Levothyroxine Sodium

Thyroid hormone Synthetic L-thyroxine (T4)

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO 0.1-0.2 mg/kg (initial), adjust based on T4 levels q12h Duration: Lifelong
Notes: Start at lower end, recheck T4 at 4-6 weeks, adjust dose. Administer on empty stomach or consistently with food.
Cat PO 0.05-0.1 mg/cat (initial) q12h Duration: Lifelong
Notes: Use lower dose, monitor T4 levels. Cats are sensitive to overdosage.
Horse PO 10-20 mg/horse (initial) q24h Duration: Variable
Notes: Absorption is poor; monitor thyroid levels. Not commonly used.
Cattle PO Not established Not established Duration: Not established
Notes: Not commonly used; consult veterinary endocrinologist.

Clinical Indications & Species Uses

General Indications
  • Replacement therapy for hypothyroidism in various species
Dog (Canine)
  • Hypothyroidism (primary, secondary, tertiary)
  • Replacement therapy after thyroidectomy
  • Management of myxedema coma (adjunctive)
Cat (Feline)
  • Hypothyroidism (rare, usually iatrogenic after treatment of hyperthyroidism)
  • Replacement therapy after thyroidectomy
Horse (Equine)
  • Hypothyroidism (rare)
  • Equine metabolic syndrome (investigational, not standard)
Cattle (Bovine)
  • May be used experimentally for reproductive disorders

Pharmacology & Mechanism of Action

Drug Class: Thyroid hormone | Pharmacological Group: Synthetic L-thyroxine (T4)

Mechanism of Action: Levothyroxine sodium is a synthetic form of the endogenous thyroid hormone thyroxine (T4). It is converted in peripheral tissues to the more active triiodothyronine (T3) via deiodination. T3 binds to nuclear thyroid hormone receptors, modulating gene transcription and increasing the synthesis of proteins involved in cellular metabolism, growth, and differentiation. This results in increased basal metabolic rate, oxygen consumption, and heat production, and affects nearly all organ systems.

Pharmacodynamics: Levothyroxine increases the metabolic rate of body tissues, enhances carbohydrate and lipid metabolism, and stimulates protein synthesis. It increases heart rate and cardiac contractility, enhances gastrointestinal motility, and promotes normal growth and development. In hypothyroid animals, it restores normal thyroid hormone levels, alleviating clinical signs such as lethargy, weight gain, dermatologic changes, and reproductive abnormalities.

⚡ Pharmacokinetics Summary

Absorption: Levothyroxine is well absorbed from the gastrointestinal tract, but absorption is variable and influenced by food, gastric pH, and concurrent medications. In dogs, oral bioavailability is approximately 20-40% when given with food, but can be higher when given on an empty stomach. In horses, absorption is poor and erratic.
Distribution: Levothyroxine is extensively bound to plasma proteins (thyroxine-binding globulin, transthyretin, albumin). It distributes into tissues, with a volume of distribution of about 0.2-0.3 L/kg in dogs. It crosses the placenta and is distributed into milk in small amounts.
Metabolism: Levothyroxine is metabolized primarily in the liver, kidneys, and other tissues by deiodination to T3 and reverse T3 (rT3). It also undergoes conjugation (glucuronidation and sulfation) and deamination. The metabolic clearance is increased by drugs that induce hepatic enzymes (e.g., phenobarbital).
Excretion: The metabolites are excreted in the bile and feces, with a small amount in the urine. In dogs, the elimination half-life is approximately 12-24 hours. In cats, it is about 8-12 hours. In horses, the half-life is shorter, around 6-8 hours.
Half-Life: Dogs: 12-24 hours; Cats: 8-12 hours; Horses: 6-8 hours
Bioavailability: Oral: 20-40% in dogs (fasted), lower with food; variable in other species
Protein Binding: >99% bound to plasma proteins (thyroxine-binding globulin, transthyretin, albumin)

Available Formulations & Strengths

Oral Tablet 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg (PO)
Injectable Solution 200 mcg/mL (for IV use in myxedema coma) (IV)

Contraindications & Clinical Warnings

Contraindications:
  • Hypersensitivity to levothyroxine or any component
  • Untreated adrenal insufficiency (Addison's disease)
  • Untreated thyrotoxicosis
  • Acute myocardial infarction (in humans; use with caution in animals)
  • Concurrent use with ketamine (risk of hypertension and tachycardia)
Warnings & Clinical Precautions:
  • Use with caution in animals with cardiovascular disease (e.g., heart failure, hypertension) as it may exacerbate conditions.
  • Use with caution in animals with diabetes mellitus; may increase insulin requirements.
  • Use with caution in animals with adrenal insufficiency; may precipitate adrenal crisis.
  • Monitor thyroid hormone levels regularly to avoid overdosage or underdosage.
  • In cats, use with caution as they are sensitive to thyroid hormone supplementation.
  • Do not use in animals with known hypersensitivity.
  • Administer consistently with respect to meals to maintain stable absorption.

Adverse Effects & Reactions

Common:

  • Polyphagia
  • Weight loss
  • Increased thirst and urination
  • Hyperactivity
  • Tachycardia
  • Panting

Serious / Severe:

  • Cardiac arrhythmias
  • Hypertension
  • Thyrotoxicosis (overdosage)
  • Adrenal crisis (in animals with underlying adrenal insufficiency)

Rare:

  • Allergic reactions (urticaria, angioedema)
  • Seizures (in overdosage)

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Phenobarbital Increases hepatic metabolism of levothyroxine, reducing its efficacy. Moderate
Rifampin Increases metabolism of levothyroxine, reducing its efficacy. Moderate
Sucralfate Decreases absorption of levothyroxine; separate administration by at least 2 hours. Moderate
Aluminum hydroxide antacids Decreases absorption of levothyroxine; separate administration by at least 2 hours. Moderate
Iron supplements Decreases absorption of levothyroxine; separate administration by at least 2 hours. Moderate
Calcium carbonate Decreases absorption of levothyroxine; separate administration by at least 2 hours. Moderate
Ketamine May increase risk of hypertension and tachycardia. High
Tricyclic antidepressants May potentiate effects of both drugs on the cardiovascular system. Moderate

Overdose & Toxicity Management

Signs of Toxicity:

  • Vomiting
  • Diarrhea
  • Hyperactivity
  • Tachycardia
  • Tremors
  • Hyperthermia
  • Seizures
  • Cardiac arrhythmias

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Induce vomiting if recent ingestion and animal is stable. Administer activated charcoal to reduce absorption. Provide supportive care including IV fluids, cooling measures for hyperthermia, and antiarrhythmic drugs if needed. Beta-blockers (e.g., propranolol) may be used to control tachycardia. Monitor thyroid hormone levels and cardiac function. In severe cases, consider administration of cholestyramine to enhance elimination.

Food Animal Withdrawal Times

Not approved for use in food animals; withdrawal times not established. Use in food animals is off-label and requires veterinary oversight.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 20-25°C (68-77°F), excursions permitted between 15-30°C (59-86°F).

Light Sensitivity: Light-sensitive — protect from direct exposure.

Handling & Special Conditions: Protect from light and moisture. Keep in original container.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for use in dogs and cats for hypothyroidism. Not approved for other species.

Extra-Label (Off-Label) Use: In the US, extra-label use in food animals is prohibited unless under a valid VCPR and with appropriate withdrawal times established. Not approved for use in food animals.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Levothyroxine is the drug of choice for replacement therapy in hypothyroid dogs. It is important to diagnose hypothyroidism based on clinical signs and thyroid function tests (e.g., low total T4, high TSH). Therapy should be individualized, and monitoring of serum T4 levels is essential to avoid under- or over-dosing. In dogs, the goal is to maintain serum T4 within the normal reference range (typically 1-4 μg/dL) at 4-6 hours post-pill. Cats are more sensitive, and lower doses are used. In horses, oral absorption is poor, and parenteral forms are not practical; thus, levothyroxine is rarely used. For food animals, there are no approved indications, and extra-label use is discouraged due to lack of withdrawal data. Always consider concurrent diseases (e.g., adrenal insufficiency, diabetes) and adjust therapy accordingly. Patient compliance is critical; administer consistently with or without food to maintain stable absorption.

References & Literature

  • 📚 Plumb's Veterinary Drug Handbook
  • 📚 Papich Veterinary Pharmacology and Therapeutics
  • 📚 Compendium of Veterinary Products (CVP)