Leuprolide｜Huagongshe

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HCID 657181Erstellt: 27. Oktober 2026

Leuprolide

LEUPROLIDE · Lucrin · Leuplin · a-43818 · Carcinil · Enantone · nghormone · LEUPRORELIN

https://huagongshe.com/de/chemical/657181

Molekülstruktur von Leuprolide

Identifikatoren & physikalische Daten

CAS No.	53714-56-0
Summenformel	C59H84N16O12
Durchschnittliche Molmasse	1.209,4 g/mol
Monoisotopische Masse	1.208,64546213 g/mol
SMILES	CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@@H]1CCC(=O)N1
InChIKey	GFIJNRVAKGFPGQ-LIJARHBVSA-N
PubChem CID	657181
ChEMBL	CHEMBL1201199
ChEBI	CHEBI:6427
EC No.	633-395-9
DTXSID	DTXSID50872411

Chemische & physikalische Eigenschaften

XLogP	0,7
Polarare Oberfläche (TPSA)	432
H-Brücken-Donoren	15
H-Brücken-Akzeptoren	14
Frei drehbare Bindungen	32
Schwere Atome	87
Formalladung	0
Komplexität	2.390
Color/Form	Fluffy solid
Human Drugs	EMA approved medicines: Human medicineHormones and antihormones
Schmelzpunkt	150-155
Optical Rotation	Specific optical rotation: -31.7 deg @ 25 °C/D (c=1 in 1% HOAc)
Dichte	1.44±0.1 g/cm3(Predicted)
Lagerbedingungen	−20°C
Löslichkeit	DMSO (Slightly), Methanol (Slightly), Water (Slightly)Soluble in water at 1mg/ml
pKa (Säurekonstante)	9.82±0.15(Predicted)
Stabilität	Hygroscopic
InChIKey	RGLRXNKKBLIBQS-VAZQWRJQNA-N
CAS Datenbank	53714-56-0(CAS DataBase Reference)

Sicherheit & Vorschriften

GHS-Einstufung	DangerH360 (100%): May damage fertility or the unborn child [Danger Reproductive toxicity]P203, P280, P318, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 40 reports by companies from 3 notifications to the ECHA C&L Inventory.
Special Reports	Plosker GL, Brogden RNLeuprorelin: Review of its Pharmacology and Therapeutic Use in Prostatic Cancer, Endometriosis and Other Sex Hormone-Related DisordersDrugs 48 (Dec): 930-67 (1994)
Hazard Classes and Categories	Repr. 1A (100%)
Reinigungsverfahren	/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Spill kits containing all materials needed to clean up spills of hazardous drugs should be assembled or purchased. These kits should be readily available in all areas where hazardous drugs are routinely handled. If hazardous drugs are being prepared or administered in a nonroutine area (home setting or unusual patient-care area), a spill kit should be obtained by the drug handler. The kit should include two pairs of disposable gloves (one outer pair of utility gloves and one inner latex pair)low-permeability, disposable protective garments (coveralls or gown and shoe covers)safety glasses or splash gogglesrespiratorabsorbent, plastic-backed sheets or spill padsdisposable towelingat least 2 sealable thick plastic hazardous waste disposal bags (prelabeled with an appropriate warning label)a disposable scoop for collecting glass fragmentsand a puncture-resistant container for glass fragments. All individuals who routinely handle hazardous drugs must be trained in proper spill management and cleanup procedures. Spills and breakages must be cleaned up immediately according to the following procedures. If the spill is not located in a confined space, the spill area should be identified and other people should be prevented from approaching and spreading the contamination. Wearing protective apparel from the spill kit, workers should remove any broken glass fragments and place them in the puncture-resistant container. Liquids should be absorbed with a spill padpowder should be removed with damp disposable gauze pads or soft toweling. The hazardous material should be completely removed and the area rinsed with water and then cleaned with detergent. The spill cleanup should proceed progressively from areas of lesser to greater contamination. The detergent should be thoroughly rinsed and removed. All contaminated materials should be placed in the disposal bags provided and sealed and transported to a designated containment receptacle. Spills occurring in the biohazard cabinet should be cleaned up immediately

Anwendungen & Verwendung

Verwenden

Gonadotropin releasing hormone (gonadorelin) analogue; treatment of prostate cancer.

Entsorgungsverfahren

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 LEUPROLIDE (8 total), please visit the HSDB record page.

Preventive Measures

/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 LEUPROLIDE (19 total), please visit the HSDB record page.

Personal Protective Equipment (PPE)

/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 lotstherefore, 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/

Wechselwirkungen

OBJECTIVE: To assess the efficacy of combining sodium etidronate with low doses of the 19-nor-testosterone progestin norethindrone or using high doses of norethindrone alone as prophylaxis against the vasomotor instability and bone density loss induced by GnRH agonists alone. METHODS: Eleven patients enrolled in this randomized study received the long-acting GnRH agonist leuprolide acetate 3.75 mg intramuscularly every 4 weeks for 24 weeks. Six patients (group I) self-administered sodium etidronate 400 mg/day orally for 14 days followed by calcium carbonate 500 mg/day orally for the next 42 days during three 56-day cycles. This regimen was supplemented by norethindrone 2.5 mg/day orally. Five patients (group II) self-administered norethindrone 10 mg/day orally. Two sets of controls were used. Group III consisted of ten previously reported patients who received the same GnRH agonist only. Group IV comprised 12 regularly cycling untreated controls. Bone mineral density, vasomotor symptoms, circulating estrogens, and lipids were assessed serially. RESULTS: The significant vasomotor instability (P < .Ol) and bone mineral density loss (-4.8 +/- 0.9%P < .05) experienced by patients in group III was prevented in those ln groups I and II despite maintenance of a persistent hypoestrogenlc state. Bone density changes ln groups I and II were similar to those in untreated controls (group IV). Persistent decreases in high-density lipoprotein (HDL) cholesterol (P = .005) and increases in the low-density lipoprotein-to-HDL ratio (P < .05) were noted only in group II patients receiving supplemental high-dose norethindrone. CONCLUSION: These preliminary data suggest that the addition of cyclic sodium etidronate in combination with low-dose norethindrone to GnRH agonists is an effective means of ameliorating the hypoestrogenic side effects induced by GnRH agonist alone.

Hepatotoxicity

Leuprolide 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 leuprolide therapy have generally been transient and asymptomatic, resolving even with drug continuation and rarely requiring dose modification or discontinuation. Despite use for several decades, leuprolide has not been linked to convincing cases of clinically apparent liver injury. Routine monitoring of patients for liver test abnormalities is not recommended.

Unerwünschte Wirkungen

Adverse reactions are reported to be different in children versus adults. Typically leuprolide is well tolerated in children, but the most common complaint is local pain at the injection site, which occurs in 10% of cases. Other common reactions include weight change, mood changes, skin rash, acne vulgaris, seborrhea, vaginal discharge, vaginal hemorrhage, and vaginitis. Reports also exist of anaphylactic reactions. In adults, the most common adverse reactions are injection site pain, flushing, hot flashes, headaches, and migraines. Other reported adverse effects include alopecia, nausea, vomiting, diarrhea, GI upset, fatigue, edema, insomnia, upper respiratory infection, fever, nasal congestion, altered mood, weight gain, vaginitis, testicular atrophy, weakness, dizziness, hyperlipidemia, hyperglycemia, impotence, decreased libido, dermatological changes, and arthropathy. Reduced fertility has been noted but typically reverses with the cessation of the drug. There are also reports of amenorrhea in women.

Toxizitätsübersicht

Leuprolide might cause fetal harm when given to a pregnant woman. In clinical trials, there has not been any reported overdose with leuprolide. Studies of increased doses of leuprolide show that patients tolerate the drug well. However, practitioners should avoid using dosage forms of leuprolide that contain benzyl alcohol in neonates. "Gasping syndrome" is fatal toxicity that can occur in neonates, and it has correlated with large amounts of benzyl alcohol. This gasping syndrome includes CNS dysfunction, respiratory distress, metabolic acidosis, and hypotension.

Medical Surveillance

/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/

Human Toxicity Excerpts

A case of rapid uterine enlargement and subsequent urinary retention occurring 7 days after GnRH-a administration in a 53-year-old premenopausal woman with myomas is presented. Rapid uterine enlargement was presumed to be caused by hyperestrogenism shortly after GnRH-a administration. The patient was treated with an indwelling Foley catheter for 2 weeks until the uterus decreased to near baseline dimensions. The patient's uterus continued to decrease in size during the 12 weeks she received GnRH-a and she underwent an uneventful total abdominal hysterectomy and bilateral salpingectomy/oophorectomy after donating 2 units of autologous blood. This case illustrates that adverse effects from GnRH-a treatment may be caused by the transient increase in ovarian steroid secretion shortly after drug administration.OBJECTIVES: This is the first multicenter, double-blind randomized clinical trial that compares a depot gonadotropin-releasing hormone agonist with danazol in the treatment of endometriosis. Efficacy results have been previously reportedthis report focuses on safety data. STUDY DESIGN: A total of 270 patients from 22 centers were randomly selected to receive either leuprolide acetate depot (3.75 mg injected monthly) or danazol (800 mg administered orally daily). Safety outcomes included adverse effects, clinical laboratory changes, and bone mineral density changes. RESULTS: Most patients receiving either drug reported side effects, most of which were related to the hypoestrogenism of leuprolide (e.g., vasodilatation) and relative hyperandrogenism of danazol (e.g., weight gain). Similarly small numbers of patients dropped out of the two treatment groups because of the side effects encountered. Leuprolide depot caused a greater decrease in bone densitypreliminary data suggest a return to baseline on cessation of the drug. Danazol was associated with alteration of serum lipids, specifically a significant decrease ln high-density lipoprotein. CONCLUSIONS: Although side effects were commonly reported in both groups, the drugs were similarly safe in terms of the absence of serious complications and the results of cessation of therapy. Side effects were largely reversible on discontinuation of medication. More longitudinal data are necessary before the possibility of long-term risks can be excluded, especially as they pertain to bone mineral density and lipids.The non-surgical treatment of endometriosis involves hormone therapy that either affects the lesions directly, or indirectly inhibits endometrial proliferation and induces atrophy through estrogen deprivation, or through a combination of these effects. The medications used to treat endometriosis are progestins (e.g. norethindrone, medroxyprogesterone acetate), oral contraceptives (e.g. estrogen-progesterone acetate), androgens and their derivatives (e.g., danazol, gestrinonel, and gonadotropin-releasing hormone (GnRH) agonists (e.g., buserelin, leuprolide acetate, nafarelin, goserelin, tryptorelin). Agents such as GnRH agonists that produce sustained and prolonged hypoestrogenemia, similar to the postmenopausal hypogonadal state, can have a significant negative impact on trabecular bone mass. Initial studies with dual-photon absorptiometry were unable to detect any appreciable bone loss with GnRH agonists. Later studies, however, have invariably found significant bone loss as early as 3 months after the start of treatment. Quantitated computerized tomography always shows significant trabecular bone loss of the vertebrae and hip with GnRH agonists. Depot preparations appear to produce more marked loss than daily intranasal sprays. Recovery of bone loss may take 6-12 months after the end of therapy, with considerable individual variations. /Leuprolide acetate/The histologic features of the testes of 4 patients with disseminated prostatic carcinoma who received at least one yr of daily treatment with leuprolide (6-D-leucine-9-(N-ethyl-L-prolinamide)-10-deglycinamide-luteinizing hormone-releasing factor) and subsequently underwent bilateral orchiectomy were examined. In marked contrast to the testes from 5 control patients, the testes of these leuprolide treated patients demonstrated absence of spermatogenesis, Leydig cell hypoplasia, and Leydig cell inactivity.For more Human Toxicity Excerpts (Complete) data for LEUPROLIDE (6 total), please visit the HSDB record page.

Non-Human Toxicity Excerpts

Studies in rats and mice for two years at daily subcutaneous doses of 0.6 to 4 mg/kg body weight and up to 60 mg/kg respectively, found only an increased incidence of benign pituitary hyperplasia and benign pituitary adenomas at 24 months in the rats.Studies in rabbits at doses of 0.00024, 0.0024, and 0.024 mg/kg (1/600 to 1/6 the human dose) on day 6 of pregnancy found a dose-related increase in major fetal abnormalitiesthese effects did not occur at similar doses in rats. The two higher doses in rabbits and highest dose in rats were associated with increased fetal mortality and decreased fetal weights.The effects of continuous or twice daily subcutaneous injections of leuprolide acetate and goserelin acetate on accelerated weight gain were studied in female rats. Both drugs produced similar effecs on body weight. When leuprolide acetate was given in twice daiy injections, the adrenal weight increased after 21 days of treatment, whereas administration by osmotic minipumps produced no significant effect. However, when goserelin acetate was givenPrevious studies addressing the ovarian protective effects of luteinizing hormone releasing hormone agonists (LHRHa) against adverse effects of chemotherapy have examined histologic and/or hormonal parameters without evaluating reproductive performance. In this report, we initially established a model for chronic treatment of female rats with cyclophosphamide that allowed long term survival. In a second experiment, thirty seven female cycling rats (age: 70 days) were divided into 4 treatment groups. They were given either cyclophosphamide (4 mg/kg/day, 5 days/week) for a total of 76 days (217 mg/kg) and/or the LHRHa leuprolide (Lupron) 5 ug/day by subcutaneous minipump (Alza) for 96 days. LHRHa was started 10 days before cyclophosphamide and ended 12 days after the last cyclophosphamide injection. All LHRHa-treated rats entered persistent diestrus. At the end of treatment, most rats treated with cyclophosphamide only were in persistent estrus. Breeding was started at 218 days of age. A laparotomy to count implantation sites was performed 15 to 16 days after vaginal plug/sperm was demonstrated. All nonpregnant rats were remated. Chi square and ANOVA were used for statistical analysis. The data presented demonstrate that: 1. LHRHa given before and after cyclophosphamide increased the pregnancy rate/mating (from 4/11 to 9/10P < 0.05), the number of implantations/mated rat (from 2.5 + or - 1.4 to 13.7 + or - 1.7P < 0.01), and reduced the need for remating (from 7/11 to 1/10P < O.05)2. LHRHa-treated rats performed better than controls. It was concluded that LHRHa protects against chemotherapy-induced fertility reduction in female rats.For more Non-Human Toxicity Excerpts (Complete) data for LEUPROLIDE (6 total), please visit the HSDB record page.

Probable Routes of Human Exposure

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The danger to health-care personnel from handling a hazardous drug stems from a combination of its inherent toxicity and the extent to which workers are exposed to the drug in the course of carrying out their duties. This exposure may be through inadvertent ingestion of the drug on foodstuffs (eg, workers' lunches), inhalation of drug dusts or droplets or direct skin contact. /Antineoplastic agents/