Thyrolar

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Thyrolar

Classes

Thyroid Agents

Administration

 
NOTE: Liotrix products made by different manufacturers may not be interchangeable. Patients should not have their brands of medication switched without prescriber approval.

Oral Administration

Administer on an empty stomach with a glass of water at least 30—60 minutes before breakfast. Administer apart from medications known to decrease thyroid hormone absorption (e.g., calcium salts, see Drug Interactions).

Oral Solid Formulations

Tablets may be crushed and suspended in a small amount (5—10 ml or 1—2 teaspoonfuls) of water, and administered by spoon or dropper for those unable to swallow whole tablets. Do not store the suspension.
Tablets may also be crushed and sprinkled over a small amount of food (e.g., cooked cereal or apple sauce). Do not mix crushed tablets with enteral feedings or soybean-based infant formulas.

Adverse Reactions
Severe

atrial fibrillation / Early / Incidence not known
heart failure / Delayed / Incidence not known

Moderate

hyperthyroidism / Delayed / Incidence not known
sinus tachycardia / Rapid / Incidence not known
palpitations / Early / Incidence not known
peripheral edema / Delayed / Incidence not known
heat intolerance / Early / Incidence not known
thyrotoxicosis / Delayed / Incidence not known
chest pain (unspecified) / Early / Incidence not known
pseudotumor cerebri / Delayed / Incidence not known

Mild

pruritus / Rapid / Incidence not known
urticaria / Rapid / Incidence not known
vomiting / Early / Incidence not known
anorexia / Delayed / Incidence not known
irritability / Delayed / Incidence not known
nausea / Early / Incidence not known
menstrual irregularity / Delayed / Incidence not known
headache / Early / Incidence not known
weight loss / Delayed / Incidence not known
fever / Early / Incidence not known
tremor / Early / Incidence not known
anxiety / Delayed / Incidence not known
insomnia / Early / Incidence not known
diaphoresis / Early / Incidence not known
diarrhea / Early / Incidence not known
alopecia / Delayed / Incidence not known

Boxed Warning
Obesity treatment

The use of liotrix for obesity treatment is not justified or recommended. Normal replacement doses are not effective, and large doses that would be required for reducing weight in euthyroid patients could lead to serious or even life-threatening toxicity. This is particularly dangerous when thyroid agents are administered along with sympathetic amines that are also often used for weight loss.

Common Brand Names

Thyrolar

Dea Class

Rx

Description

Oral mixture of 2 synthetic thyroid hormones: T4 (levothyroxine) and T3 (liothyronine), in a 4-to-1 ratio by weight, respectively
Used for hypothyroidism of almost any etiology, including congenital hypothyroidism (cretinism) and myxedema in adults and pediatric patients
Levothyroxine is the preferred replacement therapy for routine use; combination of T3 an T4 therapy may be useful in select patients, such as those with symptoms despite stabilization of a dose for T4 replacement
A "Liotrix-1" synthetic tablet is roughly comparable to a porcine thyroid USP 1 grain (60 mg) tablet (e.g., Armour Thyroid)

Dosage And Indications
For the treatment of hypothyroidism of any etiology, except transient hypothyroidism during the recovery phase of subacute thyroiditis. This category includes cretinism (congenital hypothyroidism), myxedema, and ordinary hypothyroidism in patients of any age (pediatrics, adults, the elderly), or state (including pregnancy); primary hypothyroidism resulting from functional deficiency, primary atrophy, partial or total absence of thyroid gland, or the effects of surgery, radiation, or drugs with or without the presence of goiter; and secondary (pituitary), or tertiary (hypothalamic) hypothyroidism. Oral dosage (Thyrolar tablets) Adults

Initially, 1 tablet of Thyrolar-1/2 (25 mcg T4 with 6.25 mcg T3) PO once daily. A lower starting dosage of 1 tablet of Thyrolar-1/4 (12.5 mcg T4 with 3.1 mcg T3) PO once daily is recommended for those with long-standing myxedema or if cardiovascular disease is suspected. Increase the dosage every 2 to 3 weeks in increments of 1 tablet of Thyrolar-1/4 as needed until the appropriate response is obtained. Typical maintenance dose: 50 to 100 mcg T4 with 12.5 to 25 mcg T3 per daily (e.g., Thyrolar-1 as 1 tablet PO once daily up to Thyrolar-2 as 1 tablet PO once daily). Per treatment guidelines, levothyroxine is the preferred treatment for hypothyroidism.

Adolescents

Typical adolescent maintenance doses for congenital hypothyroidism are similar to adult ranges and are usually more than 75 mcg T4 with 18.75 mcg T3 PO once daily. Titrate dosage every 2 to 3 weeks as needed until the appropriate response is obtained. The American Academy of Pediatrics and other guidelines recommend use of levothyroxine.

Children 6 to 12 years

The usual dosage range for congenital hypothyroidism is 50 to 75 mcg T4 with 12.5 to 18.75 mcg T3 given PO once daily. Titrate the dosage every 2 to 3 weeks as needed until the appropriate response is obtained. The American Academy of Pediatrics and other guidelines recommend use of levothyroxine.

Children 1 to 5 years

The usual dosage range for congenital hypothyroidism is 37.5 to 50 mcg T4 with 9.35 to 12.5 mcg T3 PO given once daily. Titrate the dosage every 2 to 3 weeks as needed until appropriate response is obtained. Treatment for cretinism should be initiated immediately upon diagnosis and continued for life unless transient hypothyroidism is suspected, then therapy may be interrupted for 2 to 8 weeks after the age of 3 years for assessment. Cessation of therapy may be justified in patients who have maintained a normal TSH during those 2 to 8 weeks. The American Academy of Pediatrics and other guidelines recommend use of levothyroxine.

Infants 6 months up to 12 months

The usual dosage range for congenital hypothyroidism is 25 to 37.5 mcg T4 with 6.25 to 9.35 mcg T3 PO once daily. Titrate the dosage every 2 to 3 weeks as needed until appropriate response is obtained. Treatment should be initiated immediately upon diagnosis and continued for life unless re-evaluation at approximately 3 years of age suggests a trial discontinuation of treatment at that time. The American Academy of Pediatrics and other guidelines recommend use of levothyroxine.

Neonates and Infants less than 6 months

The usual dosage range for congenital hypothyroidism is 12.5 to 25 mcg T4 with 3.1 to 6.25 mcg T3 given PO once daily. Titrate the dosage every 2 to 3 weeks as needed until appropriate response is obtained. Treatment should be initiated immediately upon diagnosis and continued for life unless re-evaluation at approximately 3 years of age suggests a trial discontinuation of treatment at that time. The American Academy of Pediatrics and other guidelines recommend use of levothyroxine.

For thyroid suppression testing as an aid for hyperthyroidism diagnosis in patients with signs of mild hyperthyroidism in whom baseline laboratory tests appear normal, or to demonstrate thyroid gland autonomy in patients with Grave's ophthalmology. Oral dosage (Thyrolar tablets) Adults

Usual suppressive dosage based on dosage of T-4 (levothyroxine) is 1.56 mcg/kg/day PO for 7 to 10 days. Radioactive iodine uptake is determined before and after administration of exogenous thyroid hormone. A 50% or greater suppression of uptake indicates a normal thyroid-pituitary axis and thus rules out thyroid gland autonomy.

Dosing Considerations
Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are necessary.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are necessary.

Drug Interactions

Acarbose: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued.
Alendronate: (Moderate) Separating times of administration of alendronate from levothyroxine and other medications will maximize alendronate absorption and clinical benefit. For example, administering the levothyroxine dose at bedtime can avoid this interaction with alendronate. The bioavailability of alendronate was slightly decreased when alendronate and levothyroxine were co-administered to healthy subjects The mean AUC and Cmax of alendronate decreased by 7% and 9%, respectively. Alendronate should always be administered upon arising for the day and at least 30 minutes before the first food, beverage, or other medication of the day. To minimize interactions, levothyroxine is also best taken on an empty stomach with a glass of water.
Alendronate; Cholecalciferol: (Moderate) Separating times of administration of alendronate from levothyroxine and other medications will maximize alendronate absorption and clinical benefit. For example, administering the levothyroxine dose at bedtime can avoid this interaction with alendronate. The bioavailability of alendronate was slightly decreased when alendronate and levothyroxine were co-administered to healthy subjects The mean AUC and Cmax of alendronate decreased by 7% and 9%, respectively. Alendronate should always be administered upon arising for the day and at least 30 minutes before the first food, beverage, or other medication of the day. To minimize interactions, levothyroxine is also best taken on an empty stomach with a glass of water.
Alogliptin: (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
Alogliptin; Metformin: (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin. (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
Alogliptin; Pioglitazone: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued. (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
Alpha-glucosidase Inhibitors: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued.
Aluminum Hydroxide: (Moderate) To minimize an interaction, administer thyroid hormones at least 4 hours before or after antacids or other drugs containing aluminum hydroxide. Aluminum hydroxide, often found in antacids, interferes with the intestinal absorption of thyroid hormones. Gastric acidity is an essential requirement for adequate absorption of levothyroxine.
Aluminum Hydroxide; Magnesium Carbonate: (Moderate) To minimize an interaction, administer thyroid hormones at least 4 hours before or after antacids or other drugs containing aluminum hydroxide. Aluminum hydroxide, often found in antacids, interferes with the intestinal absorption of thyroid hormones. Gastric acidity is an essential requirement for adequate absorption of levothyroxine.
Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) To minimize an interaction, administer thyroid hormones at least 4 hours before or after antacids or other drugs containing aluminum hydroxide. Aluminum hydroxide, often found in antacids, interferes with the intestinal absorption of thyroid hormones. Gastric acidity is an essential requirement for adequate absorption of levothyroxine.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after a dose of simethicone. Concurrent use may reduce the efficacy of levothyroxine by binding and delaying or preventing oral absorption, potentially resulting in hypothyroidism. Simethicone has been reported to chelate oral levothyroxine within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. (Moderate) To minimize an interaction, administer thyroid hormones at least 4 hours before or after antacids or other drugs containing aluminum hydroxide. Aluminum hydroxide, often found in antacids, interferes with the intestinal absorption of thyroid hormones. Gastric acidity is an essential requirement for adequate absorption of levothyroxine.
Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) To minimize an interaction, administer thyroid hormones at least 4 hours before or after antacids or other drugs containing aluminum hydroxide. Aluminum hydroxide, often found in antacids, interferes with the intestinal absorption of thyroid hormones. Gastric acidity is an essential requirement for adequate absorption of levothyroxine.
Amiodarone: (Moderate) Amiodarone has a complex effect on the metabolism of thyroid hormones and can alter thyroid function tests in many patients. Since approximately 37% of amiodarone (by weight) is iodine, maintenance doses of 200 to 600 mg of amiodarone/day result in ingestion of 75 to 225 mg/day of organic iodide, resulting in much higher total iodine stores in the body. In addition, amiodarone decreases T4 5'-deiodinase activity, which decreases the peripheral conversion of T4 to T3, leading to decreased serum T3. Serum T4 levels are usually normal but may be slightly increased. TSH concentrations usually increase during amiodarone therapy, but after 3 months of continuous administration, TSH concentrations often return to normal. However, amiodarone can cause hypothyroidism or hyperthyroidism, including life-threatening thyrotoxicosis. Therefore, patients receiving levothyroxine and amiodarone should be monitored for changes in thyroid function; because of the slow elimination of amiodarone and its metabolites, abnormal thyroid function tests may persists for weeks or months after amiodarone drug discontinuation.
Amobarbital: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
Amoxapine: (Minor) Thyroid hormones may increase receptor sensitivity and enhance the effects of amoxapine. Although this drug combination appears to be safe, clinicians should be aware of the remote possibility of exaggerated cardiovascular side effects such as arrhythmias and CNS stimulation.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
Asparaginase Erwinia chrysanthemi: (Moderate) Some hypothyroid patients receiving asparaginase may require reduced doses of thyroid hormone. Other patients may remain euthyroid during combined treatment. Monitor TSH levels and monitor for symptoms of hyperthyroidism; a free-T4 concentration may be useful to assess euthyroidism. Asparaginase may decrease the serum TBG (thyroxine-binding globulin) concentration. Decreased amounts of TBG may result in an increased clinical response to thyroid hormones.
Aspirin, ASA; Butalbital; Caffeine: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
Aspirin, ASA; Omeprazole: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
Barbiturates: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
Beta-agonists: (Moderate) Monitor blood pressure and heart rate during concomitant beta-agonist and thyroid hormone use. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.
Beta-blockers: (Minor) Because thyroid hormones cause cardiac stimulation including increased heart rate and increased contractility, the effects of beta-blockers may be reduced by thyroid hormones. The reduction of effects may be especially evident when a patient goes from a hypothyroid to a euthyroid state or when excessive amounts of thyroid hormone is given to the patient.
Butabarbital: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
Butalbital; Acetaminophen: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
Butalbital; Acetaminophen; Caffeine: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
Butalbital; Acetaminophen; Caffeine; Codeine: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
Butalbital; Aspirin; Caffeine; Codeine: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
Calcium Acetate: (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
Calcium Carbonate: (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
Calcium Carbonate; Magnesium Hydroxide: (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
Calcium Carbonate; Simethicone: (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
Calcium Chloride: (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
Calcium Gluconate: (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
Calcium: (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
Calcium; Vitamin D: (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
Canagliflozin: (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
Canagliflozin; Metformin: (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin. (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
Carbamazepine: (Minor) Use carbamazepine and thyroid hormones together with caution. Carbamazepine may inhibit the binding of thyroid hormones to carrier proteins, resulting in a transient increase in free thyroid hormones followed by an overall decrease in total thyroid hormone concentrations. Carbamazepine reduces serum protein binding of levothyroxine, and total and free-T4 may be reduced by 20% to 40%, but most patients have normal serum TSH levels and are clinically euthyroid. Monitor thyroid hormone parameters.
Chlorpropamide: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
Cholestyramine: (Moderate) Administer oral levothyroxine or other oral thyroid hormones at least 4 hours before a dose of cholestyramine. Cholestyramine and other bile acid sequestrants have been shown to decrease the oral absorption of thyroid hormones. Monitor thyroid function periodically to ensure proper clinical management.
Chromium: (Moderate) Advise patients to separate chromium supplement ingestion from taking their oral thyroid hormone. For example, taking oral thyroid hormones 1 hours before or 3 hours after chromium picolinate ingestion should minimize an interaction. Chromium could potentially decrease the oral absorption of thyroid hormones. In one study of normal volunteers, the subjects (n = 7) ingested levothyroxine sodium, either taken separately or co-administered with chromium picolinate. Serum thyroxine was measured at intervals over a 6-hour period following drug ingestion. Chromium picolinate significantly decreased the serum thyroxine concentrations. (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
Cocaine: (Moderate) The concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further.
Colesevelam: (Moderate) Administer oral levothyroxine or other oral thyroid hormones at least 4 hours before a dose of colesevelam. Colesevelam and other bile acid sequestrants have been shown to decrease the oral absorption of thyroid hormones. Monitor thyroid function periodically to ensure proper clinical management.
Colestipol: (Moderate) Administer oral levothyroxine or other oral thyroid hormones at least 4 hours before a dose of colestipol. Colestipol and other bile acid sequestrants have been shown to decrease the oral absorption of thyroid hormones. Monitor thyroid function periodically to ensure proper clinical management.
Cyclosporine: (Moderate) Serum trough cyclosporine concentrations appear to be reduced by concurrent oral cyclosporine and levothyroxine use. Claosely monitor cyclosporine concentrations with concomitant levothyroxine therapy. Among 10 patients who took cyclosporine (Neoral) capsules twice daily for at least a year and oral levothyroxine 100 mcg daily for at least 3 months, the trough serum cyclosporine concentration was significantly lower as compared with values from 30 patients who only took cyclosporine. The mechanism of the interaction may be decreased oral cyclosporine absorption. Cyclosporine is a substrate of P-glycoprotein (P-gp), and levothyroxine appears to be an inducer of intestinal P-gp.
Dapagliflozin: (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
Dapagliflozin; Metformin: (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin. (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
Dapagliflozin; Saxagliptin: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed. (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
Dexlansoprazole: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
Didanosine, ddI: (Moderate) Oral thyroid hormones should be taken at least 2 hours before the administration of certain didanosine formulations to avoid an interaction. Certain didanosine, ddI formulations contain buffers (e.g., chewable/dispersible tablets and oral powder for solution) or are mixed with antacids (e.g., pediatric powder for oral solution). Thyroid hormones are susceptible to drug interactions with buffers/antacids containing aluminum, magnesium, or calcium, which may chelate thyroid hormones within the GI tract and decrease oral thyroid hormone absorption. Gastric acidity is also an essential requirement for adequate absorption of levothyroxine. Hypothyroidism may occur if doses are not separated. The delayed-release didanosine capsules (e.g., Videx EC) do not contain a buffering agent and are not expected to interact with thyroid hormones.
Digoxin: (Minor) Thyroid disease is known to alter the response to digoxin. Digoxin toxicity is more likely to occur in patients with hypothyroidism, while the response to digoxin is diminished in patients with hyperthyroidism. These reactions should be kept in mind when therapy with thyroid hormones is begun or interrupted. When hypothyroid patients are administered thyroid hormone, the dose requirement of digoxin may be increased.
Dulaglutide: (Minor) When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued. Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis.
Empagliflozin: (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
Empagliflozin; Linagliptin: (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued. (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents, such as linagliptin, if thyroid hormones are added or discontinued.
Empagliflozin; Linagliptin; Metformin: (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin. (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued. (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents, such as linagliptin, if thyroid hormones are added or discontinued.
Empagliflozin; Metformin: (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin. (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
Enteral Feedings: (Contraindicated) Certain foods, beverages, and enteral feedings can inhibit the absorption of thyroid hormones. To minimize the risk of an interaction, thyroid hormones should be administered on an empty stomach with a glass of water at least 30 to 60 minutes prior to food or enteral feedings. Foods that may decrease thyroid hormone absorption include soybean flour and soy-based infant formulas or enteral feedings, as well as high fiber diets, cottonseed meal, and walnuts. In addition to decreasing the oral absorption of thyroid hormones, limited data indicate that soy containing foods and supplements may also influence thyroid physiology. Concentrated soy isoflavones (e.g., genistein and daidzein) may interfere with thyroid peroxidase catalyzed iodination of thyroglobulin, resulting in a decreased production of thyroid hormones and an increased secretion of TSH endogenously. More studies are required to assess the exact mechanism of this interaction. Caution should be used in administering soy isoflavone supplements concurrently with thyroid hormones. Limited data show that coffee has the potential to impair T4 intestinal absorption. In one report, T4 intestinal absorption was evaluated after the administration of 200 mcg L-thyroxine (L-T4) swallowed with coffee/espresso, water, or water followed 60 minutes later by coffee/espresso. Researchers found that administration with coffee/espresso significantly lowered average serum T4 (p<0.001) and peak serum T4 concentrations (p<0.05) when compared to L-T4 taken with water alone. Coffee/espresso taken 60 minutes after L-T4 ingestion had no significant effect on T4 intestinal absorption. It is prudent to remind patients that thyroid hormones should be separated from food and beverages (other than water), including coffee, by at least 30 to 60 minutes.
Ertugliflozin; Metformin: (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin.
Ertugliflozin; Sitagliptin: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
Esomeprazole: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
Estrogens: (Minor) The administration of estrogens can increase circulating concentrations of thyroxine-binding globulin, sex hormone-binding globulin, and cortisol-binding globulin. Increased amounts of thyroxine-binding globulin may result in a reduced clinical response to thyroid hormones. Some hypothyroid patients on estrogen may require larger doses of thyroid hormones. Monitor thyroid-stimulating hormone (TSH) level and follow the recommendation for thyroid hormone replacement.
Exenatide: (Minor) When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued. Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis.
Ferric Maltol: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased oral absorption of the thyroid hormone. For example, ferrous sulfate likely forms a ferric-thyroxine complex.
Folic Acid, Vitamin B9: (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
Food: (Contraindicated) Certain foods, beverages, and enteral feedings can inhibit the absorption of thyroid hormones. To minimize the risk of an interaction, thyroid hormones should be administered on an empty stomach with a glass of water at least 30 to 60 minutes prior to food or enteral feedings. Foods that may decrease thyroid hormone absorption include soybean flour and soy-based infant formulas or enteral feedings, as well as high fiber diets, cottonseed meal, and walnuts. In addition to decreasing the oral absorption of thyroid hormones, limited data indicate that soy containing foods and supplements may also influence thyroid physiology. Concentrated soy isoflavones (e.g., genistein and daidzein) may interfere with thyroid peroxidase catalyzed iodination of thyroglobulin, resulting in a decreased production of thyroid hormones and an increased secretion of TSH endogenously. More studies are required to assess the exact mechanism of this interaction. Caution should be used in administering soy isoflavone supplements concurrently with thyroid hormones. Limited data show that coffee has the potential to impair T4 intestinal absorption. In one report, T4 intestinal absorption was evaluated after the administration of 200 mcg L-thyroxine (L-T4) swallowed with coffee/espresso, water, or water followed 60 minutes later by coffee/espresso. Researchers found that administration with coffee/espresso significantly lowered average serum T4 (p<0.001) and peak serum T4 concentrations (p<0.05) when compared to L-T4 taken with water alone. Coffee/espresso taken 60 minutes after L-T4 ingestion had no significant effect on T4 intestinal absorption. It is prudent to remind patients that thyroid hormones should be separated from food and beverages (other than water), including coffee, by at least 30 to 60 minutes.
Furosemide: (Moderate) Use high doses (more than 80 mg) of furosemide and thyroid hormones together with caution. High doses of furosemide may inhibit the binding of thyroid hormones to carrier proteins, resulting in a transient increase in free thyroid hormones followed by an overall decrease in total thyroid hormone concentrations.
Glimepiride: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
Glipizide: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
Glipizide; Metformin: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed. (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin.
Glyburide: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
Glyburide; Metformin: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed. (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin.
Hydantoins: (Minor) Hydantoin anticonvulsants induce hepatic microsomal enzymes and may increase the metabolism of thyroid hormones, leading to reduced efficacy of the thyroid hormone.
Imatinib: (Moderate) Monitor thyroid stimulating hormone (TSH) concentrations carefully when tyrosine kinase inhibitors like imatinib are used in patients taking thyroid hormones. Cases of clinical hypothyroidism have occurred in patients taking imatinib.
Indinavir: (Moderate) Closely monitor the thyroid status of any patient taking thyroid hormones concurrently with indinavir. Hyperthyroidism was reported in a patient when indinavir was added to a stable levothyroxine dosing regimen. Indinavir inhibits UDP-glucuronosyl transferase, which may have decreased the metabolism of the thyroid hormone and may explain the increased thyroxine levels observed. Patients receiving levothyroxine should be carefully monitored when indinavir is started; if hyperthyroidism is detected, reducing the levothyroxine dose should reestablish a euthyroid state. Theoretically, similar interactions may occur between indinavir and other thyroid hormones, given that both T4 and T3 are metabolized to some degree via hepatic UDP-glucuronosyl transferase.
Insulin Degludec; Liraglutide: (Minor) When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued. Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis.
Insulin Glargine; Lixisenatide: (Minor) When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued. Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis.
Insulins: (Minor) Monitor patients receiving insulin closely for changes in diabetic control whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued. Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced.
Iodine; Potassium Iodide, KI: (Moderate) Antithyroid agents should generally not be administered with the thyroid hormones due to their opposing effects. However, in selected cases some clinicians coadminister T4 (e.g., levothyroxine) to circumvent drug-induced hypothyroidism when large suppressive doses of antithyroid agents are administered for long periods of time. However, clinical and biochemical euthyroid status may usually be maintained with careful titration of the antithyroid agent dosage alone.
Iodoquinol: (Moderate) Iodoquinol should be used with caution in patients treated with thyroid hormones. Iodine-containing compounds like iodoquinol may result in overt thyroid disease. Increased uptake of iodine by the thyroid may lead to changes in thyroid status, especially in patients with pre-existing thyroid disease. Iodoquinol has been shown to interfere with thyroid function tests for up to 6 months.
Iron Salts: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased oral absorption of the thyroid hormone. For example, ferrous sulfate likely forms a ferric-thyroxine complex.
Iron Sucrose, Sucroferric Oxyhydroxide: (Moderate) Administer oral thyroid hormones at least 4 hours before or after oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral iron supplements.
Iron: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased oral absorption of the thyroid hormone. For example, ferrous sulfate likely forms a ferric-thyroxine complex.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Rifampin increases thyroid hormone metabolism by inducing uridine 5-diphospho-glucuronosyltransferase (UGT) and leads to lower T4 serum levels. Clinicians should be alert for a decreased response to thyroid hormones if rifampin is used during thyroid hormone therapy.
Isoniazid, INH; Rifampin: (Moderate) Rifampin increases thyroid hormone metabolism by inducing uridine 5-diphospho-glucuronosyltransferase (UGT) and leads to lower T4 serum levels. Clinicians should be alert for a decreased response to thyroid hormones if rifampin is used during thyroid hormone therapy.
Ketamine: (Moderate) Ketamine should be administered cautiously to patients receiving levothyroxine because concomitant use can cause marked hypertension and tachycardia.
Lansoprazole: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
Lanthanum Carbonate: (Moderate) Administer oral thyroid hormones at least 4 hours before or after the administration of lanthanum carbonate. Concurrent use may reduce the efficacy of levothyroxine by binding and delaying or preventing oral absorption, potentially resulting in hypothyroidism. Thyroid stimulating hormone (TSH) concentrations should be carefully monitored. The bioavailability of levothyroxine was decreased by approximately 40% when administered with lanthanum carbonate.
L-Asparaginase Escherichia coli: (Moderate) Some hypothyroid patients receiving asparaginase may require reduced doses of thyroid hormone. Other patients may remain euthyroid during combined treatment. Monitor TSH levels and monitor for symptoms of hyperthyroidism; a free-T4 concentration may be useful to assess euthyroidism. Asparaginase may decrease the serum TBG (thyroxine-binding globulin) concentration. Decreased amounts of TBG may result in an increased clinical response to thyroid hormones.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased oral absorption of the thyroid hormone. For example, ferrous sulfate likely forms a ferric-thyroxine complex.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased oral absorption of the thyroid hormone. For example, ferrous sulfate likely forms a ferric-thyroxine complex.
Linagliptin: (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents, such as linagliptin, if thyroid hormones are added or discontinued.
Linagliptin; Metformin: (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin. (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents, such as linagliptin, if thyroid hormones are added or discontinued.
Liraglutide: (Minor) When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued. Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis.
Lixisenatide: (Minor) When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued. Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis.
Lonapegsomatropin: (Minor) Excessive use of thyroid hormones with growth hormone (somatropin, rh-GH) may accelerate epiphyseal closure. However, untreated hypothyroidism may interfere with growth response to somatropin. Patients receiving concomitant therapy should be monitored closely to ensure appropriate therapeutic response to somatropin.
Magnesium: (Moderate) Administer thyroid hormones at least 4 hours before or after antacids, dietary supplements, or other drugs containing magnesium. Magnesium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of levothyroxine with products containing oral cations, such as antacids or dietary supplements.
Maprotiline: (Minor) Thyroid hormones may increase receptor sensitivity and enhance the effects of maprotiline.
Meglitinides: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
Metformin: (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin.
Metformin; Repaglinide: (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin.
Metformin; Rosiglitazone: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued. (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin.
Metformin; Saxagliptin: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed. (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin.
Metformin; Sitagliptin: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed. (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin.
Methohexital: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
Miglitol: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued.
Naproxen; Esomeprazole: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased oral absorption of the thyroid hormone. For example, ferrous sulfate likely forms a ferric-thyroxine complex.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased oral absorption of the thyroid hormone. For example, ferrous sulfate likely forms a ferric-thyroxine complex.
Omeprazole: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
Omeprazole; Sodium Bicarbonate: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
Orlistat: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after a dose of orlistat. Concurrent use may reduce the efficacy of thyroid hormones by binding and delaying or preventing oral absorption, potentially resulting in hypothyroidism. Monitor TSH while orlistat is used concurrently. Hypothyroidism has been reported in patients treated concomitantly with orlistat and levothyroxine postmarketing.
Pantoprazole: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
Patiromer: (Moderate) Separate the administration of patiromer and oral levothyroxine by at least 3 hours if concomitant use is necessary. Simultaneous oral coadministration may reduce gastrointestinal absorption of levothyroxine and reduce its efficacy. Patiromer has been observed to bind some oral medications when given at the same time and separating administration by at least 3 hours has effectively mitigated this risk.
Pentobarbital: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
Phenobarbital: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
Pioglitazone: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued.
Pioglitazone; Glimepiride: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed. (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in in

creased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued.
Pioglitazone; Metformin: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued. (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin.
Polycarbophil: (Moderate) Administer thyroid hormones at least 2 hours before or after the ingestion of calcium polycarbophil. Thyroid hormones are best taken on an empty stomach, and, administration should be separated from medications that might interfere with absorption. Monitor the patient's thyroid function and clinical status if the patient is on calcium polycarbophil treatment. Dietary fiber may bind and decrease the absorption of thyroid hormones from the gastrointestinal tract. Each 625 mg of calcium polycarbophil contains a substantial amount of calcium (approximately 125 mg). Calcium salts can chelate oral thyroid hormones within the GI tract when administered simultaneously, also leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from calcium supplements and thyroid hormone interactions. In a study of 8 volunteers, the absorption of levothyroxine decreased from 89% when administered alone to only 86% when administered concomitantly with 1,000 mg of calcium polycarbophil.
Polysaccharide-Iron Complex: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased oral absorption of the thyroid hormone. For example, ferrous sulfate likely forms a ferric-thyroxine complex.
Potassium Iodide, KI: (Moderate) Antithyroid agents should generally not be administered with the thyroid hormones due to their opposing effects. However, in selected cases some clinicians coadminister T4 (e.g., levothyroxine) to circumvent drug-induced hypothyroidism when large suppressive doses of antithyroid agents are administered for long periods of time. However, clinical and biochemical euthyroid status may usually be maintained with careful titration of the antithyroid agent dosage alone.
Pramlintide: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued.
Primidone: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
Propylthiouracil, PTU: (Major) Antithyroid agents should generally not be administered with the thyroid hormones due to their opposing effects. However, in selected cases some clinicians co-administer T4 (e.g., levothyroxine) to circumvent drug-induced hypothyroidism when large suppressive doses of antithyroid agents are administered for long periods of time. However, clinical and biochemical euthyroid status may usually be maintained with careful titration of the antithyroid agent dosage alone.
Proton pump inhibitors: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
Pyridoxine, Vitamin B6: (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
Rabeprazole: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
Raloxifene: (Moderate) Patients prescribed raloxifene while taking thyroid hormones should be advised to take the drugs at separate times (e.g., 12 hours apart) until more data are available. Raloxifene may delay and reduce the oral absorption of levothyroxine (T4). In a case report, a patient with chronic but treated hypothyroidism was taking a stable dose of levothyroxine. The patient required increasing doses of levothyroxine when raloxifene was coadministered; the TSH level remained elevated and serum T4 remained decreased despite an increase in oral levothyroxine dosage. An absorption interaction was suspected and the patient rechallenged on two occasions; a decrease in serum T4 was observed whenever raloxifene and levothyroxine were administered concurrently. The patient's levothyroxine dosage requirements returned to baseline and the TSH value normalized when levothyroxine and raloxifene were administered 12 hours apart rather than simultaneously. The mechanism for the observed interaction is unknown. In theory, raloxifene might cause oral malabsorption of any thyroid hormone containing T4 (e.g., desiccated thyroid, levothyroxine, liotrix) if administered at the same time.
Rifampin: (Moderate) Rifampin increases thyroid hormone metabolism by inducing uridine 5-diphospho-glucuronosyltransferase (UGT) and leads to lower T4 serum levels. Clinicians should be alert for a decreased response to thyroid hormones if rifampin is used during thyroid hormone therapy.
Rosiglitazone: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued.
Saxagliptin: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
Secobarbital: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
Semaglutide: (Moderate) Consider additional thyroid function monitoring during concomitant use of oral thyroid hormones and oral semaglutide. Advise patients to take oral semaglutide 30 minutes before other oral medications. Concomitant use has been observed to increase levothyroxine exposure by 33% which may increase the risk for symptoms of hyperthyroidism or require a dosage adjustment. Semaglutide delays gastric emptying which may affect the absorption of other orally administered medications. This absorption interaction is not expected with subcutaneous semaglutide or intravenous levothyroxine. Additionally, levothyroxine may worsen glycemic control in patients with diabetes.
Sevelamer: (Moderate) Thyroid hormone oral administration should be separated from sevelamer administration by 4 hours. Sevelamer appears to decrease the oral absorption of thyroid hormones. In one study of normal volunteers, the subjects (n = 7) ingested orally levothyroxine sodium, either taken separately or coadministered with sevelamer. Serum thyroxine was measured at intervals over a 6-hour period following drug ingestion. Sevelamer significantly decreased the the serum thyroxine concentration. The authors concluded that patients should be advised to separate the time of ingestion of sevelamer from their thyroid hormone preparation.
Simethicone: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after a dose of simethicone. Concurrent use may reduce the efficacy of levothyroxine by binding and delaying or preventing oral absorption, potentially resulting in hypothyroidism. Simethicone has been reported to chelate oral levothyroxine within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption.
Sitagliptin: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
Sodium Ferric Gluconate Complex; ferric pyrophosphate citrate: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased oral absorption of the thyroid hormone. For example, ferrous sulfate likely forms a ferric-thyroxine complex.
Sodium Iodide: (Major) In order to increase thyroid uptake and optimize exposure of thyroid tissue to the radionucleotide, patients must discontinue all medications and supplements that may interfere with iodide uptake into thyroid tissue prior to therapy with sodium iodide I-131, including thyroid hormones. Although various protocols are used, the following withdrawal timing recommendations were set forth in a procedure guideline published by the Society of Nuclear Medicine in February 2002. It is recommended to hold alll T4 thyroid hormones (e.g., levothyroxine) 4 to 6 weeks prior, and to hold all T3 thyroid hormones (e.g., liothyronine) 2 weeks prior, to sodium iodide I-131 therapy.
Sodium Polystyrene Sulfonate: (Moderate) Administer thyroid hormones at least 4 hours apart from cation exchange resins, like sodium polystyrene sulfonate. Cation exchange resins can bind thyroxine or levothyroxine in the GI tract and inhibit oral absorption, potentially leading to hypothyroidism.
Somatropin, rh-GH: (Minor) Excessive use of thyroid hormones with growth hormone (somatropin, rh-GH) may accelerate epiphyseal closure. However, untreated hypothyroidism may interfere with growth response to somatropin. Patients receiving concomitant therapy should be monitored closely to ensure appropriate therapeutic response to somatropin.
Soy Isoflavones: (Moderate) Concentrated soy isoflavones (e.g., genistein and daidzein) may interfere with thyroid peroxidase catalyzed iodination of thyroglobulin, resulting in a decreased production of thyroid hormones and an increased secretion of TSH endogenously. Caution should be used in administering soy isoflavone supplements concurrently with thyroid hormones. More studies are required to assess the exact mechanism of this interaction.
Sucralfate: (Moderate) Administer levothyroxine at least 4 hours apart from a dose of sucralfate. Patients treated concomitantly with these drugs should be monitored for changes in thyroid function. Consider an alternative to sucralfate, if appropriate. Concurrent use of sucralfate may reduce the efficacy of levothyroxine and other thyroid hormones by binding and delaying or preventing oral absorption, potentially resulting in hypothyroidism.
Sulfonylureas: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
Sympathomimetics: (Moderate) Monitor hemodynamic parameters during concomitant sympathomimetic agent and thyroid hormone use; dosage adjustments may be necessary. Concomitant use may increase the effects of sympathomimetics or thyroid hormone.
Teduglutide: (Moderate) Monitor thyroid status and for symptoms of increased thyroid effect. Based upon the pharmacodynamic effect of teduglutide, there is a potential for increased absorption of concomitant oral medications, which should be considered if these drugs require titration or have a narrow therapeutic index, such as orally administered thyroid hormones.
Theophylline, Aminophylline: (Minor) Correction of hypothyroidism to the euthyroid state may precipitate certain drug interactions. For example, hypothyroidism causes decreased clearance of theophylline, which returns to normal in the euthyroid state. Aminophylline is converted to theophylline in the body. Aminophylline dosage adjustments may be needed with thyroid hormone replacement. (Minor) Correction of hypothyroidism to the euthyroid state may precipitate certain drug interactions. For example, hypothyroidism causes decreased clearance of theophylline, which returns to normal in the euthyroid state. Theophylline dosage adjustments may be needed with thyroid hormone replacement.
Thiazolidinediones: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued.
Tirofiban: (Minor) Data from the PRISM study, indicate that patients who received levothyroxine or omeprazole concomitantly with tirofiban had a higher rate of tirofiban clearance than patients who did not receive levothyroxine or omeprazole. The clinical significance of this is unknown.
Tirzepatide: (Minor) When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued. Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis.
Tolazamide: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
Tolbutamide: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
Tretinoin, ATRA: (Moderate) The concomitant use of systemic tretinoin, ATRA and thyroid hormones should be done cautiously due to the potential for increased intracranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Early signs and symptoms of pseudotumor cerebri include papilledema, headache, nausea, vomiting, and visual disturbances.
Tricyclic antidepressants: (Minor) Thyroid hormones may increase receptor sensitivity and enhance the effects of tricyclic antidepressants. Although this drug combination appears to be safe, be aware of the possibility of exaggerated cardiovascular side effects such as arrhythmias and CNS stimulation.
Vonoprazan; Amoxicillin: (Moderate) Monitor for altered response to thyroid hormones if coadministered with vonoprazan. Vonoprazan reduces intragastric acidity, which may decrease the absorption of oral thyroid hormones reducing their efficacy.
Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) Monitor for altered response to thyroid hormones if coadministered with vonoprazan. Vonoprazan reduces intragastric acidity, which may decrease the absorption of oral thyroid hormones reducing their efficacy.
Warfarin: (Moderate) The concurrent use of thyroid hormones and warfarin potentiates anticoagulation effects of warfarin. The mechanism of this interaction may be the increased catabolism of vitamin K clotting factors as the hypothyroid state is corrected. As a result, the hypoprothrombinemic response to warfarin occurs earlier and to a greater degree. Dextrothyroxine has been shown to potentiate the effects of warfarin. Dextrothyroxine may increase the affinity of warfarin for its receptor sites in addition to increasing the catabolism of vitamin K dependent clotting factors. A reduction in the dosage of warfarin is recommended with concomitant therapy.

How Supplied

Thyrolar Oral Tab: 12.5-50mcg, 25-100mcg, 3.1-12.5mcg, 37.5-150mcg, 6.25-25mcg

Maximum Dosage

Liotrix has a narrow therapeutic index; dosage must be individualized.

Adults

Doses greater than Thyrolar-2 (100 mcg T4 and 25 mcg T3)/day PO rarely needed.

Elderly

Doses greater than Thyrolar-2 (100 mcg T4 and 25 mcg T3)/day PO rarely needed.

Adolescents

Adolescents in whom growth and puberty are complete: Doses greater than Thyrolar-2 (100 mcg T4 and 25 mcg T3)/day PO rarely needed.

Children

Individualize dosage.

Mechanism Of Action

Both levothyroxine and liothyronine possess all the actions of endogenous thyroid hormones. Liothyronine (T3) is the principal hormone that exhibits these actions whereas levothyroxine (T4) is the major hormone secreted by the thyroid gland and is metabolically deiodinated to T3 in peripheral tissues.
 
The actions of thyroid hormones are extensive. In general, thyroid hormones influence the growth and maturation of tissues, increase energy expenditure, and affect the turnover of essentially all substrates. These effects are mediated through control of DNA transcription and, ultimately, protein synthesis. Thyroid hormones play an integral role in both anabolic and catabolic processes and are particularly important to the development of the central nervous system in newborns. They regulate cell differentiation and proliferation, and aid in the myelination of nerves and the development of axonal and dendritic processes in the nervous system. Thyroid hormones, along with somatotropin, are responsible for regulating growth, particularly of bones and teeth. Thyroid hormones also decrease cholesterol concentrations in the liver and the bloodstream, and have a direct cardiostimulatory action. Cardiac consumption is increased by the administration of thyroid hormone, resulting in an increased cardiac output. Administration of exogenous thyroid hormone to patients with hypothyroidism increases the metabolic rate by enhancing protein and carbohydrate metabolism, increasing gluconeogenesis, facilitating the mobilization of glycogen stores, and increasing protein synthesis. In response to reestablishing physiologic levels of thyroid hormone, thyroid-stimulating hormone (TSH) concentrations correct if the primary disorder is at the level of the thyroid.
 
The release of T3 and T4 from the thyroid gland into the systemic circulation is regulated by TSH (thyrotropin), which is secreted by the anterior pituitary gland. Thyrotropin release is controlled by thyroid-releasing hormone (TRH) secretion from the hypothalamus and by a feedback mechanism dependent on the concentrations of circulating thyroid hormones. Because of this feedback mechanism, the administration of pharmacologic doses of exogenous thyroid hormone to patients with a normal thyroid suppresses endogenous thyroid hormone secretion.

Pharmacokinetics

Liotrix is administered orally. Levothyroxine is highly protein bound (99%) primarily to thyroxine binding globulin (TBG), prealbumin and albumin. These proteins have an affinity for levothyroxine to a greater extent than liothyronine. The major pathway of thyroid hormone metabolism is via sequential deiodination. T4 is primarily monodeiodinated in peripheral tissues to form 80% of circulating T3. The liver is the major site of degradation for both T4 and T3; with T4 deiodination also occurs at a number of additional sites, including the kidney and other tissues. Approximately 80% of the daily T4 dose is deiodinated to yield equal amounts of T3 and reverse T3 (rT3). Then, T3 and rT3 are further deiodinated to diiodothyronine. Thyroid hormones are also metabolized via glucuronidation and sulfation and excreted directly into the bile and gut. Enterohepatic circulation also occurs following hydrolysis in the intestine and reabsorption. Iodine liberated during metabolism is used for hormone synthesis in the thyroid gland or is excreted in the feces or urine. The half-life of levothyroxine or liothyronine is approximately 9—10 days or 1—2 days, respectively, in those with hypothyroidism. In the euthyroid patient, the mean serum half-life of levothyroxine is about 7 days, while the half-life of liothyronine is roughly 24 hours.
 
Affected cytochrome P450 isoenzymes and drug transporters: none

Oral Route

Liotrix has variable absorption of 50—95% from the gastrointestinal tract. Absorption can be increased when taken during fasting, and is reduced in those patients with congestive heart failure, malabsorption syndromes or diarrhea. In addition, absorption is affected by other medications (see Drug Interactions). It takes approximately 12—48 hours to reach peak concentrations.

Pregnancy And Lactation
Pregnancy

Thyroid hormones undergo minimal placental transfer and human experience does not indicate adverse fetal effects; do not discontinue needed replacement during pregnancy. Also, hypothyroidism diagnosed during pregnancy should be promptly treated. Measure TSH during each trimester to gauge adequacy of thyroid replacement dosage since during pregnancy the thyroid replacement requirements may increase. Immediately after obstetric delivery, dosage should return to the pre-pregnancy dose, monitor a serum TSH 6 to 8 weeks postpartum to assess for needed adjustments.

Thyroid hormones, like liotrix, are generally compatible with breast-feeding; minimal amounts of thyroid hormones are excreted in breast milk. Liotrix is a mixture of levothyroxine and liothyronine. The American Academy of Pediatrics considers the use of levothyroxine to be usually compatible with breast-feeding due to a lack of reported adverse effects in nursing infants. It should be noted that in general, adequate thyroid replacement doses are needed to maintain normal lactation and there is no reason maternal replacement should be halted due to lactation alone. Levothyroxine is often the drug of choice to treat hypothyroidism during pregnancy and lactation. However, use caution when administering liotrix to a nursing woman ; changes in thyroid status in the post-partum period may require careful monitoring and maternal dosage adjustment. Comparisons of the levels of TSH and other thyroid function tests between breast-fed and bottle-fed infants have been published. Breast milk does not provide sufficient levothyroxine (T4) or liothyronine (T3) to prevent the effects of congenital hypothyroidism; therefore serum levels of TSH in breast-fed hypothyroid infants are markedly elevated. Euthyroid babies who were breast-fed did not have differences in TSH levels when compared to euthyroid babies receiving formula feedings.