Danazol Information
Danazol ()
Danazol () Description
Danazol () is a synthetic steroid derived from ethisterone. Chemically, Danazol () is 17α-Pregna-2,4-dien-20-yno[2,3-]-isoxazol-17-ol, which has the following structural formula:
Each capsule, for oral administration, contains 50 mg, 100 mg or 200 mg of Danazol () . In addition, each capsule contains the following inactive ingredients: lactose monohydrate, magnesium stearate, sodium starch glycolate, and stearic acid.
The capsule shell contains D&C yellow no. 10, gelatin, silicon dioxide, sodium lauryl sulfate, and titanium dioxide. The 50 mg and 100 mg capsule shells also contain FD&C yellow no. 6. The 200 mg capsule shell also contains FD&C red no. 40 and D&C red no. 28.
The imprinting ink contains black iron oxide, D&C yellow no. 10 aluminum lake, FD&C blue no. 1 aluminum lake, FD&C blue no. 2 aluminum lake, FD&C red no. 40 aluminum lake, pharmaceutical glaze, and propylene glycol.
Danazol () Clinical Pharmacology
Danazol () 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. Danazol () 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 Danazol () to receptors of gonadal steroids at target organs. In addition, Danazol () 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 Danazol () is doubled the increase in plasma levels is only about 35% to 40%.
Separate single dosing of 100 mg and 200 mg capsules of Danazol () 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 Danazol () by about 30 minutes.
In the treatment of endometriosis, Danazol () 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 Danazol () on the pituitary-ovarian axis.
In the treatment of fibrocystic breast disease, Danazol () 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 Danazol () is reversible. Ovulation and cyclic bleeding usually return within 60 to 90 days when therapy with Danazol () is discontinued.
In the treatment of hereditary angioedema, Danazol () 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, Danazol () 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.
Danazol () Indications And Usage
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. Danazol () 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.
Danazol () Contraindications
Danazol () should not be administered to patients with:
Danazol ()
Danazol () Precautions
Because Danazol () may cause some degree of fluid retention, conditions that might be influenced by this factor, such as epilepsy, migraine, or cardiac or renal dysfunction, require careful observation.
Since hepatic dysfunction manifested by modest increases in serum transaminase levels has been reported in patients treated with Danazol () , periodic liver function tests should be performed (see and ).
Administration of Danazol () has been reported to cause exacerbation of the manifestations of acute intermittent porphyria. (See .)
Danazol () Adverse Reactions
The following events have been reported in association with the use of Danazol () :
Androgen like effects include weight gain, acne and seborrhea. Mild hirsutism, edema, hair loss, voice change, which may take the form of hoarseness, sore throat or of instability or deepening of pitch, may occur and may persist after cessation of therapy. Hypertrophy of the clitoris is rare.
Other possible endocrine effects include menstrual disturbances in the form of spotting, alteration of the timing of the cycle and amenorrhea. Although cyclical bleeding and ovulation usually return within 60-90 days after discontinuation of therapy with Danazol () , persistent amenorrhea has occasionally been reported.
Flushing, sweating, vaginal dryness and irritation and reduction in breast size, may reflect lowering of estrogen. Nervousness and emotional lability have been reported. In the male a modest reduction in spermatogenesis may be evident during treatment. Abnormalities in semen volume, viscosity, sperm count, and motility may occur in patients receiving long-term therapy.
Hepatic dysfunction, as evidenced by reversible elevated serum enzymes and/or jaundice, has been reported in patients receiving a daily dosage of Danazol () of 400 mg or more. It is recommended that patients receiving Danazol () be monitored for hepatic dysfunction by laboratory tests and clinical observation. Serious hepatic toxicity including cholestatic jaundice, peliosis hepatis, and hepatic adenoma have been reported. (See and )
Abnormalities in laboratory tests may occur during therapy with Danazol () including CPK, glucose tolerance, glucagon, thyroid binding globulin, sex hormone binding globulin, other plasma proteins, lipids and lipoproteins.
The following reactions have been reported, a causal relationship to the administration of Danazol () has neither been confirmed nor refuted: urticaria, pruritus and rarely, nasal congestion; headache, nervousness and emotional lability, dizziness and fainting, depression, fatigue, sleep disorders, tremor, paresthesias, weakness, visual disturbances, and rarely, benign intracranial hypertension, anxiety, changes in appetite, chills, and rarely convulsions, Guillain-Barre syndrome; gastroenteritis, nausea, vomiting, constipation, and rarely, pancreatitis; muscle cramps or spasms, or pains, joint pain, joint lockup, joint swelling, pain in back, neck, or extremities, and rarely, carpal tunnel syndrome which may be secondary to fluid retention; hematuria, prolonged posttherapy amenorrhea; an increase in red cell and platelet count. Reversible erythrocytosis, leukocytosis or polycythemia may be provoked. Eosinophilia, leukopenia and thrombocytopenia have also been noted. rashes (maculopapular, vesicular, papular, purpuric, petechial), and rarely, sun sensitivity, Stevens-Johnson syndrome; increased insulin requirements in diabetic patients, change in libido, elevation in blood pressure, and rarely, cataracts, bleeding gums, fever, pelvic pain, nipple discharge. Malignant liver tumors have been reported in rare instances, after long-term use.
Danazol () Dosage And Administration
The total daily dosage of Danazol () for fibrocystic breast disease ranges from 100 mg to 400 mg given in two divided doses depending upon patient response. A nonhormonal method of contraception is recommended when Danazol () is administered at this dose, since ovulation may not be suppressed.
In most instances, breast pain and tenderness are significantly relieved by the first month and eliminated in 2 to 3 months. Usually elimination of nodularity requires 4 to 6 months of uninterrupted therapy. Regular menstrual patterns, irregular menstrual patterns, and amenorrhea each occur in approximately one-third of patients treated with 100 mg of Danazol () . Irregular menstrual patterns and amenorrhea are observed more frequently with higher doses. Clinical studies have demonstrated that 50% of patients may show evidence of recurrence of symptoms within one year. In this event, treatment may be reinstated.
Danazol () How Supplied:
Danazol () Capsules, USP are available as:
Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).
Store at 20° to 25° C (68° to 77° F) [See USP Controlled Room Temperature].
Manufactured By:
BARR LABORATORIES, INC.
Pomona, NY 10970
Manufactured For:
TEVA PHARMACEUTICALS USA
Sellersville, PA 18960
Iss. 4/2009
Danazol () Principal Display Panel
Danazol ()
Capsules, USP
50 mg
Rx only
100 CAPSULES
TEVA
Danazol () Principal Display Panel
Danazol ()
Capsules, USP
100 mg
Rx only
100 CAPSULES
TEVA
Danazol () Principal Display Panel
Danazol ()
Capsules, USP
200 mg
Rx only
100 CAPSULES
TEVA
