Felimazole
Felimazole Uses, Dosage, Side Effects, Food Interaction and all others data.
Felimazole is a thionamide antithyroid agent that inhibits the synthesis of thyroid hormones. It was first introduced as an antithyroid agent in 1949 and is now commonly used in the management of hyperthyroidism, particularly in those for whom more aggressive options such as surgery or radioactive iodine therapy are inappropriate.
On a weight basis, methimazole is 10 times more potent than the other major antithyroid thionamide used in North America, propylthiouracil, and is the active metabolite of the pro-drug carbimazole, which is an antithyroid medication used in the United Kingdom and parts of the former British Commonwealth. Traditionally, methimazole has been preferentially used over propylthiouracil due to the risk of fulminant hepatotoxicity carried by the latter, with propylthiouracil being preferred in pregnancy due to a perceived lower risk of teratogenic effects. Despite documented teratogenic effects in its published labels, the true teratogenicity of methimazole appears to be unclear and its place in therapy may change in the future.
Felimazole inhibits the synthesis of thyroid hormones resulting in an alleviation of hyperthyroidism. Onset of action occurs within 12 to 18 hours, and its duration of action is 36 to 72 hours, likely due to concentration of methimazole and some metabolites within the thyroid gland after administration.
| Trade Name | Felimazole |
| Availability | Prescription only |
| Generic | Methimazole |
| Methimazole Other Names | Methimazole, Thiamazol, Thiamazole, Thiamazolum, Tiamazol |
| Related Drugs | propylthiouracil, Tapazole, potassium iodide, reserpine, iodine / potassium iodide |
| Type | Tablet, sugar coated |
| Formula | C4H6N2S |
| Weight | Average: 114.169 Monoisotopic: 114.025168892 |
| Protein binding | Methimazole exhibits little-to-no protein binding, existing primarily as free drug in the serum. |
| Groups | Approved |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Felimazole is a thionamide antithyroid agent that inhibits the actions of thyroid peroxidase, leading to a reduction in thyroid hormone synthesis and amelioration of hyperthyroidism.
In the United States, methimazole is indicated for the treatment of hyperthyroidism in patients with Graves' disease or toxic multinodular goiter for whom thyroidectomy or radioactive iodine therapy are not appropriate treatment options. Felimazole is also indicated for the amelioration of hyperthyroid symptoms in preparation for thyroidectomy or radioactive iodine therapy.
In Canada, methimazole carries the above indications and is also indicated for the medical treatment of hyperthyroidism regardless of other available treatment options.
Felimazole is also used to associated treatment for these conditions: Graves' Disease, Hyperthyroidism, Toxic multinodular goiter
How Felimazole works
Felimazole's primary mechanism of action appears to be interference in an early step in thyroid hormone synthesis involving thyroid peroxidase (TPO), however the exact method through which methimazole inhibits this step is unclear. TPO, along with hydrogen peroxide, normally catalyzes the conversion of iodide to iodine and then further catalyzes the incorporation of this iodine onto the 3 and/or 5 positions of the phenol rings of tyrosine residues in thyroglobulin. These thyroglobulin molecules then degrade within thyroid follicular cells to form either thyroxine (T4) or tri-iodothyronine (T3), which are the main hormones produced by the thyroid gland.
Felimazole may directly inhibit TPO, but has been shown in vivo to instead act as a competitive substrate for TPO, thus becoming iodinated itself and interfering with the iodination of thyroglobulin. Another proposed theory is that methimazole’s sulfur moiety may interact directly with the iron atom at the centre of TPO’s heme molecule, thus inhibiting its ability to iodinate tyrosine residues. Other proposed mechanisms with weaker evidence include methimazole binding directly to thyroglobulin or direct inhibition of thyroglobulin itself.
Toxicity
The oral LD50 of methimazole in rats is 2250 mg/kg. Signs and symptoms of methimazole overdose may include gastrointestinal distress, headache, fever, joint pain, pruritus, and edema. More serious adverse effects, such as aplastic anemia or agranulocytosis, may manifest within hours to days. Hepatitis, nephrotic syndrome, exfoliative dermatitis, and CNS effects such as neuropathy or CNS depression/stimulation are also potential, albeit less frequent, results of overdose.
Management of overdose involves supportive treatment as dictated by the patient's status. This may involve monitoring of the patient's vital signs, blood gases, serum electrolytes, or bone marrow function as indicated.
Food Interaction
No interactions found.Felimazole Drug Interaction
Moderate: metoprolol, metoprolol, metoprolol, metoprololUnknown: aspirin, aspirin, apixaban, apixaban, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, acetaminophen, acetaminophen, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol, cetirizine, cetirizine
Felimazole Disease Interaction
Volume of Distribution
The apparent volume of distribution of methimazole has been reported as roughly 20 L. Following oral administration, methimazole is highly concentrated in the thyroid gland - intrathyroidal methimazole levels are approximately 2 to 5 times higher than peak plasma levels, and remain high for 20 hours after ingestion.
Elimination Route
Absorption of methimazole after oral administration is rapid and extensive, with an absolute bioavailability of approximately 0.93 and a Tmax ranging from 0.25 to 4.0 hours. Cmax is slightly, but not significantly, higher in hyperthyroid patients, and both Cmax and AUC are significantly affected by the oral dose administered.
Half Life
Following a single intravenous bolus injection of 10mg of methimazole, the t1/2 of the distribution phase was 0.17 hours and the t1/2 of the elimination phase was 5.3 hours. Felimazole's primary active metabolite, 3-methyl-2-thiohydantoin, has a half-life approximately 3 times longer than its parent drug. Renal impairment does not appear to alter the half-life of methimazole, but patients with hepatic impairment showed an increase in half-life roughly proportional to the severity of their impairment - moderate insufficiency resulted in a elimination t1/2 of 7.1 hours, while severe insufficiency resulted in an elimination t1/2 of 22.1 hours.
There does not appear to be any significant differences in half-life based on thyroid status (i.e. no difference between euthyroid and hyperthyroid patients).
Clearance
Following a single intravenous bolus injection of 10mg of methimazole, clearance was found to be 5.70 L/h. Renal impairment does not appear to alter clearance of methimazole, but patients with hepatic impairment showed a reduction in clearance roughly proportional to the severity of their impairment - moderate insufficiency resulted in a clearance of 3.49 L/h, while severe insufficiency resulted in a clearance of 0.83 L/h.
There does not appear to be any significant differences in clearance based on thyroid status (i.e. no difference between euthyroid and hyperthyroid patients).
Elimination Route
Urinary excretion of unchanged methimazole has been reported to be between 7% and 12%. Elimination via feces appears to be limited, with a cumulative fecal excretion of 3% after administration of methimazole. Enterohepatic circulation also appears to play a role in the elimination of methimazole and its metabolites, as significant amounts of these substances are found in the bile post-administration.
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