Cytomel

Thyroid Agents

Oral Administration

Administer orally on an empty stomach with a glass of water at least 30 to 60 minutes before breakfast. Administer apart from medications known to decrease oral absorption.

Injectable Administration

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Intravenous Administration

Liothyronine sodium injection is for intravenous administration only. Do not give intramuscularly or subcutaneously.
No dilution is necessary; give by direct intravenous injection.
Careful cardiac monitoring (e.g., heart rate, blood pressure) is recommended during intravenous use.

Severe

arrhythmia exacerbation / Early / 1.0-10.0
cardiac arrest / Early / Incidence not known
myocardial infarction / Delayed / Incidence not known
heart failure / Delayed / Incidence not known
atrial fibrillation / Early / Incidence not known
craniosynostosis / Delayed / Incidence not known
epiphyseal closure / Delayed / Incidence not known
increased intracranial pressure / Early / Incidence not known
serum sickness / Delayed / Incidence not known
angioedema / Rapid / Incidence not known

Moderate

sinus tachycardia / Rapid / 1.0-10.0
phlebitis / Rapid / 0-1.0
elevated hepatic enzymes / Delayed / Incidence not known
hyperthyroidism / Delayed / Incidence not known
infertility / Delayed / Incidence not known
thyrotoxicosis / Delayed / Incidence not known
heat intolerance / Early / Incidence not known
dyspnea / Early / Incidence not known
angina / Early / Incidence not known
hypertension / Early / Incidence not known
peripheral edema / Delayed / Incidence not known
palpitations / Early / Incidence not known
hypotension / Rapid / Incidence not known
growth inhibition / Delayed / Incidence not known
pseudotumor cerebri / Delayed / Incidence not known
osteoporosis / Delayed / Incidence not known
osteopenia / Delayed / Incidence not known
wheezing / Rapid / Incidence not known

Mild

alopecia / Delayed / Incidence not known
amenorrhea / Delayed / Incidence not known
emotional lability / Early / Incidence not known
weight loss / Delayed / Incidence not known
fever / Early / Incidence not known
nausea / Early / Incidence not known
anorexia / Delayed / Incidence not known
weakness / Early / Incidence not known
hyperhidrosis / Delayed / Incidence not known
abdominal pain / Early / Incidence not known
appetite stimulation / Delayed / Incidence not known
muscle cramps / Delayed / Incidence not known
diarrhea / Early / Incidence not known
irritability / Delayed / Incidence not known
fatigue / Early / Incidence not known
headache / Early / Incidence not known
vomiting / Early / Incidence not known
flushing / Rapid / Incidence not known
hyperactivity / Early / Incidence not known
insomnia / Early / Incidence not known
tremor / Early / Incidence not known
anxiety / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
rash / Early / Incidence not known
arthralgia / Delayed / Incidence not known
pruritus / Rapid / Incidence not known

Obesity treatment

Liothyronine should not be used for obesity treatment or weight loss. In euthyroid patients, thyroid hormone doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious manifestations of toxicity and hyperthyroidism, especially if used with anorexic agents such as the sympathomimetic amines.[46855] [54444]

Cytomel, Triostat

Rx

Oral and parenteral synthetic form of the thyroid hormone triiodothyronine (T3); faster onset of action (no need to peripherally convert T4 to T3) vs. levothyroxine
Used for myxedema coma in combination with levothyroxine; monitor for cardiostimulatory effects
Levothyroxine (T4) alone is preferred for routine therapy of hypothyroidism; however, partial replacement with T3 is used in selected patients after T4 dose stabilization

For the treatment of hypothyroidism of any etiology, except during the recovery phase of subacute thyroiditis; used as a replacement in primary (thyroidal), secondary (pituitary), tertiary (hypothalamic), congenital (cretinism), or acquired hypothyroidism. For the treatment of hypothyroidism. Oral dosage Adults

Initially, 25 mcg PO once daily. Increase dosage by 25 mcg/day or less every 1 to 2 weeks as required. Maintenance dose is usually 25 to 75 mcg PO once daily. Use lower initial doses and slower titration in debilitated patients or those with known cardiovascular disease: Initially, 5 mcg PO once daily; with a suggested titration schedule of 5 mcg/day every 1 to 2 weeks as required.[46855] Per treatment guidelines, levothyroxine is the preferred treatment for hypothyroidism. There is insufficient evidence to suggest that liothyronine-only therapy is a safe or advantageous treatment for hypothyroidism in the general population, including in hypothyroid patients with obesity and dyslipidemia.[60310]

Geriatric Adults

Initially, 5 mcg PO once daily with a suggested titration schedule of 5 mcg/day every 1 or 2 weeks as required. Usual maintenance dose is 25 to 75 mcg PO once daily.[46855] Per treatment guidelines, levothyroxine is the preferred treatment for hypothyroidism. There is insufficient evidence to suggest that liothyronine-only therapy is a safe or advantageous treatment for hypothyroidism in the general population, including in hypothyroid patients with obesity and dyslipidemia.[60310]

Children and Adolescents

Initially, 5 mcg PO once daily with a suggested titration schedule of 5 mcg/day every 3 to 4 days until the desired response is achieved. Usual maintenance dose is 25 to 75 mcg PO once daily. In patients at risk of hyperactivity, start at one-fourth of the recommended full replacement dose, and increase on a weekly basis by this same increment until the desired response is attained.[46855] Per treatment guidelines, levothyroxine is the preferred treatment for hypothyroidism. There is insufficient evidence to suggest that liothyronine-only therapy is a safe or advantageous treatment of hypothyroidism in the general population, including in hypothyroid patients with obesity and dyslipidemia.[60310]

For congenital hypothyroidism (cretinism). Oral dosage Neonates and Infants

Initially, 5 mcg PO once daily. Increase dose in 5 mcg increments every 3 to 4 days as required. Infants a few months old may require maintenance doses of 20 mcg PO once daily. In newborns (0 to 3 months) at risk of cardiac failure, consider a lower starting dose. Increase the dose as needed based on clinical and laboratory response. At 1 year of age, a maintenance dose of 50 mcg PO once daily may be required.[46855] 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.[46855] The American Academy of Pediatrics and other clinical guidelines prefer levothyroxine over liothyronine for treatment.[22902] [60310]

Children and Adolescents

Initially, 5 mcg PO once daily. Increase dose in 5 mcg increments every 3 to 4 days as required; at 1 year of age, a maintenance dose of 50 mcg PO once daily may be required. Children older than 3 years of age may require the usual adult maintenance dose (i.e., 25 to 75 mcg/day PO).[46855] Initiate treatment immediately upon diagnosis and continue 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. In patients at risk of hyperactivity, start at one-fourth the recommended full replacement dose, and increase on a weekly basis by this same increment until the desired replacement dose is attained.[46855] The American Academy of Pediatrics and other clinical guidelines prefer levothyroxine over liothyronine for treatment.[22902] [60310]

Adults

The usual adult maintenance dose is 25 to 75 mcg/day PO. If treatment is continued into adult age, then treatment is continued for life.

For the treatment of myxedema coma. Intravenous dosage Adults

Initially, 25 mcg to 50 mcg IV is recommended. Use a lower initial dose of 10 mcg to 20 mcg IV in adults with known or suspected cardiovascular disease. Administer subsequent doses based on continuous monitoring of the patient's clinical condition and response to therapy. Normally at least 4 hours and no more than 12 hours should elapse between doses to assess therapeutic response and avoid fluctuations in hormone levels. Use caution when adjusting dose due to the potential for precipitating cardiovascular events in susceptible patients. Administration of at least 65 mcg/day IV, when used as monotherapy, has been associated with lower mortality. MAX: There is limited experience with a total daily dose of more than 100 mcg/day IV.[54444] IMPORTANT:Simultaneous administration of glucocorticoids is required at or before the start of treatment to prevent acute adrenocortical insufficiency and shock. CONVERSION TO ORAL TREATMENT: Resume oral therapy when the patient is clinically stable and able to take oral medications. When switching to oral therapy with levothyroxine after the patient is stabilized, discontinue liothyronine IV gradually as there is a delay in the onset of levothyroxine activity.[54444] GUIDELINES: Per guidelines, levothyroxine IV remains the therapy of choice. Conversion of T4 to T3 may be decreased in some patients with myxedema coma, and clinicians may consider liothyronine IV in addition to levothyroxine IV for selected patients. High doses should be avoided due to an association of high serum T3 with mortality in these patients. Guidelines recommend a liothyronine 5 to 20 mcg IV loading dose, followed by 2.5 to 10 mcg IV every 8 hours, with lower doses chosen for smaller, older patients and those with a history of coronary artery disease or arrhythmia. Therapy can continue until the patient is clearly recovering (e.g., until the patient regains consciousness and clinical parameters have improved).

For diagnostic use in thyroid suppression testing (T3 suppression test) to differentiate a suspected mild hyperthyroidism diagnosis or thyroid gland autonomy. Oral dosage Adults

75 mcg to 100 mcg PO once daily for 7 days. Radioactive iodine uptake is determined before and after the 7-day administration of liothyronine. If thyroid function is under normal control, the radioiodine uptake will drop significantly after treatment. A 50% or greater suppression of uptake indicates a normal thyroid-pituitary axis and thus rules out thyroid gland autonomy.

As an adjunct to surgery and radioiodine (RAI) therapy in the management of well-differentiated thyroid cancer. Oral dosage Adults

The dose should target TSH levels within the desired therapeutic range. This may require higher doses of thyroid hormone than those typically used for other indications, depending on the target level for TSH suppression. LIMITATION OF USE: Liothyronine is not indicated for suppression of benign thyroid nodules and nontoxic diffuse goiter in iodine-sufficient patients as there are no clinical benefits and overtreatment with may induce hyperthyroidism. GUIDELINES: Per guidelines, levothyroxine is the preferred agent, but liothyronine may be used for short-term replacement of levothyroxine when necessary; thyroid hormone must be withdrawn for several weeks prior to RAI remnant ablation/treatment or diagnostic scanning.

For use as triiodothyronine replacement therapy for organ preservation† of heart transplantation donors prior to procurement. Intravenous dosage Heart donors

Initial dose of 2 mcg IV repeated hourly as needed according to response to treatment and condition of donor until excision of heart. Max: 0.6 mcg/kg IV administered an average of 139 minutes prior to organ procurement.

†Indicates off-label use

Hepatic Impairment

No specific dosage adjustments are needed for patients with hepatic impairment; dosing is individualized to achieve therapeutic goals.

Renal Impairment

Liothyronine is known to be substantially excreted by the kidney, and the risk of toxic reactions may be increased in patients with renal impairment. Care should be used during initial dose selection. Dosing is individualized to achieve therapeutic goals.

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.
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.
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.
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 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; 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. Howev

er, 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.
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.

Cytomel/Liothyronine/Liothyronine Sodium Oral Tab: 5mcg, 25mcg, 50mcg
Liothyronine/Liothyronine Sodium/Triostat Intravenous Inj Sol: 1mL, 10mcg

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

Adults

There is limited clinical experience with more than 100 mcg/day PO or IV.

Geriatric

There is limited clinical experience with more than 100 mcg/day PO or IV.

Adolescents

Adolescents in whom growth and puberty are complete: There is limited clinical experience with more than 100 mcg/day PO or IV.

Children

Oral dosage must be individualized to age, weight, growth, and clinical status; if more than 3 years of age, adult dosages may be required (adult usual Max: 100 mcg/day PO). There is limited experience with IV use; safety and efficacy of IV use in pediatric patients have not been established.

Infants

Individualize dosage.

Neonates

Individualize dosage.

Thyroid hormones increase the body's metabolic rate, enhancing oxygen consumption by most tissues of the body. They exert a profound effect on virtually every organ system in the body, being especially important in the development of the central nervous system. Liothyronine exhibits the actions of the biologically active form of the endogenous thyroid hormone, triiodothyronine. T3 is 4 times more active than T4, but lower serum levels are maintained. In vitro studies indicate that T3 increases aerobic mitochondrial function, which increases the rate of synthesis and utilization of high-energy myocardial phosphates. Through stimulation of myosin ATPase tissue lactic acid is reduced. It is now well-established that 80% of circulating T3 results from peripheral conversion of T4, with the remainder secreted from the thyroid gland. Approximately 45% of T4 is converted to inactive reverse T3 (rT3) and 35% to 40% to biologically active T3. Iodothyronine 5'-deiodinase, the membrane-bound enzyme responsible for the extrathyroidal conversion of T4 to T3, has the greatest activity in the liver and kidney. Enzymatic conversion also occurs through a PTU-insensitive 5'-deiodinase found primarily in the pituitary and central nervous system. Conversion may be inhibited during times of stress or illness, diverting T4 to the inactive reverse T3 (rT3). It seems that the binding of T3 to a nuclear thyroid hormone receptor initiates the majority of the effects produced in the tissues by thyroid hormones. Most synthetic and natural thyroid hormone analogs will bind to this protein, but T3 has a 10 times greater receptor affinity than does T4.[46855] [54444]
 
The release of T3 and T4 from the thyroid gland into the systemic circulation is regulated by TSH (thyrotropin, also known as thyroid stimulating hormone), which is secreted by the anterior pituitary gland. Thyrotropin release is controlled by the secretion of thyroid-releasing hormone (TRH) from the hypothalamus and by a feedback mechanism dependent on the concentrations of circulating thyroid hormones. Because of this feedback mechanism, the administration of pharmacological doses of exogenous thyroid hormones, including liothyronine, to patients with normal thyroid function suppresses endogenous thyroid hormone secretion.[46855] [54444]
 
Correction of hypothyroidism through the administration of liothyronine or other thyroid hormones will increase cardiac consumption, resulting in increased cardiac output, ventricular contractility and heart rate with a decrease in total systemic vascular resistance. An increase in the rate and depth of respiration, vasodilation, motility of the gastrointestinal tract and an improved return to consciousness are also produced. Thyroid hormones increase the metabolic rate, which corrects hypothermia, by enhancing protein and carbohydrate metabolism, increasing gluconeogenesis, facilitating the mobilization of glycogen stores, and increasing protein synthesis. The number and activity of mitochondria in almost all cells of the body are increased. In primary hypothyroidism, TSH levels should correct when normal levels of thyroid hormone are established.[46855] [54444]

Liothyronine may be administered intravenously or orally. Liothyronine is more readily available for use by the body tissues than levothyroxine as it is not as firmly bound to serum proteins, permitting more rapid cell penetration. The higher affinity of levothyroxine (T4) for both thyroid-binding globulin (TBG) and thyroid-binding prealbumin as compared to triiodothyronine (T3) partially explains the higher serum levels and longer half-life of the former hormone. Both protein-bound hormones exist in reverse equilibrium with minute amounts of free hormone. The free hormone portions account for the metabolic activity. The major pathway of thyroid hormone metabolism is through sequential deiodination. Approximately 80% of circulating T3 is derived from peripheral T4 by monodeiodination. The liver is the major site of degradation for both T4 and T3, and T3 is further deiodinated to diiodothyronine. Thyroid hormones are also metabolized via conjugation with glucuronides and sulfates and excreted directly into the bile and gut where they undergo enterohepatic recirculation. Thyroid hormones are primarily eliminated by the kidneys. A portion of the conjugated hormone reaches the colon unchanged and is eliminated in the feces. The biological half-life is 2.5 days.
 
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: None

Oral Route

Within 4 hours after oral administration, 95% of an oral dose is absorbed from the gastrointestinal tract. Onset of activity is seen within a few hours. Maximum pharmacological activity occurs within 2 to 3 days, providing early clinical response.

Intravenous Route

A single intravenous dose of liothyronine sodium produces a detectable metabolic response within 2 to 4 hours and a maximum therapeutic response within 2 days.

Pregnancy

The clinical experience to date does not indicate any adverse effect on fetuses when thyroid hormones such as liothyronine are administered during pregnancy. On the basis of current knowledge, thyroid replacement therapy to hypothyroid women should not be discontinued during pregnancy. Thyroid hormones undergo minimal placental transfer. Hypothyroidism that is diagnosed during pregnancy should be promptly treated.[46855] [54444] During pregnancy, T4 is thought to be crucial for fetal brain development, and guidelines recommend that levothyroxine be the preferred drug vs. liothyronine for treatment in the pregnant patient. Measure TSH and free-T4 as soon as pregnancy is confirmed and, at a minimum, during each trimester to gauge the adequacy of thyroid replacement dosage since during pregnancy thyroid requirements may increase. For patients with serum TSH above the normal trimester-specific range, increase the dose of thyroid hormone and measure TSH every 4 weeks until a stable dose is reached and serum TSH is within the normal trimester-specific range. Immediately after obstetric delivery, dosage should return to the pre-pregnancy dose; monitor thyroid function tests 4 to 8 weeks postpartum to assess for needed adjustments.[46855] [54444]

In general, thyroid hormones are compatible with breast-feeding. Changes in thyroid status in the post-partum period may require careful monitoring and maternal dosage adjustment. In general, adequate thyroid status is needed to maintain normal lactation, and there is no reason maternal replacement should be halted due to lactation alone. Limited published studies report that liothyronine is present in human milk. There is insufficient information to determine the effects of liothyronine on the breastfed infant and no available information on the effects of liothyronine on milk production. However, thyroid hormones do not have a known tumorigenic potential and are not associated with reports of serious adverse reactions in nursing infants.[46855] [54444] Levothyroxine (T4) is often the preferential drug to treat hypothyroidism in most patients and is considered compatible with breast-feeding.[27500] [60310] The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for the drug and any potential adverse effects on the breastfed infant from liothyronine or the underlying maternal condition.[46855] [54444]