ZENDOL

                  

                           ZENDOL

                Rx

                               Danazol Capsules IP.

         _________  ___________________

DESCRIPTIONS :

                     Danazol, which is a synthetic hormone derived from ethisterone. It is identified as 17 alpha-pregnancy-2, 4-dien-20-no  (2,   3-d)  isoxazole-17-ol,   chemically. Each hard gelatin capsule contains 50 mg or 100 mg or 200 mg of danazol. 

 PHARMACOLOGICAL ACTION:

                        Danazol inhibits secretions of pituitary gonadotrophins in both males and females thus suppressing the pituitary-gonadal axis. 

Proven reports indicate Danazol to be non-commital in case of estrogenic or progestational activity. However, it does possess mild androgenic activity. 

Endometriosis is treated by Danazol which renders the endometrium inactive while effecting the regression of ectopic endometrial tissue. Endoscopic observation reveals that the complete resolution of endometrial lesions occurs in most cases. Changes in vaginal cytology and cervical mucus reflects the suppressive effect of Danazol on the pituitary-ovarian axis. 

Patients may experience one or two additional menstrual periods when treated with Danazol, depending on the dosage used and the stage of the cycle. They then become anovulatory and amenorrhoeic with occasional spotting for the duration of treatment. Pelvic pain is usually relieved within the first few weeks after initiation of therapy; relief of dyspareunia and induration of the cul-de-sac takes a somewhat longer time. Ovulation and predictable cyclic bleeding generally return with discontinuation of therapy, usually within 60 to 90 days. 

INDICATION:

Danazol is recommended for the treatment of endometriosis, associated infertility, benign breast disease (chronic cystic mastitis, mastodynia), menorrhagia, gynecomastia, and primary constitutional precocious puberty. 

CONTRAINDICATION :

During pregnancy: Reproductive studies in animals do not attribute any embryotoxic or teratogenic effects to Danazol administration. Clinically, however, safe use of the drug in pregnancy has not been established. Therefore, Danazol should not be administered to pregnant women. Moreover, to avoid pregnancy women should use nonhormonal contraceptive methods during Danazol therapy. Discontinuation of the drug is strongly recommended if a patient becomes pregnant during treatment. Continuing treatment may result in an androgenic effect on the female fetus. 

Danazol should not be administered to patients who are breastfeeding. 

Therapy with steroids alkylated at the 17  -position has been associated with serious toxicity  (cholestatic jaundice, peliosis hepatis, and hepatic adenomas). The physician should be alert to the possibility that such toxicity may develop with danazol. 

Patients should be watched closely for signs of virilization. Some androgenic effects may not be reversible even when drug administration is stopped. 

PRECAUTIONS :

                         It is possible that danazol may cause some degree of fluid retention. Here, conditions such as epilepsy, migraine, or renal dysfunction, require careful observation. Since hepatic dysfunction has been reported in patients treated with danazol periodic liver function tests should be performed. 

Therapy with danazol is discouraged in patients with porphyria since it may increase ALA Synthetase activity and hence porphyrin metabolism

DRUG INTERACTION :

                  Prolongation of prothrombin time occurs in patients stabilized on warfarin. Danazol may cause an increase in carbamazepine levels in patients taking both drugs and elevate insulin requirements in diabetic patients.

ADVERSE / SIDE REACTIONS:

                        Acne, edema, mild hirsutism, decrease in breast size, deepening of the voice, oiliness of the skin or hair, weight gain, and rarely, clitoral hypertrophy. 

Hypoestrogenic manifestations such as sweating, vaginitis including itching, dryness, burning have been reported. 

A short-term change in the form of decreased high-density lipoproteins and possibly increased low-density lipoproteins has been reported during danazol therapy. 

In patients, a daily intake of danazol of 400 mg or more, hepatic abnormalities, as evidenced by reversible elevated serum enzymes and/or jaundice has been reported. 

Laboratory tests like CPK, glucose tolerance, glucagon, thyroid-binding globulin, sex hormone-binding globulin, other plasma proteins, lipids, and lipoproteins may show abnormalities during danazol therapy. 

Skin rashes, flushing, dizziness, headache, nervousness, benign intracranial hypertension, thrombotic events, including sagittal sinus thrombosis and cerebrovascular accident (CVA). Nausea, backache, and hair loss are the other reactions that have been reported infrequently. 

DOSAGE & ADMINISTRATION : 

The following dosage regimens are recommended and should be adjusted according to the condition being treated and the patient's response:

(a) Females (adult) :

Endometriosis and associated infertility: 200-800 mg daily in divided doses. Dosage should be increased (but not to exceed 800 mg per day) if symptoms are not relieved in 30 to 60 days at lower doses (200-400 mg per day). Treatment should continue uninterrupted for 3 to 6 months but may be extended to 9 months if necessary. 

Benign breast disease (chronic cystic mastitis, virginal breast hyperplasia, mazoplasia, mastodynia):100-400 mg daily, in divided doses. Increase dosage if symptoms are not relieved in 30 to 60 days, at a lower dose. Treatment may continue for up to 3 to 6 months. 

Menorrhagia: 200 mg daily, for 12 weeks. Exceptional cases may need up to 400 mg daily. 

Therapy should begin during menstruation. Otherwise, appropriate tests should be performed to ensure that the patient is not pregnant while on therapy with Gynaecomastia.

(b) Males :

Gynaecomastia: 200 to 800 mg daily, in divided doses, with respect to the patient's age and weight. 

An inconsiderable reduction in spermatogenesis may be evident during treatment. Dysfunctions in semen volume, viscosity, sperm count and motility may occur in patients receiving long term therapy.

(c) Children:

Primary constitutional precocious puberty: 100 to 400 mg daily, according to patient's age and weight. 

For this, a twice-daily administration is recommended. Treatment may be reconstituted if symptoms recur after the termination of medication. 

STORAGE :

Store below 30-degree c. Protect from light and moisture 

Presentation :

Capsules of 50 mg, 100 m,g, and 200 mg, in blisters of 10 capsules each.

         

            Manufactured by ;

   Maneesh Pharmaceuticals Ltd.