An Outbreak of Pyrimethamine Toxicity in Patients with Ischaemic Heart Disease in Pakistan

• DOI: 10.1111/bcpt.12206
• Publication Date: 2014-02-03T16:44:16Z
• Authors: Muhammad Zaman Kh...; Hafiz Ijaz Ahmad; Javed Akram; Noshin Wasim Yusuf; Umair Kamran
• Keywords: Adult; Aged, 80 and over; Male; 2. Zero hunger; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Platelet Count; Myocardial Ischemia; Comorbidity; Middle Aged; 3. Good health; Leukocyte Count; 03 medical and health sciences; Logistic Models; Pyrimethamine; 0302 clinical medicine; Multivariate Analysis; Humans; Female; Pakistan; Isosorbide; Prospective Studies; Drug Contamination; Aged

AbstractWe investigated an outbreak of darkening of skin, bleeding from multiple sites, leucopenia and thrombocytopenia in ischaemic heart disease patients. Case patients were defined as patients who had received medicines from the pharmacy ofPunjabInstitute ofCardiology between 1December 2011 and 12January 2012 and who developed any one of the following: darkening of skin, bleeding from any site, thrombocytopenia and leucopenia. Clinical and drug‐related data were abstracted. All 664 case patients had received iso‐sorbide‐mono‐nitrate contaminated with about 50 mg of pyrimethamine, and 151 (23%) died. The median age of 117 patients admitted atJinnahHospitalLahore was 57 years (range, 37–100) and 92 (79%) were male. The median time from intake of medicine to presentation was 37 days (range 13–72). Symptoms and signs included bleeding (in 95% of the patients), skin hyperpigmentation (in 61%), diarrhoea (in 53%) and abdominal pain (in 48%). At presentation, the median white cell count was 2.3 × 109/L (range, 0.1 × 109–16.0 × 109), the median hemoglobin concentration was 109 g/L (range 58–169) and the median platelet count was 18 × 109/L (range, 0 × 109–318 × 109). Bone marrow examination revealed trileneage dysplasia and severe megaloblastosis. The predictors of mortality included presentation prior to 15January 2012, age more than 57 years, hypotension and leukocyte count less than 1.5 × 109/L. None of the patients who died receivedCalcium folinate because all deaths occurred prior to contaminant identification. We describe an outbreak of pyrimethamine toxicity in ischaemic heart disease patients receiving medicines from a single pharmacy due to accidental contamination of iso‐sorbide mono‐nitrate tablets at industrial level. Late recognition of illness resulted in high mortality.