Dosing and uses of Zoladex, Zoladex LA (goserelin)
Adult dosage forms and strengths
implant
- 3.6mg
- 10.8mg
Prostate Cancer
Monthly implant: 3.6 mg SC q28days
3-months implant: 10.8 mg SC q12week
Treat long-term
Place in upper abdominal walL
Breast Cancer
3.6 mg implant SC q28days
Treat long-term
Place in upper abdominal walL
Endometriosis
3.6 mg implant SC q28days
Treat for 6 months
Place in upper abdominal walL
Endometrial Thinning
3.8 mg SC q28days for 1 or 2 doses
Renal Impairment
Dose adjustment not necessary
Hepatic Impairment
Dose adjustment not necessary
Pediatric dosage forms and strengths
Safety and efficacy not established
Zoladex, Zoladex LA (goserelin) adverse (side) effects
>10%
Flushing (46-96%)
Vaginitis (5-75%)
Hot flashes (62%)
Reduced libido (47-61%)
Mood swings (60%)
Depression (women 54%)
Sweating (16-45%)
Acne (42%)
Diarrhea (40%)
Breast atrophy (33%)
Headache (women 32-75%)
Seborrhea (26%)
Tumor flare (23%)
Sexual dysfunction (21%)
Peripheral edema (21%)
Erectile dysfunction (18%)
Pain (8-17%)
UTI (13%)
1-10%
Nausea (9%)
Lethargy (8%)
Rash (6%)
Chronic obstructive pulmonary disease (5%)
Congestive heart failure(5%)
Cerebrovascular accident (1-5%)
Renal impairment (1-5%)
Headache (men 1-5%)
Depression (men 1-5%)
Immune hypersensitivity reaction (>1%)
Frequency not defined
Asthenia
Hypercalcemia
Cystitis
Dysmenorrhea
Hirsutism
Dyspareunia
Breast changes
Implant site reactions
Bone pain
Spinal cord compression (rare)
Postmarketing Reports
Bone mineral density: Osteoporosis, decreased bone mineral density, bony fracture in men
Cardiovascular: DVT, PE, MI, stroke, TIA observed in women treated with GnRH agonists
Ovarian cyst: Ovarian cyst formation and, in combination with gonadotropins, ovarian hyperstimulation syndrome
Changes in blood pressure: Hypotension and hypertension
Pituitary apoplexy and tumors: Pituitary apoplexy
Acne: Usually within 1 month of starting treatment
Other: Psychotic disorders, convulsions, mood swings
Warnings
Contraindications
Hypersensitivity to LHRH, LHRH-agonists, any component of product
Pregnancy (for endometriosis), lactation, undiagnosed abnormal vaginal bleeding
Cautions
Manifestations of disease may worsen at beginning of therapy
Increase in cervical resistance may occur; caution is recommended when dilating the cervix for endometrial ablation
Avoid pregnancy; premenopausal women should use nonhormonal contraception until >12 wk following end of treatment
Risk of reduced glucose tolerance in men
Males at risk of ureteral obstruction or spinal compression
Risk of pituitary apoplexy (rare)
Ongoing analysis found that men receiving GnRH agonists for prostate cancer were at a small increased risk for diabetes, heart attack, stroke, and sudden death
Do not exceed 1 year treatment duration with GnRH angonists in women except when treating breast cancer
Androgen deprivation therapy may prolong the QT interval; consider risks and benefits
Hypercalcemia has been reported in patients with bone metastases treated with goserelin; monitor and manage appropriately
Increased risk of myocardial infarction, sudden cardiac death and stroke reported in association with use of GnRH analogs in men; monitor for cardiovascular disease and manage according to current clinical practice
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
Pregnancy must be excluded for use in benign gynecological conditions
Transient worsening of tumor symptoms may occur during first few weeks of therapy, which may include ureteral obstruction and spinal cord compression; monitor patients at risk for complications of tumor flare
Injection site injury and vascular injury including pain, hematoma, hemorrhage and hemorrhagic shock, requiring blood transfusions and surgical intervention, reported; use extra care when administering to patients with low BMI and/or to patients receiving full dose anticoagulation
Pregnancy and lactation
Pregnancy category: D (advanced breast cancer); X (endometriosis, endometrial thinning)
Lactation: excretion in milk unknown; not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Zoladex, Zoladex LA (goserelin)
Mechanism of action
Gonadotropin-releasing hormone (LHRH) analog; chronic stimulation of goserelin results in suppresion of LH, FSH serum levels
Pharmacokinetics
Half-Life: 2-4 hr
Protein Bound: 27%
Time to Peak: 12-15 days (male); 8-22 days (female)
Vd: 44.1 L (Male); 20.3 L (female)
Excretion: Urine (90%)
Absorption
- 3.6 mg: absorbed slowly during first 8 days, then more rapid continuous release
- 10.8 mg: peak level within 24 hr, then decline until day 4, then concentrations stabilize