EUTHYROX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EUTHYROX (EUTHYROX).
Synthetic levothyroxine is a T4 hormone that is converted to T3, binding to thyroid hormone receptors to regulate gene transcription, increasing basal metabolic rate, cardiac output, and thermogenesis.
| Metabolism | Partially deiodinated to active T3 and inactive reverse T3 (rT3) in liver, kidney, and other tissues. Conjugation with glucuronides and sulfates. Minimal CYP450 involvement. |
| Excretion | Primarily renal (approximately 40-50% as unchanged drug and metabolites), with about 20% fecal elimination via bile. Minor biliary excretion. |
| Half-life | Terminal half-life: 6-7 days in euthyroid individuals. Longer in hypothyroidism (9-10 days) and shorter in hyperthyroidism (3-4 days). Clinically, steady-state achieved in 4-6 weeks. |
| Protein binding | >99.9% bound to thyroxine-binding globulin (TBG), transthyretin (TTR), and albumin. Lewothyroxine is the active form. |
| Volume of Distribution | 0.10-0.15 L/kg, reflecting distribution primarily into extracellular fluid and tissues with high affinity binding to thyroid hormone receptors. |
| Bioavailability | Oral: 50-80% (variable, influenced by food, GI disease, and formulation). IV: 100%. |
| Onset of Action | Oral: clinical effects noticeable within 3-5 days. IV: onset within 6-8 hours. |
| Duration of Action | Clinical effects last approximately 2-3 weeks after discontinuation due to long half-life. However, T4 levels remain elevated for up to 6 weeks. |
| Molecular Weight | 776.87 |
Initial adult dose 25-50 mcg orally once daily; titrate by 12.5-25 mcg increments every 4-6 weeks; maintenance dose typically 100-200 mcg daily.
| Dosage form | TABLET |
| Renal impairment | No renal adjustment required as levothyroxine is primarily metabolized and excreted in feces. Monitor TSH and free T4 in patients with severe renal impairment. |
| Liver impairment | No specific Child-Pugh adjustment; however, severe hepatic impairment may reduce T4 to T3 conversion; monitor thyroid function tests. |
| 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. Administer orally once daily. |
| Geriatric use | Elderly patients (especially >65 years) or those with cardiovascular disease: start at 12.5-25 mcg orally once daily; increase by 12.5 mcg every 4-6 weeks; lower maintenance doses often required. |
| 1st trimester | Levothyroxine is safe and essential in pregnancy; dose adjustments are often needed due to increased maternal thyroid-binding globulin and increased fetal thyroid hormone requirements. Monitor TSH levels closely. |
| 2nd trimester | Continue therapy; doses may need to be increased by 30–50% above preconception dose. Monitor TSH every 4–6 weeks. |
| 3rd trimester | Continue therapy; adjust dose to maintain TSH within trimester-specific reference range. Postpartum dose reduction may be needed. |
Clinical note
Comprehensive clinical and safety monograph for EUTHYROX (EUTHYROX).
| Placental transfer | Limited placental transfer; levothyroxine crosses the placenta in small amounts, but maternal levels are essential for fetal neurodevelopment. Endogenous fetal thyroid function begins around 12 weeks, requiring maternal hormone until then. |
| Breastfeeding | Levothyroxine is excreted into breast milk in minimal amounts, insufficient to affect infant thyroid function. Considered compatible with breastfeeding; monitor infant thyroid function if clinically indicated. |
■ FDA Black Box Warning
Not approved for weight loss. Doses above physiologic requirements may produce serious or life-threatening toxicity, especially when used with sympathomimetic amines.
| Common Effects | Palpitations Vomiting Anxiety Diarrhea Weight loss Nervousness Increased appetite Tremors |
| Serious Effects |
Untreated subclinical or overt hyperthyroidismUncorrected adrenal insufficiencyRecent myocardial infarctionHypersensitivity to levothyroxine or any excipient
| Precautions | Cardiovascular effects (angina, arrhythmias, hypertension) in patients with underlying heart disease. Risk of thyrotoxic crisis if dose is excessive. Adrenal insufficiency: adjust corticosteroid dose before starting in patients with adrenal insufficiency. Diabetes mellitus: may increase blood glucose and require adjustment of antidiabetic therapy. Osteoporosis: chronic TSH suppression increases risk of bone loss. Interactions with anticoagulants (warfarin), antidiabetic agents, and SSRIs. Discontinue use for weight loss due to serious toxicity. |
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| Lactation Rating | L1 (Safe) |
| Teratogenic Risk | EUTHYROX (levothyroxine) is a thyroid hormone replacement. Maternal hypothyroidism itself carries significant risks to the fetus, including neurodevelopmental deficits, preterm birth, and low birth weight. The drug does not cross the placenta significantly; fetal thyroid function is independent. No known teratogenic effects from levothyroxine at therapeutic doses. First trimester: essential for maternal euthyroidism to prevent fetal neurodevelopmental impairment. Second and third trimesters: maintenance of maternal euthyroidism supports normal fetal growth and development. Insufficient treatment increases risks. |
| Fetal Monitoring | Monitor maternal thyroid function (TSH, free T4) every 4 weeks during pregnancy (especially first trimester) and after dose adjustments. Adjust dose to maintain TSH within trimester-specific reference ranges. Fetal monitoring includes ultrasound for growth, heart rate, and anatomy as per standard obstetric care. No specific fetal drug toxicity monitoring required. |
| Fertility Effects | Untreated hypothyroidism can cause menstrual irregularities, anovulation, and impaired fertility. Restoration of euthyroidism with levothyroxine normalizes reproductive function. No direct adverse effects on fertility from levothyroxine; it improves fertility outcomes in hypothyroid women. |
| Food/Dietary | Levothyroxine absorption is decreased by high-fiber foods (e.g., bran, whole grains), soy products, grapefruit juice, walnuts, and cottonseed meal. Also, calcium-fortified foods and beverages can reduce absorption. Take levothyroxine at least 4 hours apart from these foods. Avoid concomitant ingestion with coffee or milk; if needed, maintain consistency. Caffeine may slightly reduce absorption. |
| Clinical Pearls | Levothyroxine (EUTHYROX) is the standard therapy for hypothyroidism. Absorption is reduced by calcium, iron, soy, and fiber; take on an empty stomach 30-60 minutes before breakfast. Dose adjustments needed in pregnancy, weight changes, and with interacting drugs (e.g., estrogens, rifampin, phenytoin). Monitor TSH 6-8 weeks after dose change. In hyperthyroidism, rapid levothyroxine withdrawal can precipitate thyroid storm; taper cautiously. For myxedema coma, use IV levothyroxine (not oral). When switching from a T3-containing preparation, cross-titration is required. |
| Patient Advice | Take levothyroxine exactly as prescribed, at the same time each day. · Take on an empty stomach, at least 30-60 minutes before breakfast or any food. · Do not take with calcium supplements, iron supplements, antacids, or high-fiber foods; separate by at least 4 hours. · Do not stop or change dose without consulting your doctor. · If you miss a dose, take it as soon as you remember, but skip if it is almost time for the next dose; do not double dose. · Report symptoms of hyperthyroidism (rapid heart rate, palpitations, anxiety, weight loss) or hypothyroidism (fatigue, weight gain, cold intolerance). · Blood tests (TSH) will be done regularly to monitor dose. · Tell your doctor if you are pregnant, planning pregnancy, or breastfeeding. · Keep all medications out of reach of children. |