Usage
Flutamide is a nonsteroidal antiandrogen, specifically classified as an antineoplastic agent, primarily used to treat advanced prostate cancer. It acts by competitively binding to androgen receptors, thereby inhibiting the effects of androgens (like testosterone) on tumor growth. It is typically used in combination with a luteinizing hormone-releasing hormone (LHRH) agonist.
Alternate Names
Flutamide is also known by its brand name Eulexin®. There are no widely recognized international or regional variations of the generic name.
How It Works
Pharmacodynamics: Flutamide exerts its antiandrogenic effects by competitively binding to cytosolic androgen receptors, preventing the formation of the receptor-androgen complex that normally translocates to the nucleus and initiates transcription of androgen-responsive genes. This, in turn, reduces the expression of proteins involved in prostate cancer cell growth and proliferation.
Pharmacokinetics: Flutamide is well-absorbed orally. It is extensively metabolized in the liver primarily by the CYP1A2 enzyme, resulting in the formation of several active metabolites, including hydroxyflutamide. It is primarily excreted in the urine, with a smaller amount eliminated in feces.
Mode of Action: Flutamide works at the cellular level by directly blocking the action of androgens within prostate cancer cells.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Flutamide primarily acts through competitive binding to androgen receptors. It inhibits the binding of androgens to their receptors, thus preventing the receptor activation necessary for the androgens’ biological effects. It is metabolized via hepatic CYP1A2 and CYP3A4 pathways.
Elimination Pathways: Flutamide is eliminated primarily through hepatic metabolism followed by renal excretion of the metabolites.
Dosage
Standard Dosage
Adults:
The standard dose is 250 mg (two 125 mg capsules or one 250 mg tablet) orally every 8 hours, for a total daily dose of 750 mg.
Children:
Flutamide is not indicated for use in children. It can cause feminization in male children and is unsafe for female children.
Special Cases:
- Elderly Patients: No specific dosage adjustments are typically required for elderly patients. However, caution is advised, and close monitoring is recommended, considering potential age-related decline in hepatic and renal function.
- Patients with Renal Impairment: No specific dose adjustment is necessary for patients with renal impairment. However, caution is recommended.
- Patients with Hepatic Dysfunction: Flutamide is contraindicated in patients with severe hepatic impairment. Caution is advised in patients with mild to moderate hepatic impairment, and close monitoring of liver function tests is essential. Dose reduction may be considered based on clinical judgment.
- Patients with Comorbid Conditions: Use with caution in patients with cardiovascular disease, diabetes, or pre-existing liver conditions.
Clinical Use Cases
Flutamide is not indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its use is limited to prostate cancer management.
Dosage Adjustments
Dose adjustments may be necessary based on individual patient response, tolerance, and hepatic function. If severe side effects occur, especially those related to the liver, the dose should be reduced or the treatment discontinued.
Side Effects
Common Side Effects
- Hot flashes
- Decreased libido
- Impotence
- Gynecomastia (breast enlargement)
- Diarrhea
- Nausea and vomiting
- Drowsiness
Rare but Serious Side Effects
- Hepatotoxicity (liver damage) – Signs include jaundice, dark urine, pale stools, abdominal pain, and fatigue. Requires immediate medical attention.
- Interstitial pneumonitis (lung inflammation)
- Methemoglobinemia (blood disorder)
Long-Term Effects
Long-term effects can include chronic liver disease if hepatotoxicity is not managed appropriately.
Adverse Drug Reactions (ADR)
Clinically significant ADRs include hepatotoxicity and interstitial pneumonitis. Any signs or symptoms suggestive of these conditions warrant immediate medical attention and discontinuation of flutamide.
Contraindications
- Hypersensitivity to flutamide
- Severe hepatic impairment (liver disease)
- Use in women, especially during pregnancy and breastfeeding
- Use in children
Drug Interactions
Flutamide interacts with various medications, including:
- Anticoagulants (e.g., warfarin) – increased risk of bleeding
- CYP1A2 inducers (e.g., rifampin) – decreased flutamide effectiveness
- CYP1A2 inhibitors (e.g., cimetidine) – increased risk of flutamide toxicity
- Testosterone and other androgens – antagonistic effects
Pregnancy and Breastfeeding
Flutamide is contraindicated in women, especially during pregnancy and breastfeeding. It is classified as FDA Pregnancy Category D and can cause fetal harm and developmental abnormalities. It is not known whether flutamide is excreted in breast milk.
Drug Profile Summary
- Mechanism of Action: Competitive inhibitor of androgen receptors, blocking androgen effects on prostate cancer cells.
- Side Effects: Hot flashes, decreased libido, gynecomastia, diarrhea, nausea, hepatotoxicity (rare but serious).
- Contraindications: Hypersensitivity, severe liver disease, use in women and children.
- Drug Interactions: Anticoagulants, CYP1A2 inducers/inhibitors, androgens.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: 250 mg orally every 8 hours (total daily dose 750 mg).
- Monitoring Parameters: Liver function tests, prostate-specific antigen (PSA) levels.
Popular Combinations
Flutamide is commonly used in combination with LHRH agonists (e.g., leuprolide, goserelin) to treat prostate cancer. The LHRH agonist suppresses testicular androgen production, while flutamide blocks the action of any remaining androgens, providing a more complete androgen blockade.
Precautions
- General Precautions: Assess liver function before and during treatment. Monitor for signs of hepatotoxicity.
- Specific Populations: Flutamide is contraindicated in women and children. Use cautiously in elderly patients and those with pre-existing liver or cardiovascular disease.
- Lifestyle Considerations: Patients should avoid excessive alcohol intake, as it may exacerbate potential liver toxicity.
FAQs
Q1: What is the recommended dosage for Flutamide?
A: The standard adult dosage is 250 mg orally every 8 hours (750 mg total daily dose).
Q2: What are the common side effects?
A: Common side effects include hot flashes, decreased libido, gynecomastia, diarrhea, nausea/vomiting, and drowsiness.
Q3: What are the serious side effects to watch out for?
A: Serious side effects include liver damage (hepatotoxicity) and lung inflammation (interstitial pneumonitis). Contact a doctor immediately if signs of these conditions develop.
Q4: Can Flutamide be used in women?
A: No, flutamide is contraindicated in women, especially during pregnancy and breastfeeding.
Q5: What are the main drug interactions with Flutamide?
A: Significant interactions can occur with anticoagulants (e.g., warfarin), CYP1A2 inducers/inhibitors, and androgens.
Q6: How does Flutamide work in prostate cancer?
A: It blocks the action of androgens (like testosterone) by binding to androgen receptors, thereby inhibiting tumor growth.
Q7: What should patients be monitored for during treatment?
A: Monitor liver function tests regularly and watch for signs of hepatotoxicity, such as jaundice, dark urine, and fatigue.
Q8: Is Flutamide safe for patients with kidney problems?
A: No dosage adjustment is usually necessary, but caution is advised and careful monitoring is recommended.
Q9: What if a patient misses a dose?
A: Do not double the dose. Take the missed dose as soon as remembered, unless it is almost time for the next dose. Then, skip the missed dose and return to the regular schedule.
