Allopurinol

Registered South African indications:

• Prophylactic treatment of gout and hyperuricaemia associated with other conditions
• Treatment of hyperuricaemia
  - Associated with leukaemia
  - Resulting from radiotherapy or the use of anti-neoplastic medicines such as mercaptopurine
  - During treatment with diuretics of the thiazide or similar type

Contraindications

South African recommendations

• Hypersensitivity to allopurinol or to any of the excipients
• Severe renal disorder
• Severe hepatic disorder
• An acute gout attack
• Patients who have exhibited serious adverse effects from the medicine
• In children, except those with malignancy
• Pregnancy
• Lactation

Recommendations in other jurisdictions

• Hypersensitivity to the active substance(s) or to any of the excipients

Cautions

• Pregnancy (Recommendations in other jurisdictions)
• Breastfeeding (Recommendations in other jurisdictions)
• Mild to moderate renal impairment (South African recommendations)
• Renal impairment (Recommendations in other jurisdictions)
• Mild to moderate hepatic impairment (South African recommendations)
• Hepatic impairment (Recommendations in other jurisdictions)
• Elderly
• Skin rash 
• HLA-B*5801 allele 
• Chronic renal failure
• Hypertension 
• Cardiac insufficiency 
• Acute gout 
• Malignant disease and its treatment 
• Lesch-Nyhan syndrome
• Uric acid renal stones 
• Galactose intolerance 
• Lapp lactose deficiency 
• Glucose-galactose malabsorption

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

Dosages below include:

• South African registered indications and dosages

South African registered indications and dosages

Prophylactic treatment of gout and hyperuricaemia
- Associated with other conditions

• Oral (tab): Initial: 50mg, 12hrly; Increase dose as required up to 200-400mg, dly in divided doses. In severe conditions: Doses of up to 600mg may be necessary

Treatment of hyperuricaemia
- Associated with leukaemia

• Oral (tab): Initial: 200mg, 8hrly commencing if possible 2-3 days before radiotherapy or the commencement of treatment with antineoplastic medicines; Maintenance: Usually 300-400mg daily

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Fluid intake should be sufficient to maintain daily urinary volume above 2 litres

Paed. forms avail. in SA and covered in this monograph: tab

Dosages below include:

• South African registered indications and dosages

South African registered indications and dosages

Treatment of hyperuricaemia
- Associated with leukaemia

• Oral (tab): 8mg/kg, dly

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Allopurinol is contraindicated in children, except those with malignancy

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Fluid intake should be sufficient to maintain daily urinary volume above 2 litres

Pregnancy 

South African recommendations

• Contraindicated

Recommendations in other jurisdictions

• Caution
• There is inadequate evidence of the safety of allopurinol in human pregnancy, although it has been in wide use for many years without apparent ill consequence. Use in pregnancy only when there is no safer alternative and when the disease itself carries risks for the mother or unborn child

Breastfeeding 

South African recommendations

• Contraindicated
• Allopurinol should not be given to nursing mothers since it is excreted in breastmilk

Recommendations in other jurisdictions

• Caution; not recommended 
• Allopurinol and its metabolite oxypurinol is excreted in the human breast milk. Allopurinol during breastfeeding is not recommended. Reports indicate that allopurinol and oxypurinol are excreted in human breast milk.
• Concentrations of 1.4mg/litre allopurinol and 53.7mg/litre oxipurinol have been demonstrated in breast milk from a woman taking allopurinol 300mg/day. However, there are no data concerning the effects of allopurinol or its metabolites on the breastfed baby

Renal Impairment

South African recommendations

• Mild to moderate: Caution; dose adjustment recommended
  Allopurinol may be effective in patients with impaired renal function
  Dosage must be reduced in patients with renal impairment in proportion to the reduction in glomerular filtration
  Reduced doses should be used in patients with renal impairment
  Patients under treatment for hypertension or cardiac insufficiency, for example with diuretics or ACE inhibitors, may have some concomitant impairment of renal function and allopurinol should be used with care in this group
• Severe: Contraindicated

Recommendations in other jurisdictions

• Caution; dose adjustment recommended
  Allopurinol should be introduced at low dosage, e.g. 100mg/day, to reduce the risk of adverse reactions and increased only if the serum urate response is unsatisfactory

  Extra caution should be exercised if renal function is poor
  In severe renal insufficiency, it may be advisable to use less than 100mg per day or to use single doses of 100mg at longer intervals than one day
  The amount and frequency of dosage may require reduction as indicated by monitoring serum uric acid levels
  Schedule for guidance in adults: If facilities are available to monitor plasma oxipurinol concentrations, the dose should be adjusted to maintain plasma oxipurinol levels below 100micromol/litre (15.2mg/l)
  Renal dialysis: Allopurinol and its metabolites are removed by renal dialysis. If dialysis is required two or three times a week, an alternative schedule of 300-400mg allopurinol after each dialysis, with non in the interim, should be considered

Hepatic Impairment 

South African recommendations

• Mild to moderate: Caution; dose adjustment recommended
  Reduced doses should be used in patients with hepatic impairment
• Severe: Contraindicated

Recommendations in other jurisdictions

• Caution; dose adjustment recommended
  Reduced doses should be used in patients with impaired hepatic function. Periodic liver function tests are recommended during the early stages of therapy

Elderly

• Caution; no dose adjustment recommended
  Dose should be maintained at the minimum necessary to maintain normal serum and urinary urate levels

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Depression
• Coma
• Paralysis
• Neuropathy peripheral
• Paraesthesia
• Somnolence
• Headache Dysguesia

Cardiovascular Disorders

• Angina pectoris  
• Bradycardia
• Hypertension

Gastrointestinal Disorders

• Nausea and vomiting  
• Haematemesis
• Steotorrhoea
• Stomatitis
• Change of bowel habit

Hepatobiliary Disorders

• Abnormal liver function test  
• Hepatitis

Genitourinary Disorders

• Haematuria
• Azotaemia

Endocrine and Metabolic Disorders

• Diabetes mellitus
• Hyperlipidaemia
• Infertility male
• Erectile dysfunction
• Gynaecomastia

Skin and Subcutaneous Tissue Disorders

• Rash
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Angioedema
• Drug eruption
• Alopecia
• Hair colour changes  

Immune, Blood and Lymphatic System Disorders

• Agranulocytosis
• Aplastic anaemia
• Thrombocytopenia
• Hypersensitivity
• Angioimmunoblastic T-cell lymphoma

Sensory Disorders

• Cataract
• Visual impairment
• Maculopathy
• Vertigo

Others

• Oedema
• Malaise
• Asthenia
• Pyrexia
• Furuncle

• Warfarin
• Azathioprine
• 6-Mercaptopurine
• Vidarabine
• Salicylates
• Uricosuric agents
• Chlorpropamide
• Phenytoin
• Theophylline
• Ampicillin
• Amoxicillin
• Ciclosporin
• Cyclophosphamide
• Doxorubicin
• Bleomycin
• Procarbazine
• Mechloroethamine
• Didanosine
• Diuretics
• Angiotensin-converting enzyme inhibitors

• Renal function
• Hepatic function  
• Oxipurinol concentration
• Serum uric acid concentrations  
• Full blood count
• Hydration status

Allopurinol inhibits xanthine oxidase, the enzyme catalyzing the oxidation of hypoxanthine to xanthine and xanthine to uric acid.

Tablet 100mg

• Austell Allopurinol (Austell Laboratories)
• Lessuric 100 (Austell Laboratories)
• Puricos (Pharmacare)
• Sandoz Allopurinol (Sandoz)
• Zorikos 100 (Forrester Pharma)
• Zyloprim (Pharmacare) originator

Tablet 300mg

• Adco-Allopurinol (Adcock)
• Austell Allopurinol (Austell Laboratories)
• Lessuric 300 (Austell Laboratories)
• Lonol (Pharmacare)
• Puricos (Pharmacare)
• Sandoz Allopurinol (Sandoz)
• Zorikos 300 (Forrester Pharma)
• Zyloprim (Pharmacare) originator