Methimazole is an anti-thyroid medication used to treat hyperthyroidism by inhibiting the production of thyroid hormones. Despite its effectiveness, it is listed by NIOSH as a hazardous drug, necessitating caution in its use and handling.
The NIOSH Criteria for a Hazardous Drug
NIOSH classifies drugs as hazardous if they exhibit characteristics such as carcinogenicity, teratogenicity, reproductive toxicity, organ toxicity at low doses, genotoxicity, or a toxicity profile similar to existing hazardous drugs. Methimazole is included due to its developmental and reproductive toxicity risks.
Reproductive and Developmental Risks (Teratogenicity)
A primary reason for methimazole's hazardous classification is its potential to harm a fetus during pregnancy, particularly in the first trimester. It crosses the placenta and is linked to methimazole embryopathy, a pattern of birth defects. These defects can include aplasia cutis, craniofacial malformations, and gastrointestinal malformations. Due to these risks, propylthiouracil (PTU) is often used in the first trimester, although methimazole may be preferred later in pregnancy as PTU carries a higher risk of severe liver damage.
Other Health Risks and Toxicities
Methimazole can also cause other serious adverse effects, including a potentially fatal reduction in white blood cells (agranulocytosis), liver damage (hepatotoxicity), and inflammation of blood vessels (vasculitis). Studies in rats have also indicated a potential link to thyroid carcinoma at high doses, though its relevance to humans is unclear.
Risks for Healthcare Workers and Caregivers
Handling methimazole can pose risks to healthcare workers and caregivers through skin contact, inhalation of dust, or accidental ingestion. USP General Chapter <800> provides guidelines for safe handling to minimize exposure. Precautions include avoiding breaking tablets, wearing gloves when handling the medication (especially broken tablets or topical forms), washing hands after administration, and pregnant individuals avoiding handling the drug.
Comparison: Methimazole vs. Propylthiouracil (PTU)
Both methimazole and PTU treat hyperthyroidism but have different safety profiles, particularly during pregnancy.
| Feature | Methimazole | Propylthiouracil (PTU) |
|---|---|---|
| First Trimester Use | Not recommended due to higher risk of specific congenital malformations (methimazole embryopathy). | Preferred choice as it's associated with a lower risk of birth defects compared to methimazole. |
| Second/Third Trimester | Often the preferred drug. | Use is often avoided due to a black box warning for severe liver toxicity. |
| Liver Toxicity Risk | Lower risk compared to PTU, especially in pediatric patients. | Higher risk of severe hepatotoxicity, including fatal cases and need for liver transplant. |
| Dosing Frequency | Typically once daily. | Often requires multiple daily doses. |
Conclusion
Methimazole is classified as a hazardous drug due to its risk of serious birth defects and other potential toxicities like agranulocytosis and liver damage. This classification emphasizes the need for careful evaluation by doctors, particularly for women who could become pregnant, and the implementation of strict safe-handling procedures for anyone in contact with the medication. While vital for hyperthyroidism treatment, awareness of its hazardous nature is crucial for safety.
For more information on hazardous drug guidelines, you can visit the NIOSH website.
