Overview
DESCRIPTION Eulexin ® capsules contain flutamide, an acetanilid, nonsteroidal, orally active antiandrogen having the chemical name, α,α,α-trifluoro-2-methyl-4'-nitro- m -propionotoluidide. Each capsule contains 125 mg flutamide. The compound is a buff to yellow powder with a molecular weight of 276.
Mechanism of Action
CLINICAL PHARMACOLOGY General In animal studies, flutamide demonstrates potent antiandrogenic effects. It exerts its antiandrogenic action by inhibiting androgen uptake and/or by inhibiting nuclear binding of androgen in target tissues or both. Prostatic carcinoma is known to be androgen-sensitive and responds to treatment that counteracts the effect of androgen and/or removes the source of androgen, e.g., castration. Elevations of plasma testosterone and estradiol levels have been noted following flutamide administration. Pharmacokinetics Absorption Analysis of plasma, urine, and feces following a single oral 200 mg dose of tritium-labeled Eulexin ® to human volunteers showed that the drug is rapidly and completely absorbed.
Indications
- INDICATIONS AND USAGE Eulexin ® capsules are indicated for use in combination with LHRH-agonists for the management of locally confined Stage B 2 -C and Stage D 2 metastatic carcinoma of the prostate. Stage B 2 -C Prostatic Carcinoma Treatment with Eulexin ® capsules and the goserelin acetate implant should start eight weeks prior to initiating radiation therapy and continue during radiation therapy. Stage D 2 Metastatic Carcinoma To achieve benefit from treatment, Eulexin ® capsules should be initiated with the LHRH-agonist and continued until progression.
Common Doses
- 750 mg
Dosage
DOSAGE AND ADMINISTRATION The recommended dosage is 2 capsules 3 times a day at 8 hour intervals for a total daily dose of 750 mg.
Black Box Warning
WARNINGS Hepatic Injury There have been postmarketing reports of hospitalization and rarely death due to liver failure in patients taking Eulexin ® . Evidence of hepatic injury included elevated serum transaminase levels, jaundice, hepatic encephalopathy and death related to acute hepatic failure. The hepatic injury was reversible after discontinuation of therapy in some patients. Approximately half of the reported cases occurred within the initial 3 months of treatment with Eulexin ® . Serum transaminase levels should be measured prior to starting treatment with Eulexin ® .
Contraindications
- CONTRAINDICATIONS Eulexin ® capsules are contraindicated in patients who are hypersensitive to Eulexin ® or any component of this preparation. Eulexin ® capsules are contraindicated in patients with severe hepatic impairment (baseline hepatic enzymes should be evaluated prior to treatment).
Side Effects
- ADVERSE REACTIONS Stage B 2 -C Prostatic Carcinoma Treatment with Eulexin ® capsules and the goserelin acetate implant did not add substantially to the toxicity of radiation treatment alone. The following adverse experiences were reported during a multicenter clinical trial comparing Eulexin ® + goserelin acetate implant + radiation versus radiation alone. The most frequently reported (greater than 5%) adverse experiences are listed below: Adverse Events During Acute Radiation Therapy (within first 90 days of radiation therapy) (n=231) Goserelin Acetate Implant + Eulexin ® + Radiation (n=235)...
Interactions
- Drug Interactions Increases in prothrombin time have been noted in patients receiving long-term warfarin therapy after Eulexin ® was initiated. Therefore close monitoring of prothrombin time is recommended and adjustment of the anticoagulant dose may be necessary when Eulexin ® capsules are administered concomitantly with warfarin.