Propylthiouracil and ANCA vasculitis

• The Netherlands Pharmacovigilance Centre Lareb received seven well-documented reports on propylthiouracil and anti-neutrophil cytoplasmic antibody (ANCA) positive vasculitis.

  Propylthiouracil is an antithyroid agent and is indicated for the treatment of hyperthyroidism. It is pharmacologically categorized within the group thionamide or thioamide derivates. Propylthiouracil inhibits the synthesis of thyroid hormones through several ways, resulting in a reduction or disappearance of symptoms of hyperthyroidism.

  (ANCA-associated) Vasculitis (AAV)
  Vasculitis is a group of autoimmune diseases characterized by inflammation of the vessel walls.

  One of the various forms of vasculitis is Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), which is characterized by the presence of ANCAs. ANCAs are autoantibodies directed against enzymes in the granules of polynuclear neutrophils and monocytes. AAV affects the small and medium vessels, potentially causing damage to several organs.

  In terms of mechanism, it is still unclear how drugs can cause ANCA-associated vasculitis.

  Although Grave’s disease (and other autoimmune diseases) might have a predisposing role, antithyroid drug therapy could also play a role in developing ANCA positivity.

  SmPC
  Stopping the offending drug in time is important to prevent further disease progression and may be sufficient for patients with mild symptoms. Early detection of drug-induced AAV is important to prevent further disease progression. Therefore, attention is warranted for the association between propylthiouracil and drug-induced (ANCA-associated) vasculitis.

  ANCA-associated vasculitis is labeled as an adverse drug reaction of propylthiouracil in both the US and UK Summary of Product Characteristics (SmPCs). Possible addition of this adverse drug reaction to the Dutch SmPC of propylthiouracil is at European level being investigated.

  The full overview of the reports can be found here.