Bipolar I disorder (Endoxifen)
ZONALTA (Endoxifen), being an active metabolite of tamoxifen, warnings and precautions of tamoxifen will also be applicable to ZONALTA and hence, the same have been mentioned here accordingly.
Hematologic Events
Hematological effects of ZONALTA administered orally are not known. However, thrombolism may be more common in patients treated with tamoxifen, though this is not certain, as patients with cancer are at increased risk anyway. A small reduction in antithrombin III concentration was noted in a study of 11 postmenopausal women treated with tamoxifen, and no significant reduction was seen in a group of premenopausal women. There is evidence of an increased incidence of thromboembolic events, including deep vein thrombosis and pulmonary embolism, during tamoxifen citrate therapy.
Endocrine and Reproductive Systems
ZONALTA’s anti-estrogenic adverse events in pre or post-menopausal women are unknown. However, the anti-estrogenic effects of tamoxifen in premenopausal women receiving therapeutic doses can cause irregular menses. Anti-estrogenic adverse effects in women treated with tamoxifen include vasomotor symptoms (hot flushes), vaginal bleeding and pruritis vulvae.
Effects in Metastatic Breast Cancer Patients
As with other additive hormonal therapy (estrogens and androgens), hypercalcemia has been reported in some breast cancer patients with bone metastases within a few weeks of starting treatment with tamoxifen citrate. If hypercalcemia does occur, appropriate measures should be taken and, if severe, ZONALTA citrate should be discontinued.
Effects on the Uterus-Endometrial Cancer and Uterine Sarcoma
An increased incidence of uterine malignancies has been reported in association with tamoxifen citrate treatment. The underlying mechanism is unknown, but may be related to the estrogen-like effect of tamoxifen citrate. Most uterine malignancies seen in association with tamoxifen citrate are classified as adenocarcinoma of the endometrium. However, rare uterine sarcomas, including malignant mixed mullerian tumors (MMMT), have also been reported.
Non-Malignant Effects on the Uterus
Increased incidences of endometrial changes including hyperplasia and polyps have been reported in association with tamoxifen citrate treatment. There have been a few reports of endometriosis and uterine fibroids in women receiving tamoxifen citrate. Ovarian cysts have also been observed in a small number of premenopausal patients with advanced breast cancer who have been treated with tamoxifen citrate. Tamoxifen citrate has also been reported to cause menstrual irregularity or amenorrhea.
Hepatic Effects
Tamoxifen citrate has been associated with changes in liver enzyme levels, and on rare occasions, a spectrum of more severe liver abnormalities including fatty liver, cholestasis, hepatitis and hepatic necrosis. Few cases of liver cancer have been reported with tamoxifen citrate in clinical trials.
Effects on the Eye
Ocular disturbances, including corneal changes, decrement in color vision perception, retinal vein thrombosis, and retinopathy have been reported in patients receiving tamoxifen citrate. An increased incidence of cataracts and the need for cataract surgery have been reported in patients receiving tamoxifen citrate.
Pregnancy Category D
There are no adequate and well-controlled trials of ZONALTA and tamoxifen in pregnant women. There have been a small number of reports of vaginal bleeding, spontaneous abortions, birth defects, and fetal deaths in pregnant women with tamoxifen citrate. If ZONALTA is used during pregnancy, or the patient becomes pregnant while taking this drug, or within approximately two months after discontinuing therapy, the patient should be apprised of the potential risks to the fetus including the potential long-term risk of a DES-like syndrome.
General
Decreases in platelet counts, usually to 50,000-100,000/mm³, infrequently lower, have been occasionally reported in patients taking tamoxifen citrate for breast cancer. In patients with significant thrombocytopenia, rare hemorrhagic episodes have occurred, but it is uncertain if these episodes are due to tamoxifen citrate therapy. Leukopenia has been observed, sometimes in association with anemia and/or thrombocytopenia. There have been rare reports of neutropenia and pancytopenia in patients receiving tamoxifen citrate; this can sometimes be severe.
ZONALTA Contraindications
ZONALTA is contraindicated in patients who have a history of hypersensitivity to tamoxifen or any of the constituents of endoxifen citrate. ZONALTA is contraindicated in patients who require concomitant coumarin-type anticoagulant therapy or in patients with a history of deep vein thrombosis or pulmonary embolus.
Adverse Reactions of ZONALTA (Endoxifen)
The most frequently reported AEs with ZONALTA (in descending order of occurrence) were headache, vomiting, insomnia. There were no deaths, serious or significant AEs during the conduct of the trial. Other side effects were: gastritis, epigastric discomfort, diarrhoea, restlessness, somnolence etc.