Leuprorelin acetate

Recently, a Japanese research group published preclinical safety and efficacy data of an oral antiestrogen (TZE-5323) (Saito et al. 2003). This drug has been shown to have a strong affinity for human ERa and ER/i and a dose-dependent capacity to inhibit estradiol-stimulated transcriptional activation (Saito et al. 2003). In the experimental endometriosis model in rats, TZE-5323 dose-dependently reduced the volume of the endometrial implant with an effectiveness similar to that of danazol and leuprorelin acetate without causing significant changes in bone mineral density and in serum estradiol levels (Saito et al. 2003). 

Leuprorelin acetate Nafarelin acetate C2H5-NH-Pro-Arg-Leu-D-Leu-Tyr-Ser-Trp-His-5oxo pro NH2-Gly-Pro-Arg-Leu-D-Ala-Tyr-Ser-Try-His-5oxo pro 1... 

Management of endometriosis, uterine leiomyomata (Fibroids) CAS Registry 53714-56-0 (leuprorelin) 74381-53-6 (leuprorelin acetate) 5-oxo-L-prolyl-L-his tidyl-L-tryptophyl-L- seryl-L-tyrosyl-D-le ucyl-L-leucyl-L-argi nyl-A-ethyl-L-prolin amide acetate NA... 

A 61-year-old man with a 7-year history of diabetes, well-controlled with diet and acarbose, developed prostate cancer and was given leuprorelin acetate and flutamide. After the second injection of leuprorelin his fasting glucose and hemoglobin Alc concentrations were markedly raised (23 mmol/1 and 11% respectively). 

A 75-year-old man developed a high fever and cough immediately after an injection of leuprorelin acetate 3.75 mg and 8 days after starting flutamide 375 mg/ day (7). He died of respiratory failure after a month, and interstitial pneumonitis was confirmed postmortem. 

Injection site reactions are common with gonadorelin receptor agonists. In 119 women randomized to subcutaneous triptorelin a local reaction (redness, pain, or bruising) was present after 1 hour in 24% and persisted for 24 hours in 9.5% (41). In another study in 105 women randomized to leuprorelin acetate, moderate local reactions occurred in 24% and severe reactions in 1% (42). 

A 78-year-old man treated with subcutaneous leuprorelin acetate had repeated local reactions, with erythema, induration, abscesses, and an ulcer on one hip (44). 

A 73-year-old man with prostate cancer received leuprorelin acetate injections and developed a subcutaneous nodule at the injection site. Histology showed epithelioid granulomata with multinuclear giant cells. 

A 29-year-old woman with polycystic ovary syndrome had her first in vitro fertilization cycle of leuprorelin acetate, FSH, and human chorionic gonadotropin (hCG) (67). Within 2 days she complained of abdominal distension, shortness of breath, and abdominal pain. Over the next few days she developed massive ovarian enlargement, ascites, hyponatremia, respiratory failure, and renal insufficiency. This was further complicated by duodenal perforation, probably due to severe physical stress. 

Ovarian hyperstimulation syndrome occurred in a woman with polycystic ovarian syndrome, 3 weeks after an intramuscular injection of leuprorelin acetate for endometriosis (68). She was later given further courses of the drug without this complication. 

A previously healthy 34-year-old woman who underwent ovulation induction with leuprorelin acetate and FSH developed abdominal ascites due to OHSS, followed by acute aphasia and right hemiparesis (76). The stroke was caused by a large intracardiac thrombus. 

Azuma T, Kurimoto S, Mikami K, Oshi M. Interstitial pneumonitis related to leuprorelin acetate and flutamide. J Urol 1999 161(1) 221. 

Minagawa K, Sueoka H. [Seizure exacerbation by the use of leuprorelin acetate for treatment of central precocious puberty in a female patient with symptomatic localization-related epilepsy. ]No To Hattatsu 1999 31(5) 466-8. 

Tanaka T, Niimi H, Matsuo N, Fujieda K, Tachibana K, Ohyama K, Satoh M, Kugu K. Results of long-term followup after treatment of central precocious puberty with leuprorelin acetate evaluation of effectiveness of treatment and recovery of gonadal function. The TAP-144-SR Japanese study group on central precocious puberty. J Clin Endocrinol Metab 2005 90 1371-6. 

Yamano Z, Kusuda Y, Hara S, Shimogaki H, Hamani G. Cutaneous epithelioid granulomas caused by subcutaneous infusion of leuprorelin acetate. A case report. Acta Urol Japan 2004 50 199-202. 

Yasukawa K, Sawamura D, Sugawara H, Kato N. Leuprorelin acetate granulomas case reports and review of the literature. Br J Dermatol 2005 152 1045-7. 

Common Name Leuprolide acetate Leuprorelin acetate... 

Based on these limitations, only a limited number of drug delivery systems based on biodegradable polymers have so far been successfully commercialized. One example is Lupron Depot one-month injectable microspheres of PLGA containing leuprorelin acetate (LH-RH agonist) for the treatment of endometriosis and prostatic cancer [31,32]. 

Figure 11.3 Effects of the estrous cycle on vaginal absorption of leuprorelin acetate, phenol red and insulin in rats...

Fig. 40 Preparation of leuprorelin acetate containing microcapsules according to the in-water-drying process.

Toguchi H, Ogawa Y, Okada H, Yamamoto M. [Once-a-month injectable microcapsules of leuprorelin acetate]. Yakugaku Zasshi 1991 Aug lll(8) 397-409. 

Okada H. One-and three-month release injectable microspheres of the LH-RH superagonist leuprorelin acetate. Adv Drug Del Rev 1997 28 43-70. 

H CKcada. Y Doken, Y Ogawa, H Toguchi. Preparation of 3-month depot injectable microsphere.s of leuprorelin acetate using biodegradable polymers. Pharm. Rc.s. 11 1143-1147. 1994. 

Leuprorelin acetate 11-25 mg subcutaneously every 12 weeks for 48 weeks was compared with placebo in 204 Japanese men with spinal and bulbar muscular atrophy in a randomized trial. There were more hot flushes with leu-prorehn (10/100 versus 2/99), but the rates of other adverse reactions were similar to those with placebo [8 . ... 

Drug formulations In patients, mean age 73 years, with prostate cancer, a study of the use of leuprorelin acetate 11.25 mg injections every 3 months for 12 months ( = 58), compared with six monthly injections of depot leuprorelin acetate containing either 22.5 or 30 mg ( = 120), the results suggested no differences in adverse reactions [10 ]. Rushing was the most common adverse reaction it occurred in 43% of those who received 11.25 mg and in 34% of those who received 30 mg. Increased sweating was also slightly more common in those who received 11.25 mg. Injection site... 

Tunn UW, Wiedey K. Safety and clinical efficacy of a new 6-month depot formulation of leuprorelin acetate in patients with prostate cancer in Europe. Prostate Cancer Prostatic Dis 2009 12 83-7. 

Anaphylaxis A Japanese man with no history of allergies developed anaphylaxis to leuprorelin acetate depot while receiving treatment for metastatic prostate cancer [9 ]. 

In 2001 the man, aged 68, received subcutaneous injection of a 3.75 mg 1-month leuprorelin acetate depot. At the sixth injection, a local skin reaction with erythema and induration was observed at the site of injection. 

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