TGP Levothyroxine Sodium

Each tablet contains Levothyroxine (as sodium) 50 mcg.

Pharmacology: Pharmacodynamics: Levothyroxine sodium is the monosodium salt of the levorotary isomer of thyroxine.
Thyroxine (T4) is a naturally occurring hormone produced by the thyroid gland and converted to the more active hormone triiodothyronine (T3) in peripheral tissues. The precise signals controlling the conversion of T4 to T3 within the cell are not known. The thyroid hormones are required for normal growth and development, particularly of the nervous system. They increase the resting or basal metabolic rate of the whole organism and have stimulatory effects on the heart, skeletal muscle, liver and kidney. Thyroid hormones enhance lipolysis and the utilization of carbohydrate.
Pharmacokinetics: Levothyroxine sodium is variably but adequately absorbed from the gastrointestinal tract following oral administration. Fasting increases absorption. Once in the circulation, levothyroxine sodium is extensively protein bound, principally to thyroxine-binding globulin (TBG) but also to a lesser extent to thyroxine-binding pre-albumin (TBPA) or to albumin.
Levothyroxine sodium has a plasma half-life in euthyroidism of about 6 to 7 days; the half-life is prolonged in hypothyroidism and reduced in hyperthyroidism.
Levothyroxine sodium is primarily metabolized in the liver and kidney to tri-iodothyronine (liothyronine) and, about 40%, to inactive reverse triiodothyronine (reverse T3) both of which undergo further deiodination to inactive metabolites. Further metabolites result from the deamination and decarboxylation of levothyroxine sodium to tetrac.
Levothyroxine sodium is reported to undergo enterohepatic recycling and excretion in the faeces.
The distribution of thyroid hormones across the placenta and into breast milk is discussed under Pregnancy and Breast feeding.

It is used as replacement therapy in the treatment of hypothyroidism, to suppress TSH production in the treatment of thyroid carcinoma and as a diagnostic agent for the differential diagnosis of hypothyroidism.

In hypothyroidism an initial adult dose of 50 to 100 mcg daily by mouth may be increased by 25 to 50 mcg at intervals of about 4 weeks until the thyroid deficiency is corrected ad maintenance dose is established.
The adult maintenance dose is usually between 100 and 200 mcg daily. In elderly patients, in those with cardiovascular disorder, or in those with severe hypothyroidism of long standing, the treatment should be introduces more gradually: an initial dose of 12.5 to 50 mcg daily increased by increments of 12.5 to 25 mcg at intervals of about 4 weeks maybe appropriate.
In children, individualization of dosage and monitoring of treatment is especially important. One recommended regimen for the treatment of congenital hypothyroidism is 10 to 15 micrograms per kg body-weight daily, adjusted as necessary. Another regimen suggests an initial dose of 5 to 10 micrograms per kg daily in children up to 1 month of age (or 5 micrograms per kg in children over 1 month), adjusted in steps of 25 micrograms every 2 to 4 weeks until mild toxic symptoms appear, at which time the dosage is slightly reduced. For juvenile myxedema, children over 1 year of age may be given 2.5 to 5 micrograms per kg body-weight daily initially.

Gastric lavage or emesis is required if the patient is seen within several hours of taking the dose. In addition to exaggeration of side effects the following symptoms may be seen: agitation, confusion, irritability, hyperactivity, headache, sweating, mydriasis, tachycardia, arrhtythmias, tachypnea, pyrexia, increased bowel movements and convulsions. The appearance of clinical hyperthyroidism may be delayed for up to five days.
Treatment is symptomatic, and tachycardia has been controlled in adults by 40 mg doses of propranolol given every six hours and other symptoms by diazepam and/or chlorpromazine as appropriate.

Hypersensitivity to any component of the preparation. Thyrotoxicosis.

Levothyroxine sodium is contraindicated in untreated hyperthyroidism. It should be used with extreme caution in patients with cardiovascular disorders including angina, heart failure, myocardial infarction, and hypertension; lower initial doses, smaller increments, and longer intervals between increases should be used as necessary. An ECG performed before starting treatment with levothyroxine sodium may help to distinguish underlying myocardial ischaemia from changes induced by hypothyroidism. Levothyroxine sodium should also be introduced very gradually in elderly patients and those with long-standing hypothyroidism to avoid any sudden increase in metabolic demands. It should not be given to patients with adrenal insufficiency without adequate corticosteroid cover otherwise the thyroid replacement therapy might precipitate an acute adrenal crisis. Care is also required when levothyroxine sodium is given to patients with diabetes mellitus or diabetes insipidus.
Tests if thyroid functions are subject to alteration by a number of nonthyroidal clinical conditions and by a wide variety of drugs, some of which are mentioned under interactions.
Adrenocortical insufficiency precautions: Thyroid-hormone replacement without concomitant treatment with corticosteroids may precipitate acute adrenocortical insufficiency in patients with impaired adrenocortical function, including those with subclinical or unrecognized adrenocortical disease. Prompt diagnosis and replacement of corticosteroids can prevent the development of a potentially fatal crisis. It has been pointed out that a raised concentration of thyroid-stimulating-hormone alone may not necessarily imply hypothyroidism in patients with chronic adrenocortical insufficiency. Even confirmed hypothyroidism in these patients may not be permanent.

Most authorities consider that thyroid hormones do not readily cross the placenta. Placental transfer has been reported, but in amounts so limited that a mother with physiological concentrations of levothyroxine sodium and tri-iodothyronine would not provide normal thyroid hormone concentrations to a fetus with congenital hypothyroidism.
Minimal amounts of thyroid hormones are distributed into breast milk. There is sufficient thyroid hormone to meet the biological needs of a sucking infant with a nonfunctioning thyroid gland but it has been suggested that levothyroxine sodium in breast milk might mask any hypothyroidism in the sucking newborn.

The following effects are indicative of excessive dosage, and usually disappear on reduction of dosage or withdrawal of treatment for a few days. Anginal pain, cardiac arrhythmias, palpitation, and cramps in skeletal muscle; also tachycardia, diarrhea, vomiting, tremors, restlessness, excitability, insomnia, headache, flushing, sweating, excessive loss of weight and muscular weakness. Rarely hypersensitivity reactions such as skin rash and pruritis have been reported. Rare cases of pseudotumour cerebri (benign intracranial hypertension) have been reported, especially in children.

Levothyroxine sodium increases the effect of anticoagulants and it maybe necessary to reduce the dose of anticoagulant if excessive hypoprothrombinaemia and bleeding are to be avoided.
Phenytoin levels maybe increased by levothyroxine sodium.
Anticonvulsants such as carbamazepine and phenytoin enhance the metabolism of thyroid hormones and may displace them from plasma proteins.
Initiation or discontinuation of anticonvulsant therapy may alter levothyroxine sodium dose requirements.
If co-administered with cardiac glycosides, adjustment of dosage of cardiac glycoside maybe necessary.
The effects of sympathomimetic agents are also enhanced.
Levothyroxine sodium increases receptor sensitivity to catecholamines thus accelerating the response to tricyclic antideppressants.
Cholestyramine given concurrently reduces the gastrointestinal absorption of levothyroxine sodium.
Co-administration of oral contraceptives may result in an increased dosage requirement of thyroid therapy.
A number of drugs may affect thyroid function tests and this should be borne in mind when monitoring a patient on levothyroxine sodium therapy.

Store at temperatures not exceeding 30°C. Protect from light.

Thyroid Hormones

H03AA01 - levothyroxine sodium ; Belongs to the class of thyroid hormones.

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