Hyperthyroidism associated with Graves disease, toxic multinodular goiter, toxic adenoma (labeled uses), or iodine-induced thyrotoxicosis (off-label use) :
Note: May use in combination with beta-blockade to manage hyperthyroid symptoms prior to definitive therapy (ie, radioactive iodine therapy or surgery) or as chronic low-dose treatment; for iodine-induced thyrotoxicosis, may be used as an adjunct to beta-blockade for severe or prolonged (eg, >1 month) symptoms or in patients with underlying heart disease (Ref).
Oral: Initial: Individualize initial dose based on clinical status and gland size; free T4 levels may be used to guide initial therapy (Ref):
Free T4 levels 1 to 1.5 times ULN: 5 to 10 mg once daily.
Free T4 levels >1.5 to 2 times ULN (or iodine-induced thyrotoxicosis): 10 to 20 mg once daily.
Free T4 levels >2 times ULN: 20 to 40 mg/day. To achieve euthyroidism more quickly and reduce GI-related adverse effects, may give in 2 to 3 divided doses (especially with doses >30 mg/day) (Ref).
Dose adjustment: Oral: Usual maintenance dose: 5 to 10 mg once daily. Assess free T4 and total T3 at 4- to 6-week intervals; when normal, reduce dose by 30% to 50% and repeat thyroid function tests in 4 to 6 weeks; continue to adjust dose to achieve euthyroidism (Ref).
Duration of therapy: Depends on etiology and plans for definitive therapy:
Patients undergoing definitive therapy: Prior to definitive therapy, continue until euthyroid (typically 4 to 6 weeks); discontinue 2 to 3 days before radioactive iodine therapy or on the day of thyroidectomy (Ref).
Patients not undergoing definitive therapy: For Graves disease, continue for 12 to 18 months, then assess for remission; for toxic multinodular goiter/toxic adenoma, continue indefinitely (Ref).
Iodine-induced thyrotoxicosis: Taper and discontinue therapy as iodine load is cleared (Ref).
Thyroid storm (alternative to propylthiouracil) (off-label use): Note: Use in combination with other appropriate agents; if iodine is administered, delay iodine administration by ≥1 hour after methimazole (Ref).
Oral: Initial: 20 mg every 4 to 6 hours (Ref); once clinically stable, dose may be given less frequently (eg, 20 mg once or twice daily) (Ref). In patients who cannot take methimazole by mouth, alternative administration routes (eg, nasogastric, rectal) may be considered (Ref).
Thyrotoxicosis, type I amiodarone-induced (off-label use):
Oral: Initial: 30 to 40 mg once daily; adjust dose to achieve euthyroidism (eg, free T4, total T3, TSH levels in the normal range); if high doses (eg, >30 mg/day) are required after 3 to 6 months, it may be more effective to administer in 2 to 3 divided doses (Ref). Note: If etiology of amiodarone-induced thyrotoxicosis (eg, type I or type II) cannot be determined or if patient is clinically unstable, use in combination with a glucocorticoid (Ref).
Duration of therapy: Depends on whether amiodarone therapy will be continued:
Continuing amiodarone: Continue methimazole indefinitely (Ref).
Discontinuing amiodarone: Taper methimazole slowly (eg, over months) to avoid recurrence of thyrotoxicosis (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: No dosage adjustment necessary for any degree of kidney impairment (Ref).
Hemodialysis, intermittent (thrice weekly): Dialyzable (~30% to 40%) (Ref): No supplemental dose or dosage adjustment necessary; when scheduled dose falls on a hemodialysis day, administer after hemodialysis (Ref).
Peritoneal dialysis: Likely to be somewhat dialyzable: No dosage adjustment necessary (Ref).
CRRT: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary; when scheduled dose falls on a PIRRT day, administer after PIRRT (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing.
(For additional information see "Methimazole: Pediatric drug information")
Hyperthyroidism: Infants, Children, and Adolescents: Oral: Initial: 0.4 mg/kg/day in 3 divided doses (approximately every 8 hours); maintenance 0.2 mg/kg/day in 3 divided doses (50% of initial)
Graves disease (Ref): Note: In severe cases, higher doses may be required (50% to 100% higher); once patient euthyroid, reduce dose by ≥50% to maintain euthyroid; duration of therapy usually 1 to 2 years
Weight-based dosing: Infants, Children, and Adolescents: Oral: Initial: 0.2 to 0.5 mg/kg/dose once daily (range: 0.1 to 1 mg/kg/dose)
Fixed dosing (using 1/4, 1/2, or whole tablets): Oral:
Infants: 1.25 mg/day
Children 1 to 5 years: 2.5 to 5 mg/day
Children 5 to 10 years: 5 to 10 mg/day
Children ≥10 years and Adolescents: 10 to 20 mg/day
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
Methimazole may cause agranulocytosis, a rare but potentially life-threatening adverse reaction that is reversible upon discontinuation. Patients should report immediately any sign/symptoms of infection (eg, fever, flu-like symptoms, pharyngitis) so a WBC can be assessed (Ref).
Mechanism: May be through direct toxicity, but more recent evidence supports an immune-mediated mechanism (Ref).
Onset: Varied; most cases occur within the first 3 months of treatment (mean 42 days) but can occur later (Ref).
Risk factors:
• Doses >30 mg/day (possible risk factor) (Ref)
• Age >40 years (possible risk factor) (Ref)
• Genetic variants: HLA-B*27:05 (Europeans) (Ref); HLA‐B*38:02 (Han Chinese) (Ref); HLA‐DRB1*08:03 (Han Chinese) (Ref); Nox3 variants (encodes NADPH oxidase) (Ref).
Methimazole may rarely cause life-threatening hepatotoxicity, including acute hepatic failure and hepatitis (usually cholestatic) (Ref). Hepatotoxicity is reversible with discontinuation. Patients with hepatotoxicity due to methimazole may be at increased risk for hepatotoxicity with propylthiouracil (Ref).
Mechanism: Dose-related; not clearly established. Possible mechanisms include reactive metabolite formation and immune-mediated reaction (Ref).
Onset: Varied; typically within 2 days to 3 months of initiation (Ref).
Risk factors:
• Higher doses (Ref)
• Older age (Ref)
• Polymorphism in SLCO1B1*1a and SLCO1B1*1b (Ref)
• Carriers of the HLA-C*03:02 allele (Ref)
Methimazole may cause a lupus-like syndrome, a rare but potentially life-threatening adverse reaction that is reversible with discontinuation and additional treatment (Ref). Manifestations may range from cutaneous involvement to lupus nephritis (Ref).
Mechanism: Not clearly established; hypothesized to be an autoimmune response in genetically predisposed individuals (Ref).
Onset: Varied; typically manifesting weeks to months after initiation (Ref).
Risk factors:
• IgA deficiency (Ref)
Acute pancreatitis is a rare, but potentially life-threatening adverse effect of methimazole (Ref). Pancreatitis is typically reversible upon discontinuation but has resulted in death (Ref).
Mechanism: Non–dose-related. While the exact mechanism is unknown, it follows a pattern of a hypersensitivity-type reaction with rechallenge reactions occurring at a shorter latency (Ref).
Onset: Varied; typically occurs within the first 90 days of therapy (Ref).
Risk factors:
• Older age (Ref)
Although this adverse reaction is more common with propylthiouracil, cases of vasculitis with methimazole have been discussed in the literature (Ref), most notably involving the kidneys, lungs, and skin. Many of these cases involve a positive antineutrophil cytoplasmic antibody (ANCA). ANCA-positive cases involve an inflammatory and necrotic process impacting small vessels. Pulmonary capillaritis and diffuse pulmonary alveolar hemorrhage has been described (Ref). This adverse reaction is potentially life-threatening without intervention but is reversible with discontinuation and supportive care. A review of ANCA-positive vasculitis cases possibly associated with methimazole reported a prevalence range of 0% to 16% with a median prevalence of 6% (Ref).
Onset: Delayed; the median time to vasculitis presentation was 42 months (Ref).
Risk factors:
• Younger age (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined:
Cardiovascular: Edema, periarteritis
Dermatologic: Alopecia, pruritus, skin pigmentation, skin rash
Endocrine & metabolic: Hypothyroidism
Gastrointestinal: Enlargement of salivary glands, epigastric distress, nausea, vomiting
Hematologic & oncologic: Granulocytopenia, lymphadenopathy
Nervous system: Drowsiness, drug fever, headache, paresthesia, vertigo
Neuromuscular & skeletal: Arthralgia, myalgia
Postmarketing:
Cardiovascular: Cerebral vasculitis (Tripodi 2008), hypersensitivity angiitis (Ribeiro 2013), vasculitis (Balavoine 2015)
Dermatologic: Urticaria (Kubota 2016)
Endocrine & metabolic: Insulin autoimmune syndrome (Chen 2018, Gomez 2012)
Gastrointestinal: Acute pancreatitis (Brix 2020), ageusia (Hallman 1953), gastrointestinal hemorrhage (Minkley 2011)
Hematologic & oncologic: Agranulocytosis (Cooper 2005), aplastic anemia (Josol 2010), hypoprothrombinemia (Minkley 2011)
Hepatic: Acute hepatic failure (Wang 2014), hepatitis (Wang 2014), hepatotoxicity (Wang 2014), jaundice (Wang 2014)
Nervous system: Neuritis (Roldan 1972), neuropathy
Neuromuscular & skeletal: Lupus-like syndrome (Beernaert 2020)
Renal: Acute kidney injury (Shell 2020), glomerulonephritis (Hori 1996), nephritis (Reynolds 1979)
Respiratory: Pulmonary alveolar hemorrhage (Arai 2018)
Hypersensitivity to methimazole or any component of the formulation.
Canadian labeling: Additional contraindications (not in US labeling): Breastfeeding, history of acute pancreatitis after administration of methimazole.
Concerns related to adverse effects:
• Dermatologic effects: Antithyroid agents have been associated with dermatologic reactions. Discontinue in the presence of a severe reaction.
• Fever: Discontinue in the presence of unexplained fever.
• Hypothyroidism: May cause hypothyroidism; routinely monitor TSH and free T4 levels, adjust dose to maintain euthyroid state.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral:
Tapazole: 5 mg [DSC], 10 mg [DSC]
Generic: 5 mg, 10 mg
Yes
Tablets (methIMAzole Oral)
5 mg (per each): $0.44 - $0.89
10 mg (per each): $0.77 - $1.54
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral:
Tapazole: 5 mg [contains corn starch]
Tapazole: 10 mg, 20 mg [DSC]
Generic: 5 mg, 10 mg
Rectal: In thyroid storm, rectal administration has been described (Ref).
Oral: May administer without regard to food.
Hazardous agent (NIOSH 2016 [group 3]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Hyperthyroidism: Treatment of hyperthyroidism in patients with Graves disease or toxic multinodular goiter for whom surgery or radioactive iodine therapy is not appropriate; amelioration of hyperthyroid symptoms in preparation for thyroidectomy or radioactive iodine therapy.
Iodine-induced thyrotoxicosis; Thyroid storm; Thyrotoxicosis, type I amiodarone-induced
MethIMAzole may be confused with methazolAMIDE, metOLazone
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Cardiac Glycosides: Antithyroid Agents may increase the serum concentration of Cardiac Glycosides. Risk C: Monitor therapy
MetyraPONE: Antithyroid Agents may diminish the diagnostic effect of MetyraPONE. Management: Consider alternatives to the use of the metyrapone test in patients taking antithyroid agents. Risk D: Consider therapy modification
Myelosuppressive Agents: May enhance the neutropenic effect of Antithyroid Agents. Risk C: Monitor therapy
PrednisoLONE (Systemic): MethIMAzole may decrease the serum concentration of PrednisoLONE (Systemic). Risk C: Monitor therapy
Sodium Iodide I131: Antithyroid Agents may diminish the therapeutic effect of Sodium Iodide I131. Management: Discontinue antithyroid medications at least 3 days before sodium iodide I-131 administration, and avoid concurrent use. Risk X: Avoid combination
Theophylline Derivatives: Antithyroid Agents may increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Antithyroid Agents may diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Patients taking methimazole should use effective contraception and postpone becoming pregnant until a stable euthyroid state is achieved. Patients taking methimazole should notify their health care provider immediately once pregnancy is suspected. The decision to continue antithyroid medications during pregnancy should be individualized (ATA [Alexander 2017]).
Methimazole crosses the placenta.
Congenital anomalies have been observed in neonates exposed in utero to methimazole in the first trimester and include anomalies of the upper GI tract (esophageal atresia with or without tracheoesophageal fistula), respiratory tract (choanal atresia), skin (aplasia cutis), and facial dysmorphism. Additional abdominal wall defects (umbilicocele), ventricular septal defects, and defects of the eye and urinary system have also been reported (ATA [Alexander 2017]). Hypothyroidism may occur in the newborn.
Uncontrolled maternal hyperthyroidism may result in adverse neonatal and maternal outcomes. Adverse outcomes associated with poorly controlled thyrotoxicosis include pregnancy loss, pregnancy induced hypertension, maternal congestive heart failure, and thyroid storm, as well as prematurity, low birth weight, intrauterine growth restriction, and stillbirth (ATA [Alexander 2017]).
To avoid potential teratogenic effects, antithyroid drugs may be discontinued as soon as pregnancy is detected in select patients with well-controlled Graves disease at low risk for relapse; close monitoring of maternal and fetal thyroid function recommended (ATA [Alexander 2017]). When treatment is necessary, antithyroid drugs are the treatment of choice for the control of hyperthyroidism during pregnancy, although recommendations for specific agents vary by guideline. Methimazole is generally avoided during the first trimester but may be used later in pregnancy (ACOG 2020; ATA [Alexander 2017]). Dose requirements of methimazole may be decreased as pregnancy progresses. To prevent adverse pregnancy outcomes, the lowest effective dose should be used to keep the maternal TT4/FT4 at or just above the pregnancy specific upper limit of normal (ACOG 2020; ATA [Alexander 2017]).
Methimazole is present in breast milk.
Information related to the presence of methimazole in breast milk is available from 6 lactating women with Graves disease following a single dose of methimazole 15 mg. Peak methimazole concentrations were 0.32 ± 0.10 mcg/mL (breast milk) and 0.31 ± 0.09 mcg/mL (maternal plasma) 2 hours after administration. The half-life of methimazole was calculated to be 4.2 ± 0.8 hours in breast milk. Twelve hours after the dose, breast milk concentrations of methimazole had decreased to 0.03 ± 0.01 mcg/mL (Abe 1995).
Based on available data, thyroid function is normal in infants exposed to lower doses of methimazole via breast milk. In addition, IQ and physical development up to 74 months of age were not impaired in a long-term study of breastfed infants whose mothers were receiving treatment with methimazole. The treatment of hyperthyroidism in breastfeeding patients is the same as non-breastfeeding females. The lowest effective dose should be used; maternal doses of methimazole ≤20 mg/day are advised in breastfeeding patients. Infants exposed to antithyroid medications via breast milk should be monitored for adequate growth and development; routine tests of thyroid function are not recommended (ATA [Alexander 2017]). Taking the dose of methimazole after breastfeeding may help decrease potential infant exposure by providing a 3- to 4-hour interval before the next feed (Amino 2020).
Signs and symptoms of illness (ie, fever, sore throat, skin eruptions, general malaise).
CBC with differential (baseline and if development of febrile illness or pharyngitis occurs); signs/symptoms of bone marrow suppression; prothrombin time (especially before surgical procedures); LFTs (bilirubin, alkaline phosphatase, ALT, AST) at baseline and if symptoms of liver injury occur (eg, anorexia, pruritus, right upper quadrant pain) (ATA [Ross 2016]).
Thyroid function tests:
Serum free T4 and total T3 at 4- to 6-week intervals during dose titration, then every 2 to 3 months once euthyroid levels are achieved (with long-term therapy [ie, >18 months] may extend interval to every 4 to 6 months); in patients with Graves disease, if thyrotropin receptor antibodies (TRAbs) are negative, thyroid function tests should be monitored every 2 to 3 months for the first 6 months after discontinuing therapy, then at 4- to 6-month intervals for the next 6 months, then every 6 to 12 months thereafter (ATA [Ross 2016]).
Thyroid-stimulating hormone (TSH) periodically throughout treatment; TSH is not an adequate parameter to assess initial response as levels may remain suppressed for several months after starting therapy (ATA [Ross 2016]).
TRAb in patients with Graves disease prior to stopping medication; elevation at the end of therapy decreases likelihood of remission (ATA [Ross 2016]).
Pregnant patients: Free T4 and total T3 every 2 to 4 weeks until stabilized (ACOG 2020). Free T4, total T4, and TSH approximately every 4 weeks throughout pregnancy. TRAb once pregnancy is confirmed, at 18 to 22 weeks' gestation, and 30 to 34 weeks' gestation (ATA [Alexander 2017]).
Inhibits the synthesis of thyroid hormones by blocking the oxidation of iodine in the thyroid gland; blocks synthesis of thyroxine and triiodothyronine (T3); does not inactivate circulating T4 and T3
Onset of action: Antithyroid: 12 to 18 hours (Clark 2006).
Duration: 36 to 72 hours (Clark 2006).
Absorption: Almost complete (Clark 2006).
Distribution: Concentrated in thyroid gland, Vd/F: 0.66 L/kg (Jansson 1985).
Protein binding, plasma: None (Cooper 2005).
Metabolism: Hepatic.
Bioavailability: ~93% (Clark 2006).
Half-life elimination: 4 to 6 hours (Clark 2006).
Time to peak, serum: 1 to 2 hours (Clark 2006).
Excretion: Urine (<10% unchanged) (Jansson 1985).
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