Interacting drugs- summary 

Danazol +  Insulin

increased  insulin requirements increase in diabetes. Abnormal tolerance tests seen Warfarin incr prolongation of prothrombin time reported with concomitant use

Evidence of increased incidence of insulin resistence.

Potententiates action of anticogulants

Elevation of liver function test values.

Serum cyclosporin levels increased.

Oral contraceptives interfere with danazol action.

Anti-epileptic dose may require adjustment.

Endometriosis, fibrocystic breast disease, heriditary angioedema..

Interacting drugs- summary Danazol + Insulin incr insulin requirements increase in diabetes. Abnormal tolerance tests seen Warfarin incr prolongation of prothrombin time reported with concomitant use

Oedema, weight gain, sweating, acne, hirsutism, rash, flushing, oily skin and hair, deepening of voice, nausea, vaginitis, clitoral hypertrophy, amenorrhoea, hepatic dysfunction, CNS or GI disturbances, benign intracranial hypertension, changes in breast size(usually decrease).

Pregnancy,therapy should begin during menstruation or subsequent to test to ensure patient is not pregnant. Porphyria, lactation, renal or cardiac oedema.

Special precautions: Epilepsy, migraine, hepatic or renal dysfunction. Periodic monitoring of liver function. Possible decreased glucose tolerance. History of jaundice with oral contraceptives.

Severe hypertension. Diabetes. Suseptibilty to weight gain.

Indications: Endometriosis, fibrocystic breast disease, heriditary angioedema.

Dosage: Endometriosis- 800mg 3 times/day in divided doses.

Fibrocystic breast disease - 100 to 400mg/day in divided doses.

For Availability/supplies 

EVIDENCE BASED MEDICINE (April 2003) Premenstrual sydrome Comparative effectiveness of various intreventions Beneficial Overall Premenstrual Syndrome Symptoms

1. Prostagalndin inhibitors (e.g. Indomethicin)

2. Selective serotonin Reuptake Inhibitors (e.g. Fluoxetine, Seratinine, Fluvoxamine)

Breast symptoms only

1. Leuteal phase control

2. Bromocriptine Bloatedness and Swelling

Spironolactone/ diuretics Likely to be beneficial

1. Tobolone

2. Oestrogen

3. Vitamin B-6

4. Evening primrose B-6

Trade-off between Benefits and Harms

1. Danazol

2. Gonodotropin-releasing hormone (GnRH analogues)

3. Non-SSRI antidepressants/ anxiolytics

4. Hysterectomy with/without oophorectomy

Unknown effectiveness

1. Progesterone

2. Progestogens

3. Oral contraceotives

4. Cognitive behaviour treatment

5. Dietary supplements

6. Relaxation treatment

7. Endometrial ablation

8. Laproscipic bilateral oophorectomy

KEY POINTS

1. Trials have found that SSRIs and prostagalndin inhibitors relieve premenstrual symptoms. Antidepressants and ovulation suppression with danazol and GnRH analoges are also effective but have significant adverse effects, including the masculanising effects of danazol and the menopausal effects of GnHR analogues.

2. There is a limited evidence suggesting that oestrogen, viatmin-B6 , evening Primrose Oil and excercise may also be beneficoial

3. Trials have found that bromocriptine is effective for breast symptoms and diuretics are effective for bloatedness and swelling. Both can have adverse efects.

4. There is no good evidence to support the use of progesterone or oral contraceptives

5. Few treatments have been adequately validated in trials.

Gynecomastia- ( 1789 ) 

Under usual conditions no breast tissue is palpable in the normal adult man. However enlargement of male breast can either occur as a manifeastation of normal physiological development at certain stages of life or as the due either to normal or abnormal causes the enlargement is believed to result from disturbances of trhe normal ratio of active androgen in plasma or within thebreasat itself. Earler gynaecomastia is charactewrized by proliferation of both the fibroblastic stroma and the duct system. Treatment Prophylactic radiation of the breasts prior to the institution of diethylstilbestrol therapy appearsto be effective in preventing the development of gynaecomastia and has a low complication rate of the age group affected.

Drugs causing adversse reaction- Gynaecomastia 

1. Estrogens

2. Testosterone

3. Spironolactone

4. Digitalis

5. Reserpine

6. Methyldopa

7. Isoniazid

8. Ethionamide

9. Griseofluvin

1.Notify physician if masculinizing effects occurs(eg. abnormal growth of facial or other fine body hair,deepening of the voice).

2. Use non-hormonal contraceptive measures during therapy.

3. Discontinue use if pregnancy is suspected.

1. Allergies- Tell your doctor if you have ever had any unusual or allergic reactions to danozol or other related medicines. Also tell your doctor if youn are allergic to any other substances such as foods, preservatives or dyes.

2. Pregnancy- danozol is not recommended for use during pregnancy.

3. Breast feeding- not recommended

4. Children- danozol may cause male like changes in females children and cause premature sexual development in male children.

5. Elderly- androgens used in older males may increase the risk of developing prostrate enlargement or cancer.

6. Other medicines- tell your doctor if you are taking any of the following- anticoagulant -dazazol may increae the effects of these medicines and possibly increase the risk of severe bleeding

7. Other medical problems- tell your doctor if you have any other medical problems- Diabetes mellitus -danazol may increase blood glucose levels Epilepsy or Kidney disease or Migraine headaches - these conditions can be made worse by fluid retention (keeping too much water ) that can caused by danazol Liver disease

8. Missed dose- If you miss a dose of this medicine take it as soon as possible. However if it is almost time for your next dose go back to your regular dosing schedule. Do not double doses.

Pharmacology: A synthetic androgen derived from ethisterone,danazol supresses the pituitary axis by inhibiting the output of pitutary gonadatropins. It also has weak,dose related androgenic activity and is not estrogenic or progestational.

Pharmacokinetics: Blood levels of danazol do not increase propotionately with increase in dose. When the dose is doubled plasma levles increase only about 35% to 40%.

Pregnancy: If a patient becomes pregnant while taking danazol, appraise her of the potential risks to the fetus.