Methimazole affects the production of thyroid hormone and is useful in treating conditions related to thyroid hormone, especially thyrotoxicosis. Thus, it is considered a thyroid blocking agent. This activity reviews methimazole's indications, interactions, adverse effects, and other pharmacodynamic and pharmacokinetic factors. In addition, it highlights the role of the interprofessional team in improving care for patients receiving methimazole for conditions where it has an indicated therapeutic value. Objectives:
FDA-approved Indications
Non-FDA-approved Indications
Methimazole (MMI) is an anti-thyroid drug that belongs to drug class thionamides. The primary mechanism of action of methimazole is to block thyroid hormone production from the thyroid gland. It interferes with the step that causes the iodination of tyrosine residues in thyroglobulin, mediated by the enzyme thyroid peroxidase, thus preventing the synthesis of thyroxine (T4) and triiodothyronine(T3).[4] An additional mechanism is by inhibiting the iodotyrosyl residues from the coupling. Methimazole may also interfere with the oxidation of the iodide ion and iodotyrosyl groups. Eventually, thyroglobulin gets depleted, and circulating thyroid hormone levels decrease. It may also help to control diseases by affecting the overall immune system. Various studies show the reduction of immune molecules like intracellular adhesion molecule 1, soluble interleukin 2, and anti-thyrotropin receptor antibody over time, thus alleviating immune-related hyperthyroid issues.[5] Whether or not the improvements in the patient profile are due to this or the improvement of thyroid function remains unclear. However, this drug does not affect the existing thyroxine (T4) and triiodothyronine (T3) in the circulation or stored in the thyroid gland. Similarly, there have been no observations of alterations in the effectiveness of exogenously administered thyroid hormones. Methimazole is available as oral tablets in 5 mg and 10 mg strengths. The starting dose is between 20 to 40 mg per day, depending upon the severity of the disease.[6]
The treatment of thyroid storm includes a starting dose of 60 to 80 mg/day orally until achieving control, also given at 8-hour intervals. Adjust the subsequent doses and duration of treatment as per patient response. Methimazole has a narrow therapeutic window. Therefore it is essential to note the maximally allowed dosage.
The side effects of methimazole are mostly dose-related, like (most commonly) hives and itching, which improves with anti-histaminic medications or by discontinuing the drug. Serious adverse effects: Agranulocytosis
Hepatotoxicity
Teratogenicity
Hypothyroidism
Drug Interactions
Contraindications
Monitoring
The common symptoms of methimazole overdosage are nausea, vomiting, epigastric discomfort, fever, joint pain, itching, body ache, and swelling.[18]
Treatment In a drug overdose, initiate supportive therapy as per the patient's condition. Consider the possibility of multiple drug overdose and drug-drug interactions. Ensure patient's airway, support ventilation, and hemodynamic stability. Monitor for serum electrolytes, blood gases, and patient's vitals. Consider giving activated charcoal to decrease the absorption of the medicine from the stomach before it reaches peak plasma concentration. Physicians, nurses, and pharmacists in many parts of the world continue to use methimazole because of its effectiveness and low cost for treating hyperthyroidism (mainly for Graves disease). However, it is essential to know the side effects of methimazole, particularly severe drug allergy when taken with multiple medications, and side effects with the use of any thioamide medication in general. Furthermore, it is imperative to counsel the patient about rare side effects like agranulocytosis or liver failure before starting the medication. In general, methimazole prescribing should be from an endocrinologist, with patient monitoring by the primary care provider and nurse practitioner. Dose changes must not occur without first consulting with the endocrinologist. The pharmacist should verify all dosing, perform mediation reconciliation, and report any concerns to the healthcare team. Nursing can verify medication compliance along with the pharmacist, as well as observe for any adverse effects. It is essential to communicate openly with all interprofessional team members to improve patient safety and better patient outcomes associated with methimazole use.[Level V] Review Questions1. Azizi F, Amouzegar A, Tohidi M, Hedayati M, Khalili D, Cheraghi L, Mehrabi Y, Takyar M. Increased Remission Rates After Long-Term Methimazole Therapy in Patients with Graves' Disease: Results of a Randomized Clinical Trial. Thyroid. 2019 Sep;29(9):1192-1200. [PubMed: 31310160] Azizi F, Takyar M, Madreseh E, Amouzegar A. Treatment of Toxic Multinodular Goiter: Comparison of Radioiodine and Long-Term Methimazole Treatment. Thyroid. 2019 May;29(5):625-630. [PubMed: 30803411] 3.Kravets I. Hyperthyroidism: Diagnosis and Treatment. Am Fam Physician. 2016 Mar 01;93(5):363-70. [PubMed: 26926973] 4.Abraham P, Acharya S. Current and emerging treatment options for Graves' hyperthyroidism. Ther Clin Risk Manag. 2010 Feb 02;6:29-40. [PMC free article: PMC2817786] [PubMed: 20169034] 5.Sonnet E, Massart C, Gibassier J, Allannic H, Maugendre D. Longitudinal study of soluble intercellular adhesion molecule-1 (ICAM-1) in sera of patients with Graves' disease. J Endocrinol Invest. 1999 Jun;22(6):430-5. [PubMed: 10435852] 6.Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, Rivkees SA, Samuels M, Sosa JA, Stan MN, Walter MA. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016 Oct;26(10):1343-1421. [PubMed: 27521067] 7.Edmonds CJ, Tellez M. Treatment of Graves' disease by carbimazole: high dose with thyroxine compared to titration dose. Eur J Endocrinol. 1994 Aug;131(2):120-4. [PubMed: 8075780] 8.Benker G, Reinwein D, Kahaly G, Tegler L, Alexander WD, Fassbinder J, Hirche H. Is there a methimazole dose effect on remission rate in Graves' disease? Results from a long-term prospective study. The European Multicentre Trial Group of the Treatment of Hyperthyroidism with Antithyroid Drugs. Clin Endocrinol (Oxf). 1998 Oct;49(4):451-7. [PubMed: 9876342] 9.Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, Grobman WA, Laurberg P, Lazarus JH, Mandel SJ, Peeters RP, Sullivan S. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid. 2017 Mar;27(3):315-389. [PubMed: 28056690] 10.Drugs and Lactation Database (LactMed) [Internet]. National Library of Medicine (US); Bethesda (MD): 2006. Methimazole. [PubMed: 30000083] 11.Takata K, Kubota S, Fukata S, Kudo T, Nishihara E, Ito M, Amino N, Miyauchi A. Methimazole-induced agranulocytosis in patients with Graves' disease is more frequent with an initial dose of 30 mg daily than with 15 mg daily. Thyroid. 2009 Jun;19(6):559-63. [PubMed: 19445623] 12.Mandel SJ, Cooper DS. The use of antithyroid drugs in pregnancy and lactation. J Clin Endocrinol Metab. 2001 Jun;86(6):2354-9. [PubMed: 11397822] 13.Barbero P, Valdez R, Rodríguez H, Tiscornia C, Mansilla E, Allons A, Coll S, Liascovich R. Choanal atresia associated with maternal hyperthyroidism treated with methimazole: a case-control study. Am J Med Genet A. 2008 Sep 15;146A(18):2390-5. [PubMed: 18698631] 14.Abalovich M, Amino N, Barbour LA, Cobin RH, De Groot LJ, Glinoer D, Mandel SJ, Stagnaro-Green A. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2007 Aug;92(8 Suppl):S1-47. [PubMed: 17948378] 15.Inoue M, Arata N, Koren G, Ito S. Hyperthyroidism during pregnancy. Can Fam Physician. 2009 Jul;55(7):701-3. [PMC free article: PMC2718594] [PubMed: 19602653] 16.Vicente N, Cardoso L, Barros L, Carrilho F. Antithyroid Drug-Induced Agranulocytosis: State of the Art on Diagnosis and Management. Drugs R D. 2017 Mar;17(1):91-96. [PMC free article: PMC5318340] [PubMed: 28105610] 17.Lipsky JJ, Gallego MO. Mechanism of thioamide antithyroid drug associated hypoprothrombinemia. Drug Metabol Drug Interact. 1988;6(3-4):317-26. [PubMed: 2482800] 18.Wiberg JJ, Nuttall FQ. Methimazole toxicity from high doses. Ann Intern Med. 1972 Sep;77(3):414-6. [PubMed: 4115455] |