Agranulocytosis is potentially a serious side effect.
Patients should be instructed to report to their physicians any symptoms 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), hepatitis, or exfoliative dermatitis.
The patient’s bone marrow function should be monitored.
Due to the similar hepatic toxicity profiles of methimazole and propylthiouracil, attention is drawn to the severe hepatic reactions which have occurred with both drugs.
There have been rare reports of fulminant hepatitis, hepatic necrosis, encephalopathy, and death.
Symptoms suggestive of hepatic dysfunction (anorexia, pruritus, right upper quadrant pain, etc.) should prompt evaluation of liver function.
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.
Methimazole can cause fetal harm when administered to a pregnant woman.
Methimazole readily crosses the placental membranes and can induce goiter and even cretinism in the developing fetus.
In addition, rare instances of congenital defects: aplasia cutis, as manifested by scalp defects; esophageal atresia with tracheoesophageal fistula; and choanal atresia with absent/ hypoplastic nipples, have occurred in infants born to mothers who received methimazole during pregnancy.
If methimazole 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 methimazole, it may be appropriate to use other agents in pregnant women requiring treatment for hyperthyroidism.
Postpartum patients receiving methimazole should not nurse their babies.
Drug Interactions Anticoagulants (oral) – The activity of oral anticoagulants may be potentiated by anti-vitamin-K activity attributed to methimazole.
β-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.
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, nephrotic 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.
Treatment 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.
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 and pregelatinized starch.
The molecular weight is 114.17, and the molecular formula is C 4 H 6 N 2 S.
The structural formula is as follows: 1815e5b6-figure-01
Methimazole Tablets, USP 5 mg – white to off-white, round, biconvex tablets, with “B” to the left and “P” to right of the break line on one side and “655” on the other.
They are available in: Bottles of 100: NDC 64376-655-01 Methimazole Tablets, USP 10 mg – white to off-white, round, biconvex tablets, with “B” to the left and “P” to right of the break line on one side and “656” on the other.
They are available in: Bottles of 100: NDC 64376-656-01 KEEP THIS AND ALL DRUGS OUT OF REACH OF CHILDREN.
Dispense in a tight, light-resistant container.
Keep tightly closed.
INDICATIONS AND USAGE
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.
Pediatric use (See DOSAGE AND ADMINISTRATION ).
Pregnancy Category D ( See WARNINGS ) 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.
Nursing Mothers The drug appears in human breast milk and its use is contraindicated in nursing mothers (see WARNINGS ).
DOSAGE AND ADMINISTRATION
Methimazole is administered orally.
It is usually given in 3 equal doses at approximately 8-hour intervals.
Adults 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.
Pediatric 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.