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. |
| Molecular Weight | 776.87 |
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 | Levothyroxine is essential for maternal and fetal health; hypothyroidism must be treated. No known teratogenic risk at therapeutic doses. Dose adjustments may be required due to increased thyroid-binding globulin. |
| 2nd trimester | Continue therapy; dose adjustments often needed as pregnancy progresses. Monitor thyroid function closely. |
| 3rd trimester | Continue therapy; postpartum dose reduction likely. Monitor thyroid function. |
Clinical note
Comprehensive clinical and safety monograph for LEVOXYL (LEVOXYL).
| Placental transfer | Limited placental transfer; levothyroxine crosses the placenta minimally. However, fetal thyroid function depends on maternal supply in early pregnancy. |
| Breastfeeding | Levothyroxine is excreted into breast milk in very low amounts, insufficient to affect infant thyroid function. Compatible with breastfeeding with monitoring of maternal thyroid status. |
■ FDA Black Box Warning
Not indicated for treatment of obesity or weight loss; ineffective and dangerous at high doses.
| Serious Effects |
Untreated thyrotoxicosisUncorrected adrenal insufficiencyHypersensitivity to levothyroxine or any component of the formulation
| 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. |
| Food/Dietary | Avoid high-fiber diets, soy products, walnuts, cottonseed meal, and calcium-fortified orange juice within 4 hours of dosing. Grapefruit juice may reduce absorption. Consistency in timing and dietary habits is important. Iron and calcium supplements, antacids, and sucralfate should be separated by at least 4 hours. |
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| Lactation Rating | L1 (Safe) |
| 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. |
| 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. |
| Clinical Pearls | LEVOXYL is a brand of levothyroxine sodium; absorption is reduced by food, especially fiber, soy, and calcium-fortified juices. Administer on an empty stomach 30-60 minutes before breakfast with a full glass of water. Dose adjustments are needed in pregnancy, GI disorders, and with interacting drugs. Monitor TSH 6-8 weeks after dose change. Avoid switching brands without retesting TSH due to bioavailability differences. |
| Patient Advice | Take this medication on an empty stomach, at least 30-60 minutes before your first meal of the day, with a full glass of water. · Do not take with other medications, supplements, or foods that may interfere (e.g., iron, calcium, antacids, high-fiber foods, soy). · Take the same brand consistently; do not switch brands without consulting your doctor. · Do not stop or change dose without consulting your doctor; symptoms of hypothyroidism may return. · Store at room temperature away from light and moisture. · If you miss a dose, take it as soon as you remember unless it is close to the next dose; skip the missed dose if it is almost time for the next dose. Do not double dose. |