Prescription Required
In stock
Manufacturer
HERITAGE PHARMA
SKU
23155007101

methimazole 10 mg tablet

Generic
$0.13 / tablet
$0.77 / tablet
$0.64 / tablet
+ -
1,000 tablets Available
Total Price:

Uses

Hyperthyroidism

Methimazole is used in patients with Graves' disease with hyperthyroidism or toxic multinodular goiter for whom surgery or radioactive iodine therapy is not an appropriate treatment option. The drug also is used to ameliorate symptoms of hyperthyroidism in preparation for thyroidectomy or radioactive iodine therapy.

Some clinicians state that methimazole should be used in virtually every patient who chooses antithyroid drug therapy for the treatment of Graves' disease, except during the first trimester of pregnancy when propylthiouracil is preferred (see Pregnancy under Cautions: Pregnancy and Lactation), in the treatment of thyroid storm (see Thyrotoxic Crisis under Uses: Hyperthyroidism), and in patients with minor adverse reactions to methimazole who refuse radioactive iodine therapy or surgery.

Because of postmarketing reports of severe liver injury in pediatric patients receiving propylthiouracil, methimazole is the preferred agent when an antithyroid drug is required for a pediatric patient.(See Cautions: Pediatric Precautions.)

Thioamide antithyroid agents (e.g., methimazole, propylthiouracil) are used to control the symptoms of hyperthyroidism associated with Graves' disease and maintain the patient in a euthyroid state for a period of several years (generally 1-2 years) until a spontaneous remission occurs. Thioamide antithyroid agents do not affect the underlying cause of hyperthyroidism. Spontaneous remission does not occur in all patients receiving therapy with thioamide antithyroid agents, and most patients eventually require ablative therapy (i.e., surgery, radioactive iodine). The minimum duration of thioamide therapy necessary before assessing whether spontaneous remission has occurred is not clearly established. However, some clinicians state that if methimazole is chosen as the primary therapy for Graves' disease, the drug should be continued for approximately 12-18 months in adults or 1-2 years in children, then tapered or discontinued if thyrotropin (thyroid stimulating hormone, TSH) concentrations return to normal at that time. If adults or children with Graves' disease remain hyperthyroid after completing a course of methimazole, treatment with radioactive iodine or thyroidectomy should be considered. Some clinicians state that treatment with low-dose methimazole for longer than 12-18 months in adults may be considered in patients not in remission who prefer this pharmacologic approach. Methimazole therapy also may be continued in children until the child is considered old enough for radioactive iodine therapy or surgery.

Methimazole is used to return the hyperthyroid patient to a normal metabolic state prior to thyroidectomy and to control the thyrotoxic crisis that may accompany thyroidectomy. (See Thyrotoxic Crisis under Uses: Hyperthyroidism.) Some clinicians recommend that, whenever possible, adults or children with Graves' disease undergoing thyroidectomy or adults with toxic adenoma or toxic multinodular goiter undergoing surgery be rendered euthyroid with methimazole prior to the procedure.

Methimazole is used as an adjunct to radioactive iodine therapy in patients who require control of symptoms of hyperthyroidism prior to and after administration of radioactive iodine until the ablative effects of the iodine occur. However, the beneficial and detrimental effects and optimal sequencing of antithyroid drugs before or after radioactive iodine therapy have not been clearly established. Some clinicians recommend that pretreatment with methimazole prior to radioactive iodine therapy for Graves' disease, toxic adenoma, or toxic multinodular goiter be considered in adults who are at increased risk for complications due to worsening of hyperthyroidism (e.g., geriatric patients, patients with severe hyperthyroidism [e.g., extremely symptomatic, free thyroxine (T4) estimates 2-3 times the upper limit of normal] or substantial comorbidities [e.g., cardiovascular disease]). However, conflicting opinions exist, and other clinicians state that pretreatment with methimazole prior to radioactive iodine therapy is not necessary because there is insufficient evidence to indicate that radioactive iodine worsens the clinical or biochemical aspects of hyperthyroidism, and that pretreatment with methimazole will only delay treatment with radioactive iodine. In addition, some evidence indicates that pretreatment with methimazole may reduce the efficacy of subsequent radioactive iodine therapy. In children with Graves' disease having total T4 concentrations exceeding 20 mcg/dL or free T4 estimates exceeding 5 ng/dL who are to receive radioactive iodine therapy, some clinicians suggest pretreatment with methimazole and β-adrenergic blockade until total T4 and/or free T4 estimates normalize before proceeding with radioactive iodine.

Antithyroid agents do not induce remission in patients with nodular thyroid disease (i.e., toxic adenoma, toxic multinodular goiter), and discontinuance of therapy results in relapse. Therefore, some clinicians suggest that adults with overt toxic adenoma or toxic multinodular goiter be treated with either radioactive iodine therapy or thyroidectomy, and that long-term methimazole therapy be avoided. However, these clinicians state that long-term (life-long) antithyroid drug therapy may be the best choice for some geriatric or otherwise ill patients with limited longevity and increased surgical risk who can be monitored regularly (e.g., residents of nursing homes or other care facilities where compliance with radiation safety regulations may be difficult) or for patients who prefer this pharmacologic approach.

Thyrotoxic Crisis

In the management of thyrotoxic crisis, thioamide antithyroid agents are used to inhibit thyroid hormone synthesis. Because propylthiouracil also blocks the peripheral conversion of thyroxine to triiodothyronine, it theoretically may be more useful than methimazole or carbimazole (not commercially available in the US) in the management of thyrotoxic crisis. Iodides (e.g., potassium iodide, strong iodine solution) are given to inhibit the release of thyroid hormone from the gland but may subsequently be used as a substrate for thyroid hormone synthesis; therefore, treatment with a thioamide antithyroid agent is usually initiated before iodide therapy. A β-adrenergic blocking agent (e.g., propranolol) is also usually given concomitantly to manage peripheral signs and symptoms of hyperthyroidism, particularly cardiovascular effects (e.g., tachycardia).

Dosage and Administration

Administration

Methimazole is administered orally. The manufacturer states that the total daily dosage is usually given in 3 equally divided doses at approximately 8-hour intervals. Alternatively, some clinicians state that methimazole may be administered as a single daily dose.

Dosage

Adult Dosage

The manufacturer states that the initial adult dosage of methimazole is 15, 30-40, or 60 mg daily for the treatment of mild, moderately severe, or severe hyperthyroidism, respectively. Alternatively, for the treatment of Graves' disease, some clinicians recommend an initial adult methimazole dosage of 10-20 mg daily to restore euthyroidism. In general, most patients improve considerably or achieve normal thyroid function following 4-12 weeks of therapy, after which dosage may be decreased while maintaining normal thyroid function. Subsequent dosage should be carefully adjusted according to the patient's tolerance and therapeutic response. The manufacturer states that the adult maintenance dosage is 5-15 mg daily. Alternatively, for the treatment of Graves' disease, some clinicians generally recommend an adult maintenance dosage of 5-10 mg daily.(See Cautions: Precautions and Contraindications.)

If methimazole is used during pregnancy for the management of hyperthyroidism, the manufacturer states that a sufficient, but not excessive, dosage of methimazole is necessary; the lowest possible dosage of methimazole to control the maternal disease should be used. The manufacturer states that because thyroid dysfunction diminishes in many women as the pregnancy proceeds, a reduction in dosage of antithyroid therapy may be possible, and, in some patients, use of antithyroid therapy can be discontinued 2-3 weeks before delivery.(See Pregnancy under Cautions: Pregnancy and Lactation.)

For the treatment of thyrotoxic crisis (i.e., thyroid storm) in adults, some clinicians recommend a methimazole dosage of 60-80 mg daily.

The optimum duration of antithyroid therapy remains to be clearly established. However, some clinicians state that if methimazole is chosen as the primary therapy for Graves' disease in adults, the drug should be continued for approximately 12-18 months, then tapered or discontinued if thyrotropin (thyroid stimulating hormone, TSH) concentrations return to normal at that time. If a patient with Graves' disease remains hyperthyroid after completing a course of methimazole, treatment with radioactive iodine or thyroidectomy should be considered. However, treatment with low-dose methimazole for longer than 12-18 months may be considered in adult patients not in remission who prefer this pharmacologic approach.

If methimazole is used prior to thyroidectomy or surgery to render adults euthyroid, the drug should be discontinued at the time of the procedure.

If methimazole is used as pretreatment prior to radioactive iodine therapy, some clinicians recommend that methimazole be discontinued 2-7 days before administration of radioactive iodine, restarted 3-7 days after radioactive iodine, and generally tapered over 4-6 weeks as thyroid function normalizes and radioactive iodine becomes effective.

Pediatric Dosage

For the treatment of hyperthyroidism in children, the manufacturer states that the initial dosage of methimazole is 0.4 mg/kg daily. The manufacturer states that the maintenance dosage in children is approximately one-half of the initial dosage. Alternatively, for the treatment of Graves' disease, some clinicians state that the usual dosage of methimazole in children is 0.2-0.5 mg/kg daily, with a range of 0.1-1 mg/kg daily. These clinicians also suggest the following general dosages, calculated based on the patient's age and rounded to the nearest quarter-, half-, or whole-tablet dosage strengths: 1.25 mg daily for infants; 2.5-5 mg daily for children 1-5 years of age; 5-10 mg daily for children 5-10 years of age; and 10-20 mg daily for children 10-18 years of age. Patients with severe clinical or biochemical hyperthyroidism may receive methimazole dosages that are 50-100% higher than those usually recommended for the treatment of Graves' disease. When thyroid hormone concentrations normalize, these clinicians state that methimazole dosages may be reduced by 50% or more to maintain a euthyroid state.

The optimum duration of antithyroid therapy remains to be clearly established. However, some clinicians state that if methimazole is chosen as first-line therapy for Graves' disease in children, the drug should be continued for 1-2 years and then discontinued, or dosage reduced, to assess whether the patient is in remission. If the patient is not in remission following 1-2 years of methimazole therapy, treatment with radioactive iodine or thyroidectomy should be considered, depending on the age of the patient. Alternatively, methimazole may be continued for extended periods as long as adverse effects do not occur and hyperthyroidism is controlled; this approach may be used as a bridge to radioactive iodine therapy or surgery at a later age if remission still has not occurred. Low-dose methimazole may be continued in selected situations in which radioactive iodine therapy or surgery may not be suitable or possible.

If methimazole is used prior to thyroidectomy to render children with Graves' disease euthyroid, some clinicians state that methimazole is usually administered for 1-2 months in preparation for the procedure.

If methimazole is used as pretreatment prior to radioactive iodine therapy in children with Graves' disease, some clinicians recommend that methimazole be discontinued 3-5 days before administration of radioactive iodine. Although some clinicians restart antithyroid drugs after radioactive iodine therapy, other clinicians state that this practice is seldom required in children.

Cautions

Adverse Effects

Adverse dermatologic effects are most commonly reported. Minor adverse effects of methimazole include rash, urticaria, pruritus, abnormal hair loss, skin pigmentation, edema, nausea, vomiting, epigastric distress, loss of taste, arthralgia, myalgia, paresthesia, and headache. Drowsiness, neuritis, vertigo, jaundice, sialadenopathy, and lymphadenopathy also have occurred in patients receiving the drug.(See Cautions: Hepatic Effects.) In one patient, peripheral neuritis occurred during long-term (23 months) therapy with methimazole but disappeared following discontinuance of the drug.

Although reported much less frequently, severe adverse effects of methimazole include inhibition of myelopoieses (agranulocytosis [see Cautions: Agranulocytosis], granulocytopenia, thrombocytopenia, and aplastic anemia); drug fever; lupus-like syndrome; insulin autoimmune syndrome (which can result in hypoglycemic coma); hepatitis (see Cautions: Hepatic Effects); periarteritis; and hypoprothrombinemia. Nephritis occurs very rarely in patients receiving methimazole.

Agranulocytosis

Agranulocytosis is a potentially life-threatening adverse effect of methimazole therapy. Most cases of agranulocytosis appear to occur within the first 2 months of therapy, but rarely may occur after 4 months of therapy. Although methimazole-induced agranulocytosis may be dose related (possibly occurring more frequently with higher dosages of the drug), agranulocytosis may occur irrespective of dosage, length of treatment, or previous exposure to the antithyroid drug, and may occur more frequently in geriatric patients. The mechanism(s) of methimazole-induced agranulocytosis has not been determined, but antigranulocyte antibodies have been reported in some patients with thioamide-induced agranulocytosis; a direct toxic effect of these drugs on bone marrow has not been excluded as an additional possible cause.

Hepatic Effects

Although there have been reports of hepatotoxicity (including acute liver failure) associated with methimazole, the risk of hepatotoxicity appears to be lower with methimazole than with propylthiouracil, especially in pediatric patients.(See Cautions: Pediatric Precautions.) Jaundice associated with methimazole-induced hepatitis may persist for several weeks after discontinuance of the drug.

Hypothyroidism

Methimazole may cause hypothyroidism necessitating routine monitoring of thyrotropin (thyroid stimulating hormone, TSH) and free thyroxine (T4) concentrations; dosage should be adjusted to maintain a euthyroid state.(See Cautions: Precautions and Contraindications.) Because methimazole readily crosses the placenta, the drug can cause fetal goiter and cretinism when administered to a pregnant woman.(See Pregnancy under Cautions: Pregnancy and Lactation.)

Precautions and Contraindications

Some clinicians suggest that a baseline complete blood count, including white count with differential, be performed prior to initiating antithyroid drug therapy in patients with Graves' disease. Patients receiving methimazole should be closely monitored and should be instructed to contact their clinician immediately if signs or symptoms of illness, particularly sore throat, skin eruptions, fever, chills, headache, or general malaise, occur; it is particularly important to carefully monitor for these signs and symptoms during the early stages of methimazole therapy since methimazole-induced agranulocytosis usually occurs during the first several months of therapy. Leukopenia, thrombocytopenia, and/or aplastic anemia (pancytopenia) also may occur. Leukocyte and differential counts should be performed in patients who develop fever or sore throat or other signs or symptoms of illness while receiving the drug. Methimazole should be used with extreme caution in patients receiving other drugs known to cause agranulocytosis. The manufacturer states that methimazole 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. Some clinicians state that patients should be informed of the adverse effects associated with methimazole (e.g., agranulocytosis) and advised to immediately discontinue the drug and promptly contact their clinician if fever or pharyngitis occurs. In a patient who develops agranulocytosis or other serious adverse effects while receiving either methimazole or propylthiouracil, some clinicians state that use of the other drug also is contraindicated because of the risk of cross-sensitivity between the two drugs. Because methimazole may cause hypoprothrombinemia and bleeding, prothrombin time should be monitored during therapy, particularly prior to surgery (see Drug Interactions: Anticoagulants).

Some clinicians suggest that liver function tests, including alkaline phosphatase, aminotransferase, and bilirubin, be performed prior to initiating antithyroid drug therapy in patients with Graves' disease. Patients should be informed of the adverse hepatic effects associated with methimazole and advised to immediately discontinue the drug and promptly contact their clinician if pruritic rash, jaundice, acholic stools, dark urine, arthralgias, abdominal pain, nausea, or fatigue occurs. Patients with symptoms suggestive of hepatic dysfunction (e.g., anorexia, pruritus, right upper-quadrant pain) should have prompt evaluation of their liver function (alkaline phosphatase, bilirubin) and hepatocellular integrity (ALT, AST). If there is evidence of a clinically important liver abnormality, including hepatic aminotransferase concentrations exceeding 3 times the upper limit of normal, the manufacturer states that the drug should be discontinued promptly.

Thyroid function should be monitored periodically in patients receiving methimazole. In patients with Graves' disease, some clinicians state that thyroid function (e.g., serum free T4, serum free or total triiodothyronine [T3], TSH) should be monitored before initiating therapy and then every 4-8 weeks thereafter (with subsequent dosage adjustments as needed) until thyroid function is stable or the patient is euthyroid; once the patient is euthyroid, thyroid function may be monitored every 2-3 months. Early in the course of antithyroid therapy, serum TSH concentration is not a reliable parameter to monitor because it may remain suppressed for several months after initiation of therapy despite normalization of free T4 concentrations. The finding of a suppressed TSH concentration during this period, therefore, does not indicate a need for a dosage increase. However, once clinical evidence of resolution of hyperthyroidism occurs, the finding of an elevated serum TSH concentration indicates that a lower maintenance dosage of methimazole should be employed. Monitoring serum T3 concentrations may sometimes be useful for dosage adjustment; in patients in whom total or free T3 concentrations remain elevated despite low, normal, or reduced free T4 concentrations, an increase in antithyroid dosage may be necessary. When methimazole is discontinued in patients with Graves' disease, thyroid function should be monitored every 1-3 months for 6-12 months to diagnose relapse early, and patients should be advised to contact clinicians if symptoms of hyperthyroidism occur.

Methimazole is contraindicated in patients who are hypersensitive to the drug or any ingredient in the formulation. Cross-sensitivity between thioamides may occur (i.e., in approximately 50% of patients switched from one thioamide agent to the other). In patients who develop agranulocytosis or other serious adverse effects while receiving either methimazole or propylthiouracil, some clinicians state that use of the other drug also is contraindicated because of the risk of cross-sensitivity between the two drugs. In patients experiencing serious allergic reactions to methimazole, some clinicians state that using the alternative antithyroid drug (i.e., propylthiouracil) is not recommended.

Pediatric Precautions

Because of postmarketing reports of severe liver injury in pediatric patients receiving propylthiouracil, methimazole is preferred over propylthiouracil when an antithyroid drug is required for a pediatric patient.(See Uses: Hyperthyroidism.) During postmarketing experience, cases of severe liver injury, including hepatic failure requiring liver transplantation or resulting in death, have been reported in pediatric patients receiving propylthiouracil; however, no such cases have been reported in pediatric patients treated with methimazole.(See Cautions: Precautions and Contraindications.)

Pregnancy and Lactation

Pregnancy

Methimazole readily crosses the placental membranes and may cause fetal harm, particularly when administered in the first trimester of pregnancy. The drug can also cause fetal goiter and hypothyroidism (cretinism) when administered to a pregnant woman.

In April 2010, the US Food and Drug Administration (FDA) reported a review of postmarketing data analyzing the potential for birth defects associated with use of propylthiouracil or methimazole during pregnancy. FDA found that congenital malformations were reported approximately 3 times more often with prenatal exposure to methimazole compared with propylthiouracil (29 cases with methimazole; 9 cases with propylthiouracil). In addition, there was a distinct and consistent pattern of congenital malformations associated with the use of methimazole that was not found with propylthiouracil. Approximately 90% of the congenital malformations with methimazole were craniofacial malformations (e.g., scalp epidermal aplasia [aplasia cutis], facial dysmorphism, choanal atresia). In most of the cases, there were multiple malformations that frequently included a combination of craniofacial defects and GI atresia or aplasia. These specific birth defects were associated with the use of methimazole during the first trimester of pregnancy but were not found when the drug was administered later in pregnancy. In contrast, FDA did not find a consistent pattern of birth defects associated with the use of propylthiouracil and concluded that there is no convincing evidence of an association between propylthiouracil use and congenital malformations, even with use during the first trimester.

Despite the potential fetal hazard, antithyroid agents are still considered the therapy of choice for the management of hyperthyroidism during pregnancy. Since methimazole may be associated with the rare development of fetal abnormalities, such as aplasia cutis, craniofacial malformations (facial dysmorphism, choanal atresia), and GI malformations (esophageal atresia with or without tracheoesophageal fistula, umbilical abnormalities), propylthiouracil is the preferred agent when an antithyroid drug is indicated during organogenesis in the first trimester of pregnancy or just prior to the first trimester of pregnancy. Patients receiving methimazole should be switched to propylthiouracil if pregnancy is confirmed in the first trimester. Because of the potential adverse maternal effects of propylthiouracil (e.g., hepatotoxicity), however, it may be preferable to switch from propylthiouracil to methimazole for the second and third trimesters (i.e., after the first trimester). If the patient is switching from propylthiouracil to methimazole, thyroid function should be assessed after 2 weeks and then every 2-4 weeks thereafter. It is not known if the risk of methimazole-induced aplasia cutis or embryopathy outweighs the risk of propylthiouracil-induced hepatotoxicity.

If methimazole is used during pregnancy for the management of hyperthyroidism, the manufacturer states that a sufficient, but not excessive, dosage of methimazole is necessary; the lowest possible dosage of methimazole to control the maternal disease should be used. Some clinicians state that antithyroid drug therapy should be initiated or adjusted to maintain maternal free thyroxine (T4) concentrations at or just above the upper limit of normal (ULN) of the nonpregnant reference range, or to maintain total T4 concentrations at 1.5 times the ULN or the free T4 index in the ULN, while using the lowest possible dosage of antithyroid drugs. In women receiving antithyroid drugs during pregnancy, free T4 and TSH concentrations should be monitored approximately every 2-6 weeks. The manufacturer states that because thyroid dysfunction diminishes in many women as pregnancy proceeds, a reduction in dosage of antithyroid therapy may be possible, and, in some patients, use of antithyroid therapy can be discontinued 2-3 weeks before delivery.

Patients should be advised to contact their clinician immediately about their therapy if they are or plan to become pregnant while receiving an antithyroid drug. If methimazole is used during pregnancy or if the patient becomes pregnant while receiving the drug, the patient should be advised of the potential hazard to the fetus; in addition, when considering antithyroid drug use during pregnancy, the patient should be informed of the risks of methimazole-associated fetal malformations, as well as the risks of propylthiouracil-associated hepatotoxicity.

Lactation

Methimazole is distributed into milk. However, several studies found no effect on clinical status in nursing infants of women receiving methimazole, particularly if thyroid function is monitored at frequent (weekly or biweekly) intervals. A long-term study of 139 thyrotoxic lactating women and their infants failed to demonstrate toxicity in infants who are breast-fed by women receiving methimazole.

Methimazole generally is compatible with breast-feeding, and moderate dosages of the drug (i.e., 20-30 mg daily) appear to be safe during breast-feeding. Because of concerns regarding severe hepatotoxicity (i.e., hepatic necrosis in either woman or child) associated with maternal use of propylthiouracil, some clinicians consider methimazole to be the preferred antithyroid drug in nursing women. If an antithyroid drug is used in nursing women, some clinicians recommend that the drug be administered after a feeding and in divided doses, and that thyroid function be monitored in nursing infants.

Drug Interactions

Drugs Known to Cause Agranulocytosis

Methimazole should be used with extreme caution in patients receiving other drugs known to cause agranulocytosis. (See Cautions: Agranulocytosis and also see Cautions: Precautions and Contraindications.)

Anticoagulants

Because of the potential inhibition of vitamin K activity by methimazole, the activity of oral anticoagulants (e.g., warfarin) may be increased. However, methimazole also may decrease the anticoagulant effect of warfarin. Additional monitoring of prothrombin time (PT)/international normalized ratio (INR) should be considered, particularly prior to surgery. Dosage adjustment of warfarin may be necessary.

β-Adrenergic Blocking Agents

Hyperthyroidism may cause an increased clearance of β-adrenergic blocking agents with a high extraction ratio. Dosage reduction of the β-adrenergic blocking agent may be needed when a hyperthyroid patient becomes euthyroid.

Digitalis Glycosides

Serum digitalis concentrations may be increased when hyperthyroid patients receiving a stable digitalis glycoside regimen become euthyroid; dosage reduction of the digitalis glycoside may be needed.

Theophylline

Theophylline clearance may decrease when hyperthyroid patients receiving a stable theophylline regimen become euthyroid; dosage reduction of theophylline may be needed.

Pharmacokinetics

Methimazole is rapidly absorbed from the GI tract following oral administration with peak plasma concentrations occurring within about 1 hour. Methimazole readily crosses the placenta and is distributed into milk in concentrations approximately equal to those in maternal serum. Methimazole is metabolized in the liver. The elimination half-life of methimazole reportedly ranges from about 5-13 hours. The drug is excreted in urine. In one study, about 12% of a dose was excreted in urine within 24 hours.

Write Your Own Review
You're reviewing:METHIMAZOLE 10 MG TABLET
Your Rating