Trade Names:Zoladex- Implant 3.6 mg- Implant 10.8 mgZoladex 3.6 mg (Canada)Zoladex LA (Canada)
Synthetic analog of gonadotropin-releasing hormone (GnRH) that acts as potent inhibitor of pituitary gonadotropin secretion.
T max for the 3.6 mg implant is 12 to 15 days in men and 8 to 22 days in women. T max for the 10.8 mg implant is 2 h in men. C max for the 3.6 mg implant is about 1.46 ng/mL in women and 2.84 ng/mL in men and for the 10.8 mg is about 8 ng/mL in men.
Vd is 44.1 L in men and 20.3 L in women. Protein binding is 27%.
Hydrolysis of the C-terminal amino acids.
The t 1/ 2 for the 3.6 mg implant is 4.2 h in men and 2.3 h in women. More than 90% is excreted in urine, 20% unchanged. Mean systemic Cl for the 3.6 mg implant is 111 mL/min in men and to 164 mL/min in women.
2 to 4 wk.
In CrCl less than 20 mL/min, the t 1/ 2 is 12.1 h.Increased body weight
A decline in AUC of about 1% to 2.5% was observed with a kg increase in body weight.
Palliative treatment of advanced breast cancer in pre- and peri-menopausal women; treatment of endometriosis; as an endometrial thinning agent prior to endometrial ablation for dysfunctional uterine bleeding.Goserelin 3.6 and 10.8 mg implants
Palliative treatment of advanced carcinoma of the prostate; in combination with flutamide for management of locally confined Stage T2b-T4 (Stage B2-C) carcinoma of the prostate.
Breast-feeding; women being treated for endometriosis or endometrial thinning who are or may become pregnant; known hypersensitivity to LHRH, LHRH agonist analogs, or any component of the product; 10.8 mg goserelin implant is not indicated in women.
Subcutaneous 3.6 mg implant every 28 days into upper abdominal wall by sterile technique under health care provider's supervision.Adults 12 weeks
Subcutaneous 10.8 mg implant every 12 wk into upper abdominal wall by sterile technique under health care provider's supervision.Advanced Breast CancerAdults
Subcutaneous (3.6 mg only). Intended for long-term administration unless clinically inappropriate.EndometriosisAdults
Subcutaneous (3.6 mg only). Current recommended duration of treatment is 6 mo.Endometrial ThinningAdults
Subcutaneous (3.6 mg only). Recommendation is 1 or 2 depots, given 4 wk apart. When 1 depot is administered, surgery should be at 4 wk. When 2 depots are administered, surgery should be within 2 to 4 wk following the second depot.Prostatic CarcinomaAdults
Subcutaneous (3.6 or 10.8 mg). Intended for long-term administration unless clinically inappropriate.Stage B2 to C Prostatic CarcinomaAdults
Subcutaneous (3.6 or 10.8 mg only). When given in combination with radiotherapy and flutamide, start treatment 8 wk prior to initiating radiotherapy and continue during radiation therapy. A regimen using goserelin 3.6 mg depot 8 wk before radiotherapy, followed in 28 days by the 10.8 mg depot, can be administered. Alternatively, 4 injections of 3.6 mg depot can be administered at 28 day intervals, 2 depots preceding the 2 during radiotherapy.
Store preloaded syringe in foil pouch at controlled room temperature (less than 77°F). Do not remove syringe from foil pouch until just prior to use.
None well documented.
Results may be misleading.Estrogen
Drug may cause initial transient increase in serum levels in women.Hypercalcemia in patients with bone metastases
Drug may cause initial transient increase.Testosterone
Drug may cause initial transient increases in serum levels in men.
Vasodilation (57%); migraine (7%); hypertension (6%); chest pain, hemorrhage, palpitations, tachycardia (at least 1%)Men
CHF (5%); angina pectoris, arrhythmia, cerebral ischemia, cerebrovascular accident, chest pain, heart failure, hypertension, MI, peripheral vascular disorder, pulmonary embolus, varicose veins (greater than 1% but less than 5%).
Headache (75%); emotional lability (60%); depression (54%); insomnia, asthenia (11%); dizziness (6%); fatigue, lethargy, malaise, nervousness (5%); hypertonia, abnormal thinking, anxiety, paresthesia somnolence (at least 1%).Men
Lethargy (8%); dizziness, insomnia (5%); anxiety, depression, headache, paresthesia (greater than 1% but less than 5%).
Hot flashes (96%); sweating (45%); acne (42%); seborrhea (26%); hirsutism (7%); hair disorder (4%); pruritus (2%); alopecia, dry skin, ecchymosis, skin discoloration (at least 1%).Men
Hot flashes (62%); rash, sweating (6%); herpes simplex, pruritus (greater than 1% but less than 5%).
Pharyngitis (6%); amblyopia, dry eyes (at least 1%).
Nausea, abdominal pain (11%); vomiting (4%); increased appetite (2%); anorexia, constipation, diarrhea, dry mouth, dyspepsia, flatulence (at least 1%).Men
Anorexia, nausea (5%); abdominal pain, constipation, diarrhea, hematemesis, ulcer, vomiting (greater than 1% but less than 5%).
Vaginitis (75%); decreased libido (61%); breast atrophy (33%); breast enlargement, pelvic symptoms (18%); dyspareunia (14%); increased libido (12%); breast pain, dysmenorrhea (7%); uterine hemorrhage (6%); vulvovaginitis (5%); menorrhagia (4%); urinary frequency, UTI, vaginal hemorrhage (at least 1%).Men
Sexual dysfunction (21%); decreased erections (18%); lower UTIs (13%); bladder neoplasm, breast swelling and tenderness, hematuria, impotence, renal function impairment, urinary obstruction, urinary frequency, urinary incontinence, urinary infrequency, urinary retention, urinary tract disorder, UTI (greater than 1% but less than 5%).
Anemia (greater than 1% but less than 5%).
Elevated liver enzymes (ALT, AST) (at least 1%).
Weight gain (3%).Men
Diabetes mellitus, gout, hyperglycemia, weight increase (greater than 1% but less than 5%); decreased bone mineral density and bony fracture in men, osteoporosis (postmarketing).
Back pain (7%); myalgia (3%); leg cramps (2%); arthralgia, joint disorder (at least 1%).Men
Back pain (greater than 1% but less than 5%).
Sinusitis (3%); bronchitis, epistaxis, increased cough, rhinitis (at least 1%).Men
Upper respiratory infection (7%); chronic obstructive pulmonary disease (5%); dyspnea, increased cough, pneumonia (greater than 1% but less than 5%).
Tumor flare (23%); peripheral edema (21%); pain (17%); infection (13%); flu syndrome (5%); voice alterations (3%), edema, fever (at least 1%).Men
Pain, edema (8%); flu syndrome, sepsis, peripheral edema (greater than 1% but less than 5%).
MonitorTestosterone/Prostatic acid phosphatase
Ensure serum testosterone and prostatic acid phosphatase are periodically measured in patient being treated for prostate cancer to assess therapeutic response.
Category D (breast cancer); Category X (endometriosis, endometrial thinning, 10.8 mg strength).
Undetermined. Discontinue the drug prior to breast-feeding.
Safety and efficacy not established.
Antibody formation to goserelin has been observed. Anaphylactic reactions are possible.
Isolated cases of spinal cord compression and ureteral obstruction have been reported in men. Use with caution in patients prone to these problems.
Decreases in vertebral trabecular bone mineral density have been observed; patients with certain risk factors (eg, alcohol or tobacco abuse, family history of osteoporosis) may be at additional risk.
Drug initially causes transient increase in estrogen. Worsening of signs and symptoms of breast cancer, such as bone pain, may occur during the first few weeks of treatment.
Drug initially causes transient increase in testosterone. Worsening of signs and symptoms of prostate cancer, such as bone pain, may occur during first few weeks of treatment.
The 10.8 mg implant is not indicated in women as the data are insufficient to support reliable suppression of serum estradiol.
Clinical studies suggest the addition of HRT (estrogens or progestins) to goserelin may decrease the occurrence of vasomotor symptoms and vaginal dryness associated with hypoestrogenism without compromising the efficacy of goserelin in relieving pelvic symptoms. The optimal drugs, dose, and duration of treatment not established.
Hypercalcemia has occurred in some prostate and breast cancer patients with bone metastases after starting goserelin treatment. Ensure serum calcium levels are monitored in patient being treated for prostate or breast cancer. Inform health care provider immediately if hypercalcemia is noted or patient develops signs or symptoms of hypercalcemia (eg, polyuria, confusion, drowsiness). Be prepared to treat appropriately (eg, sodium chloride 0.9% injection, furosemide).
Hypoestrogenism may be induced by goserelin, which results in loss of bone mineral density over the course of treatment and may be irreversible. Adverse reactions occurring with hypoestrogenism most frequently include hot flashes, headaches, vaginal dryness, emotional lability, changes in libido, depression, sweating, and change in breast size.
As with other hormonal interventions that disrupt pituitary-gonadal axis, some patients may experience a delay in return to menses and, rarely, patients may experience persistent amenorrhea.
Some women experience vaginal bleeding of variable duration and intensity. The bleeding represents estrogen withdrawal bleeding and is expected to stop spontaneously.
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