Levothyroxine

[MaNiCC]

Levothyroxine, also L-thyroxine, synthetic T4, or 3,5,3′,5′-tetraiodo-L-thyronine, is a synthetic form of thyroxine (thyroid hormone), used as a hormone replacement for patients with thyroid problems. The natural hormone is chemically in the chiral L-form, as is the pharmaceutical agent. Dextrothyroxine (D-thyroxine) briefly saw research as an anticholesterol agent but was pulled due to cardiac side-effects.
Common brand names include Thyrax, Euthyrox, Levaxin, L-thyroxine, Eltroxin and Thyrax Duotab in Europe; Thyrox in South Asia; Eutirox, Levoxyl and Synthroid in North America. There are also numerous generic versions.

3,5,3′,5′-Tetraiodo-L-thyronine
Identifiers
CAS number 51-48-9
ATC code H03AA01
PubChem CID 853
DrugBank APRD00235

Chemical data
Formula C15H11I4NO4
Mol. mass 776.87
SMILES eMolecules & PubChem
Synonyms O-(4-hydroxy-3,5-diiodophenyl)-3,5-diiodo-L-tyrosine

Pharmacokinetic data
Bioavailability ~100%
Metabolism Mainly in liver, kidneys, brain and muscles
Half-life ca. 7 days (in hyperthyroidism 3-4 days, in hypothyroidism 9-10 days)
Excretion Through feces and urine

Therapeutic considerations
Pregnancy cat. A(US)
Legal status ℞ Prescription only
Routes Oral, Intravenous
Uses
This medicine is a hormone replacement usually given to patients with thyroid problems, specifically, hypothyroidism.
It also has been given to people who have goiter or an enlarged thyroid gland.

Dosage for humans and precautions
Dosages vary according to the age groups and the individual condition of the patient, body weight and compliance to the medication and diet. Maximum dosage may reach 400 µg per day but that is rare. Monitoring of the patients condition and adjustment of the dosage is periodical and necessary.
Levothyroxine is taken on an empty stomach approximately half an hour to an hour before meals to maximize its absorption, often with water to ease swallowing and help the tablet dissolve for absorption.
There are also foods and other substances that can interfere with absorption of thyroxine replacement. Patients under treatment ought to avoid taking calcium and iron supplements within 4 hours, as well as soy products within 3 hours of the medication, as these can reduce absorption of the drug. Grapefruit juice may delay the absorption of levothyroxine, but it is not believed to have a significant effect on bioavailability. Other substances that reduce absorption are aluminium and magnesium containing antacids, simethicone or sucralfate, cholestyramine, colestipol, Kayexalate. Recently, in a study of 8 women, it has been discovered that coffee may interfere with the intestinal absorption of levothyroxine, though at a level less than eating bran. Different substances cause other adverse effects that may be severe. Ketamine may cause hypertension and tachycardia and tricyclic and tetracyclic antidepressants increase its toxicity. On the other hand Lithium can cause hyperthyroidism (but most often hypothyroidism) by affecting iodine metabolism of the thyroid itself and thus inhibits synthetic levothyroxine as well.

Veterinary use
The dosage for dogs with hypothyroidism is usually a twice daily dose of between 10-40 µg per kg of body weight. Usually at the beginning of the treatment, the lowest dose is used and 4 weeks later the blood values are checked to see if the drug has responded. The dosage is increased as necessary until normal levels are achieved.
Adverse effects
Patients prescribed too high of a dose of levothyroxine may experience the effects which mimic hyperthyroidism. Commonly this can result in heart palpitations, nervousness, headache, insomnia, weight loss, and increased appetite. Allergic reactions to the drug are characterized by symptoms such as difficulty breathing, shortness of breath, or swelling of the face and tongue.
Acute overdose may cause fever, hypoglycemia, heart failure, coma and unrecognized adrenal insufficiency. Acute massive overdose may be life-threatening; treatment should be symptomatic and supportive. Massive overdose may require beta-blockers for increased sympathomimetic activity.
The effects of overdosing appear 6 hours to 11 days after ingestion.
Marketing and approvals in the United States
Synthroid is the most prescribed brand of T4 in the United States. Synthroid was marketed in 1955, but was not FDA approved at that time as it was “generally regarded safe”. In the 1990s, in response to debate as to whether Synthroid was more effective than other levothyroxine preparations, (which ended up concluding that there was little difference between Synthroid and generic brands) all levothyroxine preparations were required to undergo the formal FDA approval process. Synthroid was approved by the FDA on 24 July 2002.



Levothyroxine 25 µg tablets