Leuprorelin
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| Routes of administration | Implant / Injection |
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| Elimination half-life | 3 hours |
| Excretion | Renal |
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| ECHA InfoCard | 100.161.466 |
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| Formula | C59H84N16O12 |
| Molar mass | 1209.4 g/mol g·mol−1 |
Leuprorelin (INN) or leuprolide acetate (USAN) is a gonadotropin-releasing hormone analog (GnRH analog). Proper Sequence: p-Glu-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHEt
Mode of action
Leuprolide acts at pituitary GnRH receptors. It acts as an antagonist to the secretion of gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) when administered continuously, though initially there may be a flare-up of hormone release. However, it becomes a GnRH receptor agonist when administered in a pulsatile fashion, causing pituitary secretion of LH and FSH.
Clinical usage
Like other GnRH agonists, leuprolide may be used in the treatment of: hormone-responsive cancers such as prostate cancer or breast cancer, estrogen-dependent conditions (such as endometriosis[1] or uterine fibroids), to treat precocious puberty,[2] and to control ovarian stimulation in In Vitro Fertilization (IVF). It is considered a possible treatment for paraphilias.[3]
A 2005 paper suggested it as a treatment for autism,[4] the hypothetical method of action being that autism is caused by mercury, with the additional assumption that mercury binds irreversibly to testosterone and therefore leuprolide can help cure autism by lowering the testosterone level and thereby the mercury level.[5]
Leuprolide has been tested as a treatment for reducing sexual urges in pedophiles and other cases of paraphilia. [6][7]
Leuprolide is also under investigation for possible use in the treatment of mild to moderate Alzheimer's disease.[8]
Approvals
- Lupron Injection (5 mg/mL for daily subcutaneous injection) was first approved by the FDA for treatment of advanced prostate cancer on April 9, 1985.
- Lupron Depot (7.5 mg/vial for monthly intramuscular depot injection) was first approved by the FDA for palliative treatment of advanced prostate cancer on January 26, 1989, and subsequently in 22.5 mg/vial and 30 mg/vial for intramuscular depot injection every 3 and 4 months, respectively. 3.75 mg/vial and 11.25 mg/vial dosage forms were subsequently approved for subcutaneous depot injection every month and every 3 months, respectively for treatment of endometriosis or fibroids. 7.5 mg/vial, 11.25 mg/vial, and 15 mg/vial dosage forms were subsequently approved for subcutaneous depot injection for treatment of children with central precocious puberty.
- Viadur (72 mg yearly subcutaneous implant) was first approved by the FDA for palliative treatment of advanced prostate cancer on March 6, 2000.
- Eligard (7.5 mg for monthly subcutaneous depot injection) was first approved by the FDA for palliative treatment of advanced prostate cancer on January 24, 2002, and subsequently in 22.5 mg, 30 mg, and 45 mg doses for subcutaneous depot injection every 3, 4, and 6 months, respectively.
Leuprolide acetate is marketed by Bayer AG under the brand name Viadur, by Sanofi-Aventis under the brand name Eligard, and by TAP Pharmaceuticals (1985-2008) and Abbott Laboratories (2008-current) under the brand name Lupron. It is available as a slow-release implant or subcutaneous/intramuscular injection.
In the UK, leuprorelin is marketed by Wyeth as Prostap SR(one month injection) and Prostap 3 (three month injection).
References
- ^ Crosignani PG, Luciano A, Ray A, Bergqvist A (2006). "Subcutaneous depot medroxyprogesterone acetate versus leuprolide acetate in the treatment of endometriosis-associated pain". Human reproduction (Oxford, England). 21 (1): 248–56. doi:10.1093/humrep/dei290. PMID 16176939.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Badaru A, Wilson DM, Bachrach LK; et al. (2006). "Sequential comparisons of one-month and three-month depot leuprolide regimens in central precocious puberty". The Journal of clinical endocrinology and metabolism. 91 (5): 1862–7. doi:10.1210/jc.2005-1500. PMID 16449344.
{{cite journal}}: Explicit use of et al. in:|author=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Saleh F, Niel T, Fishman M (2004). "Treatment of paraphilia in young adults with leuprolide acetate: a preliminary case report series". J Forensic Sci. 49 (6): 1343–8. doi:10.1520/JFS2003035. PMID 15568711.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Geier M, Geier D (2005). "The potential importance of steroids in the treatment of autistic spectrum disorders and other disorders involving mercury toxicity". Med Hypotheses. 64 (5): 946–54. doi:10.1016/j.mehy.2004.11.018. PMID 15780490.
- ^ Allen A (2007-05-28). "Thiomersal on trial: the theory that vaccines cause autism goes to court". Slate. Retrieved 2008-01-30.
- ^ Schober JM, Byrne PM, Kuhn PJ. (2006). "Leuprolide acetate is a familiar drug that may modify sex-offender behaviour: the urologist's role". BJU international. 97 (4): 684–6. doi:10.1111/j.1464-410X.2006.05975.x. PMID 16536753.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Schober JM, Kuhn PJ, Kovacs PG, Earle JH, Byrne PM, Fries RA. (2005). "Leuprolide acetate suppresses pedophilic urges and arousability". Archives of Sexual Behavior. 34 (6): 691–705. doi:10.1007/s10508-005-7929-2. PMID 16362253.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Doraiswamy PM, Xiong GL. (2006). "Pharmacological strategies for the prevention of Alzheimer's disease". Expert Opin Pharmacother. 7 (1): 1–10. doi:10.1517/14656566.7.1.1. PMID 16370917.
There are thousands of MedWatch reports documenting adverse events for this drug noted on the FDA Website at FDA.gov. Further, an article by Carla K. Johnson of the AP, dated August 26, 2009 noted a recent study that found that this prostate cancer drug is very risky especially for me with heart problems. The AP article stated, "The hormone treatment was linked with a 96 percent higher risk of death after adjusting for other risk factors." A similar study issued in JAMA in July 2008 also found that the drug offered no life-prolonging benefits in men with advanced prostate cancer vs. men who did not take any form of hormone therapy, or conservative management. Women with Endometriosis also suffer significant side effects. FDA has documented literally thousands of MedWatch reports from women who have taken this drug. Another reliable source with documented information is lupronvictimshub.com. Carefully review the labeling, which was recently undated to include the adverse event of "pituitary approplexy" (bleeding-out of a tumor on the pituitary gland) See FDA Website. Also, in June of 2009 the label was changed again to warn about "convulsion" in the post-marketing surveillance. The label shows that 98% of women had adverse events including 65% suffering headache/migraine, 31% depression, 31% insomnia, and 25% Nausea/vomiting. Many other adverse events are listed in the label. See full label at FDA.gov. The label also notes that women with no history of depression or psychiatric illness reported suicidal ideation and attempt. See also the National Women's Health Network Article on Lupron Depot from November December 2008.
External links
- Lupron Injection (package insert from abbott)
- Reforming (purportedly) Non-Punitive Responses to Sexual Offending (journal article discussing use of Lupron as a form of reforming sex offender law)