Propylthiouracil, and methimazole, and carbimazole-related hepatotoxicity

Expert Opin Drug Saf. 2014 Oct;13(10):1397-406. doi: 10.1517/14740338.2014.953796. Epub 2014 Aug 26.

Abstract

Introduction: Propylthiouracil (PTU) has been used for the treatment of hyperthyroidism since the 1940s, but over the years reports of significant hepatotoxicity have come forth, particularly in children. This led to a black box warning being issued by the US FDA in 2009, followed by a similar warning by the European Medicines Agency and the United Kingdom Medicines and Healthcare Regulatory Agency later that year.

Areas covered: This article provides a concise review of the data on hepatotoxicity associated with the currently available antithyroid drugs: PTU, methimazole (MMI) and carbimazole. The differences in mechanism are examined in detail, as well as clinical presentation, management and monitoring. Use in special populations and trends in use of antithyroid medication are also discussed.

Expert opinion: PTU is known to cause severe hepatic failure, particularly in children. Its use in children should be avoided. In adults, it is beneficial to use in the first trimester of pregnancy and thyroid storm. In the rest of the adult population, it should be used with caution. Carbimazole and MMI are associated with less severe hepatic injury and should be preferred when choosing thionamides as a treatment option.

Keywords: carbimazole; hepatotoxicity; methimazole; propylthiouracil.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Adult
  • Antithyroid Agents / adverse effects*
  • Antithyroid Agents / therapeutic use
  • Carbimazole / adverse effects
  • Carbimazole / therapeutic use
  • Chemical and Drug Induced Liver Injury / epidemiology
  • Chemical and Drug Induced Liver Injury / etiology*
  • Chemical and Drug Induced Liver Injury / physiopathology
  • Child
  • Drug Labeling
  • Female
  • Humans
  • Hyperthyroidism / drug therapy
  • Methimazole / adverse effects
  • Methimazole / therapeutic use
  • Pregnancy
  • Propylthiouracil / adverse effects*
  • Propylthiouracil / therapeutic use
  • Severity of Illness Index

Substances

  • Antithyroid Agents
  • Methimazole
  • Propylthiouracil
  • Carbimazole