Methimazole is an oral thioimidazole antithyroid agent used in adult and pediatric patients. Antithyroid agents are indicated for various hyperthyroid conditions, including maintenance of a euthyroid state in patients with Graves' disease until spontaneous remission occurs. Treatment options for Graves' disease include antithyroid drugs, radioactive iodine therapy, and surgical thyroidectomy. In most patients with Graves' disease, remission doesn't last after antithyroid medications, even after years of treatment. However, since some pediatric patients experience remission over time, antithyroid medications are still considered first-line treatment in this population. Although methimazole and propylthiouracil (PTU) are both used to treat Graves' disease, methimazole is considered first-line antithyroid treatment, except in the first trimester of pregnancy, where teratogenesis is a concern, or in cases of drug allergy or intolerance. Methimazole is less likely to induce hepatotoxicity than propylthiouracil, especially in pediatric patients. PTU has an unacceptable risk of hepatotoxicity in children; there are reports of fulminant hepatic necrosis and liver failure requiring liver transplantation.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Hazardous Drugs Classification
-NIOSH 2016 List: Group 2
-NIOSH (Draft) 2020 List: Table 2
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure and require additional protective equipment. Oral liquid drugs require double chemotherapy gloves and protective gown; may require eye/face protection.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
-Administer orally at the same time(s) each day in relation to meals.
Minor adverse dermatologic reactions, including rash, alopecia, skin hyperpigmentation, urticaria, and pruritus, have been reported in patients receiving methimazole. Exfoliative dermatitis, a severe cutaneous eruption, has been reported in overdose situations.
Agranulocytosis (severe neutropenia), leukopenia, thrombocytopenia, pancytopenia, and aplastic anemia can occur with methimazole due to inhibition of myelopoiesis. Agranulocytosis has been reported in approximately 0.3% of adult patients taking methimazole. Data on the prevalence of agranulocytosis in pediatric patients are unavailable, but it is estimated to be very low. Most adverse events occur within the first 3 months of therapy, however, agranulocytosis may develop several months after initiation. Advise patients to report symptoms of sore throat, fever, and general malaise promptly to their prescriber for evaluation, as these symptoms may be suggestive of agranulocytosis. Obtain a CBC with differential during febrile illness and at the onset of pharyngitis in all patients taking antithyroid medication. Discontinue methimazole if agranulocytosis or aplastic anemia develops and monitor the patient's CBC with differential.
Hypothyroidism can occur with prolonged use of methimazole. Periodic monitoring of thyroid function is warranted, and the finding of an elevated TSH warrants a decrease in the methimazole dosage.
Cases of vasculitis, (leukocytoclastic cutaneous vasculitis, acute kidney injury and glomerulonephritis, alveolar/pulmonary hemorrhage, CNS vasculitis, and neuropathy), resulting in severe complications, have been reported in patients receiving methimazole therapy, although the risk is much less with methimazole compared with propylthiouracil. Most cases were associated with antineutrophilic cytoplasmic antibodies (ANCA)-positive vasculitis. Risk factors for ANCA-positive vasculitis are duration of therapy, young age, and Asian ethnicity. In some cases, vasculitis resolved/improved with drug discontinuation; however, more severe cases required treatment with additional measures including corticosteroids, immunosuppressant therapy, and plasmapheresis. If vasculitis is suspected, discontinue therapy and initiate appropriate intervention. Other adverse events noted with methimazole include arthralgia, myalgia, edema, nephrotic syndrome, drug fever, lupus-like symptoms, insulin autoimmune syndrome (hypoglycemia and hypoglycemic coma), lymphadenopathy, periarteritis, and sialadenitis. Arthralgia can occur more frequently when higher doses are used.
Drowsiness, neuritis, paresthesias, headache, and vertigo have occurred in patients receiving methimazole. Peripheral neuropathy has been reported in overdose situations.
Hepatotoxicity, including acute hepatic failure, rarely occurs during therapy with methimazole, but can be fatal. Methimazole-induced hepatotoxicity can manifest as jaundice, hepatic encephalopathy, hepatic necrosis, and/or hepatitis. Promptly evaluate liver function for symptoms such as anorexia, pruritus, and right upper quadrant pain. Discontinue drug treatment in the event of clinically significant evidence of liver abnormality, including elevated hepatic enzymes exceeding 3 times the upper limit of normal (ULN). Jaundice may persist for several weeks after methimazole discontinuation. Cholestasis and hepatocellular injury are more common in adults compared with pediatric patients.
Gastrointestinal adverse reactions noted with methimazole include nausea, vomiting, dysgeusia, and epigastric distress.
Teratogenesis is a serious concern with methimazole if administered during early pregnancy during the period of organogenesis. Methimazole crosses the placental membranes and can cause fetal harm when administered in the first trimester of pregnancy. Rare instances of congenital defects, including aplasia cutis, craniofacial malformations (facial dysmorphism; choanal atresia), gastrointestinal malformations (esophageal atresia with or without tracheoesophageal fistula), omphalocele and abnormalities of the omphalomesenteric duct have occurred in infants born to mothers who received methimazole in the first trimester of pregnancy. Because of the risk for congenital malformations associated with use of methimazole in the first trimester of pregnancy, the use other agents (e.g., propylthiouracil) is preferred in the first trimester. However, given the potential maternal adverse effects of propylthiouracil (e.g., hepatotoxicity), it is often preferable to switch therapy to methimazole for the second and third trimesters. Because methimazole crosses placental membranes and can induce goiter and cretinism in the developing fetus, hyperthyroidism should be closely monitored in pregnant women and treatment adjusted such that a sufficient, but not excessive, dose is given.
Methimazole may also cause hypoprothrombinemia and bleeding; monitor prothrombin time during therapy, especially before surgical procedures.
Methimazole is contraindicated in patients with a history of hypersensitivity to the drug, including a history of serious rash or skin eruption, drug-induced liver disease, or drug-induced agranulocytosis. If a patient develops agranulocytosis or other serious side effects while taking either methimazole or propylthiouracil, use of the other medication is contraindicated due to the high risk of cross-reactivity between the two medications. Agranulocytosis (severe neutropenia) is the most serious adverse reaction of methimazole, and is most likely immune-mediated. Thrombocytopenia, leukopenia and aplastic anemia (pancytopenia) may also occur. Use methimazole with caution in patients with bone marrow suppression or risk factors for methimazole hematologic toxicity or in patients receiving other drugs known to cause agranulocytosis. In adults, agranulocytosis is dose dependent and rarely occurs at lower doses (15 mg/day or less). Methimazole doses greater than 1 mg/kg/day (Max: 30 mg/day) should generally be avoided in pediatric patients. Most adverse events occur within the first 3 months of therapy, however, agranulocytosis may develop several months after initiation. Advise patients to report symptoms of sore throat, fever, and general malaise promptly to their prescriber for evaluation, as these symptoms may be suggestive of agranulocytosis. Obtain a CBC with differential during febrile illness and at the onset of pharyngitis in all patients taking antithyroid medication. Discontinue methimazole if agranulocytosis or aplastic anemia develops and monitor the patient's CBC with differential.
In general, use methimazole with caution in patients with pre-existing hepatic disease. Although there have been reports of hepatotoxicity (including acute hepatic failure and hepatitis) associated with methimazole, the risk of hepatotoxicity is less with methimazole than with propylthiouracil, especially in the pediatric population. If symptoms suggestive of hepatic dysfunction (i.e., anorexia, jaundice, pruritus, right upper quadrant pain) occur, evaluate liver function tests (i.e., bilirubin, alkaline phosphatase, ALT, AST) promptly. Discontinue drug treatment in the event of clinically significant evidence of liver abnormality, including hepatic transaminase values exceeding 3 times the upper limit of normal (ULN).
Females of childbearing potential who are taking methimazole should inform their prescriber if they desire to become pregnant or think they may be pregnant. Teratogenesis is a serious concern with methimazole if administered during early pregnancy during the period of organogenesis. Methimazole crosses the placental membranes and can cause fetal harm when administered in the first trimester of pregnancy. Rare instances of congenital defects, including aplasia cutis, craniofacial malformations (facial dysmorphism; choanal atresia), gastrointestinal malformations (esophageal atresia with or without tracheoesophageal fistula), omphalocele and abnormalities of the omphalomesenteric duct have occurred in babies born to mothers who received methimazole in the first trimester of pregnancy. Because of the risk for congenital malformations associated with the use of methimazole in the first trimester of pregnancy, the use of other agents (e.g., propylthiouracil) is preferred in the first trimester. However, given the potential maternal adverse effects of propylthiouracil (e.g., hepatotoxicity), it is often preferable to switch therapy to methimazole for the second and third trimesters. Because methimazole crosses placental membranes and can induce goiter and cretinism in the developing fetus, pregnant patients with hyperthyroidism should be closely monitored and treatment adjusted such that a sufficient, but not excessive, the dose is given. Because thyroid dysfunction may improve as pregnancy proceeds in some patients, it may be possible to discontinue antithyroid therapy 2 to 3 months prior to delivery after careful clinical evaluation of thyroid function.
The American Thyroid Association (ATA) guidelines recommend that low to moderate doses (e.g., methimazole up to a maximal dose of 20 mg/day) be used during lactation. A small, but detectable amount of methimazole is transferred into breast milk and therefore the lowest effective dose should always be administered. Several studies have found no effect on the clinical status of nursing infants exposed to methimazole via breast milk. Additionally, a long-term study of 139 thyrotoxic lactating mothers and their infants failed to demonstrate toxicity in infants breastfed during maternal treatment with methimazole. Monitor thyroid function at frequent (weekly or biweekly) intervals. The ATA recommends that breastfed children of individuals treated with methimazole be monitored for appropriate growth and development during routine pediatric health and wellness evaluations. Routine assessment of serum thyroid function in the child is not recommended.
Cases of vasculitis, (leukocytoclastic cutaneous vasculitis, acute kidney injury and glomerulonephritis, alveolar/pulmonary hemorrhage, CNS vasculitis, and neuropathy), resulting in severe complications, have been reported in patients receiving methimazole therapy, although the risk of vasculitis is less with methimazole than with propylthiouracil. Most cases were associated with antineutrophilic cytoplasmic antibodies (ANCA)-positive vasculitis. The risk of vasculitis appears to increase with duration of therapy as opposed to other adverse effects seen with antithyroid drugs. Pediatric and Asian patients also appear to be at higher risk for ANCA-positive vasculitis. In some cases, vasculitis resolved/improved with drug discontinuation; however, more severe cases required treatment with additional measures including corticosteroids, immunosuppressant therapy, and plasmapheresis. If vasculitis is suspected, discontinue therapy and initiate appropriate intervention.
Counsel patients about stopping biotin and biotin-containing supplements for at least 2 days prior to thyroid testing. Biotin in blood or other samples taken from patients who are ingesting higher biotin dosages (i.e., doses of 10 to 300 mg biotin/day) in dietary supplements, including multivitamins, prenatal vitamins, and supplements for hair, skin, and nail growth, can cause clinically significant laboratory test interference in assays that use biotin-streptavidin technology. One patient reportedly had abnormal thyroid function tests (TFTs) that did not match the clinical context after starting biotin. Within 3 days of stopping supplementation with biotin, repeated TFTs were normal. Then, biotin was reintroduced to the same patient, and TFTs taken 16 hours after the last dose and after an overnight fast showed further evidence of biotin immunoassay interference. Discuss dietary supplement intake, particularly those that may contain biotin, with patients and communicate to the lab conducting testing if the patient reports taking biotin-containing supplements. Consider laboratory test interference from biotin as a possible source of error if the lab test result does not match the clinical presentation of the patient and report any adverse events thought to be due to biotin interference to the lab test manufacturer and the FDA.
For the treatment of thyrotoxicosis, including hyperthyroidism, Graves' disease, toxic multinodular goiter, and thyroid storm*:
-for the treatment of thyrotoxicosis, including hyperthyroidism, Graves' disease, and toxic multinodular goiter:
Oral dosage:
Adults: 5 to 10 mg PO once daily for free T4 1 to 1.5 times the upper limit of normal; 10 to 20 mg PO once daily for free T4 1.5 to 2 times the upper limit of normal; and 30 to 40 mg PO once daily for free T4 2 to 3 times the upper limit of normal, initially. A split dose may be more effective than a single daily dose when more rapid biochemical control is needed in persons with severe thyrotoxicosis. Taper dose to 5 to 10 mg/day as the patient becomes euthyroid. The FDA-approved dosage is 15 mg/day PO for mild hyperthyroidism; 30 to 40 mg/day PO for moderately severe hyperthyroidism; and 60 mg/day PO for severe hyperthyroidism divided every 8 hours, initially. Usual maintenance dose: 5 to 15 mg/day.
Children and Adolescents 11 to 17 years: 0.15 to 0.5 mg/kg/dose PO once daily or 10 to 20 mg PO once daily, initially. An initial dose of 0.15 to 0.3 mg/kg/dose will normalize thyroid hormone concentrations in most patients within the first 4 to 6 weeks. Larger doses may be needed in more severe, symptomatic cases or if thyroid hormone concentrations do not fall as expected. Increase the dose by 25% or more if the patient remains hyperthyroid. Dose range: 0.1 to 1 mg/kg/day. Max: 30 mg/day. Reduce dose by 25% to 50% as the patient becomes euthyroid. Usual maintenance dose: one-half of the initial dose PO once daily. The FDA-approved dosage is 0.4 mg/kg/day PO divided every 8 hours, initially. Usual maintenance dose: approximately one-half of the initial dose divided every 8 hours.
Children 6 to 10 years: 0.15 to 0.5 mg/kg/dose PO once daily or 5 to 10 mg PO once daily, initially. An initial dose of 0.15 to 0.3 mg/kg/dose will normalize thyroid hormone concentrations in most patients within the first 4 to 6 weeks. Larger doses may be needed in more severe, symptomatic cases or if thyroid hormone concentrations do not fall as expected. Increase the dose by 25% or more if the patient remains hyperthyroid. Dose range: 0.1 to 1 mg/kg/day. Max: 30 mg/day. Reduce dose by 25% to 50% as the patient becomes euthyroid. Usual maintenance dose: one-half of the initial dose PO once daily. The FDA-approved dosage is 0.4 mg/kg/day PO divided every 8 hours, initially. Usual maintenance dose: approximately one-half of the initial dose divided every 8 hours.
Children 1 to 5 years: 0.15 to 0.5 mg/kg/dose PO once daily or 2.5 to 5 mg PO once daily, initially. An initial dose of 0.15 to 0.3 mg/kg/dose will normalize thyroid hormone concentrations in most patients within the first 4 to 6 weeks. Larger doses may be needed in more severe, symptomatic cases or if thyroid hormone concentrations do not fall as expected. Increase the dose by 25% or more if the patient remains hyperthyroid. Dose range: 0.1 to 1 mg/kg/day. Reduce dose by 25% to 50% as the patient becomes euthyroid. Usual maintenance dose: one-half of the initial dose PO once daily. The FDA-approved dosage is 0.4 mg/kg/day PO divided every 8 hours, initially. Usual maintenance dose: approximately one-half of the initial dose divided every 8 hours.
Infants: 0.15 to 0.5 mg/kg/dose PO once daily or 1.25 mg PO once daily, initially. An initial dose of 0.15 to 0.3 mg/kg/dose will normalize thyroid hormone concentrations in most patients within the first 4 to 6 weeks. Larger doses may be needed in more severe, symptomatic cases or if thyroid hormone concentrations do not fall as expected. Increase the dose by 25% or more if the patient remains hyperthyroid. Dose range: 0.1 to 1 mg/kg/day. Reduce dose by 25% to 50% as the patient becomes euthyroid. Usual maintenance dose: one-half of the initial dose PO once daily. The FDA-approved dosage is 0.4 mg/kg/day PO divided every 8 hours, initially. Usual maintenance dose: approximately one-half of the initial dose divided every 8 hours.
Neonates*: 0.2 to 0.5 mg/kg/day PO divided twice daily. Dose range: 0.2 to 1 mg/kg/day. Reduce dose as the patient becomes euthyroid.
-for the treatment of thyroid storm*:
Oral dosage:
Adults: 20 mg PO every 6 to 8 hours.
Infants, Children, and Adolescents: 0.5 to 1 mg/kg/day PO divided every 6 to 8 hours.
Maximum Dosage Limits:
-Adults
60 mg/day PO.
-Geriatric
60 mg/day PO.
-Adolescents
0.4 mg/kg/day PO is FDA-approved maximum dosage; however, doses up to 1 mg/kg/day (Max: 30 mg/day) PO have been used off-label.
-Children
0.4 mg/kg/day PO is FDA-approved maximum dosage; however, doses up to 1 mg/kg/day (Max: 30 mg/day) PO have been used off-label.
-Infants
0.4 mg/kg/day PO is FDA-approved maximum dosage; however, doses up to 1 mg/kg/day PO have been used off-label.
-Neonates
Safety and efficacy have not been established; however, doses up to 1 mg/kg/day PO have been used off-label.
Patients with Hepatic Impairment Dosing
No specific recommendations for dosage adjustments are available. Discontinue if clinically significant evidence of hepatic dysfunction (e.g., LFT elevations) occurs during use.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Acebutolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Amiodarone: (Moderate) In hyperthyroid patients, the combination of amiodarone and methimazole has been associated with a greater decrease in serum triiodothyronine and thyroxine levels, as compared to the administration of methimazole alone. This may be due to increased iodide release associated with amiodarone. Monitor serum T3 and T4 levels in patients receiving combination therapy.
Atenolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Atenolol; Chlorthalidone: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Beta-blockers: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Betaxolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Bisoprolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Brimonidine; Timolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Carteolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Carvedilol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Deferiprone: (Major) Avoid concomitant use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis, such as methimazole; however, if this is not possible, closely monitor the absolute neutrophil count and interrupt deferiprone therapy if neutropenia develops.
Digoxin: (Minor) Serum concentrations of digoxin can increase as hyperthyroidism is corrected. In patients receiving antithyroid therapy, the dosage of digoxin may need to be reduced as the patient becomes euthyroid.
Dorzolamide; Timolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Esmolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Iodine; Potassium Iodide, KI: (Moderate) Potassium iodide should not be used concurrently with other antithyroid agents. Agents such as methimazole and propylthiouracil, PTU can increase the likelihood of hypothyroidism when used in combination with potassium iodide.
Iodoquinol: (Moderate) Iodoquinol should be used with caution in patients treated with thyroid agents. Iodine-containing compounds like iodoquinol may result in overt thyroid disease.
Labetalol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Levobunolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Macimorelin: (Major) Avoid use of macimorelin with drugs that may blunt the growth hormone response to macimorelin, such as antithyroid agents. Healthcare providers are advised to discontinue antithyroid therapy at least 1 week before administering macimorelin. Use of these medications together may impact the accuracy of the macimorelin growth hormone test.
Metoprolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Metoprolol; Hydrochlorothiazide, HCTZ: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Nadolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Nebivolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Nebivolol; Valsartan: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Pindolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Potassium Iodide, KI: (Moderate) Potassium iodide should not be used concurrently with other antithyroid agents. Agents such as methimazole and propylthiouracil, PTU can increase the likelihood of hypothyroidism when used in combination with potassium iodide.
Propranolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Sodium Iodide: (Contraindicated) The recent intake of antithyroid agents will affect the uptake of radioiodide from sodium iodide, I-131; patients must discontinue all medications and supplements that may interfere with iodide uptake into thyroid tissue prior to therapy with sodium iodide I-131. Various protocols are used. Many manufacturers state that concurrent antithyroid agents should be discontinued at least 3 to 4 days before administration of radioiodide. The following withdrawal timing recommendations were set forth in a procedure guideline published by the Society of Nuclear Medicine in February 2002. Antithyroid agents may affect iodide protein binding for an average of 5 days after administration; allow a 3 day wash out period for the antithyroid agent (e.g., PTU, methimazole) prior to sodium iodide I-131 administration. The antithyroid agent may be resumed 2 to 3 days after treatment. When patients are taking sodium iodide (non-radioiodide) for supplementation in TPN, the effect of the iodide on antithyroid therapy should be considered.
Sotalol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Theophylline, Aminophylline: (Minor) Patients with hyperthyroidism may exhibit accelerated clearance of theophylline. Correction of hyperthyroidism can lead to a decrease in theophylline clearance. Theophylline serum concentrations should be monitored closely during the initial stages of treatment for hyperthyroidism.
Timolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Warfarin: (Moderate) The interaction between thioamine antithyroid agents and warfarin is variable. The effects of warfarin can be enhanced due to the vitamin K antagonistic properties of methimazole or propylthiouracil, PTU. Isolated cases have reported hypoprothrombinemia due to methimazole or propylthiouracil, which may be additive with warfarin. In addition, as hyperthyroidism is corrected, the anticoagulant effect of warfarin can diminish due to a change in the clearance rate of endogenous clotting factors. Thus, administration of antithyroid agents such as methimazole or PTU can also reduce the effectiveness of warfarin. INRs should be monitored closely whenever methimazole is added or discontinued during warfarin therapy or when the thyroid status of a patient is expected to change. Warfarin dosage should be adjusted accordingly based on the INR and the clinical goals for the patient.
Methimazole directly interferes with the first step in thyroid hormone biosynthesis in the thyroid gland. By acting as a substrate for the catalyst thyroid peroxidase, methimazole inhibits the incorporation of iodide into the thyroid hormone precursor, thyroglobulin. Consequently, the drug is iodinated and degraded within the thyroid gland. Oxidized iodine is diverted away from thyroglobulin, which effectively diminishes the biosynthesis of thyroid hormone. An additional mechanism is the inhibition of iodotyrosyl residues coupling to form thyroglobulin. Methimazole may interfere with the oxidation of the iodide ion and iodotyrosyl groups. Eventually, thyroglobulin is depleted and circulating thyroid hormone levels diminish. Methimazole does not alter the action of existing thyroxine (T4) and triiodothyronine (T3) in the circulation or stored in the thyroid gland. Similarly, no alterations in the effectiveness of exogenously administered thyroid hormones have been observed.
Methimazole is administered orally. Once absorbed, methimazole is actively concentrated by the thyroid gland. The Vd of methimazole in adults has reported to be approximately 0.6 L/kg. Protein binding is insignificant, as a result, methimazole is excreted more readily into breast milk than other drugs in its class. The drug also readily crosses the placenta. Methimazole undergoes hepatic metabolism with no active metabolites. Renal excretion is less than 10%. The elimination half-life is approximately 4 to 6 hours. However, the intrathyroidal residence of methimazole is up to 24 hours, onset of action is 12 to 18 hours, and duration of action is 36 to 72 hours. The plasma elimination half-life of methimazole is not appreciably altered by the patient's thyroid status.
Affected cytochrome P450 isoenzymes and drug transporters: none
-Route-Specific Pharmacokinetics
Oral Route
Methimazole is rapidly absorbed from the gastrointestinal tract and shows high bioavailability after oral administration (approximately 93%), reaching peak serum concentrations within 1 to 2 hours after administration. However, it usually takes 2 to 4 months of treatment to achieve initial euthyroid status; response rates are dependent on several pharmacodynamic and patient variables.
-Special Populations
Hepatic Impairment
A prolonged elimination-half life of methimazole has been observed in the presence of hepatic impairment in adult patients; the prolongation was proportional to the degree of hepatic impairment.
Renal Impairment
Data in adult patients have shown that renal impairment has no effect on the pharmacokinetics of methimazole.
Pediatrics
Methimazole pharmacokinetics were evaluated in 9 pediatric patients (aged 6 to 15 years) in the thyrotoxic state who received a single oral dose of 20 mg/m2. The Cmax was 4.4 to 12.6 micromol/L (median: 9.2 micromol/L) at 0.5 to 4 hours after drug administration, AUC was 32.8 to 77.9 micromol/L x hour (median: 65.1 micromol/L x hour), Vd was 0.516 to 0.913 L/kg (median: 0.602 L/kg), and elimination half-life was 2.73 to 6.04 hours (median: 4.75 hours). Intrathyroidal concentrations were measured in another 9 patients (4 adolescents; 5 adults) who underwent thyroidectomy and received methimazole doses ranging from 15 to 60 mg/day. Drug concentrations in the thyroid gland ranged from 3.5 to 23.8 micromol/kg tissue and were higher than plasma concentrations obtained at the time of surgery. Based on these results, methimazole intrathyroidal concentrations were maintained for 16 to 24 hours in spite of a short plasma half-life.