Sulfasalazine: Interference with dihydronicotinamide-adenine dinucleotide/ dihydronicotinamide-adenine dinucleotide phosphate (NADH/NADPH) reaction assays


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In general, sulfasalazine is indicated for the treatment of ulcerative colitis, Crohn’s disease and rheumatoid arthritis.



The National Pharmaceutical Regulatory Agency (NPRA) received information from the European Medicines Agency (EMA) on the association of sulfasalazine with interference of dihydronicotinamide-adenine dinucleotide/ dihydronicotinamide-adenine dinucleotide phosphate (NADH/NADPH) reaction assays. The product registration holders were requested by EMA to amend the product information to include this new safety information. This action was taken based on available data from Eudravigilance and the literature.1

Sulfasalazine is metabolised to sulfapyridine and both compounds show strong ultraviolet absorbance at wavelength 340 nm, which is the same wavelength used for measuring NADH or NADPH in several assays, giving rise to possible interference. Among assays which use NADH and NADPH in the reaction include alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase-muscle/brain (CK-MB), glutamate dehydrogenase (GLDH), ammonia, thyroxine and glucose.2


Adverse Drug Reaction Reports

NPRA has received 246 reports with 471 adverse events suspected to be related to sulfasalazine. However, no event related to interference with NADH/NADPH reaction assays has been reported.3


Advice for Healthcare Professionals



  1. European Medicine Agency (2019). PRAC recommendations on signals.
  2. Marianne L. Bergmann and Anne Schmedes (2016): Therapeutic concentrations of sulfasalazine interfere with ammonia, but not with alanine-aminotransferase determination in enzymatic tests. Scandinavian Journal of Clinical and Laboratory Investigation.
  3. The Malaysian Adverse Drug Reactions database, NPRA [Accessed: November 2019]



This publication is aimed at health professionals. The information is meant to provide updates on medication safety issues, and not as a substitute for clinical judgement. While reasonable care has been taken to verify the accuracy of the information at the time of publication, the NPRA shall not be held liable for any loss whatsoever arising from the use of or reliance on this publication.