Androgen deprivation therapy may prolong the QT/QTc interval. Providers should consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients with congenital long QT syndrome, congestive heart failure, frequent electrolyte abnormalities, and in patients taking drugs known to prolong the QT interval. Electrolyte abnormalities should be corrected. Consider periodic monitoring of electrocardiograms and electrolytes.
Androgen deprivation therapy may prolong the QT/QTc interval. Providers should consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients with congenital long QT syndrome, congestive heart failure, frequent electrolyte abnormalities, and in patients taking drugs known to prolong the QT interval. Electrolyte abnormalities should be corrected. Consider periodic monitoring of electrocardiograms and electrolytes.
|clinicalTrials=There is limited information regarding <i>Clinical Trial Experience</i> of {{PAGENAME}} in the drug label.
|clinicalTrials======Clinical Trials=====
* ZOLADEX has been found to be generally well tolerated in clinical trials. Adverse reactions reported in these trials were rarely severe enough to result in the patients' withdrawal from ZOLADEX treatment. As seen with other hormonal therapies, the most commonly observed adverse events during ZOLADEX therapy were due to the expected physiological effects from decreased testosterone levels. These included hot flashes, sexual dysfunction and decreased erections.
=====Body as a Whole=====
* Tumor Flare Phenomenon: Initially, ZOLADEX, like other GnRH agonists, causes transient increases in serum levels of testosterone. A small percentage of patients experienced a temporary worsening of signs and symptoms, usually manifested by an increase in cancer-related pain which was managed symptomatically. Isolated cases of exacerbation of disease symptoms, either ureteral obstruction or spinal cord compression, occurred at similar rates in controlled clinical trials with both ZOLADEX and orchiectomy. The relationship of these events to therapy is uncertain
=====Stage B2-C Prostatic Carcinoma=====
* Treatment with ZOLADEX and flutamide did not add substantially to the toxicity of radiation treatment alone. The following adverse experiences were reported during a multicenter clinical trial comparing ZOLADEX + flutamide + radiation versus radiation alone. The most frequently reported (greater than 5%) adverse experiences are listed below:
: [[File:Goserelin Adv effects table 1 and 2.png|none|500px]]
* Additional adverse event data was collected for the combination therapy with radiation group over both the hormonal treatment and hormonal treatment plus radiation phases of the study. Adverse experiences occurring in more than 5% of patients in this group, over both parts of the study, were hot flashes (46%), diarrhea (40%), nausea (9%), and skin rash (8%).
=====Cardiovascular=====
=====Prostatic Carcinoma=====
* Two controlled clinical trials using ZOLADEX 10.8 mg versus ZOLADEX 3.6 mg were conducted. During a comparative phase, patients were randomized to receive either a single 10.8 mg implant or three consecutive 3.6 mg implants every 4 weeks over weeks 0-12. During this phase, the only adverse event reported in greater than 5% of patients was hot flashes, with an incidence of 47% in the ZOLADEX 10.8 mg group and 48% in the ZOLADEX 3.6 mg group.
* From weeks 12-48 all patients were treated with a 10.8 mg implant every 12 weeks. During this noncomparative phase, the following adverse events were reported in greater than 5% of patients:
The following adverse events were reported in greater than 1%, but less than 5% of patients treated with ZOLADEX 10.8 mg implant every 12 weeks. Some of these are commonly reported in elderly patients.
=====Digestive=====
======WHOLE BODY======
* Abdominal pain
* Back pain
* Flu syndrome
* Headache
=====Endocrine=====
* Sepsis
* Aggravation reaction
======CARDIOVASCULAR======
* Angina pectoris
* Cerebral ischemia
=====Hematologic and Lymphatic=====
* Cerebrovascular accident
* Heart failure
* Pulmonary embolus
* Varicose veins
======DIGESTIVE======
=====Metabolic and Nutritional=====
* Diarrhea
* Hematemesis
======ENDOCRINE======
* Diabetes mellitus
======HEMATOLOGIC======
=====Musculoskeletal=====
* Anemia
======METABOLIC======
* Peripheral edema
======NERVOUS SYSTEM======
* Dizziness
=====Neurologic=====
* Paresthesia
* Urinary retention
======RESPIRATORY======
* Cough increased
* Dyspnea
=====Respiratory=====
* Pneumonia
======SKIN======
* Herpes simplex
* Pruritus
======UROGENITAL=====
=====Skin and Hypersensitivy Reactions=====
* Bladder neoplasm
* Breast pain
* Hematuria
* Impotence
* Urinary frequency
=====Special Senses=====
* Urinary incontinence
* Urinary tract disorder
* Urinary tract infection
* Urination impaired
* The following adverse events not already listed above were reported in patients receiving ZOLADEX 3.6 mg in other clinical trials. Inclusion does not necessarily represent a causal relationship to ZOLADEX 10.8 mg.
=====Urogenital=====
======WHOLE BODY======
* Allergic reaction
* Chills
* Fever
* Infection
=====Miscellaneous=====
* Injection site reaction
* Lethargy
* Malaise
======CARDIOVASCULAR======
<!--Postmarketing Experience-->
* Arrhythmia
|postmarketing=There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
* Chest pain
* Hemorrhage
=====Body as a Whole=====
* Hypertension
* Migraine
* Myocardial infarction
* Palpitations
=====Cardiovascular=====
* Peripheral vascular disorder
* Tachycardia
======DIGESTIVE======
* Anorexia
=====Digestive=====
* Constipation
* Dry mouth
* Dyspepsia
* Flatulence
=====Endocrine=====
* Increased appetite
* Nausea
* Ulcer
* Vomiting
=====Hematologic and Lymphatic=====
======HEMATOLOGIC======
* Ecchymosis
======METABOLIC======
* Edema
=====Metabolic and Nutritional=====
* Gout
* Hyperglycemia
* Weight increase
======MUSCULOSKELETAL======
=====Musculoskeletal=====
* Arthralgia
* Hypertonia
* Joint disorder
* Leg cramps
=====Neurologic=====
* Myalgia
* Osteoporosis
======NERVOUS SYSTEM======
* Anxiety
=====Respiratory=====
* Depression
* Emotional lability
* Headache
* Insomnia
=====Skin and Hypersensitivy Reactions=====
* Nervousness
* Somnolence
* Thinking abnormal
======RESPIRATORY======
=====Special Senses=====
* Bronchitis
* Chronic obstructive pulmonary disease
* Epistaxis
* Rhinitis
=====Urogenital=====
* Sinusitis
* Upper respiratory infection
* Voice alterations
======SKIN======
=====Miscellaneous=====
* Acne
* Alopecia
* Dry skin
* Hair disorders
* Rash
* Seborrhea
* Skin discoloration
* Sweating
======SPECIAL SENSES======
* Amblyopia
* Dry eyes
======UROGENITAL======
* Breast tenderness
* Decreased erections
* Renal insufficiency
* Sexual dysfunction
* Urinary obstruction
======Changes in Laboratory Values During Treatment
* Plasma Enzymes: Elevation of liver enzymes (AST, ALT) have been reported in female patients exposed to ZOLADEX 3.6 mg (representing less than 1% of all patients). There was no other evidence of abnormal liver function. Causality between these changes and ZOLADEX have not been established.
* Lipids: In a controlled trial in females, ZOLADEX 3.6 mg implant therapy resulted in a minor, but statistically significant effect on serum lipids (i.e., increases in LDL cholesterol of 21.3 mg/dL; increases in HDL cholesterol of 2.7 mg/dL; and triglycerides increased by 8.0 mg/dL).
|postmarketing=* The following adverse reactions have been identified during post-approval use of ZOLADEX. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
======Hypercalcemia======
* In patients with bone metastases.
======Bone Mineral Density======
* Osteoporosis, decreased bone mineral density and bony fracture in men.
======Changes in Blood Pressure======
* Hypotension and hypertension have been reported. These changes are usually transient, resolving either during continued therapy or after cessation of therapy.
======Pituitary Apoplexy and Tumors======
* Pituitary apoplexy (a clinical syndrome secondary to infarction of the pituitary gland) and pituitary adenoma have been diagnosed. Most of the pituitary apoplexy cases occurred within 2 weeks of the first dose, and some occurred within the first hour. In these cases, pituitary apoplexy has presented as sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, and sometimes cardiovascular collapse. Immediate medical attention has been required. Pituitary tumors have been reported.
======Acne======
* Usually within one month of starting treatment.
======Other Adverse Reactions======
* Psychotic disorders, convulsions and mood swings.
<!--Drug Interactions-->
|drugInteractions=* Drug
:* Description
<!--Use in Specific Populations-->
|useInPregnancyFDA=* '''Pregnancy Category'''
|useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
|drugInteractions=* No formal drug-drug interaction studies have been performed.
* No drug interaction studies with other drugs have been conducted with ZOLADEX. No confirmed interactions have been reported between ZOLADEX and other drugs.
=====Drug/Laboratory Test Interactions=====
* Administration of ZOLADEX in therapeutic doses results in suppression of the pituitary-gonadal system. Because of this suppression, diagnostic tests of pituitary-gonadotropic and gonadal functions conducted during treatment may show results which are misleading.
|FDAPregCat=X
|useInPregnancyFDA=* Based on mechanism of action in humans and findings of increased pregnancy loss in animal studies, ZOLADEX may cause fetal harm when administered to a pregnant woman. Expected hormone changes that occur with ZOLADEX treatment increase the risk for pregnancy loss. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus [seeCONTRAINDICATIONS (4.2)].
* ZOLADEX crosses the placenta in rats and rabbits following subcutaneous administration. Administration of goserelin to pregnant rats and rabbits during organogenesis resulted in increased preimplantation loss and increased resorptions. When pregnant rats received goserelin throughout gestation and lactation, there was a dose-related increase in umbilical hernia in offspring. In additional reproduction studies in rats, goserelin decreased fetus and pup survival. Human dose/exposure multiples could not be calculated from available animal data.
* Actual animal doses: rat (≥ 2 mcg/kg/day for pregnancy loss; ≥ 10 mcg/kg/day for umbilical hernia in offspring); rabbits (> 20 mcg/kg/day).
|useInPregnancyAUS=There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
|useInLaborDelivery=There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
|useInLaborDelivery=There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
|useInNursing=There is no FDA guidance on the use of {{PAGENAME}} with respect to nursing mothers.
|useInNursing=* It is not known if goserelin is excreted in human milk. Goserelin is excreted in the milk of lactating rats. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from ZOLADEX, a decision should be made to either discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
|useInPed=There is no FDA guidance on the use of {{PAGENAME}} with respect to pediatric patients.
|useInPed=* Safety and effectiveness in pediatric patients have not been established.
|useInGeri=There is no FDA guidance on the use of {{PAGENAME}} with respect to geriatric patients.
|useInGeri=* There is no need for any dosage adjustment when administering ZOLADEX 10.8 mg to geriatric patients.
|useInGender=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
|useInGender=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
|useInRace=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
|useInRace=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
|useInRenalImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with renal impairment.
|useInRenalImpair=* In clinical trials with the solution formulation of goserelin, subjects with impaired renal function (creatinine clearance < 20 mL/min) had a serum elimination half-life of 12.1 hours compared to 4.2 hours for subjects with normal renal function (creatinine clearance > 70 mL/min). However, there was no evidence for any accumulation of goserelin on multiple dosing of the ZOLADEX 10.8 mg depot to subjects with impaired renal function. There was no evidence for any increase in incidence of adverse events in renally impaired patients administered the 10.8 mg depot. These data indicate that there is no need for any dosage adjustment when administering ZOLADEX 10.8 mg to subjects with impaired renal function.
|useInHepaticImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with hepatic impairment.
|useInHepaticImpair=* The total body clearances and serum elimination half-lives were similar between normal subjects and patients with moderate hepatic impairment (alanine transaminase < 3xULN and asparate aminotransferase < 3xULN) when treated with a 250 mcg subcutaneous formulation of goserelin. This pharmacokinetic study indicates that no dose adjustment is needed in patients with moderately impaired liver function. There is no pharmacokinetic data with goserelin in patients with severe hepatic insufficiency.
|useInReproPotential=There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
|useInReproPotential=There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
|useInImmunocomp=There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.
|useInImmunocomp=There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.
<!--Administration and Monitoring-->
<!--Administration and Monitoring-->
|othersTitle=Body Weight
|useInOthers=* A decline of approximately 1 to 2.5% in the AUC after administration of a 10.8 mg depot was observed with a kilogram increase in body weight. In obese patients who have not responded clinically, testosterone levels should be monitored closely.
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Overview
Goserelin is a Gonadotropin Releasing Hormone (GnRH) agonist that is FDA approved for the treatment of locally confined carcinoma of the prostate, and palliative treatment of advanced carcinoma of the prostate. Common adverse reactions include hot flashes, sexual dysfunction, decreased erections and lower urinary tract symptoms.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Indications
Stage B2-C Prostatic Carcinoma
ZOLADEX is indicated for use in combination with flutamide for the management of locally confined Stage T2b-T4 (Stage B2-C) carcinoma of the prostate. Treatment with ZOLADEX and flutamide should start 8 weeks prior to initiating radiation therapy and continue during radiation therapy
Dosage
When ZOLADEX is given in combination with radiotherapy and flutamide for patients with Stage T2b-T4 (Stage B2-C) prostatic carcinoma, treatment should be started 8 weeks prior to initiating radiotherapy and should continue during radiation therapy. A treatment regimen using one ZOLADEX 3.6 mg depot, followed in 28 days by one ZOLADEX 10.8 mg depot, should be administered.
Prostatic Carcinoma
ZOLADEX is indicated in the palliative treatment of advanced carcinoma of the prostate.
In controlled studies of patients with advanced prostatic cancer comparing ZOLADEX 3.6 mg to orchiectomy, the long-term endocrine responses and objective responses were similar between the two treatment arms. Additionally, duration of survival was similar between the two treatment arms in a major comparative trial.
In controlled studies of patients with advanced prostatic cancer, ZOLADEX 10.8 mg implant produced pharmacodynamically similar effect in terms of suppression of serum testosterone to that achieved with ZOLADEX 3.6 mg implant. Clinical outcome similar to that produced with the use of the ZOLADEX 3.6 mg implant administered every 28 days is predicted with the ZOLADEX 10.8 mg implant administered every 12 weeks.
The automatic safety feature of the syringe aids in the prevention of needlestick injury.
Dosage
For the management of advanced prostate cancer, ZOLADEX is intended for long-term administration unless clinically inappropriate.
Renal or Hepatic Impairment
No dosage adjustment is necessary for patients with renal or hepatic impairment.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Goserelin in adult patients.
Non–Guideline-Supported Use
Breast cancer, Adjuvant treatment of hormone receptor-positive, axillary lymph node-positive disease in premenopausal women[1][2]
There is limited information regarding FDA-Labeled Use of Goserelin in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Goserelin in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Goserelin in pediatric patients.
Contraindications
Hypersensitivity
Anaphylactic reactions to ZOLADEX have been reported in the medical literature. ZOLADEX is contraindicated in those patients who have a known hypersensitivity to GnRH, GnRH agonist analogues or any of the components in ZOLADEX.
Pregnancy
Expected hormonal changes that occur with ZOLADEX treatment increase the risk for pregnancy loss. ZOLADEX may cause fetal harm when administered to a pregnant woman. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus
Warnings
Tumor Flare Phenomenon
Initially, ZOLADEX, like other GnRH agonists, causes transient increases in serum levels of testosterone. Transient worsening of symptoms, or the occurrence of additional signs and symptoms of prostatic cancer, may occasionally develop during the first few weeks of ZOLADEX treatment. A small number of patients may experience a temporary increase in bone pain, which can be managed symptomatically. As with other GnRH agonists, isolated cases of ureteral obstruction and spinal cord compression have been observed. If spinal cord compression or renal impairment secondary to ureteral obstruction develops, standard treatment of these complications should be instituted, and in extreme cases an immediate orchiectomy.
Hypersensitivity
Hypersensitivity, antibody formation and acute anaphylactic reactions have been reported with GnRH agonist analogues.
Of 115 women worldwide treated with ZOLADEX and tested for development of binding to goserelin following treatment with ZOLADEX, one patient showed low-titer binding to goserelin. On further testing of this patient's plasma obtained following treatment, her goserelin binding component was found not to be precipitated with rabbit antihuman immunoglobulin polyvalent sera. These findings suggest the possibility of antibody formation.
Hyperglycemia and Diabetes
Hyperglycemia and an increased risk of developing diabetes have been reported in men receiving GnRH agonists. Hyperglycemia may represent development of diabetes mellitus or worsening of glycemic control in patients with diabetes. Monitor blood glucose and/or glycosylated hemoglobin (HbA1c) periodically in patients receiving a GnRH agonist and manage with current practice for treatment of hyperglycemia or diabetes.
Cardiovascular Diseases
Increased risk of developing myocardial infarction, sudden cardiac death and stroke has been reported in association with use of GnRH agonists in men. The risk appears low based on the reported odds ratios, and should be evaluated carefully along with cardiovascular risk factors when determining a treatment for patients with prostate cancer. Patients receiving a GnRH agonist should be monitored for symptoms and signs suggestive of development of cardiovascular disease and be managed according to current clinical practice.
Effect on QT/QTc Interval
Androgen deprivation therapy may prolong the QT/QTc interval. Providers should consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients with congenital long QT syndrome, congestive heart failure, frequent electrolyte abnormalities, and in patients taking drugs known to prolong the QT interval. Electrolyte abnormalities should be corrected. Consider periodic monitoring of electrocardiograms and electrolytes.
Adverse Reactions
Clinical Trials Experience
Clinical Trials
ZOLADEX has been found to be generally well tolerated in clinical trials. Adverse reactions reported in these trials were rarely severe enough to result in the patients' withdrawal from ZOLADEX treatment. As seen with other hormonal therapies, the most commonly observed adverse events during ZOLADEX therapy were due to the expected physiological effects from decreased testosterone levels. These included hot flashes, sexual dysfunction and decreased erections.
Tumor Flare Phenomenon: Initially, ZOLADEX, like other GnRH agonists, causes transient increases in serum levels of testosterone. A small percentage of patients experienced a temporary worsening of signs and symptoms, usually manifested by an increase in cancer-related pain which was managed symptomatically. Isolated cases of exacerbation of disease symptoms, either ureteral obstruction or spinal cord compression, occurred at similar rates in controlled clinical trials with both ZOLADEX and orchiectomy. The relationship of these events to therapy is uncertain
Stage B2-C Prostatic Carcinoma
Treatment with ZOLADEX and flutamide did not add substantially to the toxicity of radiation treatment alone. The following adverse experiences were reported during a multicenter clinical trial comparing ZOLADEX + flutamide + radiation versus radiation alone. The most frequently reported (greater than 5%) adverse experiences are listed below:
Additional adverse event data was collected for the combination therapy with radiation group over both the hormonal treatment and hormonal treatment plus radiation phases of the study. Adverse experiences occurring in more than 5% of patients in this group, over both parts of the study, were hot flashes (46%), diarrhea (40%), nausea (9%), and skin rash (8%).
Prostatic Carcinoma
Two controlled clinical trials using ZOLADEX 10.8 mg versus ZOLADEX 3.6 mg were conducted. During a comparative phase, patients were randomized to receive either a single 10.8 mg implant or three consecutive 3.6 mg implants every 4 weeks over weeks 0-12. During this phase, the only adverse event reported in greater than 5% of patients was hot flashes, with an incidence of 47% in the ZOLADEX 10.8 mg group and 48% in the ZOLADEX 3.6 mg group.
From weeks 12-48 all patients were treated with a 10.8 mg implant every 12 weeks. During this noncomparative phase, the following adverse events were reported in greater than 5% of patients:
The following adverse events were reported in greater than 1%, but less than 5% of patients treated with ZOLADEX 10.8 mg implant every 12 weeks. Some of these are commonly reported in elderly patients.
WHOLE BODY
Abdominal pain
Back pain
Flu syndrome
Headache
Sepsis
Aggravation reaction
CARDIOVASCULAR
Angina pectoris
Cerebral ischemia
Cerebrovascular accident
Heart failure
Pulmonary embolus
Varicose veins
DIGESTIVE
Diarrhea
Hematemesis
ENDOCRINE
Diabetes mellitus
HEMATOLOGIC
Anemia
METABOLIC
Peripheral edema
NERVOUS SYSTEM
Dizziness
Paresthesia
Urinary retention
RESPIRATORY
Cough increased
Dyspnea
Pneumonia
SKIN
Herpes simplex
Pruritus
=UROGENITAL
Bladder neoplasm
Breast pain
Hematuria
Impotence
Urinary frequency
Urinary incontinence
Urinary tract disorder
Urinary tract infection
Urination impaired
The following adverse events not already listed above were reported in patients receiving ZOLADEX 3.6 mg in other clinical trials. Inclusion does not necessarily represent a causal relationship to ZOLADEX 10.8 mg.
WHOLE BODY
Allergic reaction
Chills
Fever
Infection
Injection site reaction
Lethargy
Malaise
CARDIOVASCULAR
Arrhythmia
Chest pain
Hemorrhage
Hypertension
Migraine
Myocardial infarction
Palpitations
Peripheral vascular disorder
Tachycardia
DIGESTIVE
Anorexia
Constipation
Dry mouth
Dyspepsia
Flatulence
Increased appetite
Nausea
Ulcer
Vomiting
HEMATOLOGIC
Ecchymosis
METABOLIC
Edema
Gout
Hyperglycemia
Weight increase
MUSCULOSKELETAL
Arthralgia
Hypertonia
Joint disorder
Leg cramps
Myalgia
Osteoporosis
NERVOUS SYSTEM
Anxiety
Depression
Emotional lability
Headache
Insomnia
Nervousness
Somnolence
Thinking abnormal
RESPIRATORY
Bronchitis
Chronic obstructive pulmonary disease
Epistaxis
Rhinitis
Sinusitis
Upper respiratory infection
Voice alterations
SKIN
Acne
Alopecia
Dry skin
Hair disorders
Rash
Seborrhea
Skin discoloration
Sweating
SPECIAL SENSES
Amblyopia
Dry eyes
UROGENITAL
Breast tenderness
Decreased erections
Renal insufficiency
Sexual dysfunction
Urinary obstruction
======Changes in Laboratory Values During Treatment
Plasma Enzymes: Elevation of liver enzymes (AST, ALT) have been reported in female patients exposed to ZOLADEX 3.6 mg (representing less than 1% of all patients). There was no other evidence of abnormal liver function. Causality between these changes and ZOLADEX have not been established.
Lipids: In a controlled trial in females, ZOLADEX 3.6 mg implant therapy resulted in a minor, but statistically significant effect on serum lipids (i.e., increases in LDL cholesterol of 21.3 mg/dL; increases in HDL cholesterol of 2.7 mg/dL; and triglycerides increased by 8.0 mg/dL).
Postmarketing Experience
The following adverse reactions have been identified during post-approval use of ZOLADEX. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Hypercalcemia
In patients with bone metastases.
Bone Mineral Density
Osteoporosis, decreased bone mineral density and bony fracture in men.
Changes in Blood Pressure
Hypotension and hypertension have been reported. These changes are usually transient, resolving either during continued therapy or after cessation of therapy.
Pituitary Apoplexy and Tumors
Pituitary apoplexy (a clinical syndrome secondary to infarction of the pituitary gland) and pituitary adenoma have been diagnosed. Most of the pituitary apoplexy cases occurred within 2 weeks of the first dose, and some occurred within the first hour. In these cases, pituitary apoplexy has presented as sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, and sometimes cardiovascular collapse. Immediate medical attention has been required. Pituitary tumors have been reported.
Acne
Usually within one month of starting treatment.
Other Adverse Reactions
Psychotic disorders, convulsions and mood swings.
Drug Interactions
No formal drug-drug interaction studies have been performed.
No drug interaction studies with other drugs have been conducted with ZOLADEX. No confirmed interactions have been reported between ZOLADEX and other drugs.
Drug/Laboratory Test Interactions
Administration of ZOLADEX in therapeutic doses results in suppression of the pituitary-gonadal system. Because of this suppression, diagnostic tests of pituitary-gonadotropic and gonadal functions conducted during treatment may show results which are misleading.
Based on mechanism of action in humans and findings of increased pregnancy loss in animal studies, ZOLADEX may cause fetal harm when administered to a pregnant woman. Expected hormone changes that occur with ZOLADEX treatment increase the risk for pregnancy loss. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus [seeCONTRAINDICATIONS (4.2)].
ZOLADEX crosses the placenta in rats and rabbits following subcutaneous administration. Administration of goserelin to pregnant rats and rabbits during organogenesis resulted in increased preimplantation loss and increased resorptions. When pregnant rats received goserelin throughout gestation and lactation, there was a dose-related increase in umbilical hernia in offspring. In additional reproduction studies in rats, goserelin decreased fetus and pup survival. Human dose/exposure multiples could not be calculated from available animal data.
Actual animal doses: rat (≥ 2 mcg/kg/day for pregnancy loss; ≥ 10 mcg/kg/day for umbilical hernia in offspring); rabbits (> 20 mcg/kg/day).
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Goserelin in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Goserelin during labor and delivery.
Nursing Mothers
It is not known if goserelin is excreted in human milk. Goserelin is excreted in the milk of lactating rats. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from ZOLADEX, a decision should be made to either discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
Geriatic Use
There is no need for any dosage adjustment when administering ZOLADEX 10.8 mg to geriatric patients.
Gender
There is no FDA guidance on the use of Goserelin with respect to specific gender populations.
Race
There is no FDA guidance on the use of Goserelin with respect to specific racial populations.
Renal Impairment
In clinical trials with the solution formulation of goserelin, subjects with impaired renal function (creatinine clearance < 20 mL/min) had a serum elimination half-life of 12.1 hours compared to 4.2 hours for subjects with normal renal function (creatinine clearance > 70 mL/min). However, there was no evidence for any accumulation of goserelin on multiple dosing of the ZOLADEX 10.8 mg depot to subjects with impaired renal function. There was no evidence for any increase in incidence of adverse events in renally impaired patients administered the 10.8 mg depot. These data indicate that there is no need for any dosage adjustment when administering ZOLADEX 10.8 mg to subjects with impaired renal function.
Hepatic Impairment
The total body clearances and serum elimination half-lives were similar between normal subjects and patients with moderate hepatic impairment (alanine transaminase < 3xULN and asparate aminotransferase < 3xULN) when treated with a 250 mcg subcutaneous formulation of goserelin. This pharmacokinetic study indicates that no dose adjustment is needed in patients with moderately impaired liver function. There is no pharmacokinetic data with goserelin in patients with severe hepatic insufficiency.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Goserelin in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Goserelin in patients who are immunocompromised.
Body Weight
A decline of approximately 1 to 2.5% in the AUC after administration of a 10.8 mg depot was observed with a kilogram increase in body weight. In obese patients who have not responded clinically, testosterone levels should be monitored closely.
Administration and Monitoring
Administration
Oral
Intravenous
Monitoring
There is limited information regarding Monitoring of Goserelin in the drug label.
Description
IV Compatibility
There is limited information regarding IV Compatibility of Goserelin in the drug label.
Overdosage
Acute Overdose
Signs and Symptoms
Description
Management
Description
Chronic Overdose
There is limited information regarding Chronic Overdose of Goserelin in the drug label.
Pharmacology
There is limited information regarding Goserelin Pharmacology in the drug label.
