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Tirosint (Levothyroxine Sodium) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

Drugs Known to Affect Thyroid Hormone Pharmacokinetics

Many drugs affect thyroid hormone pharmacokinetics (e.g., absorption, synthesis, secretion, catabolism, protein binding, and target tissue response) and may alter the therapeutic response to TIROSINT. In addition, thyroid hormones and thyroid status have varied effects on the pharmacokinetics and actions of other drugs.

A listing of drug interactions with L-thyroxine (T4) is provided in the following tables. These tables should not be seen as comprehensive due to the introduction of new drugs that interact with the thyroidal axis or the discovery of previously unknown interactions. The prescriber should be aware of this fact and should consult appropriate reference sources (e.g., prescribing information of newly approved drugs, medical literature) for additional information if a drug-drug interaction with levothyroxine is suspected.

Table 2: Drugs That May Decrease T4 Absorption (Hypothyroidism)
Drug or Drug Class Effect
Potential impact: Concurrent use may reduce the efficacy of levothyroxine by binding and delaying or preventing absorption, potentially resulting in hypothyroidism.
Calcium Carbonate
Ferrous Sulfate
Calcium carbonate may form an insoluble chelate with levothyroxine, and ferrous sulfate likely forms a ferric-thyroxine complex. Administer levothyroxine at least 4 hours apart from these agents.
Orlistat Patients treated concomitantly with orlistat and levothyroxine should be monitored for changes in thyroid function.
Bile Acid Sequestrants
-Colesevelam
-Cholestyramine
-Colestipol
Ion Exchange Resins
-Kayexalate
-Sevelamer
Bile acid sequestrants and ion exchange resins are known to decrease levothyroxine absorption. Administer levothyroxine at least 4 hours prior to these drugs or monitor thyrotropin-stimulating hormone (TSH) levels.
Other drugs:
Sucralfate
Antacids
- Aluminum & Magnesium Hydroxides
- Simethicone
Table 3: Drugs That May Alter T4 and Triiodothyronine (T3) Serum Transport Without Effecting Free Thyroxine (FT4) Concentration (Euthyroidism)
Drugs That May Increase Serum Thyroxine-Binding Globulin (TBG) Concentration Drugs That May Decrease Serum TBG Concentration
Clofibrate
Estrogen-containing oral contraceptives
Estrogens (oral)
Heroin / Methadone
5-Fluorouracil
Mitotane
Tamoxifen
Androgens / Anabolic Steroids
Asparaginase
Glucocorticoids
Slow-Release Nicotinic Acid
Drugs That May Cause Protein-Binding Site Displacement
Potential impact: Administration of these agents with levothyroxine results in an initial transient increase in FT4. Continued administration results in a decrease in serum T4 and normal FT4 and TSH concentrations, and patients are likely clinically euthyroid.
Salicylates (> 2 g/day) Salicylates inhibit binding of T4 and T3 to TBG and transthyretin. An initial increase in serum FT4 is followed by return of FT4 to normal levels with sustained therapeutic serum salicylate concentrations, although total T4 levels may decrease by as much as 30%.
Other drugs:
Furosemide (> 80 mg IV)
Heparin
Hydantoins
Non-Steroidal Anti-inflammatory Drugs
- Fenamates
- Phenylbutazone
Table 4: Drugs That May Alter Hepatic Metabolism of T4 (Hypothyroidism)
Drug or Drug Class Effect
Potential impact: Stimulation of hepatic microsomal drug-metabolizing enzyme activity may cause increased hepatic degradation of levothyroxine, resulting in increased levothyroxine requirements.
Carbamazepine
Hydantoins
Phenytoin and carbamazepine reduce serum protein binding of levothyroxine, and total and FT4 may be reduced by 20% to 40%, but most patients have normal serum TSH levels and are clinically euthyroid. Close monitoring of thyroid hormone parameters is recommended.
Other drugs:
Phenobarbital
Rifampin
Table 5: Drugs That May Decrease Conversion of T4 to T3
Drug or Drug Class Effect
Potential impact: Administration of these enzyme inhibitors decreases the peripheral conversion of T4 to T3, leading to decreased T3 levels. However, serum T4 levels are usually normal but may occasionally be slightly increased.
Beta-adrenergic antagonists
(e.g., Propranolol > 160 mg/day)
In patients treated with large doses of propranolol (> 160 mg/day), T3 and T4 levels change slightly, TSH levels remain normal, and patients are clinically euthyroid. It should be noted that actions of particular beta-adrenergic antagonists may be impaired when the hypothyroid patient is converted to the euthyroid state.
Glucocorticoids
(e.g., Dexamethasone ≥ 4 mg/day)
Short-term administration of large doses of glucocorticoids may decrease serum T3 concentrations by 30% with minimal change in serum T4 levels. However, long-term glucocorticoid therapy may result in slightly decreased T3 and T4 levels due to decreased TBG production (See above).
Other:
Amiodarone

Antidiabetic Therapy

Addition of levothyroxine to antidiabetic or insulin therapy may result in increased antidiabetic agent or insulin requirements. Careful monitoring of diabetic control is recommended, especially when thyroid therapy is started, changed, or discontinued.

Oral Anticoagulants

Levothyroxine increases the response to oral anticoagulant therapy. Therefore, a decrease in the dose of anticoagulant may be warranted with correction of the hypothyroid state or when the TIROSINT dose is increased. Coagulation tests should be closely monitored to permit appropriate and timely dosage adjustments.

Digitalis Glycosides

The therapeutic effects of digitalis glycosides may be reduced by levothyroxine. Serum digitalis glycoside levels may be decreased when a hypothyroid patient becomes euthyroid, necessitating an increase in the dose of digitalis glycosides.

Antidepressant Therapy

Concurrent use of tricyclic (e.g., Amitriptyline) or tetracyclic (e.g., Maprotiline) antidepressants and levothyroxine may increase the therapeutic and toxic effects of both drugs, possibly due to increased receptor sensitivity to catecholamines. Toxic effects may include increased risk of cardiac arrhythmias and central nervous system stimulation; onset of action of tricyclics may be accelerated. Administration of sertraline in patients stabilized on levothyroxine may result in increased levothyroxine requirements.

Ketamine

Concurrent use may produce marked hypertension and tachycardia; cautious administration to patients receiving thyroid hormone therapy is recommended.

Sympathomimetics

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.

Tyrosine-Kinase Inhibitors

Concurrent use of tyrosine-kinase inhibitors such as imatinib may cause hypothyroidism. TSH levels should be closely monitored in such patients.

Drug-Food Interactions

Consumption of certain foods may affect levothyroxine sodium absorption thereby necessitating adjustments in dosing. Soybean flour, cotton seed meal, walnuts, and dietary fiber may bind and decrease the absorption of levothyroxine sodium from the GI tract.

Drug-Laboratory Test Interactions

Changes in TBG concentration must be considered when interpreting T4 and T3 values, which necessitates measurement and evaluation of unbound (free) hormone and/or determination of the free T4 index (FT4I). Pregnancy, infectious hepatitis, estrogens, estrogen-containing oral contraceptives, and acute intermittent porphyria increase TBG concentrations. Decreases in TBG concentrations are observed in nephrosis, severe hypoproteinemia, severe liver disease, acromegaly, and after androgen or corticosteroid therapy. Familial hyper- or hypo-thyroxine binding globulinemias have been described, with the incidence of TBG deficiency approximating 1 in 9000.

OVERDOSAGE

The signs and symptoms of overdosage are those of hyperthyroidism. [See Warnings and Precautions and Adverse Reactions (6) ] In addition, confusion and disorientation may occur. Cerebral embolism, shock, coma, and death have been reported. Seizures have occurred in a 3-year-old child ingesting 3.6 mg of levothyroxine. Symptoms may not necessarily be evident or may not appear until several days after ingestion of levothyroxine sodium.

Treatment of Overdosage

Levothyroxine sodium should be reduced in dose or temporarily discontinued if signs or symptoms of overdosage occur.

To obtain up-to-date information about the treatment of overdose, a good resource is the certified Regional Poison Control Center. In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in the patient.

In the event of an overdose, appropriate supportive treatment should be initiated as dictated by the patient's medical status.

CONTRAINDICATIONS

  • Do not give TIROSINT to anyone who may be unable to swallow a capsule, including young children (generally under 6 years of age) because of the risk of aspiration.
  • Levothyroxine is also contraindicated in patients with: Acute myocardial infarction: administration of levothyroxine in this setting can exacerbate angina and increase the risk of arrhythmia.
  • Uncorrected adrenal insufficiency since thyroid hormones may precipitate an acute adrenal crisis by increasing the metabolic clearance of glucocorticoid [See Warnings and Precautions].

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