Allopurinol oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of allopurinol.
Drugs List
Therapeutic Indications
Uses
Gout (prophylaxis)
Hyperuricaemia
Prophylaxis against recurrent renal calcium stones
Reduction of urate/uric acid formation in conditions where urate/uric acid deposition has occurred (e.g. gouty arthritis, skin tophi, nephrolithiasis) or is a risk (e.g. treatment of malignancy which could result in acute uric acid nephropathy, or enzyme disorders leading to excess urate e.g. Lesch-Nyhan syndrome).
Management of 2,8-dihydroxyadenine (2,8-DHA) renal stones related to deficient activity of adenine phosphoribosyltransferase.
Management of recurrent mixed calcium oxalate renal stones in the presence of hyperuricosuria, when fluid, dietary and other measures have failed.
Dosage
Adults
Initial dose 100mg daily increasing only if serum urate does not decrease to desirable level.
Mild conditions: 100mg to 200mg daily.
Moderately severe conditions: 300mg to 600mg daily.
Severe conditions: 700mg to 900mg daily.
If dose is calculated on a mg/kg bodyweight basis, a dose of 2mg/kg to 10mg/kg daily should be used.
Children
Rarely indicated in children except in malignant conditions (in particular leukaemia) and certain enzyme disorders such as Lesch-Nyhan syndrome.
Children aged 15 to 18 years: (See Dosage; Adults).
Children aged 1 month to 15 years: 10mg/kg to 20mg/kg daily (up to a maximum of 400mg daily).
Patients with Renal Impairment
Severe renal impairment: Consider daily dose of less than 100mg, or single doses of 100mg at intervals of longer than one day.
Adjust dose to maintain plasma oxipurinol concentrations below 100micromol/l (15.2mg/l) if possible.
Allopurinol and its metabolites are removed by renal dialysis. If dialysis is required two to three times a week, consider giving 300mg to 400mg of allopurinol immediately after each dialysis with no doses in between.
Additional Dosage Information
If the daily dose exceeds 300mg and gastrointestinal intolerance occurs, consider divided doses.
Treatment of high urate turnover conditions e.g. neoplasia, Lesch-Nyhan syndrome
Existing hyperuricaemia and/or hyperuricosuria should be corrected with allopurinol before starting cytotoxic therapy. Ensure adequate hydration to maintain optimum diuresis and attempt alkalisation of the urine to increase solubility of urinary urate/uric acid. The dose of allopurinol should be at the lower end of the recommended regimen.
Contraindications
Galactosaemia
Precautions and Warnings
Breastfeeding
Glucose-galactose malabsorption syndrome
Hepatic impairment
Lactose intolerance
Pregnancy
Renal impairment
Thyroid dysfunction
Do not initiate during an acute attack of gout
Reduce dose in patients with hepatic impairment
Reduce dose in patients with renal impairment
Administer anti-inflammatory in first month:Reduces risk of gouty arthritis
Confirm HLA-B 5801 status in Han Chinese, Thai and Korean patients
Contains lactose
Advise patient to avoid aluminium hydroxide 3 hours before or after dose
Ensure patient has adequate fluid intake
Never rechallenge treatment after a severe hypersensitivity reaction
Advise patient to seek medical advice if severe skin reaction occurs
Discontinue if hypersensitivity reactions occur
Discontinue treatment if skin rash or other allergic reaction occurs
In conditions where the rate of urate formation is greatly increased (e.g. malignancy), the absolute concentration of xanthine in the urine could rise sufficiently to allow deposition in the urinary tract. This risk may be minimised by adequate hydration to achieve optimal urine dilution.
Adequate therapy with allopurinol will lead to dissolution of large uric acid renal pelvic stones, with the remote possibility of impaction in the ureter.
Hypersensitivity syndrome, Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported during allopurinol treatment. Carriers of the HLA-B*5801 allele appear to be at an increased risk, particularly those of Han Chinese, Thai or Korean descent. Pre-treatment screening for the allele is recommended in patient subgroups where this genotype has a high prevalence. Patients identified as carriers of the allele should not initiate treatment unless there is no alternative therapeutic option and benefits outweigh potential risks. If used, monitor closely for signs of hypersensitivity and inform patients to stop treatment immediately at the first appearance of any symptoms. Where genotyping is unavailable, decision to initiate treatment should be made on a risk benefit basis. It should be noted, SJS/TEN can also occur in patients negative for HLA-B*5801, irrespective of their ethnic origin.
Pregnancy and Lactation
Pregnancy
Use allopurinol with caution during pregnancy.
Manufacturers advise that although allopurinol has been widely used during pregnancy without apparent harm, there is insufficient evidence of safety and it should only be used if there is no safer alternative and the condition itself poses a risk to the mother and baby.
Animal studies have shown conflicting results regarding foetal abnormalities.
Lactation
Use allopurinol with caution during breastfeeding.
Manufacturers state that allopurinol is not recommended during breastfeeding.
Allopurinol and its metabolite oxipurinol are excreted in human breast milk, however the effect on the infant is unknown.
Side Effects
Agranulocytosis
Alopecia
Altered bowel habit
Altered liver function tests
Anaphylaxis
Angina
Angioedema
Angioimmunoblastic lymphadenopathy
Aplastic anaemia
Arthralgia
Asthenia
Ataxia
Bradycardia
Cataracts
Coma
Depression
Diabetes mellitus
Discolouration of hair
Drug rash with eosinophilia and systemic symptoms (DRESS)
Eosinophilia
Erectile dysfunction
Exfoliative rash
Fever
Fixed drug eruption
Furunculosis
Granulomatous hepatitis
Gynaecomastia
Haematemesis
Haematuria
Headache
Hepatic impairment
Hepatic necrosis
Hepatitis
Hyperlipidaemia
Hypersensitivity reactions
Hypertension
Lymphadenopathy
Macular abnormalities
Maculopapular rash
Malaise
Male infertility
Nausea
Neuropathy
Oedema
Paraesthesia
Paralysis
Pruritic rash
Purpura
Rash
Renal impairment
Somnolence
Steatorrhoea
Stevens-Johnson syndrome
Stomatitis
Taste disturbances
Thrombocytopenia
Toxic epidermal necrolysis
Vasculitis
Vertigo
Visual disturbances
Vomiting
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: May 2019
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
Summary of Product Characteristics: Uricto 100mg tablets. Ennogen Ltd. Revised January 2018.
Summary of Product Characteristics: Uricto 300mg tablets. Ennogen Ltd. Revised January 2018.
Summary of Product Characteristics: Zyloric tablets 100mg. Aspen. Revised February 2019.
Summary of Product Characteristics: Zyloric tablets 300mg. Aspen. Revised February 2019.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 10 May 2019
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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