Liothyronine | Levothyroxine

Oral capsule: Administer orally at the same time each day, ideally 30–60 minutes before breakfast on an empty stomach to optimize T4 absorption (which is lower — ~60–80% — compared to T3's ~95%). Avoid co-administration within 4 hours of calcium, iron, antacids, proton pump inhibitors, or bile acid sequestrants, all of which reduce levothyroxine absorption significantly. Swallow whole; do not crush or chew. Consistency of timing relative to meals is critical for stable serum levels, particularly for the T4 component.

Dosing of each component is individualized and determined by the prescriber based on clinical status, serum TSH, free T4, and free T3 levels.

• T4 component: Typical adult replacement doses range from 50–200 mcg/day, with starting doses of 25–50 mcg in elderly patients or those with cardiovascular disease.
• T3 component: Starting doses of 5–25 mcg/day; upward titration proceeds cautiously in 5–12.5 mcg increments every 2–4 weeks.
• The ratio of T4 to T3 in a combination formula is tailored to approximate physiologic thyroid output and the patient's individual conversion capacity.
• Monitor TSH, free T4, and free T3 periodically; in combination therapy, total T3 measurement may help guide acute adequacy since TSH tracks T4 levels more closely.
• Final formulation strength and dosing schedule are determined solely by the prescriber.

• Levothyroxine (T4): A prohormone that is peripherally deiodinated (primarily in the liver and kidney) to the biologically active T3 by type 1 and type 2 deiodinases. T4 itself binds thyroid hormone receptors with lower affinity than T3, serving mainly as a reservoir. It has a long half-life (~8 days), producing stable serum concentrations and predictable TSH feedback.
• Liothyronine (T3): Binds with high affinity to nuclear thyroid hormone receptors (THR-α and THR-β), directly activating gene transcription and protein synthesis. It increases basal metabolic rate, cardiac output, thermogenesis, protein and lipid metabolism, and CNS maturation. Onset of action is within hours; maximum effect within 2–3 days. It does not require deiodination for activity, making it particularly useful in patients with impaired T4-to-T3 conversion.

Clinical context: Combination T3/T4 therapy is considered for patients with persistent hypothyroid symptoms despite adequate levothyroxine monotherapy and normalized TSH — a population in whom impaired peripheral T4-to-T3 conversion (e.g., due to deiodinase polymorphisms or autoimmune thyroid disease) may leave tissue T3 levels suboptimal. It may also be used during thyroid cancer radioiodine preparation and in select cases of myxedema management.

Monitoring considerations:

• Measure TSH, free T4, and free T3 at baseline, 6–8 weeks after any dose change, then every 6–12 months when stable.
• Monitor for symptoms of over-replacement (palpitations, heat intolerance, insomnia, weight loss, tremor).
• Bone mineral density in long-term therapy, particularly in postmenopausal women.
• Adjust anticoagulant and antidiabetic doses as needed when initiating or changing thyroid therapy.

Contraindications:

• Uncorrected adrenal insufficiency
• Acute myocardial infarction (without hypothyroidism) or uncontrolled cardiac arrhythmias
• Not for weight loss or obesity treatment

Warnings & Precautions:

• Both components carry risk of thyrotoxicosis with over-replacement — cardiac arrhythmias, angina, and bone loss are primary concerns
• The T3 component has a faster onset and shorter half-life, increasing risk of supratherapeutic peak levels if not carefully titrated
• Elderly and cardiac patients require slower titration with smaller increments
• Pregnancy requires close monitoring — dose requirements often increase and must be adjusted per trimester-specific TSH targets

Drug Interactions:

• Calcium, iron, antacids, PPIs: significantly reduce T4 (levothyroxine) absorption — separate by ≥4 hours
• Warfarin: enhanced anticoagulation — monitor INR at each dose change
• Rifampin, phenobarbital, carbamazepine: increased thyroid hormone metabolism
• Amiodarone: inhibits peripheral T4-to-T3 conversion, altering T3 levels
• Sympathomimetics, tricyclic antidepressants: potentiated effects — monitor cardiovascular status

Common Side Effects: Signs of over-replacement — palpitations, tachycardia, weight loss, tremor, insomnia, heat intolerance, sweating, diarrhea, anxiety.

Store at controlled room temperature (20–25°C / 68–77°F), away from light and moisture. Do not expose to extreme heat or cold. Keep in the original dispensing container with the cap tightly closed. Observe the beyond-use date assigned by Genesis Compounding. Discard unused medication appropriately.

Why combine T3 and T4 instead of levothyroxine alone?

Some patients do not adequately convert T4 to the active T3 in peripheral tissues, resulting in persistent hypothyroid symptoms despite a normal TSH on levothyroxine alone. A compounded combination allows the prescriber to fine-tune each hormone fraction individually.

How are the doses of T3 and T4 determined in the combination?

The prescriber individuates the ratio based on laboratory values (TSH, free T3, free T4), symptom response, body weight, cardiovascular status, and the patient's conversion capacity. There is no single fixed ratio appropriate for all patients.

Should I take this with food?

Take on an empty stomach, 30–60 minutes before breakfast, for optimal T4 absorption. The T3 component absorbs rapidly regardless of food, but consistency of administration timing is important for stable levels.

How often will I need lab tests?

Typically at 6–8 weeks after any dose change, then every 6–12 months when stable. The prescriber may order TSH, free T4, and free T3 depending on clinical context.

Is this combination FDA-approved?

Commercial liothyronine and levothyroxine products are each FDA-approved individually; this specific compounded combination is a prescriber-directed, patient-specific preparation under 503A compounding rules and has not been evaluated by the FDA for safety or efficacy as a compounded product.