preloder

Methimazole


Methimazole

prevents the

thyroid gland

from producing too much thyroid hormone.

Methimazole

is used to treat hyperthyroidism (overactive thyroid). It is also used before thyroid surgery or

radioactive iodine

treatment.

Methimazole

may also be

used for

purposes not listed in this

medication

guide.
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

    ).












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