Hypothyroidism - Primary (thyroidal), secondary (pituitary), & tertiary (hypothalamic) hypothyroidism & subclinical hypothyroidism. Pituitary TSH Suppression
This preparation contains synthetic Levothyroxine (also called Thyroxine or T4) which is identical to the natural hormone T4, produced in the Thyroid gland. About 30% of T4 is converted to the much more active Triiodothyronine (T3) in peripheral tissues. TBG (Thyroxine Binding Globulin) is the major carrier of T4. This binding protects T4 from metabolism and excretion resulting in its long half-life in the circulation. Only about 0.03% of total T4 in plasma is unbound. The half-life of elimination of T4 is 6 to 7 days. In hyperthyroidism, the half-life is shortened to 3 or 4 days, whereas in hypothyroidism it may be 9 to 10 days. In conditions associated with reduced protein in plasma as in nephrosis or hepatic cirrhosis or when binding to protein is inhibited by certain drugs the half-life of T4 may be shortened. The liver is the major site of degradation of Thyroid hormones. T4 is conjugated with Glucuronic and Sulphate conjugates through the Phenolic hydroxyl group and excreted in the urine.There is an enterohepatic circulation of the Thyroid hormones, since they are liberated by hydrolysis in the intestine and reabsorbed. Because of the long half-life of T4, a steady blood level of the biologically more active T3 can be obtained from one single daily dose of Levothyroxine. Therefore, variations in the therapeutic effect are unlikely once the correct dosage has been established.
Dosing must be individualized & adjustments made based on periodic assessment of the patient’s clinical response & laboratory parameters. a) Adult Dosage Initial starting dose: 25-50 mcg/day, with gradual increments in dose at 6-8 week intervals as needed. The dose is generally adjusted in 12.5-25 mcg increments until the patient with primary hypothyroidism is clinically euthyroid & the serum TSH has normalized. In patients with severe hypothyroidism: 12.5- 25 mcg/day with gradual increment of 25 mcg/ day every 2-4 weeks. In patients with secondary (pituitary) or tertiary (hypothalamic) hypothyroidism: The dose should be titrated until the patient is clinically euthyroid & the serum free- T4 level is restored to the upper half of the normal range. For patients older than 50 years or for patients under 50 years of age with underlying cardiac disease: 1.7 mcg/kg/day. b) Pediatric Dosage Newborns The recommended starting dose is 10-15 mcg/ kg/day. In infants with very low (< 5 mcg/dL) or undetectable serum T4 concentrations, the recommended initial starting dose is 50 mcg/ day. Infants & Children Initial dose is 25 mcg/day with increments of 25 mcg every 2-4 weeks until the desired effect is achieved. c) Daily dose per Kg body weight 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 but growth & puberty incomplete: 2-3 mcg/kg/day Growth & puberty complete: 1.7 mcg/kg/day
Concurrent use of tri/tetracyclic antidepressants and Levothyroxine may increase the therapeutic and toxic effects of both drugs, possibly due to increased receptor sensitivity to catecholamines.Toxic effects may include increased risk of cardiac arrhythmias and CNS stimulation; onset of action of tricyclics may be accelerated. Administration of sertraline in patients stabilized on Levothyroxine may result in increased Levothyroxine requirements. Addition of Levothyroxine to antidiabetic or insulin therapy may result in increased antidiabetic agent or insulin requirements. Careful monitoring of diabetic control is recommended, especially when thyroid therapy is started, changed, or discontinued. Serum digitalis glycoside levels may be reduced in hyperthyroidism or when the hypothyroid patient is converted to the euthyroid state. Therapeutic effect of digitalis glycosides may be reduced.
Contraindicated in the following conditions: • Untreated subclinical or overt thyrotoxicosis of any etiology & acute myocardial infarction, • Uncorrected adrenal Levothyroxine has a narrow therapeutic index. So, careful dosage titration is necessary to avoid the consequences of over- or under-treatment.
Adverse reactions associated with Levothyroxine therapy are primarily those of hyperthyroidism due to therapeutic overdose. They include the following: fatigue, increased appetite, weight loss, heat intolerance, fever, excessive sweating, headache, nervousness, anxiety, irritability, tremors, muscle weakness, palpitations etc.
US FDA Pregnancy Category A. Pregnancy may increase Levothyroxine requirements. Thyroid hormones are excreted minimally in human milk; caution should be exercised when it is administered to a nursing woman.
The signs and symptoms of overdose are those of hyperthyroidism - agitation, confusion, irritability, hyperactivity, headache, sweating, mydriasis, tachycardia, arrhythmias, tachypnoea, pyrexia, increased bowel movements and convulsions. Cerebral embolism, shock, coma, and death have been reported. Symptoms may not necessarily be evident or may not appear until several days after ingestion of Levothyroxine Sodium. Dose of Levothyroxine Sodium should be reduced or temporarily discontinued if signs or symptoms of overdosage occur. Treatment is symptomatic.
Store below 30°C and dry place, protect from light. Keep out of the reach of children.
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