Search The Medical Knowledge Base

Drug Details

Danol 100mg Capsules, Danol 200mg Capsules

• Drug Class Description
  Gonadotrophin release inhibitors.
• Generic Name
  Danazol - menorrhagia
• Presentation
  Capsule Danol 100mg: Hard gelatine, size 3 lok-cap capsules with grey and opaque white bodies containing a white or almost white powder, with 'DANOL 100' printed in black ink. Closed joint length; 15.9 mm ± 0.3 mm. Danol 200mg: Hard gelatine, size 1 lok-cap capsules with brown caps and opaque white bodies containing white or almost white powder, with 'DANOL 200' printed in black ink. Closed joint length; 19.4 mm ± 0.3 mm.
• Description
  Each capsule contains 100mg of danazol. Also contains 62 mg of lactose monohydrate. Each capsule contains 200 mg of danazol. Also contains 76.6 mg of lactose monohydrate
• Indications
  

  Danol capsules are recommended for the treatment of:

  Endometriosis: treatment of endometriosis-associated symptoms or/and to reduce the extent of endometriosis foci. Danazol may be used either in conjunction with surgery or, as sole hormonal therapy, in patients not responding to other treatments.

  Benign fibrocystic breast disease: symptomatic relief of severe pain and tenderness. Danazol should be used only in patients not responsive to other therapeutic measures or for whom such measures are inadvisable.

• Adult Dosage
  

  Adults:

  Danol capsules should be given as a continuous course, dosage being adjusted according to the severity of the condition and the patient's response. A reduction in dosage once a satisfactory response has been achieved may prove possible. In fertile females, Danol capsules should be started during menstruation, preferably on the first day, to avoid exposing a pregnancy to its possible effects. Where doubt exists, appropriate checks should be made to exclude pregnancy before starting medication. Females of child-bearing age should employ non-hormonal contraception throughout the course of treatment.

  In endometriosis the recommended dosage is 200mg to 800mg daily in a course of treatment lasting normally three to six months. Dosage should be increased if normal cyclical bleeding still persists after two months therapy, a higher dosage (not exceeding 800mg per day) may also be needed for severe disease.

  In benign fibrocystic breast disease, treatment should commence at a dose of 300mg daily, a course of treatment normally lasting 3 to 6 months.

  Elderly: Danol is not recommended.

  Children: Danol is not recommended.

  The capsules are for oral administration.

  
  

• Child Dosage
  

  Danol is not recommended.

  
  

• Elderly Dosage
  

  Danol is not recommended.

• Contra Indications
  

  1. Pregnancy

  2. Breast feeding

  3. Markedly impaired hepatic, renal or cardiac function

  4. Porphyria

  5. Active thrombosis or thromboembolic disease and a history of such events

  6. Androgen dependent tumour

  7. Undiagnosed abnormal genital bleeding.

  8. Hypersensitivity to danazol or to any of the excipients.

• Special Precautions
  

  Special warnings

  In the event of virilisation, Danol should be withdrawn. Androgenic reactions generally prove reversible, but continued use of Danol after evidence of androgenic virilisation increases the risk of irreversible androgenic effects.

  Danol should be stopped if any clinically significant adverse event arises, and particularly if there is evidence of papilloedema, headache, visual disturbances or other signs or symptoms of raised intracranial pressure, jaundice or other indication of significant hepatic disturbance, thrombosis or thromboembolism.

  Whilst a course of therapy may need to be repeated, care should be observed as no safety data are available in relation to repeated courses of treatment over time. The long-term risk of 17-alkylated steroids (including benign hepatic adenomata, peliosis hepatis and hepatic carcinoma), should be considered when danazol, which is chemically related to those compounds, is used.

  Data, from two case-control epidemiological studies, were pooled to examine the relationship between endometriosis, endometriosis treatments and ovarian cancer. These preliminary results suggest that the use of danazol might increase the baseline risk of ovarian cancer in - patients treated for endometriosis.

  Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

   

  Precautions

  In view of its pharmacology, known interactions and side effects, particular care should be observed when using Danol in patients with hepatic or renal disease, hypertension or other cardiovascular disease and in any state which may be exacerbated by fluid retention as well as in diabetes mellitus, polycythaemia, epilepsy, lipoprotein disorder, and in those who have shown marked or persistent androgenic reaction to previous gonadal steroid therapy.

  Caution is advised in patients with migraine.

  Until more is known, caution is advised in the use of Danol in the presence of known or suspected malignant disease (see also contra-indications). Before treatment initiation, the presence of hormone-dependent carcinoma should be excluded at least by careful clinical examination, as well as if breast nodules persist or enlarge during danazol treatment.

  In addition to clinical monitoring in all patients, appropriate laboratory monitoring should be considered which may include periodic measurement of hepatic function and haematological state. For long-term treatment (> 6 months) or repeated courses of treatment, biannual hepatic ultrasonography is recommended.

  Danazol should be initiated during menstruation. An effective, non-hormonal method of contraception should be employed.

  The lowest effective dose of Danol should always be sought.

• Interactions
  

  Anti-convulsant therapy: Danol may affect the plasma level of carbamazepine and possibly the patient's response to this agent and to phenytoin. With phenobarbital it is likely that similar interaction would occur.

  Anti-diabetic therapy: Danol can cause insulin resistance.

  Oral anti-coagulant therapy: Danol can potentiate the action of warfarin.

  Anti-hypertensive therapy: Possibly through promotion of fluid retention, Danol can oppose the action of anti-hypertensive agents.

  Ciclosporin and tacrolimus: Danol can increase the plasma level of ciclosporin and tacrolimus, leading to an increase of the renal toxicity of these drugs.

  Concomitant steroids: Although specific instances have not been described, it is likely that interactions will occur between Danol and gonadal steroid therapy.

  Migraine therapy: Danol may itself provoke migraine and possibly reduce the effectiveness of medication to prevent that condition.

  Ethyl alcohol: Subjective intolerance in the form of nausea and shortness of breath has been reported.

  Alpha calcidol: Danol may increase the calcaemic response in primary hypoparathyroidism necessitating a reduction in dosage of this agent.

  Interactions with laboratory function tests: Danazol treatment may interfere with laboratory determination of testosterone or plasma proteins

• Adverse Drug Reactions
  

  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