goserelin (Rx)

>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

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 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.

Mechanism of Action

Gonadotropin-releasing hormone (LHRH) analog; chronic stimulation of goserelin results in suppression 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