levothyroxine

Synthetic form of thyroxine (T₄). Replacement of or supplementation to endogenous thyroid hormones.
Principal effect is increasing metabolic rate of body tissues:
- Promote gluconeogenesis,
- Increase utilization and mobilization of glycogen stores,
- Stimulate protein synthesis,
- Promote cell growth and differentiation,
- Aid in the development of the brain and CNS.

Therapeutic effects:

Replacement in hypothyroidism to restore normal hormonal balance.
Suppression of thyroid cancer.

Pharmacokinetics ⬆ ⬇

Absorption: Levothyroxine is variably (40–80%) absorbed from the GI tract.

Distribution: Distributed into most body tissues.

Protein Binding: >99%.

Metabolism/Excretion: Metabolized by the liver and other tissues to active T3. Thyroid hormone undergoes enterohepatic recirculation and is excreted in the feces via the bile.

Half-Life: 6–7 days.

Time/Action Profile ⬆ ⬇

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1–3 wk	1–3 wk
IV	6–8 hr	24 hr	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Recent MI;
Hyperthyroidism.

Use Cautiously in:

Cardiovascular disease (initiate therapy with lower doses);
Severe renal impairment;
Uncorrected adrenocortical disorders;
Pedi: Monitor neonates and infants for cardiac overload, arrhythmias, and aspiration during first 2 wk of therapy;
Geri: Older adults are extremely sensitive to thyroid hormones; initial dose should be ↓.

Adv. Reactions/Side Effects ⬆ ⬇

Usually only seen when excessive doses cause iatrogenic hyperthyroidism

CV: angina, arrhythmias, tachycardia

Derm: sweating

Endo: heat intolerance, hyperthyroidism, menstrual irregularities

GI: abdominal cramps, diarrhea, vomiting

Metab: weight loss

MS: accelerated bone maturation in children

Neuro: headache, insomnia, irritability

Interactions ⬆ ⬇

Drug-drug:

Cholestyramine, colesevelam, colestipol, and sodium polystyrene sulfonate may bind to and ↓ absorption of orally administered levothyroxine; administer levothyroxine ≥4 hr prior to these medications or monitor TSH levels.
Phosphate binders, including calcium carbonate, ferrous sulfate, lanthanum carbonate, and sevelemer, may bind to and ↓ absorption of orally administered levothyroxine; administer levothyroxine ≥4 hr apart from these medications.
Absorption may be ↓ by orlistat, proton pump inhibitors, sucralfate, antacids, and simethicone.
Phenobarbital and rifampin may ↓ levels and effectiveness; may need to ↑ levothyroxine dosage.
May ↑ the risk of bleeding with warfarin.
May ↑ requirement for insulin or oral hypoglycemic agents in patients with diabetes.
May ↓ the therapeutic effects of digoxin; may need to ↑ digoxin dosage.
Concurrent use with ketamine may lead to significant hypertension and tachycardia.
↑cardiovascular effects with adrenergics (sympathomimetics).
Biotin may interfere with thyroid function test assays; discontinue biotin or biotin-containing supplements for ≥2 days before assessing TSH and/or T4 levels.

Drug-Food:

Foods or supplements containing calcium, iron, magnesium, or zinc may bind levothyroxine and prevent complete absorption.
Absorption may be delayed when used with grapefruit juice.

Route/Dosage ⬆ ⬇

PO (Adults ): Hypothyroidism: 1.6 mcg/kg once daily; may ↑ by 12.5–25 mcg/day every 4–6 wk until patient clinically euthyroid based on signs/symptoms and TSH levels.
PO Geriatric Patients and Patients with Cardiac Disease): 12.5–25 mcg once daily; may ↑ by 12.5–25 mcg/day every 6–8 wk until patient clinically euthyroid based on signs/symptoms and TSH levels.
PO (Children >12 yr): 2–3 mcg/kg/day (≥150 mcg/day).
PO (Children 6–12 yr): 4–5 mcg/kg/day (100–125 mcg/day).
PO (Children 1–5 yr): 5–6 mcg/kg/day (75–100 mcg/day).
PO (Children 6–12 mo): 6–8 mcg/kg/day (50–75 mcg/day).
PO (Infants 3–6 mo): 8–10 mcg/kg/day (25–50 mcg/day).
PO (Infants 0–3 mo or Infants at Risk for Cardiac Failure): 10–15 mcg/kg/day or 25 mcg/day; may ↑ after 4–6 wk to 50 mcg.
IM IV (Adults ): Hypothyroidism: 50–100 mcg/day as a single dose. Myxedema coma/stupor: 300–500 mcg IV; additional 100–300 mcg may be given on 2nd day, followed by daily administration of smaller doses.
IM IV (Children ): Hypothyroidism: 50–80% of the oral dose.

Availability ⬆ ⬇

(Generic available)

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
Capsules (Tirosint): 13 mcg; 25 mcg; 50 mcg; 75 mcg; 88 mcg; 100 mcg; 112 mcg; 125 mcg; 137 mcg; 150 mcg; 175 mcg; 200 mcg
Oral solution: 13 mcg/mL; 20 mcg/mL; 25 mcg/mL; 50 mcg/mL; 75 mcg/mL; 88 mcg/mL; 100 mcg/mL; 112 mcg/mL; 125 mcg/mL; 137 mcg/mL; 150 mcg/mL; 175 mcg/mL; 200 mcg/mL
Powder for injection: 100 mcg/vial; 200 mcg/vial; 500 mcg/vial
Solution for injection: 20 mcg/mL; 40 mcg/mL; 100 mcg/mL

Assessment ⬆ ⬇

Assess apical pulse and BP prior to and periodically during therapy. Assess for tachyarrhythmias and chest pain.
Children: Monitor height, weight, and psychomotor development.

Lab Test Considerations:

Monitor thyroid function studies prior to and during therapy. For adults, monitor serum TSH levels in adults 6–8 wk after change in dose or changing from one brand to another. When on a stable dose, evaluate TSH every 6–12 mo and with clinical changes. For pediatric patients, monitor TSH and total or free T4 2 and 4 wk after start of therapy, 2 wk after any change in dose, and then every 3–12 mo after dose stabilization until growth is completed.
- Monitor blood and urine glucose in diabetic patients. Insulin or oral hypoglycemic dose may need to be increased.

Toxicity and Overdose:

Overdose is manifested as hyperthyroidism (tachycardia, chest pain, nervousness, insomnia, diaphoresis, tremors, weight loss). Usual treatment is to withhold dose for 2–6 days and then resume at a lower dose. Acute overdose is treated by induction of emesis or gastric lavage, followed by activated charcoal. Sympathetic overstimulation may be controlled by antiadrenergic drugs (beta blockers), such as propranolol. Oxygen and supportive measures to control symptoms are also used.

Implementation ⬆ ⬇

High Alert: Do not confuse levothyroxine with lamotrigine, Lanoxin, or liothyronine.
PO: Administer with a full glass of water, on an empty stomach, 30–60 min before breakfast, to prevent insomnia.
- Initial dose is low, especially in patients with cardiac disease and older adults. Dose is ↑ gradually based on thyroid function tests.
- For patients with difficulty swallowing, tablets can be crushed and placed in 5–10 mL of water and administered immediately via dropper or spoon; do not store suspension.

IV Administration:

IV Push: Reconstitution: Reconstitute the 200-mcg and 500-mcg vials with 2 or 5 mL, respectively, of 0.9% NaCl without preservatives (diluent usually provided).Concentration: 100 mcg/mL. Shake well to dissolve completely. Administer solution immediately after preparation; discard unused portion.
Rate: Administer at a rate of 100 mcg over 1 min. Do not add to IV infusions; may be administered through Y-tubing.
Y-Site Incompatibility: Do not admix with other IV solutions.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of levothyroxine to patient.
Instruct patient to take medication as directed at the same time each day. Take missed doses as soon as remembered unless almost time for next dose. If more than 2–3 doses are missed, notify health care professional. Do not discontinue without consulting health care professional.
- Explain to patient that medication does not cure hypothyroidism; it provides a thyroid hormone supplement. Therapy is lifelong.
- Advise patient to notify health care professional if headache, nervousness, diarrhea, excessive sweating, heat intolerance, chest pain, ↑ HR, palpitations, weight loss >2 lb/wk, or any unusual symptoms occur.
- Caution patient to avoid taking other medications concurrently with thyroid preparations unless instructed by health care professional. Advise patient to take 4 hr apart from antacids, iron, and calcium supplements. Advise patient to stop biotin-containing supplements ≥ 2 days before assessing TSH or T4 levels.
- Instruct patient to inform health care professionals of thyroid therapy.
- Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Pregnancy may ↑ thyroid requirements. Monitor serum TSH levels and adjust levothyroxine dose accordingly during pregnancy. Since postpartum TSH levels are similar to preconception values, levothyroxine dose should return to prepregnancy dose immediately after delivery.
- Emphasize importance of follow-up exams to monitor effectiveness of therapy. Thyroid function tests are performed at least yearly.
Pedi: Discuss with parents the need for routine follow-up studies to ensure correct development. Inform patient that partial hair loss may be experienced by children on thyroid therapy. This is usually temporary.

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