Danocrine

Danazol is used to treat endometriosis (a condition in which the type of tissue that lines the uterus [womb] grows in other areas of the body and causes infertility, pain before and during menstrual periods, pain during and after sexual activity, and heavy or irregular bleeding)..Danazol is also used to treat fibrocystic breast disease (swollen, tender breasts with noncancerous lumps) when other treatments are not successful. Danazol is also used to prevent attacks in people with hereditary angioedema (inherited condition that causes episodes of swelling in the hands, feet, face, airway, or intestines). Danazol is in a class of medications called androgenic hormones. It works to treat endometriosis by shrinking the displaced tissue of the uterus. It works to treat fibrocystic breast disease by blocking the release of hormones that cause the breast pain and lumps. It works to treat hereditary angioedema by increasing the amount of a natural substance in the body.

Danazol is a man-made form of a steroid. Danazol affects the ovaries and pituitary gland and prevents the release of certain hormones in the body.

Danazol is used to treat endometriosis and fibrocystic breast disease. Danazol is also used to prevent attacks of angioedema in people with an inherited form of this disorder (hereditary angioedema).

Danazol may also be used for purposes not listed in this medication guide.

You should not use this medication if you are allergic to danazol, or if you have porphyria, a history of stroke or blood clot, or severe problems with your heart, liver, or kidney. You also should not take danazol if you are pregnant or breast-feeding, if you have breast or uterine cancer, or if you have abnormal vaginal bleeding that has not been checked by a doctor.

Danazol can harm an unborn baby or cause vaginal birth defects in a newborn female infant. Do not use if you are pregnant.

You may need to have a negative pregnancy test before starting this treatment.

Use a barrier form of birth control (such as a condom or diaphragm with spermicide). Hormonal contraception (such as birth control pills, injections, implants, skin patches, and vaginal rings) may not be effective enough to prevent pregnancy during your treatment with danazol.

Your medication needs may change if you become ill, have a fever or infection, or if you have surgery or a medical emergency. Tell your doctor about any such situation that affects you. Do not change your medication dose or schedule without your doctor's advice.

It may take several weeks before your symptoms improve. Keep using the medication as directed and tell your doctor if your symptoms do not improve or if they get worse during treatment.

Call your doctor at once if you have a serious side effect such as sudden numbness or weakness, problems with vision or speech, chest pain, sudden cough, or wheezing, swelling, rapid weight gain, feeling short of breath, ringing in your ears, dizziness, nausea, pain behind your eyes, stomach pain and loss of appetite, dark urine, or jaundice (yellowing of the skin or eyes).

You should not use this medication if you are allergic to danazol, or if you have:

• severe heart disease, a history of stroke or blood clot;
• severe kidney disease;
• severe liver disease;
• a hormone-related cancer such as breast or uterine cancer;
• porphyria (a genetic enzyme disorder that causes symptoms affecting the skin or nervous system);
• abnormal vaginal bleeding that has not been checked by a doctor; or
• if you are pregnant or breast-feeding.

To make sure you can safely take danazol, tell your doctor if you have any of these other conditions:

• heart disease, high blood pressure, coronary artery disease, congestive heart failure;
• high cholesterol or triglycerides;
• a history of breast cancer;
• diabetes;
• hypoparathyroidism, or low levels of calcium in your blood;
• a seizure disorder;
• kidney or liver disease; or
• migraine headaches.

FDA pregnancy category X. This medication can harm an unborn baby or cause vaginal birth defects in a newborn female infant. Do not use danazol if you are pregnant. Stop taking danazol and tell your doctor right away if you become pregnant during treatment.

You may need to have a negative pregnancy test before starting this treatment.

Use a barrier form of birth control (such as a condom or diaphragm with spermicide). Hormonal contraception (such as birth control pills, injections, implants, skin patches, and vaginal rings) may not be effective enough to prevent pregnancy during your treatment with danazol.

Danazol can pass into breast milk and may harm a nursing baby. You should not breast-feed while you are using danazol.

Taking danazol to treat endometriosis may increase your risk of ovarian cancer. Talk with your doctor about your individual risk.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Tell your doctor about all other medicines you use, especially:

• carbamazepine (Carbatrol, Equetro, Tegretol);
• cyclosporine (Gengraf, Neoral, Sandimmune);
• insulin or oral diabetes medications;
• tacrolimus (Prograf);
• a blood thinner such as warfarin (Coumadin, Jantoven); or
• cholesterol lowering medicines such as atorvastatin (Lipitor, Caduet), fluvastatin (Lescol), lovastatin (Mevacor, Altoprev, Advicor), pitavastatin (Livalo), pravastatin (Pravachol), rosuvastatin (Crestor), or simvastatin (Zocor, Simcor, Vytorin, Juvisync).

This list is not complete and other drugs may interact with danazol. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Danocrine is a prescription medication used to treat endometriosis and fibrocystic breast disease. Danocrine is also used in men and women to prevent attacks of angioedema.

Danocrine belongs to a group of drugs called androgens. These work by decreasing the amount of certain hormones.

This medication comes in a capsule (by mouth) form and is usually taken two to three times a day.

Common side effects of Danocrine include weight gain, acne, and sweating.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Call your doctor for instructions if you have missed doses for more than 2 days in a row.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Danazol is used to treat a number of different medical problems. These include:

• Endometriosis.
• Fibrocystic breast disease (cysts in the breasts).
• Hereditary angioedema (swelling of the different parts of the body, such as abdomen or stomach, arms, legs, throat, skin, or sexual organs.

This medicine is available only with your doctor's prescription.

Danocrine suppresses the pituitary-ovarian axis. This suppression is probably a combination of depressed hypothalamic-pituitary response to lowered estrogen production, the alteration of sex steroid metabolism, and interaction of danazol with sex hormone receptors. The only other demonstrable hormonal effect is weak androgenic activity. Danocrine depresses the output of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

Recent evidence suggests a direct inhibitory effect at gonadal sites and a binding of Danocrine to receptors of gonadal steroids at target organs. In addition, Danocrine has been shown to significantly decrease IgG, IgM and IgA levels, as well as phospholipid and IgG isotope autoantibodies in patients with endometriosis and associated elevations of autoantibodies, suggesting this could be another mechanism by which it facilitates regression of the disease.

Bioavailability studies indicate that blood levels do not increase proportionally with increases in the administered dose. When the dose of Danocrine is doubled the increase in plasma levels is only about 35% to 40%.

Separate single dosing of 100 mg and 200 mg capsules of Danocrine to female volunteers showed that both the extent of availability and the maximum plasma concentration increased by three-to-four fold, respectively, following a meal (> 30 grams of fat), when compared to the fasted state. Further, food also delayed mean time to peak concentration of Danocrine by about 30 minutes.

In the treatment of endometriosis, Danocrine alters the normal and ectopic endometrial tissue so that it becomes inactive and atrophic. Complete resolution of endometrial lesions occurs in the majority of cases.

Changes in vaginal cytology and cervical mucus reflect the suppressive effect of Danocrine on the pituitary-ovarian axis.

In the treatment of fibrocystic breast disease, Danocrine usually produces partial to complete disappearance of nodularity and complete relief of pain and tenderness. Changes in the menstrual pattern may occur.

Generally, the pituitary-suppressive action of Danocrine is reversible. Ovulation and cyclic bleeding usually return within 60 to 90 days when therapy with Danocrine is discontinued.

In the treatment of hereditary angioedema, Danocrine at effective doses prevents attacks of the disease characterized by episodic edema of the abdominal viscera, extremities, face, and airway which may be disabling and, if the airway is involved, fatal. In addition, Danocrine corrects partially or completely the primary biochemical abnormality of hereditary angioedema by increasing the levels of the deficient C1 esterase inhibitor (C1EI). As a result of this action the serum levels of the C4 component of the complement system are also increased.

Endometriosis

Danocrine is indicated for the treatment of endometriosis amenable to hormonal management.

Fibrocystic Breast Disease

Most cases of symptomatic fibrocystic breast disease may be treated by simple measures (e.g., padded brassieres and analgesics).

In infrequent patients, symptoms of pain and tenderness may be severe enough to warrant treatment by suppression of ovarian function. Danocrine is usually effective in decreasing nodularity, pain, and tenderness. It should be stressed to the patient that this treatment is not innocuous in that it involves considerable alterations of hormone levels and that recurrence of symptoms is very common after cessation of therapy.

Hereditary Angioedema

Danocrine is indicated for the prevention of attacks of angioedema of all types (cutaneous, abdominal, laryngeal) in males and females.

Because Danocrine may cause some degree of fluid retention, conditions that might be influenced by this factor, such as epilepsy, migraine, or cardiac or renal dysfunction, polycythemia and hypertension require careful observation. Use with caution in patients with diabetes mellitus.

Since hepatic dysfunction manifested by modest increases in serum transaminases levels has been reported in patients treated with Danocrine, periodic liver function tests should be performed (see WARNINGS and ADVERSE REACTIONS).

Administration of danazol has been reported to cause exacerbation of the manifestations of acute intermittent porphyria. (See CONTRAINDICATIONS.)

Laboratory monitoring of the hematologic state should be considered.

Drug Interactions

Prolongation of prothrombin time occurs in patients stabilized on warfarin. Therapy with danazol may cause an increase in carbamazepine levels in patients taking both drugs. Danazol can cause insulin resistance when used with antidiabetic drugs.

Danazol can raise the plasma level of cyclosporin and tacrolimus, leading to an increase of the renal toxicity of these drugs.

Danazol can increase the calcemic response to alpha calcidol in primary hypoparathyroidism.

Danazol can diminish the effectiveness of antihypertensive agents.

Laboratory Tests

Danazol treatment may interfere with laboratory determinations of testosterone, androstenedione and dehydroepiandrosterone. Other metabolic events include a reduction in thyroid binding globulin and T4 with increased uptake of T3, but without disturbance of thyroid stimulating hormone or of free thyroxin index.

Carcinogenesis, Mutagenesis, Impairment of Fertility

See WARNINGS section for information on carcinogenesis.

Pregnancy, Teratogenic Effects

(See CONTRAINDICATIONS.) Pregnancy Category X. Danocrine administered orally to pregnant rats from the 6th through the 15th day of gestation at doses up to 250 mg/kg/day (7–15 times the human dose) did not result in drug-induced embryotoxicity or teratogenicity, nor difference in litter size, viability or weight of offspring compared to controls. In rabbits, the administration of Danocrine on days 6–18 of gestation at doses of 60 mg/kg/day and above (2–4 times the human dose) resulted in inhibition of fetal development.

Nursing Mothers

(See CONTRAINDICATIONS.)

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.