propylthiouracil
Regulatory sources consulted
Approved indications
- Graves disease or toxic multinodular goiter when methimazole is not tolerated and radioactive iodine or surgery is unsuitable; preparation for thyroidectomy or radioiodine in those circumstances.
Contraindications
Absolute
- Hypersensitivity to propylthiouracil or components.
Clinical warnings
- Boxed warning · Serious warning: it may cause acute liver injury, liver failure, transplantation, or death. Reserve it for methimazole intolerance or when surgery/radioiodine is unsuitable; stop for hepatic symptoms. — FDA, set_id 53c5f586-3e72-479d-89ba-379683c8f6ba
- Major warning · It may cause agranulocytosis. For fever, sore throat, or infection, stop and obtain an urgent blood count. Vasculitis and drug-induced lupus have also been reported. — FDA, set_id 53c5f586-3e72-479d-89ba-379683c8f6ba
Drug interactions
- ModerateOral anticoagulants
Mechanism: Changes in thyroid status may alter anticoagulant response.
Recommendation: Monitor INR and adjust the anticoagulant when starting, titrating, or stopping.
FDA, set_id 53c5f586-3e72-479d-89ba-379683c8f6ba
Adverse events
Common (≥1%)
Rash, itching, nausea, vomiting, arthralgia, and taste disturbance
Rare but serious
Liver failure, agranulocytosis, aplastic anemia, and ANCA vasculitis
Pregnancy and lactation
It may be the antithyroid drug of choice when treatment is needed during or just before the first trimester; use the lowest effective dose and reassess afterward. It passes into milk and requires a clinical decision and infant thyroid monitoring.
Recent literature (PubMed)
Drug-induced vasculitis (DIV) is a rare form of vasculitis related to the use of various drugs. DIV primarily affects small to medium size vessels, but it can potentially involve vessels of any size. Differentiating between primary systemic vasculitis and DIV can be challenging; however, it is crucial, so that the offending agent can be discontinued promptly. The clinical phenotype of DIV is protean and depends on the size of the affected vessels. It ranges from arthralgias, to an isolated cutaneous rash, to severe single or multi-organ involvement. While withdrawal of the offending drug is the most important step in management, a significant number of patients require immunosuppressive therapy for varying periods of time. DIV can affect any vascular bed size, leading to protean vasculitic syndromes. Increased awareness among general practitioners, specialty, and subspecialty physicians is crucial for early recognition, and withdrawal of drug for better outcomes.
Hyperthyroidism caused by Graves' disease (GD) is a relatively rare disease in children. Treatment options are the same as in adults - antithyroid drugs (ATD), radioactive iodine (RAI) or thyroid surgery, but the risks and benefits of each modality are different. The European Thyroid Association guideline provides new recommendations for the management of pediatric GD with and without orbitopathy. Clinicians should be alert that GD may present with behavioral changes or declining academic performance in children. Measurement of serum TSH receptor antibodies is recommended for all pediatric patients with hyperthyroidism. Management recommendations include the first-line use of a prolonged course of methimazole/carbimazole ATD treatment (3 years or more), a preference for dose titration instead of block and replace ATD, and to avoid propylthiouracil use. Where definitive treatment is required either total thyroidectomy or RAI is recommended, aiming for complete thyroid ablation with a personalized RAI activity. We recommend avoiding RAI in children under 10 years of age but favor surgery in patients with large goiter. Pediatric endocrinologists should be involved in all cases.
The purpose of this meta-analysis was to assess the safety of the anti-thyroid drugs (ATDs) propylthiouracil (PTU) and methimazole (MMI) in the treatment of hyperthyroidism during pregnancy. From inception until June 2, 2022, all available studies were searched in PubMed, Web of Science, Cochrane, EBSCO, Embase, Scopus, and CNKI. Thirteen articles satisfying the inclusion criteria were examined. Our meta-analysis indicated that pregnant women treated with MMI had a higher risk of congenital anomalies than those treated with PTU (OR 0.80, 95%CI 0.69-0.92, P = 0.002, I2 = 41.9%). Shifting between MMI and PTU during pregnancy did not reduce the risk of birth defects compared to PTU alone (OR 1.18, CI 1.00 to 1.40, P = 0.061, I2 = 0.0%). There were no statistically significant differences in hepatotoxicity (OR 1.54, 95%CI 0.77-3.09, P = 0.221, I2 = 0.0%) or miscarriage (OR 0.89, 95%CI 0.72-1.11, P = 0.310, I2 = 0.0%) between PTU and MMI exposure. The study confirmed propylthiouracil is a safer alternative to methimazole for treating hyperthyroidism in pregnant women, and it is appropriate to treat maternal thyroid disease with PTU during the first trimester of pregnancy. However, it is not clear whether switching between propylthiouracil and methimazole is a better option than treating PTU alone during pregnancy. Further studies on this matter may be needed to develop new evidence-based guidelines for the treatment of pregnant women with hyperthyroidism.