Adverse Reactions in Antifolate-Treated Toxoplasmic Retinochoroiditis

Adv Exp Med Biol. 2018:1108:37-48. doi: 10.1007/5584_2018_262.

Abstract

This study seeks to define factors affecting the development of adverse reactions to intensive therapy of toxoplasmic retinochoroiditis with antifolate agents (pyrimethamine/sulfadoxine) and antibiotics followed by secondary antifolate prophylaxis. The study was of retrospective and observational nature. Medical files were reviewed of 551 patients suffering from ocular toxoplasmosis during 1994-2013. All patients were treated with the same protocol: 3-week intensive pyrimethamine/sulfadoxine plus antibiotic/steroid therapy. Three hundred and fourteen out of the 551 patients qualified for the subsequent 6-month long secondary antifolate prophylaxis. The type and occurrence rate of adverse reactions were taken into account. The probability of an adverse reaction during the intensive therapy phase was 33.4%. Hypertransaminasemia was the most common event observed in 24.6% of the patients, but it assumed a severe character in just 0.9%, with male gender and age over 25 years being the predisposing factors. Less common adverse effects included thrombocytopenia (8.3%), hypersensitivity skin reactions (3.0%), and abdominal pain (1.4%). The adverse effects of secondary antifolate prophylaxis, most commonly hypersensitivity skin reactions and hypertransaminasemia, followed by thrombocytopenia and abdominal pain, were observed in 4.9% of the patients. Ten of them (2.7%) had to discontinue the treatment while eight others continued with pyrimethamine alone without further adverse effects, which suggests that discontinuation of the sulfonamide decreased the propensity for adverse reactions. The treatment strategy in these patients differed from previous reports in that it used lower doses of pyrimethamine/sulfonamide, with no folinic acid supplementation. Nonetheless, the rate and severity of adverse events were no greater than those noticed with traditional regimens, with higher antifolate doses and folinic acid supplementation. We conclude that the dose and drug-mitigated treatment strategy we employed deserves consideration as a promising alternative to traditional treatments for ocular toxoplasmosis.

Keywords: Adverse reactions; Antifolates; Ocular toxoplasmosis; Retinochoroiditis; Risk factors; Secondary prophylaxis; Treatment.

MeSH terms

  • Anti-Infective Agents / adverse effects*
  • Anti-Infective Agents / therapeutic use
  • Female
  • Folic Acid Antagonists / adverse effects*
  • Folic Acid Antagonists / therapeutic use
  • Humans
  • Male
  • Pyrimethamine / adverse effects
  • Pyrimethamine / therapeutic use
  • Retrospective Studies
  • Sulfadoxine / adverse effects
  • Sulfadoxine / therapeutic use
  • Toxoplasmosis, Ocular / drug therapy*

Substances

  • Anti-Infective Agents
  • Folic Acid Antagonists
  • Sulfadoxine
  • Pyrimethamine