Methimazole

Methimazole is a popular antithyroid drug used for treating hyperthyroid cats in the U.S., particularly when radioiodine is not readily available or is cost prohibitive.

Overview

• Methimazole is approved for use in animals (Felimazole; dechra-us.com) and humans.

• Methimazole compounded with pluronic lecithin organogel (PLO) is one of few veterinary drugs with demonstrated efficacy when administered transdermally.

  • Concentration: 50 mg/mL

  • Starting dose: 2.5 mg/cat q12h

Toxicities

• Dose-dependent

  • In 10%–20% of cats treated with oral methimazole, mild-to-moderate vomiting, diarrhea, and decreased appetite typically developed during the first 4 weeks of treatment.^1,2

    • GI signs are significantly less common in cats receiving transdermal treatment than in those receiving oral methimazole.¹

  • Cats often develop mild increases in BUN and creatinine with treatment to the euthyroid state.³

    • Low urine specific gravity and high serum thyroxine (T₄) concentrations may increase risk for posttreatment development of azotemia,⁴ although cats with highly concentrated urine can still be at risk.⁵

    • Serum T₄ concentrations should be targeted to the mid-normal range, as overtreatment to low serum T₄ can worsen azotemia and lead to shortened survival times.⁶

• Idiosyncratic

  • Acute, apparently nondose-dependent (ie, idiosyncratic) toxicities can develop at 1–4 weeks of treatment and typically include

    • Facial excoriation around the neck and pinnae, blood dyscrasia (eg, neutropenia, thrombocytopenia), and new hepatopathy

    • Leukopenia resulting from only lymphopenia does not indicate methimazole discontinuation.

  • Idiosyncratic hepatopathy is typically a mixed pattern (ie, with elevations in both hepatocellular and cholestatic enzymes) and may involve hyperbilirubinemia.

    • Liver enzyme activity should be compared with values obtained before treatment, as many hyperthyroid cats have elevated ALT and/or ALP at diagnosis.⁷

      • These should resolve with treatment.

  • Cats may develop myasthenia gravis, characterized by neuromuscular weakness and positive acetylcholine receptor autoantibodies during the first few months of treatment^8,9; however, this is rare.

Management of Adverse Events

• For simple GI upset without biochemistry abnormalities, discontinue methimazole until signs resolve.

  • Restart at a 50% dose reduction or switch to transdermal methimazole.¹

• Idiosyncratic toxicities fail to respond to dose reduction.

  • Discontinue methimazole and schedule alternative treatment (eg, radioiodine, Hill’s Prescription Diet y/d Feline Thyroid Health [hillsvet.com], thyroidectomy).

    • For facial excoriation and if pruritus is severe, consider short-term antiinflammatory doses of prednisolone.

    • For blood dyscrasia, evaluate for fever or bruising.

      • Neutropenia and thrombocytopenia will typically resolve after drug discontinuation without additional intervention.¹⁰

      • In cases of severe neutropenia (ie, <1000–1500 µL), antibiotics (eg, amoxicillin–clavulanate) may be indicated.

      • Recheck CBC 1 week after discontinuation.

    • For hepatopathy, consider short-term treatment with glutathione precursor (eg, S-adenosylmethionine [SAMe])

      • Recheck liver enzyme activity 1–2 weeks after discontinuation.

    • For myasthenia gravis, consider pyridostigmine treatment.

      • Follow clinical response and acetylcholine receptor antibody titers after discontinuation.

Monitoring

• Clinical monitoring by owners is important, as toxicities can develop between routine rechecks.

• Rechecks at 2 and 4 weeks after treatment initiation should be sufficient to determine euthyroidism and presence of toxicity.

  • Along with monitoring serum T₄ concentrations and general clinical status, cats should be monitored for

    • New azotemia via BUN, creatinine, and urine specific gravity

    • Idiosyncratic toxicity via CBC and liver enzyme activities

• Once euthyroid state reached, routinely (q3–6mo) check renal values, blood pressure, and serum T₄ concentrations.