Clinical medicine profile
Flutamide
Androgen Receptor Inhibitor [EPC]
- Route
- See product SmPC
- Schedule
- POM
- ATC
- Not assigned
- PPB status
- registered
Safety essentials
The information most likely to change a prescribing or dispensing decision.
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 ® . Eulexin ® is not recommended in patients whose ALT values exceed twice the upper limit of normal. Serum transaminase levels should then be measured monthly for the first 4 months of therapy, and periodically thereafter. Liver function tests also should be obtained at the first signs and symptoms suggestive of liver dysfunction, e.g., nausea, vomiting, abdominal pain, fatigue, anorexia, "flu-like" symptoms, hyperbilirubinuria, jaundice or right upper quadrant tenderness. If at any time, a patient has jaundice, or their ALT rises above 2 times the upper limit of normal, Eulexin ® should be immediately discontinued with close follow-up of liver function tests until resolution.
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).
Precautions
- WARNINGS Hepatic Injury SEE BOXED WARNINGS Use in Women Eulexin ® capsules are for use only in men.
- This product has no indication for women and should not be used in this population, particularly for nonserious or nonlife-threatening conditions.
- Fetal toxicity Eulexin ® may cause fetal harm when administered to a pregnant woman (see Pregnancy ).
- Aniline toxicity One metabolite of Eulexin ® is 4-nitro-3-fluoro-methylaniline.
- Several toxicities consistent with aniline exposure, including methemoglobinemia, hemolytic anemia and cholestatic jaundice have been observed in both animals and humans after Eulexin ® administration.
- In patients susceptible to aniline toxicity (e.g. persons with glucose-6-phosphate dehydrogenase deficiency, hemoglobin M disease and smokers), monitoring of methemoglobin levels should be considered.
Dosing matrix
Population and organ-function guidance, shown together for faster comparison.
Prostate Cancer: Adults-250mg TID. Stage B2-C Prostatic Carcinoma: Adults-Start treat-ment at 8 weeks prior to initiating radiation therapy and continue during radiation therapy. Stage D2 Metastatic Carcinoma: Adults: Initiate flutamide capsules with the LHRH agonist and continue until progression.
See label paediatric section if present; otherwise use paediatric formulary — do not extrapolate adult doses.
Review renal impairment dosing; many agents need CrCl/eGFR adjustment.
- CrCl 0–120: Confirm renal dosing in product SmPC / primary label.
Review hepatic impairment dosing; monitor LFTs if agent is hepatically cleared or hepatotoxic.
Use, effects & interactions
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.
Adverse 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) Radiation Only % All % All Rectum/Large Bowel 80 76 Bladder 58 60 Skin 37 37 Adverse Events During Late Radiation Phase (after 90 days of radiation therapy) (n=231) Goserelin Acetate Implant + Eulexin ® + Radiation (n=235) Radiation Only % All % All Diarrhea 36 40 Cystitis 16 16 Rectal Bleeding 14 20 Proctitis 8 8 Hematuria 7 12 Additional adverse event data were collected for the combination therapy with radiation group over both the hormonal treatment and hormonal treatment plus radiation phases of the study.
- Adverse experiences occurring in more than 5% of patients in this group, over both parts of the study, were hot flashes (46%), diarrhea (40%), nausea (9%), and skin rash (8%).
- Stage D 2 Metastatic Carcinoma The following adverse experiences were reported during a multicenter clinical trial comparing Eulexin ® + LHRH agonist versus placebo + LHRH agonist.
- The most frequently reported (greater than 5%) adverse experiences during treatment with Eulexin ® capsules in combination with an LHRH agonist are listed in the table below.
- For comparison, adverse experiences seen with an LHRH agonist and placebo are also listed in the following table.
- (n=294) Eulexin ® + LHRH agonist (n=28) Placebo + LHRH agonist % All % All Hot Flashes 61 57 Loss of Libido 36 31 Impotence 33 29 Diarrhea 12 4 Nausea/Vomiting 11 10 Gynecomastia 9 11 Other 7 9 Other GI 6 4 As shown in the table, for both treatment groups, the most frequently occurring adverse experiences (hot flashes, impotence, loss of libido) were those known to be associated with low serum androgen levels and known to occur with LHRH agonists alone.
- The only notable difference was the higher incidence of diarrhea in the Eulexin ® + LHRH agonist group (12%), which was severe in 5% as opposed to the placebo + LHRH agonist (4%), which was severe in less than 1%.
- In addition, the following adverse reactions were reported during treatment with Eulexin ® + LHRH agonist.
- Cardiovascular System: hypertension in 1% of patients.
- Central Nervous System : CNS (drowsiness/confusion/depression/anxiety/nervousness) reactions occurred in 1% of patients.
- Gastrointestinal System : anorexia 4%, and other GI disorders occurred in 6% of patients.
- Hematopoietic System : anemia occurred in 6%, leukopenia in 3%, and thrombocytopenia in 1% of patients.
Drug interactions
Open multi-drug checker ↗- Professional use: confirm indication, dose, duration, monitoring and patient counselling points against current Kenya STG / EML and the product SmPC.
- Document allergy status and key interactions.
Mechanism & disposition
It competes with testosterone and its metabolite, dihydrotestosterone for binding to androgen receptors in the prostate gland.
Read complete mechanism
It competes with testosterone and its metabolite, dihydrotestosterone for binding to androgen receptors in the prostate gland. By doing so, it prevents them from stimulating the prostate cancer cells to grow. [It is a substituted anilide]
Product-specific
Product-specific
See product SmPC
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. Following a single 250 mg oral dose to normal adult volunteers, the biologically active alpha-hydroxy...
In male rats administered an oral 5 mg/kg dose of 14 C-flutamide neither flutamide nor any of its metabolites is preferentially accumulated in any tissue except the prostate. Total drug levels were highest 6 hours after drug administration in all tissues. Levels declined at rough...
The composition of plasma radioactivity, following a single 200 mg oral dose of tritium-labeled Eulexin ® to normal adult volunteers, showed that Eulexin ® is rapidly and extensively metabolized, with Eulexin ® comprising only 2.5% of plasma radioactivity 1 hour after administrat...
Eulexin ® and its metabolites are excreted mainly in the urine with only 4.2% of a single dose excreted in the feces over 72 hours. Plasma Pharmacokinetics of flutamide and Hydroxyflutamide in Geriatric Volunteers (mean ± SD) Single Dose flutamide Hydroxyflutamide Steady-State fl...
for the alpha-hydroxylated metabolite of Eulexin ® is approximately 6 hours. Eulexin ® , in vivo , at steady-state plasma concentrations of 24 to 78 ng/mL, is 94% to 96% bound to plasma proteins. The active metabolite of Eulexin ® , in vivo , at steady-state plasma concentrations...
Pregnancy, lactation & diet
Pregnancy Pregnancy Category D There was decreased 24 hour survival in the offspring of pregnant rats treated with Eulexin ® at doses of 30, 100 or 200 mg/kg/day (approximately 3, 9 and 19 times the human dose). A slight increase in minor variations in the development of the sternebrae and vertebrae was seen in fetuses of rats treated with two higher doses. Feminization of the male rats also occurred at the two higher dose levels. There was a decreased survival rate in the offspring of rabbits receiving the highest dose (15 mg/kg/day, equal to 1.4 times the human dose).
Assess infant risk vs benefit of maternal therapy; prefer agents with lactation data.
Brands & loaded prices
| Brand | Manufacturer | Pack | Observed price |
|---|---|---|---|
| No reviewed brand listings are linked yet. | |||
Sources & review state
Decision support only. Confirm patient-specific decisions against the current product SmPC, Kenya STG/EML, and professional judgement.