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Methimazole

Pronunciation

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 (surgery or radioactive iodine therapy is not appropriate); amelioration of hyperthyroid symptoms in preparation for thyroidectomy or radioactive iodine therapy.

Use: Unlabeled

Thyrotoxicosis or thyrotoxic crisis

Contraindications

Hypersensitivity to methimazole or any component of the formulation

Dosing: Adult

Note: Usually administered in 3 equally divided doses at approximately 8-hour intervals.

Hyperthyroidism: Oral: Initial: 15 mg daily in 3 divided doses for mild hyperthyroidism; 30 to 40 mg daily in 3 divided doses for moderately severe hyperthyroidism; 60 mg daily in 3 divided doses for severe hyperthyroidism; maintenance: 5 to 15 mg daily (may be given as a single daily dose in many cases) (Mandana 2004)

Adjust dosage as required to achieve and maintain serum T3, T4, and TSH levels in the normal range. An elevated T3 may be the sole indicator of inadequate treatment. An elevated TSH indicates excessive antithyroid treatment.

Hyperthyroidism associated with Graves’ disease: Oral:

Manufacturer’s labeling: Initial: 15 mg daily in 3 divided doses for mild hyperthyroidism; 30 to 40 mg daily in 3 divided doses for moderately severe hyperthyroidism; 60 mg daily in 3 divided doses for severe hyperthyroidism; maintenance: 5 to 15 mg daily.

Alternate dosing:Initial: 10 to 20 mg once daily to restore euthyroidism; maintenance: 5 to 10 mg once daily for a total of 12 to 18 months, then taper or discontinue if TSH is normal at that time (Bahn 2011).

Iodine-induced thyrotoxicosis (off-label use): Oral: 20 to 40 mg daily given either once or twice daily (Bahn 2011)

Thyrotoxicosis or thyroid storm (off-label use): Oral: Note: Recommendations vary; use in combination with other specific agents. Dosages of 20 to 25 mg every 6 hours have been used; once stable, dosing frequency may be reduced to once or twice daily (Nayak 2006). The American Thyroid Association and the American Association of Clinical Endocrinologists recommend 60 to 80 mg daily (Bahn 2011). Rectal administration has also been described (Nabil, 1982).

Thyrotoxicosis, type I amiodarone-induced (off-label use): Oral: 40 mg once daily to restore euthyroidism (generally 3 to 6 months). Note: If high doses continue to be required, dividing the dose may be more effective (Bahn 2011).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Usually administered in 3 equally divided doses at approximately 8-hour intervals.

Hyperthyroidism: Oral: Initial: 0.4 mg/kg/day in 3 divided doses; maintenance: 0.2 mg/kg/day in 3 divided doses

Hyperthyroidism associated with Graves’ disease: Oral:

Manufacturer’s labeling: Initial: 0.4 mg/kg/day in 3 divided doses; maintenance: 0.2 mg/kg/day in 3 divided doses

Alternate dosing: Initial: 0.2 to 0.5 mg/kg once daily (range: 0.1 to 1 mg/kg/day) to restore euthyroidism, then reduce dose by 50% or more and continue for a total of 1 to 2 years; may then discontinue or reduce dose to assess if patient is in remission. Note: In severe cases, initial doses that are 50% to 100% higher may be used (Bahn 2011).

The following dosing approach may also be used (Bahn 2011):

Infants: 1.25 mg daily

Children 1 to 5 years: 2.5 to 5 mg daily

Children 5 to 10 years: 5 to 10 mg daily

Children and Adolescents 10 to 18 years: 10 to 20 mg daily

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

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 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

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. Avoid combination

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

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

Sodium Iodide I131: Antithyroid Agents may diminish the therapeutic effect of Sodium Iodide I131. Management: Discontinue antithyroid therapy 3-4 days prior to sodium iodide I-131 administration. Avoid combination

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

TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification

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

Adverse Reactions

Frequency not defined.

Cardiovascular: Antineutrophil cytoplasmic antibody-positive vasculitis, edema, hypersensitivity angiitis, periarteritis

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

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

Endocrine & metabolic: Goiter, hypoglycemic coma, insulin autoimmune syndrome, weight gain

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

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

Hepatic: Hepatic necrosis, hepatitis, jaundice

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

Renal: Nephritis

Miscellaneous: Fever

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. Use with caution with concomitant use of other drugs known to cause myelosuppression (particularly agranulocytosis). Monitor patients closely; discontinue if significant bone marrow suppression occurs, particularly agranulocytosis or aplastic anemia.

• Dermatitis: Antithyroid agents have been associated with rare but severe dermatologic reactions. Discontinue in the presence of exfoliative dermatitis.

• 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: ANCA-positive vasculitis may develop during therapy; discontinue use in the presence of vasculitis.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Monitoring Parameters

Monitor for signs of hypothyroidism, hyperthyroidism, free T4, T3; CBC with differential, liver function (baseline and as needed), serum thyroxine, free thyroxine index; prothrombin time (especially before surgical procedures)

Pregnancy Risk Factor

D

Pregnancy Considerations

Methimazole has been found to readily cross the placenta. Congenital anomalies, including esophageal atresia, choanal atresia, aplasia cutis, and dysmorphic facies, have been observed in neonates born to mothers taking methimazole during pregnancy (Stangaro-Green 2011). Nonteratogenic adverse events, including fetal and neonatal hypothyroidism, have been observed following maternal methimazole use. The transfer of thyroid-stimulating immunoglobulins can stimulate the fetal thyroid in utero and transiently after delivery and may increase the risk of fetal or neonatal hyperthyroidism (De Groot 2012; Stangaro-Green 2011).

Uncontrolled maternal hyperthyroidism may result in adverse neonatal outcomes (eg, prematurity, low birth weight, infants born small for gestational age) and adverse maternal outcomes (eg, pre-eclampsia, congestive heart failure) (ACOG 2002; Stangaro-Green 2011). To prevent adverse fetal and maternal events, normal maternal thyroid function should be maintained prior to conception and throughout pregnancy. Antithyroid treatment is recommended for the control of hyperthyroidism during pregnancy. Due to an increased risk of congenital anomalies with methimazole, propylthiouracil is preferred during the first trimester of pregnancy and methimazole is preferred during the second and third trimesters of pregnancy (ACOG 2002; De Groot 2012; Stangaro-Green 2011). If drug therapy is changed, maternal thyroid function should be monitored after 2 weeks and then every 2 to 4 weeks (De Groot 2012).

The severity of hyperthyroidism may fluctuate throughout pregnancy and may result in decreased dose requirements or discontinuation of methimazole 2 to 3 weeks prior to delivery.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience itching, change in taste, dizziness, fatigue, muscle pain, joint pain, hair loss, numbness or tingling, skin discoloration, vomiting, or nausea. Have patient report immediately to prescriber signs of infection, signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of lupus (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), signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating), severe headache, bruising, bleeding, severe loss of strength and energy, or edema (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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