Overview
11 DESCRIPTION ZOLADEX (goserelin implant) is a GnRH agonist. Goserelin acetate is chemically described as an acetate salt of [D-Ser(Bu t ) 6 ,Azgly 10 ]. Its chemical structure is pyro-Glu-His-Trp-Ser-Tyr-D-Ser(Bu t )-Leu-Arg-Pro-Azgly-NH 2 acetate [C 59 H 84 N 18 O 14· (C 2 H 4 O 2 ) x where x = 1 to 2.4].
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action ZOLADEX is a synthetic decapeptide analogue of GnRH. ZOLADEX 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. 12.2 Pharmacodynamics Following initial administration in males, ZOLADEX causes an initial increase in serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels with subsequent increases in serum levels of testosterone.
Indications
- 1 INDICATIONS AND USAGE ZOLADEX is a Gonadotropin Releasing Hormone (GnRH) agonist indicated for: Use in combination with flutamide for the management of locally confined carcinoma of the prostate ( 1.1 ) Palliative treatment of advanced carcinoma of the prostate ( 1.2 ) The management of endometriosis ( 1.3 ) Use as an endometrial-thinning agent prior to endometrial ablation for dysfunctional uterine bleeding ( 1.4 ) Use in the palliative treatment of advanced breast cancer in pre- and perimenopausal women ( 1.5 ) 1.
Common Doses
- 3.6 mg
- 10.8 mg
Dosage
2 DOSAGE AND ADMINISTRATION ZOLADEX, at a dose of 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 [see Dosage and Administration ( 2.7 )]. While a delay of a few days is permissible, every effort should be made to adhere to the 28-day schedule. ZOLADEX 3.6 mg should be administered subcutaneously every 28 days ( 2.1 , 2.7 ) For the management of endometriosis, the recommended duration of administration is 6 months for women 18 years of age and older ( 2.3 ) 2.
Contraindications
- 4 CONTRAINDICATIONS Hypersensitivity ( 4.1 ) Pregnancy unless used for treatment of advanced breast cancer ( 4.2 ) 4.1 Hypersensitivity Anaphylactic reactions to ZOLADEX 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 ZOLADEX [see Warnings and Precautions ( 5.6 )]. 4.2 Pregnancy ZOLADEX is contraindicated during pregnancy unless ZOLADEX is being used for palliative treatment of advanced breast cancer.
Side Effects
- 6 ADVERSE REACTIONS The most common, clinically significant adverse reactions occurring in >10% of men: hot flashes, sexual dysfunction, decreased erections and lower urinary tract symptoms ( 6 ) 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 ( 6 ) Tumor flare can occur on the initiation of ZOLADEX for both men and women being treated for cancer ( 6 )...
Interactions
- 7 DRUG INTERACTIONS No formal drug-drug interaction studies have been performed. No confirmed interactions have been reported between ZOLADEX and other drugs. None 7.1 Drug/Laboratory Test Interactions Administration of ZOLADEX in therapeutic doses results in suppression of the pituitary-gonadal system. Because of this suppression, diagnostic tests of pituitary-gonadotropic and gonadal functions conducted during treatment and until the resumption of menses may show results which are misleading. Normal function is usually restored within 12 weeks after treatment is discontinued.