Liver flutamide

Flutamide is an androgen receptor antagonist that achieves peak concentrations approximately 2 to 4 hours after an oral dose. Flutamide is metabolized extensively, with a terminal half-life of about 8 hours. Bicalutamide achieves peak concentrations approximately 6 hours after the dose, with a terminal half-life of 6 to 10 days. Bicalutamide undergoes stereospecihc metabolism, where the S-enantiomer is cleared more rapidly by the liver than the -enantiomer. Nilutamide achieves peak serum concentrations between 1 to 4 hours after an oral dose and has a terminal half-life of 38 to 60 hours. Nilutamide is metabolized extensively, with less than 2% excreted as unchanged drug by the kidney. Side effects common to these agents are hot flashes, gynecomastia, and decreased libido. Flutamide tends to be associated with more diarrhea and requires three-times-daily administration, whereas bicalutamide is dosed once daily. Nilutamide may cause interstitial pneumonia and is associated with the visual disturbance of delayed adaptation to darkness. 

Flutamide 750 mg/day Gynecomastia Hot flushes Gastrointestinal disturbances (diarrhea) Liver function test abnormalities Breast tenderness Methemoglobinemia... 

Flutamide -nonsteroidal antiandrogen -endocrine effects -hot flashes -decreased libido -gynecomastia -impotence -galactorrhea -diarrhea -nausea and vomiting -myalgias -elevated liver function tests... 

The adverse effects of antiandrogens are gynecomastia, hot flushes, GI disturbances, liver function test abnormalities, and breast tenderness. GI disturbances consist of diarrhea for flutamide and bicalutamide and nausea or constipation for nilutamide. Flutamide is also associated with methemoglobinemia, whereas nilutamide causes visual disturbances (impaired dark adaptation), alcohol intolerance, and interstitial pneumonitis. 

Flutamide 250 mg/tid orally Mild nausea Hot flushes, transient elevations in liver function tests... 

Flutamide is a non-steroidal antiandrogen that is used to treat prostatic cancer. Its most common adverse effects are liver damage and photosensitivity. 

Flutamide can cause liver damage, which can occasionally be fatal (12). 

A 74-year-old man developed life-threatening acute liver failure while taking flutamide (13). Other causes of acute liver failure were ruled out and there was no evidence of active prostate cancer or liver metastases. 

The authors suggested that mitochondrial dysfunction is implicated in flutamide-associated liver damage. 

Three patients with advanced prostate carcinoma who took flutamide 250 mg tds for 20-22 weeks developed signs of liver damage (jaundice, anorexia, nausea, dark urine) and changes in liver function tests (high transaminases and bilirubin), indicative of acute hepatitis flutamide was withdrawn and there was spontaneous remission over the next 8 weeks (14). 

Of 123 patients who had taken flutamide, 33 had liver disorders, mostly within 9 months (16). Three variables, body mass index, a past history of hver disorders, and raised transaminases were significantly related to the incidence of hver disorders. Smoking was related to a lower incidence. 

Lubbert C, Wiese M, Haupt R, Ruf BR. Ikterus und schwere Leberfunktionsstorung bei der hormonablativen Behandlung des Prostatakarzinoms. [Toxic hepatitis and liver failure under therapy with flutamide.] Internist (Berl) 2004 45(3) 333 0. 

Famularo G, De Simone C, Minisola G, Nicotra GC. Flutamide-associated acute liver failure. Ann Ital Med Int 2003 18(4) 250-3. 

Flutamide use is limited due to reports of fatal hepatitis requiring monitoring of liver function during therapy. Pregnancy must be avoided due to the risk of feminization of a male fetus. ... 

A recently completed NCI intergroup trial involving 1387 evaluable stage D2 prostate cancer patients failed to show any significant survival benefits for the combination of orchiectomy plus flutamide over orchiectomy alone. Like other studies of CAB, overall survival was longest in patients with minimal disease. Diarrhea, elevated liver function tests, and anemia were more common in those patients who received flutamide. 

Kashimshetty, R., Desai, V.G., Kale, V.M., Lee, T., Moland, C.L., Branham, W.S., New, L.S.,Chan, E.C.,Younis, H., Boelsterh, U.A. (2009). Underlying mitochondrial dysfunction triggers flutamide-induced oxidative liver injury in a mouse model of idiosyncratic drug toxicity. Toxicology and Applied Pharmacology, 238, 150-159. 

Liver The use of flutamide for hirsutism in premenopausal women over 15 years has been reported [116 ]. The dosage of flutamide, alone or in combination with oral... 

---