Tapazole

Tapazole

thiamazole

Manufacturer:

A. Menarini

Distributor:

Zuellig
Full Prescribing Info
Contents
Methimazole.
Description
Methimazole, 1-methyl-imidazole-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. The molecular weight is 114.16 and the empirical formula is C4H6N2S. It is an orally administered antithyroid drug.
Action
Pharmacology: Methimazole inhibits the synthesis of thyroid hormones and thus is effective in the treatment of hyperthyroidism. It 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.
Methimazole is readily absorbed from the GIT. 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/Uses
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.
Dosage/Direction for Use
Methimazole is administered orally. It is usually given in 3 equal doses at approximately 8-hr intervals.
Adults: Initial Daily Dose: 15 mg for mild hyperthyroidism, 30-40 mg for moderately severe hyperthyroidism and 60 mg for severe hyperthyroidism, divided into 3 doses at 8-hr intervals. Maintenance Dose: 5-15 mg daily.
Overdosage
Symptoms: 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 in patients >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.
Treatment: In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs and unusual drug kinetics in patients.
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 GIT 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.
Contraindications
Presence of hypersensitivity to methimazole and in nursing mothers because methimazole is excreted in milk.
Warnings
Agranulocytosis is potentially a serious side effect. Patients should be instructed to report to their physicians any symptoms of agranulocytosis eg, fever or sore throat. Leukopenia, thrombocytopenia and aplastic anemia (pancytopenia) may also occur. Tapazole 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 have a 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 eg, 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 methimazole, the patient should be warned of the potential hazard to the fetus.
Since the previously mentioned 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.
Special 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 known 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 (see General Precautions).
Periodic monitoring of thyroid function is warranted and the finding of an elevated TSH warrants a decrease in the dosage of methimazole.
Carcinogenicity, Mutagenicity & 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 2 higher doses. The clinical significance of these findings is unclear.
Use in pregnancy & lactation: (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 2-3 weeks before delivery.
Methimazole appears in human breast milk and its use is contraindicated in nursing mothers (see Warnings).
Use in children: See Dosage & Administration.
Use In Pregnancy & Lactation
Warnings: 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 eg, 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 methimazole, the patient should be warned of the potential hazard to the fetus.
Since the previously mentioned 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.
Use in pregnancy & lactation: (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 2-3 weeks before delivery.
Methimazole appears in human breast milk and its use is contraindicated in nursing mothers (see Warnings).
Adverse Reactions
Major adverse reactions (which occur with much less frequency than the minor adverse reactions) include inhibition or myelopoiesis (agranulocytosis, granulocytopenia and thrombocytopenia), aplastic anemia, drug fever, a lupus-like syndrome, insulin autoimmune syndrome (which can result in hypoglycemic coma), hepatitis (jaundice may persist for several weeks after discontinuation of Tapazole), 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 <4000/mm3), often with relative granulopenia.
Drug Interactions
Anticoagulants (Oral): The activity of anticoagulants may be potentiated by anti-vitamin K activity attributed to methimazole.
β-Adrenergic Blocking Agents: Hyperthyroidism may cause an increased clearance of β-blockers with a high extraction ratio. A dose reduction of β-adrenergic blocking agents 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.
Storage
Store at temperatures not exceeding 30°C.
MIMS Class
ATC Classification
H03BB02 - thiamazole ; Belongs to the class of sulfur-containing imidazole derivative agents. Used in the management of thyroid diseases.
Presentation/Packing
Tab 5 mg (white) x 100's. 20 mg x 100's.
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in