II. Indications
- Hyperthyroidism in children and adolescents
- Pregnancy (PTU)
- Severe Grave's Disease (e.g. Thyroid Storm)
- Subclinical Hyperthyroidism
III. Mechanism
- Thionamides block T3 and T4 synthesis (by inhibiting Thyroid peroxidase)
IV. Dose: Grave's Disease
- Target dose to Free T4 high end of normal range
- Methimazole (Tapazole)
- Preferred first-line agent
- Advantages over Propylthiouracil (PTU)
- Once daily dosing
- Decreases T4 and T3 levels more rapidly
- Much safer than PTU
- Lower risk of Agranulocytosis at moderate doses
- Does not carry the same liver toxicity risk as PTU
- Dosing: Hyperthyroidism
- Start: 10-30 mg PO qd
- Titrate Methimazole dose down after 4-6 weeks
- Goal: maintain normal Thyroid function
- Dose: reduce to 5-10 mg per day
- Dosing: Other
- Subclinical Hyperthyroidism: 5 mg PO qd
- Propylthiouracil (PTU)
- Indications (reasons to use PTU instead of Methimazole)
- Lactation
- Pregnancy (both PTU and Methimazole are Category D)
- Use PTU in first trimester
- Use Methimazole in second and third trimester
- Dosing: Hyperthyroidism
- Start: 100 mg po tid
- Maximum: 150 mg every 6-8 hours
- Titrate PTU dose down after 4-6 weeks
- Goal: maintain normal Thyroid function
- Dose: reduce to 50-100 mg per day
- Dosing: Other
- Thyroid Storm: 1 gram load, then 300 mg PO q6 hours
- Subclinical Hyperthyroidism: 50-100 mg PO qd
- Indications (reasons to use PTU instead of Methimazole)
V. 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)
- 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
- 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
VI. 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
VII. Efficacy: Predictors of Relapse (occurs in 30-70% of cases within first year)
- Tobacco Abuse
- Large Goiter
- Thyroid Stmulating Antibody high at end of treatment
VIII. References
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| propylthiouracil (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| PROPYLTHIOURACIL 50 MG TABLET | Generic | $0.62 each |
| methimazole (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| METHIMAZOLE 10 MG TABLET | Generic | $0.13 each |
| METHIMAZOLE 5 MG TABLET | Generic | $0.11 each |
Ontology: Methimazole (C0025644)
| Definition (MSH) | A thioureylene antithyroid agent that inhibits the formation of thyroid hormones by interfering with the incorporation of iodine into tyrosyl residues of thyroglobulin. This is done by interfering with the oxidation of iodide ion and iodotyrosyl groups through inhibition of the peroxidase enzyme. |
| Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
| MSH | D008713 |
| SnomedCT | 37656002, 404864000 |
| LNC | LP18583-2, MTHU004698 |
| English | 1 Methyl 2 mercaptoimidazole, 1-Methyl-2-mercaptoimidazole, Mercasolyl, Mercazolyl, Merkazolil, Methimazole, Methylmercaptoimidazole, Methymazol, Thiamazole, Thimazol, Tiamazol, 2H-Imidazole-2-thione, 1,3-dihydro-1-methyl-, methimazole, METHIMAZOLE, Methimazole preparation, methimazole (medication), Methimazole [Chemical/Ingredient], tiamazol, thiamazole, Methimazole (substance), Methimazole (product), Thiamazole preparation |
| Swedish | Metimazol |
| Spanish | preparado de metimazol, metimazol (sustancia), metimazol, preparado de metimazol (sustancia), preparado de tiamazol, metimazol (producto), Metimazol, Tiamazol |
| Czech | methimazol |
| Finnish | Metimatsoli |
| Russian | METIMAZOL, MERKAZOLIL, TIMAZOL, МЕРКАЗОЛИЛ, МЕТИМАЗОЛ, ТИМАЗОЛ |
| Japanese | チアマゾール, メルカプトメチルイミダゾール, メルカゾール, チマゾール, メチマゾール |
| Croatian | METIMAZOL |
| Polish | Metimazol |
| French | Thiamazol, Thiamazole |
| German | Methimazol, Methymazol, Thiamazol |
| Italian | Metimazolo |
| Portuguese | Metimazol, Tiamazol |
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 |
Ontology: Thioamides (C0039875)
| Definition (CSP) | compounds of the type R-(C=S)-N=. |
| Definition (MSH) | Organic compounds containing the radical -CSNH2. |
| Concepts | Organic Chemical (T109) |
| MSH | D013854 |
| SnomedCT | 406762005 |
| English | Thioamides, Thioamides [Chemical/Ingredient], thioamides, thioamide, Thioamide (substance), Thioamide |
| Swedish | Tioamider |
| Czech | thioamidy |
| Finnish | Tioamidit |
| Russian | TIOAMIDY, ТИОАМИДЫ |
| Polish | Tioamidy |
| Spanish | tioamida (sustancia), tioamida, Tioamidas |
| French | Thioamides |
| German | Thioamide |
| Italian | Tioamidi |
| Portuguese | Tioamidas |
Ontology: Antithyroid Agents (C0040125)
| Definition (MSH) | Agents that are used to treat hyperthyroidism by reducing the excessive production of thyroid hormones. |
| Definition (CSP) | any agent or substance which suppresses, prevents or opposes the biosynthesis of thyroid hormones. |
| Concepts | Pharmacologic Substance (T121) , Hormone (T125) |
| MSH | D013956 |
| SnomedCT | 5067008, 418416001 |
| English | Antagonists, Thyroid, Antithyroid Drugs, Drugs, Antithyroid, Thyroid Antagonists, thyroid inhibitor, Agents, Antithyroid, Antithyroid Agents, THYROID ANTAG, ANTITHYROID AGENTS, anti-thyroid agents, anti-thyroid agents (medication), thyroid antagonists, [HS852] ANTITHYROID AGENTS, antithyroid drug, inhibitors thyroid, antithyroid agents, antithyroid preparations, antithyroid drugs, Thyroid Antagonist, ANTITHYROID PREPARATIONS, Thyroid antagonists, Antithyroid drugs, Antithyroid agent (product), Antithyroid agent, Thyroid inhibitor preparation, antithyroid agent, Antithyroid preparation, NOS, Thyroid inhibitor preparation, NOS, Antithyroid Agent, Antithyroid agent (substance) |
| Spanish | agente antitiroideo (sustancia), agente antitiroideo, Antitiroideos, Agentes Antitiroideos, Efecto Antitiroideo, preparado antitiroideo (producto), preparado antitiroideo (sustancia), preparado antitiroideo, preparado inhibidor tiroideo, Antagonistas Tiroideos |
| French | Anti-thyroïdiens, Agents antithyroïdiens, Thyréostatiques, Médicaments antithyroïdiens, Agents anti-thyroïdiens, Médicaments anti-thyroïdiens, Antithyroïdiens |
| Swedish | Tyreostatika |
| Czech | thyreostatika, tyreostatika, antithyreoidní látky |
| Finnish | Tyreostaatit |
| Italian | Sostanze antitiroidee, Antagonisti tiroidei, Farmaci antitiroidei |
| Russian | TIREOIDNYKH GORMONOV ANTAGONISTY, STRUMOGENNYE FAKTORY, ANTITIREOIDNYE VESHCHESTVA, АНТИТИРЕОИДНЫЕ ВЕЩЕСТВА, СТРУМОГЕННЫЕ ФАКТОРЫ, ТИРЕОИДНЫХ ГОРМОНОВ АНТАГОНИСТЫ |
| Japanese | 甲状腺拮抗物質, 抗甲状腺薬, 甲状腺腫誘発物質, 抗甲状腺剤, 甲状腺きっ抗剤 |
| Croatian | ANTITIREOIDNE TVARI |
| Polish | Tyreostatyki, Goitrogeny, Środki przeciwtarczycowe, Strumigeny |
| Portuguese | Antitireóideos, Antitireoidianos, Efeito Antitireóideo, Agentes Antitireoidianos, Agentes Antitireóideos, Antagonistas Tireóideos |
| Norwegian | Thyreoideaantagonister, Antithyreoideapreparater, Tyreostatika |
| German | Antithyreodika, Thyreostatika |
Ontology: Tapazole (C0728778)
| Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
| MSH | D008713 |
| English | tapazole, Tapazole, Eli Lilly Brand of Methimazole, Jones Brand of Methimazole |
