Indications

Thyrin (Levothyroxine Sodium) is indicated for:

Replacement therapy in hypothyroidism of any etiology.
Replacement therapy should not be initiated in transient hypothyroidism during the recovery phase of subacute thyroiditis.
Suppression of Thyroid Stimulating Hormone (TSH) levels in the presence of goitre, thyroid nodules, and after radiological and/or surgical treatment of thyroid cancer.
Suppression of the goitrogenic effects of other drugs such as lithium.
As a diagnostic aid in thyroid suppression tests.

Pharmacology

Levothyroxine (T4) is a synthetic form of thyroxine, identical to the natural hormone produced by the thyroid gland.

Approximately 30% of T4 is converted in peripheral tissues to triiodothyronine (T3), the more biologically active thyroid hormone.
Thyroxine-binding globulin (TBG) is the major carrier protein for T4.
Only about 0.03% of circulating T4 remains unbound.
The elimination half-life of T4 is approximately 6 to 7 days.
In hyperthyroidism, the half-life decreases to 3 to 4 days, while in hypothyroidism it may increase to 9 to 10 days.
Levothyroxine is metabolized mainly in the liver and excreted through urine after conjugation.
Due to its long half-life, a stable blood concentration can usually be maintained with once-daily dosing.

Dosage and Administration

Adults

Initial Dose

25-50 mcg daily.
Increase gradually every 2-6 weeks as required.

Severe Hypothyroidism

Start with 12.5-25 mcg daily.
Increase by 25 mcg every 2-4 weeks based on clinical and laboratory assessment.

Secondary or Tertiary Hypothyroidism

Adjust dose until the patient becomes clinically euthyroid and free T4 levels are restored to the upper half of the normal range.

Adults >50 Years or Patients with Cardiac Disease

Approximately 1.7 mcg/kg/day.

Pediatric Dosage

Newborns

Recommended starting dose: 10-15 mcg/kg/day.
Lower starting doses may be considered in infants at risk of cardiac failure.
In infants with very low or undetectable serum T4 concentrations, an initial dose of 50 mcg/day may be used.

Infants and Children

For chronic or severe hypothyroidism:

Initial dose: 25 mcg/day.
Increase by 25 mcg every 2-4 weeks until the desired response is achieved.

Recommended Daily Doses

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 (growth and puberty incomplete): 2-3 mcg/kg/day
Growth and puberty complete: 1.7 mcg/kg/day

Dosage should be adjusted according to clinical response and laboratory findings.

Drug Interactions

Tricyclic and tetracyclic antidepressants may have increased therapeutic and toxic effects when administered with levothyroxine.
Sertraline may increase levothyroxine requirements.
Levothyroxine may increase insulin or oral antidiabetic drug requirements.
Serum digitalis glycoside levels may decrease when hypothyroid patients become euthyroid.

Contraindications

Untreated subclinical or overt thyrotoxicosis.
Acute myocardial infarction.
Uncorrected adrenal insufficiency.

Side Effects

Side effects are generally associated with excessive dosing and symptoms of hyperthyroidism.

General

Fatigue
Increased appetite
Weight loss
Heat intolerance
Excessive sweating

Central Nervous System

Headache
Hyperactivity
Nervousness
Anxiety
Irritability
Emotional instability
Insomnia

Musculoskeletal

Tremors
Muscle weakness

Cardiovascular

Palpitations
Tachycardia
Arrhythmias
Increased pulse rate
Elevated blood pressure

Respiratory

Dyspnoea

Gastrointestinal

Diarrhoea
Vomiting
Abdominal cramps

Dermatological

Hair loss
Itching

Pregnancy and Lactation

Pregnancy Category A

Pregnancy may increase levothyroxine requirements.
Thyroid hormones are secreted in very small amounts into breast milk.
Adequate replacement doses are generally necessary to maintain normal lactation.

Precautions and Warnings

Patients with pituitary-related hypothyroidism may also have adrenal insufficiency which should be treated before starting levothyroxine.
Careful dose titration is required in patients with cardiovascular disease or long-standing severe hypothyroidism.
Excessive initial doses may worsen angina, arrhythmias, myocardial infarction, cardiac failure, or hypertension.
Significant body weight changes may require dose adjustments.
TSH monitoring is generally used to establish the correct dose in primary hypothyroidism.

Overdose

Symptoms of overdose resemble hyperthyroidism and may include:

Agitation
Confusion
Irritability
Hyperactivity
Headache
Sweating
Dilated pupils
Tachycardia
Arrhythmias
Tachypnoea
Fever
Increased bowel movements
Convulsions

Severe cases may result in shock, coma, or death.

Management

Reduce the dose or temporarily discontinue treatment.
Provide symptomatic and supportive care.