Flutamide is an oral antiandrogen used in prostate cancer, usually in combination with GnRH analogues (chemical castration). It blocks the action of testosterone on tumour cells. It has potentially serious liver toxicity, so liver function must be monitored before and during treatment.
Also known as: Flutamida, Eulexin
Flutamide + warfarin: flutamide may increase the anticoagulant effect (prothrombin time) — monitor INR.
The flutamide label documents increases in prothrombin time in patients receiving warfarin ("Increases in prothrombin time have been noted in patients receiving warfarin therapy"), and the Prontuário records the same ("Increases the effect of warfarin"). The mechanism is not fully established, but the effect translates into increased bleeding risk. The prostate cancer patient on combined therapy with warfarin (e.g., for atrial fibrillation or thromboembolism) should have frequent INR in the first weeks of the combination and after any dose change of either drug. Adjust the warfarin dose to target and instruct the patient to watch for bleeding signs (gums, epistaxis, bruising, dark stools).
Flutamide + warfarin: monitor INR when starting or adjusting flutamide — it may increase the anticoagulant effect.
The FDA label documents: "Increases in prothrombin time have been noted in patients receiving warfarin therapy". The Prontuário confirms: "Increases the effect of warfarin". The mechanism is not fully established, but the combination requires INR monitoring.
Frequent INR during the first weeks of the combination and after any dose change.
Bleeding (gums, epistaxis, bruising), dark urine or stools, INR above target.
Monitor INR when starting, adjusting or stopping flutamide in patients anticoagulated with warfarin; adjust warfarin dose as needed.
DailyMed/FDA (NIH/NLM) — approved Flutamide label (EULEXIN): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0a905e25-42b6-4937-a689-f01a8f22e644 ; approved Warfarin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057 ; Prontuário Terapêutico do INFARMED (11th ed., 2012) — Flutamide, 16.2.2.2
Alcohol may worsen the hepatic toxicity associated with flutamide.
Limit alcohol intake, especially in patients with borderline liver function.
DailyMed/FDA (NIH/NLM) — approved Flutamide label (EULEXIN): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0a905e25-42b6-4937-a689-f01a8f22e644
Serious hepatic toxicity (boxed warning) — contraindicated in severe hepatic impairment; risk of liver injury in patients with pre-existing hepatic disease.
Liver function tests before starting and during treatment; discontinue if significant transaminase elevation.
DailyMed/FDA (NIH/NLM) — approved Flutamide label (EULEXIN): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0a905e25-42b6-4937-a689-f01a8f22e644
Indication restricted to prostate cancer (male population); do not use in pregnant women (label: "Use in Women" — contraindication).
Not applicable in pregnancy (indication exclusively male).
Not applicable (male indication).
Not applicable.
DailyMed/FDA (NIH/NLM) — approved Flutamide label (EULEXIN): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0a905e25-42b6-4937-a689-f01a8f22e644
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Antiandrogen that blocks testosterone and dihydrotestosterone binding to the androgen receptor in prostate cells, complementing the chemical castration induced by GnRH analogues.
Competitive inhibition of androgen binding to the androgen receptor, preventing stimulation of hormone-dependent tumour growth; it does not suppress testosterone production (hence combination with GnRH analogues).
Good oral absorption after administration; kinetics do not differ by race (no clinically observed differences in "absorption, distribution, metabolism, or excretion due to race").
Extensively metabolised in the liver — the parent compound represents only ~2% of circulating drug; the active metabolite is 2-hydroxyflutamide, with conjugation and renal elimination.
Half-life of the alpha-hydroxylated metabolite of approximately 6 hours ("half-life for the alpha-hydroxylated metabolite... is approximately 6 hours"); the active metabolite (2-hydroxyflutamide) has a half-life of about 8 hours.
