Methimazole

Methimazole
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vignesh Ponnusamy, M.B.B.S. [2]

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Overview

Methimazole is an antithyroid agent that is FDA approved for the {{{indicationType}}} of hyperthyroidism. Common adverse reactions include skin rash, urticaria, nausea, vomiting, epigastric distress, arthralgia, paresthesia, loss of taste, abnormal loss of hair, myalgia, headache, pruritus, drowsiness, neuritis, edema, vertigo, skin pigmentation, jaundice, sialadenopathy, and lymphadenopathy.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Hyperthyroidism

• Methimazole is indicated in the medical treatment of hyperthyroidism. Long-term therapy may lead to remission of the disease.

• Methimazole may be used to ameliorate hyperthyroidism in preparation for subtotal thyroidectomy or radioactive iodine therapy.

• Methimazole is also used when thyroidectomy is contraindicated or not advisable.

• Methimazole is administered orally. It is usually given in 3 equal doses at approximately 8-hour intervals.

• The initial daily dosage is 15 mg for mild hyperthyroidism, 30 to 40 mg for moderately severe hyperthyroidism, and 60 mg for severe hyperthyroidism, divided into 3 doses at 8-hour intervals. The maintenance dosage is 5 to 15 mg daily.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Methimazole in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Methimazole in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Hyperthyroidism

• Dosing Information

• Initially, the daily dosage is 0.4 mg/kg of body weight divided into 3 doses and given at 8-hour intervals. The maintenance dosage is approximately 1/2 of the initial dose.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Methimazole in pediatric patients.

Non–Guideline-Supported Use

Disorder of thyroid gland; Prophylaxis - Toxicity due to radiotherapy; Prophylaxis

• Dosing Information

• Methimazole 0.5 milligrams/kilogram body mass in 2 doses.

Contraindications

• Methimazole is contraindicated in the presence of hypersensitivity to the drug and in nursing mothers because the drug is excreted in milk.

Warnings

• Congenital Malformations

• Methimazole readily crosses the placental membranes and can cause fetal harm, particularly when administered in the first trimester of pregnancy. Rare instances of congenital defects, including aplasia cutis, craniofacial malformations (facial dysmorphism; choanal atresia) and gastrointestinal malformations (esophageal atresia with or without tracheoesophageal fistula; umbilical abnormalities) have occurred in infants born to mothers who received TAPAZOLE during pregnancy. If TAPAZOLE is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be warned of the potential hazard to the fetus.
• Since the above congenital defects have been reported in offspring of patients treated with TAPAZOLE, it may be appropriate to use other agents in pregnant women requiring treatment for hyperthyroidism, particularly during organogenesis, in the first trimester of pregnancy. If TAPAZOLE is used, the lowest possible dose to control the maternal disease should be given.

• Agranulocytosis

• Agranulocytosis is potentially a life-threatening adverse reaction of TAPAZOLE therapy. Patients should be instructed to immediately report to their physicians any symptoms suggestive of agranulocytosis, such as fever or sore throat. Leukopenia, thrombocytopenia, and aplastic anemia (pancytopenia) may also occur. The drug 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.

• Liver Toxicity

• Although there have been reports of hepatotoxicity (including acute liver failure) associated with TAPAZOLE, the risk of hepatotoxicity appears to be less with methimazole than with propylthiouracil, especially in the pediatric population. Symptoms suggestive of hepatic dysfunction (anorexia, pruritis, right upper quadrant pain, etc.) should prompt evaluation of liver function (bilirubin, alkaline phosphatase) and hepatocellur integrity (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.

• Hypothyroidism

• TAPAZOLE can cause hypothyroidism necessitating routine monitoring of TSH and free T4 levels with adjustments in dosing to maintain a euthyroid state. Because the drug readily crosses placental membranes, methimazole can cause fetal goiter and cretinism when administered to a pregnant woman. For this reason, it is important that a sufficient, but not excessive, dose be given during pregnancy.

Precautions

• General

• Patients who receive methimazole should be under close surveillance and should be cautioned to report immediately any evidence of illness, particularly sore throat, skin eruptions, fever, headache, or general malaise. In such cases, white-blood cell and differential counts should be made to determine whether agranulocytosis has developed. Particular care should be exercised with patients who are receiving additional drugs know to cause agranulocytosis.

• Laboratory Tests

• Because methimazole may cause hypoprothrombinemia and bleeding, prothrombin time should be monitored during therapy with the drug, especially before surgical procedures.
• Periodic monitoring of thyroid function is warranted, and the finding of an elevated TSH warrants a decrease in the dosage of methimazole.

Adverse Reactions

Clinical Trials Experience

• Major adverse reactions (which occur with much less frequency than the minor adverse reactions) include inhibition of myelopoiesis (agranulocytosis, granulocytopenia, and thrombocytopenia), aplastic anemia, drug fever, a lupuslike syndrome, insulin autoimmune syndrome (which can result in hypoglycemic coma), hepatitis (jaundice may persist for several weeks after discontinuation of the drug), periarteritis, and hypoprothrombinemia. Nephritis occurs very rarely.

• Minor adverse reactions include skin rash, urticaria, nausea, vomiting, epigastric distress, arthralgia, paresthesia, loss of taste, abnormal loss of hair, myalgia, headache, pruritus, drowsiness, neuritis, edema, vertigo, skin pigmentation, jaundice, sialadenopathy, and lymphadenopathy.

• It should be noted that about 10% of patients with untreated hyperthyroidism have leukopenia (white-blood cell count of less than 4,000/mm3 ), often with relative granulopenia.

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Methimazole in the drug label.

Drug Interactions

• Anticoagulants (oral)

• The activity of oral anticoagulants may be potentiated by anti-vitamin-K activity attributed to methimazole.

• ß-adrenergic blocking agents

• Hyperthyroidism may cause an increased clearance of beta blockers with a high extraction ratio. A dose reduction of beta-adrenergic blockers may be needed when a hyperthyroid patient becomes euthyroid.

• Digitalis glycosides

• Serum digitalis levels may be increased when hyperthyroid patients on a stable digitalis glycoside regimen become euthyroid; a reduced dosage of digitalis glycosides may be required.

• Theophylline

• Theophylline clearance may decrease when hyperthyroid patients on a stable theophylline regimen become euthyroid; a reduced dose of theophylline may be needed.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

• Pregnancy Category D

• Methimazole used judiciously is an effective drug in hyperthyroidism complicated by pregnancy. In many pregnant women, the thyroid dysfunction diminishes as the pregnancy proceeds; consequently, a reduction in dosage may be possible. In some instances, use of methimazole can be discontinued 2 or 3 weeks before delivery.

Pregnancy Category (AUS):

• Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Methimazole in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Methimazole during labor and delivery.

Nursing Mothers

• The drug appears in human breast milk and its use is contraindicated in nursing mothers.

Pediatric Use

• Because of postmarketing reports of severe liver injury in pediatric patient treated with propylthiouracil, TAPAZOLE is the preferred choice when an antithyroid drug is required for a pediatric patient.

Geriatic Use

There is no FDA guidance on the use of Methimazole with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Methimazole with respect to specific gender populations.

Race

There is no FDA guidance on the use of Methimazole with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Methimazole in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Methimazole in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Methimazole in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Methimazole in patients who are immunocompromised.

Administration and Monitoring

Administration

• Oral

Monitoring

There is limited information regarding Monitoring of Methimazole in the drug label.

IV Compatibility

There is limited information regarding IV Compatibility of Methimazole in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

• Signs and Symptoms Symptoms may include nausea, vomiting, epigastric distress, headache, fever, joint pain, pruritus, and edema. Aplastic anemia (pancytopenia) or agranulocytosis may be manifested in hours to days. Less frequent events are hepatitis, nephritic syndrome, exfoliative dermatitis, neuropathies, and CNS stimulation or depression. Although not well studied, methimazole-induced agranulocytosis is generally associated with doses of 40 mg or more in patients older than 40 years of age. No information is available on the median lethal dose of the drug or the concentration of methimazole in biologic fluids associated with toxicity and/or death.

Management

• To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the “Physicians' Desk Reference (PDR)”. In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in your patient.

• Protect the patient's airway and support ventilation and perfusion. Meticulously monitor and maintain, within acceptable limits, the patient's vital signs, blood gases, serum electrolytes, etc. The patient's bone marrow function should be monitored. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which, in many cases, is more effective than emesis or lavage; consider charcoal instead of or in addition to gastric emptying. Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed. Safeguard the patient's airway when employing gastric emptying or charcoal.

• Forced diuresis, peritoneal dialysis, hemodialysis, or charcoal hemoperfusion have not been established as beneficial for an overdose of methimazole.

Chronic Overdose

There is limited information regarding Chronic Overdose of Methimazole in the drug label.

Pharmacology

Mechanism of Action

• Methimazole inhibits the synthesis of thyroid hormones and thus is effective in the treatment of hyperthyroidism. The drug does not inactivate existing thyroxine and triiodothyronine that are stored in the thyroid or circulating in the blood nor does it interfere with the effectiveness of thyroid hormones given by mouth or by injection.

• The actions and use of methimazole are similar to those of propylthiouracil. On a weight basis, the drug is at least 10 times as potent as propylthiouracil, but methimazole may be less consistent in action.

Structure

• Methimazole (1-methylimidazole-2-thiol) is a white, crystalline substance that is freely soluble in water. It differs chemically from the drugs of the thiouracil series primarily because it has a 5- instead of a 6-membered ring.

• Each tablet contains 5 or 10 mg (43.8 or 87.6 µmol) methimazole, an orally administered antithyroid drug.

• Each tablet also contains lactose monohydrate, magnesium stearate, potato starch, and talc.

• The molecular weight is 114.17, and the molecular formula is C4H6N2S. The structural formula is as follows:

This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Methimazole in the drug label.

Pharmacokinetics

• Methimazole is readily absorbed from the gastrointestinal tract. It is metabolized rapidly and requires frequent administration.

• Methimazole is excreted in the urine.

• In laboratory animals, various regimens that continuously suppress thyroid function and thereby increase TSH secretion result in thyroid tissue hypertrophy. Under such conditions, the appearance of thyroid and pituitary neoplasms has also been reported. Regimens that have been studied in this regard include antithyroid agents as well as dietary iodine deficiency, subtotal thyroidectomy, implantation of autonomous thyrotropic hormone-secreting pituitary tumors, and administration of chemical goitrogens.

Nonclinical Toxicology

• In a 2 year study, rats were given methimazole at doses of 0.5, 3, and 18 mg/kg/day. These doses were 0.3, 2, and 12 times the 15 mg/day maximum human maintenance dose (when calculated on the basis of surface area). Thyroid hyperplasia, adenoma, and carcinoma developed in rats at the two higher doses. The clinical significance of these findings is unclear.

Clinical Studies

There is limited information regarding Clinical Studies of Methimazole in the drug label.

How Supplied

• Methimazole Tablets, USP 5 mg white, round, flat-faced, bevelled-edged tablets with “VM” on one side and scored on the other.

• They are available in:

• Bottles of 100 NDC 0677-1945-01

• Methimazole Tablets, USP 10 mg white, round, flat-faced, bevelled-edged tablets with “XM” on one side and scored on the other.

• They are available in:

• Bottles of 100 NDC 0677-1946-01

• Store at controlled room temperature, 20°- 25°C (68°- 77°F).

• Dispense in tight, light-resistant container.

Storage

There is limited information regarding Methimazole Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Methimazole in the drug label.

Precautions with Alcohol

• Alcohol-Methimazole interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

• TAPAZOLE®

Look-Alike Drug Names

• methimazole® — metolazone®

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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