Fatal Intoxications Due to Administration of Isosorbide Tablets Contaminated with Pyrimethamine.

In January 2012, 664 cases of pyrimethamine toxicity and 151 deaths were reported among cardiac patients that had recently received free medicines from pharmacy of Punjab Institute of Cardiology, Lahore, Pakistan. These patients, ages ranged from 58 to 75 years, were prescribed simvastatin, clopidogrel, aspirin soluble, isosorbide mononitrate, and amlodipine. On examination of medications being given to them, it was found that a particular batch of isosorbide mononitrate tablets was contaminated with 50 mg pyrimethamine. Cardiac patients were taking isosorbide contaminated with pyrimethamine twice daily (100 mg pyrimethamine/day), whereas therapeutic dose of pyrimethamine for malaria is 25 mg/week. Postmortem urine, cardiac blood, and femoral blood specimens of three deceased males were submitted to author's laboratory for analysis. Postmortem toxicological analysis revealed that pyrimethamine concentration fell within the range of 1-10 µg/mL by liquid chromatography. Clinical, autopsy, histopathological, and toxicological findings strongly suggested toxicity due to pyrimethamine accumulation that resulted in deaths of these cardiac patients.

Ronidazole toxicosis in 3 society finches (Lonchura striata).

A group of finches were accidentally overdosed with ronidazole, a 5-nitroimidazole used for treatment of trichomoniasis. Finches developed neurologic signs on the third day of treatment and were euthanized (or died). Three finches were submitted for necropsy. Focal necrosis of the cerebellar nucleus was seen in all 3 birds, as characterized by neuronal necrosis, vacuolation of the neuropil, gemistocytic astrocytosis, hemorrhage, and axonal swelling (spheroids) with demyelination. The liver from 1 finch was analyzed for ronidazole and its metabolite, 2-hydroxymethyl-1-methyl-5-nitroimidazole, by high-performance liquid chromatography-mass spectrometry. Ronidazole was detected in the liver tissue at 2,700 ng/g (wet weight), and 2-hydroxymethyl-1-methyl-5-nitroimidazole was detected at 140 ng/g (wet weight).

Improving the safety of intravenous admixtures: lessons learned from a Pentostam overdose.

CASE STUDY: Weaknesses in the multistep process of admixture preparation and administration resulted in a patient with cutaneous leishmaniasis (CL) receiving a 10-fold intravenous (IV) overdose of Pentostam (sodium stibogluconalte), a rarely used drug. LESSONS LEARNED: A review of this adverse event resulted in five recommendations: (1) Provide staffing continuity among pharmacists and pharmacy technicians preparing and nurses administering the admixture; (2) Take time to ensure thorough and deliberative consideration ofquestions or concerns about admixture preparation; (3) Use due diligence in performing double checks of admixture calculations; (4) Know the drug and seek clarification when appropriate; and (5) Examine label information carefully. PROGRESS UPDATE: Two changes were made to improve patientsafety. First, a form was developed to accompany the preparation of complex IV drugs, including chemoltherapy solutions and nonformulary IV admixtures; the form is consistently used. Second, the pharmacy service developed information sheets for 12 high-risk drugs frequently used in IV admixtures. DISCUSSION: The medical center had processes in place to prevent medication errors, yet an error occurred nonetheless. Weaknesses were identified in staff communication, quality assurance checks, and product labeling. Also, nurses and pharmacists had less than adequate information about new or unusually dosed medications.

Sodium stibogluconate (pentostan) overdose in a patient with acquired immunodeficiency syndrome.

A 32-year-old man with acquired immunodeficiency syndrome (AIDS) admitted to the hospital for treatment of visceral leishmaniasis was inadvertently given 10 times the prescribed first dose of sodium stibogluconate ([Sb] 6.5 g instead of 0.65 g). He experienced no immediate major toxicity during the first 48 hours, but a significant rise of pancreatic enzyme activities was observed (amylase at 10 times the upper limit of normal, lipase at 50 times the upper limit of normal) without clinical signs or indications on computed tomography (CT) of pancreatitis. The third day after the overdose, he developed appendicitis, which appeared coincidental; he recovered uneventfully from surgery. Most of the overdose of Sb was eliminated within the first few hours. Pharmacokinetics remained linear; the rapid, long elimination half-lives (2.7 hours and 54 hours, respectively) were similar to those in previously published results. The administration of a chelating agent, dimercaptosuccinic acid (DMSA), 72 hours after the Sb overdose did not modify the pharmacokinetics of the medication.