Flutamide

Registered South African indications:

• Advanced prostatic carcinoma (stage 4 untreated)

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients

Cautions

• Renal impairment
• Hepatic impairment
• Porphyria
• Cardiac disease or risk factors thereof
  - Myocardial infarction
  - Cardiac insufficiency
  - Serum lipoproteins
  - Insulin sensitivity
  - Obesity
• Pre-existing oedema or ankle swelling
• History of QT prolongation or risk factors thereof
• Diabetes
• High fracture risk
• Osteoporosis
• Risk factors for decreased bone mineral content and/or bone mass
  - Chronic alcohol and/or tobacco use
  - Presumed or marked family history of osteoporosis
  - Chronic use of agents that can reduce bone mass
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: tab

Used for the treatment of         

• Advanced prostatic carcinoma
  -  Monotherapy for advanced stage 4 untreated prostatic carcinoma
  - Advanced prostatic carcinoma in which suppression of testosterone effects is indicated
  - In combination with LHRH agonist on commencement of treatment or as adjunctive therapy in patients already receiving an LHRH agonist
  - Surgically castrated patients

Consult specialist for dosages and regimens

No information available

Pregnancy

• Not indicated for use in women
• Flutamide is intended only for use in male patients. Contraceptive measures should be taken during treatment
• Flutamide may cause foetal harm when administered to a pregnant woman
• In animal studies, the reproductive toxicity of flutamide was associated with the anti-androgenic activity of this agent. There was decreased 24-hour survival in the offspring of rats treated with flutamide at doses of 30, 100, or 200mg/kg/day (approximately 3, 9, and 19 times the human dose) during pregnancy. A slight increase in minor variations in the development of the sternebra and vertebra was seen in foetuses of rats at the two higher doses. Feminisation of the males also occurred at the two higher dose levels. There was a decreased survival rate in the offspring of rabbits receiving the highest dose (15mg/kg/day; equal to 1.4 times the human dose)
• No studies have been conducted in pregnant women. Therefore, the possibility that flutamide may cause foetal harm if administered to a pregnant woman must be considered

Breastfeeding

• Not indicated for use in women
• Flutamide is intended only for use in male patients. No studies have been conducted in breastfeeding women. Therefore, the possibility that flutamide may be present in the breast milk of breastfeeding women must be considered

Renal Impairment

• Caution; no dose adjustment recommended
  Further caution necessary in patients undergoing haemodialysis since flutamide is not cleared by haemodialysis

Hepatic Impairment

• Caution; no information available
  Long-term treatment should only be initiated after careful assessment of the individual benefits and risks

Elderly    

• No dose adjustment recommended

Porphyria Information

• Probably porphyrinogenic (PRP)

Drugs in Sport

• Permitted - No warnings

Adverse reactions reported in flutamide monotherapy

Central Nervous System Disorders

• Insomnia
• Anxiety
• Depression
• Dizziness
• Headache
• Somnolence
• Asthenia
• Decreased libido

Cardiovascular Disorders

• QT prolongation
• Hypertension
• Lymphoedema
• Hot flushes
• Chest pain

Respiratory Disorders

• Interstitial pneumonitis
• Dyspnoea
• Cough

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea
• Non-specific abdominal disorders
• Constipation
• Ulcer-like pain
• Dyspepsia
• Colitis
• Heartburn

Hepatobiliary Disorders

• Hepatitis
• Abnormal liver function test

Genitourinary Disorders

• Gynaecomastia
• Breast pain
• Breast tenderness
• Galactorrhoea
• Increased testosterone levels (reversible)
• Decreased sperm counts

Endocrine and Metabolic Disorders

• Increased appetite
• Anorexia
• Thirst

Musculoskeletal Disorders

• Muscle cramps
• Weakness

Skin and Subcutaneous Tissue Disorders

• Urticaria
• Pruritis
• Ecchymosis
• Alteration of hair growth pattern
• Loss of hair
• Photosensitivity reactions

Immune, Blood and Lymphatic System Disorders

• Herpes zoster
• Neoplasm of the male breast
• Lupus-like syndrome
• Oedema

Sensory Disorders

• Blurred vision

Adverse reactions reported in flutamide & LHRH analogue combination therapy 

Central Nervous System Disorders

• Depression
• Anxiety
• Numbness
• Confusion
• Nervousness
• Drowsiness
• Decreased libido

Cardiovascular Disorders 

• Hot flushes
• Hypertension
• Thromboembolism

Respiratory Disorders

• Pulmonary symptoms
• Dyspnoea
• Interstitial lung disease

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea
• Non-specific abdominal disorders
• Abdominal pain

Hepatobiliary Disorders

• Hepatitis
• Hepatic dysfunction
• Jaundice
• Cholestatic jaundice
• Hepatic encephalopathy
• Liver cell necrosis
• Hepatotoxicity with fatal outcome
• Changes in liver function
• Increased blood urea nitrogen
• Increased creatinine

Genitourinary Disorders

• Genitourinary tract symptoms
• Dysuria
• Changes in urinary frequency
• Change in urine colour (amber or yellow-green)
• Impotence
• Gynaecomastia

Endocrine and Metabolic Disorders

• Anorexia
• Hyperglycaemia
• Aggravation of diabetes mellitus

Musculoskeletal Disorders

• Neuromuscular symptoms
• Reduced bone mineral density
• Osteoporotic disorders
• Arthralgia
• Myalgia

Skin and Subcutaneous Tissue Disorders

• Rash
• Photosensitivity reactions
• Erythema
• Ulcers
• Bullous eruptions
• Epidermal necrolysis
• Injection site irritation

Immune, Blood and Lymphatic System Disorders

• Anaemia
• Leucopenia
• Thrombocytopenia
• Haemolytic anaemia
• Megalocytic anaemia
• Methemoglobinemia
• Sulfhaemoglobinaemia
• Macrocytic anaemia
• Oedema

• Theophylline
• Anticoagulants
• Warfarin
• Hepatotoxic agents
• QT prolonging agents
• Class IA antiarrhythmics
• Quinidine
• Disopyramide
• Class III antiarrhythmics
• Amiodarone
• Sotalol
• Dofetilide
• Ibutilide
• Methadone
• Moxifloxacin
• Antipsychotics

• Hepatic function
• Prostate specific antigen

None routine. Specific cases may require:

• Sperm count
• Blood glucose and/or HbA1C
• Bone mineral density
• Methemoglobin levels

Flutamide is a non-steroidal, highly specific, orally active anti-androgenic agent. The biological activity of oral flutamide is attributable to its pharmacologically active metabolite, hydroxyflutamide, which is believed to exert an anti-androgenic effect directly on the target tissues, either by inhibiting androgen uptake or by blocking cytoplasmic and nuclear binding of androgen.

Tablet 250mg

• Eulexin (Schering-Plough) originator
• Flutahexal (Sandoz)
• Flutaplex (Teva) 
• Spec Flutamide (Specpharm)