Goserelin

Soluble

2.83e-02 g/L

FDA approved drugs -> Active ingredient

Hormones and antihormones

Off-white powder. Freely soluble in acetic acid; soluble in water, 0.1M HCl, 0.1M NaCl, dimethylformamide, dimethylsulfoxide. Insoluble in acetone, chloroform, ether. /Acetate/

Solid. Freely soluble in glacial acetic acid /Acetate/

Danger

H317 (89.5%): May cause an allergic skin reaction [Warning Sensitization, Skin]

P203, P233, P260, P261, P271, P272, P280, P284, P302+P352, P304+P340, P317, P318, P321, P333+P317, P342+P316, P362+P364, P403, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 19 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl goserelin acetate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Goserelin acetate/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Methods for transporting hazardous drugs to the health-care setting should be consistent with environmental protection and national or local regulations for transporting hazardous substances. When hazardous drugs are being transported to the home-care setting, appropriate containers (eg, lined cardboard boxes) and procedures should be used to prevent breakage and contain leakage. ... The drugs must be securely capped or sealed and properly packaged and protected during transport to reduce further the chance of breakage and spillage in a public area such as a corridor or elevator. /Antineoplastic agents/

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ All contaminated disposables should be contained in sealable bags for transfer to larger waste containers. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ All bottles must be discarded as contaminated waste after decontamination of the biohazard cabinet. All protective apparel (gown, gloves, goggles, and respirator) should be discarded as contaminated waste. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The contaminated filters must be removed, bagged in thick plastic and prepared for disposal in a hazardous waste dump site or incinerator licensed by the Environmental Protection Agency (EPA). /Antineoplastic agents/

For more Disposal Methods (Complete) data for GOSERELIN (8 total), please visit the HSDB record page.

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Accidental contamination of the health-care environment, resulting in exposure of personnel, patients, visitors, and family members to hazardous substances, is prevented by maintaining the physical integrity and security of packages of hazardous drugs. 1. Access to all areas where hazardous drugs are stored is limited to specified authorized staff. 2. A method should be present for identifying to personnel those drugs that require special precautions (eg, cytotoxics). One way to accomplish this is to apply appropriate warning labels to all hazardous drug containers, shelves, and bins where the drug products are stored. ... 3. A method of identifying, for patients and family members, those drugs that require special precautions in the home should be in place. This may be accomplished in the health-care setting, by providing specific labeling for discharge medications, along with written instructions. 4. Methods for identifying shipping cartons of hazardous drugs should be required from manufacturers and distributors of these drugs. 5. Written procedures for handling damaged packages of hazardous drugs should be maintained. Personnel involved in shipping and receiving hazardous drugs should be trained in these procedures, including the proper use of protective garments and equipment. Damaged shipping cartons of hazardous drugs should be received and opened in an isolated area (eg, in a laboratory fume hood, if available, not in a vertical laminar airflow biological safety cabinet used for preparing sterile products). /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Facilities (eg, shelves, carts, counters, and trays) for storing hazardous drugs are designed to prevent breakage and to limit contamination in the event of leakage. Bins, shelves with barriers at the front, or other design features that reduce the chance of drug containers falling to the floor should be used. Hazardous drugs requiring refrigeration should be stored separately from nonhazardous drugs in individual bins designed to prevent breakage and to contain leakage. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Until the reproductive risks (or lack thereof) associated with handling hazardous drugs within a safety program have been substantiated, staff who are pregnant or breast-feeding should be allowed to avoid contact with these drugs. Policies should be in effect that provide these individuals with alternative tasks or responsibilities if they so desire. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The pharmacy should provide access to information on toxicity, treatment of acute exposure (if available), chemical inactivators, solubility and stability of hazardous drugs (including investigational agents) used in the workplace. /Antineoplastic agents/

For more Preventive Measures (Complete) data for GOSERELIN (20 total), please visit the HSDB record page.

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Protective apparel: Disposable closed-front gown or coveralls, disposable utility gloves over disposable latex gloves, NIOSH-approved air-purifying half-mask respirator equipped with a high efficiency filter, and eye protection should be worn. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Class 100 clean-air work stations, both horizontal and vertical airflow (with no containment characteristics), are inappropriate engineering controls for handling hazardous drugs because they provide no personnel protection and permit environmental contamination. Although there are no engineering controls designed specifically for the safe handling of hazardous chemicals as sterile products, Class II contained vertical-flow biological safety cabinets (biohazard cabinets) have been adopted for this use. Biohazard cabinetry is, however, designed for the handling of infectious agents, not hazardous chemicals. ... Based on design, ease of use, and cost considerations, Class II contained-vertical-flow biohazard cabinetry is currently recommended for use in preparing sterile doses of hazardous drugs. Class II cabinetry design and performance specifications are defined in NSF Standard 49. Biological safety cabinets selected for use with hazardous drugs should meet NSF Standard 49 specifications to ensure the maximum protection from these engineering controls. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Workers should wear powder free, disposable surgical latex gloves of good quality when preparing hazardous drugs. Selection criteria for gloves should include thickness (especially at the fingertips where stress is the greatest), fit, length, and tactile sensation. ... The practice of double gloving is supported by research that indicates that many glove materials vary in drug permeability even within lots; therefore, double gloving is recommended. ... In general, surgical latex gloves fit better, have appropriate elasticity for double gloving and maintaining the integrity of the glove-gown interface, and have sufficient tactile sensation (even during double gloving) for stringent aseptic procedures. ... Powdered gloves should be avoided. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Workers who are not protected by the containment environment of a biohazard cabinet should use respiratory protection when handling hazardous drugs. Respiratory protection should be an adjunct to and not a substitute for engineering controls. Surgical masks of all types provide no respiratory protection against powdered or liquid aerosols of hazardous drugs. In situations where workers may be exposed to potential eye contact with hazardous drugs, an appropriate plastic face shield or splash goggles should be worn. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ During compounding of hazardous drugs (eg, crushing, dissolving, and preparing an ointment), workers should wear low permeability gowns and double gloves. Compounding should take place in a protective area such as a disposable glove box. If compounding must be done in the open, an area away from drafts and traffic must be selected, and the worker should use appropriate respiratory protection. /Antineoplastic agents/

Goserelin has been associated with mild serum enzyme elevations during therapy in 3% to 5% of patients, but values above 3 times the upper limit of normal are rare, being reported in less than 1% of recipients. The serum enzyme elevations during goserelin therapy have generally been transient and asymptomatic, resolving even with drug continuation and rarely requiring dose modification or discontinuation. Despite use for several decades, goserelin has been linked to only a single, and not entirely convincing, case of clinically apparent liver injury. Routine monitoring of patients for liver test abnormalities is not recommended.

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ There is no method available for routine monitoring of personnel for evidence of hazardous drug exposure. Tests for the presence of mutagens or chromosomal damage are not drug specific and are of value only in controlled studies. Chemical analysis of urine for the presence of hazardous drugs at the sensitivity level needed to detect occupational exposure is limited to a few drugs and is not yet commercially available. /Antineoplastic agents/

/CASE REPORTS/ Relapsing polychondritis is a chronic rheumatologic disorder of unknown etiology. Cutaneous manifestations occur in nearly half of the patients and often precede cartilaginous involvement. ... The case of a man with a history of prostatic adenocarcinoma who underwent monthly injections of goserelin (Zoladex), an LH-RH analogue /is presented/. Five months after the beginning of the treatment, he presented cutaneous manifestations, which then recurred monthly, after each goserelin injection. After goserelin interruption and replacement with another treatment (cyproterone acetate), the patient was asymptomatic for 2 months. A cutaneous relapse then occurred followed by a typical cartilaginous involvement. ...

/CASE REPORTS/ A 30-year old female who initially had typical endometriosis treated according to a standard regimen later developed numerous highly vascular endometrial polyps on the vagina, cervix, ureter, serosal surfaces of the uterus, pouch of Douglas (POD) and other areas of pelvic peritoneum as well as the endometrium 8 months after withdrawal of treatment with Zoladex gonadotrophin releasing hormone (GnRH) agonist used for treatment of this disease. /It is/ postulate/d/ that these polyps developed as a rebound phenomenon upon withdrawal of Zoladex. /Zoladex/

/CASE REPORTS/ Women suffering from endometriosis are treated with long-acting analogues of gonadotropin-releasing hormone (GnRH). This is a case of hypersensitivity reaction to a goserelin acetate implant that manifested as an anaphylactic reaction. This is the first report of a hypersensitivity reaction to the GnRH analogue, goserelin acetate (Zoladex). /Zoladex/

/CASE REPORTS/ An 8-year-old girl with idiopathic central precocious puberty experienced multiple episodes of anaphylaxis after receiving a goserelin acetate implant. She was hospitalized and treated with epinephrine, antihistamine, and corticosteroids. The goserelin implant was surgically excised; however, anaphylactic symptoms continued for 4 days after excision. Less severe systemic symptoms recurred 6 weeks after removal; these were possibly due to leakage of the depot drug into subcutaneous tissues. It was noted that 3 years earlier, the patient had developed a similar, milder systemic allergic reaction to leuprolide acetate that required treatment with oral prednisone and antihistamines. Intradermal testing yielded positive results for leuprolide. Gonadotropin-releasing hormone (GnRH) analogs, including leuprolide acetate and goserelin acetate, are commonly prescribed for patients with prostatic carcinoma, endometriosis, and precocious puberty. A literature review identified a single case report of a systemic hypersensitivity reaction involving goserelin acetate and several reports of systemic hypersensitivity reactions associated with leuprolide acetate. ... No reports of systemic reactions to GnRH analogs in pediatric patients /were found/. ...

For more Human Toxicity Excerpts (Complete) data for GOSERELIN (9 total), please visit the HSDB record page.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Subcutaneous implant of Zoladex in male and female rats once every 4 weeks for 1 year and recovery for 23 weeks at doses of about 80 and 150 ug/kg (males) and 50 and 100 ug/kg (females) daily (about 3 to 9 times the recommended human dose on a mg/sq m basis) resulted in an increased incidence of pituitary adenomas. An increased incidence of pituitary adenomas was also observed following subcutaneous implant of Zoladex in rats at similar dose levels for a period of 72 weeks in males and 101 weeks in females. The relevance of the rat pituitary adenomas to humans has not been established. Subcutaneous implants of Zoladex every 3 weeks for 2 years delivered to mice at doses of up to 2400 ug/kg/day (about 70 times the recommended human dose on a mg/sq m basis) resulted in an increased incidence of histiocytic sarcoma of the vertebral column and femur.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Administration of goserelin led to changes that were consistent with gonadal suppression in both male and female rats as a result of its endocrine action. In male rats administered 500-1000 ug/kg/day (about 30-60 times the recommended human dose on a mg/sq m basis), a decrease in weight and atrophic histological changes were observed in the testes, epididymis, seminal vesicle and prostate gland with complete suppression of spermatogenesis. In female rats administered 50-1000 ug/kg/day (about 3-60 times the recommended daily human dose on a mg/sq m basis), suppression of ovarian function led to decreased size and weight of ovaries and secondary sex organs; follicular development was arrested at the antral stage and the corpora lutea were reduced in size and number. Except for the testes, almost complete histologic reversal of these effects in males and females was observed several weeks after dosing was stopped; however, fertility and general reproductive performance were reduced in those that became pregnant after goserelin was discontinued. Fertile matings occurred within 2 weeks after cessation of dosing, even though total recovery of reproductive function may not have occurred before mating took place; and, the ovulation rate, the corresponding implantation rate, and number of live fetuses were reduced.

/GENOTOXICITY/ Mutagenicity tests using bacterial and mammalian systems for point mutations and cytogenetic effects have provided no evidence for mutagenic potential.

Emergency and supportive measures. Maintain an open airway and assist ventilation if necessary. Treat coma, seizures, hypotension, and arrhythmias if they occur. Treat nausea and vomiting with metoclopramide and fluid loss caused by gastroenteritis with intravenous crystalloid fluids. /Antineoplastic agents/

Bone marrow depression should be treated with the assistance of an experienced hematologist or oncologist. /Antineoplastic agents/

Decontamination. Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. /Antineoplastic agents/

Enhanced elimination. Because of the rapid intracellular incorporation of most of these agents, dialysis and other extracorporeal removal procedures are generally not effective. /Antineoplastic agents/

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl goserelin acetate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Goserelin acetate/

L02AE03

L - Antineoplastic and immunomodulating agents

QL - Antineoplastic and immunomodulating agents

The pharmacokinetics of goserelin have been determined in both male and female healthy volunteers and patients. In these studies, goserelin was administered as a single 250µg (aqueous solution) dose and as a single or multiple 3.6 mg depot dose by subcutaneous route.

Goserelin is a synthetic decapeptide analogue of LHRH. Goserelin acts as a potent inhibitor of pituitary gonadotropin secretion when administered in the biodegradable formulation. The result is sustained suppression of LH and serum testosterone levels.

Zoladex is a synthetic decapeptide analogue of LHRH. Zoladex acts as a potent inhibitor of pituitary gonadotropin secretion when administered in the biodegradable formulation. Following initial administration, ZOLADEX causes an initial increase in serum-luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels with subsequent increases in serum levels of testosterone. Chronic administration of Zoladex leads to sustained suppression of pituitary gonadotropins, and serum levels of testosterone consequently fall into the range normally seen in surgically castrated men approximately 21 days after initiation of therapy. This leads to accessory sex organ regression. In animal and in in vitro studies, administration of goserelin resulted in the regression or inhibition of growth of the hormonally sensitive dimethylbenzanthracene (DMBA)-induced rat mammary tumor and Dunning R3327 prostate tumor. In clinical trials using Zoladex 3.6 mg with follow-up of more than 2 years, suppression of serum testosterone to castrate levels has been maintained for the duration of therapy.

4-5 hours

When administered as a solution, goserelin is rapidly absorbed and eliminated from serum with a mean elimination half-life (t1/2beta) of 4.2 hours in males and 2.3 hours in females.

Subjects with impaired renal function (creatinine clearance less than 20 mL/min) had a serum elimination half-life of 12.1 hours compared to 4.2 hours for subjects with normal renal function.

Hepatic

Metabolism of goserelin, by hydrolysis of the C-terminal amino acids, is the major clearance mechanism. The major circulating component in serum appeared to be 1-7 fragment, and the major component present in urine of one healthy male volunteer was 5-10 fragment. The metabolism of goserelin in humans yields a similar but narrow profile of metabolites to that found in other species. All metabolites found in humans have also been found in toxicology species.

0F65R8P09N

GOSERELIN

Established Pharmacologic Class [EPC] - Gonadotropin Releasing Hormone Receptor Agonist

Mechanisms of Action [MoA] - Gonadotropin Releasing Hormone Receptor Agonists

Goserelin is a Gonadotropin Releasing Hormone Receptor Agonist. The mechanism of action of goserelin is as a Gonadotropin Releasing Hormone Receptor Agonist.

GOSERELIN

Antineoplastic agents that are used to treat hormone-sensitive tumors. Hormone-sensitive tumors may be hormone-dependent, hormone-responsive, or both. A hormone-dependent tumor regresses on removal of the hormonal stimulus, by surgery or pharmacological block. Hormone-responsive tumors may regress when pharmacologic amounts of hormones are administered regardless of whether previous signs of hormone sensitivity were observed. The major hormone-responsive cancers include carcinomas of the breast, prostate, and endometrium; lymphomas; and certain leukemias. (From AMA Drug Evaluations Annual 1994, p2079)

Inactive orally, rapidly absorbed following subcutaneous administration.

Clearance of goserelin following subcutaneous administration of a radiolabeled solution of goserelin was very rapid and occurred via a combination of hepatic and urinary excretion. More than 90% of a subcutaneous radiolabeled solution formulation dose of goserelin was excreted in urine.

44.1 ± 13.6 L [subcutaneous administration of 250 mcg]

121 +/- 42.4 mL/min [prostate cancer with 10.8 mg depot]

The apparent volume of distribution determined after subcutaneous administration of 250 ug aqueous solution of goserelin was 44.1 + or - 13.6 liters for healthy males. The plasma protein binding of goserelin was found to be 27%.

The overall pharmacokinetic profile of goserelin following administration of a Zoladex 10.8 mg depot to patients with prostate cancer was determined. The initial release of goserelin from the depot was relatively rapid resulting in a peak concentration at 2 hours after dosing. From Day 4 until the end of the 12-week dosing interval, the sustained release of goserelin from the depot produced reasonably stable systemic exposure. ... There is no clinically significant accumulation of goserelin following administration of four depots administered at 12-week intervals.

Treatment of prostate cancer

THERAP CAT: Antineoplastic (hormonal)

Use (kg) in USA (2002): 1

[4-D-serine]goserelin; [9-D-proline]goserelin; [5-D-tyrosine]goserelin; [2-D-histidine]goserelin; [7-D-leucine]goserelin; [6-[O-(1,1-dimethylethyl)-L-serine]]goserelin; 1-carbamoylyl-2-[5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-O-(1,1-dimethylethyl)-D-seryl-L-leucyl-L-arginyl]diazane; 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-O-(1,1-dimethylethyl)-D-seryl-L-leucyl-L-arginyl-L-prolinohydrazide; [1-(5-oxo-D-proline)]goserelin; endo-8a,8b-di-L-proline-goserelin; endo-8a-L-proline-goserelin; O4-acetylgoserelin