What are the side effects of Propylthiouracil (PTU)?

Side Effects of Propylthiouracil (PTU)

PTU carries serious risks of severe liver injury including liver failure and death, particularly in children, and should be discontinued immediately if any signs of hepatic dysfunction appear. 1

Life-Threatening Side Effects

Hepatotoxicity (Most Critical)

• Severe liver injury, liver failure, liver transplantation, or death can occur in both adults and children, with particularly high risk in pediatric patients 1, 2
• Liver failure occurs in approximately 0.03% of PTU-exposed patients, with PTU causing 2.4 times higher odds of liver injury compared to methimazole and 3.96 times higher odds of elevated transaminases 3, 4
• Onset is rapid and unpredictable, typically within the first 6 months of therapy, making routine biochemical monitoring ineffective at preventing severe outcomes 1, 5
• Immediate discontinuation is mandatory if patients develop: fever, loss of appetite, nausea, vomiting, fatigue, itching, right upper abdominal pain, dark urine, pale stools, or jaundice 1
• In pregnancy, PTU can cause maternal liver failure and death, as well as in utero exposure leading to neonatal liver failure and death 1

Agranulocytosis

• Occurs in 0.2-0.5% of patients (approximately 0.16% of PTU-exposed individuals, with PTU showing 0.27% incidence vs 0.11% for methimazole) 1, 3
• Typically develops within the first 3 months of therapy and is potentially life-threatening 1, 3
• Patients must immediately report fever, chills, or sore throat 6, 1
• Obtain complete blood count immediately and discontinue PTU if agranulocytosis is suspected 6, 1

Vasculitis

• Can result in severe complications and death, including ANCA-positive vasculitis 1
• Manifestations include: glomerulonephritis, leukocytoclastic cutaneous vasculitis, alveolar/pulmonary hemorrhage, cerebral angiitis, and ischemic colitis 1
• Discontinue immediately if patients develop: skin changes (red/purple discoloration, rash, pain, swelling), urinary changes (pink/dark/foamy urine, decreased output), or respiratory symptoms (shortness of breath, coughing up blood) 1

Common Side Effects

Gastrointestinal

• Nausea, vomiting, and upper stomach pain or tenderness are among the most frequently reported adverse effects 1

Musculoskeletal

• Joint pain, muscle pain, and nerve pain occur commonly 1

Dermatologic

• Itching, tingling, loss of hair, and skin rash 1
• Severe skin reactions including Stevens-Johnson syndrome can occur rarely but may be life-threatening 1

Neurologic

• Headache, sleepiness, dizziness, and drowsiness (patients should avoid driving or operating machinery if affected) 1

Other Common Effects

• Loss or change in taste, enlarged salivary glands or lymph nodes, and swelling (edema) 1

Additional Serious Risks

Hematologic Complications

• Leukopenia, thrombocytopenia, and aplastic anemia (pancytopenia) may occur 1
• Increased bleeding risk, especially with surgery or concurrent anticoagulant use 1

Thyroid Dysfunction

• Hypothyroidism can develop, requiring routine TSH and free T4 monitoring with dose adjustments 1
• PTU crosses the placenta and can cause fetal goiter and cretinism in pregnant women 1

Critical Monitoring and Management Points

Timing of Adverse Events

• 83% of serious side effects (agranulocytosis and liver failure) occur within 3 months of starting treatment 3
• 25% of cases occur during hyperthyroidism relapse 3

Special Population Considerations

• PTU is NOT recommended for pediatric patients except when methimazole is not tolerated and surgery/radioactive iodine are inappropriate, due to higher risk of liver failure 1, 5
• In pregnancy, PTU is preferred only in the first trimester due to lower teratogenic risk compared to methimazole, but should be switched to methimazole in second and third trimesters due to hepatotoxicity risk 7, 4
• Birth defects occur in 3.4% of PTU-exposed pregnancies, which is 75 times more common than maternal agranulocytosis or liver failure during pregnancy 3

Drug Interactions

• PTU affects warfarin (increased bleeding risk), cardiac medications, antihypertensives, digoxin, and theophylline 1