Methimazole (MMI) is an anti-thyroid drug that belongs to drug class thionamides; the FDA approved uses of which include:
The non-FDA approved use of MMI includes treating thyrotoxicosis/thyroid storm.
The primary mechanism of action of methimazole is to block the production of thyroid hormone 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). 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 that reduction of immune molecules like intracellular adhesion molecule 1, soluble interleukin 2, and anti-thyrotropin receptor antibody over time, thus ameliorating immune-related hyperthyroid issues. Whether or not the improvements in the patient profile are due to this, or because of improvement of thyroid function, remains unclear.
However, there is no effect of this drug on 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 administration is via the oral route. The starting dose is between 20 to 40 mg per day, depending upon the severity.
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. The minor ones like (most commonly) hives and itching, improve with anti-histaminic medications or by discontinuing the drug.
Serious adverse effects include:
Methimazole is contraindicated if there is hypersensitivity to the drug or any of its components.
Patients receiving MMI should be closely monitored and cautioned to immediately report any signs of illness, especially fever, sore throat, malaise, headache. If so, obtain total and differential cell counts and look for any evidence of agranulocytosis. Extra care is necessary for patients who receive additional drugs that could potentially cause agranulocytosis.
MMI is known to cause hypoprothrombinemia and bleeding. Monitor prothrombin time for such patients, especially before surgery.
Both propylthiouracil and methimazole appear in low concentrations in the breast milk but do not influence the infant thyroid function, and breastfeeding is permissible on moderate doses of these agents. Those with elevated antibody levels need assessment for fetal and neonatal thyroid dysfunction. On ultrasound features of fetal thyroid dysfunction include growth restriction, advanced bone age, goiter, or cardiac failure. According to the guidelines of the American Thyroid Association (ATA), low to moderate doses of MMI (i.e., 20 to 30 mg/day) can and should be used during lactation, since research has observed no significant adverse outcomes. It also recommends regular monitoring of the infant's thyroid function, and that lactating mothers take their thyroid medication in divided doses, preferably immediately following a feeding.
Thyroid function tests are necessary at regular intervals, in case any dosing adjustments are needed.
Any patient who gets pregnant or intends to get pregnant while on any anti-thyroid medication should immediately report to their doctor for a change of therapy.
The common symptoms of methimazole overdosage are nausea, vomiting, epigastric discomfort, fever, joint pain, itching, body ache, and swelling.
In cases of a drug overdose, initiate supportive therapy as per the patient's condition.
Physicians, nurses, and pharmacists in many parts of the world continue to use methimazole because of its effectiveness and low cost for treatment of hyperthyroidism (mainly for Graves disease).
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 the 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 back to the healthcare team. Nursing can verify medication compliance along with the pharmacist, as well as observe for any adverse effects. Only with open communication with members of the interprofessional team can the outcomes be improved and the adverse effects of the drug reduced. [Level V]
|||Abraham P,Acharya S, Current and emerging treatment options for Graves' hyperthyroidism. Therapeutics and clinical risk management. 2010 Feb 2; [PubMed PMID: 20169034]|
|||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. Journal of endocrinological investigation. 1999 Jun; [PubMed PMID: 10435852]|
|||Edmonds CJ,Tellez M, Treatment of Graves' disease by carbimazole: high dose with thyroxine compared to titration dose. European journal of endocrinology. 1994 Aug; [PubMed PMID: 8075780]|
|||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. Clinical endocrinology. 1998 Oct; [PubMed PMID: 9876342]|
|||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 : official journal of the American Thyroid Association. 2009 Jun; [PubMed PMID: 19445623]|
|||Mandel SJ,Cooper DS, The use of antithyroid drugs in pregnancy and lactation. The Journal of clinical endocrinology and metabolism. 2001 Jun; [PubMed PMID: 11397822]|
|||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. American journal of medical genetics. Part A. 2008 Sep 15; [PubMed PMID: 18698631]|
|||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. The Journal of clinical endocrinology and metabolism. 2007 Aug; [PubMed PMID: 17948378]|
|||Vicente N,Cardoso L,Barros L,Carrilho F, Antithyroid Drug-Induced Agranulocytosis: State of the Art on Diagnosis and Management. Drugs in R [PubMed PMID: 28105610]|
|||Lipsky JJ,Gallego MO, Mechanism of thioamide antithyroid drug associated hypoprothrombinemia. Drug metabolism and drug interactions. 1988; [PubMed PMID: 2482800]|
|||Methimazole 2006; [PubMed PMID: 30000083]|