Class: Antithyroid Agents
ATC Class: H03BB02
VA Class: HS852
CAS Number: 60-56-0
Brands: Tapazole
Introduction
Antithyroid agent;a b o thioimidazole-derivative.b
Uses for Methimazole
Hyperthyroidism
Palliative treatment of hyperthyroidism.a b c o Therapy maintains patient in euthyroid state for a period of several (generally 1–2) years until spontaneous remission occurs;a b c o however, spontaneous remission does not occur in all patients, and most patients eventually require ablative therapy (i.e., surgery, radioactive iodine).b Because methimazole does not affect underlying cause of hyperthyroidism, generally avoid long-term use; minimum duration of therapy necessary before assessing whether spontaneous remission has occurred not clearly established.b
May be used in juvenile hyperthyroidism to delay ablative therapy; if remission does not occur, may continue methimazole for several years to postpone ablation until child is older.b
Amelioration of hyperthyroidism in preparation for surgical treatment (e.g., subtotal thyroidectomy).a b c j o Therapy with methimazole returns the hyperthyroid patient to a normal metabolic state prior to thyroidectomy and controls the thyrotoxic crisis that may accompany thyroidectomy.b Also used when thyroidectomy is contraindicated or not advisable.a
Amelioration of hyperthyroidism in preparation for radioactive iodine therapya b c o (e.g., in geriatric patients, in patients with cardiac disease).e j Therapy with methimazole controls symptoms of hyperthyroidism before and during radioactive iodine therapy until the ablative effects of iodine occur.b However, pretreatment with thioamides may lower the cure rate and increase the need for subsequent doses of radioactive iodine.c
Because of ease of administration and better adherence, methimazole generally is preferred over propylthiouracil for management of most hyperthyroid situations (except during pregnancy or lactation or for management of thyrotoxic crisis).c d
Thyrotoxic Crisis
May be used for management of thyrotoxic crisis,b although not considered antithyroid agent of first choice.c Usually initiated before iodide (e.g., potassium iodide, strong iodine solution) therapy.b
Methimazole Dosage and Administration
General
May use a β-adrenergic blocking agent (e.g., propranolol) concomitantly to manage peripheral signs and symptoms of hyperthyroidism, particularly cardiovascular effects (e.g., tachycardia).b c
Administration
Administer orally.a b c o May administer rectally†c d as extemporaneously prepared suppositories.c
Oral Administration
Some manufacturers recommend administering daily dosage orally in 3 equally divided doses at approximately 8-hour intervals.a b o In adults, some clinicians suggest administering as a single daily dose or, alternatively, in divided doses.c d j
Dosage
Pediatric Patients
Hyperthyroidism
Palliative Treatment to Achieve Spontaneous Remission
Oral
Initially, 0.4 mg/kg daily given in 3 equally divided doses at approximately 8-hour intervals.a b o Continue therapy at initial dosage for about 4–8 weeks until symptoms resolve and euthyroidism is achieved.c d j Then gradually taper to a dosage that maintains euthyroidism.c d j
Maintenance dosage: Approximately half of initial dosage.a b o
Optimum duration of therapy not clearly established.b If relapse occurs following discontinuance of therapy, initially reinstitute methimazole,b c then consider alternate forms of therapy.b
Adults
Hyperthyroidism
Palliative Treatment to Achieve Spontaneous Remission
Oral
Initially, some manufacturers recommend 15 mg daily for mild hyperthyroidism, 30–40 mg daily for moderately severe hyperthyroidism, or 60 mg daily for severe hyperthyroidism.a b o Continue therapy at initial dosage for about 4–8 weeks until symptoms resolve and euthyroidism is achieved.c d j Then gradually taper to a dosage that maintains euthyroidism.c d j
Usual maintenance dosage: 5–30 mg daily.a b c d j o
Optimum duration of therapy not clearly established;b most data support duration of 12–18 months.c l If relapse occurs following discontinuance of therapy, initially reinstitute methimazole,b c then consider alternate forms of therapy.b According to some clinicians, may continue thioamide therapy indefinitely if well tolerated and if alternative therapies (e.g., surgery, radioactive iodine) are not desired.c
Preparation for Surgical Treatment
Oral
Initially, some manufacturers recommend 15 mg daily for mild hyperthyroidism, 30–40 mg daily for moderately severe hyperthyroidism, or 60 mg daily for severe hyperthyroidism.a b
Some clinicians recommend continuing therapy at initial dosage for about 6–8 weeks until euthyroidism is achieved; then add iodide therapy for 10–14 days (to decrease vascularity of thyroid gland) before surgery.j
Preparation for Radioactive Iodine Therapy
Oral
Initially, some manufacturers recommend 15 mg daily for mild hyperthyroidism, 30–40 mg daily for moderately severe hyperthyroidism, or 60 mg daily for severe hyperthyroidism.a b
Some clinicians recommend continuing therapy at initial dosage until euthyroidism is achieved; then discontinue methimazole 4–6 days before radioactive iodine therapy.c j May reinstitute methimazole 4 days after radioactive iodine therapy as needed (e.g., in patients with cardiac disease).j
Prescribing Limits
Adults
Hyperthyroidism
Oral
Some clinicians recommend avoiding dosages >40 mg daily if possible.b (See Hematologic Effects under Cautions.)
Special Populations
Hepatic Impairment
No specific dosage recommendations at this time.101
Renal Impairment
No specific dosage recommendations at this time.101
Geriatric Patients
No specific dosage recommendations at this time.101
Pregnancy
If methimazole is used during pregnancy, reduction in methimazole dosage may be possible because thyroid dysfunction diminishes in many women as pregnancy proceeds; in some patients, methimazole can be discontinued 2–3 weeks before delivery.101 (See Pregnancy under Cautions.)
Cautions for Methimazole
Contraindications
Use in nursing women, according to some manufacturers.a o (See Lactation under Cautions.)
Hypersensitivity to methimazole or any ingredient in the formulation.a b o
Warnings/Precautions
Warnings
Hematologic Effects
Risk of agranulocytosis;a b d f j o usually occurs within first 2 months of therapy, but rarely may occur after 4 months of therapy.b Increased risk in patients >40 years of age and in patients receiving dosages >40 mg daily.b c n Use with caution in patients >40 years of age.b n
Leukopenia, thrombocytopenia, and aplastic anemia (pancytopenia) also may occur.a o Hypoprothrombinemia and bleeding reported rarely with thioamides.c j (See Laboratory Monitoring under Cautions.)
Monitor patient carefully for signs or symptoms of illness (e.g., sore throat, skin eruptions, fever, chills, headache, general malaise), particularly during early stages of therapy.b c If fever, sore throat, or other signs or symptoms of illness occur, determine leukocyte and differential counts to assess whether agranulocytosis has developed.a b o When evaluating myelopoietic response to methimazole, consider that leukopenia (i.e., WBC <4000/mm3) occurs in 10% of untreated hyperthyroid patients and often is associated with relative granulocytopenia.a b
If agranulocytosis, pancytopenia, or fever occurs, discontinue methimazole and initiate appropriate supportive and symptomatic therapy.a b o Monitor bone marrow function.a o
Hepatic Effects
Fulminant hepatitis,a b o hepatic necrosis,a b o encephalopathy,a b o cholestatic jaundice,c d and deatha o reported rarely.a b Jaundice associated with methimazole-induced hepatitis may persist for several weeks after discontinuance of the drug.b
Promptly evaluate liver function if symptoms suggestive of hepatic dysfunction (e.g., anorexia, pruritus, right upper-quadrant pain) occur.a b o If clinically relevant liver abnormality (e.g., hepatic aminotransferase concentrations >3 times the ULN) is detected, discontinue methimazole promptly.a b o If hepatitis occurs, discontinue methimazole and initiate appropriate supportive and symptomatic therapy;a b o rechallenge with alternative thioamide not recommended because death has been reported.c
Dermatologic Effects
If exfoliative dermatitis occurs, discontinue methimazole and initiate appropriate supportive and symptomatic therapy.a b o
Fetal/Neonatal Morbidity
May cause fetal harm (i.e., induction of goiter, hypothyroidism, or cretinism).101 a b o Teratogenic effects (e.g., aplasia cutis, esophageal atresia with tracheoesophageal fistula, choanal atresia with absent/hypoplastic nipples) reported rarely in infants.101 108 a d o
Congenital malformations reported approximately 3 times more often with prenatal exposure to methimazole compared with propylthiouracil.112 Distinct and consistent pattern of congenital malformations associated with the use of methimazole, but not with propylthiouracil, particularly craniofacial malformations (e.g., scalp epidermal aplasia [aplasia cutis], facial dysmorphism, choanal atresia).112 Specific birth defects were associated with use of methimazole during the first trimester of pregnancy and not found when the drug was administered later in pregnancy.112 FDA has not found a consistent pattern of birth defects associated with use of propylthiouracil and has concluded there is no convincing evidence of an association between propylthiouracil use and congenital malformations, even with use during the first trimester.112
If used during pregnancy or if pregnancy occurs during therapy, apprise of potential fetal hazard.101 a o
For management of hyperthyroidism during pregnancy, consider alternative antithyroid agent.a o (See Pregnancy under Cautions.)
Sensitivity Reactions
Cross-sensitivity
Cross-sensitivity between thioamides likely to occurc f (i.e., in approximately 50% of patients switched from one thioamide agent to the other).d j
Major Toxicities
Immunologic Effects
Antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis with acute renal failure, arthritis, skin ulcerations, and a vasculitic rash reported rarely.d If these symptoms occur, discontinue methimazole promptly.d
General Precautions
Laboratory Monitoring
Before initiating thioamide therapy, some clinicians recommend obtaining baseline thyroxine (T4) and TSH concentrations.c Baseline WBC with differential and liver function tests also may be useful in evaluating thioamide-induced adverse effects (e.g., leukopenia and/or agranulocytosis, hepatotoxicity).c
Monitor thyroid function periodicallya (e.g., 4–6 weeks after initiation of therapy; after any dosage adjustmentsc ); decrease dosage if TSH is elevated.a Once euthyroidism is achieved, monitor thyroid function every 3–6 months.c
Determine leukocyte and differential counts in patients who develop any signs or symptoms of illness (e.g., fever, sore throat) during therapy.b d f
Monitor PT during therapy, particularly before surgical procedures, because of possible risk of hypoprothrombinemia and bleeding.a o
Hypothyroidism
Possible hypothyroidism following long-term therapy.b
Specific Populations
Pregnancy
Category D.a h o (See Fetal/Neonatal Morbidity under Cautions.)
Despite potential fetal hazard, antithyroid agents still considered therapy of choice for management of hyperthyroidism during pregnancy.108 d e Since methimazole may be associated with the rare development of fetal abnormalities (e.g., aplasia cutis, choanal atresia), propylthiouracil may be preferred when an antithyroid drug is indicated during organogenesis, in the first trimester of pregnancy, or just prior to the first trimester of pregnancy.100 103 106 107 108 109 (See Fetal/Neonatal Morbidity under Cautions.) May be preferable to switch from propylthiouracil to methimazole for the second and third trimesters, because of potential maternal adverse effects of propylthiouracil (e.g., hepatotoxicity).109 Not known if risk of methimazole-induced aplasia cutis or embryopathy outweighs risk of propylthiouracil-induced hepatotoxicity.104
If used during pregnancy, administer lowest effective dosage to maintain T4 concentrations at high end of normal range.108 c d e f h As thyroid dysfunction improves during course of pregnancy, may reduce methimazole dosage; in some patients, may discontinue methimazole 2–3 weeks before delivery.101 a b o
Lactation
Distributed into milk.a b d h Some manufacturers state use is contraindicated in nursing women.101 a o However, AAP and some other clinicians consider methimazole to be compatible with breast-feeding although some recommend administration after a feeding.108 110 d f h i
Adult Use
Patients >40 years of age; use with caution because of increased risk of agranulocytosis.b n (See Hematologic Effects under Cautions.)
Common Adverse Effects
Rash,a b c d f j l o urticaria,a b d o pruritus,a b o skin pigmentation,a b o abnormal hair loss,a b o nausea,a b f l o vomiting,a b l o arthritis,f arthralgia,a b d j o myalgia,a b o paresthesia,a b o fever, f j l anorexia,f loss of tastea b f o or smell,f epigastric distress,a b o edema,a b o headache,a b o drowsiness,a b o neuritis,a b o vertigo,a b o jaundice,a b o sialadenopathy,a b o lymphadenopathy.a b o
Interactions for Methimazole
Drugs Known to Cause Agranulocytosis
Use concomitantly with extreme caution.a b
Specific Drugs
Drug
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Interaction
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Comments
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Anticoagulants, oral (e.g., warfarin)
|
Potentiation of anticoagulant effects during hyperthyroid state;g possible decreased anticoagulant effects when hyperthyroid patients receiving a stable anticoagulant dosage become euthyroidd g
|
Monitor PT;k increase in warfarin dosage may be needed when patient becomes euthyroidd g
|
β-Adrenergic blocking agents (e.g., propranolol)
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Possible increased clearance of β-adrenergic blocking agents during hyperthyroid statea o
|
Reduction of β-blocker dosage may be needed when patient becomes euthyroida o
|
Digitalis glycosides (e.g., digoxin)
|
Possible increased serum digitalis concentrations when hyperthyroid patients receiving a stable digitalis glycoside regimen become euthyroida o
|
Reduction of digitalis glycoside dosage may be needed when patient becomes euthyroida o
|
Theophylline
|
Possible decreased theophylline clearance when hyperthyroid patients on a stable theophylline regimen become euthyroida o
|
Reduction of theophylline dosage may be needed when patient becomes euthyroida o
|
Methimazole Pharmacokinetics
Absorption
Bioavailability
Readily and rapidly absorbed from the GI tract following oral administration.a b d j o Peak plasma concentrations attained within about 1 hour.b j
Onset
Slow onset because thioamides block synthesis (rather than release) of thyroid hormones; some symptomatic improvement should be noted 2–3 weeks after initiation of therapy.c
Duration
Approximately 40 hours.c d
Distribution
Extent
Readily crosses the placenta.a b d e f h j o
Distributed into milka d j o (in concentrations approximately equal to those in maternal serum).b
Elimination
Metabolism
Metabolized rapidly.a
Elimination Route
Excreted in urine;a b o approximately 12% of dose excreted in urine within 24 hours.b
Half-life
5–13 hours.b d
Stability
Storage
Oral
Tablets
Tight, light resistant containers at 20–25°C.a o
ActionsActions
Inhibits the synthesis of thyroid hormonesa c f l o by interfering with the incorporation of iodine into tyrosyl residues of thyroglobulin;b c j also inhibits the coupling of these iodotyrosyl residues to form iodothyronine.b j
Exact mechanism(s) not fully elucidated; however, methimazole may interfere with the oxidation of iodide ion and iodotyrosyl groups.b
Limited evidence suggests that coupling reaction is more sensitive to antithyroid agents than the iodination reaction.b
Does not inhibit the action of thyroid hormones already formed and present in the thyroid gland or circulation; also does not interfere with effectiveness of exogenously administered thyroid hormones.a b o Patients whose thyroid gland contains a relatively high concentration of iodine (e.g., from prior ingestion, from administration during diagnostic radiologic procedures) may respond relatively slowly to antithyroid agents.b
Unlike propylthiouracil, does not inhibit peripheral deiodination of T4 to triiodothyronine (T3).b c d j
Advice to Patients
Importance of informing a clinician immediately if signs or symptoms of illness (e.g., sore throat, skin eruptions, fever, chills, headache, general malaise) occur.a b c j o (See Hematologic Effects under Cautions.)
Importance of informing a clinician immediately if symptoms suggestive of hepatic dysfunction (e.g., anorexia, pruritus, right upper-quadrant pain) occur.a o (See Hepatic Effects under Cautions.)
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.a o
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.a o Necessity for clinicians to advise pregnant women of risk to the fetus.a o
Importance of informing patients of other important precautionary information.a o (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Methimazole
Routes
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Dosage Forms
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Strengths
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Brand Names
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Manufacturer
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Oral
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Tablets
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5 mg*
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Methimazole Tablets Tapazole (scored)
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King
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10 mg *
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Methimazole Tablets Tapazole (scored)
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King
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Comparative Pricing
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Methimazole 10MG Tablets (PAR): 100/$63.99 or 200/$119.98
Methimazole 5MG Tablets (SANDOZ): 90/$31 or 100/$33
Tapazole 10MG Tablets (KING PHARMA): 100/$146 or 200/$282.96
Tapazole 5MG Tablets (KING PHARMA): 100/$87.99 or 300/$240.97
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions February 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
References
100. Food and Drug Administration. FDA Alert: Propylthiouracil-induced liver failure. Rockville, MD; 2009 Jun 4. From FDA website. Accessed 2009 Oct 28.
101. Actavis Totowa LLC. Methimazole tablets prescribing information. Totowa, NJ; 2007 Jun.
103. Bahn RS, Burch HS, Cooper DS et al. The Role of Propylthiouracil in the Management of Graves' Disease in Adults: report of a meeting jointly sponsored by the American Thyroid Association and the Food and Drug Administration. Thyroid. 2009; 19:673-4. [PubMed 19583480]
104. Eunice Kennedy Shriver National Institute of Child Health and Human Development. Hepatic toxicity following treatment for pediatric Graves’ disease meeting: October 28, 2008. Conference proceeding. Available from website. Accessed 2009 Oct 30.
106. Rivkees SA, Mattison DR. Propylthiouracil (PTU) hepatotoxicity in children and recommendations for discontinuation of use. Int J Pediatr Endocrinol. 2009. Article ID 132041. DOI:10.1155/2009/132041.
107. Cooper DS, Rivkees SA. Putting propylthiouracil in perspective. J Clin Endocrinol Metab. 2009; 94:1881-2. [PubMed 19401361]
108. Abalovich M, Amino N, Barbour LA et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2007; 92:S1-47. [PubMed 17948378]
109. Dava Pharmaceuticals, Inc. Propylthiouracil tablets prescribing information. Fort Lee, NJ; 2010 Jan.
110. American Academy of Pediatrics Committee on Drugs. The transfer of drugs and other chemicals into human milk. Pediatrics. 2001; 108:776-89. [PubMed 11533352]
112. Food and Drug Administration. FDA drug safety communication: New boxed warning on severe liver injury with propylthiouracil. Rockville, MD; 2010 Apr 21. Available from FDA website (). Accessed 2010 Sep 8.
a. King Pharmaceuticals, Inc. Tapazole (methimazole) tablets prescribing information. Bristol, TN; 2006 Jul.
b. AHFS drug information 2007. McEvoy GK, ed. Methimazole. Bethesda, MD: American Society of Health-System Pharmacists; 2007:3249-50.
c. Dong BJ. Endocrine Disorders. In: Koda-Kimble MA, Young LY, Kradjan WA et al, eds. Applied therapeutics: the clinical use of drugs. 8th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005:49-1–49-39.
d. Anon. Drugs for hypothyroidism and hyperthyroidism. Treat Guidel Med Lett. 2006; 4:17-24.
e. American Association of Clinical Endocrinologists. Medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006 amended version. Endocr Pract. 2002; 8:457-69. [PubMed 15260011]
f. American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists, number 37, August 2002: Thyroid disease in pregnancy. Obstet Gynecol. 2002; 100:387-96. [PubMed 12166417]
g. Baxter K, ed. Stockley's Drug Interactions. 7th edition. London, UK: Pharmaceutical Press; 2006: 317-8.
h. Methimazole. In: Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005:1027-35.
i. Ressel G. Practice Guidelines: AAP updates statement for transfer of drugs and other chemicals into breast milk. Am Fam Physician. 2002 Mar. From American Family Physician website ()
j. Talbert RL. Thyroid disorders. In: DiPiro JT, Talbert RL, Yee GC et al, eds. Pharmacotherapy: a pathophysiologic approach. 6th ed. New York: The McGraw-Hill Companies, Inc.; 2005:1369-90.
k. Beta blockers/thioamines. In: Tatro DS, Olin BR, Hebel SK eds. Drug Interactions Facts. St. Louis, MO: Wolters Kluwer Health, Inc.; 2006:161.
l. Abraham P, Avenell A, Watson WA et al. Antithyroid drug regimen for treating Graves’ hyperthyroidism. Cochrane Database Syst Rev. 2005; 18:CD003420.
n. Cooper DS, Goldminz D, Levin AA et al. Agranulocytosis associated with antithyroid drugs: Effects of patient age and drug dose. Ann Intern Med. 1983; 98:26-9. [PubMed 6687345]
o. Centrix Pharmaceutical, Inc. Northyx (methimazole) tablets prescribing information. Birmingham, AL; 2007 Apr.
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