Thyroxine

Thyroxine

[1 tablet 7 cents]

ADMINISTRATION ROUTES:

  • PO

ALTERNATIVE NAMES: Eltroxin, Levothyroxine (Goldshield), Synthyroid

ICU INDICATIONS:

  1. treatment of hypothyroidism

PRESENTATION AND ADMINISTRATION:

  • PO:
    Eltroxin 50mcg and 100mcg tablets (white to off white)
    Levothyroxine (Goldshield) 50mcg and 100mcg tablets (white) Synthyroid 50mcg tablets (white) and 100mcg tablets (yellow)

DOSAGE:

  • PO:
    Thyroid hormone replacement:
    Usual dosage range 50-200mcg daily

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:

  • Dose as in normal renal function

DOSAGE IN PAEDIATRICS:

  • PO:
    Thyroid hormone replacement:
    Usual dose range is 100mcg/m2 rounded to the nearest quarter tablet daily (see PRECAUTIONS Paediatric Use)

CLINICAL PHARMACOLOGY:

  • Thyroxine is a thyroid hormone.

CONTRAINDICATIONS:

  1. uncorrected adrenal insufficiency

WARNINGS

  • Patients with underlying cardiovascular disease: Exercise caution when administering levothyroxine to patients with cardiovascular disorders and to the elderly in whom there is an increased risk of occult cardiac disease. In these patients, levothyroxine therapy should be initiated at lower doses than those recommended in younger individuals or in patients without cardiac disease.

PRECAUTIONS

  • General: Levothyroxine has a narrow therapeutic index. Regardless of the indication for use, careful dosage titration is necessary to avoid the consequences of over- or under- treatment.
  • Laboratory Tests: It is reasonable to check thyroid hormone levels in patients on thyroxine when they are admitted to the intensive care unit; however, interpretation of thyroid hormone levels in the setting of critical illness can be difficult
  • Drug/Laboratory Test Interactions : None known

IMPORTANT DRUG INTERACTIONS FOR THE ICU

  • Many drugs affect thyroid hormone pharmacokinetics and metabolism (e.g., absorption, synthesis, secretion, catabolism, protein binding, and target tissue response) and may alter the therapeutic response. In addition, thyroid hormones and thyroid status have varied effects on the pharmacokinetics and actions of other drugs.
  • Drugs that may decrease thyroid hormone secretion, which may result in hypothyroidism: Aminoglutethimide, amiodarone, iodide (including iodine-containing radiographic contrast agents), lithium, methimazole, propylthiouracil (PTU), sulfonamides, tolbutamide:
    • Long-term lithium therapy can result in goiter in up to 50% of patients, and either subclinical or overt hypothyroidism, each in up to 20% of patients.
    • Oral cholecystographic agents and amiodarone are slowly excreted, producing more prolonged hypothyroidism than parenterally administered iodinated contrast agents.
    • Long-term aminoglutethimide therapy may minimally decrease T4 and T3 levels and increase TSH, although all values remain within normal limits in most patients.
  • Drugs that may increase thyroid hormone secretion, which may result in hyperthyroidism: Amiodarone, iodide (including iodine-containing radiographic contrast agents):
    • Iodide and drugs that contain pharmacologic amounts of iodide may cause hyperthyroidism in euthyroid patients with Grave’s disease previously treated with antithyroid drugs or in euthyroid patients with thyroid autonomy (e.g., multinodular goiter or hyperfunctioning thyroid adenoma). Hyperthyroidism may develop over several weeks and may persist for several months after therapy discontinuation.
    • Amiodarone may induce hyperthyroidism by causing thyroiditis.
  • Drugs that may decrease T4 absorption, which may result in hypothyroidism:
    Antacids (aluminum and magnesium); hydroxides (simethicone); bile acid sequestrants (cholestyramine, colestipol); calcium carbonate; cation exchange resins (kayexalate); ferrous sulfate; sucralfate:

    • Concurrent use may reduce the efficacy of levothyroxine by binding and delaying or preventing absorption, potentially resulting in hypothyroidism. 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.
  • Drugs that may increase serum TBG concentration:
    Clofibrate, estrogen-containing oral contraceptives, estrogens (oral), heroin/methadone, 5-fluorouracil, mitotane, tamoxifen.
  • Drugs that may decrease serum TBG concentration:
    /anabolic steroids, asparaginase, glucocorticoids, slow-release nicotinic acid.
  • Drugs that may cause protein-binding site displacement:
    Frusemide (>80 mg IV); heparin; hydantoins; non-steroidal anti-inflammatory drugs (fenamates, phenylbutazone); salicylates (>2 g/day):

    • 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, therefore, patients are clinically euthyroid.
    • 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%.
  • Drugs That May Alter T4 and T3 Metabolism:
    Drugs that may increase hepatic metabolism, which may result in hypothyroidism: Carbamazepine, hydantoins, phenobarbital, rifampin:

    • Stimulation of hepatic microsomal drug-metabolizing enzyme activity may cause increased hepatic degradation of levothyroxine, resulting in increased levothyroxine requirements.
    • Phenytoin and carbamazepine reduce serum protein binding of levothyroxine, and total- and free-T4 may be reduced by 20-40%, but most patients have normal serum TSH levels and are clinically euthyroid.
  • Drugs That May Decrease T4 5 alpha-Deiodinase Activity:
    Amiodarone; beta-adrenergic antagonists

    • 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.
    • 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.
  • 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).
  • Miscellaneous:
    • Anticoagulants (coumarin derivatives, indandione derivatives):
      Thyroid hormones appear to increase the catabolism of vitamin K-dependent clotting factors, thereby increasing the anticoagulant activity of oral anticoagulants. Concomitant use of these agents impairs the compensatory increases in clotting factor synthesis. Prothrombin time should be carefully monitored in patients taking levothyroxine and oral anticoagulants and the dose of anticoagulant therapy adjusted accordingly.
    • Antidepressants, tricyclics:
      Concurrent use of tri/tetracyclic 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 CNS stimulation; onset of action of tricyclics may be accelerated. Administration of sertraline in patients stabilized on levothyroxine may result in increased levothyroxine requirements.
    • Antidiabetic agents: biguanides, meglitinides, sulfonylureas, thiazolidediones, insulin:
      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.
    • Cardiac glycosides:
      Serum digitalis glycoside levels may be reduced in hyperthyroidism or when the hypothyroid patient is converted to the euthyroid state. Therapeutic effect of digitalis glycosides may be reduced.
    • Ketamine:
      Concurrent use may produce marked hypertension and tachycardia; cautious administration to patients receiving thyroid hormone therapy is recommended. Methylxanthine bronchodilators Decreased theophylline clearance may occur in hypothyroid patients; clearance returns to normal when the euthyroid state is achieved.
    • Radiographic agents:
      Thyroid hormones may reduce the uptake of 123I, 131I, and 99mTc.
    • 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.

ADVERSE REACTIONS

Adverse reactions associated with levothyroxine therapy are primarily those of hyperthyroidism due to therapeutic overdosage.

  • General: Fatigue, increased appetite, weight loss, heat intolerance, fever, excessive sweating.
  • Central Nervous System: Headache, hyperactivity, nervousness, anxiety, irritability, emotional lability, insomnia.
  • Musculoskeletal: Tremors, muscle weakness. Cardiovascular: Palpitations, tachycardia, arrhythmias, increased pulse and blood pressure, heart failure, angina, myocardial infarction, cardiac arrest.
  • Respiratory: Dyspnea.
  • Gastrointestinal: Diarrhoea, vomiting, abdominal cramps and elevations in liver function tests.
  • Dermatologic: Hair loss, flushing. Endocrine: Decreased bone mineral density.
  • Reproductive: Menstrual irregularities, impaired fertility.

Critical Care Drug Manual

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