| Androgenic effects include weight gain, increased appetite, acne and seborrhoea. Hirsutism, hair loss, voice change, which may take the form of hoarseness, sore throat or of instability or deepening of pitch may occur. Hypertrophy of the clitoris as well as fluid retention are rare. Other possible endocrine effects include menstrual disturbances in the form of spotting, alteration of the timing of the cycle and amenorrhoea. Although cyclical bleeding and ovulation usually return within 60-90 days after Danol, persistent amenorrhoea has occasionally been reported. Flushing, vaginal dryness, changes in libido, irritation and reduction in breast size may reflect a lowering of oestrogen. In the male a modest reduction in spermatogenesis may be evident during treatment. Insulin resistance may be increased in diabetes mellitus but symptomatic hypoglycaemia in non-diabetic patients has also been reported as has an increase in plasma glucagon level. Coupled with elevated plasma insulin levels, danazol can also cause a mild impairment of glucose tolerance. Danol may aggravate epilepsy and expose the condition in those so predisposed. Cutaneous reactions include rashes, which may be maculopapular, petechial or purpuric or may take an urticarial form and may be accompanied by facial oedema. Associated fever has also been reported. Rarely, sun-sensitive rash has been noted. Inflammatory erythematous nodules, changes in skin pigmentation, exfoliative dermatitis and erythema multiforme have also been reported. Musculo-skeletal reactions include backache and muscle cramps which can be severe, creatine phosphokinase levels may also rise. Muscle tremors, fasciculation, limb pain, joint pain and joint swelling have also been reported. Cardiovascular reactions may include hypertension, palpitations and tachycardia. Thrombotic events have also been observed. Sagittal sinus and cerebrovascular thrombosis as well as arterial thrombosis have been observed. Cases of myocardial infarction have been reported. Benign intracranial hypertension, visual disturbances such as blurring of vision, difficulty in focusing,difficulty in wearing contact lenses and refraction disorders requiring correction have been noted. Haematological responses include an increase in red cell and platelet count. Reversible polycythaemia may be provoked. Eosinophilia, leucopenia thrombocytopenia and splenic peliosis have also been noted. Hepatic–pancreatic reactions include isolated increases in serum transaminase levels and rarely cholestatic jaundice and benign hepatic adenomata and pancreatitis. Very rarely peliosis hepatitis as well as malignant hepatic tumour have been observed with long term use. Fluid retention may explain the occasional reports of carpal tunnel syndrome. Danol capsules may also provoke migraine. Possible psychical reactions include emotional lability, anxiety, depressed mood and nervousness. Dizziness, vertigo, nausea, headache, fatigue and epigastric and pleuritic pain have also been noted. A temporary alteration of lipoproteins in the form of an increase in LDL cholesterol, a decrease in HDL cholesterol, affecting all subfractions, and a decrease in apolipoproteins AI and AII have been reported with Danol in the female. Other metabolic events have been reported, including induction of aminolevulinic acid (ALA) synthetase, and reduction in thyroid binding globulin, T4, with increased uptake of T3 but without disturbance of thyroid stimulating hormone or free levothyroxine index, is also likely during therapy. Haematuria has rarely been reported with prolonged use in patients with hereditary angioedema. Cases of interstitial pneumonitis have been reported | |