Liomny (liothyronine sodium)

The oral liothyronine dosage regimen for hypothyroidism or pituitary TSH suppression is dependent upon a variety of factors including patient age, body weight, cardiovascular status, concomitant medical conditions and medications, concurrently administered food, and nature of the treated condition. Dosage of oral liothyronine should be individualized and dosage adjustments undertaken based on periodic assessment of clinical response and laboratory parameters.

If an adequate oral liothyronine replacement dose is administered but clinical and laboratory evidence of hypothyroidism persist, the clinician should evaluate the patient for inadequate absorption, poor compliance, drug interactions, or a combination of these factors.

Liothyronine sodium is administered orally or by IV injection. Liothyronine injection should not be administered intramuscularly or subcutaneously.

Liothyronine tablets should be stored between 15-30degreesC. Liothyronine for injection should be stored under refrigeration (2-8degreesC).

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Agents That Affect Iodide/Radioactive Iodide

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Many compounds can affect iodide protein binding and alter iodide pharmacokinetics and pharmacodynamics.(1)

CLINICAL EFFECTS: Compounds that affect iodide pharmacokinetics and pharmacodynamics may impact the effectiveness of radioactive iodide.(1)

PREDISPOSING FACTORS: Compounds that affect iodide pharmacokinetics and pharmacodynamics are expected to have the most impact during therapy using radioactive iodide. Diagnostic procedures would be expected to be impacted less.

PATIENT MANAGEMENT: Discuss the use of agents that affect iodide pharmacokinetics and pharmacodynamics with the patient's oncologist.(1) Because indocyanine green contains sodium iodide, the iodine-binding capacity of thyroid tissue may be reduced for at least one week following administration. Do not perform radioactive iodine uptake studies for at least one week following administration of indocyanine green.(2) The manufacturer of iopamidol states administration may interfere with thyroid uptake of radioactive iodine and decrease therapeutic and diagnostic efficacy. Avoid thyroid therapy or testing for up to 6 weeks post administration of iopamidol.(3)

DISCUSSION: Many agents interact with radioactive iodine. The average duration of effect is: anticoagulants - 1 week antihistamines - 1 week anti-thyroid drugs, e.g: carbimazole, methimazole, propylthiouracil - 3-5 days corticosteroids - 1 week iodide-containing medications, e.g: amiodarone - 1-6 months expectorants - 2 weeks Lugol solution - 3 weeks saturated solution of potassium iodine - 3 weeks vitamins - 10-14 days iodide-containing X-ray contrast agents - up to 1 year lithium - 4 weeks phenylbutazone - 1-2 weeks sulfonamides - 1 week thyroid hormones (natural or synthetic), e.g.: thyroxine - 4 weeks tri-iodothyronine - 2 weeks tolbutamide - 1 week topical iodide - 1-9 months (1)

Agents That Affect Iodide/Sodium Iodide I 131

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Many compounds can affect iodide protein binding and alter iodide pharmacokinetics and pharmacodynamics.(1,2)

CLINICAL EFFECTS: Compounds that affect iodide pharmacokinetics and pharmacodynamics may impact the effectiveness of radioactive iodide.(1,2)

PREDISPOSING FACTORS: Compounds that affect iodide pharmacokinetics and pharmacodynamics are expected to have the most impact during therapy using radioactive iodide. Diagnostic procedures would be expected to be impacted less.

PATIENT MANAGEMENT: Discuss the use of agents that affect iodide pharmacokinetics and pharmacodynamics with the patient's oncologist.(1,2) Because indocyanine green contains sodium iodide, the iodine-binding capacity of thyroid tissue may be reduced for at least one week following administration. Do not perform radioactive iodine uptake studies for at least one week following administration of indocyanine green.(3) The manufacturer of iopamidol states administration may interfere with thyroid uptake of radioactive iodine and decrease therapeutic and diagnostic efficacy. Avoid thyroid therapy or testing for up to 6 weeks post administration of iopamidol.(4)

DISCUSSION: Many agents interact with radioactive iodine. The average duration of effect is: anticoagulants - 1 week antihistamines - 1 week anti-thyroid drugs, e.g: carbimazole, methimazole, propylthiouracil - 3-5 days corticosteroids - 1 week iodide-containing medications, e.g: amiodarone - 1-6 months expectorants - 2 weeks Lugol solution - 3 weeks saturated solution of potassium iodine - 3 weeks vitamins - 10-14 days iodide-containing X-ray contrast agents - up to 1 year lithium - 4 weeks phenylbutazone - 1-2 weeks sulfonamides - 1 week thyroid hormones (natural or synthetic), e.g.: thyroxine - 4 weeks tri-iodothyronine - 2 weeks tolbutamide - 1 week topical iodide - 1-9 months (1,2)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Thyroid Preparations/Calcium; Iron; Sucralfate

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The mechanism by which malabsorption of thyroid preparations occurs from calcium-containing products is presumed to be a binding of the medication to the thyroid hormone, forming an insoluble or nonabsorbable complex.(1-3) Iron may form a ferric-thyroxine complex with thyroid agents, preventing their absorption from the gastrointestinal tract.(1,4) Sucralfate binds to other agents in the gastrointestinal tract and alters absorption of other drugs, including thyroid agents.(1,5)

CLINICAL EFFECTS: The simultaneous administration of thyroid preparations with calcium, iron, or sucralfate may result in decreased levels and clinical effects of thyroid preparations.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Instruct patients to separate the administration time of thyroid preparations from calcium or iron by as much time as possible, preferably by at least four hours.(1) Administer thyroid preparations at least 2 hours before sucralfate.(5) Patients taking thyroid preparations and calcium- or iron-containing products or sucralfate should be monitored for changes in thyroid function. The dosage of the thyroid preparation may need to be increased. Separating the administration times of the thyroid preparation and the calcium- or iron-containing products or sucralfate may decrease the effects of the interaction.(1-5)

DISCUSSION: In a pharmacokinetic study 8 healthy, euthyroid adults were given levothyroxine alone and levothyroxine coadministered with calcium carbonate, calcium citrate, or calcium acetate in doses containing 500 mg elemental calcium. The coadministration of each of the three calcium preparations significantly reduced levothyroxine absorption by about 20%-25% compared with levothyroxine given alone.(3) In a study in 14 subjects, the simultaneous administration of thyroxine with ferrous sulfate for 12 weeks resulted in an increase in the mean level of thyroid stimulating hormone (TSH) from 1.6+/-0.4 mU/L to 5.4+/-2.8 mU/L. Mixing thyroxine with ferrous sulfate in vitro resulted in a poorly soluble complex.(4) In a study in 20 hypothyroid patients, the simultaneous administration of levothyroxine and calcium carbonate (1200 mg) daily for three months resulted in reductions in the mean free T4 and total T4 levels. These values increased in most patients following the discontinuation of calcium carbonate. A concurrent in-vitro study found that calcium carbonate adsorbed levothyroxine in solution at a pH of 2, gastric pH, but not at a pH of 7.4.(6) One author reported three cases of decreased levothyroxine efficacy following the addition of calcium carbonate to therapy.(7) In a study in 5 healthy subjects, levothyroxine (five 200 mcg tablets) was administered in 3 different dosing regimens: after an overnight fast, with the fifth and final dose of sucralfate (1 gram every 6 hours) and 8 hours after the second and final dose of sucralfate (2 grams every 12 hours). When administered alone, 80% of levothyroxine was absorbed within 6 hours of administration, compared to 23% when administered concurrently with sucralfate. There was no difference in levothyroxine absorption when administered alone or 8 hours after sucralfate.(8) There are several case reports documenting decreased effects of thyroid supplementation as the result of simultaneous administration of sucralfate.(9,10) One or more of the drug pairs linked to this monograph have been included in a list of interactions that could be considered for classification as "non-interruptive" in EHR systems. This DDI subset was vetted by an expert panel commissioned by the U.S. Office of the National Coordinator (ONC) for Health Information Technology.

Thyroid Preparations/Carbimazole; Methimazole

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Methimazole can affect the therapeutic response to thyroid hormone therapy. It decreases thyroid hormone secretion. Thyroid hormone therapy can antagonize the pharmacologic effects of methimazole by supplying an exogenous source of thyroid hormone. Carbimazole is a prodrug of methimazole.(1)

CLINICAL EFFECTS: Concurrent use of carbimazole or methimazole and thyroid hormones may result in opposing effects.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Concurrent use of carbimazole or methimazole and thyroid hormones should be avoided.

DISCUSSION: The 2016 American Thyroid Association guidelines recommended avoiding the concurrent use of methimazole and thyroid preparations for "block and replace" therapy to make a patient euthyroid. Meta-analyses have shown that a higher prevalence of adverse events occurs with block-and-replace regimens than dose titration.(2) The 2018 European Thyroid Association guidelines state that methimazole (30 mg) may be given combined with levothyroxine supplement ion for block-and-replace therapy to avoid drug-induced hypothyroidism but methimazole dose titration is the preferred therapy.(3)

Thyroid Preparations/Ciprofloxacin

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Ciprofloxacin may inhibit organic anion transporting polypeptide (OATP) 1A2 in the intestines, either through competitive or direct inhibition.(1)

CLINICAL EFFECTS: The simultaneous administration of thyroid preparations and ciprofloxacin may result in decreased levels and clinical effects of thyroid hormones.(1)

PREDISPOSING FACTORS: This interaction may be more significant in patients receiving long term courses of ciprofloxacin.

PATIENT MANAGEMENT: Patients taking thyroid preparations and ciprofloxacin should be monitored for changes in thyroid function. Separating the administration times of the thyroid preparation and ciprofloxacin by 6 hours, may decrease the effects of the interaction.(1,2)

DISCUSSION: In a study, 8 healthy individuals received single doses of levothyroxine (100 mcg) combined with placebo or ciprofloxacin (750 mg). The simultaneous administration of ciprofloxacin significantly decreased the T4 AUC by 39% (p=0.035). The reduction in T4 AUC after coadministration of ciprofloxacin with levothyroxine is consistent with inhibition of an intestinal T4 uptake transport.(1) In a case report, two patients with hypothyroidism and receiving levothyroxine developed decreased T4 levels after taking ciprofloxacin for 3-4 weeks.(2)

Thyroid Preparations/Estrogens

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Estrogens increase thyroxine-binding globulin (TBG) levels by increasing its biosynthesis and decreasing its clearance.(1) Hypothyroid patients who start estrogens may be unable to compensate for this increase and may have decreased serum free T4 (FT4) concentrations and increased TSH.(1,2)

CLINICAL EFFECTS: The coadministration of thyroid preparations and estrogens may result in decreased levels and clinical effects of thyroid hormones.(1-4)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients taking thyroid preparations and who start or stop estrogens should be monitored for changes in thyroid function. The dosage of the thyroid preparation may need to be increased.(1-4)

DISCUSSION: In a prospective observational study, 25 post-menopausal women with hypothyroidism on stable levothyroxine therapy for at least 9 months started on estrogen replacement therapy. After 12 weeks, mean serum FT4 levels decreased significantly from 1.7 +/- 0.4 ng/dL to 1.4 +/-0.3 mg/dL and TSH increased significantly from 0.9 +/-1.1 to 3.2 +/- 3.1 milli-units/L.(1)

Thyroid Preparations/Glp-1 Receptor Agonists

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The exact mechanism is unknown but may be related to decreased GI motility resulting in increased absorption of levothyroxine. Weight loss may also cause stable doses of levothyroxine to be too high for weight-based dosing.(1)

CLINICAL EFFECTS: Concurrent administration of GLP-1 receptor agonists and thyroid preparations may increase the clinical effects of the thyroid agent, resulting in symptoms of hyperthyroidism.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients taking thyroid preparations and GLP-1 receptor agonists should be monitored for changes in thyroid function. Symptoms of hyperthyroidism include weight loss, rapid heartbeat, nervousness, sweating, tremor, fatigue, and difficulty sleeping. The dosage of levothyroxine may need to be adjusted accordingly.

DISCUSSION: In an open-label, one-sequence, crossover, 2-part trial examining the effect of administering 14 mg oral semaglutide and levothyroxine together, a 33% increase in levothyroxine AUC was identified. The trial also examined the impact of SNAC , the absorption enhancer in oral GLP-1 receptor agonists, and found that SNAC alone did not impact absorption of levothyroxine.(2) In a single-center, prospective trial, participants with diabetes without thyroid disease were given exenatide and TSH levels were measured. After 6 months of treatment, mean TSH concentration decreased from 2.3 to 1.8 without impact to T4 and T3. The mechanism that was proposed was that exenatide can increase the sensitivity of the hypothalamus or pituitary gland to the thyroid hormone negative feedback or increase the number of receptors on the hypothalamus or pituitary gland. No relationship was found between weight change and TSH level.(3) In a case report, a post-thyroidectomy patient on a stable dose of levothyroxine (125 mcg daily) started concurrent subcutaneous semaglutide therapy. Five months after starting treatments together, she started experiencing palpitations, perspiration, and heat intolerance. The levothyroxine dose was decreased to 88 mcg daily resulting in a resolution of symptoms.(4) In another case report, a 43-year-old female patient was on a stable dose of levothyroxine (200 mcg) and started on subcutaneous semaglutide. After 5 months, her TSH level dropped to 0.01 ng/dL and levothyroxine was reduced to 150 mcg daily.(5)

Thyroid Preparations/Imatinib;Sunitinib

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The suspected mechanism responsible for this phenomenon is an induction of non-deiodination clearance. The induction of uridine diphosphate-glucuronyl transferases (UGTs) by imatinib and sunitinib decreases levels of the thyroid preparations.(1)

CLINICAL EFFECTS: The coadministration of thyroid preparations and imatinib and sunitinib may result in decreased levels and clinical effects of thyroid hormones.(1-3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients taking thyroid preparations and imatinib or sunitinib should be monitored for changes in thyroid function. The dosage of the thyroid preparation may need to be increased.(1-3)

DISCUSSION: In a case report, 8 patients had undergone thyroidectomy and used levothyroxine and imatinib. These patients had an increase need for levothyroxine levels and were monitored for elevations in thyrotropin indicating worsening hypothyroidism.(2) A case report of a 73 year old man who was treated with imatinib and levothyroxine developed worsening hypothyroidism. An increase in levothyroxine dosage was needed.(3) In a case report, a 59 year old woman was taking levothyroxine therapy for hypothyroidism secondary to subtotal thyroidectomy and was recently started on imatinib for chronic myeloid leukemia. The patient developed clinical signs of hypothyroidism and required an increased dose of levothyroxine.(4) In a case report, a 73 year old woman was taking levothyroxine and developed fatigue, nausea, cold-intolerance, hair-loss, brittle nails, progressive weakness, and impressive facial oedema 6 months after starting imatinib. The patient levothyroxine was increased and she remained euthyroid, but the imatinib was discontinued due to extreme fatigue and periorbital oedema. Five months later the patient was stared on sunitinib and her levothyroxine dose was increased. The patient developed similar symptoms to imatinib reaction.(5) In a case report, a patient receiving sunitinib for metastatic papillary renal cell cancer developed high thyroid stimulating hormone levels and severe symptoms despite receiving L-thyroxine.(6)

Thyroid Preparations/Orlistat

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Orlistat may bind to the thyroid preparation in the small intestine, decreasing systemic absorption.(1-4)

CLINICAL EFFECTS: Concurrent administration of orlistat and thyroid preparations may decrease the clinical effects of the thyroid agent.(1-4) Hypothyroidism has been reported.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Separate the administration times of orlistat and thyroid preparations by at least 4 hours. Patients receiving concurrent therapy should be monitored for changes in thyroid function.(1-3)

DISCUSSION: In a case report, a post-thyroidectomy patient on a stable dose of levothyroxine (250 mcg daily) started concurrent orlistat therapy. Within two weeks of starting orlistat therapy, she felt experienced cold intolerance and felt lethargic and tired. She was found be severely hypothyroid and the orlistat was discontinued. Within two weeks, her symptoms improved and, within 4 weeks, her thyroid levels normalized.(4)

Thyroid Preparations/Patiromer

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Patiromer may bind to thyroid preparations.(1)

CLINICAL EFFECTS: Concurrent use may result in decreased gastrointestinal absorption and loss of efficacy of the thyroid preparation.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of patiromer recommends that you administer patiromer at least 3 hours before or 3 hours after levothyroxine.(1)

DISCUSSION: A study in healthy volunteers showed that patiromer decreased the systemic exposure of coadministered levothyroxine. No interaction was seen when these drugs were taken 3 hours apart.(1)

Thyroid Preparations/Polystyrene Sulfonate

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Polystyrene sulfonate may bind and delay or prevent the absorption of thyroid preparations from the gastrointestinal tract.(1)

CLINICAL EFFECTS: Simultaneous administration of polystyrene sulfonate may result in decreased levels of and effectiveness from thyroid preparations.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of levothyroxine states that levothyroxine should be administered at least 4 hours apart from polystyrene sulfonate.(1)

DISCUSSION: Because polystyrene sulfonate may bind and delay or prevent the absorption of levothyroxine from the gastrointestinal tract, the US manufacturer of levothyroxine states that levothyroxine should be administered at least 4 hours apart from polystyrene sulfonate.(1)

Thyroid Preparations/Rifampin

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Rifampin is an organic anion transporting polypeptide (OATP) inhibitor and has been found to decrease measured free T4 when taking thyroid replacements. The mechanism for the rifampin effect may be due to induction of hepatic metabolic and biliary clearance. It is also possible that rifampin may have increased net intestinal absorption of L-T4 through inhibition of P-glycoprotein, an intestinal efflux transporter.

CLINICAL EFFECTS: The concurrent or recent use of rifampin may result in altered levels and clinical effects of thyroid hormones. Some patients may experience increased thyroid hormone effects, while others may experience decreased effects.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients taking thyroid preparations and rifampin should be monitored for changes in thyroid function. Symptoms of hyperthyroidism include weight loss, rapid heartbeat, nervousness, sweating, tremor, fatigue, and difficulty sleeping. Symptoms of hypothyroidism include fatigue, sluggishness, constipation, stiffness, muscle cramps, loss of appetite, excessive weight gain, or dry skin. The dosage of levothyroxine may need to be adjusted accordingly.

DISCUSSION: In a study, 8 healthy individuals received 100 mcg of levothyroxine combined with placebo or rifampin 600 mg. The coadministration of rifampin significantly increased the 4 AUC by 25% (p=0.003). Levothyroxine absorptions with rifampin was 125% compared to controls.(1) In contrast to this study, two case reports exist documenting decreased effects of levothyroxine during concurrent rifampin. In a case report, a 31 year old woman had a total thyroidectomy and was receiving levothyroxine and was recently started on rifampin. The patient did not develop symptoms of hypothyroidism, but had a decrease in serum thyroxine levels and free thyroxine index during rifampin therapy and an increase in serum thyrotropin levels.(2) In a case report of a 50 year old male, stable on levothyroxine, who exhibited significantly elevated TSH levels during therapy with rifampin. The patient's TSH levels returned to baseline 9 days after discontinuing rifampin.(3)

Thyroid Preparations/Ritonavir

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Thyroid preparations are substrates for uridine diphosphate glucuronosyltransferase (UGT). Also, levothyroxine is converted to the thyroid hormone triiodothyronine (T3) which is further metabolized via UGT.(1) Ritonavir may induce UGT and may increase metabolism of levothyroxine and T3.(1)

CLINICAL EFFECTS: The concurrent use of ritonavir may result in decreased levels and clinical effects of the thyroid preparation.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients taking thyroid preparations and ritonavir should be monitored for changes in thyroid function. Symptoms of hypothyroidism include fatigue, sluggishness, constipation, stiffness, muscle cramps, loss of appetite, excessive weight gain, or dry skin. The dosage of the thyroid preparation may need to be adjusted accordingly.

DISCUSSION: A case report of a 29 year old male with auto-immune thyroiditis was stabilized on levothyroxine 125 mcg daily for one year when concurrent therapy with stavudine 40 mg twice daily, lamivudine 150 mg twice daily, ritonavir 600 mg twice daily, and saquinavir 400 mg twice daily was started. One month after concurrent therapy, the patient's thyroid stimulating hormone (TSH) increased to 18.47 mIU/L (a 2.7-fold increase) requiring a dose increase of levothyroxine to 250 mcg daily. Subsequently, ritonavir was discontinued with a decrease in levothyroxine dose to 125 mcg daily with stabilization of TSH at 7.32 mIU/L.(2) A case report of a 58 year old female on zidovudine, lamivudine, and lopinavir/ritonavir underwent a total thyroidectomy with subsequent introduction of levothyroxine. Levothyroxine was titrated to 225 mcg daily along with the addition of liothyronine. Due to persistently elevated TSH values (range 47.6 - 85.1 mIU/L), lopinavir/ritonavir was then withdrawn and two months later TSH and T4 levels returned to normal, 4.1 mIU/L and 12.1 pmol/L, respectively. Eight months later lopinavir/ritonavir was reintroduced and 1 month later TSH and T4 increased to 42.9 mIU/L and 10.6 mIU/L, respectively. Again, lopinavir/ritonavir was withdrawn and TSH and T4 values returned to normal, 1.1 mIU/L and 13.4 pmol/L, respectively.(3) A case report of a 37 year old female on abacavir/lamivudine and lopinavir/ritonavir details the management course of hypothyroidism over a six year period, including during 3 pregnancies. After a total thyroidectomy, the patient was started on levothyroxine 75 mcg daily. Post-surgical levels of TSH and T4 (during patient's second pregnancy) increased to 94.3 mIU/L and 6.1 mIU/L, respectively, and peaked at 125.89 mIU/L and 7.7 mIU/L, respectively. Levothyroxine doses were increased to 175 mcg daily over the following year (during the patient's second and third pregnancies) to achieve decreased TSH and T4 values of 8.58 mIU/L and 12.8 mIU/L, respectively. TSH values rose again to 17.23 mIU/L and ritonavir was withdrawn from therapy. The patient was then maintained on levothyroxine 125 mcg daily with a TSH of 0.12 - 0.42 mIU/L over the next 2 years.(1)

Thyroid Preparations/Sertraline

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The mechanism by which sertraline lowers serum thyroid hormone concentrations is uncertain. One reported case in which sertraline caused a low serum total thyroxine concentration is believed to be caused by sertraline increasing the clearance of the thyroxine.(1)

CLINICAL EFFECTS: The coadministration of thyroid preparations and sertraline may result in decreased levels and clinical effects of thyroid hormones.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients taking thyroid preparations and sertraline should be monitored for changes in thyroid function. The dosage of the thyroid preparation may need to be increased.

DISCUSSION: In a case report of 9 levothyroxine treated patients with hypothyroidism, who were treated with sertraline, all were found to have elevated serum thyrotropin concentrations. Elevated thyrotropin levels are indicative of a decrease in the efficacy of levothyroxine. The dose of levothyroxine was increased for all patients. Required dosage adjustments ranged from 11% to 50%.(1) In a study, patients with major depression and hypothyroidism on adequate levothyroxine therapy were treated with either fluoxetine or sertraline. The results of this study showed no change in thyroid levels among hypothyroid patients on levothyroxine therapy who were treated with either fluoxetine or sertraline.(2)

Thyroid Preps/Bile Acid Sequestrants; Lanthanum; Sevelamer

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Bile acid sequestrants, lanthanum and sevelamer may decrease the gastrointestinal absorption of thyroid drugs.(1)

CLINICAL EFFECTS: Simultaneous administration of a bile acid sequestrant, lanthanum or sevelamer may result in decreased absorption and effectiveness of thyroid drugs.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: For maximal bioavailability, thyroid preparations should be taken on an empty stomach at least 4 hours apart from bile acid sequestrants and sevelamer.(1-3) Thyroid preparations should be taken at least 2 hours apart from lanthanum.(4)

DISCUSSION: The effect of cholestyramine on the absorption of thyroid drugs appears to be clinically significant, resulting in approximately a 50% decrease in thyroid absorption. Cholestyramine has been used to treat thyroid overdoses. When administered with colesevelam (3.75 g), the area-under-curve (AUC) and maximum concentration (Cmax) of levothyroxine (600 mcg) decreased by 22% and by 33%, respectively. When administered 1 hour prior to colesevelam, the AUC of levothyroxine increased by 6% and the Cmax of levothyroxine decreased by 2%, respectively. When administered 4 hours prior to colesevelam, the AUC and Cmax of levothyroxine increased by 1% and 8%, respectively. Although used for hyperphosphatemia, sevelamer is linked to this monograph due to its structural and pharmacologic similarities to colesevelam. Both agents are non-absorbed cross linked polymers with a high affinity for bile acids.(2,3) An in vivo study in healthy subjects evaluated the bioavailability of levothyroxine 1 mg when given with or without sevelamer 800 mg. Concomitant administration of sevelamer decreased levothyroxine AUC by 46%.(13) One case report described a newly diagnosed hypothyroid patient with a TSH of 297 mU/L (reference 0.03 - 4.20 mU/L). She took her daily levothyroxine with her morning blood pressure medications, acetaminophen, B-vitamins and sevelamer 3200 mg. Over 3 months of treatment her levothyroxine dose was increased to 150 mcg daily but the TSH remained high at 196 mU/L. Her levothyroxine dose was changed to an evening dose taken at least 4 hours after medications. Three weeks later she was symptomatically improved and TSH had decreased to 19 mU/L. She was inadvertently rechallenged on the morning levothyroxine and sevelamer regimen due to a hospitalization. After the hospital stay her TSH risen to 76 mU/L; on return to her evening regimen her TSH again normalized.(14)

Thyroid Preps/Soybean Infant Formula; Nutritional Therapy

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Soy-based formula and nutritional therapy may bind to thyroid preparations, decreasing their absorption.(1-3) Also, many products may contain iron, which may also bind to thyroid preparations.(1)

CLINICAL EFFECTS: Concurrent use of soy-based formula or nutritional therapy may result in increased TSH levels.(1-3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients receiving soy-based formula or nutritional therapy should be closely monitored for elevated TSH levels. The dosage of the thyroid preparation may need to increase during the use of soy-based products.(1-3) Instruct patients to take soy-based formula or nutritional therapy at the same time every day relative to tiratricol dosing.(4,5)

DISCUSSION: In a retrospective comparison of 78 infants with congenital hypothyroidism, 8 infants fed a soy-based formula had prolonged increase of TSH and time to TSH normalization, higher first TSH on treatment, and there was a larger percentage with increased TSH at 4 months of age when compared to 70 infants on a non-soy diet.(2) In a case report of 3 infants with congenital hypothyroidism, infants required 18-25% higher dosages of levothyroxine while receiving soy-based formulas.(3) In a case report, the administration of levothyroxine concurrently with a soy protein dietary supplement resulted in decreased absorption of levothyroxine and the need for higher oral doses of levothyroxine to attain therapeutic serum thyroid hormone levels.(6)

Thyroid/Selected Anticoagulants

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Unknown. However, thyroid hormones may influence concentrations of vitamin K-dependent clotting factors.

CLINICAL EFFECTS: Concurrent use of vitamin K antagonists and thyroid hormones may increase the risk for bleeding. Hypothyroidism may increase the oral anticoagulant requirements. Administration of thyroid hormones or hyperthyroidism may decrease oral anticoagulant requirements.

PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs).

PATIENT MANAGEMENT: Monitor prothrombin activity and adjust the anticoagulant dosage accordingly during initiation of warfarin therapy in patients receiving thyroid replacement therapy, during the initiation or titration of thyroid replacement therapy in patients receiving warfarin, or if any changes in thyroid function occur. If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug.

DISCUSSION: Any change in thyroid status in patients stabilized on warfarin may necessitate a change in warfarin dosage requirements. Initiation of thyroid replacement therapy in patients stabilized on warfarin may result in increases in the effects of warfarin. A decrease in the dose of warfarin usually becomes necessary within one to four weeks after starting therapy with thyroid compounds. Warfarin therapy should be initiated in low doses in patients who are hyperthyroid. In a 16 year population based nested matched case control study, 10,532 hospitalizations for hemorrhage were evaluated and matched to 40,595 controls. The primary analysis showed no increase in risk of hemorrhage in older patients on warfarin initiated on levothyroxine in previous 30 days (OR 1.11, 95% CI 0.67-1.86). When patients were matched up to 90 days prior to the hemorrhage event, there was no significant association with levothyroxine 31-60 days prior to index date (OR 0.75 95% CI 0.26-2.25) or 61-90 days prior to index date (OR 0.67 95% CI 0.15-3.01). A retrospective, self-controlled study of 102 patients on chronic warfarin therapy were included if the patient had INR results 90 days before and after starting levothyroxine. The mean warfarin dose/INR ratio in the pre-period and post-period had no significant change (p=0.825). In patients who achieved euthyroid during post-period, warfarin dose/INR ratio was numerically lower in the post-period but not statistically significant (13.42 versus 12.7, respectively; p=0.338). In patients initiated on levothyroxine doses greater than 50 mcg, pre-period and post-period warfarin dose/INR ratio also had no significant difference (p>0.2).

*Uncorrected adrenal insufficiency.

*Untreated thyrotoxicosis.

*Hypersensitivity to any of the active or extraneous ingredients of the formulation.

*Concomitant use of IV liothyronine and artificial patient rewarming.

• Thyrotoxicosis crisis

• Primary adrenocortical insufficiency
• Thyrotoxicosis

• Coronary artery disease
• Diabetes mellitus
• Hypertension

The most common adverse reactions of oral liothyronine therapy are primarily hyperthyroidism-related due to therapeutic overdosage and include arrhythmias, myocardial infarction, dyspnea, headache, nervousness, irritability, insomnia, tremors, muscle weakness, increased appetite, weight loss, diarrhea, heat intolerance, menstrual irregularities, and skin rash. Hypersensitivity reactions (e.g., urticaria, pruritus, skin rash, angioedema, GI symptoms, fever, arthralgia, serum sickness, wheezing) to inactive ingredients in oral thyroid hormone products have been reported.

The most common adverse reactions of IV liothyronine therapy include arrhythmia (6%) and tachycardia (3%). Approximately 2% of patients experience cardiopulmonary arrest, hypotension, and myocardial infarction. Angina, congestive heart failure, fever, hypertension, phlebitis, and twitching have been reported in approximately <=1% of patients.

Less Frequent

• Osteopenia

Rare or Very Rare

• Abnormal hepatic function tests
• Acute myocardial infarction
• Angina
• Angioedema
• Cardiac arrest
• Cardiac arrhythmia
• Dyspnea
• Heart failure
• Idiopathic intracranial hypertension
• Mood changes
• Seizure disorder
• Skin rash
• Slipped capital epiphyses
• Tachycardia
• Urticaria

More Frequent

• Female infertility

Less Frequent

• Hypertension
• Weight loss

Rare or Very Rare

• Abdominal pain with cramps
• Alopecia
• Chest pain
• Diarrhea
• Fatigue
• Fever
• Flushing
• Headache disorder
• Heat intolerance
• Hyperhidrosis
• Increased appetite
• Increased pulse rate
• Insomnia
• Irregular menstrual periods
• Irritability
• Menstrual disorder
• Muscle spasm
• Muscle weakness
• Nervousness
• Palpitations
• Symptoms of anxiety
• Tremor
• Vomiting

No enhanced messaging available.

In pediatric patients with congenital hypothyroidism, oral thyroid hormone therapy should be initiated immediately upon diagnosis in order to prevent adverse effects on intellectual development, growth, and maturation; therapy is generally lifelong in these patients. During the first 2 weeks of thyroid agent therapy, infants should be closely monitored for cardiac overload, arrhythmias, and aspiration resulting from avid suckling.

Pediatric patients with congenital or acquired hypothyroidism should be monitored closely to avoid undertreatment or overtreatment. Undertreatment may result in negative effects on intellectual development and growth while overtreatment may result in craniosynostosis in infants and accelerate the aging of bones, resulting in premature epiphyseal closure and compromised adult stature.

In pediatric patients with acquired hypothyroidism administered oral thyroid hormone therapy, a period of catch-up growth may occur, which may be adequate in some cases to achieve normal adult height. In children with severe or long-standing hypothyroidism, catch-up growth may not be adequate to achieve normal adult height.

If a diagnosis of permanent hypothyroidism has not been established in a pediatric patient, oral thyroid hormone therapy should be discontinued for a trial period, but only after the patient is >=3 years of age. Clinicians should obtain various laboratory tests (e.g., serum TSH, T4, T3) at the end of the trial period and use results to guide diagnosis and treatment.

Pseudotumor cerebri and slipped capital femoral epiphysis have been reported in pediatric patients receiving oral thyroid agent therapy.

The efficacy and safety of IV liothyronine have not been established in pediatric patients.

The required oral liothyronine dosage may increase during pregnancy in patients with pre-existing hypothyroidism. For patients with serum TSH above the normal trimester-specific range, clinicians should increase the liothyronine dosage and measure TSH every 4 weeks until a stable dose is achieved and serum TSH is within the normal trimester-specific range.

The oral liothyronine dosage should be reduced to pre-pregnancy levels immediately after delivery. Serum TSH levels should be measured 4 to 8 weeks postpartum to ensure an appropriate liothyronine dosage.

In pregnant women, data from postmarketing studies have not reported increased rates of fetal malformations, miscarriages, or other adverse maternal or fetal outcomes with liothyronine therapy. No animal studies evaluating use of liothyronine during pregnancy have been conducted.

Untreated hypothyroidism during pregnancy is associated with risks to the mother and fetus; liothyronine therapy should not be discontinued during pregnancy. If hypothyroidism is diagnosed during pregnancy, clinicians should promptly treat the condition. Thyroid stimulating hormone (TSH) levels may increase during pregnancy and should be monitored, with liothyronine dosage adjusted as appropriate. The liothyronine dose should be returned to the pre-pregnancy dose immediately after delivery since postpartum TSH levels are similar to preconception values.

Liothyronine is present in human milk. There is insufficient information available to determine the effects of the drug on the breastfeeding infant or milk production. The developmental and health benefits of breastfeeding should be considered along with the clinical need for liothyronine and any potential adverse effects on the breastfed infant or from the underlying maternal condition.

Geriatric patients should be initiated on less than the full replacement dose of oral liothyronine due to the increased prevalence of cardiovascular disease in this patient population.

Hypothyroidism: in elderly patients, start with 5 mcg once daily and increase by 5 mcg increments at the recommended intervals.

Liothyronine oral therapy should be initiated at less than the full replacement dose in geriatric patients due to the increased prevalence of cardiovascular disease in this patient population. The most common arrhythmia observed among geriatric patients with thyroid hormone overtreatment is atrial fibrillation.

Clinical studies of IV liothyronine therapy did not include a sufficient number of patients >=65 years of age to determine whether they respond differently from younger patients; however, other clinical experience has not reported differences in response between geriatric and younger patients. In geriatric patients, the dose of IV liothyronine should be initiated at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy in this patient population.

Since IV liothyronine is excreted by the kidneys, clinicians should monitor renal function in geriatric patients.