VA Class:HS852
ATC Class:H03BB02
Methimazole is a thioimidazole-derivative antithyroid agent.
Methimazole is used in patients with Graves' disease with hyperthyroidism or toxic multinodular goiter for whom surgery or radioactive iodine therapy is not an appropriate treatment option.101, 118 The drug also is used to ameliorate symptoms of hyperthyroidism in preparation for thyroidectomy or radioactive iodine therapy.101, 118
Some clinicians state that methimazole should be used in virtually every patient who chooses antithyroid drug therapy for the treatment of Graves' disease, except during the first trimester of pregnancy when propylthiouracil is preferred (see Pregnancy under Cautions: Pregnancy and Lactation), in the treatment of thyroid storm (see Thyrotoxic Crisis under Uses: Hyperthyroidism), and in patients with minor adverse reactions to methimazole who refuse radioactive iodine therapy or surgery.118
Because of postmarketing reports of severe liver injury in pediatric patients receiving propylthiouracil, methimazole is the preferred agent when an antithyroid drug is required for a pediatric patient.101, 118 (See Cautions: Pediatric Precautions.)
Thioamide antithyroid agents (e.g., methimazole, propylthiouracil) are used to control the symptoms of hyperthyroidism associated with Graves' disease and maintain the patient in a euthyroid state for a period of several years (generally 1-2 years) until a spontaneous remission occurs.118 Thioamide antithyroid agents do not affect the underlying cause of hyperthyroidism. Spontaneous remission does not occur in all patients receiving therapy with thioamide antithyroid agents, and most patients eventually require ablative therapy (i.e., surgery, radioactive iodine). The minimum duration of thioamide therapy necessary before assessing whether spontaneous remission has occurred is not clearly established. However, some clinicians state that if methimazole is chosen as the primary therapy for Graves' disease, the drug should be continued for approximately 12-18 months in adults or 1-2 years in children, then tapered or discontinued if thyrotropin (thyroid stimulating hormone, TSH) concentrations return to normal at that time.118, 122, 123, 124, 125 If adults or children with Graves' disease remain hyperthyroid after completing a course of methimazole, treatment with radioactive iodine or thyroidectomy should be considered.118 Some clinicians state that treatment with low-dose methimazole for longer than 12-18 months in adults may be considered in patients not in remission who prefer this pharmacologic approach.118 Methimazole therapy also may be continued in children until the child is considered old enough for radioactive iodine therapy or surgery.118
Methimazole is used to return the hyperthyroid patient to a normal metabolic state prior to thyroidectomy and to control the thyrotoxic crisis that may accompany thyroidectomy. (See Thyrotoxic Crisis under Uses: Hyperthyroidism.) Some clinicians recommend that, whenever possible, adults or children with Graves' disease undergoing thyroidectomy or adults with toxic adenoma† or toxic multinodular goiter undergoing surgery be rendered euthyroid with methimazole prior to the procedure.118
Methimazole is used as an adjunct to radioactive iodine therapy in patients who require control of symptoms of hyperthyroidism prior to and after administration of radioactive iodine until the ablative effects of the iodine occur.118, 123, 129, 130, 131 However, the beneficial and detrimental effects and optimal sequencing of antithyroid drugs before or after radioactive iodine therapy have not been clearly established.129 Some clinicians recommend that pretreatment with methimazole prior to radioactive iodine therapy for Graves' disease, toxic adenoma†, or toxic multinodular goiter be considered in adults who are at increased risk for complications due to worsening of hyperthyroidism (e.g., geriatric patients, patients with severe hyperthyroidism [e.g., extremely symptomatic, free thyroxine (T4) estimates 2-3 times the upper limit of normal] or substantial comorbidities [e.g., cardiovascular disease]).118 However, conflicting opinions exist, and other clinicians state that pretreatment with methimazole prior to radioactive iodine therapy is not necessary because there is insufficient evidence to indicate that radioactive iodine worsens the clinical or biochemical aspects of hyperthyroidism, and that pretreatment with methimazole will only delay treatment with radioactive iodine.118 In addition, some evidence indicates that pretreatment with methimazole may reduce the efficacy of subsequent radioactive iodine therapy.118, 122, 123, 129, 130 In children with Graves' disease having total T4 concentrations exceeding 20 mcg/dL or free T4 estimates exceeding 5 ng/dL who are to receive radioactive iodine therapy, some clinicians suggest pretreatment with methimazole and β-adrenergic blockade until total T4 and/or free T4 estimates normalize before proceeding with radioactive iodine.118
Antithyroid agents do not induce remission in patients with nodular thyroid disease (i.e., toxic adenoma†, toxic multinodular goiter), and discontinuance of therapy results in relapse.118 Therefore, some clinicians suggest that adults with overt toxic adenoma or toxic multinodular goiter be treated with either radioactive iodine therapy or thyroidectomy, and that long-term methimazole therapy be avoided.118 However, these clinicians state that long-term (life-long) antithyroid drug therapy may be the best choice for some geriatric or otherwise ill patients with limited longevity and increased surgical risk who can be monitored regularly (e.g., residents of nursing homes or other care facilities where compliance with radiation safety regulations may be difficult) or for patients who prefer this pharmacologic approach.118
In the management of thyrotoxic crisis, thioamide antithyroid agents are used to inhibit thyroid hormone synthesis. Because propylthiouracil also blocks the peripheral conversion of thyroxine to triiodothyronine, it theoretically may be more useful than methimazole or carbimazole (not commercially available in the US) in the management of thyrotoxic crisis. Iodides (e.g., potassium iodide, strong iodine solution) are given to inhibit the release of thyroid hormone from the gland but may subsequently be used as a substrate for thyroid hormone synthesis; therefore, treatment with a thioamide antithyroid agent is usually initiated before iodide therapy. A β-adrenergic blocking agent (e.g., propranolol) is also usually given concomitantly to manage peripheral signs and symptoms of hyperthyroidism, particularly cardiovascular effects (e.g., tachycardia).
Methimazole is administered orally.101 The manufacturer states that the total daily dosage is usually given in 3 equally divided doses at approximately 8-hour intervals.101 Alternatively, some clinicians state that methimazole may be administered as a single daily dose.118
The manufacturer states that the initial adult dosage of methimazole is 15, 30-40, or 60 mg daily for the treatment of mild, moderately severe, or severe hyperthyroidism, respectively.101 Alternatively, for the treatment of Graves' disease, some clinicians recommend an initial adult methimazole dosage of 10-20 mg daily to restore euthyroidism.118 In general, most patients improve considerably or achieve normal thyroid function following 4-12 weeks of therapy, after which dosage may be decreased while maintaining normal thyroid function.118, 122, 123, 124 Subsequent dosage should be carefully adjusted according to the patient's tolerance and therapeutic response. The manufacturer states that the adult maintenance dosage is 5-15 mg daily.101 Alternatively, for the treatment of Graves' disease, some clinicians generally recommend an adult maintenance dosage of 5-10 mg daily.118 (See Cautions: Precautions and Contraindications.)
If methimazole is used during pregnancy for the management of hyperthyroidism, the manufacturer states that a sufficient, but not excessive, dosage of methimazole is necessary; the lowest possible dosage of methimazole to control the maternal disease should be used.101 The manufacturer states that because thyroid dysfunction diminishes in many women as the pregnancy proceeds, a reduction in dosage of antithyroid therapy may be possible, and, in some patients, use of antithyroid therapy can be discontinued 2-3 weeks before delivery.101 (See Pregnancy under Cautions: Pregnancy and Lactation.)
For the treatment of thyrotoxic crisis (i.e., thyroid storm) in adults, some clinicians recommend a methimazole dosage of 60-80 mg daily.118
The optimum duration of antithyroid therapy remains to be clearly established. However, some clinicians state that if methimazole is chosen as the primary therapy for Graves' disease in adults, the drug should be continued for approximately 12-18 months, then tapered or discontinued if thyrotropin (thyroid stimulating hormone, TSH) concentrations return to normal at that time.118, 122, 123, 124, 125 If a patient with Graves' disease remains hyperthyroid after completing a course of methimazole, treatment with radioactive iodine or thyroidectomy should be considered.118 However, treatment with low-dose methimazole for longer than 12-18 months may be considered in adult patients not in remission who prefer this pharmacologic approach.118
If methimazole is used prior to thyroidectomy or surgery to render adults euthyroid, the drug should be discontinued at the time of the procedure.118
If methimazole is used as pretreatment prior to radioactive iodine therapy, some clinicians recommend that methimazole be discontinued 2-7 days before administration of radioactive iodine, restarted 3-7 days after radioactive iodine, and generally tapered over 4-6 weeks as thyroid function normalizes and radioactive iodine becomes effective.118, 122, 123, 130
For the treatment of hyperthyroidism in children, the manufacturer states that the initial dosage of methimazole is 0.4 mg/kg daily.101 The manufacturer states that the maintenance dosage in children is approximately one-half of the initial dosage.101 Alternatively, for the treatment of Graves' disease, some clinicians state that the usual dosage of methimazole in children is 0.2-0.5 mg/kg daily, with a range of 0.1-1 mg/kg daily.118 These clinicians also suggest the following general dosages, calculated based on the patient's age and rounded to the nearest quarter-, half-, or whole-tablet dosage strengths: 1.25 mg daily for infants; 2.5-5 mg daily for children 1-5 years of a 5-10 mg daily for children 5-10 years of a and 10-20 mg daily for children 10-18 years of age.118 Patients with severe clinical or biochemical hyperthyroidism may receive methimazole dosages that are 50-100% higher than those usually recommended for the treatment of Graves' disease.118 When thyroid hormone concentrations normalize, these clinicians state that methimazole dosages may be reduced by 50% or more to maintain a euthyroid state.118
The optimum duration of antithyroid therapy remains to be clearly established. However, some clinicians state that if methimazole is chosen as first-line therapy for Graves' disease in children, the drug should be continued for 1-2 years and then discontinued, or dosage reduced, to assess whether the patient is in remission.118 If the patient is not in remission following 1-2 years of methimazole therapy, treatment with radioactive iodine or thyroidectomy should be considered, depending on the age of the patient.118 Alternatively, methimazole may be continued for extended periods as long as adverse effects do not occur and hyperthyroidism is controlled; this approach may be used as a bridge to radioactive iodine therapy or surgery at a later age if remission still has not occurred.118 Low-dose methimazole may be continued in selected situations in which radioactive iodine therapy or surgery may not be suitable or possible.118
If methimazole is used prior to thyroidectomy to render children with Graves' disease euthyroid, some clinicians state that methimazole is usually administered for 1-2 months in preparation for the procedure.118
If methimazole is used as pretreatment prior to radioactive iodine therapy in children with Graves' disease, some clinicians recommend that methimazole be discontinued 3-5 days before administration of radioactive iodine.118 Although some clinicians restart antithyroid drugs after radioactive iodine therapy, other clinicians state that this practice is seldom required in children.118
Adverse dermatologic effects are most commonly reported. Minor adverse effects of methimazole include rash, urticaria, pruritus, abnormal hair loss, skin pigmentation, edema, nausea, vomiting, epigastric distress, loss of taste, arthralgia, myalgia, paresthesia, and headache.101 Drowsiness, neuritis, vertigo, jaundice, sialadenopathy, and lymphadenopathy also have occurred in patients receiving the drug.101 (See Cautions: Hepatic Effects.) In one patient, peripheral neuritis occurred during long-term (23 months) therapy with methimazole but disappeared following discontinuance of the drug.
Although reported much less frequently, severe adverse effects of methimazole include inhibition of myelopoieses (agranulocytosis [see Cautions: Agranulocytosis], granulocytopenia, thrombocytopenia, and aplastic anemia); drug fever; lupus-like syndrome; insulin autoimmune syndrome (which can result in hypoglycemic coma); hepatitis (see Cautions: Hepatic Effects); periarteritis; and hypoprothrombinemia.101 Nephritis occurs very rarely in patients receiving methimazole.101
Agranulocytosis is a potentially life-threatening adverse effect of methimazole therapy.101 Most cases of agranulocytosis appear to occur within the first 2 months of therapy, but rarely may occur after 4 months of therapy. Although methimazole-induced agranulocytosis may be dose related (possibly occurring more frequently with higher dosages of the drug), agranulocytosis may occur irrespective of dosage, length of treatment, or previous exposure to the antithyroid drug, and may occur more frequently in geriatric patients.118, 122, 123, 126, 127, 128 The mechanism(s) of methimazole-induced agranulocytosis has not been determined, but antigranulocyte antibodies have been reported in some patients with thioamide-induced agranulocytosis; a direct toxic effect of these drugs on bone marrow has not been excluded as an additional possible cause.
Although there have been reports of hepatotoxicity (including acute liver failure) associated with methimazole, the risk of hepatotoxicity appears to be lower with methimazole than with propylthiouracil, especially in pediatric patients.101 (See Cautions: Pediatric Precautions.) Jaundice associated with methimazole-induced hepatitis may persist for several weeks after discontinuance of the drug.101
Methimazole may cause hypothyroidism necessitating routine monitoring of thyrotropin (thyroid stimulating hormone, TSH) and free thyroxine (T4) concentrations; dosage should be adjusted to maintain a euthyroid state.101 (See Cautions: Precautions and Contraindications.) Because methimazole readily crosses the placenta, the drug can cause fetal goiter and cretinism when administered to a pregnant woman.101 (See Pregnancy under Cautions: Pregnancy and Lactation.)
Precautions and Contraindications
Some clinicians suggest that a baseline complete blood count, including white count with differential, be performed prior to initiating antithyroid drug therapy in patients with Graves' disease.118 Patients receiving methimazole should be closely monitored and should be instructed to contact their clinician immediately if signs or symptoms of illness, particularly sore throat, skin eruptions, fever, chills, headache, or general malaise, occur; it is particularly important to carefully monitor for these signs and symptoms during the early stages of methimazole therapy since methimazole-induced agranulocytosis usually occurs during the first several months of therapy. Leukopenia, thrombocytopenia, and/or aplastic anemia (pancytopenia) also may occur.101 Leukocyte and differential counts should be performed in patients who develop fever or sore throat or other signs or symptoms of illness while receiving the drug.101 Methimazole should be used with extreme caution in patients receiving other drugs known to cause agranulocytosis.101 The manufacturer states that methimazole should be discontinued in the presence of agranulocytosis, aplastic anemia (pancytopenia), ANCA-positive vasculitis, hepatitis, or exfoliative dermatitis, and the patient's bone marrow indices should be monitored.101 Some clinicians state that patients should be informed of the adverse effects associated with methimazole (e.g., agranulocytosis) and advised to immediately discontinue the drug and promptly contact their clinician if fever or pharyngitis occurs.101, 118 In a patient who develops agranulocytosis or other serious adverse effects while receiving either methimazole or propylthiouracil, some clinicians state that use of the other drug also is contraindicated because of the risk of cross-sensitivity between the two drugs.118 Because methimazole may cause hypoprothrombinemia and bleeding, prothrombin time should be monitored during therapy, particularly prior to surgery (see Drug Interactions: Anticoagulants).101
Some clinicians suggest that liver function tests, including alkaline phosphatase, aminotransferase, and bilirubin, be performed prior to initiating antithyroid drug therapy in patients with Graves' disease.118 Patients should be informed of the adverse hepatic effects associated with methimazole and advised to immediately discontinue the drug and promptly contact their clinician if pruritic rash, jaundice, acholic stools, dark urine, arthralgias, abdominal pain, nausea, or fatigue occurs.118 Patients with symptoms suggestive of hepatic dysfunction (e.g., anorexia, pruritus, right upper-quadrant pain) should have prompt evaluation of their liver function (alkaline phosphatase, bilirubin) and hepatocellular integrity (ALT, AST).101 If there is evidence of a clinically important liver abnormality, including hepatic aminotransferase concentrations exceeding 3 times the upper limit of normal, the manufacturer states that the drug should be discontinued promptly.101
Thyroid function should be monitored periodically in patients receiving methimazole.101 In patients with Graves' disease, some clinicians state that thyroid function (e.g., serum free T4, serum free or total triiodothyronine [T3], TSH) should be monitored before initiating therapy and then every 4-8 weeks thereafter (with subsequent dosage adjustments as needed) until thyroid function is stable or the patient is euthyroid; once the patient is euthyroid, thyroid function may be monitored every 2-3 months.118, 122, 123, 124 Early in the course of antithyroid therapy, serum TSH concentration is not a reliable parameter to monitor because it may remain suppressed for several months after initiation of therapy despite normalization of free T4 concentrations.118, 122, 123, 124 The finding of a suppressed TSH concentration during this period, therefore, does not indicate a need for a dosage increase.123 However, once clinical evidence of resolution of hyperthyroidism occurs, the finding of an elevated serum TSH concentration indicates that a lower maintenance dosage of methimazole should be employed.101, 123 Monitoring serum T3 concentrations may sometimes be useful for dosage adjustment; in patients in whom total or free T3 concentrations remain elevated despite low, normal, or reduced free T4 concentrations, an increase in antithyroid dosage may be necessary.122, 123, 124 When methimazole is discontinued in patients with Graves' disease, thyroid function should be monitored every 1-3 months for 6-12 months to diagnose relapse early, and patients should be advised to contact clinicians if symptoms of hyperthyroidism occur.118
Methimazole is contraindicated in patients who are hypersensitive to the drug or any ingredient in the formulation.101 Cross-sensitivity between thioamides may occur118, 121 (i.e., in approximately 50% of patients switched from one thioamide agent to the other).122 In patients who develop agranulocytosis or other serious adverse effects while receiving either methimazole or propylthiouracil, some clinicians state that use of the other drug also is contraindicated because of the risk of cross-sensitivity between the two drugs.118 In patients experiencing serious allergic reactions to methimazole, some clinicians state that using the alternative antithyroid drug (i.e., propylthiouracil) is not recommended.118
Because of postmarketing reports of severe liver injury in pediatric patients receiving propylthiouracil, methimazole is preferred over propylthiouracil when an antithyroid drug is required for a pediatric patient.101, 118 (See Uses: Hyperthyroidism.) During postmarketing experience, cases of severe liver injury, including hepatic failure requiring liver transplantation or resulting in death, have been reported in pediatric patients receiving propylthiouracil; however, no such cases have been reported in pediatric patients treated with methimazole.109, 117 (See Cautions: Precautions and Contraindications.)
Methimazole readily crosses the placental membranes and may cause fetal harm, particularly when administered in the first trimester of pregnancy.101 The drug can also cause fetal goiter and hypothyroidism (cretinism) when administered to a pregnant woman.101
In April 2010, the US Food and Drug Administration (FDA) reported a review of postmarketing data analyzing the potential for birth defects associated with use of propylthiouracil or methimazole during pregnancy.112 FDA found that congenital malformations were reported approximately 3 times more often with prenatal exposure to methimazole compared with propylthiouracil (29 cases with methimazole; 9 cases with propylthiouracil).112 In addition, there was a distinct and consistent pattern of congenital malformations associated with the use of methimazole that was not found with propylthiouracil.112 Approximately 90% of the congenital malformations with methimazole were craniofacial malformations (e.g., scalp epidermal aplasia [aplasia cutis], facial dysmorphism, choanal atresia).112 In most of the cases, there were multiple malformations that frequently included a combination of craniofacial defects and GI atresia or aplasia.112 These specific birth defects were associated with the use of methimazole during the first trimester of pregnancy but were not found when the drug was administered later in pregnancy.112 In contrast, FDA did not find a consistent pattern of birth defects associated with the use of propylthiouracil and concluded that there is no convincing evidence of an association between propylthiouracil use and congenital malformations, even with use during the first trimester.112
Despite the potential fetal hazard, antithyroid agents are still considered the therapy of choice for the management of hyperthyroidism during pregnancy.108, 118, 119, 122 Since methimazole may be associated with the rare development of fetal abnormalities, such as aplasia cutis, craniofacial malformations (facial dysmorphism, choanal atresia), and GI malformations (esophageal atresia with or without tracheoesophageal fistula, umbilical abnormalities), propylthiouracil is the preferred agent when an antithyroid drug is indicated during organogenesis in the first trimester of pregnancy or just prior to the first trimester of pregnancy.100, 101, 103, 106, 107, 108, 109, 118, 119 Patients receiving methimazole should be switched to propylthiouracil if pregnancy is confirmed in the first trimester.119 Because of the potential adverse maternal effects of propylthiouracil (e.g., hepatotoxicity), however, it may be preferable to switch from propylthiouracil to methimazole for the second and third trimesters (i.e., after the first trimester).108, 109, 118, 119 If the patient is switching from propylthiouracil to methimazole, thyroid function should be assessed after 2 weeks and then every 2-4 weeks thereafter.108 It is not known if the risk of methimazole-induced aplasia cutis or embryopathy outweighs the risk of propylthiouracil-induced hepatotoxicity.104
If methimazole is used during pregnancy for the management of hyperthyroidism, the manufacturer states that a sufficient, but not excessive, dosage of methimazole is necessary; the lowest possible dosage of methimazole to control the maternal disease should be used.101 Some clinicians state that antithyroid drug therapy should be initiated or adjusted to maintain maternal free thyroxine (T4) concentrations at or just above the upper limit of normal (ULN) of the nonpregnant reference range, or to maintain total T4 concentrations at 1.5 times the ULN or the free T4 index in the ULN, while using the lowest possible dosage of antithyroid drugs.108, 119 In women receiving antithyroid drugs during pregnancy, free T4 and TSH concentrations should be monitored approximately every 2-6 weeks.119 The manufacturer states that because thyroid dysfunction diminishes in many women as pregnancy proceeds, a reduction in dosage of antithyroid therapy may be possible, and, in some patients, use of antithyroid therapy can be discontinued 2-3 weeks before delivery.101
Patients should be advised to contact their clinician immediately about their therapy if they are or plan to become pregnant while receiving an antithyroid drug.101 If methimazole is used during pregnancy or if the patient becomes pregnant while receiving the drug, the patient should be advised of the potential hazard to the fetus; in addition, when considering antithyroid drug use during pregnancy, the patient should be informed of the risks of methimazole-associated fetal malformations, as well as the risks of propylthiouracil-associated hepatotoxicity.101, 104, 106, 109
Methimazole is distributed into milk.101 However, several studies found no effect on clinical status in nursing infants of women receiving methimazole, particularly if thyroid function is monitored at frequent (weekly or biweekly) intervals.101 A long-term study of 139 thyrotoxic lactating women and their infants failed to demonstrate toxicity in infants who are breast-fed by women receiving methimazole.101
Methimazole generally is compatible with breast-feeding, and moderate dosages of the drug (i.e., 20-30 mg daily) appear to be safe during breast-feeding.110, 119, 120, 121, 122 Because of concerns regarding severe hepatotoxicity (i.e., hepatic necrosis in either woman or child) associated with maternal use of propylthiouracil, some clinicians consider methimazole to be the preferred antithyroid drug in nursing women.118, 119 If an antithyroid drug is used in nursing women, some clinicians recommend that the drug be administered after a feeding and in divided doses, and that thyroid function be monitored in nursing infants.119
Methimazole should be used with extreme caution in patients receiving other drugs known to cause agranulocytosis.101 (See Cautions: Agranulocytosis and also see Cautions: Precautions and Contraindications.)
Because of the potential inhibition of vitamin K activity by methimazole, the activity of oral anticoagulants (e.g., warfarin) may be increased.101 However, methimazole also may decrease the anticoagulant effect of warfarin.122 Additional monitoring of prothrombin time (PT)/international normalized ratio (INR) should be considered, particularly prior to surgery.101 Dosage adjustment of warfarin may be necessary.122
Beta-Adrenergic Blocking Agents
Hyperthyroidism may cause an increased clearance of β-adrenergic blocking agents with a high extraction ratio.101 Dosage reduction of the β-adrenergic blocking agent may be needed when a hyperthyroid patient becomes euthyroid.101
Serum digitalis concentrations may be increased when hyperthyroid patients receiving a stable digitalis glycoside regimen become euthyroid; dosage reduction of the digitalis glycoside may be needed.101
Theophylline clearance may decrease when hyperthyroid patients receiving a stable theophylline regimen become euthyroid; dosage reduction of theophylline may be needed.101
In general, overdosage of methimazole may be expected to produce effects that are extensions of common adverse reactions. Symptoms may include nausea, vomiting, epigastric distress, headache, fever, joint pain, pruritus, and edema.101 Aplastic anemia (pancytopenia) or agranulocytosis may be manifested in hours to days.101 Agranulocytosis is the most serious effect associated with methimazole overdosage. Less frequent adverse effects include exfoliative dermatitis, hepatitis, nephrotic syndrome, neuropathies, and CNS stimulation or depression.101 No data are available on the median lethal dose of methimazole or the concentration of drug in biologic fluids associated with toxicity and/or death.101
Treatment of methimazole overdosage generally involves appropriate supportive care as dictated by the patient's medical status.101 Clinicians should consider consulting a poison control center for the most current information on the management of methimazole overdosage.101
Methimazole inhibits the synthesis of thyroid hormones by interfering with the incorporation of iodine into tyrosyl residues of thyroglobulin; the drug also inhibits the coupling of these iodotyrosyl residues to form iodothyronine. Although the exact mechanism(s) has not been fully elucidated, methimazole may interfere with the oxidation of iodide ion and iodotyrosyl groups. Based on limited evidence, it appears that the coupling reaction is more sensitive to antithyroid agents than the iodination reaction. Methimazole does not inhibit the action of thyroid hormones already formed and present in the thyroid gland or circulation nor does the drug interfere with the effectiveness of exogenously administered thyroid hormones. Patients whose thyroid gland contains a relatively high concentration of iodine (e.g., from prior ingestion or from administration during diagnostic radiologic procedures) may respond relatively slowly to antithyroid agents. Unlike propylthiouracil, methimazole does not inhibit the peripheral deiodination of thyroxine to triiodothyronine.
Methimazole is rapidly absorbed from the GI tract following oral administration with peak plasma concentrations occurring within about 1 hour. Methimazole readily crosses the placenta and is distributed into milk in concentrations approximately equal to those in maternal serum. Methimazole is metabolized in the liver.101 The elimination half-life of methimazole reportedly ranges from about 5-13 hours. The drug is excreted in urine. In one study, about 12% of a dose was excreted in urine within 24 hours.
Methimazole is a thioimidazole-derivative antithyroid agent. The drug differs chemically and structurally from propylthiouracil and other thiouracil derivatives in that methimazole has a 5-membered ring instead of a 6-membered ring. Although presence of a thioamide group appears to be sufficient for antithyroid activity, methimazole, like propylthiouracil and carbimazole, contains the thioureylene moiety.
Methimazole occurs as a white, crystalline substance and is freely soluble in water.101
Commercially available methimazole tablets should be stored at controlled room temperature (15-30°C).101
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets | 5 mg* | ||
Tapazole® (scored) | ||||
10 mg* | methIMAzole Tablets | |||
Tapazole® (scored) | King |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Only references cited for selected revisions after 1984 are available electronically.
100. Food and Drug Administration. FDA Alert: Propylthiouracil-induced liver failure. Rockville, MD; 2009 Jun 4. From FDA website. Accessed 2009 Oct 28. [Web]
101. King Pharmaceuticals, Inc. Tapazole® (methimazole) tablets prescribing information. Bristol, TN; 2012 Feb.
103. Bahn RS, Burch HS, Cooper DS et al. The Role of Propylthiouracil in the Management of Graves' Disease in Adults: report of a meeting jointly sponsored by the American Thyroid Association and the Food and Drug Administration. Thyroid . 2009; 19:673-4. [PubMed 19583480]
104. Eunice Kennedy Shriver National Institute of Child Health and Human Development. Hepatic toxicity following treatment for pediatric Graves' disease meeting: October 28, 2008. Conference proceeding. Available from website. Accessed 2009 Oct 30. [Web]
106. Rivkees SA, Mattison DR. Propylthiouracil (PTU) hepatotoxicity in children and recommendations for discontinuation of use. Int J Pediatr Endocrinol . 2009. Article ID 132041. DOI:10.1155/2009/132041.
107. Cooper DS, Rivkees SA. Putting propylthiouracil in perspective. J Clin Endocrinol Metab . 2009; 94:1881-2. [PubMed 19401361]
108. De Groot L, Abalovich M, Alexander EK et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab . 2012; 97:2543-65. [PubMed 22869843]
109. Actavis Elizabeth LLC. Propylthiouracil tablets prescribing information. Elizabeth, NJ; 2012 Jul.
110. American Academy of Pediatrics Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics . 2001; 108:776-89. [PubMed 11533352]
112. Food and Drug Administration. FDA drug safety communication: New boxed warning on severe liver injury with propylthiouracil. Rockville, MD; 2010 Apr 21. Available from FDA website. Accessed 2010 Sep 8. [Web]
117. Rivkees SA, Szarfman A. Dissimilar hepatotoxicity profiles of propylthiouracil and methimazole in children. J Clin Endocrinol Metab . 2010; 95:3260-7. [PubMed 20427502]
118. Bahn Chair RS, Burch HB, Cooper DS et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid . 2011; 21:593-646. [PubMed 21510801]
119. Stagnaro-Green A, Abalovich M, Alexander E et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid . 2011; 21:1081-125. [PubMedCentral][PubMed 21787128]
120. Methimazole. In: Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2011:920-5.
121. American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists, number 37, August 2002: Thyroid disease in pregnancy. Obstet Gynecol . 2002; 100:387-96. [PubMed 12166417]
122. . Drugs for thyroid disorders. Treat Guidel Med Lett . 2009; 7:57-64; quiz 2p following 64. [PubMed 19636287]
123. Franklyn JA, Boelaert K. Thyrotoxicosis. Lancet . 2012; 379:1155-66. [PubMed 22394559]
124. Cooper DS. Antithyroid drugs. N Engl J Med . 2005; 352:905-17. [PubMed 15745981]
125. Abraham P, Avenell A, McGeoch SC et al. Antithyroid drug regimen for treating Graves' hyperthyroidism. Cochrane Database Syst Rev . 2010; :CD003420. [PubMed 20091544]
126. Mutharasan P, Oatis W, Kwaan H et al. Delayed anithyroid drug-induced agranulocytosis. Endocr Pract . 2012 Jul-Aug; 18:e69-72.
127. Yang J, Zhong J, Zhou LZ et al. Sudden onset agranulocytosis and hepatotoxicity after taking methimazole. Intern Med . 2012; 51:2189-92. [PubMed 22892501]
128. Takata K, Kubota S, Fukata S et al. 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; 19:559-63. [PubMed 19445623]
129. Walter MA, Briel M, Christ-Crain M et al. Effects of antithyroid drugs on radioiodine treatment: systematic review and meta-analysis of randomised controlled trials. BMJ . 2007; 334:514. [PubMedCentral][PubMed 17309884]
130. Ross DS. Radioiodine therapy for hyperthyroidism. N Engl J Med . 2011; 364:542-50. [PubMed 21306240]
131. Seigel SC, Hodak SP. Thyrotoxicosis. Med Clin North Am . 2012; 96:175-201. [PubMed 22443970]