Side Effects of Tapazole (methimazole)

Tapazole (methimazole) is an antithyroid drug used to treat an overactive thyroid gland (hyperthyroidism). It also is used to decrease symptoms of hyperthyroidism in preparation for surgical removal of the thyroid gland or before inactivating the thyroid gland with radioactive iodine. 

Long-term use of Tapazole may lead to a remission of hyperthyroidism. Grave's disease is the most common cause of hyperthyroidism. Grave's disease is an autoimmune disease resulting from antibodies that attach to receptors on thyroid hormone-producing cells in the thyroid gland and trigger overproduction of thyroid hormone. 

An enzyme (peroxidase) produces thyroid hormones, i.e., thyroxine (T4) and triiodothyronine (T3), by combining iodine with a protein called thyroglobulin. Tapazole prevents iodine and peroxidase from their normal interactions with thyroglobulin to form T4 and T3. 

This action decreases thyroid hormone production. Tapazole also interferes with the conversion of T4 to T3. Since T3 is more potent than T4, this also reduces the activity of thyroid hormones. 

Common side effects of Tapazole include

• rash,
• itching,
• hives,
• abnormal hair loss,
• skin pigmentation,
• swelling,
• nausea,
• vomiting,
• heartburn,
• loss of taste,
• joint or muscle aches,
• numbness, and
• headache.

Serious side effects of Tapazole include

• decreased white blood cells (agranulocytosis – symptoms include infections of the throat, the gastrointestinal tract, and skin, with an overall feeling of illness and fever) and
• blood platelets (thrombocytopenia - may lead to problems with excessive bleeding), and hepatitis and death of liver cells (hepatic necrosis).

Drug interactions of Tapazole include warfarin, because Tapazole may increase the activity of warfarin by reducing the activity of vitamin K in the body.

• Hyperthyroidism increases elimination of beta-blockers. Correcting hyperthyroidism will cause less elimination of beta-blockers so the dose of beta-blockers may require reduction when hyperthyroidism is corrected. A similar reaction may also occur with digoxin and theophylline.

Using Tapazole during pregnancy could harm a fetus. Tell your doctor if you are pregnant or if you become pregnant while using Tapazole. 

Tapazole is excreted in breast milk and may potentially cause harm to the infant. Breastfeeding is not recommended while using Tapazole.

Methimazole is generally well-tolerated with side effects occurring in 3 out of every 100 patients. The most common side effects are related to the skin and include:

• rash,
• itching,
• hives,
• abnormal hair loss, and
• skin pigmentation.

Other common side effects are:

• swelling,
• nausea,
• vomiting,
• heartburn,
• loss of taste,
• joint or muscle aches,
• numbness and
• headache.

Less common but more serious side effects include a decrease in white blood cells (agranulocytosis) and blood platelets (thrombocytopenia). Symptoms and signs of agranulocytosis include infections of the throat, the gastrointestinal tract, and skin with an overall feeling of illness and fever.

Since platelets are important for the clotting of blood, thrombocytopenia may lead to problems with excessive bleeding. Hepatitis and death of liver cells (hepatic necrosis) have rarely been associated with methimazole.

Major adverse reactions (which occur with much less frequency than the minor adverse reactions) include

• inhibition of myelopoieses (agranulocytosis, granulocytopenia, thrombocytopenia, and 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 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.

Anticoagulants (Oral)

Due to potential inhibition of vitamin K activity by methimazole, the activity of oral anticoagulants (e.g., warfarin) may be increased; additional monitoring of PT/INR should be considered, especially before surgical procedures.

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 needed.

Theophylline

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