II. Indications
-
Thionamide (Methimazole or Propylthiouracil) Indications
- Hyperthyroidism in children and adolescents
- Hyperthyroidism in Pregnancy (first trimester for PTU, Methimazole after)
- Severe Grave's Disease (e.g. Thyroid Storm)
- Subclinical Hyperthyroidism
- Methimazole is the preferred first-line Thionamide (over PTU) in most cases due to lower hepatotoxicity
- Reasons to use Propylthiouracil (PTU) instead of Methimazole
- Lactation
- Pregnancy (both PTU and Methimazole are Category D)
- Use Propylthiouracil (PTU) in first trimester
- Use Methimazole in second and third trimester
III. Mechanism
IV. Medications
- Propylthiouracil (PTU) 50 mg tablets
V. Dosing: Hyperthyroidism in Adults
- Target dose to Free T4 high end of normal range
-
Hyperthyroidism
- Start
- Subclinical Hyperthyroidism: 50 to 100 mg orally divided three times daily
- Moderate Hyperthyroidism: 100 to 150 mg orally three times daily
- Severe Hyperthyroidism: 200 to 400 mg orally three times daily
- Maintenance
- Titrate Propylthiouracil (PTU) dose down after 4 to 6 weeks
- Goal: maintain normal Thyroid function
- Dose: reduce to 50-100 mg/day in divided doses
- Start
-
Thyroid Storm
- See Thyroid Storm for full protocol (Beta Blockers, Thionamides, Iodine, Glucocorticoids)
- Load 500 to 1000 mg PO, PR, or per NG
- Maintenance 200 to 250 mg (up to 400 mg) every 4 hours PO, PR, or per NG
VI. Dosing: Hyperthyroidism in Children
- Target dose to Free T4 high end of normal range
-
Hyperthyroidism
- Start
- Age >10 years old: 50 to 100 mg orally three times daily
- Age 6 to 10 years: 50 mg orally three times daily
- Age <6 years (NOT FDA approved): 5 to 7 mg/kg/day divided every 8 hours
- Maintenance
- Titrate Propylthiouracil (PTU) dose down after 4 to 6 weeks
- Goal: maintain normal Thyroid function
- Dose: reduce to 1/3 to 1/2 of initial dose
- Start
VII. Adverse effects (3 per 1000 patients)
-
Drug-Induced Agranulocytosis (more common with PTU)
- Risk increases over age 40 years
- Occurs in 0.17% of those on Methimazole
- Presentation: Infection (e.g. Pharyngitis)
- Course
- Resolves within 2-3 weeks after drug stopped
- Severe, refractory course may occur
- Contraindication to further Antithyroid Drugs
-
Jaundice
- Cholestatic Jaundice
- Occurs more commonly with Methimazole
- Hepatitis
- Occurs with both Methimazole and Propylthiouracil (PTU)
- However, PTU is higher risk of liver injury, making Methimazole preferred in most cases
- Methimazole associated hepatitis
- Incidence: 3.17 per 1000 person-years
- Acute Hepatic Failure: 0.32 per 1000 person-years
- Propylthiouracil (PTU) is associated with severe liver injury
- Adults: 1 in 10,000
- Children: 1 in 2,000
- Occurs with both Methimazole and Propylthiouracil (PTU)
- Vasculitis
- Lupus-Like Syndrome
- Aplastic Anemia
- Rash or Pruritus
- Switch from PTU to Methimazole if severe
- Arthralgia or Polyarthritis
- Fever
- Congenital abnormalities possible with Methimazole
VIII. Safety
-
Lactation
- PTU is considered safe in Lactation (however Methimazole is preferred over PTU)
- Pregnancy Category D (applies to both PTU and Methimazole)
- Propylthiouracil is preferred in first trimester (due to congenital defects with Methimazole)
- Use Methimazole instead of PTU in second and third trimester
IX. Monitoring
- Repeat examination every 3 months
- Pregnancy Test before starting therapy
- Lab Testing while on antithyroid medications: Monthly for 6 to 12 months
- Complete Blood Count (CBC)
- Obtain at baseline
- Repeat if Pharyngitis or fever occur (need not be done without symptoms or signs)
- Liver Function Tests
- Obtain at baseline and if symptoms develop
- Thyroid Function Tests (baseline, then every 4-8 weeks, then after stabilizing, every 3 months)
- Thyroid Stimulating Hormone (TSH) after stabilizing, once on every 3 month schedule
- Free T4
- Free T3
- Complete Blood Count (CBC)
- Lab Testing after completing antithyroid medications
- Obtain Thyroid Function Tests every 1-3 months for 6-12 months
- Indications to discontinue medication (via taper)
- Total treatment course of 12-18 months AND
- TSH normalized for 6-12 months
- Indications to consider Thyroid ablation
- Inadequate suppression at 12 months from initiation
X. Efficacy
- Predictors of Relapse on Thionamides (occurs in 30-70% of cases within first year)
- Tobacco Abuse
- Large Goiter
- Thyroid Stmulating Antibody high at end of treatment
XI. Resources
- Propylthiouracil (DailyMed)
XII. References
Images: Related links to external sites (from Bing)
Related Studies
propylthiouracil (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
PROPYLTHIOURACIL 50 MG TABLET | Generic | $0.42 each |
Ontology: Propylthiouracil (C0033511)
Definition (NCI) | A thiourea derivative with antithyroid property. Propylthiouracil (PTU) interferes with the oxidation of iodine possibly by interaction with peroxidase or a peroxidase-mediated complex reaction, thereby inhibiting synthesis of thyroid hormones tri-iodothyronine (T3) and thyroxine (T4). In addition, this agent inhibits the Type I 5'-deiodinase (D1), an enzyme involved in the peripheral conversion of thyroxine to tri-iodothyronine. This results in decreased plasma triodothyronine concentrations and decreased entrance of thyroxine into cells thereby reducing thyroid hormone activity. |
Definition (MSH) | A thiourea antithyroid agent. Propythiouracil inhibits the synthesis of thyroxine and inhibits the peripheral conversion of throxine to tri-iodothyronine. It is used in the treatment of hyperthyroidism. (From Martindale, The Extra Pharmacopeoia, 30th ed, p534) |
Definition (PDQ) | A thiourea derivative with antithyroid property. Propylthiouracil (PTU) interferes with the oxidation of iodine possibly by interaction with peroxidase or a peroxidase-mediated complex reaction, thereby inhibiting synthesis of thyroid hormones tri-iodothyronine (T3) and thyroxine (T4). In addition, this agent inhibits the Type I 5'-deiodinase (D1), an enzyme involved in the peripheral conversion of thyroxine to tri-iodothyronine. This results in decreased plasma triodothyronine concentrations and decreased entrance of thyroxine into cells thereby reducing thyroid hormone activity. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39288&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39288&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C781" NCI Thesaurus) |
Concepts | Pharmacologic Substance (T121) , Nucleic Acid, Nucleoside, or Nucleotide (T114) |
MSH | D011441 |
SnomedCT | 3814009, 387203007 |
LNC | LP17868-8, MTHU012366 |
English | 6-Propyl-2-Thiouracil, Propylthiouracil, 4(1H)-Pyrimidinone, 2,3-dihydro-6-propyl-2-thioxo-, 6 Propyl 2 Thiouracil, propylthiouracil, Propylthiouracil preparation, anti-thyroid agents propylthiouracil (propylthiouracil), propylthiouracil (medication), PTU (propylthiouracil), PROPYLTHIOURACIL, Propylthiouracil [Chemical/Ingredient], 6-Propyl-2-thiouracil, PTU preparation, Propylthiouracil product, Propylthiouracil (product), Propylthiouracil (substance) |
Swedish | Propyltiouracil |
Spanish | preparado de propiltiouracilo, preparado de PTU, preparado de propiltiouracilo (producto), preparado de propiltiouracilo (sustancia), propiltiouracilo (producto), propiltiouracilo (sustancia), propiltiouracilo, Propiltiouracilo |
Czech | propylthiouracil |
Finnish | Propyylitiourasiili |
Russian | PROPILTIOURATSIL, ПРОПИЛТИОУРАЦИЛ |
Polish | Propylotiouracyl |
Japanese | チウラジール, プロピルチオウラシル, プロパジール |
French | Propylthiouracile |
German | Propylthiouracil |
Italian | Propiltiouracile |
Portuguese | Propiltiouracila |