Usage
Goserelin acetate is a synthetic analogue of gonadotropin-releasing hormone (GnRH), classified as a gonadotropin-releasing hormone agonist (GnRH agonist). It is prescribed for various conditions including:
- Prostate cancer: For the palliative treatment of advanced prostate cancer and in combination with other treatments for localized disease.
- Breast cancer: Palliative treatment of advanced breast cancer in pre- and perimenopausal women.
- Endometriosis: To reduce pain and shrink endometrial lesions.
- Uterine fibroids: To shrink fibroids, reduce bleeding, and alleviate pain.
- Endometrial thinning: To prepare the lining of the uterus for endometrial ablation.
- Assisted reproduction: As part of controlled ovarian stimulation protocols.
Goserelin acetate falls under the pharmacological classifications of antineoplastic (for cancer treatment) and hormone therapy.
Mechanism of Action: Goserelin initially stimulates the pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH). However, with continued administration, it causes downregulation of GnRH receptors, leading to a decrease in LH and FSH secretion. This results in suppressed estrogen production in women and testosterone production in men, creating a “medical castration” effect.
Alternate Names
Goserelin is also known internationally as goserelin acetate. Brand names for goserelin acetate include Zoladex and Zoladex LA.
How It Works
Pharmacodynamics: Goserelin acetate binds to GnRH receptors in the pituitary gland. Initial stimulation is followed by receptor desensitization and decreased LH and FSH release. This leads to a reduction in sex hormone levels (estrogen in women, testosterone in men).
Pharmacokinetics:
- Absorption: Goserelin acetate is administered as a subcutaneous implant, which releases the drug slowly and continuously over time (28 days for 3.6mg, 84 or 112 days for 10.8mg).
- Metabolism: Primarily hepatic.
- Elimination: Primarily renal excretion.
Mode of Action: Goserelin works by initially stimulating, then suppressing, the pituitary’s release of gonadotropins, thereby decreasing sex hormone production.
Receptor Binding: Goserelin binds to and initially activates, then downregulates, GnRH receptors in the pituitary gland.
Dosage
Standard Dosage
Adults:
- 3.6 mg implant: Subcutaneously every 28 days.
- 10.8 mg implant: Subcutaneously every 12 weeks.
Children: Goserelin is not indicated for use in children.
Special Cases:
- Elderly Patients: No dose adjustment necessary.
- Patients with Renal Impairment: No dose adjustment necessary.
- Patients with Hepatic Dysfunction: No dose adjustment necessary.
- Patients with Comorbid Conditions: Patients with cardiovascular disease, diabetes, osteoporosis risk, or those on chronic medications like anticonvulsants or corticosteroids should be monitored closely.
Clinical Use Cases Goserelin’s dosage is primarily determined by the indication, not the clinical setting. Dosages described in the Standard Dosage section apply across various medical settings.
Side Effects
Common Side Effects
- Hot flashes
- Sweating
- Headache
- Vaginal dryness/bleeding (women)
- Decreased libido
- Injection site reactions
- Mood changes
Rare but Serious Side Effects
- Pituitary apoplexy
- Osteoporosis (long-term use)
- QT prolongation
- Worsening of bone pain (initial treatment for prostate cancer)
- Spinal cord compression (prostate cancer)
- Ureteric obstruction (prostate cancer)
Long-Term Effects
- Osteoporosis
- Cardiovascular disease risk
Adverse Drug Reactions (ADR)
- Hypersensitivity reactions (rare)
Contraindications
- Hypersensitivity to goserelin or GnRH analogues.
- Pregnancy (except for palliative treatment of advanced breast cancer).
- Undiagnosed vaginal bleeding.
- The 10.8 mg implant is contraindicated in women for conditions other than prostate cancer, breast cancer, endometriosis, and uterine fibroids.
Drug Interactions
- Hormonal contraceptives (decreased efficacy).
- Drugs that prolong the QT interval (increased risk of arrhythmias).
- CYP450 interactions are not prominent with goserelin.
Pregnancy and Breastfeeding
- Pregnancy Safety Category X (for endometriosis and endometrial thinning), Category D (for advanced breast cancer).
- Goserelin is contraindicated during pregnancy unless it is being used for palliative treatment of advanced breast cancer.
- Goserelin can harm the fetus and increase the risk of miscarriage.
- Breastfeeding is contraindicated while receiving goserelin.
Drug Profile Summary
- Mechanism of Action: GnRH agonist that suppresses sex hormone production.
- Side Effects: Hot flashes, sweating, headache, vaginal dryness, decreased libido, injection site reactions, mood changes. Serious but rare: Osteoporosis, QT prolongation, pituitary apoplexy.
- Contraindications: Hypersensitivity, pregnancy (except for palliative treatment of advanced breast cancer), undiagnosed vaginal bleeding.
- Drug Interactions: Hormonal contraceptives, drugs that prolong the QT interval.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: 3.6 mg SC monthly, or 10.8 mg SC every three months, depending upon the indication.
- Monitoring Parameters: Sex hormone levels, bone mineral density (with long-term use), PSA (for prostate cancer), tumor response (for cancer treatment), and symptoms of endometriosis or uterine fibroids.
Popular Combinations
- Prostate cancer: Flutamide (an antiandrogen) is often used concurrently to prevent tumor flare during initial treatment.
- Breast Cancer: May be used in sequence with aromatase inhibitors.
Precautions
- General Precautions: Exclude pregnancy, assess for risk factors for osteoporosis, monitor for cardiovascular events. Monitor QT prolongation and any other adverse events.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Goserelin acetate?
A: 3.6 mg subcutaneously every 28 days, or 10.8 mg subcutaneously every 12 weeks, depending upon the indication.
Q2: How does Goserelin differ from other GnRH agonists?
A: While similar in mechanism to other GnRH agonists like leuprolide, goserelin is available as a subcutaneous implant that provides continuous release, simplifying administration. Different formulations of other GnRH agonists may involve daily injections, monthly injections or three-monthly injections.
Q3: Can Goserelin be used in children?
A: Goserelin is not approved for use in children.
Q4: How should Goserelin be administered?
A: Administer as a subcutaneous injection into the anterior abdominal wall below the navel line using aseptic technique.
Q5: What are the common side effects patients should be aware of?
A: Hot flashes, sweating, decreased libido, mood changes, and injection site reactions are common. Discuss potential side effects with patients and offer management strategies.
Q6: Are there any specific monitoring requirements during Goserelin therapy?
A: Monitor bone mineral density during long-term treatment, especially in patients with risk factors for osteoporosis. Monitor patients with prostate cancer for disease progression (PSA levels, tumor response), and patients with other indications (endometriosis, uterine fibroids) by symptom assessment.
Q7: Can Goserelin be used during pregnancy?
A: Goserelin is contraindicated in pregnancy except for the palliative treatment of advanced breast cancer, where the benefits may outweigh the risks. It is crucial to rule out pregnancy before starting treatment for other indications.
Q8: How does Goserelin affect fertility?
A: Goserelin suppresses sex hormone production, leading to decreased fertility in both men and women. Fertility usually returns after treatment is discontinued, but it can take several months. For those who have fertility concerns, they should discuss these in full with their healthcare professional.
Q9: What should I do if a patient experiences a “tumor flare” during initial treatment for prostate cancer?
A: A transient increase in symptoms, known as a “tumor flare,” can occur in the first few weeks of treatment for prostate cancer. Concurrent use of an antiandrogen, like flutamide, can help mitigate this effect. Symptom management (analgesics, etc.) may also be necessary. The patient should be reassured that this is usually temporary.
Q10: What is the duration of treatment for endometriosis with Goserelin?
A: Treatment for endometriosis typically lasts for six months. Longer durations are not recommended for benign gynecological conditions.
