CLASSES
Anti-thyroid Agents
DESCRIPTION
Oral thioimidazole antithyroid agent; lower risk of hepatotoxicity when compared to propylthiouracil (PTU)
Used for hyperthyroid conditions including Graves disease in both adult and pediatric patients
Do not use in early pregnancy
COMMON BRAND NAMES
Northyx, Tapazole
HOW SUPPLIED
Methimazole/Northyx/Tapazole Oral Tab: 5mg, 10mg
DOSAGE & INDICATIONS
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.[61515] 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.[47198]
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.[47198]
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.[47198]
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.[47198]
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.[61515]
MAXIMUM DOSAGE
Adults
60 mg/day PO.
Geriatric
60 mg/day PO.
Adolescents
0.4 mg/kg/day PO is the FDA-approved dose; however, doses up to 1 mg/kg/day PO (Max: 30 mg) have been used off-label.
Children
0.4 mg/kg/day PO is the FDA-approved dose; however, doses up to 1 mg/kg/day PO (Max: 30 mg) have been used off-label.
Infants
0.4 mg/kg/day PO is the FDA-approved dose; 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.
DOSING CONSIDERATIONS
Hepatic Impairment
No specific recommendations for dosage adjustments are available. Discontinue if clinically important evidence of hepatic dysfunction (e.g., LFT elevation) occurs during use.
Renal Impairment
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
ADMINISTRATION
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.
Oral Administration
Administer orally at the same time(s) each day in relation to meals.
STORAGE
Northyx:
- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
Tapazole:
- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
CONTRAINDICATIONS / PRECAUTIONS
General Information
Antithyroid agents should be discontinued at least 3—4 days prior to treatment with radioiodine (sodium iodide, I-131). Typically, antithyroid agents are not reintroduced until 1 week after the radioiodine treatment.
Agranulocytosis, aplastic anemia, bone marrow suppression, geriatric, leukopenia, neutropenia, serious rash, thrombocytopenia, vasculitis
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. Cross-hypersensitivity occurs in roughly 50% of patients who have previously exhibited a major hypersensitivity to an antithyroid thioamide medication (like propylthiouracil). Agranulocytosis (severe neutropenia) is the most serious adverse reaction of methimazole, and is most likely immune-mediated. Patients should report symptoms of sore throat, fever, and general malaise promptly to their prescriber for evaluation. Thrombocytopenia, and aplastic anemia (pancytopenia) may also occur. Methimazole should be used cautiously in other patients with bone marrow suppression or risk factors for methimazole hematologic toxicity. Use with caution in adults 40 years of age or older, including the geriatric adult. Doses of greater than 40 mg/day should generally be avoided, if possible, due to the increased risk of agranulocytosis. Use methimazole with extreme caution in combination with other drugs known to cause agranulocytosis. Leukopenia occurs in 10% of untreated hyperthyroid patients and is not a contraindication for use of methimazole, however, CBCs and differentials should be monitored closely. The drug should be discontinued in the presence of agranulocytosis, aplastic anemia (pancytopenia), ANCA-positive vasculitis, hepatitis, or exfoliative dermatitis and the patient's complete blood counts (CBC) should be monitored.
Hepatic disease, hepatitis, hepatotoxicity, jaundice
In general, use methimazole with caution in patients with pre-existing hepatic disease. Although there have been reports of hepatotoxicity (including acute liver failure) associated with methimazole, the risk of hepatotoxicity is less with methimazole than with propylthiouracil, especially in the pediatric population. Symptoms suggestive of hepatic dysfunction (anorexia, jaundice, pruritus, right upper quadrant pain, etc.) should prompt evaluation of liver function tests (i.e., bilirubin, alkaline phosphatase, ALT, AST). Drug treatment should be discontinued promptly in the event of clinically significant evidence of liver abnormality including hepatic transaminase values exceeding 3 times the upper limit of normal (ULN). The drug should be discontinued in the presence of apparent drug-induced hepatitis and the patient's complete blood counts (CBC) should be monitored.
Pregnancy
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.
Breast-feeding
Methimazole is considered compatible for use during breast-feeding. Methimazole is present in breast milk. However, several studies found no effect on clinical status in nursing infants of mothers taking methimazole. A long-term study of 139 thyrotoxic lactating mothers and their infants failed to demonstrate toxicity in infants who are nursed by mothers receiving treatment with methimazole. Monitor thyroid function at frequent (weekly or biweekly) intervals. The American Thyroid Association (ATA) guidelines recommend that low to moderate doses(e.g., methimazole 20 to 30 mg/day) be used during lactation. The ATA also recommends that the infant's thyroid function be monitored regularly and that the mothers take their thyroid medication in divided doses, with doses taken immediately following a feeding.
ADVERSE REACTIONS
Severe
pancytopenia / Delayed / 0-1.0
agranulocytosis / Delayed / 0-1.0
aplastic anemia / Delayed / 0-1.0
hepatic necrosis / Delayed / 0-1.0
hepatic encephalopathy / Delayed / 0-1.0
exfoliative dermatitis / Delayed / Incidence not known
periarteritis / Delayed / Incidence not known
vasculitis / Delayed / Incidence not known
lupus-like symptoms / Delayed / Incidence not known
nephrotic syndrome / Delayed / Incidence not known
teratogenesis / Delayed / Incidence not known
Moderate
leukopenia / Delayed / 0-25.0
neutropenia / Delayed / 0-10.0
thrombocytopenia / Delayed / 0-1.0
peripheral neuropathy / Delayed / 0-1.0
hepatitis / Delayed / 0-1.0
jaundice / Delayed / 0-1.0
bleeding / Early / Incidence not known
hypoprothrombinemia / Delayed / Incidence not known
hypothyroidism / Delayed / Incidence not known
lymphadenopathy / Delayed / Incidence not known
edema / Delayed / Incidence not known
hypoglycemia / Early / Incidence not known
sialadenitis / Delayed / Incidence not known
neuritis / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
Mild
nausea / Early / 1.0-10.0
pruritus / Rapid / 3.0-5.0
rash / Early / 3.0-5.0
alopecia / Delayed / 3.0-5.0
skin hyperpigmentation / Delayed / 3.0-5.0
urticaria / Rapid / 3.0-5.0
dysgeusia / Early / 0-1.0
fever / Early / Incidence not known
arthralgia / Delayed / Incidence not known
myalgia / Early / Incidence not known
headache / Early / Incidence not known
paresthesias / Delayed / Incidence not known
vertigo / Early / Incidence not known
drowsiness / Early / Incidence not known
anorexia / Delayed / Incidence not known
vomiting / Early / Incidence not known
DRUG INTERACTIONS
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.
Bendroflumethiazide; 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.
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.
Levobetaxolol: (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.
Penbutolol: (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.
Propranolol; 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.
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.
PREGNANCY AND LACTATION
Pregnancy
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.
Methimazole is considered compatible for use during breast-feeding. Methimazole is present in breast milk. However, several studies found no effect on clinical status in nursing infants of mothers taking methimazole. A long-term study of 139 thyrotoxic lactating mothers and their infants failed to demonstrate toxicity in infants who are nursed by mothers receiving treatment with methimazole. Monitor thyroid function at frequent (weekly or biweekly) intervals. The American Thyroid Association (ATA) guidelines recommend that low to moderate doses(e.g., methimazole 20 to 30 mg/day) be used during lactation. The ATA also recommends that the infant's thyroid function be monitored regularly and that the mothers take their thyroid medication in divided doses, with doses taken immediately following a feeding.
MECHANISM OF ACTION
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.
PHARMACOKINETICS
Methimazole is administered orally. Once absorbed, methimazole is actively concentrated by the thyroid gland. 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 < 10%. The elimination half-life is approximately 5—9 hours. However, the intrathyroidal residence of methimazole is roughly 20 hours, and the duration of action 40 hours, which allows once-daily dosing some patients. The plasma elimination half-life of methimazole is not appreciably altered by the patient's thyroid status.
Oral Route
Methimazole is rapidly absorbed from the gastrointestinal tract, reaching peak serum concentrations within 1—2 hours after administration. However, it usually takes 2—4 months of treatment to achieve initial euthyroid status; response rates are dependent on several pharmacodynamic and patient variables.