Zoladex SC Injection

Goserelin is a synthetic decapeptide analogue of GnRH. Goserelin acts as an inhibitor of pituitary gonadotropin secretion when administered in the biodegradable formulation. In animal and in vitro studies, administration of goserelin resulted in the regression or inhibition of growth of the hormonally sensitive dimethylbenzanthracene (DMBA)-induced rat mammary tumor and Dunning R3327 prostate tumor.

Goserelin 3.6 mg: should be administered subcutaneously every 28 days into the anterior abdominal wall below the navel line using an aseptic technique under the supervision of a physician. While a delay of a few days is permissible, every effort should be made to adhere to the 28-day schedule.

• Stage B2-C Prostatic Carcinoma: When Goserelin is given in combination with radiotherapy and flutamide for patients with Stage T2b-T4 (Stage B2-C) prostatic carcinoma, treatment should be started 8 weeks prior to initiating radiotherapy and should continue during radiation therapy. A treatment regimen using a Goserelin 3.6 mg depot 8 weeks before radiotherapy, followed in 28 days by the Goserelin 10.8 mg depot, can be administered. Alternatively, four injections of 3.6 mg depot can be administered at 28-day intervals, two depots preceding and two during radiotherapy.
• Prostatic Carcinoma: For the management of advanced prostate cancer, Goserelin is intended for long-term administration unless clinically inappropriate.
• Endometriosis: For the management of endometriosis, the recommended duration of administration is 6 months. Currently, there are no clinical data on the effect of treatment of benign gynecological conditions with Goserelin for periods in excess of 6 months. Retreatment cannot be recommended for the management of endometriosis since safety data for retreatment are not available. If the symptoms of endometriosis recur after a course of therapy, and further treatment with Goserelin is contemplated, consideration should be given to monitoring bone mineral density. Clinical studies suggest the addition of Hormone Replacement Therapy (estrogens and/or progestins) to Goserelin is effective in reducing the bone mineral loss
• which occurs with Goserelin alone without compromising the efficacy of Goserelin in relieving the symptoms of endometriosis. The addition of Hormone Replacement Therapy may also reduce the occurrence of vasomotor symptoms and vaginal dryness associated with hypoestrogenism. The optimal drugs, dose and duration of treatment has not been established.
• Endometrial Thinning: For use as an endometrial-thinning agent prior to endometrial ablation, the dosing recommendation is one or two depots (with each depot given four weeks apart). When one depot is administered, surgery should be performed at four weeks. When two depots are administered, surgery should be performed within two to four weeks following administration of the second depot.
• Breast Cancer: For the management of advanced breast cancer, Goserelin is intended for long-term administration unless clinically inappropriate.
• Renal or Hepatic Impairment: No dosage adjustment is necessary for patients with renal or hepatic impairment.

Goserelin 10.8 mg: should be administered subcutaneously every 12 weeks into the anterior abdominal wall below the navel line using an aseptic technique under the supervision of a physician. While a delay of a few days is permissible, every effort should be made to adhere to the 12-week schedule.

• Stage B2-C Prostatic Carcinoma: When Goserelin is given in combination with radiotherapy and flutamide for patients with Stage T2b-T4 (Stage B2-C) prostatic carcinoma, treatment should be started 8 weeks prior to initiating radiotherapy and should continue during radiation therapy. A treatment regimen using one Goserelin 3.6 mg depot, followed in 28 days by one Goserelin 10.8 mg depot, should be administered.
• Prostatic Carcinoma: For the management of advanced prostate cancer, Goserelin is intended for long-term administration unless clinically inappropriate.
• Renal or Hepatic Impairment: No dosage adjustment is necessary for patients with renal or hepatic impairment.
• Women: Goserelin 10.8 mg implant is not indicated in women as the data are insufficient to support reliable suppression of serum estradiol. For female patients requiring treatment with goserelin, refer to prescribing information for Goserelin 3.6 mg implant.

Hypersensitivity: Anaphylactic reactions to Goserelin have been reported in the medical literature. ZOLADEX is contraindicated in those patients who have a known hypersensitivity to GnRH, GnRH agonist analogues or any of the components in Goserelin.

Pregnancy: Goserelin is contraindicated during pregnancy unless Goserelin is being used for palliative treatment of advanced breast cancer. Goserelin can cause fetal harm when administered to a pregnant woman. If this drug is used during pregnancy, the patient should be apprised of the potential hazard to the fetus. There is an increased risk for pregnancy loss due to expected hormone changes that occur with Goserelin treatment.

The most common, clinically significant adverse reactions occurring in >10% of men: hot flashes, sexual dysfunction, decreased erections and lower urinary tract symptoms.

The adverse event profile was similar for women treated for breast cancer, dysfunctional uterine bleeding or endometriosis and included (>20%): hot flushes, headache, sweating, acne, emotional lability, depression, decreased libido, vaginitis, breast atrophy, seborrhea, and peripheral edema. Tumor flare can occur on the initiation of Zoladex for both men and women being treated for cancer.

Goserelin is contraindicated during pregnancy unless Goserelin is being used for palliative treatment of advanced breast cancer. There are no adequate and well-controlled studies in pregnant women using Goserelin. Based on mechanism of action in humans and findings of increased pregnancy loss in animal studies, Goserelin can cause fetal harm when administered to a pregnant woman. If this drug is used during pregnancy, the patient should be apprised of the potential hazard to the fetus. There is an increased risk for pregnancy loss due to expected hormone changes that occur with Goserelin treatment. Goserelin crosses the placenta in rats and rabbits following subcutaneous administration. Administration of goserelin to pregnant rats and rabbits during organogenesis resulted in increased preimplantation loss and increased resorptions. When pregnant rats received goserelin throughout gestation and lactation, there was a dose-related increase in umbilical hernia in offspring. In additional reproduction studies in rats, goserelin decreased fetus and pup survival. Human dose/exposure multiples could not be calculated from available animal data.

It is not known if goserelin is excreted in human milk. Goserelin is excreted in the milk of lactating rats. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Goserelin, a decision should be made to either discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Women of Childbearing Potential and Pregnancy: Pregnancy must be excluded for use in benign gynecological conditions. Women should avoid pregnancy.

Tumor Flare Phenomenon: Transient worsening of tumor symptoms may occur during the first few weeks of treatment with Zoladex, which may include ureteral obstruction and spinal cord compression. Monitor patients at risk for complications of tumor flare.

Hyperglycemia and Diabetes: Hyperglycemia and an increased risk of developing diabetes have been reported in men receiving GnRH analogs. Monitor blood glucose level and manage according to current clinical practice.

Cardiovascular Diseases: Increased risk of myocardial infarction, sudden cardiac death and stroke has been reported in association with use of GnRH analogs in men. Monitor for cardiovascular disease and manage according to current clinical practice.

Hypercalcemia: Hypercalcemia has been reported in patients with bone metastases treated with Zoladex. Monitor and manage appropriately.

Hypersensitivity: Systemic hypersensitivity has been reported in patients receiving Zoladex/ Zoladex implants.

Cervical Resistance: Increase in cervical resistance may occur. Caution is recommended when dilating the cervix for endometrial ablation.

Effect on QT/QTc Interval: Androgen deprivation therapy may prolong the QT interval. Consider risks and benefits.

Injection Site Injury: Injection site injury and vascular injury have been reported during administration of Zoladex.

Depression: Depression may occur or worsen in women receiving GnRH agonists. Monitor and manage appropriately.

Keep away from light & moisture. Keep out of the reach of children.