic patients 
• Mild impairment of glucose tolerance
• Increase in low density lipoprotein cholesterol
• Decrease in high density lipoprotein cholesterol
• Decrease in apolipoproteins 
• Induction of aminolevulinic acid synthetase
• Decrease in thyroid binding globulin, T4
• Increased uptake of T3 

Musculoskeletal Disorders

• Backache 
• Muscle cramps 
• Increased creatine phosphokinase levels
• Muscle tremors
• Fasciculation
• Limb pain
• Joint pain 
• Joint swelling

Skin and Subcutaneous Tissue Disorders

• Rashes
• Urticaria
• Facial oedema
• Sun-sensitive rash
• Inflammatory erythematous nodules
• Changes in skin pigmentation
• Exfoliative dermatitis 
• Erythema multiforme 

Immune, Blood and Lymphatic System Disorders

• Increased red cell count
• Increased platelet count
• Reversible erythrocytosis 
• Polycythaemia
• Eosinophilia
• Leucopenia
• Splenic peliosis 
• Thrombocytopenia
• Fever

Sensory Disorders

• Blurred vision
• Difficulty focusing

• Anticonvulsant agents
• Antidiabetic agents
• Oral anticoagulant therapy
• Antihypertensives
• Ciclosporin
• Tacrolimus
• Steroids
• Migraine therapy
• Ethyl alcohol
• Alpha calcidol
• Statins

• Hepatic function
• Renal function
• Full blood count
• Lipid profile
• Androgenic changes

By suppressing the pituitary-ovarian axis, danazole inhibits the output of gonadotropins. Both the perovulatory surge of follicle stimulating hormone (FSH) and luteinizing hormone (LH) are suppressed and therefore ovarian oestrogen production is reduced. In the treatment of endometriosis, this action causes the normal and ectopic endometrial tissue to become inactive and atrophic. Depending on dosage, anovulation and associated amenorrhoea will occur after 1-2 menstrual cycles. In the treatment of fibrocyctic breast disease the pharmacological action may be due to the suppression of oestrogen stimulation by a result of decreased ovarian production of oestrogen.

Capsule 100mg

• Danogen (Cipla)
• Ladazol (Adcock)

Capsule 200mg

• Danogen (Cipla)
• Ladazol (Adcock)