LEVO-T
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LEVO-T (LEVO-T).
Levothyroxine is a synthetic form of thyroxine (T4), a thyroid hormone. It is deiodinated to triiodothyronine (T3), which binds to nuclear thyroid hormone receptors, resulting in modulation of gene transcription and increased metabolic rate.
| Metabolism | Hepatic metabolism via deiodination (D1, D2 isoenzymes) and conjugation (glucuronidation, sulfation); also metabolized by CYP1A1, CYP1B1, and CYP3A4; enterohepatic recirculation. |
| Excretion | Renal: ~20-40% of administered levothyroxine is excreted in urine as unchanged drug and conjugates; biliary/fecal: ~40-60% is excreted in feces via bile, largely as conjugates and minor amounts of unchanged drug. |
| Half-life | Terminal elimination half-life is approximately 6-7 days in euthyroid individuals; in hyperthyroidism, half-life shortens to 3-4 days; in hypothyroidism, it prolongs to 9-10 days. The long half-life supports once-daily dosing. |
| Protein binding | >99% bound, primarily to thyroxine-binding globulin (TBG, ~70%), transthyretin (TTR, ~10-15%), and albumin (~15-20%). |
| Volume of Distribution | Volume of distribution is approximately 10-12 L (0.15-0.17 L/kg), indicating distribution into extracellular fluid and tissues, reflecting binding to plasma proteins and tissue uptake. |
| Bioavailability | Oral bioavailability is approximately 40-80% (mean ~70%), variable due to formulation, food, and gastrointestinal conditions; intravenous administration yields 100% bioavailability. |
| Onset of Action | Oral: clinical effects (e.g., metabolic rate increase) appear within 3-5 days; intravenous: onset of action is within 6-12 hours for myxedema coma. |
| Duration of Action | Duration of action is approximately 2-3 weeks after a single oral dose, but steady state is attained after 6-8 weeks due to long half-life; clinical effects persist until hormone levels decline. |
| Action Class | H1 Antihistaminics (second Generation) |
| Brand Substitutes | LCZ Tablet, Lecope Tablet, 1-AL Tablet, Levozet Tablet, Hatric Tablet, Solvin LS Syrup, Ambrodil-LX Syrup, Zerotuss XP Syrup, Capex LS Syrup, Broxum LS Syrup |
1.6 mcg/kg orally once daily (typical adult starting dose 50-100 mcg/day); adjust by 12.5-25 mcg increments every 4-6 weeks based on TSH.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required; metabolism is independent of renal function. |
| Liver impairment | No dose adjustment required; however, in severe cirrhosis, reduce starting dose by 25-50% and titrate slowly. |
| Pediatric use | Initial dose 10-15 mcg/kg/day orally (max 50 mcg/day) for children >1 year; titrate by 12.5-25 mcg increments. For neonates (0-3 months), start at 10-15 mcg/kg/day. |
| Geriatric use | Start at lower doses (25-50 mcg/day orally) with gradual titration (increments of 12.5-25 mcg every 4-6 weeks) to avoid cardiac effects; monitor TSH closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LEVO-T (LEVO-T).
| Breastfeeding | Exogenous levothyroxine is excreted into breast milk in trace amounts (M/P ratio: approximately 0.1-0.2). Doses up to 400 mcg/day do not suppress neonatal TSH or cause thyrotoxicosis. Levothyroxine is considered compatible with breastfeeding. Monitor infant thyroid function if maternal dose is high or mother has known thyroid autoimmunity. |
| Teratogenic Risk | Levo-T (levothyroxine) is FDA pregnancy category A. Placental transfer of maternal T4 is critical for fetal neurodevelopment during first trimester before fetal thyroid function begins at 10-12 weeks. Levothyroxine replacement in hypothyroid women reduces risk of maternal complications (preeclampsia, abruption) and adverse fetal outcomes (low IQ, preterm birth, low birth weight). Overtreatment (hyperthyroidism) carries risks of miscarriage, fetal tachycardia, and growth restriction. Untreated maternal hypothyroidism increases risk of neural tube defects, cognitive impairment, and neonatal hypothyroidism. No known teratogenic effects at therapeutic doses. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Uncorrected adrenal insufficiency","Untreated thyrotoxicosis","Hypersensitivity to levothyroxine or any component"]
| Precautions | ["Cardiac toxicity (angina, arrhythmias, myocardial infarction) due to excessive dose","Thyrotoxic crisis (overdosage)","Increased bone resorption and osteoporosis risk with chronic TSH suppression","Masking of underlying cardiovascular disease","Interaction with warfarin (increased INR)","Concurrent use with antidiabetic agents (may increase insulin/oral hypoglycemic requirements)"] |
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| Fetal Monitoring | Monitor maternal serum TSH every 4-6 weeks during first half of pregnancy, then at least once per trimester. Target TSH 0.2-2.5 mIU/L in first trimester, 0.3-3.0 mIU/L in second/third. Check free T4 if TSH is abnormal. Fetal surveillance indicated if maternal thyroid disease is poorly controlled or if fetal goiter/hypothyroidism suspected (by ultrasound growth parameters, heart rate, or amniotic fluid volume). Neonatal thyroid screening (heel-stick TSH) within 24-48 hours of birth is mandatory. |
| Fertility Effects | Uncontrolled hypothyroidism (elevated TSH) causes anovulation, menstrual irregularities, hyperprolactinemia, and reduced fertility. Levothyroxine correction restores ovulatory cycles and improves pregnancy rates in infertile hypothyroid women. No direct negative effects on fertility at therapeutic doses. |