methimazole tablet King Pharmaceuticals, Inc.
Tapazole® Methimazole Tablets, USP
Tapazole® (Methimazole Tablets,
USP) (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
Each tablet also contains
lactose monohydrate, magnesium stearate, starch (corn), pregelatinized
starch and talc.
The molecular weight is 114.16,
and the molecular formula is C4H6N2S. The structural formula is as follows:
Methimazole inhibits the synthesis of thyroid hormones
and thus is effective in the treatment of hyperthyroidism. The drug
does not inactivate existing thyroxine and tri-iodothyronine 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.
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.
Indications and Usage
Tapazole is indicated in the medical treatment of
hyperthyroidism. Long-term therapy may lead to remission of the disease.
Tapazole may be used to ameliorate hyperthyroidism in preparation
for subtotal thyroidectomy or radioactive iodine therapy. Tapazole
is also used when thyroidectomy is contraindicated or not advisable.
Tapazole is contraindicated in the presence of hypersensitivity
to the drug and in nursing mothers because the drug is excreted in
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.
to the similar hepatic toxicity profiles of Tapazole 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, pruritis, 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.
can cause fetal harm when administered to a pregnant woman. Tapazole
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 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
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
Postpartum patients receiving
Tapazole should not nurse their babies.
Patients who receive Tapazole 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 known to cause agranulocytosis.
Because Tapazole may cause hypoprothrombinemia and
bleeding, prothrombin time should be monitored during therapy with
the drug, especially before surgical procedures (see General under PRECAUTIONS).
Periodic monitoring of thyroid function
is warranted, and the finding of an elevated TSH warrants a decrease
in the dosage of Tapazole.
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.
glycosides: Serum digitalis levels may be increased when
hyperthyroid patients on a stable digitalis glycoside regimen become
euthyroid; 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.
Carcinogenesis, Mutagenesis, Impairment of Fertility - 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.
Pregnancy Category D
See WARNINGS - Tapazole® 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 Tapazole can be discontinued 2 or 3 weeks
The drug appears in human breast milk and its use
is contraindicated in nursing mothers (see WARNINGS).
Major adverse reactions (which occur with much less
frequency than the minor adverse reactions) include inhibition of
myelopoieses (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,
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.
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
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.
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.
peritoneal dialysis, hemodialysis, or charcoal hemoperfusion have
not been established as beneficial for an overdose of methimazole.
Dosage and Administration
Tapazole is administered orally. Tablets are usually
given in 3 equal doses at approximately 8-hour intervals.
Adult -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
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 dosageis approximately 1/2 of the initial dose.
Tapazole Tablets are available in:
The 5-mg tablets are round, white to off-white, scored on one side
and the other side debossed with “J94”.
They are available as follows:
Bottles of 100
The 10-mg tablets are round,
white to off-white, scored on one side and the other side debossed
They are available
Bottles of 100 NDC 60793-105-01
Store at controlled room temperature, 15° to 30°C
(59° to 86°F).
as of July 2006.
Distributed by: King Pharmaceuticals,
Inc. Bristol, TN 37620