Methimazole dosing

Case Conclusion HP began methimazole therapy for her Graves hyperthyroidism. She also began propranolol to help control her tachycardia and tremor. During this time HP should avoid excessive exercise or other sympathomimetic drugs until her symptoms of tachycardia have subsided. HP will return to the clinic for follow-up in 4 weeks. At that time, methimazole dose, tolerability, compliance, and thyroid function tests will be reassessed. 

MMI and PTU can lead to methimazole embryopathy with choanal or esophageal atresia. In pregnant women the antithyroid diug dose should be minimized to prevent fetal hypothyroidism by maintaining the maternal free thyroxine serum level slightly above the upper limit of normal. 

Antithyroid drags have several side effects. The most frequent side effects are maculopapular rashes, pruritus, urticaria, fever, arthralgia and swelling of the joints. They occur in 1-5% of patients [1, 2]. Loss of scalp hair, gastrointestinal problems, elevations of bone isoenzyme of alkaline phosphatase and abnormalities of taste and smell are less common. The incidence of all these untoward reactions is similar with MMI and PTU. Side effects of MMI are dose-related, whereas those of PTU are less clearly related to dose [1]. PTU may cause slight transient increases of serum aminotransferase and y-glutamyl transpeptidase concentrations but also severe hq atotoxicity whereas methimazole or carbimazole can be associated with cholestasis. The side... 

Alternative—methimazole 30 mg enterally every 6-8 h. Reduce dose once signs/symptoms are controlled. Usual maintenance dose is 15-60 mg daily in three equally divided doses... 

When 20 mg/kg of methimazole was administered i.p. or orally to rats, urinary methimazole glucuronides accounted for 36-48% of the dose in 24 hours. The only other urinary metabolite accounted for 10-20% and was not characterized. An additional 14-20% of methimazole was excreted unchanged in 24 hour urine. The bile contained methimazole glucuronide and two unidentified metabolites. One of which was the same as the unidentified urinary metabolites. Plasma proteins bound 5% of methimazole which had no affinity for any specific tissue. Methimazole had a much greater CHCI3/H2O partition coefficient and 1 0 solubility than did propylthiouracil. Between 77 and 95% of the methimazole was excreted in the urine and approximately 10% in the bile. Since fecal excretion was neglegible an enter-ohepatic circulation was present. The half life of urinary excretion was 5-7 hours regardless of the route of administration (15). 

METHIMAZOLE Usually given in 3 equal doses at approximately 8 hour intervals. 

Methimazole (Tapazole) [Antithyroid Agent] Uses Hyperthy-roidism, thyrotoxicosis, pr for thyroid surgery or radiation Action Blocks T3 T4 formation Dose Adults. Initial 15-60 mg/d PO tid Maint 5-15 mg PO daily Peds. Initial 0.4-0.7 mg/kg/24 h PO tid Maint V h- U h of initial dose PO daily w/ food Caution [D, +/-] Contra Breast-feeding Disp Tabs SE GI upset, dizziness, blood dyscrasias Interactions t Effects OF digitalis glycosides, metoprolol, propranolol X effects OF anticoagulants, theophylline X effects W/ amiodarone EMS None OD May cause N/V, HA, abd pain, fever, and pale skin symptomatic and supportive... 

The initial dose for carbimazole or methimazole is 20-60 mg/day until the patient is rendered euthyroid with maintenance therapy of 5-15 mg/day. For propylthiouracil the initial dose is 300 50 mg/day with maintenance doses of 50-150 mg/day. Higher doses are sometimes used in severe disease. Two different treatment regimens may be used (1) titration regimen, to try to achieve a euthyroid state by dose tritation and (2) block-replacement regimen, with... 

In contrast, methimazole is completely absorbed but at variable rates. It is readily accumulated by the thyroid gland and has a volume of distribution similar to that of propylthiouracil. Excretion is slower than with propylthiouracil 65-70% of a dose is recovered in the urine in 48 hours. 

Radioiodine therapy utilizing 1311 is the preferred treatment for most patients over 21 years of age. In patients without heart disease, the therapeutic dose may be given immediately in a range of 80-120 M3i/g of estimated thyroid weight corrected for uptake. In patients with underlying heart disease or severe thyrotoxicosis and in elderly patients, it is desirable to treat with antithyroid drugs (preferably methimazole) until the patient is euthyroid. The medication is then stopped for 5-7 days before... 

He CT, Hsieh AT, Pei D, et al. Comparison of single daily dose of methimazole and propylthiouracil in the treatment of Graves hyperthyroidism. Clin Endocrinol. 2004 60 676-681. 

Disposition in the Body. Rapidly and almost completely absorbed after oral administration and converted to the active metabolite methimazole. Almost completely excreted in the urine in 24 hours as metabolites 3-methyl-2-thiohydantoin has been identified as a minor metabolite in urine and plasma. About 3% of a dose is eliminated in the faeces. 

Carbimazole and methimazole (the chief metabolite of carbimazole) (t) 6h) and propylthiouracil (t) 2 h) are commonly used, but t) matters little since the drugs accumulate in the thyroid and act there for 30-40 h thus a single daily dose suffices. 

Pharmacokinetics PTU is rapidly absorbed. The oral bioavailabi% of 50% to 80% may be due to a large hepatic first-pass effect. Methimazole is completely absorbed. The duration of action for PTU is approximately 7 hours and therefore requires multiple daily doses (every 6 to 8 hours). 

A Methimazole has a longer TV2 than PTU and can be dosed once daily PTU requires three to four daily doses, which may affect compliance. PTU does not cause pretibial myxedema rather Graves hyperthyroidism leads to pretibial myxedema. Methimazole does not interact with amiodarone however, amiodarone can affect thyroid function, leading to both hypo- and hyperthyroidism. PTU therapy may result in spontaneous remission, but patients typically require therapy for many years (1 to 15 years). 

Methimazole is indicated in the treatment of hyperthyroid-i.sm. It is more potent than propylthiouracil. The side effects are similar to those of propylthiouracil. As with other antithyroid drugs, patients using this drug should be under medical supervision. Also, like the other antithyroid drugs, methimazole is mo.st effective if the total daily dose is subdivided and given at 8-hour intervals. 

The antithyroid compounds currently used in the United States are propylthiouracil (6- -propylthiouracil) and methimazole (/-methyl-2-mercaptoimidazole Tapazole). In Great Britain and Europe, carbimazole (Neo-mercazole), a carbethoxy derivative of methimazole, is available, and its antithyroid action is due to its conversion to methimazole after absorption. Measurements of the course of organification of radioactive iodine by the thyroid show that absorption of effective amounts of propylthiouracil follows within 20 to 30 minutes of an oral dose, and that the duration of action of the compounds used clinically is brief. The effect of a dose of 100 mg of propylthiouracil begins to wane in 2 to 3 hours, and even a 500-mg dose is completely inhibitory for only 6 to 8 hours. As little as 0.5 mg of methimazole similarly decreases the organification of radioactive iodine in the thyroid gland, but a single dose of 10 to 25 mg is needed to extend the inhibition to 24 hours. 

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