FLUTAN

Indications

• Advanced prostate cancer
• Metastatic prostate cancer
• Hormone-responsive malignancies

Dosage

Adults: The typical adult dose is 250 mg taken three times a day.

Mechanism of action

Flutamide acts by binding to androgen receptors, thereby blocking the effects of both endogenous and exogenous testosterone. It is a potent inhibitor of testosterone-stimulated prostatic DNA synthesis and inhibits the prostate's nuclear uptake of androgens.

Pharmacodynamics

Flutamide exhibits strong antiandrogenic effects, demonstrated in animal studies. It inhibits androgen uptake and/or nuclear binding of androgens in target tissues. Prostatic carcinoma, being androgen-sensitive, can be effectively treated by counteracting androgen effects, which flutamide achieves, leading to elevated plasma testosterone and estradiol levels following administration.

Pharmacokinetics

Flutamide is rapidly absorbed following oral administration. It undergoes extensive hepatic metabolism, primarily via cytochrome P450 enzymes. The elimination half-life is approximately 5 to 6 hours. The drug is excreted mainly via urine, with metabolites contributing to its pharmacological effects. Due to its hepatic metabolism, caution is advised in patients with liver impairment.

Contra-indications

• Severe hepatic impairment
• Serum transaminases greater than 2–3 times the upper limit of normal

Adverse effects

• Bone pain
• Breast abnormalities
• Cervical mucus increased
• Cholelithiasis
• Depression
• Erectile dysfunction
• Erythema nodosum
• Feminization
• Fluid retention
• Gynaecomastia
• Headaches
• Hypercalcaemia
• Hypertension
• Increased risk of thrombosis
• Jaundice
• Mood altered
• Nausea
• Skin reactions
• Sodium retention
• Testicular atrophy
• Uterine disorders
• Vomiting
• Weight changes
• Withdrawal symptoms
• Hepatic function abnormalities
• Alopecia
• Anxiety
• Cardiovascular disorder
• Chest pain
• Constipation
• Dizziness
• Dyspnoea
• Gastrointestinal disorders
• Insomnia
• Libido decreased
• Lymphoedema
• Photosensitivity reaction
• QT interval prolongation

Interactions

• Anti-androgens
• Diethylstilbestrol

Precautions

• Avoid excessive alcohol consumption
• Caution in diabetes
• Caution in patients with cardiac disease
• Caution in renal impairment
• Caution in hepatic impairment
• Monitor liver function before starting treatment
• Monitor bone mineral density before starting treatment

Pregnancy

In the first trimester, high doses associated with normal vaginal carcinoma and urogenital abnormalities.

Breast-feeding

Caution is advised as flutamide may affect the infant.

Storage

Store in a cool, dry place away from direct sunlight, at room temperature.

Formulations

• Tablets: 250 mg

Mechanism of action

Flutamide is a nonsteroidal antiandrogen that blocks the action of both endogenous and exogenous testosterone by binding to the androgen receptor. In addition Flutamide is a potent inhibitor of testosterone-stimulated prostatic DNA synthesis. Moreover, it is capable of inhibiting prostatic nuclear uptake of androgen.

Pharmacodynamics

Flutamide is a nonsteroidal antiandrogen. 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.