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Methimazole

Medically reviewed by Drugs.com. Last updated on Mar 3, 2020.

Pronunciation

(meth IM a zole)

Index Terms

  • MMI
  • Thiamazole

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Tapazole: 5 mg, 10 mg [scored]

Generic: 5 mg, 10 mg

Brand Names: U.S.

  • Tapazole

Pharmacologic Category

  • Antithyroid Agent
  • Thioamide

Pharmacology

Inhibits the synthesis of thyroid hormones by blocking the oxidation of iodine in the thyroid gland; blocks synthesis of thyroxine and triiodothyronine (T3); does not inactivate circulating T4 and T3

Absorption

Almost complete (Clark 2006)

Distribution

Concentrated in thyroid gland

Metabolism

Hepatic

Excretion

Urine

Onset of Action

Antithyroid: 12 to 18 hours (Clark 2006)

Time to Peak

Serum: 1 to 2 hours (Clark 2006)

Duration of Action

36 to 72 hours (Clark 2006)

Half-Life Elimination

4 to 6 hours (Clark 2006)

Protein Binding

Plasma: None (Cooper 2005)

Use: Labeled Indications

Hyperthyroidism: Treatment of hyperthyroidism in patients with Graves disease or toxic multinodular goiter for whom surgery or radioactive iodine therapy is not appropriate; amelioration of hyperthyroid symptoms in preparation for thyroidectomy or radioactive iodine therapy.

Off Label Uses

Iodine-induced thyrotoxicosis

Based on the American Thyroid Association guidelines for the diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis, methimazole is recommended in iodine-induced thyrotoxicosis to reduce thyroid hormone production [Ross 2016].

Thyroid storm

Based on the American Thyroid Association guidelines for the diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis, antithyroid therapy is recommended as part of a multimodal approach to the management of thyroid storm (ie, life-threatening thyrotoxicosis). Methimazole reduces thyroid hormone production. Antithyroid agents that also block peripheral conversion of T4 to T3 (eg, propylthiouracil) may be preferred over methimazole in acute settings [Ross 2016].

Thyrotoxicosis, type I amiodarone-induced

Based on the American Thyroid Association guidelines for the diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis, methimazole is recommended in overt thyrotoxicosis (type I amiodarone-induced) to reduce thyroid hormone production [Ross 2016].

Contraindications

Hypersensitivity to methimazole or any component of the formulation.

Canadian labeling: Additional contraindications (not in US labeling): Breastfeeding, history of acute pancreatitis after administration of methimazole.

Dosing: Adult

Hyperthyroidism associated with Graves disease, toxic multinodular goiter, toxic adenoma (labeled uses), or iodine-induced thyrotoxicosis (off-label use):

Note: May use in combination with beta-blockade to manage hyperthyroid symptoms prior to definitive therapy or as chronic low-dose treatment; for iodine-induced thyrotoxicosis, may be used as an adjunct to beta-blockade for severe or prolonged (eg, >1 month) symptoms or in patients with underlying heart disease (ATA [Ross 2016]; Surks 2020).

Oral: Initial: Individualize initial dose based on clinical status and gland size; free T4 levels may be used to guide initial therapy (ATA [Ross 2016]; Ross 2020a):

Free T4 levels 1 to 1.5 times ULN: 5 to 10 mg once daily.

Free T4 levels >1.5 to 2 times ULN (or iodine-induced thyrotoxicosis): 10 to 20 mg once daily.

Free T4 levels >2 times ULN: 20 to 40 mg/day. To achieve euthyroidism more quickly and reduce GI-related adverse effects, may give in 2 to 3 divided doses (especially with doses >30 mg/day) (ATA [Ross 2016]; Burch 2015; Ross 2020a).

Dose adjustment: Oral: Usual maintenance dose: 5 to 10 mg once daily. Assess free T4 and total T3 at 4- to 6-week intervals; when normal, reduce dose by 30% to 50% and repeat thyroid function tests in 4 to 6 weeks; continue to adjust dose to achieve euthyroidism (ATA [Ross 2016]; Ross 2020a; Ross 2020b).

Duration of therapy: Depends on etiology and plans for definitive therapy:

Patients undergoing definitive therapy: Prior to definitive therapy, continue until euthyroid (typically 4 to 6 weeks); discontinue 2 to 3 days before radioactive iodine therapy or on the day of thyroidectomy (ATA [Ross 2016]; Walter 2006).

Patients not undergoing definitive therapy: For Graves disease, continue for 12 to 18 months, then assess for remission; for toxic multinodular goiter/toxic adenoma, continue indefinitely (ATA [Ross 2016]).

Iodine-induced thyrotoxicosis: Taper and discontinue therapy as iodine load is cleared (Surks 2020).

Thyroid storm (alternative to propylthiouracil) (off-label use): Note: Use in combination with other appropriate agents; if iodine is administered, delay iodine administration by ≥1 hour after methimazole (ATA [Ross 2016]).

Oral: Initial: 20 mg every 4 to 6 hours (ATA [Ross 2016]; Ross 2020c); once clinically stable, dose may be given less frequently (eg, 20 mg once or twice daily) (Nayak 2006). In patients who cannot take methimazole by mouth, alternative administration routes (eg, nasogastric, rectal) may be considered (Nabil 1982; Ross 2020c).

Thyrotoxicosis, type I amiodarone-induced (off-label use):

Oral: Initial: 30 to 40 mg once daily; adjust dose to achieve euthyroidism (eg, free T4, total T3, TSH levels in the normal range); if high doses (eg, >30 mg/day) are required after 3 to 6 months, it may be more effective to administer in 2 to 3 divided doses (ATA [Ross 2016]; Burch 2015; Ross 2020d). Note: If etiology of amiodarone-induced thyrotoxicosis (eg, type I or type II) cannot be determined or if patient is clinically unstable, use in combination with a glucocorticoid (ATA [Ross 2016]; Ross 2020d).

Duration of therapy: Depends on whether amiodarone therapy will be continued:

Continuing amiodarone: Continue methimazole indefinitely (ATA [Ross 2016]; Ross 2020d).

Discontinuing amiodarone: Taper methimazole slowly (eg, over months) to avoid recurrence of thyrotoxicosis (ATA [Ross 2016]; Ross 2020d).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Hyperthyroidism: Infants, Children, and Adolescents: Oral: Initial: 0.4 mg/kg/day in 3 divided doses (approximately every 8 hours); maintenance 0.2 mg/kg/day in 3 divided doses (50% of initial)

Graves disease (ATA [Ross 2016]): Note: In severe cases, higher doses may be required (50% to 100% higher); once patient euthyroid, reduce dose by ≥50% to maintain euthyroid; duration of therapy usually 1 to 2 years

Weight-based dosing: Infants, Children, and Adolescents: Oral: Initial: 0.2 to 0.5 mg/kg/dose once daily (range: 0.1 to 1 mg/kg/dose)

Fixed dosing (using 1/4, 1/2, or whole tablets): Oral:

Infants: 1.25 mg/day

Children 1 to 5 years: 2.5 to 5 mg/day

Children 5 to 10 years: 5 to 10 mg/day

Children ≥10 years and Adolescents: 10 to 20 mg/day

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Extemporaneously Prepared

Suppositories can be made from methimazole tablets; dissolve 1200 mg methimazole in 12 mL of water and add to 52 mL cocoa butter containing 2 drops of Span 80. Stir the resulting mixture to form a water-oil emulsion and pour into 2.6 mL suppository molds to cool.

Nabil N, Miner DJ, and Amatruda JM, "Methimazole: An Alternative Route of Administration," J Clin Endo Metab, 1982, 54(1):180-1.7054215

Administration

Rectal: In thyrotoxic crisis, rectal administration has been described (Nabil 1982).

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Drug Interactions

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Cardiac Glycosides: Antithyroid Agents may increase the serum concentration of Cardiac Glycosides. Monitor therapy

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Consider therapy modification

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

PrednisoLONE (Systemic): MethIMAzole may decrease the serum concentration of PrednisoLONE (Systemic). Monitor therapy

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Sodium Iodide I131: Antithyroid Agents may diminish the therapeutic effect of Sodium Iodide I131. Management: Discontinue antithyroid medications at least 3 days before sodium iodide I-131 administration, and avoid concurrent use. Avoid combination

Theophylline Derivatives: Antithyroid Agents may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Antithyroid Agents may diminish the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Adverse Reactions

Frequency not defined:

Cardiovascular: Edema, periarteritis

Central nervous system: Drowsiness, drug fever, headache, neuritis, paresthesia, vertigo

Dermatologic: Alopecia, pruritus, skin pigmentation, skin rash, urticaria

Endocrine & metabolic: Hypoglycemic coma, hypothyroidism, insulin autoimmune syndrome

Gastrointestinal: Ageusia, enlargement of salivary glands, epigastric distress, nausea, vomiting

Hematologic & oncologic: Agranulocytosis, aplastic anemia, granulocytopenia, hypoprothrombinemia, leukopenia, lymphadenopathy, thrombocytopenia

Hepatic: Hepatitis, jaundice

Neuromuscular & skeletal: Arthralgia, lupus-like syndrome, myalgia

Renal: Nephritis

Postmarketing: Acute hepatic failure, acute pancreatitis, acute renal injury, cerebral vasculitis, glomerulonephritis, hepatotoxicity, hypersensitivity angiitis, neuropathy, pulmonary alveolar hemorrhage, vasculitis (including ANCA positive)

Warnings/Precautions

Concerns related to adverse effects:

• Bleeding: May cause hypoprothrombinemia and bleeding. Monitoring is recommended, especially before surgical procedures.

• Bone marrow suppression: May cause significant bone marrow depression; the most severe manifestation is agranulocytosis. Aplastic anemia, thrombocytopenia, and leukopenia may also occur. Monitor patients closely; use with caution with concomitant use of other drugs known to cause myelosuppression (particularly agranulocytosis). Instruct patients to report immediately any signs/symptoms of infection (eg, fever, sore throat, pharyngitis, flu-like symptoms) and to discontinue therapy immediately if symptoms suggestive of agranulocytosis are present. A CBC with differential should be performed prior to initiation of therapy, during febrile illness, and at the onset of pharyngitis in all patients during therapy (Ross 2016).

• Dermatologic effects: Antithyroid agents have been associated with dermatologic reactions. Discontinue in the presence of a severe reaction.

• Fever: Discontinue in the presence of unexplained fever.

• Hepatic effects: Hepatotoxicity (including acute liver failure) may occur. Symptoms suggestive of hepatic dysfunction (eg, anorexia, pruritus, right upper quadrant pain) should prompt evaluation. Discontinue in the presence of hepatitis and clinically significant hepatic abnormality, including transaminase >3 times upper limit of normal.

• Hypothyroidism: May cause hypothyroidism; routinely monitor TSH and free T4 levels, adjust dose to maintain euthyroid state.

• Lupus-like syndrome: A lupus-like syndrome may occur.

• Vasculitis: Cases of vasculitis resulting in severe complications have been reported. Most cases were ANCA-positive and included leukocytoclastic cutaneous vasculitis, acute kidney injury and glomerulonephritis, alveolar/pulmonary hemorrhage, CNS vasculitis and neuropathy. Discontinue use for confirmed or suspected vasculitis. Some cases resolve/improve with drug discontinuation; severe cases may require further treatment (eg, corticosteroids, plasmapheresis).

Monitoring Parameters

Signs and symptoms of illness (ie, fever, sore throat, skin eruptions, general malaise).

CBC with differential (baseline and if development of febrile illness or pharyngitis occurs); prothrombin time (especially before surgical procedures); LFTs (bilirubin, alkaline phosphatase, ALT, AST) at baseline and if symptoms of liver injury occur (Ross 2016).

Thyroid function tests:

Serum free T4 and total T3 at 4- to 6-week intervals during dose titration, then every 2 to 3 months once euthyroid levels are achieved (with long-term therapy [ie, >18 months] may extend interval to every 4 to 6 months); in patients with Graves disease, if thyrotropin receptor antibodies (TRAbs) are negative, thyroid function tests should be monitored every 2 to 3 months for the first 6 months after discontinuing therapy, then at 4- to 6-month intervals for the next 6 months, then every 6 to 12 months thereafter (ATA [Ross 2016]).

Thyroid-stimulating hormone (TSH) periodically throughout treatment; TSH is not an adequate parameter to assess initial response as levels may remain suppressed for several months after starting therapy (ATA [Ross 2016]).

TRAb in patients with Graves disease prior to stopping medication; elevation at the end of therapy decreases likelihood of remission (ATA [Ross 2016]).

Reproductive Considerations

Females taking methimazole should notify their health care provider immediately once pregnancy is suspected (Alexander 2017).

Pregnancy Considerations

Methimazole crosses the placenta.

Birth defects have been observed in neonates exposed to maternal methimazole in the first trimester of pregnancy and include anomalies of the upper gastrointestinal tract (esophageal atresia or tracheoesophageal fistula), respiratory tract (choanal atresia), skin (aplasia cutis), and facial dysmorphism. Additional abdominal wall defects (umbilicocele), ventricular septal defects, and defects of the eye and urinary system have also been reported (Alexander 2017). Hypothyroidism may occur in the newborn.

Uncontrolled maternal hyperthyroidism may result in adverse neonatal and maternal outcomes. Antithyroid drugs are the treatment of choice for the control of hyperthyroidism during pregnancy, although recommendations for specific agents vary by guideline (ACOG 2015; Alexander 2017; De Groot 2012). Dose requirements of methimazole may be decreased as pregnancy progresses. To prevent adverse pregnancy outcomes, maternal TT4/FT4 should be at or just above the pregnancy specific upper limit of normal (Alexander 2017).

Patient Education

What is this drug used for?

• It is used to treat an overactive thyroid gland.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache

• Itching

• Change in taste

• Feeling sleepy

• Muscle pain

• Joint pain

• Hair loss

• Skin discoloration

• Throwing up

• Upset stomach

• Stomach pain

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infection

• Liver problems like dark urine, feeling tired, not hungry, upset stomach, stomach pain, light-colored stools, throwing up, or yellow skin or eyes

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain

• Lupus like rash on the cheeks or other body parts, sunburn easy, muscle or joint pain, chest pain or shortness of breath, or swelling in the arms or legs

• Low blood sugar like dizziness, headache, feeling tired, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating

• Shortness of breath

• Coughing up blood

• Burning or numbness feeling

• Swollen glands

• Bruising

• Bleeding

• Severe loss of strength and energy

• Swelling

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.