Azathioprine 1–3mg/kg/day

Source: UK SPC (eMC) for Azathioprine 25 mg Film-Coated Tablets, §4.2 (https://www.medicines.org.uk/emc/product/11142/smpc). Specialist medical literature should be consulted for guidance on clinical experience in particular conditions. In transplantation, therapy should be maintained indefinitely even if only low doses are necessary, because of the risk of graft rejection. For other indications, when a therapeutic response is evident the maintenance dose should be reduced to the lowest level compatible with maintaining that response; if no improvement occurs within three months, consider withdrawing azathioprine (response may not be clinically apparent for weeks or months). DOSE-CRITICAL INTERACTION: with xanthine oxidase inhibitors such as allopurinol it is essential that only 25% of the usual azathioprine dose is given, because allopurinol decreases the rate of catabolism of azathioprine. TPMT: patients with inherited little or no thiopurine S-methyltransferase activity are at increased risk of severe toxicity from conventional doses and generally require substantial dose reduction; the optimal starting dose for homozygous deficient patients has not been established. Most heterozygous patients tolerate recommended doses but some require reduction; genotypic and phenotypic TPMT tests are available. NUDT15: patients with an inherited mutated NUDT15 gene are at increased risk of severe toxicity and generally require dose reduction, particularly homozygotes; genotypic testing may be considered before initiating therapy. In all cases close monitoring of blood counts is necessary — during the first eight weeks complete blood counts including platelets weekly, or more frequently if high dosage is used or severe renal and/or hepatic disorder is present, reducing later to at least every 3 months; interrupt treatment immediately at the first sign of an abnormal fall in blood counts. Liver function tests should be monitored routinely. ELDERLY: limited experience — monitor renal and hepatic function and consider dose reduction if there is impairment. ADMINISTRATION: may be taken with food or on an empty stomach but the method should be standardised; taking after meals appears to relieve nausea but may reduce oral absorption, so monitor therapeutic efficacy if given this way. Do not take with milk or dairy products — take at least 1 hour before or 2 hours after them. Some sections of the product information we used were incomplete — check the full SPC.

SPC §4.2 states that the posology in children is the same as in adults for both transplants and other indications, and the adult dose is expressed as a range (1 to 3 mg/kg bodyweight/day starting dose for other indications; up to 5 mg/kg/day day one then 1 to 4 mg/kg/day maintenance for transplants) — dosePerKg is therefore left null rather than picking one figure from a range. Children considered to be overweight may require doses at the higher end of the dose range, and close monitoring of response to treatment is recommended. Verify against a children's formulary and specialist literature before use; close haematological monitoring is mandatory.