Goserelin (Zoladex) is an analog of gonadotropin hormone-releasing hormone that suppresses estrogen and testosterone by inhibiting the stimulatory hormones (LH and FSH) in the pituitary gland

Goserelin (Zoladex) Uses:

• Advanced Breast Cancer (3.6 mg only):

  • Palliative treatment of advanced breast cancer in pre and perimenopausal women (estrogen and progesterone receptor values may be helpful in predicting whether goserelin is likely to be beneficial).

• Endometrial thinning (3.6 mg only):

  • Endometrial-thinning agent earlier to endometrial ablation for dysfunctional uterine bleeding.

• Endometriosis (3.6 mg only):

  • Management of endometriosis, including pain relief and reduction of endometriotic lesions for the duration of therapy (goserelin experience for endometriosis has been curtailed to women 18 years and older treated for 6 months).

• Prostate cancer, advanced (3.6 mg or 10.8 mg):

  • Palliative treatment of advanced carcinoma of the prostate.

• Prostate cancer, stage B2 to C (3.6 mg or 10.8 mg):

  • Management of locally confined stage T2b to T4 (stage B2 to C) prostate cancer (in combination with an antiandrogen [e.g. flutamide]); begin goserelin and antiandrogen therapy 8 weeks earlier to initiating radiation therapy and continue during radiation therapy.

• Off Label Use of Goserelin in Adults:

  • Advanced Breast cancer (second-line endocrine-based combination therapy);
  • Hormone therapy for transgender females (male-to-female);
  • Prevention of early menopause during chemotherapy for early-stage hormone receptor-negative breast cancer

Goserelin (Zoladex) Dose in Adults

Goserelin (Zoladex) Dose in the treatment of advanced Prostate cancer:

• Males: SubQ:

  • 28-day implant: 3.6 mg every 28 days
  • 12-week implant: 10.8 mg every 12 weeks

Goserelin (Zoladex) Dose in the treatment of stage B2 to C Prostate cancer (in combination with an antiandrogen and radiotherapy:

Note: The treatment should begin 8 weeks prior to radiotherapy.

• Males: SubQ:

  • Combination 28-day/12-week
  • implant: 3.6 mg implant, followed in 28 days by 10.8 mg implant
  • 28-day implant (alternate dosing): 3.6 mg; which need to be repeated every 28 days for a total of 4 doses

Goserelin (Zoladex) Dose in the treatment of advanced Breast cancer:

• Females:

  • SubQ: 3.6 mg every 28 days

Goserelin (Zoladex) Dose in the treatment of Endometriosis:

• Females:

  • SubQ: 3.6 mg every 28 days for 6 months

Goserelin (Zoladex) Dose in the treatment of Endometrial thinning:

• Females:

  • SubQ: 3.6 mg every 28 days for 1 or 2 doses

Goserelin (Zoladex) Dose in the treatment of Hormone therapy for transgender females (male-to-female) (adjunct therapy) (off-label use):

• SubQ: 3.6 mg every 4 weeks in combination with other appropriate agents.

Goserelin (Zoladex) Dose in the Prevention of early menopause during chemotherapy for early-stage hormone receptor-negative breast cancer (off-label):

• Adult females:

  • SubQ: 3.6 mg every 28 days starting 1-week earlier to the first chemotherapy dose;
  • However, continue it until within 2 weeks before or after the final chemotherapy dose.

Use in Children:

Not indicated.

Pregnancy Risk Factor X (endometriosis and endometrial thinning);

Risk Factor D (advanced breast cancer)

• Negative events were seen in animal reproduction studies.
• Goserelin can cause hormonal changes which increase the risk of fetal death.
• It is not recommended for use in pregnancy, unless it is being used to palliatively treat advanced breast cancer.
• Breast cancerIf the breast cancer palliative treatment is to be used during pregnancy, it should be discussed with patients about the potential for an increase in fetal loss.
• Endometrial thinning, endometrial cystitis: it is not recommended during pregnancy. 
• Therapy should be stopped for women with childbearing potential until the pregnancy is over.
• Premenopausal women who are not on hormones should use nonhormonal contraception during therapy, and for 12 weeks following the end of therapy.
• Goserelin therapy does not prevent pregnancy. Ovulation may be inhibited, menstruation may stop.
• Changes in reproductive function can occur after chronic administration.

Goserelin use during breastfeeding:

• Although it is not known if goserelin exists in breast milk, goserelin can be activated when taken orally.
• Due to the possibility of serious adverse reactions in breastfed infants, it is important to decide whether to stop breast-feeding or discontinue using the drug.
• This decision must be made taking into account the mother's need for treatment.

Dose in Kidney disease:

No dosage adjustment is necessary.

Dose in Liver disease:

No dosage adjustment is necessary.

Common Side Effects of Goserelin (Zoladex):

• Cardiovascular:

  • Vasodilatation
  • Peripheral Edema

• Central Nervous System:

  • Headache
  • Emotional Lability
  • Depression
  • Pain
  • Dyspareunia
  • Insomnia

• Dermatologic:

  • Diaphoresis
  • Acne Vulgaris
  • Seborrhea

• Endocrine & Metabolic:

  • Hot Flash
  • Decreased Libido
  • Increased Libido

• Gastrointestinal:

  • Abdominal Pain
  • Nausea

• Genitourinary:

  • Vaginitis
  • Breast Atrophy
  • Sexual Disorder
  • Breast Hypertrophy
  • Decrease In Erectile Frequency
  • Pelvic Symptoms
  • Genitourinary Signs And Symptoms

• Hematologic & Oncologic:

  • Tumor Flare

• Infection:

  • Infection

• Neuromuscular & Skeletal:

  • Decreased Bone Mineral Density
  • Weakness

Less Common Side Effects Of Goserelin (Zoladex):

• Cardiovascular:

  • Edema
  • Hypertension
  • Cardiac Failure
  • Cardiac Arrhythmia
  • Cerebrovascular Accident
  • Peripheral Vascular Disease
  • Varicose Veins
  • Chest Pain
  • Myocardial Infarction
  • Palpitations
  • Tachycardia

• Central Nervous System:

  • Lethargy
  • Migraine
  • Dizziness
  • Malaise
  • Chills
  • Anxiety
  • Nervousness
  • Voice Disorder
  • Abnormality In Thinking
  • Drowsiness
  • Paresthesia

• Dermatologic:

  • Skin Rash
  • Hair Disease
  • Pruritus
  • Alopecia
  • Skin Discoloration
  • Xeroderma

• Endocrine & Metabolic:

  • Gynecomastia
  • Hirsutism
  • Gout
  • Hyperglycemia
  • Weight Gain

• Gastrointestinal:

  • Anorexia
  • Gastric Ulcer
  • Constipation
  • Diarrhea
  • Vomiting
  • Increased Appetite
  • Dyspepsia
  • Flatulence
  • Xerostomia

• Genitourinary:

  • Pelvic Pain
  • Mastalgia
  • Uterine Hemorrhage
  • Vulvovaginitis
  • Breast Swelling
  • Urinary Tract Obstruction
  • Urinary Tract Infection
  • Urinary Frequency
  • Vaginal Hemorrhage

• Hematologic & Oncologic:

  • Anemia
  • Bruise
  • Hemorrhage

• Hypersensitivity:

  • Hypersensitivity Reaction

• Infection:

  • Sepsis

• Local:

  • Application Site Reaction

• Neuromuscular & Skeletal:

  • Myalgia
  • Leg Cramps
  • Hypertonia
  • Arthralgia
  • Arthropathy

• Ophthalmic:

  • Amblyopia
  • Dry Eye Syndrome

• Renal:

  • Renal Insufficiency

• Respiratory:

  • Upper Respiratory Tract Infection
  • Chronic Obstructive Pulmonary Disease
  • Flu-Like Symptoms
  • Pharyngitis
  • Sinusitis
  • Bronchitis
  • Cough
  • Epistaxis
  • Rhinitis

• Miscellaneous:

  • Fever

Contraindications to Goserelin (Zoladex):

• Hypersensitivity to goserelin or GnRH, GnRH analogs, GnRH-agonist analogs, and any component of the formulation
• Except for advanced breast cancer palliative care, pregnancy is not allowed

Canadian labeling:Additional contraindications not listed in the US labeling:

• Vaginal bleeding that is not diagnosed
• pregnancy,
• Breastfeeding

Warnings and precautions

• Cervical resistance

  • Endometrial ablation may increase cervical resistance.

• Reduced bone density

  • It has been reported in females and can be irreversible.
  • Be aware of other risk factors and if necessary, evaluate and implement preventive treatment.

• Hypercalcemia:

  • Patients with bone metastases and prostate cancer have been diagnosed as having hypercalcemia.
  • You should immediately take appropriate action if hypercalcemia is detected.

• Hyperglycemia:

  • Males with hyperglycemia have also been reported.
  • This could manifest as diabetes, or worsening preexisting diabetes (worsening the glycemic control).
  • It is important to monitor blood glucose and HbA levels and to manage diabetes properly.

• Hypersensitivity

  • Monitor for hypersensitivity reactions, including acute anaphylactic reactions, and antibody formation.

• Injection site injury:

  • Goserelin has been used to outline injection site and vascular injuries, which include pain, hemorhage and hemorhagic shock (requiring blood transfusions or surgery).
  • Extra caution is required when administering anticoagulation to patients with low BMI or who are receiving full-dose anticoagulation.
  • Due to the proximity of the inferior epigastric artery (and its branches) and the danger of injecting goserelin in the anterior abdominal wall, be careful
  • Be aware of the symptoms and signs of abdominal hemorhage.
  • Tell the patient to take a moment to report abdominal pain, abdominal ditention, dyspnea and dizziness, hypotension, altered level of consciousness, and/or abdominal distention.

• Pituitary apoplexy

  • GnRH agonist administration has been used to treat rare cases of pituitary hypoplexy, which is often secondary to pituitary anadenoma. Usually, the symptoms last between 1 and 2 weeks.
  • You may experience a sudden headache, nausea, vomiting, changes in visual or mental status, and sometimes, a heart attack. However, immediate medical attention is required.

• Tumor flare:

  • In men with prostate cancer, transient increases in serum estrogen and serum testosterone may cause a flare-up of symptoms and signs (tumor flare). This can occur within the first few weeks.
  • Some patients felt a temporary worsening in bone pain. This may be treated symptomatically.
  • Patients who have received treatment for prostate cancer have had spinal cord compression and obstruction of the urinary tract. In the first few weeks, ureteral obstruction, weakness and paresthesias are common.
  • You can continue with the standard treatment, but you should consider orchiectomy in extreme cases.

• Cardiovascular disease

  • The risk of developing cardiovascular disease may be increased by using androgen deprivation therapy.
  • A higher risk of stroke, sudden cardiac death, MI and other causes has been identified.
  • Be aware of the symptoms and signs of cardiovascular disease. Follow current clinical practice.
  • Patients with congenital long QT syndrome, heart disease, frequent electrolyte abnormalities, or patients on medication that prolongs the QT interval may experience prolongation.
  • Make sure to check electrolytes before initiation. Also, consider periodic electrolyte monitoring.

Goserelin: Drug Interaction

Monitoring parameters:

• Monitor blood glucose and HbA (periodically), bone mineral density, serum calcium, cholesterol/lipids;
• Monitor for the signs/symptoms of abdominal hemorrhage following injection.

Prostate cancer:

• Periodic ECG and electrolyte monitoring have to be considered.
• Monitor for weakness, paresthesias, tumor flare, urinary tract obstruction, and spinal cord compression in the first few weeks of therapy.

Transgender hormone therapy:

• Serum testosterone levels (goal <50 ng/dL) every 3 months during the first year and then annually or bi-annually;
• Serum luteinizing hormone (LH), follicle-stimulating hormone (FHS), and prolactin levels at baseline and annually;
• Routine cancer and laboratory screening as in non-transgender individuals for all tissues present.

How to administer Goserelin (Zoladex)?

SubQ:

• Administer implant by inserting a needle at a 30- to 45-degree angle into the anterior abdominal wall below the navel line.
• Use care while injecting goserelin into the anterior abdominal wall (due to the proximity of the underlying inferior epigastric artery and its branches).
• Goserelin is an implant; that's why do not attempt to eliminate air bubbles prior to injection (may displace implant). Need not to attempt to aspirate prior to injection;
• If a large vessel is penetrated, blood will be visualized in the syringe chamber (if the vessel is penetrated, withdraw the needle and inject elsewhere with a new syringe).
• Do not penetrate into muscle or peritoneum.
• If removal is required, an implant may be detected by ultrasound.
• Monitor for the signs/symptoms of abdominal hemorrhage.
• Use caution when administering goserelin to patients with a low BMI and/or to patients receiving full-dose anticoagulation.

Mechanism of action of Goserelin (Zoladex):

• Goserelin (a gonadotropin-releasing hormone [GnRH] analog) results in an initial increase in luteinizing hormone (LH) and follicle-stimulating hormone (FSH), chronic administration of goserelin results in sustained suppression of pituitary gonadotropins.
• The levels of serum testosterone are comparable to surgical castration.
• Although the exact mechanism is unknown, it could be due to changes in LH control or downregulation of LH receptors.

The beginning of action:

• Females: After 3 weeks, estrogen suppression is at postmenopausal level. FSH and LH levels are at follicular phase within 4 weeks.
• Males: Within 2 to 4 weeks of initiation, testosterone suppression affects castrate levels.

Time of action:

• Females: Estradiol and LH are generally returned to baseline within 12 weeks of the last monthly implants.
• Males: Castrate levels of testosterone are maintained throughout therapy.

Absorption when administered SubQ:

• Rapid and may be detected in serum in 30 to 60 minutes;
• 3.6 mg: released slowly in the first 8 days, then rapid and continuous release for 28 days

Protein binding:

• ~27%

Metabolism:

• Hepatic hydrolysis of the C-terminal amino acids

Time to peak Serum Concentration when administered SubQ::

• Male: 12 to 15 days,
• Female: 8 to 22 days

Excretion:

• Urine (>90%; 20% as unchanged drug)

International Brands of Goserelin:

• Zoladex
• Zoladex LA
• Zoladex Depot
• Zoladex Implant
• Zoladex Inj.
• Zoladex LA
• Zoladex LA Depot
• Zpladex

Goserelin Brand Names in Pakistan: