From the Guidelines
Yes, it is contraindicated to trial propylthiouracil (PTU) in a patient with a history of carbimazole-induced agranulocytosis. These medications share a cross-reactivity risk because both PTU and carbimazole (as well as methimazole) are thionamide antithyroid drugs with similar mechanisms of action. A patient who has experienced agranulocytosis with one thionamide has approximately a 50% chance of developing the same serious adverse reaction with another drug in this class. Agranulocytosis is a potentially life-threatening condition characterized by severely decreased neutrophil counts, leaving patients vulnerable to serious infections, as noted in the management of hyperthyroidism in pregnancy 1. For patients with thionamide-induced agranulocytosis, alternative treatment options for hyperthyroidism should be pursued instead, such as radioactive iodine therapy or thyroidectomy. In emergency situations where rapid control of thyrotoxicosis is needed before definitive treatment, non-thionamide medications like beta-blockers, corticosteroids, and iodine solutions may be used temporarily. The risk of recurrent agranulocytosis outweighs any potential benefit of trying an alternative thionamide medication.
Key considerations in managing such patients include:
- Monitoring for signs of agranulocytosis, such as sore throat and fever, and promptly discontinuing the thioamide if these symptoms develop, as advised in the treatment of hyperthyroidism 1.
- Being aware of other potential side effects of thioamides, including hepatitis, vasculitis, and thrombocytopenia.
- Considering the goal of maintaining FT4 or FTI in the high-normal range using the lowest possible thioamide dosage, although this may not be applicable if thionamides are contraindicated.
- Exploring alternative treatments that do not carry the risk of cross-reactivity and agranulocytosis, prioritizing the patient's safety and quality of life.
From the Research
Propylthiouracil (PTU) Contraindication in Patients with Carbimazole-Induced Agranulocytosis
- The use of PTU in patients with a history of carbimazole-induced agranulocytosis is a concern due to the risk of cross-reactivity between the two drugs 2.
- A study reported a case of recurrent agranulocytosis following the consecutive administration of carbimazole and PTU, highlighting the potential risk of using PTU in patients who have developed agranulocytosis with carbimazole 2.
- Another study found that agranulocytosis persisted in two cases despite a change in therapy from PTU to methimazole, suggesting that cross-reactivity between antithyroid drugs can occur 3.
- The risk of agranulocytosis with PTU is a rare but potentially fatal complication, and patients who have developed agranulocytosis with one antithyroid drug may be at increased risk of developing it with another 4, 5, 6.
- In patients with a history of carbimazole-induced agranulocytosis, alternative treatments such as radioiodine or surgery may be considered to avoid the risk of cross-reactivity with PTU 5, 6.