Safe use of thionamide class of medicinal products
05.06.2009
The U.S. Food and Drug Administration (FDA) reported on the new data indicating increased hepatotoxicity associated with the medicinal products containing propilthiouracile as active substance. It should be emphasised that no conclusion has been reached regarding the cause-effect relationship and that the FDA's information ought not to be interpreted as a recommendation to discontinue the treatment with propilthiouracile.
The FDA's Adverse Event Reporting System points to the hepatotoxicity risk, which includes serious conditions of liver failure and death, in adults and in children using propilthiouracile in comparison with those using thiamazole (methimazole).
Propilthiouracile and thiamazole belong to the thionamide class and, together with a predecessor of thiamazole - carbimazole, form a similarly efficient pharmacological therapy of thyrotoxicosis. The most frequently identified adverse reactions to antithyroid treatment are rashes and arthropathy, whereas serious adverse reactions such as agranulocytosis, hepatotoxicity and aplastic anemia are less frequent. The Agency for Medicinal Products and Medical Devices of the Republic of Croatia received reports on propilthiouracile and thiamazole related adverse reactions of skin reaction as a result of excessive sensitivity to the medicines, as well as agranulocytosis as the adverse reaction to thiamazole.
The recommendation is to carefully introduce therapy and select a medication, particularly in children, and to continuously monitor the patients in order to recognise the signs and symptoms of liver damage. Considering the possible development of agranulocytosis and a similar safety profile of propilthiouracile and thiazamole, it is not recommended to discontinue the therapy with propilthiouracile and to substitute it with thiamazole. Instead, it is necessary to assess the risk/benefit ratio individually.
We should bear in mind that, during the first trimester of pregnancy, use of propilthiouracile is more appropriate than use of thiamazole due to rare cases of embryopathy recorded in patients taking thiamazole.
The Agency reminds of the adverse reaction reporting obligation, itself continuing to actively monitor the safe use of this class of medicinal products.
