SYNTHROID
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SYNTHROID (SYNTHROID).
Synthetic levothyroxine is a replacement for endogenous thyroid hormone. It binds to thyroid hormone receptors (TRα and TRβ) in the nucleus, regulating gene transcription involved in metabolism, growth, and development.
| Metabolism | Hepatic (deiodination via D1 and D2 enzymes, conjugation with glucuronides and sulfates, and microsomal metabolism). |
| Excretion | Renal: ~20-40% of T4 and T3 metabolites excreted in urine as glucuronide and sulfate conjugates; fecal: ~40-60% as unchanged drug and conjugates via biliary elimination; minor amounts in bile and feces as deiodinated products. |
| Half-life | Levothyroxine (T4) terminal elimination half-life: 6-7 days in euthyroid patients; shortened to 3-4 days in hyperthyroidism and prolonged to 9-10 days in hypothyroidism; clinical context: supports once-daily dosing with steady-state reached after 6-8 weeks. |
| Protein binding | >99% bound primarily to thyroxine-binding globulin (TBG), with lesser binding to transthyretin (TTR) and albumin; affinity: T4 > T3. |
| Volume of Distribution | 0.10-0.15 L/kg for T4; distributes primarily into extracellular fluid and highly perfused tissues; clinical meaning: small Vd reflects extensive plasma protein binding and limited tissue distribution; hypothyroidism may increase Vd. |
| Bioavailability | Oral: 40-80% (mean ~50-75%) due to incomplete absorption; fasting and consistent intake maximize absorption; IV: 100%. |
| Onset of Action | Oral: therapeutic effect on TSH suppression and metabolic rate begins within 3-5 days; full clinical response in 2-4 weeks; IV: onset within 6-12 hours for myxedema coma. |
| Duration of Action | Duration of TSH suppression and metabolic effects persists for 2-3 weeks after discontinuation due to long half-life; clinical note: dose adjustments require 6-8 weeks to assess full effect. |
Initial adult dose 1.6 mcg/kg orally once daily, adjusted by 12.5-25 mcg increments every 6-8 weeks based on TSH levels. Maintenance dose typically 100-125 mcg/day.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for renal impairment. Monitor TSH levels in patients with end-stage renal disease as thyroid hormone requirements may be decreased. |
| Liver impairment | No specific dose adjustment for Child-Pugh class A or B. In Child-Pugh class C, initial dose reduction of 25-50% recommended due to reduced metabolism; titrate based on TSH. |
| Pediatric use | Initial dose: Birth-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 once daily orally. |
| Geriatric use | Initial dose 12.5-25 mcg orally once daily, with gradual titration by 12.5 mcg increments every 4-6 weeks. Lower doses due to decreased metabolism and increased sensitivity to thyroid hormones. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SYNTHROID (SYNTHROID).
| Breastfeeding | Levocetirizine is excreted into breast milk. M/P ratio not well defined. Small amounts of levothyroxine are excreted in breast milk, but amounts are insufficient to cause hyperthyroidism in the infant. Use is considered compatible with breastfeeding. |
| Teratogenic Risk | No known teratogenic risk; placental transfer of levothyroxine is minimal. Thyroid hormones do not cross the placenta in significant amounts. Hypothyroidism in pregnancy increases risks of miscarriage, preterm delivery, preeclampsia, and fetal neurodevelopmental deficits, but thyroxine replacement is essential and not teratogenic. |
■ FDA Black Box Warning
Not indicated for treatment of obesity or for weight loss. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may cause serious or even life-threatening toxicity.
| Serious Effects |
["Uncorrected adrenal insufficiency","Thyrotoxicosis (e.g., hyperthyroidism, thyroid storm)","Acute myocardial infarction","Hypersensitivity to any component"]
| Precautions | ["May cause thyrotoxicosis if dose is excessive (e.g., tachycardia, chest pain, arrhythmias, heat intolerance).","Cardiac toxicity: Atrial fibrillation, heart failure, myocardial ischemia.","Bone effects: Decreased bone mineral density with prolonged overtreatment.","Endocrine effects: Adrenal insufficiency unmasked (treat with corticosteroids before therapy).","Diabetes mellitus: May increase need for antidiabetic agents.","Myxedema coma: Rapid IV administration can cause arrhythmias or MI.","Concurrent warfarin: Enhanced anticoagulant effect.","Pregnancy: Dose requirements may increase."] |
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| Fetal Monitoring | Monitor maternal thyroid function (serum TSH and free T4) every 4 weeks during first half of pregnancy, then every 4-6 weeks after 20 weeks. Adjust dose to maintain TSH within trimester-specific reference ranges (first trimester: 0.1-2.5 mIU/L, second: 0.2-3.0 mIU/L, third: 0.3-3.0 mIU/L). Assess fetal growth and development by ultrasound as clinically indicated. |
| Fertility Effects | Hypothyroidism is associated with ovulatory dysfunction and infertility; thus restoration of euthyroid state with levothyroxine improves fertility. No direct adverse effect on fertility from therapeutic doses. |