Vabon

Danazol.

VABON - 100: Each capsule contains: Danazol 100 mg.
VABON (- 200): Each capsule contains: Danazol 200 mg.

Pharmacology: Pharmacokinetics: Absorption: Blood levels of danazol do not increase proportionately with increase in dose. When the dose is doubled, plasma levels increase only approximately 35% to 40%. Bioavailability and peak plasma concentrations of danazol increased by 3- to 4-fold, respectively, in healthy woman who received 100- and 200-mg of danazol as single doses with a high-fat meal (more than 30 g of fat) compared with those who received the drug under fasting conditions. In addition, administration with food delayed mean time to reach peak plasma danazol concentrations by about 30 minutes.
Distribution and Elimination: Danazol is metabolized to 2-hydroxy-methylethisterone, which appears in the plasma in a concentration 5-10 times greater than that of the unchanged drug.
Pharmacodynamics: Danazol is a synthetic derivative of ethisterone (ethinyl testosterone) with weak androgenic and anabolic properties and no estrogenic or progestrogenic activity. Danazol suppresses the pituitary-ovarian axis by inhibiting the output of pituitary gonadotropins. It also has weak, androgenic activity. Danazol depresses the output of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH). There is evidence that danazol directly inhibits the synthesis of sex steroids and binds to gonadal (sex) steroid receptors in the cytoplasm of target tissues and may thereby exhibit antiestrogen, anabolic, and weakly androgenic effects. The drug possesses weak androgenic and anabolic properties but exerts no estrogenic or progestogenic activities; androgenic activity is dose related. 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. Generally, the pituitary suppressive action is reversible. Ovulation and cyclic bleeding usually return within 60 to 90 days after therapy is discontinued.
Endometriosis: 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.
Hereditary Angioedema: Danazol prevents attacks of the disease characterized by episodic edema of the abdominal viscera, extremities, face, and airway that may be disabling and, if the airway is involved, fatal. In addition, danazol partially or completely corrects the primary biochemical abnormality of hereditary angioedema. It increases the levels of the deficient C1 esterase inhibitor, thereby increasing the serum levels of the C4 component of the complement system.

VABON is indicated for the treatment of endometriosis, associated infertility, benign breast disease including gynaecomastia, mazoplasia and mastodynia, menorrhagia, primary constitutional precocious puberty and other similar endocrine disorders, where a control of the release of pituitary gonadotropins would be of therapeutic value and also for the prophylaxis of hereditary angioedema.

VABON is administered orally. For the treatment of endometriosis and fibrocystic breast disease, administration of the drug should be initiated during menstruation.
Endometriosis: For the palliative treatment of endometriosis in patients with moderate to severe disease or in patients who are infertile because of endometriosis, the usual initial dosage of VABON is 800 mg daily given in 2 divided doses. Amenorrhea and a rapid improvement in painful symptoms are best achieved at this dosage. Subsequent dosage may be gradually reduced, depending on the patient's therapeutic response, to a level sufficient to maintain amenorrhea. For the treatment of endometriosis in patients with mild disease, the usual initial dosage is 200 - 400 mg daily given in 2 divided doses. Subsequent dosage should be adjusted according to the patient's tolerance and therapeutic response.
Fibrocystic Breast Disease: For the symptomatic management of fibrocystic breast disease, the usual dosage of VABON is 100 - 400 mg daily given in 2 divided doses. Dosage should be individualized according to severity of the disease and the patient's response to treatment. Since ovulation may not be suppressed when VABON is administered at this dosage, an effective nonhormonal method of contraception is recommended during therapy with the drug.
Hereditary Angioedema: For the prophylactic treatment of hereditary angioedema, the usual initial dosage of VABON is 200 mg 2 or 3 times daily. After an initial response is obtained, subsequent maintenance dosage should be determined by decreasing the dosage by 50% or less at intervals of 1 - 3 months or longer, depending on the frequency of attacks prior to initiation of VABON therapy. If an attack occurs during treatment with the drug, dosage may be increased by up to 200 mg daily. Dosage requirements for continuous prophylaxis should be individualized according to the patient's response to treatment.
Menorrhagia: Adults, 200 mg daily for 12 weeks. In some cases the dosage may be increased to 400 mg daily or as directed by the physicians.
Primary Constitutional Precocious Puberty: Children, 100 - 200 mg daily according to the child's age and weight.

No data available.

VABON is contraindicated in pregnant or nursing women and in patients with abnormal genital bleeding of unknown etiology. The drug is also contraindicated in patients with markedly impaired hepatic, renal, or cardiac function and in those with porphyria. VABON can induce aminoevulinate acid (ALA) synthetase activity and hence porphyrin metabolism.

Because VABON may cause fluid retention, the drug should be used with caution in patients who may be adversely affected by this condition such as those with seizure disorders, migraine, or cardiac or renal dysfunction.
Periodic evaluations of liver function should be performed in all patients receiving VABON, since the drug may cause hepatic dysfunction.
Semen should be evaluated for volume, viscosity, and sperm count and motility every 3 - 4 months during VABON therapy, especially in adolescents.
Patients should be carefully monitored for sign of virilization, since some adverse androgenic effects may not subside after discontinuance of the drug.
VABON has been associated with peliosis of the liver and benign or malignant hepatic adenoma, and such hepatic effects may not be apparent until complicated by acute, potentially life-threatening intra-abdominal hemorrhage; clinicians should be aware that such hepatotoxicity may develop during long-term administration of VABON.
Patients receiving VABON who develop signs and/or symptoms of pseudotumor cerebri (e.g., headache, nausea and vomiting, visual disturbances) should be examined for the presence of papilledema and informed to discontinue the drug immediately if any such manifestation is present; such patients should be referred to a neurologist for further evaluation and care.
Since substantial alterations in lipoprotein profiles (e.g., decreases in serum high-density lipoproteins, increases in serum low-density lipoproteins) have been reported in patients receiving VABON therapy, clinicians should be consider the potential increased risk of cardiovascular disease (e.g., coronary artery disease, atherosclerosis) versus the possible benefits of therapy.
The possibility of carcinoma of the breast should be excluded before initiating VABON therapy in patients with fibrocystic breast disease. Nodularity, pain and tenderness caused by fibrocystic breast disease may prevent recognition of underlying carcinoma before initiation of therapy. If any nodule persists or enlarges during VABON therapy, carcinoma should be considered and ruled out.

Use in pregnancy: Category X.
VABON may cause fetal harm when administered to pregnant woman. Androgenic effects including clitoral hypertrophy, labial fusion of the external genital fold to form a scrotal-like structure, ambiguous genitalia, abnormal vaginal development, and persistence of a urogenital sinus have occurred in the female offspring of woman who were given VABON during pregnancy. Spontaneous abortions have also occurred in pregnant woman who received the drug. Since the risks clearly outweigh the possible benefits in woman who are or may become pregnant, VABON is contraindicated in such woman. Woman of childbearing age should be instructed to use an effective, non hormonal method of contraception during VABON therapy and be informed of the potential hazard to the fetus should they become pregnant during therapy. In addition, a reliable pregnancy test must be performed immediately prior to beginning VABON therapy. If the drug is inadvertently administered during pregnancy or if the patient becomes pregnant while receiving the drug, administration of VABON should be discontinued, and the woman should be apprised of the potential risk to the fetus.
Use in nursing mother: Breast-feeding is contraindicated in patients taking VABON. Because of the potential for serious adverse reactions to VABON in nursing infants, a decision should be made whether to discontinue nursing or not use the drug, taking into account the importance of the drug to the woman.

Endocrine Effects: Mild hirsutism, decreased breast size, voice changes, sore throat, acne, increased oiliness of skin or hair, hair loss, weight gain, edema, clitoral hypertrophy, testicular atrophy, flushing, sweating, emotional lability, vaginitis with itching, dryness, burning, and/or bleeding, glucose intolerance.
Genitourinary Effects: Mentrual irregularities, hematuria, reduction in spermatogenesis, abnormalities in semen volume, viscosity, sperm count, and motility.
Hepatic Effects: Cholestatic jaundice, peliosis of the liver, benign or malignant hepatic adenoma.
Nervous System Effects: Benign intracranial hypertension, headache, papilledema, nausea, vomiting, anxiety, depression, dizziness, fainting, fatigue, Guillain-Barre Syndrome, nervousness, seizures, sleep disorders, syncope, paresthesias, tremor, weakness.
Cardiovascular Effects: Increased blood pressure, thromboembolism, thrombotic or thrombophlebetic events.
Dermatologic and Sensitivity Reactions: Allergic reactions, urticaria, pruritus, petechiae, rash.
GI Effects: Gastroenteritis, changes in appetite, nausea, vomiting, constipation, bleeding gum.
Musculoskeletal Effects: Muscle cramps or spasm, joint pain or swelling, locked joints, pain in the back, neck, legs, or rarely, pelvis, carpal tunnel syndrome.
Hematologic Effects: Reversible erythrocytosis, leucocytosis, polycythemia, eosinophilia, leucopenia, increased erythrocyte and platelet counts.
Ocular Effects: Visual disturbances, conjunctival edema, cataracts.
Other Adverse Effects: Fever, chills, nasal congestion, pancreatitis.

Carbamazepine: Therapy with VABON may cause an increase in Carbamazepine levels in patients taking both drugs.
Cyclosporine: An increased cyclosporine blood concentration with possible toxicity (eg, nephrotoxicity) has occurred. Monitor serum bilirubin, serum creatinine, and cyclosporine concentrations in patients receiving concomitant therapy. Adjust doses of drugs as needed.
Warfarin: Prolongation of prothrombin time has been reported with concomitant use.
Drug/Lab test interactions: VABON treatment may interfere with laboratory determinations of testosterone, androstenedione, and dehydroepiandrosterone. Abnormality in laboratory test may occur during therapy with VABON including the following: CPK, glucose tolerance, glucagon, thyroid-binding globulin, sex hormone-binding globulin, other plasma proteins, lipids, and lipoproteins.

VABON - 100: Store at temperature not exceeding 30°C and protect from light.
VABON (-200): Store at temperature not exceeding 30°C and protect from light.

Trophic Hormones & Related Synthetic Drugs

G03XA01 - danazol ; Belongs to the class of antigonadotropins and similar agents.

D