Toxicological considerations for antithyroid drugs in children

Expert Opin Drug Metab Toxicol. 2011 Apr;7(4):399-410. doi: 10.1517/17425255.2011.557068. Epub 2011 Feb 17.

Abstract

Introduction: Propylthiouracil (PTU), methimazole (MMI) and carbimazole are indicated for the treatment of hyperthyroidism in adult and pediatric patients. The aim of this review is to present all the relevant information regarding the use of antithyroid drugs (ATD) in pediatric thyrotoxic cases, the pediatric toxicology of ATD and the warning which has recently been issued for PTU by the FDA.

Areas covered: Epidemiology, diagnosis and treatment of pediatric thyrotoxicosis are all presented in this article. The authors also extensively discuss the details regarding the pharmacology, bioactivation, biodisposition, bioavailability and pharmacokinetic properties of the two main ATD (MMI and PTU).

Expert opinion: The FDA recently reported that use of PTU is associated with a higher risk for clinically serious or fatal liver injury compared to MMI in both adult and pediatric patients. They also found that congenital malformations were reported approximately three times more often with prenatal exposure to MMI compared with PTU and especially with the use of MMI during the first trimester of pregnancy. The authors believe that PTU should not be used in pediatric patients unless the patient is allergic to or intolerant of MMI, and there are no other treatment options available. That being said, PTU may be the treatment of choice during, and just before, the first trimester of pregnancy.

Publication types

  • Review

MeSH terms

  • Agranulocytosis / complications
  • Animals
  • Antithyroid Agents / therapeutic use
  • Antithyroid Agents / toxicity*
  • Carbimazole / therapeutic use
  • Carbimazole / toxicity*
  • Child
  • Child, Preschool
  • Evidence-Based Medicine
  • Female
  • Graves Disease / drug therapy
  • Humans
  • Hyperthyroidism / drug therapy
  • Liver Failure / complications
  • Methimazole / therapeutic use
  • Methimazole / toxicity*
  • Pregnancy
  • Propylthiouracil / therapeutic use
  • Propylthiouracil / toxicity*
  • Randomized Controlled Trials as Topic
  • Thyrotoxicosis / drug therapy
  • Vasculitis / complications

Substances

  • Antithyroid Agents
  • Methimazole
  • Propylthiouracil
  • Carbimazole