levothyroxine sodium (T₄ or L -thyroxine sodium)
Eltroxin, Levo-T, Levothroid, Levoxine, Levoxyl, Novothyrox, Synthroid, Unithroid

Available forms
Available by prescription only
Injection: 200 mcg/vial, 500 mcg/vial
Tablets: 25 mcg, 50 mcg, 75 mcg, 88 mcg, 100 mcg, 112 mcg, 125 mcg, 137 mcg, 150 mcg, 175 mcg, 200 mcg, 300 mcg

Indications and dosages
 Congenital hypothyroidism. Children age 1 and older: 3 to 5 mcg/kg P.O. daily until adult dose (150 mcg) is reached in early or mid-adolescence.
Children younger than age 1: Initially, 25 to 50 mcg P.O. daily.
Neonates: 37.5 mcg (25 to 50 mcg) P.O. daily.
Premature neonates under 2 kg (4.4 lb) and those at risk for cardiac failure: 25 mcg P.O. daily initially; dosage may be increased to 50 mcg daily in 4 to 6 weeks.
Alternative dosing schedule
Children older than age 12: Over 150 mcg or 2 to 3 mcg/kg daily.
Children ages 6 to 12: 100 to 150 mcg or 4 to 5 mcg/kg daily.
Children ages 1 to 5: 75 to 100 mcg or 5 to 6 mcg/kg daily.
Children ages 6 to 12 months: 50 to 75 mcg or 6 to 8 mcg/kg daily.
Children younger than age 6 months: 25 to 50 mcg or 8 to 10 mcg/kg daily.
 Myxedema coma. Adults: 300 to 500 mcg I.V. If no response occurs in 24 hours, give an additional 100 to 300 mcg I.V. in 48 hours. A maintenance dosage of 50 to 200 mcg may be given until condition stabilizes and drug can be given orally.
 Thyroid hormone replacement for atrophy of gland, surgical removal, excessive radiation or antithyroid drugs. Adults: For mild hypothyroidism-initially, 50 mcg P.O. daily, increased by 25 to 50 mcg P.O. daily q 2 to 4 weeks until desired response is achieved; may be administered by I.V. or I.M. when P.O. ingestion is precluded for long periods. Usual dose is 100 to 200 mcg daily.
 For severe hypothyroidism-12.5 to 25 mcg P.O. daily, increased by 25 to 50 mcg daily q 2 to 4 weeks until desired response is achieved.
Elderly patients: Start at 12.5 to 50 mcg P.O. daily and increase in 12.5- to 25-mcg increments q 3 to 8 weeks.
≡ Dosage adjustment. For patients with CV disease, start at 50 mcg daily and increase in 50-mcg increments at 2- to 4-week intervals.

Pharmacodynamics
Thyroid hormone replacement: Drug affects protein and carbohydrate metabolism, promotes gluconeogenesis, increases the use and mobilization of glycogen stores, stimulates protein synthesis, and regulates cell growth and differentiation.

Pharmacokinetics
Absorption: Between 50% and 80% is absorbed from the GI tract. Full effects don’t occur for 1 to 3 weeks after oral therapy begins. After I.M. administration, absorption is variable and poor.
Distribution: Distribution isn’t fully described; however, drug is distributed into most body tissues and fluids. The highest levels are found in the liver and kidneys; 99% is protein-bound.
Metabolism: Metabolized in peripheral tissues, primarily in the liver, kidneys, and intestines. About 85% of metabolized levothyroxine is deiodinated.
Excretion: Fecal excretion eliminates 20% to 40% of levothyroxine. Half-life is 6 to 7 days.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and in patients with acute MI and thyrotoxicosis uncomplicated by hypothyroidism or uncorrected adrenal insufficiency.
  Use cautiously in elderly patients and in patients with renal impairment, angina pectoris, hypertension, ischemia, or other CV disorders.

Interactions
Drug-drug. Anticoagulants: May alter anticoagulant effect. Increased levothyroxine dosage may necessitate decreased anticoagulant dosage.
Beta blockers: May decrease conversion of levothyroxine to liothyronine. Monitor patient.
Cholestyramine: May delay absorption of levothyroxine. Don’t administer together.
Corticotropin: Alters thyroid status. Monitor patient; dosage adjustments of both drugs may be needed.
Estrogens: Increases levothyroxine requirements. Monitor patient for decreased levothyroxine effect.
Hepatic enzyme inducers such as phenytoin: May increase hepatic degradation of levothyroxine and increase dosage requirements. Adjust dosages as needed.
Insulin, oral antidiabetics: Alters serum glucose levels. Adjust doses of these drugs as needed.
Somatrem: May accelerate epiphyseal maturation. Avoid use together in children if possible.
Sympathomimetics, tricyclic antidepressants: May increase effects of these drugs and may lead to coronary insufficiency or arrhythmias. Monitor patient closely if use together is needed.
Theophylline: Decreases theophylline clearance in hypothyroid patients. Clearance returns to normal when euthyroid state resumes.
Drug-herb. Horseradish: May cause abnormal thyroid function. Discourage use by patients undergoing thyroid function tests.
Kelp: May cause hyperthyroidism. Discourage use together.

Adverse reactions
CNS: nervousness, insomnia, tremor, headache, fever.
CV: tachycardia, palpitations, arrhythmias, angina pectoris, cardiac arrest.
GI: diarrhea, vomiting.
GU: menstrual irregularities.
Metabolic: weight loss.
Skin: diaphoresis, allergic skin reactions.
Other: heat intolerance.

Effects on lab test results
None reported.

Overdose and treatment
Evidence of overdose includes signs and symptoms of hyperthyroidism, including weight loss, increased appetite, palpitations, nervousness, diarrhea, abdominal cramps, sweating, tachycardia, increased blood pressure, widened pulse pressure, angina, arrhythmias, tremor, headache, insomnia, heat intolerance, fever, and menstrual irregularities.
 Treatment requires reduction of GI absorption and efforts to counteract central and peripheral effects, primarily sympathetic activity. Use gastric lavage or induce emesis (followed by activated charcoal up to 4 hours after ingestion). If the patient is comatose or is having seizures, inflate cuff on endotracheal tube to prevent aspiration. Treatment may include oxygen and artificial ventilation as needed to support respiration. It also should include appropriate measures to treat heart failure and to control fever, hypoglycemia, and fluid loss. Propranolol (or another beta blocker) may be used to combat many of the effects of increased sympathetic activity. Levothyroxine should be gradually withdrawn over 2 to 6 days, then resumed at a lower dose.

Special considerations
• Levothyroxine has predictable effects because of standard hormonal content; therefore, it’s the usual drug of choice for thyroid hormone replacement.
• Administer as a single dose before breakfast.
• Patient with history of lactose intolerance may be sensitive to Levothroid, which contains lactose.
• Synthroid 100- and 300-mcg tablets contain tartrazine, a dye that causes allergic reactions in susceptible individuals.
• When switching from levothyroxine to liothyronine, stop levothyroxine dosage when liothyronine treatment begins. After residual effects of levothyroxine have disappeared, liothyronine dosage can be increased in small increments. When switching from liothyronine to levothyroxine, begin levothyroxine therapy several days before withdrawing liothyronine to avoid relapse.
• Reconstitute Levothyroid powder for injection or levothyroxine sodium powder by adding 2 ml or 5 ml of normal saline solution for injection to vial containing 200 or 500 mcg, respectively. Shake until a clear solution is obtained. Concentration is about 100 mcg/ml.
• Reconstitute Synthroid powder for injection by adding 5 ml of normal saline solution for injection or bacteriostatic sodium chloride injection with benzyl alcohol to 200- or 500-mcg vial. Shake until a clear solution is obtained. Concentration is 40 or 100 mcg/ml, respectively. Use reconstituted solutions immediately and don’t administer with other I.V. infusion solutions.
• After an I.V. dose in patients with myxedema coma, increased responsiveness may occur within 6 to 8 hours, but maximum therapeutic effect may not occur for up to 24 hours.
• Carefully observe patient for adverse effects during initial dosage adjustment phase.
• Monitor patient for aggravation of concurrent diseases, such as Addison’s disease or diabetes mellitus.
• Levothyroxine therapy alters radioactive iodine (¹³¹I) thyroid uptake, protein-bound iodine levels, and liothyronine uptake. Patient taking levothyroxine who requires ¹³¹I uptake studies must discontinue drug 4 weeks before test.
• Protect drug from moisture and light.
Breast-feeding patients
• Minimal amounts of drug appear in breast milk. Use cautiously in breast-feeding women.
Pediatric patients
• Partial and temporary hair loss may occur during the first few months of therapy.
Geriatric patients
• Elderly patients are more sensitive to effects of drug. For patients older than age 60, initial dosage should be 25% lower than usual recommended dosage.

Patient education
• Advise taking drug at same time each day; encourage morning dosing to avoid insomnia.
• Tell patient to report headache, diarrhea, nervousness, excessive sweating, heat intolerance, chest pain, increased pulse rate, or palpitations.
• Encourage patient to use the same product consistently because all brands don’t have equal bioavailability.
• Advise patient to store drug in cool, dry place to prevent deterioration of product.
• Tell patient that replacement therapy is to be taken essentially for life, except in cases of transient hypothyroidism.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use