LEUPROLIDE MESYLATE

First approved in 1985

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C59H84N16O12.CH4O3S
Molecular Weight	1305.504
Optical Activity	UNSPECIFIED
Defined Stereocenters	9 / 9
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CS(O)(=O)=O.CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](CO)NC(=O)[C@H](CC3=CNC4=C3C=CC=C4)NC(=O)[C@H](CC5=CNC=N5)NC(=O)[C@@H]6CCC(=O)N6

InChI

InChIKey=MBIDSOMXPLCOHS-XNHQSDQCSA-N

InChI=1S/C59H84N16O12.CH4O3S/c1-6-63-57(86)48-14-10-22-75(48)58(87)41(13-9-21-64-59(60)61)68-51(80)42(23-32(2)3)69-52(81)43(24-33(4)5)70-53(82)44(25-34-15-17-37(77)18-16-34)71-56(85)47(30-76)74-54(83)45(26-35-28-65-39-12-8-7-11-38(35)39)72-55(84)46(27-36-29-62-31-66-36)73-50(79)40-19-20-49(78)67-40;1-5(2,3)4/h7-8,11-12,15-18,28-29,31-33,40-48,65,76-77H,6,9-10,13-14,19-27,30H2,1-5H3,(H,62,66)(H,63,86)(H,67,78)(H,68,80)(H,69,81)(H,70,82)(H,71,85)(H,72,84)(H,73,79)(H,74,83)(H4,60,61,64);1H3,(H,2,3,4)/t40-,41-,42-,43+,44-,45-,46-,47-,48-;/m0./s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/7533699
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/ppa/leuprolide.html | http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020011s040lbl.pdf | http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019010s033,019732s031s035s036,020517s024s028s029lbl.pdf

Leuprolide acetate is a synthetic nonapeptide analog of naturally occurring gonadotropin-releasing hormone (GnRH or LH-RH). The analog possesses greater potency than the natural hormone. It acts primarily on the anterior pituitary, inducing a transient early rise in gonadotrophin release. With continued use, leuprorelin causes pituitary desensitisation and/or down-regulation, leading to suppressed circulating levels of gonadotrophins and sex hormones. Leuprolide acetate used to treat a wide range of sex hormone-related disorders including advanced prostatic cancer, uterine leiomyomata (fibroids), endometriosis and precocious puberty.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Gonadotropin-releasing hormone receptor 41 Target ID: CHEMBL1855 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7533699	Agonist 2678

Conditions

Condition	Modality	Highest Phase	Product
Prostate cancer 178 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019010s033,019732s031s035s036,020517s024s028s029lbl.pdf	Palliative	Approved 8429	LUPRON Approved Use LEUPROLIDE ACETATE INJECTION is indicated in the palliative treatment of advanced prostatic cancer. Launch Date 1985
Endometriosis 32 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020011s040lbl.pdf	Primary	Approved 8429	LUPRON DEPOT Approved Use Endometriosis LUPRON DEPOT 3.75 mg is indicated for management of endometriosis, including pain relief and reduction of endometriotic lesions. LUPRON DEPOT monthly with norethindrone acetate 5 mg daily is also indicated for initial management of endometriosis and for management of recurrence of symptoms. (Refer also to norethindrone acetate prescribing information for WARNINGS, PRECAUTIONS, CONTRAINDICATIONS and ADVERSE REACTIONS associated with norethindrone acetate). Duration of initial treatment or retreatment should be limited to 6 months. Uterine Leiomyomata (Fibroids) LUPRON DEPOT 3.75 mg concomitantly with iron therapy is indicated for the preoperative hematologic improvement of patients with anemia caused by uterine leiomyomata. The clinician may wish to consider a one-month trial period on iron alone inasmuch as some of the patients will respond to iron alone. (See Table 1.) LUPRON may be added if the response to iron alone is considered inadequate. Recommended duration of therapy with LUPRON DEPOT 3.75 mg is up to three months. Experience with LUPRON DEPOT in females has been limited to women 18 years of age and older. Launch Date 1995
Uterine leiomyomata 8 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020011s040lbl.pdf	Primary	Approved 8429	LUPRON DEPOT Approved Use Endometriosis LUPRON DEPOT 3.75 mg is indicated for management of endometriosis, including pain relief and reduction of endometriotic lesions. LUPRON DEPOT monthly with norethindrone acetate 5 mg daily is also indicated for initial management of endometriosis and for management of recurrence of symptoms. (Refer also to norethindrone acetate prescribing information for WARNINGS, PRECAUTIONS, CONTRAINDICATIONS and ADVERSE REACTIONS associated with norethindrone acetate). Duration of initial treatment or retreatment should be limited to 6 months. Uterine Leiomyomata (Fibroids) LUPRON DEPOT 3.75 mg concomitantly with iron therapy is indicated for the preoperative hematologic improvement of patients with anemia caused by uterine leiomyomata. The clinician may wish to consider a one-month trial period on iron alone inasmuch as some of the patients will respond to iron alone. (See Table 1.) LUPRON may be added if the response to iron alone is considered inadequate. Recommended duration of therapy with LUPRON DEPOT 3.75 mg is up to three months. Experience with LUPRON DEPOT in females has been limited to women 18 years of age and older. Launch Date 1995

C_max

Value	Dose	Co-administered	Analyte	Population
32.48 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27824264	11.25 mg single, subcutaneous dose: 11.25 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:		LEUPROLIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
426.2 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27824264	11.25 mg single, subcutaneous dose: 11.25 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:		LEUPROLIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
3 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019943s031,020011s038,020708s031lbl.pdf	1 mg single, intravenous dose: 1 mg route of administration: Intravenous experiment type: SINGLE co-administered:		LEUPROLIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
54% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019943s031,020011s038,020708s031lbl.pdf	1 mg single, intravenous dose: 1 mg route of administration: Intravenous experiment type: SINGLE co-administered:		LEUPROLIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
30 mg 1 times / month multiple, subcutaneous Highest studied dose Dose: 30 mg, 1 times / month Route: subcutaneous Route: multiple Dose: 30 mg, 1 times / month Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019010s033,019732s031s035s036,020517s024s028s029lbl.pdf	unhealthy, adult n = 49 Health Status: unhealthy Condition: cancer Age Group: adult Sex: unknown Population Size: 49 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019010s033,019732s031s035s036,020517s024s028s029lbl.pdf	Other AEs: Asthenia, General body pain... Other AEs: Asthenia (6 patients) General body pain (16 patients) Headache (5 patients) Injection site reaction (4 patients) Hot flashes (23 patients) Gastrointestinal disorder (NOS) (5 patients) Dehydration (4 patients) Edema (4 patients) Disorder joint (8 patients) Myalgia (4 patients) Vertigo (3 patients) Neuromuscular disorders (3 patients) Paresthesia (4 patients) Skin reaction (6 patients) Urinary tract disorder NOS (5 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019010s033,019732s031s035s036,020517s024s028s029lbl.pdf
7.5 mg 1 times / month multiple, subcutaneous Recommended Dose: 7.5 mg, 1 times / month Route: subcutaneous Route: multiple Dose: 7.5 mg, 1 times / month Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019010s033,019732s031s035s036,020517s024s028s029lbl.pdf	unhealthy, adult n = 56 Health Status: unhealthy Condition: cancer Age Group: adult Sex: unknown Population Size: 56 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019010s033,019732s031s035s036,020517s024s028s029lbl.pdf	Other AEs: General body pain, Hot flashes... Other AEs: General body pain (13 patients) Hot flashes (32 patients) Gastrointestinal disorder (NOS) (8 patients) Edema (8 patients) Libido decreased (3 patients) Disorder urinary tract (7 patients) Impotence (3 patients) Atrophy testicular (3 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019010s033,019732s031s035s036,020517s024s028s029lbl.pdf

AEs

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:6427	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:6427
ChemicalBook	CB8398455	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8398455
MolPort	MolPort-006-069-430	https://www.molport.com/shop/molecule-link/MolPort-006-069-430
MolPort	MolPort-046-684-146	https://www.molport.com/shop/molecule-link/MolPort-046-684-146
eMolecules	30152588	https://www.emolecules.com/cgi-bin/more?vid=30152588
eMolecules	539933	https://www.emolecules.com/cgi-bin/more?vid=539933

PubMed

Title	Date	PubMed
Drug induced polymyositis secondary to leuprolide acetate (Lupron) therapy for prostate carcinoma.	1991 Sep-Oct	1954704
Adverse effects of leuprolide acetate depot treatment.	1993 Feb	8425646
Neuropsychologic dysfunction in women following leuprolide acetate induction of hypoestrogenism.	1993 Jan	8499680
Angina and myocardial infarction with use of leuprolide acetate.	1994 Jul	8030717
Pituitary apoplexy after leuprolide administration for carcinoma of the prostate.	1996 Jan	8706284
Pituitary apoplexy of a gonadotroph adenoma following gonadotrophin releasing hormone agonist therapy for prostatic cancer.	1997 Oct	9413812
Steroidal 'add-back' therapy in patients treated with GnRH agonists.	1998	9628521
Sertraline in the treatment of depression associated with gonadotropin-releasing hormone agonist therapy.	1998 Mar 15	9532352
Erectile function and nocturnal penile tumescence in patients with prostate cancer undergoing luteinizing hormone-releasing hormone agonist therapy.	1999 Jan	10221860
Lupron-induced mania.	1999 Jan 15	9951575
Macrophage Fcgamma receptors expression is altered by treatment with dopaminergic drugs.	1999 Mar	10075867
Uterine adenocarcinoma after GnRH agonist treatment.	2000 Feb	10763848
Pituitary haemorrhage after leuprolide therapy for prostatic cancer, clinically imitating acute subarachnoidal haemorrhage.	2002	12403969
Leuprolide-induced myopathy.	2002 Oct	12366635
Altered cognitive function in men treated for prostate cancer with luteinizing hormone-releasing hormone analogues and cyproterone acetate: a randomized controlled trial.	2002 Sep	12175403
Combined androgen blockade-induced anemia in prostate cancer patients without bone involvement.	2003 Mar-Apr	12820454
Quality of life compared during pharmacological treatments and clinical monitoring for non-localized prostate cancer: a randomized controlled trial.	2004 May	15142146
Leuprolide acetate suppresses pedophilic urges and arousability.	2005 Dec	16362253
Effects of gonadotrophin-releasing hormone agonists on apoptosis of granulosa cells.	2005 May	15965100
A clinical trial of combined anti-androgen and anti-heavy metal therapy in autistic disorders.	2006 Dec	17187010
Discovery of a pituitary adenoma following treatment with a gonadotropin-releasing hormone agonist in a patient with prostate cancer.	2006 Jan	16448441
Pharmacological characterization of a novel nonpeptide antagonist of the human gonadotropin-releasing hormone receptor, NBI-42902.	2007 Feb	17095587
Leuprolide acetate and central retinal vein occlusion.	2007 Nov-Dec	18050813
Transfusion-dependent anemia after initiation of androgen deprivation therapy for metastatic prostate cancer.	2007 Oct	17991572
Nonalcoholic fatty liver disease induced by leuprorelin acetate.	2008 Jan	18097299
Tricuspid valve thrombus: a case report associated with gonadotropin-releasing hormone analogue therapy and review of the literature.	2008 May	18464947
Metabolic changes during gonadotropin-releasing hormone agonist therapy for prostate cancer: differences from the classic metabolic syndrome.	2008 May 15	18348297
A possible participation of gonadotropin-releasing hormone in the neuroleptic and cataleptic effect of haloperidol.	2009 Jun	19403167
Long-term effects of GnRH agonist, GnRH antagonist, and estrogen plus progesterone treatment on apoptosis related genes in rat ovary.	2009 May	18829022
Apoplexy in non functioning pituitary adenoma after one dose of leuprolide as treatment for prostate cancer.	2010	19842040
Impacts of leuprolide acetate on quality of life in patients with prostate cancer: a prospective multicenter study.	2010 Dec	20707648
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.	2011 Jul 14	21599003
Testosterone regulates tight junction proteins and influences prostatic autoimmune responses.	2011 Jun	21761342

Patents

Sample Use Guides

In Vivo Use Guide

Dosing: Adult Prostate cancer, advanced: Note: Treatment is usually continued after development of metastatic (castration-resistant) disease. IM: Lupron Depot 7.5 mg (monthly): 7.5 mg every month or Lupron Depot 22.5 mg (3 month): 22.5 mg every 12 weeks or Lupron Depot 30 mg (4 month): 30 mg every 16 weeks or Lupron Depot 45 mg (6 month): 45 mg every 24 weeks SubQ: Eligard: 7.5 mg monthly or 22.5 mg every 3 months or 30 mg every 4 months or 45 mg every 6 months Leuprolide acetate 5 mg/mL solution: 1 mg daily Endometriosis: IM: Initial therapy may be with leuprolide alone or in combination with norethindrone; if re-treatment for an additional 6 months is necessary, concomitant norethindrone should be used. Re-treatment is not recommended for longer than one additional 6-month course. Lupron Depot: 3.75 mg every month for up to 6 months or Lupron Depot-3 month: 11.25 mg every 3 months for up to 2 doses (6 months total duration of treatment) Uterine leiomyomata (fibroids): IM (in combination with iron): Lupron Depot: 3.75 mg every month for up to 3 months or Lupron Depot-3 month: 11.25 mg as a single injection Breast cancer, premenopausal ovarian supression (off-label use): IM: Lupron Depot: 3.75 mg every 28 days for up to 24 months (Boccardo 1999) or Lupron Depot-3 month: 11.25 mg every 3 months for up to 24 months (Boccardo 1999; Schmid 2007) Treatment of paraphilia/hypersexuality (off-label use; Guay 2009; Reilly 2000): Males: IM: Note: May cause an initial increase in androgen concentrations which may be treated with an antiandrogen (eg, flutamide, cyproterone) for 1 to 2 months (Guay 2009). Avoid use in patients with osteoporosis or active pituitary pathology. SubQ: Test dose: 1 mg (observe for hypersensitivity) Depot IM: 3.75 to 7.5 mg monthly Dosing: Geriatric Refer to adult dosing. Dosing: Pediatric Precocious puberty (consider discontinuing by age 11 for females and by age 12 for males): IM: Lupron Depot-Ped (monthly): ≤25 kg: 7.5 mg every month >25 to 37.5 kg: 11.25 mg every month >37.5 kg: 15 mg every month Titrate dose upward in increments of 3.75 mg every 4 weeks if down-regulation is not achieved. Lupron Depot-Ped (3 month): 11.25 mg or 30 mg every 12 weeks SubQ (leuprolide acetate 5 mg/mL solution): Initial: 50 mcg/kg/day; titrate dose upward by 10 mcg/kg/day if down-regulation is not achieved. Note: Higher mg/kg doses may be required in younger children.

Route of Administration: Other

In Vitro Use Guide

In primary cell cultures from human prostate carcinoma leuprolide (from 5-20 ng/mL) showed a significant reduction in cell growth rate and an increase in DNA-fragmented cell number.

Name

Type

Language

LEUPROLIDE MESYLATE

Common Name

English

Leuprorelin mesilate [WHO-DD]

Common Name

English

CAMCEVI

Brand Name

English

PGLU-HIS-TRP-SER-TYR-D-LEU-LEU-ARG-PRO-NHC2H5 METHANESULFONATE

Common Name

English

PGLU-HIS-TRP-SER-TYR-D-LEU-LEU-ARG-PRO-NHC2H5 MESYLATE

Common Name

English

LEUPRORELIN MESYLATE

Common Name

English

LEUPRORELIN MESILATE

Common Name

English

1-9-LUTEINIZING HORMONE-RELEASING FACTOR (SWINE), 6-D-LEUCINE-9-(N-ETHYL-L-PROLINAMIDE)-, METHANESULFONATE (1:1)

Common Name

English

LEUPROLIDE MESYLATE [ORANGE BOOK]

Common Name

English

Code System Code Type Description

DAILYMED

8E3C3C493W