Propylthiouracil (PTU) Side Effects
PTU causes severe, potentially fatal hepatotoxicity that can occur rapidly and unpredictably, making it unsuitable for routine use, especially in children where it should be avoided entirely. 1
Life-Threatening Side Effects
Hepatotoxicity (Most Critical)
- Liver failure, need for transplantation, or death can occur in both adults and children, with particularly high risk in pediatric patients 1, 2
- Onset is rapid and unpredictable, typically within the first 6 months of therapy, making biochemical monitoring ineffective for prevention 1
- Clinical presentation ranges from asymptomatic transaminase elevation to fulminant hepatic failure 2
- Immediate discontinuation is mandatory if any hepatic symptoms develop: anorexia, pruritus, right upper quadrant pain, dark urine, pale stools, or jaundice 1
- Predominantly affects females (13 of 14 reported cases) 3
- Continued use after symptom onset can progress to fatal hepatic failure with encephalopathy 3
Agranulocytosis
- Occurs in 0.2% to 0.5% of patients, typically within the first 3 months of treatment 1
- Potentially life-threatening due to severe infection risk 1
- Patients must immediately report fever, chills, or sore throat 1
- Requires immediate drug discontinuation and bone marrow assessment 1
Vasculitis
- ANCA-positive vasculitis can result in severe complications and death 1
- Manifestations include: glomerulonephritis, leukocytoclastic cutaneous vasculitis, alveolar/pulmonary hemorrhage, cerebral angiitis, and ischemic colitis 1
- Requires immediate discontinuation and treatment with corticosteroids, immunosuppressants, or plasmapheresis 1
- Warning signs: red/purple skin changes, rash, pink or foamy urine, decreased urine output, shortness of breath, or coughing up blood 1
Pregnancy-Specific Risks
- Liver injury, liver failure, and maternal death have been documented in pregnant women taking PTU 1
- Two cases of in utero exposure resulting in newborn liver failure and death have been reported 1
- PTU crosses the placenta and can cause fetal goiter and cretinism 4, 1
- Despite these risks, PTU may be preferred in the first trimester only due to methimazole's teratogenic effects, with switching to methimazole recommended after the first trimester 4, 5
Common Side Effects
Hematologic (Beyond Agranulocytosis)
- Leukopenia, thrombocytopenia, and aplastic anemia (pancytopenia) 1
- Increased bleeding risk, particularly problematic during surgery or with concurrent anticoagulants 1
Gastrointestinal
- Nausea, vomiting, upper abdominal pain or tenderness 1
Endocrine
- Hypothyroidism requiring TSH and free T4 monitoring with dose adjustments 1
- Can cause fetal hypothyroidism when used in pregnancy 1
Dermatologic
- Itching, tingling, rash 1
- Stevens-Johnson syndrome (rare but potentially life-threatening): skin blisters, peeling rash, mouth sores 1
Neurologic and Musculoskeletal
- Dizziness, drowsiness, sleepiness (avoid driving/operating machinery) 1
- Headache, nerve pain 1
- Joint pain, muscle pain 1
Other Common Effects
- Loss or change in taste 1
- Hair loss 1
- Swelling (edema) of body, arms, legs 1
- Enlarged salivary glands or lymph nodes 1
Critical Clinical Pitfalls
Monitoring Limitations
- Routine liver function tests do NOT prevent severe hepatotoxicity due to its rapid, unpredictable onset 1
- Patient education about hepatic symptoms is more critical than laboratory monitoring 1
Pediatric Use
- PTU is not recommended for children except when methimazole is not tolerated and surgery/radioactive iodine are inappropriate 1
- No cases of liver failure have been reported with methimazole in pediatric patients, making it the clear first choice 1
Drug Interactions
- Potentiates warfarin (increased bleeding risk) 1
- Interacts with cardiac medications, antihypertensives, digoxin, and theophylline 1
Contraindicated Uses
- PTU has NO proven benefit in alcoholic liver disease and should never be used for this indication, as multiple randomized controlled trials showed no improvement in mortality or liver outcomes 4