Danocrine Information
Danocrine () Description
Danocrine () , brand of danazol, is a synthetic steroid derived from ethisterone. It is a white to pale yellow crystalline powder, practically insoluble or insoluble in water, and sparingly soluble in alcohol. Chemically, danazol is 17α-Pregna-2,4-dien-20-yno [2,3-]-isoxazol-17-ol. The molecular formula is CHNO. It has a molecular weight of 337.46 and the following structural formula:
Danocrine () capsules for oral administration contain 50 mg, 100 mg or 200 mg danazol.
Danocrine () Clinical Pharmacology
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.
Danocrine () 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. 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.
Danocrine () Contraindications
Danocrine () should not be administered to patients with:
Danocrine () Warnings
Use of danazol in pregnancy is contraindicated. A sensitive test (e.g., beta subunit test if available) capable of determining early pregnancy is recommended immediately prior to start of therapy. Additionally a non-hormonal method of contraception should be used during therapy. If a patient becomes pregnant while taking danazol, administration of the drug should be discontinued and the patient should be apprised of the potential risk to the fetus. Exposure to danazol in utero may result in androgenic effects on the female fetus; reports of clitoral hypertrophy, labial fusion, urogenital sinus defect, vaginal atresia, and ambiguous genitalia have been received. (See .)
Thromboembolism, thrombotic and thrombophlebitic events including sagittal sinus thrombosis and life-threatening or fatal strokes have been reported.
Experience with long-term therapy with danazol is limited. Peliosis hepatis and benign hepatic adenoma have been observed with long-term use. Peliosis hepatis and hepatic adenoma may be silent until complicated by acute, potentially life-threatening intraabdominal hemorrhage. The physician therefore should be alert to this possibility. Attempts should be made to determine the lowest dose that will provide adequate protection. If the drug was begun at a time of exacerbation of hereditary angioneurotic edema due to trauma, stress or other cause, periodic attempts to decrease or withdraw therapy should be considered.
Danazol has been associated with several cases of benign intracranial hypertension also known as pseudotumor cerebri. Early signs and symptoms of benign intracranial hypertension include papilledema, headache, nausea and vomiting, and visual disturbances. Patients with these symptoms should be screened for papilledema and, if present, the patients should be advised to discontinue danazol immediately and be referred to a neurologist for further diagnosis and care.
Preliminary epidemiological evidence suggests that the use of danazol might increase the baseline risk of ovarian cancer in patients being treated for endometriosis.
A temporary alteration of lipoproteins in the form of decreased high density lipoproteins and possibly increased low density lipoproteins has been reported during danazol therapy. These alterations may be marked, and prescribers should consider the potential impact on the risk of atherosclerosis and coronary artery disease in accordance with the potential benefit of the therapy to the patient.
Before initiating therapy of fibrocystic breast disease with Danocrine () , carcinoma of the breast should be excluded. However, nodularity, pain, tenderness due to fibrocystic breast disease may prevent recognition of underlying carcinoma before treatment is begun. Therefore, if any nodule persists or enlarges during treatment, carcinoma should be considered and ruled out.
Patients should be watched closely for signs of androgenic effects some of which may not be reversible even when drug administration is stopped.
Danocrine () Precautions
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 and ).
Administration of danazol has been reported to cause exacerbation of the manifestations of acute intermittent porphyria. (See .)
Laboratory monitoring of the hematologic state should be considered.
Danocrine () Adverse Reactions
The following events have been reported in association with the use of Danocrine () :
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 are menstrual disturbances including 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 Danocrine () , 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 Danocrine () of 400 mg or more. It is recommended that patients receiving Danocrine () 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 Danocrine () 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 Danocrine () 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 and erythema multiforme; : increased insulin requirements in diabetic patients, change in libido, myocardial infarction, palpitation, tachycardia, elevation in blood pressure, interstitial pneumonitis, and rarely, cataracts, bleeding gums, fever, pelvic pain, nipple discharge. Malignant liver tumors have been reported in rare instances, after long-term use.
Danocrine () Dosage And Administration
The total daily dosage of Danocrine () 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 Danocrine () 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 Danocrine () . 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.
Danocrine () How Supplied
Capsules of 200 mg (orange), bottles of 60 (NDC 0024-0305-60).Capsules of 200 mg (orange), bottles of 100 (NDC 0024-0305-06).Capsules of 100 mg (yellow), bottles of 100 (NDC 0024-0304-06).Capsules of 50 mg (orange and white), bottles of 100 (NDC 0024-0303-06).
Danocrine ()
