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Generic drug: goserelin acetate

Brand name: Zoladex

What is Zoladex (goserelin acetate), and how does it work?

Zoladex (goserelin acetate) implant is a GnRH agonist used to treat a variety of conditions, including advanced breast cancer, prostate cancer, endometriosis, and endometrial thinning. 

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.

Prostatic Carcinoma

Zoladex is indicated in the palliative treatment of advanced carcinoma of the prostate.

Endometriosis

Zoladex is indicated for the management of endometriosis, including pain relief and reduction of endometriotic lesions for the duration of therapy. Experience with Zoladex for the management of endometriosis has been limited to women 18 years of age and older treated for 6 months.

Endometrial Thinning

Zoladex is indicated for use as an endometrial-thinning agent prior to endometrial ablation for dysfunctional uterine bleeding.

Advanced Breast Cancer

Zoladex is indicated for use in the palliative treatment of advanced breast cancer in pre- and perimenopausal women.

The estrogen and progesterone receptor values may help to predict whether Zoladex therapy is likely to be beneficial.

The automatic safety feature of the syringe aids in the prevention of needlestick injury.

What are the side effects of Zoladex?

Stage B2-C Prostatic Carcinoma

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:

Table 1 : ADVERSE EVENTS DURING ACUTE RADIATION THERAPY (within first 90 days of radiation therapy)

  (n=231)
flutamide + Zoladex + Radiation		 (n=235)
Radiation Only
% All %All
Rectum/Large Bowel 80 76
Bladder 58 60
Skin 37 37

Table 2 : ADVERSE EVENTS DURING LATE RADIATION PHASE (after 90 days of radiation therapy)

  (n=231)
flutamide + Zoladex + Radiation		 (n=235)
Radiation Only
% All %All
Diarrhea 36 40
Cystitis 16 16
Rectal Bleeding 14 20
Proctitis 8 8
Hematuria 7 12

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

Prostatic Carcinoma

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.

In the controlled clinical trials of Zoladex versus orchiectomy, the following events were reported as adverse reactions in greater than 5% of the patients.

Table 3 : TREATMENT RECEIVED

ADVERSE EVENT Zoladex
(n=242) %		 ORCHIECTOMY
(n=254) %
Hot Flashes 62 53
Sexual Dysfunction 21 15
Decreased Erections 18 16
Lower Urinary Tract Symptoms 13 8
Lethargy 8 4
Pain (worsened in the first 30 days) 8 3
Edema 7 8
Upper Respiratory Infection 7 2
Rash 6 1
Sweating 6 4
Anorexia 5 2
Chronic Obstructive Pulmonary Disease 5 3
Congestive Heart Failure 5 1
Dizziness 5 4
Insomnia 5 1
Nausea 5 2
Complications of Surgery 0 18*
* Complications related to surgery were reported in 18% of the orchiectomy patients, while only 3% of Zoladex patients reported adverse reactions at the injection site. The surgical complications included scrotal infection (5.9%), groin pain (4 .7%), wound seepage (3.1%), scrotal hematoma (2.8%), incisional discomfort (1.6%) and skin necrosis (1.2%).

The following additional adverse reactions were reported in greater than 1% but less than 5% of the patients treated with Zoladex:

Females

As would be expected with a drug that results in hypoestrogenism, the most frequently reported adverse reactions were those related to this effect.

Endometriosis

In controlled clinical trials comparing Zoladex every 28 days and danazol daily for the treatment of endometriosis, the following events were reported at a frequency of 5% or greater:

Table 4 : TREATMENT RECEIVED

ADVERSE EVENT Zoladex
(n=411) %		 DANAZOL
(n=207) %
Hot Flushes 96 67
Vaginitis 75 43
Headache 75 63
Emotional Lability 60 56
Libido Decreased 61 44
Sweating 45 30
Depression 54 48
Acne 42 55
Breast Atrophy 33 42
Seborrhea 26 52
Peripheral Edema 21 34
Breast Enlargement 18 15
Pelvic Symptoms 18 23
Pain 17 16
Dyspareunia 14 5
Libido Increased 12 19
Infection 13 11
Asthenia 11 13
Nausea 8 14
Hirsutism 7 15
Insomnia 11 4
Breast Pain 7 4
Abdominal Pain 7 7
Back Pain 7 13
Flu Syndrome 5 5
Dizziness 6 4
Application Site Reaction 6 -
Voice Alterations 3 8
Pharyngitis 5 2
Hair Disorders 4 11
Myalgia 3 11
Nervousness 3 5
Weight Gain 3 23
Leg Cramps 2 6
Increased Appetite 2 5
Pruritus 2 6
Hypertonia 1 10

The following adverse events not already listed above were reported at a frequency of 1% or greater, regardless of causality, in Zoladex-treated women from all clinical trials:

Endometrial Thinning

The following adverse events were reported at a frequency of 5% or greater in premenopausal women presenting with dysfunctional uterine bleeding in Trial 0022 for endometrial thinning. These results indicate that headache, hot flushes and sweating were more common in the Zoladex group than in the placebo group.

Table 5 : ADVERSE EVENTS REPORTED AT A FREQUENCY OF 5% OR GREATER IN Zoladex AND PLACEBO TREATMENT GROUPS OF TRIAL 0022

ADVERSE EVENT Zoladex 3.6 mg
(n=180) %		 Placebo
(n=177) %
Whole Body
Headache 32 22
Abdominal Pain 11 10
Pelvic Pain 9 6
Back Pain 4 7
Cardiovascular
Vasodilatation 57 18
Migraine 7 4
Hypertension 6 2
Digestive
Nausea 5 6
Nervous
Nervousness 5 3
Depression 3 7
Respiratory
Pharyngitis 6 9
Sinusitis 3 6
Skin and appendages
Sweating 16 5
Urogenital
Dysmenorrhea 7 9
Uterine Hemorrhage 6 4
Vulvovaginitis 5 1
Menorrhagia 4 5
Vaginitis 1 6

Breast Cancer

The adverse event profile for women with advanced breast cancer treated with Zoladex is consistent with the profile described above for women treated with Zoladex for endometriosis. In a controlled clinical trial (SWOG–8692) comparing Zoladex with oophorectomy in premenopausal and perimenopausal women with advanced breast cancer, the following events were reported at a frequency of 5% or greater in either treatment group regardless of causality.

Table 6 : TREATMENT RECEIVED

ADVERSE EVENT Zoladex
(n=57) % of Pts.		 OOPHORECTOMY
(n=55) % of Pts.
Hot Flashes 70 47
Tumor Flare 23 4
Nausea 11 7
Edema 5 0
Malaise/Fatigue/Lethargy 5 2
Vomiting 4 7

In the Phase II clinical trial program in 333 pre- and perimenopausal women with advanced breast cancer, hot flashes were reported in 75.9% of patients and decreased libido was noted in 47.7% of patients. These two adverse events reflect the pharmacological actions of Zoladex.

Injection site reactions were reported in less than 1% of patients.

Hormone Replacement Therapy

Clinical studies suggest the addition of Hormone Replacement Therapy (estrogens and/or progestins) to Zoladex may decrease the occurrence of vasomotor symptoms and vaginal dryness associated with hypoestrogenism without compromising the efficacy of Zoladex in relieving pelvic symptoms. The optimal drugs, dose and duration of treatment has not been established.

Changes In Bone Mineral Density

  • After 6 months of Zoladex treatment, 109 female patients treated with Zoladex showed an average 4.3% decrease of vertebral trabecular bone mineral density (BMD) as compared to pretreatment values. BMD was measured by dual-photon absorptiometry or dual energy x-ray absorptiometry.
  • Sixtysix of these patients were assessed for BMD loss 6 months after the completion (posttherapy) of the 6- month therapy period.
  • Data from these patients showed an average 2.4% BMD loss compared to pretreatment values.
  • Twenty-eight of the 109 patients were assessed for BMD at 12 months posttherapy. Data from these patients showed an average decrease of 2.5% in BMD compared to pretreatment values. These data suggest a possibility of partial reversibility.
  • Clinical studies suggest the addition of Hormone Replacement Therapy (estrogens and/or progestins) to Zoladex is effective in reducing the bone mineral loss which occurs with Zoladex alone without compromising the efficacy of Zoladex in relieving the symptoms of endometriosis. The optimal drugs, dose and duration of treatment has not been established.

Changes In Laboratory Values During Treatment

  • Plasma Enzymes: Elevation of liver enzymes (AST, ALT) have been reported in female patients exposed to Zoladex (representing less than 1% of all patients).
  • Lipids: In a controlled trial, Zoladex therapy resulted in a minor, but statistically significant effect on serum lipids. In patients treated for endometriosis at 6 months following initiation of therapy, danazol treatment resulted in a mean increase in LDL cholesterol of 33.3 mg/dL and a decrease in HDL cholesterol of 21.3 mg/dL compared to increases of 21.3 and 2.7 mg/dL in LDL cholesterol and HDL cholesterol, respectively, for Zoladex-treated patients. Triglycerides increased by 8.0 mg/dL in Zoladex-treated patients compared to a decrease of 8.9 mg/dL in danazol-treated patients.
  • In patients treated for endometriosis, Zoladex increased total cholesterol and LDL cholesterol during 6 months of treatment. However, Zoladex therapy resulted in HDL cholesterol levels which were significantly higher relative to danazol therapy. At the end of 6 months of treatment, HDL cholesterol fractions (HDL2 and HDL2) were decreased by 13.5 and 7.7 mg/dL, respectively, for danazol-treated patients compared to treatment increases of 1.9 and 0.8 mg/dL, respectively, for Zoladex-treated patients.

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.

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What is the dosage for Zoladex?

  • Zoladex, at a dose of 3.6 mg, should be administered subcutaneously every 28 days into the anterior abdominal wall below the navel line using an aseptic technique under the supervision of a physician.
  • While a delay of a few days is permissible, every effort should be made to adhere to the 28-day schedule.

Stage B2-C Prostatic Carcinoma

  • 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 a Zoladex 3.6 mg depot 8 weeks before radiotherapy, followed in 28 days by the Zoladex 10.8 mg depot, can be administered. Alternatively, four injections of 3.6 mg depot can be administered at 28-day intervals, two depots preceding and two during radiotherapy.

Prostatic Carcinoma

  • For the management of advanced prostate cancer, Zoladex is intended for long-term administration unless clinically inappropriate.

Endometriosis

  • For the management of endometriosis, the recommended duration of administration is 6 months. Currently, there are no clinical data on the effect of treatment of benign gynecological conditions with Zoladex for periods in excess of 6 months.
  • Retreatment cannot be recommended for the management of endometriosis since safety data for retreatment are not available.
  •  If the symptoms of endometriosis recur after a course of therapy, and further treatment with Zoladex is contemplated, consideration should be given to monitoring bone mineral density.
  • Clinical studies suggest the addition of Hormone Replacement Therapy (estrogens and/or progestins) to Zoladex is effective in reducing the bone mineral loss which occurs with Zoladex alone without compromising the efficacy of Zoladex in relieving the symptoms of endometriosis.
  • The addition of Hormone Replacement Therapy may also reduce the occurrence of vasomotor symptoms and vaginal dryness associated with hypoestrogenism. The optimal drugs, dose and duration of treatment has not been established.

Endometrial Thinning

  • For use as an endometrial-thinning agent prior to endometrial ablation, the dosing recommendation is one or two depots (with each depot given four weeks apart).
  • When one depot is administered, surgery should be performed at four weeks. When two depots are administered, surgery should be performed within two to four weeks following administration of the second depot.

Breast Cancer

  • For the management of advanced breast 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.

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What drugs interact with Zoladex?

  • No formal drug-drug interaction studies have been performed. 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 and until the resumption of menses may show results which are misleading. Normal function is usually restored within 12 weeks after treatment is discontinued.

Is Zoladex safe to use while pregnant or breastfeeding?

  • Zoladex is contraindicated during pregnancy unless Zoladex is being used for palliative treatment of advanced breast cancer. There are no adequate and well-controlled studies in pregnant women using Zoladex.
  • Based on mechanism of action in humans and findings of increased pregnancy loss in animal studies, Zoladex can cause fetal harm when administered to a pregnant woman. If this drug is used during pregnancy, the patient should be apprised of the potential hazard to the fetus. There is an increased risk for pregnancy loss due to expected hormone changes that occur with Zoladex treatment.
  • It is not known if goserelin is excreted in human milk. 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.

Summary

Zoladex (goserelin acetate) implant is a GnRH agonist used to treat advanced breast cancer, prostate cancer, endometriosis, and endometrial thinning. Serious side effects vary depending on the condition treated.

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Medically Reviewed on 6/25/2021
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