Dosing
Adult dosing:
Hyperthyroidism:
Initial (mild hyperthyroidism), 15 mg/day orally divided into 3 doses at 8-hour intervals (FDA dosage)
Initial (moderately severe hyperthyroidism), 30 to 40 mg/day orally divided into 3 doses at 8-hour intervals (FDA dosage)
Initial (severe hyperthyroidism), 60 mg/day orally divided into 3 doses at 8-hour intervals (FDA dosage)
Maintenance, 5 to 15 mg/day in 3 divided doses at 8-hour intervals (FDA dosage)
Initial (free thyroxine
[T4] levels of 1 to 1.5 x ULN), 5 to 10 mg/day orally; doses may be given once daily
or split twice daily
when more rapid biochemical control required. Individualize dosage based on
symptoms, gland size, and total triiodothyronine (T3) levels, as clinically indicated (guideline dosing)
Initial (T4 levels of 1.5 to 2 x ULN), 10 to 20 mg/day orally; doses may be given once daily
or split twice daily
when more rapid biochemical control required. Individualize dosage based on
symptoms, gland size, and total T3 levels, as clinically indicated (guideline dosing)
Initial (T4 levels of 2 to 3 x ULN), 30 to 40 mg/day orally; doses may be given once daily
or split twice daily
when more rapid biochemical control required. Individualize dosage based on
symptoms, gland size, and total T3 levels, as clinically indicated (guideline dosing)
Maintenance, 5 to 10 mg/day orally; adjust dosage based on
periodic biochemical monitoring (guideline dosage)
Discontinuation, consider discontinuation if thyroid stimulating hormone
(TSH) and thyrotropin receptor antibody (TRAb) levels are normal after 12 to 18 months of therapy; may continue at low dose for longer than 12 to 18 months if clinically indicated (guideline dosage)
Radioactive iodine
(RAI) therapy: Discontinue methimazole 2 to 3 days
prior to
RAI and consider resuming 3 to 7 days after RAI administration in patients who are at increased risk for complications associated with worsening of hyperthyroidism (guideline dosing)
Thyroidectomy: Treat until euthyroid and discontinue at the time of surgery (guideline dosage).
Pregnancy – Thyrotoxicosis due to
Graves’ disease:
(Second and third trimesters) Use lowest dose to keep mother’s total thyroxine (T4) and triiodothyronine (T3) levels at or slightly above normal range for pregnancy (1.5 x non-pregnant reference ranges for second/third trimesters), keep TSH below the reference range for pregnancy, and keep free T4 at or slightly above upper limit of the pregnancy trimester reference range for the
assay. Assess at least monthly and adjust dose as required (guideline dosage)
Switching between methimazole and propylthiouracil: A dose ratio of methimazole: propylthiouracil of 1:20 may be used for
switching between drugs; however, take into account differences in duration of action and split propylthiouracil doses over the course of the day. As an example, methimazole 15 mg orally once daily
could be switched to propylthiouracil 100 mg 3 times daily (total dosage, 300 mg/day).
Thyroid storm
:
60 to 80 mg/day orally (guideline dosing)
Thyrotoxicosis, Drug-induced:
Amiodarone-induced, type 1:
Initial, 40 mg orally once daily
until patient is euthyroid, generally about 3 to 6 months; if continued high-dose therapy is required, daily dose may be divided (guideline dosing)
Iodine-induced:
20 to 40 mg orally as a single or divided dose (guideline dosing)
Pediatric dosing:
Hyperthyroidism:
Initial, 0.4 mg/kg/day orally in 3 divided doses at 8-hour intervals (FDA dosage)
Maintenance, approximately 50% of the initial dosage (FDA dosage)
Initial, 0.2 to 0.5 mg/kg/day orally in a single dose or for alternative approach based on
whole and quarter to half-tablet sizes: Infants, 1.25 mg/day; 1 to 5 years, 2.5 to 5 mg/day; 5 to 10 years, 5 to 10 mg/day; 10 to 18 years, 10 to 20 mg/day. Rarely, doses up to 50% to 100% higher may be required for severe biochemical or clinical hyperthyroidism (guideline dosing)
Maintenance, reduce dose by 50% or more to maintain euthyroid state (guideline dosing)
Discontinuation, consider reducing the dose or discontinuing after 1 to 2 years in children requiring low doses to assess whether the patient has achieved remission; alternatively, patient who is tolerating therapy may continue for extended periods.
Preparation for radioactive iodine
therapy, discontinue 2 to 3 days
before treatment; restarting methimazole usually not necessary in pediatric patients (guideline dosage).
Preparation for thyroidectomy, give methimazole for 1 to 2 months with the goal to render the patient euthyroid prior to
surgery (guideline dosage)
Indications
FDA-Labeled Indications:
Hyperthyroidism
Non-FDA Labeled Indications:
Choriocarcinoma
Disorder of thyroid gland
; Prophylaxis – Toxicity due to
radiotherapy; Prophylaxis
Pregnancy – Thyrotoxicosis due to
Graves’ disease
Thyroid eye disease; Treatment and Prophylaxis
Thyroid storm
Thyrotoxicosis, Drug-induced
Mechanism of Action
Methimazole inhibits the synthesis of thyroid hormones
and thus is effective in the
treatment of hyperthyroidism. The drug does not inactivate existing thyroxine and tri-iodothyronine 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. Methimazole is readily absorbed in the
gastrointestinal tract, metabolized in the
liver, and excreted in the
urine
Adverse Effect
Common:
Dermatologic:
Rash
Musculoskeletal:
Arthritis
Serious:
Cardiovascular:
Vasculitis
Dermatologic:
Erythroderma
Gastrointestinal:
Pancreatitis
Hematologic:
Agranulocytosis (0.3% to 1%)
Aplastic anemia
Hepatic:
Hepatotoxicity
Immunologic:
Insulin autoimmune syndrome
Contraindication
Hypersensitivity to methimazole or any component of the product
Interaction
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
.
Beta-adrenergic blocking agents:
Hyperthyroidism may cause an increased clearance of beta blockers with a high extraction ratio. A reduced dose 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.
Major:
Bupropion (probable)
Tegafur (theoretical)
Moderate:
Acenocoumarol (probable)
Anisindione (probable)
Dicumarol (probable)
Phenindione (probable)
Phenprocoumon (probable)
Warfarin (probable)
Phamacokinetics
Absorption:
Oral: readily absorbed
Metabolism:
rapidly metabolized
Excretion:
Renal
Dialyzable: not established
Precaution
Hematologic:
Agranulocytosis, potentially life-threatening, may occur; monitoring recommended if symptoms occur; discontinue use if agranulocytosis, aplastic anemia
, ANCA-positive vasculitis, hepatitis, or exfoliative dermatitis occur
Hypoprothrombinemia and bleeding may occur; monitoring recommended, especially before surgery
Hepatic:
Hepatotoxicity; monitoring recommended if symptoms occur; discontinue use if clinical evidence of abnormalities
Other:
Cross-reactivity with propylthiouracil has been reported, including antineutrophil cytoplasmic antibody-positive vasculitis, cutaneous reactions, hepatotoxicity, and agranulocytosis
Pregnancy Category
D (FDA)
Breast Feeding
WHO:
WHO documentation states insufficient data.
Infant risk cannot be ruled out.
Monitoring
Thyroid stimulating hormone
(TSH), free thyroxine
(T4):
Routinely
Clinical signs and symptoms of hyperthyroidism should be
monitored to determine therapeutic effect
.
Graves’s disease, thyroid function tests
(free T4, total triiodothyronine (T3), TSH):
At 2 to 6 weeks
after initiation, again 4 to 6 weeks
after dose change, then every 2 to 3 months once stabilized or 4- to 6-month intervals in patients stable on minimal dose and receiving long-term therapy
Graves’s disease, thyrotropin receptor antibody (TRAb) levels:
Prior to
weaning or discontinuing therapy to assist in prediction of patients with greater chance for remission with withdrawal of therapy and every 1 to 2 years in patients on long-term continued therapy
Pediatric, thyroid function tests
(free T4, total T3, TSH):
2 to 6 weeks
after initiation and again at 4 to 6 weeks
after dosage adjustment, then every 2 to 3 months once the dosage is stabilized; serum TSH may remain suppressed for several months after initiation of therapy and thus should not be the only parameter for evaluation of early therapeutic effect
Iodine-induced Thyrotoxicosis, urinary iodine (spot urine adjusted for urine creatinine concentration or a 24-hour urine iodine) to evaluate rate of clearance of iodine
Toxic Multinodular Goiter or Toxic Adenoma, thyroid function tests
:
Frequently (every 3 months) initially, especially in the
elderly, until stable function is documented and then decrease frequency
Complete blood count, including WBC count with differential and liver profile including bilirubin and transaminase levels:
Prior to
initiation of therapy. Reconsider initiating therapy if baseline absolute neutrophil counts are less than 1000/mm(3) or liver transaminase elevations are greater than 5 times the ULN
Pediatric, complete blood cell count including differential, liver function including bilirubin, transaminases, and alkaline phosphatase: At baseline
Pediatric, weight gain:
Periodically
Prothrombin time:
Especially prior to
surgical procedures
Sore throat
, skin eruptions
, fever, headache, or general malaise to detect possibility of agranulocytosis
How to Take or Administration
General Information:
The National Institute for Occupational Safety and Health (NIOSH) recommends the use of
single gloves by anyone handling intact tablets or capsules or administering from a unit-dose package.
In the
preparation of tablets or capsules, including cutting, crushing, or manipulating, or the handling of uncoated tablets, NIOSH recommends the use of
double gloves and a protective gown. Prepare in a ventilated control device, if possible. Use respiratory protection if not prepared in a control device. During administration, wear single gloves, and wear eye/face protection if the formulation is hard to swallow or if the patient may resist, vomit, or spit up.
Dosage Form
Oral Tablet:
5 MG
10 MG
Treatment
Management of Mild to Moderate Toxicity:
Treatment is symptomatic and supportive.
Management of Severe Toxicity:
Treatment is symptomatic and supportive
Toxicology
A specific toxic dose has not been established. Adverse effects at higher doses (60 mg/day) are common.
Patient Counselling or Clinical Teaching
Advise patient to report signs/symptoms of hepatotoxicity, aplastic anemia
, or infection (fever, headache, malaise, skin eruptions
, and sore throat
).
Category of Methimazole :
