Introduction
Zoladex (goserelin acetate) is a synthetic analog of gonadotropin-releasing hormone (GnRH) used primarily in the management of hormone-responsive cancers and certain gynecological conditions. Manufactured by AstraZeneca, it is formulated as a subcutaneous implant that provides sustained release of medication over periods of 1-3 months.
Mechanism of Action
Zoladex acts as a GnRH agonist. Initially, it stimulates pituitary gonadotropin release, causing a transient increase in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. With continuous administration, it downregulates GnRH receptors in the pituitary gland, leading to suppression of gonadotropin secretion and subsequent reduction in gonadal steroid production. In males, this results in decreased testosterone levels to castration range; in females, it suppresses estrogen production.
Indications
- Advanced prostate cancer (palliative treatment)
- Early-stage prostate cancer (as part of combination therapy)
- Breast cancer in pre- and perimenopausal women
- Endometriosis management (limited duration therapy)
- Endometrial thinning prior to endometrial ablation or resection
- Central precocious puberty (pediatric use in specific formulations)
Dosage and Administration
Standard dosing:- 3.6 mg implant administered subcutaneously every 28 days
- 10.8 mg implant administered subcutaneously every 12 weeks
- Administer into upper abdominal wall using sterile technique
- Local anesthetic may be used prior to implantation
- Rotate injection sites with each administration
- Renal impairment: No dosage adjustment required
- Hepatic impairment: No specific recommendations
- Elderly: No dosage adjustment required
- Pediatrics: Specific dosing for precocious puberty (specialist supervision required)
Pharmacokinetics
Absorption: Slowly released from implant, achieving steady state within 2-4 weeks Distribution: Volume of distribution approximately 44.1 L Metabolism: Undergoes hydrolysis and degradation to smaller peptides Elimination: Clearance approximately 3.1 L/h, elimination half-life 2-4 hours for goserelin Excretion: Primarily renal (90%), with 20% as unchanged drugContraindications
- Hypersensitivity to goserelin, other GnRH analogs, or implant components
- Pregnancy (Category D) and breastfeeding
- Undiagnosed abnormal vaginal bleeding
- Use in women who may become pregnant without adequate contraception
Warnings and Precautions
Initial disease flare: May cause temporary worsening of symptoms in first 1-2 weeks Bone density loss: Long-term use associated with decreased bone mineral density Cardiovascular risk: Increased risk of myocardial infarction, stroke, and sudden cardiac death Hyperglycemia/diabetes: May worsen glucose control QT prolongation: Observe caution in patients with risk factors for QT prolongation Tumor flare: Initial transient increase in tumor-related symptoms Spinal cord compression: Risk in patients with metastatic vertebral lesionsDrug Interactions
- Androgens/estrogens: May interfere with Zoladex mechanism
- Drugs affecting pituitary-gonadal axis: Potential interactions
- QT-prolonging drugs: Additive effects possible
- Corticosteroids: May alter metabolic effects
Adverse Effects
Common (>10%):- Hot flashes (57-80%)
- Sexual dysfunction (15-60%)
- Sweating (10-20%)
- Gynecomastia (1-18%)
- Decreased libido (5-15%)
- Myocardial infarction
- Cerebrovascular accident
- Spinal cord compression
- Severe hypersensitivity reactions
- Pituitary apoplexy (rare)
- Bone fracture related to osteoporosis
Monitoring Parameters
- Baseline: PSA (prostate cancer), testosterone/estradiol levels, bone density scan
- During treatment:
- Hormone levels (testosterone/estradiol) at 4 weeks and periodically - PSA levels (monthly initially, then quarterly) - Bone mineral density annually with long-term use - Lipid profile and glucose levels periodically - Blood pressure and cardiovascular assessment
- Symptoms: Hot flashes, bone pain, urinary symptoms, neurological symptoms
Patient Education
- Expect initial worsening of symptoms during first 1-2 weeks
- Hot flashes are common but typically manageable
- Use non-hormonal contraception during and for 12 weeks after treatment
- Report any new or worsening bone pain immediately
- Regular exercise and calcium/vitamin D supplementation recommended
- Monitor for signs of cardiovascular events (chest pain, shortness of breath)
- Regular follow-up appointments essential for monitoring
- Implant site may show minor bruising or tenderness
References
1. AstraZeneca Pharmaceuticals LP. (2021). Zoladex (goserelin acetate) implant prescribing information. 2. National Comprehensive Cancer Network. (2023). Prostate Cancer Guidelines, Version 4.2023. 3. Schroder FH, et al. (2012). Gonadotropin-releasing hormone antagonists in prostate cancer. New England Journal of Medicine, 367(10), 895-897. 4. Sharifi N, et al. (2020). Androgen deprivation therapy for prostate cancer: current status and future directions. JAMA Oncology, 6(1), 1-9. 5. FDA Drug Safety Communication. (2010). GnRH agonists: ongoing safety review. 6. European Association of Urology. (2022). Guidelines on Prostate Cancer. 7. American Society of Clinical Oncology. (2022). Management of Adverse Effects of Androgen Deprivation Therapy.