Description

Simple

A medication used to treat patients with low levels of thyroid hormone.

Clinical

A synthetic T4 hormone used to treat hypothyroidism that can be used along with surgery and radioiodine therapy to manage thyrotropin-dependent well-differentiated thyroid cancer.

Overview

Levothyroxine is a synthetically produced form of thyroxine, a major endogenous hormone secreted by the thyroid gland.[14] Also known as L-thyroxine or the brand name product Synthroid, levothyroxine is used primarily to treat hypothyroidism, a condition where the thyroid gland is no longer able to produce sufficient quantities of the thyroid hormones T4 (tetraiodothyronine or thyroxine) and T3 (triiodothyronine or [DB00279]), resulting in diminished down-stream effects of these hormones. Without sufficient quantities of circulating thyroid hormones, symptoms of hypothyroidism begin to develop such as fatigue, increased heart rate, depression[4], dry skin and hair, muscle cramps, constipation, weight gain, memory impairment, and poor tolerance to cold temperatures.[15,Read more

Pharmacology

Indication

Levothyroxine is indicated as replacement therapy in primary (thyroidal), secondary (pituitary) and tertiary (hypothalamic) congenital or acquired hypothyroidism. It is also indicated as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyr... Read more

Pharmacodynamic

Oral levothyroxine is a synthetic hormone that exerts the same physiologic effect as endogenous T4, thereby maintaining normal T4 levels when a deficiency is present.

Levothyroxine has a narrow therapeutic index and is titrated to maintain a euthyroid state with TSH (thyroi... Read more

Mechanism of action

Levothyroxine is a synthetically prepared levo-isomer of the thyroid hormone thyroxine (T4, a tetra-iodinated tyrosine derivative) that acts as a replacement in deficiency syndromes such as hypothyroidism. T4 is the major hormone secreted from the thyroid gland and is chemicall... Read more

Absorption

Absorption of orally administered T4 from the gastrointestinal tract ranges from 40% to 80% with the majority of the levothyroxine dose absorbed from the jejunum and upper ileum. T4 absorption is increased by fasting, and decreased in malabsorption syndromes and by certain foods such as soybeans, mi... Read more

Protein binding

Circulating thyroid hormones are greater than 99% bound to plasma proteins, including thyroxine-binding globulin (TBG), thyroxine-binding prealbumin (TBPA) and albumin (TBA). The higher affinity of both TBG and TBPA for T4 partially explains the higher serum levels, slower metabolic clearance and lo... Read more

Volume of distribution

Information currently not available.

Clearance

Information currently not available.

Half life

T4 half-life is 6 to 7 days. T3 half-life is 1 to 2 days.[15]

Route of elimination

Thyroid hormones are primarily eliminated by the kidneys. A portion of the conjugated hormone reaches the colon unchanged and is eliminated in the feces. Approximately 20% of T4 is eliminated in the stool. Urinary excretion of T4 decreases with age.[ Read more

Toxicity

LD50=20 mg/kg (orally in rat). Hypermetabolic state indistinguishable from thyrotoxicosis of endogenous origin. Symptoms of thyrotoxicosis include weight loss, increased appetite, palpitations, nervousness, diarrhea, abdominal cramps, sweating, tachycardia, increased pulse and blood press... Read more

Adverse Effects

Effect Regions Age Groups Incidences Evidence Type
Craniosynostosis US
  • infant
Varying Reports
Premature closure of the epiphyses US
  • children
Varying Reports
Wheezing US
Varying Reports
Serum Sickness US
Varying Reports
Arthralgia US
Varying Reports
Fever US
Varying Reports
Diarrhea US
Varying Reports
Vomiting US
Varying Reports
Nausea US
Varying Reports
Abdominal Pain US
Varying Reports
Angioedema US
Varying Reports
Flushing US
Varying Reports
Skin Rash US
Varying Reports
Pruritus US
Varying Reports
Urticaria US
Varying Reports
Slipped Capital Femoral Epiphysis US
  • children
Varying Reports
Pseudotumor Cerebri US
  • children
Varying Reports
Seizures US
Varying Reports
Impaired fertility US
Varying Reports
Menstrual Irregularities US
Varying Reports
Decreased bone mineral density US
Varying Reports
Rash US
Varying Reports
Flushing US
Varying Reports
Hair Loss US
Varying Reports
Increased liver function tests US
Varying Reports
Abdominal Cramps US
Varying Reports
Vomiting US
Varying Reports
Diarrhea US
Varying Reports
Dyspnea US
Varying Reports
Cardiac Arrest US
Varying Reports
Myocardial Infarction US
Varying Reports
Angina US
Varying Reports
Heart Failure US
Varying Reports
Increased blood pressure US
Varying Reports
Increased pulse US
Varying Reports
Arrhythmias US
Varying Reports
Tachycardia US
Varying Reports
Palpitations US
Varying Reports
Muscle Spasm US
Varying Reports
Muscle Weakness US
Varying Reports
Tremors US
Varying Reports
Insomnia US
Varying Reports
Emotional Lability US
Varying Reports
Irritability US
Varying Reports
Anxiety US
Varying Reports
Nervousness US
Varying Reports
Hyperactivity US
Varying Reports
Headache US
Varying Reports
Excessive sweating US
Varying Reports
Fever US
Varying Reports

Contraindications

  • Route:
    • Oral
  • Regions: Canada
  • Patient Conditions:
      • Name: Untreated subclinical or overt thryrotoxicosis
      • Drugbank Id: DBCOND0107743
  • Route:
    • Oral
  • Regions: Canada
  • Patient Conditions:
      • Name: Acute Myocardial Infarction
      • Drugbank Id: DBCOND0030399
      • Modification Of:
        • Base:
          • Name: Myocardial Infarct
          • Drugbank Id: DBCOND0032880
        • Severity:
          • Includes:
            • acute
  • Route:
    • Intravenous
    • Intramuscular
  • Dose Form:
    • Injection
  • Hypersensitivity:
    • false
  • Regions: US
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Uncorrected adrenal insufficiency
      • Drugbank Id: DBCOND0107744

Food Interactions

Avoid calcium supplements/calcium rich foods. Calcium may interfere with the absorption of this drug by forming an insoluble complex. Separate medication administration by at least 4 hours.

Avoid grapefruit products. Grapefruit may delay the absorption of this medication.

Avoid iron supplements. Iron may interfere with the absorption of this drug by forming an insoluble complex. Separate medication administration by at least 4 hours.

Avoid multivalent ions. Examples include iron, magnesium, and calcium. These are often found in antacids, vitamins, and supplements - separate medication administration by at least 4 hours.

Do not take with bran and high fiber foods. Dietary fiber, soybean flour, cottonseed meal, and walnuts may reduce the absorption of levothyroxine.

Take on an empty stomach. Levothyroxine should be taken on an empty stomach 30-60 minutes prior to the first meal of the day.