What Is Goserelin (Zoladex)? FDA Approval, Licensing in Turkey, and Reimbursement

• FDA Approved: Yes (Initial approval: 25 January 1989)
• Brand Name: Zoladex
• Active Ingredient: Goserelin
• Route of Administration: Subcutaneous (injection under the skin)
• Class: LHRH Agonist
• Category: Hormonal agent
• Manufacturer: AstraZeneca
• Distribution in Turkey: This information was not provided.
• Cancers for Which It Is Approved: Advanced prostate cancer and premenopausal and perimenopausal breast cancer suitable for hormonal intervention 

What Is Goserelin (Zoladex), and How Does It Work?

Goserelin is a hormonal agent in the LHRH (luteinizing hormone-releasing hormone) agonist class. After administration, it causes a temporary increase in follicle-stimulating hormone (FSH) and luteinizing hormone (LH) release. Subsequently, the pituitary becomes desensitized to gonadotropin-releasing hormone, suppressing gonadotropin secretion. This reduces pituitary LH and FSH release.

FDA (United States Food and Drug Administration) Approval History

• 25 January 1989: The 3.6 mg formulation was approved for palliative treatment of advanced prostate cancer.
• 7 July 1995: Additional approval was granted to the 3.6 mg formulation for advanced breast cancer and endometriosis.
• 28 July 1998: The 10.8 mg formulation, providing 12-week dosing, was approved for prostate cancer treatment.

Licensing in Turkey

The conditions/therapeutic indications for which Zoladex is licensed in Turkey are listed as follows:

Therapeutic Indications:

Prostate Cancer:

Indicated in prostate cancer suitable for hormonal intervention in the following situations: 

• Treatment of metastatic prostate cancer, where goserelin has demonstrated survival benefits comparable to surgical castration.
• Treatment of locally advanced prostate cancer as an alternative to surgical castration, where goserelin has shown comparable survival benefits relative to antiandrogen therapy.
• Adjuvant treatment with radiotherapy in patients with high-risk localized or locally advanced prostate cancer, where goserelin has demonstrated improved disease-free and overall survival.
• Neoadjuvant treatment before radiotherapy in patients with high-risk localized or locally advanced prostate cancer, where goserelin has demonstrated improved disease-free survival.
• Adjuvant treatment with radical prostatectomy in patients with locally advanced prostate cancer at high risk of progression, where goserelin has demonstrated improved disease-free survival.

Breast Cancer: 

• Used to treat advanced breast cancer in premenopausal and perimenopausal women suitable for hormonal intervention.
• Indicated as an alternative to chemotherapy included in standard treatment for pre/perimenopausal women with estrogen receptor (ER)-positive early-stage breast cancer.

Endometriosis:

• In endometriosis treatment, goserelin relieves symptoms, including pain, and reduces the number and size of endometrial lesions.
• -Endometrial Thinning:
  • Goserelin is indicated to thin the uterine endometrium before endometrial ablation or resection.
• -Uterine Fibroids:
  • Used with iron therapy to improve hematological status before surgery in anemic patients with fibroids.
• -Assisted Reproduction:
  • Used to suppress the pituitary in preparation for superovulation.

Is Zoladex (Goserelin) Reimbursed?

• Turkey's Social Security Institution (SGK) reimburses Zoladex for the following treatment indications:
• Advanced prostate cancer, premenopausal and perimenopausal breast cancer suitable for hormonal intervention, and precocious puberty.

What Is Zoladex's Status on the List of Off-Label Medicines Permitted Without Additional TİTCK Approval?

• Stage IV Breast Cancer
  • Appropriate for use in premenopausal breast cancer.
• Early-Stage Breast Cancer
  • Appropriate for use in premenopausal breast cancer.
• Metastatic Adenoid Cystic Carcinoma
  • Appropriate for treatment line 2 and beyond in androgen receptor-positive metastatic patients.

Price: Zoladex 10.8 mg costs 6317.41 TL; Zoladex Depot 3.6 mg costs 2708.59 TL. 

Pharmacokinetic Properties

• Absorption
  • The bioavailability of the subcutaneously administered medicine is 75–90%.
• Distribution
  • Goserelin's distribution has not been well characterized. It is released slowly over 28 days. Peak serum concentrations are reached 10–15 days after administration. Approximately 30% is bound to plasma proteins.
• Metabolism
  • Metabolism occurs primarily through hydrolysis of C-terminal amino acids. Goserelin is excreted almost entirely in urine. The elimination half-life is usually 4–5 hours but may extend to 12 hours in patients with impaired kidney function.

Dosing Interval

Goserelin is administered subcutaneously at 3.6 mg every 28 days or 10.8 mg every 90 days.

Drug Interactions

No well-characterized drug interaction has been identified to date.

Precautions

• A temporary tumor flare may occur at the start of goserelin treatment. It should therefore not be used in patients at risk of ureteral obstruction and/or spinal cord compression, or in those with painful bone metastases.
• Serum testosterone falls to castration levels 2–4 weeks after treatment begins.
• Use cautiously in patients with impaired kidney function.
• Patients should be informed about the possibility of hot flashes. Soy tablets (taken orally 3 times daily) may be recommended for prevention or treatment.

Side Effects

1. Hot flashes: Sudden sensations of heat that are common during treatment.
2. Loss of libido and sexual problems: Reduced sexual desire, impotence (erectile dysfunction), or breast enlargement in men (gynecomastia).
3. Tumor flare: During the first 2 weeks of treatment, temporary tumor growth may cause bone pain, urinary problems, or lower back pain. It can be prevented with antiandrogen medicines.
4. Injection-site discomfort: Pain or tenderness may occur at the administration site.
5. Changes in blood values: Cholesterol levels may increase.
6. Nausea and vomiting: Gastrointestinal symptoms that occur rarely.