Drug Interactions between azathioprine and balsalazide

MONITOR: Aminosalicylate derivatives (e.g., balsalazide, mesalamine, olsalazine, sulfasalazine) may potentiate the pharmacologic effects of purine antagonist antimetabolites (e.g., azathioprine, mercaptopurine, thioguanine). In vitro evidence indicates that aminosalicylate derivatives inhibit thiopurine methyltransferase (TPMT), the enzyme responsible for the metabolic clearance of cytotoxic thioguanine nucleotides that are formed from the antimetabolites in vivo. The interaction may be particularly severe in patients with low red blood cell TPMT activity. Even in the absence of an interaction, individuals with an inherited deficiency of TPMT are unusually sensitive to the myelosuppressive effects of purine antagonist antimetabolites and prone to developing rapid bone marrow suppression following the initiation of treatment with standard dosages. Between 0.3% to 1% of the population are TPMT-deficient and have low or no detectable TPMT activity (i.e. homozygous for low-activity alleles). Approximately 10% have intermediate TPMT activity (i.e. heterozygous for low-activity alleles), and they also tend to experience more bone marrow suppression than the majority of patients on usual dosages of the antimetabolites.

MANAGEMENT: Caution is advised if aminosalicylate derivatives must be used concomitantly with purine antagonist antimetabolites. Patients receiving the combination should be closely monitored for hematologic toxicity, and the antimetabolite dosage adjusted accordingly.