Adverse Event Profile of Pyrimethamine-Based Therapy in Toxoplasmosis: A Systematic Review

Drugs R D. 2017 Dec;17(4):523-544. doi: 10.1007/s40268-017-0206-8.

Abstract

Introduction: Approximately a third of the population worldwide is chronically infected with Toxoplasma gondii. Pyrimethamine-based regimens are recommended for the treatment of toxoplasmosis.

Objective: The aim was to evaluate the safety profile of pyrimethamine-based treatment for the three main Toxoplasma manifestations: toxoplasmic encephalitis (TE), ocular toxoplasmosis, and congenital toxoplasmosis.

Methods: PubMed, Cochrane Library, and Google Scholar databases were searched through August 1, 2016. Randomized, observational, prospective/retrospective, and cohort studies were eligible. Thirty-one studies were included with a total of 2975 patients. Of these, 13 were in congenital toxoplasmosis (n = 929), 11 in ocular toxoplasmosis (n = 1284), and seven in TE (n = 687). Across manifestations, adverse event (AE)-related treatment discontinuation and/or change in therapy involved ≤37% of patients and occurred in >55% of studies: 100% for ocular toxoplasmosis, 57.1% for TE, and 61.5% for congenital toxoplasmosis. The most commonly observed AEs were bone marrow suppression, dermatologic, and gastrointestinal (GI). The prevalence of bone marrow suppression-related AEs was ≤50% in congenital toxoplasmosis, ≤42.7% in TE, and ≤9.0% in ocular toxoplasmosis. The frequency of GI and dermatologic AEs were ≤100 and ≤11.1%, respectively, for ocular toxoplasmosis, ≤10.7 and ≤17.9% for TE, and ≤10.8 and ≤2.1% for congenital toxoplasmosis. Steven-Johnson syndrome was reported in two patients with ocular toxoplasmosis and one with TE.

Conclusion: The AE profile associated with pyrimethamine-based treatments differed by each manifestation of toxoplasmosis and within a given manifestation. Hematologic AEs occurred across all manifestations indicating the importance of monitoring the blood of patients administered pyrimethamine-based regimens.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Drug-Related Side Effects and Adverse Reactions / blood
  • Drug-Related Side Effects and Adverse Reactions / etiology*
  • Humans
  • Infectious Encephalitis / drug therapy*
  • Pyrimethamine / adverse effects*
  • Pyrimethamine / pharmacokinetics
  • Pyrimethamine / therapeutic use
  • Toxoplasmosis, Cerebral / drug therapy*
  • Toxoplasmosis, Congenital / drug therapy*
  • Toxoplasmosis, Ocular / drug therapy*

Substances

  • Pyrimethamine