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

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

Patients may experience one or two additional menstrual periods when treated with ZENDOL™, 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.

ZENDOL™ should not be administered to patients who are breast feeding.

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 virilisation. Some androgenic effects may not be reversible even when drug administration is stopped.

Therapy with Zendol™ is discouraged in patients with porphyria since it may increase ALA Synthetase activity and hence prophyrin metabolism.

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

ADVERSE REACTIONS
Acne, oedema, 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 and vaginal bleeding, nervousness and emotional lability 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 ZENDOL™ therapy.

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

Laboratory tests like CPK, glucose tolerance, glucagons, thyroid binding globulin, sex hormone binding globulin, other plasma proteins, lipids and lipoproteins may show abnormalities during ZENDOL™ 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 which have been reported infrequently.

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

(a) Female (Adult):
Endometriosis and associated infertility: 200-800 mg daily in divided doses. Dosage should be increased (but not to exceed 800mg 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 ZENDOL™.

(b) Males:
Gynaecomastia: 200-800 mg daily, in divided doses, with respect to 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: 100-400 mg daily, according to patient’s age and weight.

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

STORAGE
Store in cool, dry and dark place.

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