Goserelin (Systemic)

VA CLASSIFICATION
Primary: HS900
Secondary: AN500

Commonly used brand name(s): Zoladex; Zoladex 3-Month; Zoladex LA.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Gonadotropin-releasing hormone analog—

antiendometriotic agent—

antineoplastic—

gonadotropin inhibitor—

Indications

Accepted

Carcinoma, breast (treatment)—Goserelin, as the 3.6-mg implant,^{01} is indicated for the palliative treatment of advanced breast carcinoma in pre- and perimenopausal females.^{{01}{10}{12}{13}} The 10.8-mg implant should not be used for this indication because it has not been shown to suppress serum estradiol reliably.^{03}{14}

Carcinoma, prostatic (treatment)—Goserelin is indicated for the palliative treatment of advanced prostatic carcinoma^{{01}{03}{10}{12}{13}{14}}
—Goserelin is indicated for use in combination with radiotherapy and flutamide for the treatment of locally confined Stage T2b-T4 (Stage B2-C) prostatic carcinoma.^{03}

Endometrial thinning—Goserelin, as the 3.6-mg implant, is indicated as an endometrial thinning agent prior to endometrial ablation.^{01}{13}

Endometriosis (treatment)—Goserelin, as the 3.6-mg implant, is indicated for the management of endometriosis, including treatment of pelvic pain and reduction in the size and number of lesions.^{01}{13} The 10.8-mg implant should not be used for this indication because it has not been shown to suppress serum estradiol reliably.^{03}{14}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:


Physical description
    Goserelin acetate, dispersed in a matrix of D, L-lactic and glycolic acids copolymer, is available in a biodegradable and biocompatible, sterile, white- to cream-colored cylinder^{01}{03}.

• 3.6-mg implant: Contains 13.3 to 14.3 mg of copolymer per dose with less than 2.5% acetic acid and up to 12% goserelin-related substances^{01}.


• 10.8-mg implant: Contains 12.82 to 14.76 mg of copolymer per dose with less than 2% acetic acid and up to 10% goserelin-related substances^{03}.

Molecular weight—
    Goserelin: 1269.44^{07}{08}{09}
    Goserelin acetate: 1328

pKa—
    Goserelin: 6.2^{08}{09}

Mechanism of action/Effect:

Goserelin is a synthetic gonadotropin-releasing hormone analog (GnRHa).^{{01}{03}{08}{09}} Like naturally occurring luteinizing hormone releasing hormone (LHRH) that is produced by the hypothalamus, initial or intermittent administration of goserelin stimulates release of gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), from the anterior pituitary.^{{01}{03}{08}{09}} Long-term, sustained use of goserelin is associated with an early phase of increased LH and FSH levels, followed by their suppression^{08}.


Prostatic carcinoma:

In males, the release of LH and FSH results in a transient increase in testosterone concentrations. However, continuous daily administration of goserelin in the treatment of prostatic carcinoma suppresses secretion of LH and FSH, with a resultant fall in testosterone concentrations and a pharmacologic castration^{{01}{03}{08}{09}{10}{11}} within 2 to 4 weeks following initial administration.^{{01}{03}{08}{09}}



Endometriosis; breast carcinoma; endometrial thinning:

In females, the release of LH and FSH results in a transient increase in estradiol concentrations. However, continuous daily administration of goserelin suppresses secretion of LH and FSH, with a resultant reduction in ovarian size and function, reduction in the size of the uterus and mammary glands, and regression of sex hormone–responsive tumors.^{01} Estradiol^{01}{08}{10} and progesterone^{10} concentrations are suppressed to postmenopausal levels within 2 to 4 weeks following initial administration.^{01}{08}{10} In consequence of suppression of ovarian function, both normal and ectopic endometrial tissues become inactive and atrophic. As a result, amenorrhea usually occurs within 4 to 8 weeks of treatment initiation^{08}.


Absorption:

Slower during the first 8 days after injection of the 3.6-mg implant than during the remainder of the 28-day dosing period^{01}.

Distribution:

Following subcutaneous administration of 250 mcg of an aqueous solution of goserelin, the apparent volume of distribution was 44.1 and 20.3 L for males and females, respectively.^{01}

Protein binding:

Low (approximately 27%).^{01}{03}

Biotransformation:

Via hydrolysis of the C-terminal amino acids.^{01}{03}

Half-life:


Following subcutaneous administration of 250 mcg of an aqueous solution of goserelin:

Males with normal renal function (creatinine clearance > 70 mL per minute [mL/min]): 4.2 hours.^{01}{03}{13}

Males with renal function impairment (creatinine clearance < 20 mL/min): 12.1 hours.^{01}{03}{13}

Females: 2.3 hours.^{01}{08}


Although half-life is increased in patients with renal function impairment, dosage adjustment is not required.^{{01}{03}{10}{13}{14}}


Onset of action:

Transient increases in testosterone and estradiol concentrations occur within the first week of therapy. A decline in testosterone to castrate level^{01}{02}{03} and in estradiol to postmenopausal level^{01}{10} occurs within 2 to 4 weeks.

Time to peak concentration:


3.6-mg implant:

Males: 12 to 15 days.^{01}

Females: 8 to 22 days.^{01}



10.8-mg implant:

Males: 2 hours.^{03}{09}


Peak plasma concentration


3.6-mg implant:

Males: 2.84 ± 1.81 nanograms per mL (nanograms/mL).^{01}

Females 1.46 ± 0.82 nanograms/mL.^{01}



10.8-mg implant:

Males: 8 nanograms/mL.^{03}


Duration of action:

Suppression of testosterone concentrations to castrate levels^{{01}{03}{13}{14}} and suppression of estradiol concentrations to postmenopausal levels^{01}{13} persist for the duration of therapy.

Elimination:
    Following subcutaneous administration of the aqueous solution—

• Hepatic: < 10%.^{01}


• Renal: > 90% (20% unchanged).^{01}{03}



Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to gonadorelin (synthetic gonadotropin-releasing hormone [GnRH]), LHRH, or LHRH analogues, such as buserelin, histrelin, leuprolide, and nafarelin, may be sensitive to goserelin also.^{01}{03}

Carcinogenicity

Extensive experience with GnRHa, including with goserelin in humans, has shown no evidence of pituitary tumors in humans^{08}.

A 1-year study in male rats given daily subcutaneous doses of 80 and 150 mcg per kg of body weight (mcg/kg) and in female rats given daily subcutaneous doses of 50 and 100 mcg/kg (three to nine times the recommended human dose on a mg per square meter of body surface area [mg/m ²] basis) every 4 weeks found an increased incidence of pituitary adenomas. Similar doses given to male rats over a period of 72 weeks and to female rats over a period of 101 weeks also resulted in an increased incidence of pituitary adenomas.^{01}{03} Relevance of these data to humans has not been established; animal data suggest that the effects on the pituitary are a species-specific response^{08}.

A 2-year study in mice given daily subcutaneous doses of up to 2400 mcg/kg (approximately 70 times the recommended human dose on a mg/m ² basis) every 3 weeks found an increased incidence of histiocytic sarcoma of the vertebral column and femur.^{01}{03}

Mutagenicity

Mutagenicity tests using bacterial and mammalian systems for point mutations and cytogenetic effects were negative.^{{01}{03}{08}{09}}

Pregnancy/Reproduction
Fertility—
Suppression of estrogen and testosterone secretion results in impairment of fertility in males and females and is consistent with the expected gonadal suppression action of goserelin. Menses should resume within 8 weeks after discontinuation of therapy. Of 500 patients treated for endometriosis for 6 months and followed for 1 year, 100 patients (20%) became pregnant. Of 177 patients thought to be infertile, 53 patients (30%) conceived.^{08}

Studies in male rats found that goserelin produced changes consistent with gonadal suppression as a result of its endocrine action, including decreased weight and atrophic histological changes in the testes, epididymis, seminal vesicle, and prostate gland with complete suppression of spermatogenesis.^{01}{03} In female rats, suppression of ovarian function resulted in decreased size and weight of the ovaries and secondary sex organs. Also, follicular development was arrested at the antral stage and the corpora lutea were reduced in size and number.^{01}{03} Except for the testes, almost complete histologic reversal of these changes occurred several weeks after the end of dosing.^{01}{03} In male and female dogs, suppression of fertility was fully reversible when treatment was stopped after continuous administration of goserelin at 20 to 40 times the recommended daily human dose (on a mg/m ² basis) for 1 year.^{01}{03}

Pregnancy—
Goserelin is not recommended for use during pregnancy.^{01}{03}{13} Goserelin can cause serious adverse effects in the fetus. The pre-existence of a pregnancy should be ruled out prior to its use.^{01}{13} When used every 28 days, goserelin usually inhibits ovulation and stops menstruation. However, contraception cannot be ensured. A nonhormonal contraceptive method should be used by all premenopausal females during^{01}{13} and for 12 weeks following goserelin therapy.^{01}

Goserelin crosses the placenta of rats and rabbits following subcutaneous doses of 50 and 1000 mcg/kg, respectively. Dose-related increases in pregnancy loss and embryotoxicity and fetotoxicity were seen in rats and rabbits at doses equivalent to one tenth and two times the maximum recommended daily human dose, respectively, on a mg/m² basis. A decrease in fetal and pup survival also was seen in a reproduction study in rats.^{01}

FDA Pregnancy Category D (for treatment of advanced breast carcinoma).^{01}

FDA Pregnancy Category X (for treatment of endometriosis or endometrial thinning).^{01}

Breast-feeding

Goserelin is distributed into the milk of lactating rats.^{01} It is not known whether goserelin is distributed into human breast milk.^{{01} {03}} However, goserelin is not recommended for use by nursing mothers.^{01}{13}

Pediatrics

Appropriate studies on the relationship of age to the effects of goserelin have not been performed in pediatric patients up to 18 years of age. Safety and efficacy have not been established^{01}.


Geriatrics


Appropriate studies on the relationship of age to the effects of goserelin have not been performed in the geriatric population. However, clinical trials were conducted mainly in older patients and geriatrics-specific problems that would limit the usefulness of this medication in the elderly are not expected.^{05}


Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results
» Pituitary gonadotropic function testing and
» Gonadal function testing    (therapeutic doses of goserelin suppress the pituitary-gonadal hormone regulatory system;^{{01}{03}{13}{14}} baseline values usually are restored within 8 to 12 weeks after treatment is discontinued^{01}{13})

With physiology/laboratory test values
Acid phosphatase    (values may increase early in treatment of prostatic carcinoma but usually decrease to or near baseline by the fourth week; may decrease to below baseline levels if elevated values were present before treatment^{13})


Alanine aminotransferase (ALT [SGPT]) and
Aspartate aminotransferase (AST [SGOT])    (increased serum values have been reported in females^{01}{03}{13})


» Bone mineral density    (bone mineral density usually decreases, more substantially in females than in males, with losses being greater in females with osteoporotic risk factors; may be irreversible^{01}{13}{14})


Calcium, serum    (concentrations may be increased, usually in patients with bone metastases^{01}{03})


Estradiol, serum    (concentrations may increase early in treatment of females with breast cancer, become suppressed within 3 weeks of treatment, and remain suppressed throughout treatment^{01}{13})


High-density lipoprotein (HDL) cholesterol and
Low-density lipoprotein (LDL) cholesterol and
Total cholesterol and
Triglycerides    (concentrations may be increased^{01}{03}{13})


Testosterone, serum     (concentrations usually are increased in males during the first week of therapy, become suppressed within 3 weeks of treatment, and remain suppressed throughout treatment^{{01}{03}{11}{13}{14}})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Sensitivity to gonadorelin (synthetic gonadotropin-releasing hormone [GnRH]) or to gonadotropin-releasing hormone analogs (GnRHa), such as buserelin, goserelin, histrelin, leuprolide, and nafarelin^{01}{03}{08}
For endometrial thinning or treatment of endometriosis:
Conditions causing decrease in bone density or
Osteoporosis, or history of, or family history of    (hypoestrogenism-induced loss of bone mineral density may occur in females treated with goserelin and may be irreversible; major risk factors include chronic alcohol and/or tobacco abuse, family history of severe osteoporosis, and chronic use of medications, such as anticonvulsants or corticosteroids, that decrease bone mineral density; goserelin should be used with caution in these patients^{01}{13}{14})


» Uterine bleeding, abnormal, undiagnosed    (use of goserelin may delay diagnosis^{08})


For treatment of prostatic carcinoma:
» Urinary tract obstruction or history of    (existing urinary obstruction should be treated before beginning treatment with goserelin; for patients with a history of urinary tract obstruction, there is an increased incidence of a disease flare during initial goserelin treatment because of the initial increase in serum testosterone concentrations;^{11} close monitoring is recommended during the first month of treatment and catheterization may be needed on its occurrence^{{01}{03}{08}{09}})


» Vertebral metastases    (risk of spinal cord compression and neurologic problems, including paralysis, as a result of a disease flare during first few weeks of goserelin treatment;^{11} close monitoring is recommended during the first month of treatment^{{01}{03}{13}{14}})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Bone density assessment    (recommended as needed to monitor response in patients during long-term use of goserelin, including treatment of endometriosis for longer than 6 months^{08})


For endometrial thinning or treatment of endometriosis
Pregnancy test    (recommended for females of reproductive potential if treatment is not started during menstruation, if irregular menstrual cycles exist, or if a scheduled dose is delayed^{08})


For treatment of prostatic carcinoma
Acid phosphatase, plasma prostatic or serum or
Prostate-specific antigen (PSA) concentrations, serum and
Testosterone concentrations, serum    (recommended at periodic intervals to monitor response in patients with prostatic carcinoma^{03}{13}{14})


Bone scans    (recommended as needed to monitor response in patients at risk for vertebral metastases ^{13})


Imaging studies    (intravenous pyelogram, computerized tomography [CT] scan, and/or ultrasonography may be used to diagnose or assess obstructive uropathy in patients at risk for obstructive uropathy^{13}{14})




Side/Adverse Effects

Note: Many of the side/adverse effects of goserelin are related to hypoestrogenism in females and hypotestosteronism in males. The reversibility of clinical hypogonadism produced by goserelin has not been established for long-term use. ^{{01} {03} {08} {09}}
There is a risk of increased loss of vertebral trabecular bone density during treatment for endometriosis or breast cancer; some of this loss may be irreversible. However, the loss usually is small when treatment is limited to 6 months for endometriosis, except in patients with existing risk factors (e.g., history of osteoporosis). Decreased bone density also has been reported in males who have had an orchiectomy or who have been treated with a gonadotropin-releasing hormone analog (GnRHa). ^{{01} {03} {08} {09}}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent—> 5%
In females and males
    
Cardiac arrhythmias or palpitations (fast or irregular heartbeat)^{{01}{03}{08}{09}}


Incidence rare—< 5%
In females and males
    
Anaphylaxis (changes in facial skin color; fast or irregular breathing; puffiness or swelling of the eyelids or around the eyes; shortness of breath, troubled breathing, tightness in chest, and/or wheezing; skin rash, hives, and/or itching; sudden, severe decrease in blood pressure and collapse )^{{01}{03}{08}{09}}
    
bone, muscle, or joint pain, continuing ^{{01}{03}{08}{09}}
    
paresthesias ^{{01}{03}{08}{09}}(numbness or tingling of hands or feet)
    
syncope ^{08}(fainting)

In females only
    
Androgenic effects ^{01}{08}( deepening of voice; increased hair growth )
    
personality or behavioral changes (anxiety; mental depression; mood changes; nervousness)^{01}{08}

In males only
    
Angina or myocardial infarction ( pains in chest)^{03}{09}
    
pulmonary embolism (sudden shortness of breath)
    
thrombophlebitis ^{03}{09}(pains in groin or legs, especially calves of legs)




Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
—> 50%In females and males
    
Hot flashes ^{{01}{03}{08}{09}}(sudden sweating and feelings of warmth)

In females only
    
Amenorrhea (stopping of menstrual periods), or spotting ( light, irregular vaginal bleeding)^{01}{08}


Incidence less frequent—5 to 13%
In females and males
    
Blurred vision ^{{01}{03}{08}{09}}
    
decreased libido ^{{08}{01}{03}{08}{09}}( decreased interest in sexual intercourse)
    
dizziness ^{{01}{03}{08}{09}}
    
edema (swelling of feet or lower legs)^{{01}{03}{08}{09}}
    
headache ^{{01}{03}{08}{09}}
    
injection site reaction (burning, itching, redness, or swelling at place of injection)^{{01}{03}{08}{09}}
    
nausea or vomiting ^{{01}{03}{08}{09}}
    
swelling or increased tenderness of breasts ^{{01}{03}{08}{09}}
    
trouble in sleeping ^{{01}{03}{08}{09}}
    
weight gain ^{{01}{03}{08}{09}}

In females only
    
Endometriotic disease flare, transient (pelvic pain)^{01}{08}
    
vaginitis ^{01}{08}(burning, dryness, or itching of vagina)

Note: An endometriotic disease flare, with a transient increase in symptoms (pelvic pain, dysmenorrhea, dyspareunia, pelvic tenderness, induration), may occur shortly after initiation of therapy for endometriosis as a result of the temporary increase in serum estradiol ^{{01} {08}}.


In males only
    
Constipation ^{03}{09}
    
decreased size of testicles ^{03}{09}
    
impotence (inability to have or keep an erection)^{03}{09}
    
prostatic carcinoma disease flare, transient (bone pain)^{03}{09}

Note: A prostatic carcinoma disease flare, with a transient, sometimes severe, increase in bone or tumor pain, may occur shortly after initiation of therapy for prostatic carcinoma, usually is associated with the increase in serum testosterone, and usually subsides with continued goserelin treatment. Analgesics may be required during this time. Other signs and symptoms of prostatic carcinoma, including difficult urination and spinal compression ^{{03} {09}}, also may worsen transiently. In addition, worsening of neurologic signs and symptoms in patients with vertebral metastases may result in temporary weakness and paresthesias of the lower extremities; paralysis, with or without fatal complications, is possible ^{{03} {09}}.







Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Goserelin (Systemic) .
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to gonadorelin (synthetic gonadotropin-releasing hormone [GnRH]) or to gonadotropin-releasing hormone analogs (GnRHa), such as buserelin, goserelin, histrelin, leuprolide, or nafarelin

Pregnancy—Not recommended for use during pregnancy; pregnancy should be ruled out prior to use of goserelin; nonhormonal contraceptive should be used during and for 12 weeks following therapy





Breast-feeding—Not recommended for use by nursing mothers
Other medical problems, especially undiagnosed, abnormal uterine bleeding (for endometrial thinning or endometriosis); urinary tract obstruction or history of (for prostatic carcinoma); or vertebral metastases (for prostatic carcinoma)

Proper use of this medication
» Importance of continuing medication despite side effects

» Proper dosing
Missed dose: Receiving as soon as possible ^{{08} {09}}

Precautions while using this medication
» Importance of close monitoring by the physician ^{08}

» Notifying physician if regular menstruation continues following regular use of goserelin or if regular menstrual periods do not begin again within 2 to 3 months after discontinuing medication; however, missing one or more successive doses may cause breakthrough menstrual bleeding ^{{01} {08}}

For women of reproductive potential, using a nonhormonal contraceptive while being treated with goserelin


Side/adverse effects
Signs of potential side effects, especially cardiac arrhythmias or palpitations; anaphylaxis; bone, muscle, or joint pain; paresthesias; syncope; androgenic effects (for females only); personality or behavioral changes (for females only); angina or myocardial infarction (for males only); pulmonary embolism (for males only); or thrombophlebitis (for males only)


General Dosing Information
Patients receiving goserelin should be under supervision of a physician experienced in its use. Administration of goserelin should be carried out, using sterile technique, under supervision of a physician.^{01}{03}

If the implant needs to be removed for any reason, it can be located by ultrasound^{01}{03}.

Dosage adjustment is not needed for patients with hepatic or renal function impairment^{{01}{03}{13}{14}}.

For endometrial thinning
When used as an endometrial thinning agent, goserelin may cause an increase in cervical resistance. Therefore, care should be taken when dilating the cervix.^{01}{13}

For treatment of endometriosis
It is recommended that therapy begin with the first day of the menstrual cycle after pregnancy has been ruled out^{08}.

Development of amenorrhea is usually evidence of a clinical response, although spotting or bleeding from the atrophic endometrium can still occur^{08}.

Therapy should continue uninterrupted for 6 months. Re-treatment is not recommended. However, if re-treatment is contemplated, bone density should be assessed prior to beginning treatment, to verify that values are in the normal range^{01}{08}.

For treatment of prostatic carcinoma
A 10.8-mg, 3-month implant of goserelin suppresses testosterone levels equivalent to a 3.6-mg implant inserted every 28 days^{03}.

For treatment of side/adverse effects
Recommended treatment:

• Bone pain—Mild oral analgesics with rest or, if severe, parenteral narcotics. Bone pain usually subsides after 2 weeks^{08}.


• Urinary obstruction, worsening of, in treatment of prostatic carcinoma—Catheterization if needed. Urinary obstruction usually resolves after the first week of goserelin therapy^{08}.



Parenteral Dosage Forms

Note: The available dosage form contains goserelin acetate, but dosage and strength are expressed in terms of the base.

GOSERELIN ACETATE IMPLANTS

Usual adult dose
Breast carcinoma
Subcutaneous (into upper abdominal wall), 3.6 mg (base) every twenty-eight days.^{01}{13}

Prostatic carcinoma


Advanced:
Subcutaneous (into upper abdominal wall), 3.6 mg (base) every twenty-eight days^{01}{13} or 10.8 mg every twelve weeks^{03}{14}.



Stage B2–C:
Subcutaneous (into upper abdominal wall), 10.8 mg (base) every twelve weeks given in combination with radiotherapy and flutamide.^{03}

Treatment should begin eight weeks prior to initiating radiotherapy and should continue during radiation treatment. A treatment regimen using one goserelin 3.6-mg implant, followed in twenty-eight days by one goserelin 10.8-mg implant, should be administered.^{03}Alternatively, one goserelin 3.6-mg implant may be injected every twenty-eight days for two doses preceding radiotherapy and one goserelin 3.6-mg implant may be injected every twenty-eight days for two doses during radiotherapy.^{01}


Endometrial thinning
Subcutaneous (into upper abdominal wall), 3.6 mg (base) every twenty-eight days for one or two doses. If only one dose is administered, endometrial ablation should be performed at four weeks. If two doses are administered, endometrial ablation should be performed within two to four weeks after administration of the second dose.^{01}

Endometriosis
Subcutaneous (into upper abdominal wall), 3.6 mg (base) every twenty-eight days for six months.^{01}{08}

Note: Safety of goserelin when used for this indication for re-treatment or for periods greater than six months has not been established.^{01}{13}



Usual pediatric dose
Carcinoma, breast or
Carcinoma, prostate or
Endometrial thinning
Children up to 18 years of age—Safety and efficacy have not been established^{01}{13}.

Endometriosis
Children up to 18 years of age—Safety has not been established^{01}{13}.


Size(s) usually available:
U.S.—



1-month formulation


3.6 mg (base) (preloaded in a special single-use syringe) (Rx) [Zoladex^{01}]



3-month formulation


10.8 mg (base) (preloaded in a special single-use syringe) (Rx) [Zoladex 3-Month^{03}]

Canada—



1-month formulation


3.6 mg (base) (preloaded in a special single-use syringe) (Rx) [Zoladex^{13}]



3-month formulation


10.8 mg (base) (preloaded in a special single-use syringe) (Rx) [Zoladex LA^{14}]

Packaging and storage:
Store below 25 °C (77 °F),^{{01}{03}{13}{14}} unless otherwise specified by manufacturer. Protect from light. Protect from moisture.^{08}{09}

Revised: 06/09/2000

References

1. Product Information: Zoladex®, goserelin acetate implant 3.6 mg. Zeneca Pharmaceuticals, Wilmington, DE, (PI revised 2/1999) reviewed 5/2000.
   

2. Schroder FH, editor. New treatment modalities in prostatic cancer: LHRH superagonists. Symposium held during World Congress of Oncology, Budapest, Hungary, August 26, 1986. Am J Clin Oncol 1988; 11 Suppl 1: S1-S46.
   

3. Product Information: Zoladex® 3-month 10.8 mg Depot, goserelin acetate implant 10.8 mg. Zeneca Pharmaceuticals, Wilmington, DE, (PI revised 2/1999) reviewed 5/2000.
   

4. Reviewers' responses to panel question #1, 1991.
   

5. Reviewers' responses to panel question #2, 1991.
   

6. Reviewers' responses to panel question #3, 1991.
   

7. Canada JR, editor. USP dictionary of USAN and international drug names 1998. Rockville, MD: The United States Pharmacopeial Convention, Inc.; 1997. p. 346.
   

8. Zoladex product monograph (Zeneca—Canada), Rev 03/14/97, Rec 08/01/97.
   

9. Zoladex LA product monograph (Zeneca—Canada), Rev 01/29/97, Rec 08/01/97.
   

10. Erlichman C, Loprinzi CL. Hormonal therapies. In: DeVita VT, Hellman S, Rosenberg SA, editors. Cancer: principles and practice of oncology. 5th ed. Philadelphia: Lippincott-Raven Publishers; 1997. p. 400-1.
    

11. Oesterling J, Fuks Z, Lee CT, et al. Cancers of the genitourinary system. Cancer of the prostate. In: DeVita VT, Hellman S, Rosenberg SA, editors. Cancer: principles and practice of oncology. 5th ed. Philadelphia: Lippincott-Raven Publishers; 1997. p. 1365.
    

12. Reviewers' responses to Hematologic-Oncologic Disease Advisory Panel Memo #9 of 01/30/97.
    

13. Product Information: Zoladex®, goserelin acetate. AstraZeneca Canada. In: Welbanks L (ed): Compendium of Pharmaceuticals and Specialties, 35th ed. Canadian Pharmaceutical Association, Ottawa, Ontario, Canada, 2000: p. 1800–1802.
    

14. Product Information: Zoladex® LA, goserelin acetate. AstraZeneca Canada. In: Welbanks L (ed): Compendium of Pharmaceuticals and Specialties, 35th ed. Canadian Pharmaceutical Association, Ottawa, Ontario, Canada, 2000: p. 1802–1803.