LEVOXYL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LEVOXYL (LEVOXYL).
Levothyroxine is a synthetic thyroid hormone (T4) that is deiodinated to triiodothyronine (T3) in peripheral tissues, binding to thyroid hormone receptors in the nucleus and increasing metabolic rate, protein synthesis, and oxygen consumption.
| Metabolism | Hepatic and renal deiodination to active T3 and inactive metabolites; also undergoes glucuronidation and sulfation; CYP450 induction (e.g., rifampin, phenytoin) can increase clearance. |
| Excretion | Renal (30-50% as unchanged drug and conjugates); fecal (biliary, 20-40% as conjugates); total clearance approximates 1-2 L/day in euthyroid patients. |
| Half-life | 6-7 days in euthyroid patients; prolonged in hypothyroidism (9-10 days), shortened in hyperthyroidism (3-4 days); clinical steady-state after 6-8 weeks of consistent dosing. |
| Protein binding | 99.6% bound to thyroxine-binding globulin (TBG), transthyretin (TTR), and albumin. |
| Volume of Distribution | 0.10-0.15 L/kg (approximately 10-12 L total); reflects extensive binding to plasma proteins and limited tissue distribution. |
| Bioavailability | Oral: 60-80% (variable due to food, GI conditions, and other drugs); IV: 100%. |
| Onset of Action | Oral: 3-5 days for initial clinical effect; IV: 6-12 hours for onset in myxedema coma. |
| Duration of Action | Oral: 2-3 weeks after discontinuation due to slow elimination; clinical effects persist for weeks; IV: effects last 1-2 weeks after single dose. |
Initial adult dose: 25-50 mcg orally once daily; titrate by 12.5-25 mcg every 6-8 weeks based on TSH. Maintenance dose: 50-200 mcg orally once daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for renal impairment; monitor TSH. In end-stage renal disease, starting dose 25-50 mcg orally once daily with conservative titration. |
| Liver impairment | No established Child-Pugh based guidelines; severe hepatic impairment may reduce T4 to T3 conversion; start at lower dose (e.g., 25-50 mcg) and titrate cautiously. |
| Pediatric use | Weight-based: 0-3 months: 10-15 mcg/kg/day; 3-6 months: 8-10 mcg/kg/day; 6-12 months: 6-8 mcg/kg/day; 1-5 years: 5-6 mcg/kg/day; 6-12 years: 4-5 mcg/kg/day; >12 years: 2-3 mcg/kg/day. Oral daily dosage; titrate every 2-4 weeks based on TSH and T4. |
| Geriatric use | Start at lower dose (25-50 mcg orally once daily) due to increased sensitivity and higher risk of cardiac effects; adjust in 12.5-25 mcg increments every 6-8 weeks; consider lower target TSH (0.5-1.5 mIU/L) in patients >65 years. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LEVOXYL (LEVOXYL).
| Breastfeeding | Levothyroxine is safe during breastfeeding. It is secreted into breast milk in minimal amounts, with an M/P ratio of approximately 0.3. It is not expected to cause adverse effects in breastfed infants, as the amount is insufficient to affect neonatal thyroid function or suppress TSH. The manufacturer recommends monitoring infants for signs of thyroid dysfunction if maternal doses are very high. |
| Teratogenic Risk | Levothyroxine (LEVOXYL) is FDA Pregnancy Category A. In the first trimester, maternal hypothyroidism increases risk of fetal neurodevelopmental deficits; levothyroxine therapy reduces this risk. No teratogenic effects from levothyroxine itself. In second and third trimesters, adequate maternal thyroid hormone is critical for fetal brain development; untreated maternal hypothyroidism can lead to intellectual disability. No known fetal risks from levothyroxine at therapeutic doses. |
■ FDA Black Box Warning
Not indicated for treatment of obesity or weight loss; ineffective and dangerous at high doses.
| Serious Effects |
Untreated adrenal insufficiency; untreated thyrotoxicosis; recent myocardial infarction; hypersensitivity to levothyroxine or any inactive ingredients.
| Precautions | Cardiac toxicity (arrhythmias, ischemia, heart failure) in overdosage; bone density reduction with prolonged high doses; adrenal insufficiency crisis in undiagnosed adrenal insufficiency; overtreatment in elderly or patients with cardiovascular disease; concomitant use with anticoagulants requires monitoring. |
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| Fetal Monitoring | Monitor maternal TSH and free T4 every 4-6 weeks during pregnancy, especially in the first half. Adjust dose to maintain TSH within trimester-specific reference ranges (first trimester: 0.2-2.5 mIU/L; second: 0.3-3.0; third: 0.5-3.5). Monitor fetal growth and development via ultrasound. Assess fetal thyroid function if maternal antibodies or iodine deficiency present. |
| Fertility Effects | Untreated hypothyroidism can cause ovulatory dysfunction, anovulation, and infertility due to disruption of the hypothalamic-pituitary-gonadal axis. Levothyroxine replacement therapy restores euthyroidism, thereby normalizing menstrual cycles and improving fertility outcomes. No direct adverse effects of levothyroxine on fertility; may increase pregnancy rates in hypothyroid women. |