Version May 2024
Breast cancer, advanced: Pre- and perimenopausal patients: SUBQ: 3.6 mg every 28 days.
Breast cancer, early stage, premenopausal ovarian preservation during chemotherapy (off-label use): SUBQ: 3.6 mg once every 28 days starting at least 1 to 2 weeks prior to the first chemotherapy dose; continue until within 2 weeks before or after the final chemotherapy dose (Ref).
Breast cancer, premenopausal ovarian suppression during adjuvant endocrine therapy (off-label use): SUBQ: 3.6 mg every 28 days for ~5 years (Ref).
Breast cancer in male patients, hormone receptor-positive (off-label use): Note: Should be used in combination with an aromatase inhibitor (Ref).
Adva nced or metastatic disease: SUBQ: 3.6 mg once every 4 weeks until disease progression or unacceptable toxicity (Ref). Endocrine therapy for males with advanced or metastatic, hormone receptor-positive, HER2-negative breast cancer may be sequenced as in females (Ref).
Endometrial thinning: SUBQ: 3.6 mg every 28 days for 1 or 2 doses prior to endometrial ablation. Perform surgery at 4 weeks (if administering 1 dose) or within 2 to 4 weeks (following administration of the second depot).
Endometriosis: SUBQ: 3.6 mg every 28 days for 6 months.
Hormone therapy for transgender females (assigned male at birth), adjunct (off-label use): SUBQ: 3.6 mg every 4 weeks in combination with other appropriate agents (Ref).
Prostate cancer, advanced:
28-day implant: SUBQ: 3.6 mg every 28 days.
12-week implant: SUBQ: 10.8 mg every 12 weeks.
Prostate cancer, stage B2 to C, in combination with an antiandrogen and radiotherapy; begin 8 weeks prior to radiotherapy:
Combination 28-day/12-week implant: SUBQ: 3.6 mg, followed in 28 days by 10.8 mg.
28-day implant (alternate dosing): SUBQ: 3.6 mg; repeated every 28 days for a total of 4 doses.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary.
No dosage adjustment necessary.
Bone mineral density loss: Institute preventative treatment if necessary.
Bone pain worsening (temporary): Manage symptomatically.
Cardiovascular disease (signs/symptoms): Manage according to current clinical practice.
Hypercalcemia: Initiate appropriate management if hypercalcemia occurs.
Hyperglycemia: Manage hyperglycemia and/or diabetes as clinically appropriate.
Pituitary apoplexy: Requires immediate medical attention.
Tumor flare, cord compression, or urinary tract obstruction (in prostate cancer): Manage with standard treatment; consider orchiectomy for extreme cases.
Males: Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Peripheral edema (females: 21%; males: 1% to 5%), vasodilation (females: 57%)
Dermatologic: Acne vulgaris (females: 42%), diaphoresis (females: 16% to 45%; males: 6%), seborrhea (females: 26%)
Endocrine & metabolic: Decreased libido (females: 48% to 61%), hot flash (females: 70% to 96%; males: 60% to 62%), increased libido (females: 12%)
Gastrointestinal: Abdominal pain (1% to 11%), nausea (5% to 11%)
Genitourinary: Breast atrophy (females: 33%), breast hypertrophy (females: 18%), decrease in erectile frequency (18%), dyspareunia (females: 14%), genitourinary signs and symptoms (lower; males: 13%), pelvic symptoms (females: 18%), sexual disorder (males: 21%), vaginitis (75%)
Hematologic & oncologic: Tumor flare
Infection: Infection (females: 13%)
Nervous system: Asthenia (5% to 11%), depression (females: 54%; males: 1% to 5%), emotional lability (females: 60%), headache (females: 32% to 75%; males: 1% to 5%), insomnia (5% to 11%), pain (8% to 17%)
Neuromuscular & skeletal: Decreased bone mineral density
1% to 10%:
Cardiovascular: Acute myocardial infarction (males: 1% to 5%), angina pectoris (males: 1% to 5%), cardiac arrhythmia (males: 1% to 5%), chest pain (1% to 5%), edema (5% to 7%), heart failure (males: 5%), hypertension (6%), palpitations (females: 1% to 5%), peripheral vascular disease (males: 1% to 5%), pulmonary embolism (males: 1% to 5%), tachycardia (females: 1% to 5%), varicose veins (males: 1% to 5%)
Dermatologic: Alopecia (females: 1% to 5%), ecchymoses (females: 1% to 5%), hair disease (females: 4%), pruritus (2%), skin discoloration (females: 1% to 5%), skin rash (6%), xeroderma (females: 1% to 5%)
Endocrine & metabolic: Diabetes mellitus (males: 1% to 5%), gynecomastia (males: 8%), hirsutism (females: 7%), hyperglycemia (males: 1% to 5%), weight gain (3%)
Gastrointestinal: Anorexia (5%), constipation (1% to 5%), diarrhea (1% to 5%), dyspepsia (females: 1% to 5%), flatulence (females: 1% to 5%), gastric ulcer (males: 1% to 5%), hematemesis (males: 1% to 5%), increased appetite (females: 2%), vomiting (4%), xerostomia (females: 1% to 5%)
Genitourinary: Bladder neoplasm (males: 1% to 5%), breast swelling (males: 1% to 5%), breast tenderness (males: 1% to 5%), dysmenorrhea (1% to 5%), hematuria (males: 1% to 5%), impotence (males: 1% to 5%), mastalgia (7%), pelvic pain (6% to 9%), urinary frequency (1% to 5%), urinary incontinence (males: 1% to 5%), urinary retention (males: 1% to 5%), urinary tract abnormality (males: 1% to 5%), urinary tract infection (1% to 5%), urinary tract obstruction (males: 1% to 5%), urination disorder (males: 1% to 5%), uterine hemorrhage (6%), vaginal hemorrhage (1% to 5%), vulvovaginitis (5%)
Hematologic & oncologic: Anemia (males: 1% to 5%), hemorrhage (females: 1% to 5%)
Hypersensitivity: Hypersensitivity reaction (females: 1% to 5%)
Infection: Herpes simplex infection (males: 1% to 5%), sepsis (males: 1% to 5%)
Local: Application-site reaction (females: 6%)
Nervous system: Abnormality in thinking (females: 1% to 5%), anxiety (1% to 5%), cerebral ischemia (males: 1% to 5%), cerebrovascular accident (males: 1% to 5%), chills (males: 1% to 5%), dizziness (5% to 6%), drowsiness (females: 1% to 5%), fatigue (females: ≤5%), hypertonia (females: 1%), lethargy (≤8%), malaise (females: ≤5%), migraine (females: 7%), nervousness (females: 3% to 5%), paresthesia (1% to 5%), voice disorder (females: 3%)
Neuromuscular & skeletal: Arthralgia (females: 1% to 5%), arthropathy (females: 1% to 5%), back pain (4% to 7%), gout (males: 1% to 5%), lower limb cramp (females: 2%), myalgia (females: 3%), ostealgia (males: 6%)
Ophthalmic: Amblyopia (females: 1% to 5%), dry eye syndrome (females: 1% to 5%)
Renal: Renal insufficiency (males: 1% to 5%)
Respiratory: Bronchitis (females: 1% to 5%), chronic obstructive pulmonary disease (males: 5%), cough (1% to 5%), dyspnea (males: 1% to 5%), epistaxis (females: 1% to 5%), flu-like symptoms (5%), pharyngitis (females: 5%), pneumonia (males: 1% to 5%), rhinitis (females: 1% to 5%), sinusitis (females: 1% to 5%), upper respiratory tract infection (males: 7%)
Miscellaneous: Fever (1% to 5%)
<1%:
Hepatic: Increased serum alanine aminotransferase, increased serum aspartate aminotransferase
Local: Injection-site reaction
Frequency not defined: Endocrine & metabolic: Decreased HDL cholesterol, increased HDL cholesterol, increased LDL cholesterol, increased serum triglycerides
Postmarketing:
Cardiovascular: Deep vein thrombosis, hypotension, vascular injury
Endocrine & metabolic: Hypercalcemia (patients with bone metastases), hypovolemic shock, pituitary apoplexy, pituitary neoplasm (including adenoma)
Genitourinary: Ovarian cyst, ureteral obstruction
Hypersensitivity: Anaphylaxis
Local: Bleeding at injection site, hematoma at injection site, pain at injection site
Nervous system: Psychotic reaction, seizure, spinal cord compression, suicidal ideation, suicidal tendencies, transient ischemic attacks
Neuromuscular & skeletal: Bone fracture, osteoporosis
Known hypersensitivity to goserelin, gonadotropin-releasing hormone (GnRH), GnRH agonist analogues, or any component of the formulation; during pregnancy for the treatment of endometriosis or endometrial thinning.
Canadian labeling: Additional contraindications (not in the US labeling): Undiagnosed vaginal bleeding, pregnancy, breastfeeding.
Concerns related to adverse effects:
• Cervical resistance: Cervical resistance may be increased; use caution when dilating the cervix for endometrial ablation.
• Decreased bone density: Decreased bone mineral density has been reported in females and may be irreversible; use caution if other risk factors are present.
• Hypercalcemia: Hypercalcemia has been reported in patients with prostate cancer and breast cancer with bone metastases.
• Hyperglycemia: Hyperglycemia has been reported in patients with prostate cancer and may manifest as diabetes or worsening of preexisting diabetes (worsening glycemic control).
• Hypersensitivity: Hypersensitivity reactions (including acute anaphylactic reactions) and antibody formation may occur.
• Injection site injury: Injection site and vascular injury, including pain, hematoma, hemorrhage, and hemorrhagic shock (requiring blood transfusions or surgical intervention) have been reported with goserelin. Use extra caution when administering to patients with a low BMI and/or to patients receiving full dose anticoagulation. Use caution while injecting goserelin into the anterior abdominal wall (due to the proximity of underlying inferior epigastric artery and its branches). Inform patient to immediately report abdominal pain, abdominal distention, dyspnea, dizziness, hypotension, and/or altered level of consciousness.
• Pituitary apoplexy: Rare cases of pituitary apoplexy (frequently secondary to pituitary adenoma) have been observed with gonadotropin-releasing hormone (GnRH) agonist administration (onset from 1 hour to usually <2 weeks); may present as sudden headache, vomiting, visual or mental status changes, and, infrequently, cardiovascular collapse; immediate medical attention required.
• Psychiatric effects: Symptoms of emotional lability (eg, crying, irritability, anger, aggression, impatience) have been reported with GnRH agonists, including goserelin; monitor for the development or worsening of psychiatric symptoms.
• Psychiatric events: Depression (new or worsening), including rare reports of suicidal ideation and attempt, has been reported in women being treated with GnRH agonists, including goserelin. Consider referral to a mental health professional in patients with new or worsening depression.
• Tumor flare: Transient increases in serum testosterone (in patients with prostate cancer) and estrogen (in patients with breast cancer) may result in a worsening of disease signs and symptoms (tumor flare) during the first few weeks of treatment. Some patients experienced a temporary worsening of bone pain, which may be managed symptomatically. Spinal cord compression and urinary tract obstruction have been reported in patients with prostate cancer; symptoms include ureteral obstruction, weakness, and paresthesias in first few weeks of therapy.
Disease-related concerns:
• Cardiovascular disease: Androgen deprivation therapy may increase the risk for cardiovascular disease (Levine 2010). An increased risk for myocardial infarction, sudden cardiac death, and stroke has been observed. Androgen deprivation therapy may cause prolongation of the QT/QTc interval; evaluate risk versus benefit in patients with congenital long QT syndrome, heart failure, frequent electrolyte abnormalities, and in patients taking medication known to prolong the QT interval.
Special populations:
• Body weight: A decreased AUC may be observed when using the 3-month implant in patients with obesity. Use extra care when administering to patients with a low BMI to avoid injection site injury.
Dosage form specific issues:
• Implant removal: If removal is necessary, implant may be located by ultrasound.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Implant, Subcutaneous:
Zoladex: 3.6 mg (1 ea); 10.8 mg (1 ea)
No
Implant (Zoladex Subcutaneous)
3.6 mg (per each): $1,135.73
10.8 mg (per each): $3,184.32
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Implant, Subcutaneous:
Zoladex: 3.6 mg (1 ea)
Zoladex LA: 10.8 mg (1 ea)
SUBQ: Administer implant by inserting needle into the anterior abdominal wall below the navel line at a 30- to 45-degree angle in a continuous motion until the protective sleeve touches the patient's skin; grasp barrel at the finger grip and fully depress plunger. Use caution while injecting goserelin into the anterior abdominal wall (due to the proximity of underlying inferior epigastric artery and its branches). Goserelin is an implant; therefore, do not attempt to eliminate air bubbles prior to injection (may displace implant). Do not attempt to aspirate prior to injection; if a large vessel is penetrated, blood will be visualized in the syringe chamber (if vessel is penetrated, withdraw needle and inject elsewhere with a new syringe). Do not penetrate into muscle or peritoneum. Implant may be detected by ultrasound if removal is required. Monitor for signs/symptoms of abdominal hemorrhage. Use extra care when administering goserelin to patients with a low BMI and/or to patients receiving full dose anticoagulation. Refer to product labeling for additional details.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Breast cancer, advanced (3.6 mg only): Palliative treatment of advanced breast cancer in pre- and perimenopausal patients (estrogen and progesterone receptor values may help to predict if goserelin is likely to be beneficial).
Endometrial thinning (3.6 mg only): Endometrial-thinning agent prior 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 limited to patients ≥18 years of age 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 [eg, flutamide]); begin goserelin and antiandrogen therapy 8 weeks prior to initiating radiation therapy and continue during radiation therapy.
Breast cancer, advanced, with endocrine-based combination therapy; Breast cancer, early stage, premenopausal ovarian preservation during chemotherapy; Breast cancer, premenopausal ovarian suppression during adjuvant endocrine therapy; Breast cancer in male patients, hormone receptor-positive; Hormone therapy for transgender females (assigned male at birth)
The Institute for Safe Medication Practices (ISMP) includes this medication (when treating endometriosis or endometrial thinning) among its list of drugs that have a heightened risk of causing significant patient harm when used in error.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Choline C 11: Luteinizing Hormone-Releasing Hormone Analogs may diminish the therapeutic effect of Choline C 11. Risk C: Monitor therapy
Corifollitropin Alfa: Luteinizing Hormone-Releasing Hormone Analogs may enhance the therapeutic effect of Corifollitropin Alfa. Risk X: Avoid combination
Flotufolastat F18: Androgen Deprivation Therapy Agents may diminish the diagnostic effect of Flotufolastat F18. Management: Androgen deprivation therapy (ADT) may result in changes in the uptake of flotufolastat F18 in prostate cancer. The impact of ADT on the performance of flotufolastat F18 is unknown, but use of alternative agents should be considered. Risk D: Consider therapy modification
Gallium Ga 68 PSMA-11: Androgen Deprivation Therapy Agents may diminish the therapeutic effect of Gallium Ga 68 PSMA-11. Management: Androgen deprivation therapy (ADT) may result in changes in the uptake of gallium Ga 68 PSMA-11 (gozetotide) in prostate cancer. The impact of ADT on the performance of gallium Ga 68 PSMA-11 is unknown, but use of alternative agents should be considered. Risk D: Consider therapy modification
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Indium 111 Capromab Pendetide: Luteinizing Hormone-Releasing Hormone Analogs may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Risk X: Avoid combination
Piflufolastat F18: Androgen Deprivation Therapy Agents may diminish the diagnostic effect of Piflufolastat F18. Management: Androgen deprivation therapy (ADT) may result in changes in the uptake of piflufolastat F18 in prostate cancer. The impact of ADT on the performance of piflufolastat F18 is unknown, but use of alternative agents should be considered. Risk D: Consider therapy modification
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
When used for endometriosis or endometrial thinning, patients who could become pregnant should not receive goserelin until pregnancy has been excluded. Nonhormonal contraception is recommended for premenopausal patients during therapy and for 12 weeks after therapy is discontinued. Although ovulation is usually inhibited and menstruation may stop, pregnancy prevention is not ensured during goserelin therapy. Changes in reproductive function may occur following chronic administration.
Goserelin may prevent premature ovarian failure when added to chemotherapy in patients with early stage hormone receptor negative breast cancer. In one study, patients followed for 5 years were less likely to experience ovarian failure and more likely to become pregnant than patients who did not receive goserelin in addition to their chemotherapy. The desire to become pregnant and the incidence of prior pregnancies was not considered in the analysis, and pregnancies occurred in some patients who were not attempting to conceive (Moore 2015; Moore 2019). Use of gonadotropin-releasing hormone (GnRH) agonists such as goserelin for preserving ovarian function and potentially maintaining future fertility may be considered for some premenopausal patients undergoing chemotherapy (ACOG 2018; ASCO [Oktay 2018]).
Goserelin may also cause erectile dysfunction and decreased libido. Intermittent therapy (if possible and if clinically appropriate) may improve quality of life in patients treated for prostate cancer (Semet 2017).
Goserelin induces hormonal changes, which increase the risk for fetal loss.
Outcome data following inadvertent goserelin exposure during pregnancy are limited (Hill 2011; Ishizuka 2016).
Use is contraindicated during pregnancy for the treatment of endometriosis or endometrial thinning. If used for the palliative treatment of breast cancer during pregnancy, the potential for increased fetal loss should be discussed with the patient.
It is not known if goserelin is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, a decision should be made to discontinue breastfeeding or to discontinue the drug, considering the importance of treatment to the mother.
Monitor blood glucose and HbA1c (periodically and as clinically necessary), bone mineral density, serum calcium, cholesterol/lipids. Monitor for signs/symptoms of abdominal hemorrhage (following injection), depression (especially in females), hypersensitivity reaction, and pituitary apoplexy (eg, sudden headache, vomiting, visual or mental status changes, and, infrequently, cardiovascular collapse).
Breast cancer (ovarian suppression during adjuvant endocrine therapy; off-label use): Monitor for physiologic changes that may be indicative of ovarian function recovery (eg, resumption of menses, cyclical fluctuations in climacteric symptoms) (ASCO [Burstein 2016]).
Endometriosis, endometrial thinning: Evaluate pregnancy status prior to use.
Prostate cancer: Consider periodic ECG and electrolyte monitoring (correct electrolytes prior to treatment initiation). Monitor testosterone levels if desired clinical response is not observed, particularly in patients with obesity. Monitor for weakness, paresthesias, tumor flare, urinary tract obstruction, and spinal cord compression in first few weeks of therapy; monitor for signs/symptoms of cardiovascular disease.
Transgender hormone therapy (off-label use): Serum testosterone levels (goal <50 ng/dL) every 3 months during the first year and then annually or biannually; serum luteinizing hormone, follicle-stimulating hormone, and prolactin levels at baseline and annually; routine cancer and laboratory screening as in non-transgender individuals for all tissues present (ES [Hembree 2017]; Mueller 2011).
Cardiovascular monitoring for patients with prostate cancer: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking; baseline and serial ECGs are recommended in patients at risk of QTc prolongation during androgen deprivation therapy (ADT); estimate 10-year cardiovascular disease risk in patients without cardiovascular disease at baseline; assess cardiovascular risk annually during ADT (ASCO [Armenian 2017]; ESC [Lyon 2022]).
Goserelin (a gonadotropin-releasing hormone [GnRH] analog) causes an initial increase in luteinizing hormone (LH) and follicle stimulating hormone (FSH), chronic administration of goserelin results in a sustained suppression of pituitary gonadotropins. Serum testosterone falls to levels comparable to surgical castration. The exact mechanism of this effect is unknown, but may be related to changes in the control of LH or down-regulation of LH receptors.
Onset:
Females: Estradiol suppression reaches postmenopausal levels within 3 weeks and FSH and LH are suppressed to follicular phase levels within 4 weeks of initiation.
Patients with prostate cancer: Testosterone suppression reaches castrate levels within 2 to 4 weeks after initiation.
Duration:
Females: Estradiol, LH and FSH generally return to baseline levels within 12 weeks following the last monthly implant.
Patients with prostate cancer: Testosterone levels maintained at castrate levels throughout the duration of therapy.
Absorption: SUBQ: Rapid and can be detected in serum in 30 to 60 minutes; 3.6 mg: released slowly in first 8 days, then rapid and continuous release for 28 days.
Distribution: Vd: Male: 44.1 L; Female: 20.3 L.
Protein binding: ~27%.
Metabolism: Hepatic hydrolysis of the C-terminal amino acids.
Time to peak, serum: SUBQ: Male: 12 to 15 days, Female: 8 to 22 days.
Excretion: Urine (>90%; 20% as unchanged drug).
Sex: The total body Cl of goserelin was significantly (P <0.05) greater (163.9 vs 110.5 L/min) in females compared with males.
Body weight: A decline in AUC of approximately 1% to 2.5% was observed with a kg increase in body weight.
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