CYTOMEL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CYTOMEL (CYTOMEL).
Liothyronine (T3) is a synthetic thyroid hormone that binds to thyroid hormone receptors in the nucleus, altering gene transcription and increasing basal metabolic rate, protein synthesis, and cardiovascular function.
| Metabolism | Primarily hepatic conjugation (glucuronidation and sulfation) and minor deiodination; not extensively metabolized by cytochrome P450. |
| Excretion | Liothyronine (T3) is primarily eliminated by hepatic metabolism (deiodination and conjugation). Approximately 50-60% of a dose is excreted in urine as metabolites, with less than 5% as unchanged drug. Fecal excretion accounts for about 20-30% via biliary elimination of conjugates. |
| Half-life | The terminal elimination half-life of liothyronine is approximately 1.0-2.5 days in euthyroid individuals, but may be prolonged in hypothyroidism (up to 3-4 days) and shortened in hyperthyroidism. Clinical context: This short half-life allows rapid dose titration and withdrawal for thyroid suppression tests. |
| Protein binding | 99.7% bound to plasma proteins, primarily thyroxine-binding globulin (TBG) (80%), transthyretin (10%), and albumin (10%). |
| Volume of Distribution | Volume of distribution is approximately 0.4-0.6 L/kg, indicating distribution into total body water. Clinical meaning: Vd is lower than for T4 due to higher protein binding; rapid distribution into tissues occurs. |
| Bioavailability | Oral bioavailability is approximately 95% (range 90-100%) when taken on an empty stomach; food may slightly reduce absorption. Intravenous bioavailability is 100%. |
| Onset of Action | Oral: Onset of action is 2-4 hours, with peak effect occurring at 2-3 days. Intravenous: Onset within 2-4 hours, peak effect at 12-48 hours. Clinical note: Full therapeutic effect may require several days due to tissue distribution and peripheral conversion to T4. |
| Duration of Action | Duration of action is approximately 3-5 days after a single oral dose, but steady-state is achieved within 3-4 days of daily dosing. Liothyronine has a shorter duration compared to levothyroxine, making it suitable for thyroid suppression testing and short-term therapy. |
Initial adult dose 25 mcg orally once daily; titrate by 12.5-25 mcg increments every 1-2 weeks based on TSH and clinical response. Usual maintenance dose 50-100 mcg once daily. Maximum dose 100 mcg daily.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment required for renal impairment. |
| Liver impairment | No specific dose adjustment required for hepatic impairment; monitor thyroid function closely. |
| Pediatric use | Initial 5 mcg orally once daily; increase by 5 mcg every 2-4 weeks based on thyroid function and clinical response. Maintenance: 25-50 mcg once daily. Weight-based: 1.6-2.6 mcg/kg/day. |
| Geriatric use | Start with lower initial dose of 12.5-25 mcg orally once daily; titrate slowly (increase by 12.5 mcg every 2-4 weeks) due to increased sensitivity and higher risk of cardiac complications. Monitor TSH closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CYTOMEL (CYTOMEL).
| Breastfeeding | Liothyronine (T3) is excreted into human breast milk in low concentrations; M/P ratio not established. Exogenous T3 may suppress endogenous maternal thyroid function. Benefits of breastfeeding generally outweigh minimal risk; infant thyroid function should be monitored if mother requires high doses. Use with caution. |
| Teratogenic Risk | Pregnancy category A. Thyroid hormones do not readily cross the placenta in early pregnancy; insufficient maternal thyroid hormone may cause fetal neurodevelopmental deficits. In first trimester, untreated maternal hypothyroidism linked to miscarriage and fetal anomalies; replacement therapy reduces risk. Second and third trimesters: maternal hypothyroidism associated with preterm birth, low birth weight, and impaired cognitive development; adequate dosing is critical. No evidence of teratogenicity at therapeutic doses. |
■ FDA Black Box Warning
Not approved for weight loss; serious cardiovascular toxicity or death may occur, especially when used with sympathomimetic amines.
| Serious Effects |
["Untreated thyrotoxicosis","Acute myocardial infarction","Uncorrected adrenal insufficiency"]
| Precautions | ["Cardiovascular adverse effects (angina, arrhythmias, hypertension, myocardial infarction)","Thyrotoxicosis from excessive dosing","May increase anticoagulant effect of warfarin","May reduce glycemic control in diabetes","Bone demineralization with prolonged use"] |
| Food/Dietary | High-fiber foods, walnuts, soybean flour, and cottonseed meal may reduce absorption. Avoid excessive intake of iodine-rich foods (e.g., kelp, seaweed). Maintain consistent dietary habits for stable drug absorption. |
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| Fetal Monitoring | Monitor maternal thyroid function tests (TSH, free T4, free T3) every 2–4 weeks during pregnancy, particularly after dose changes. Fetal monitoring: ultrasound for growth and anatomy, nonstress testing in cases of poor control. Neonatal: check thyroid function at birth. |
| Fertility Effects | Euthyroid state is necessary for normal ovulation and fertility. Untreated hypo- or hyperthyroidism can cause menstrual irregularities and infertility. Restoration of euthyroidism with liothyronine typically normalizes reproductive function. |
| Clinical Pearls | Initiate at low doses (5-12.5 mcg/day) in elderly or cardiac patients; increase gradually every 1-2 weeks. Monitor TSH, T3, and T4 levels; T3 therapy can cause rapid swings in thyroid hormone levels. Use with caution in adrenal insufficiency, coronary artery disease, or diabetes insipidus. May increase warfarin sensitivity; reduce anticoagulant dose. Discontinue 2-4 weeks before thyroid uptake scans. |
| Patient Advice | Take exactly as prescribed; do not change dose without consulting your doctor. · Take on an empty stomach, at least 30 minutes before food or other medications. · Notify your doctor if you experience chest pain, rapid heartbeat, nervousness, or excessive sweating. · Do not stop suddenly; abrupt withdrawal can cause hypothyroid symptoms. · Inform all healthcare providers you are taking this medication. · May increase sensitivity to blood thinners; report signs of bleeding. |