Euthycin
Levothyroxine sodium tablet

Presentation
Euthycin : Each tablet contains Levothyroxine Sodium BP 50 micrograms.

Description
Thyroxine (T4) is a naturally occurring hormone produced by the thyroid gland & converted to the more active hormone triiodothyronine (T3) in peripheral tissues. Euthycin (Levothyroxine sodium) is used in thyroxine replacement therapy. The thyroid hormones are required for normal growth and development particularly of the nervous system. Levothyroxine is incompletely and variably absorbed from the gastrointestinal tract. The half-life of T4 in normal plasma is 6-7 days while that of T3 is about 1 day. The plasma half-lives of T4 and T3 are decreased in hyperthyroidism and increased in hypothyroidism. Levothyroxine is largely bound to plasma protein, mainly to thyroxine binding globulin (TBG) but also to prealbumin and less avidly to albumin. The unbound or free fraction, although only about 0.03% of total levothyroxine, is of course the fraction available for peripheral action and conversion to the more active metabolite triiodothyronine (T3). Levothyroxine is extensively metabolized in the thyroid, liver, kidney, and anterior pituitary gland. It is excreted in urine and feces, partly as free drug and partly as conjugates and deiodinated metabolites. Between 30 and 55% of the dose is excreted in the urine and 20-40% in the feces.

Indications
1. Congenital hypothyroidism
2. Acquired hypothyroidism
* Primary thyroid failure
* Autoimmune
* Post surgery
* Postradioiodine therapy
* Drug therapy
* Myxedema coma
3. Hypothyroidism secondary to pituitary/hypothalamic diseases
4. Suppression of goiter
5. In conjunction with antithyroid drugs in treatment of thyrotoxicosis

Dosage and Administration
In adult patients without cardiac problems: Initially adult oral dose is 50-100 micrograms daily, preferably in the fasting state, adjusted in steps of 50 micrograms every 3-4 weeks until normal metabolism maintained. The patient's well being and thyroid function tests are reassessed after 6-8 weeks. The daily dosage may then require further minor adjustment so as to ensure clinical and biochemical euthyroidism. It is important to correct any steroid deficiency first before initiating thyroxine replacement therapy.
In the elderly and in patients with cardiac problems: Initially 25 micrograms daily or 50 micrograms on alternate days adjusted in steps of 25 micrograms every 4 weeks until euthyroid.
Maintenance therapy: The usual maintenance dose to relieve hypothyroidism is 100-200 micrograms daily, which can be administered as a single dose.
Neonates and children: Replacement therapy should be started as soon as the diagnosis is made to prevent the mental and physical retardation that would otherwise occur. The initial diagnosis and cause can be reappraised when the infant is 1 year old.

Age Daily dose per kg of body weight
0 - 6 mos 8 - 10 mcg
6 - 12 mos 6 - 8 mcg
1 - 5 yrs 5 - 6 mcg
6 - 12 yrs 4 - 5 mcg

o To be adjusted on the basis of clinical response and laboratory tests

Side effects
Side effects may include anginal pain, arrhythmias, palpitation, skeletal muscle cramps, tachycardia, diarrhoea, vomiting, tremors, restlessness, excitability, insomnia, headache, flushing, sweating, fever, heat intolerance, excessive loss of weight and muscular weakness.

Precautions
Levothyroxine should be used with caution in patients with cardiovascular disorders, including angina, coronary artery disease, and hypertension, and in the elderly who have a greater likelihood of occult cardiac disease. Use of levothyroxine in patients with concomitant diabetes mellitus, diabetes insipidus or adrenal cortical insufficiency may aggravate the intensity of their symptoms. Appropriate adjustments of the various therapeutic measures directed at these concomitant endocrine diseases may therefore be required.

Interference with clinical pathology tests
Levothyroxine interferes with tests
Serum T4, T3 and TSH can be measured in patients taking levothyroxine to determine optimum replacement dosage and compliance. Levothyroxine may suppress radioiodine uptake in normal individuals.
Factors interfere with the measurement of T4
Increased binding to TBG during pregnancy and with estrogen therapy will increase total (but not free) T4 levels. Loss of protein as a result of nephrotic syndrome or liver diseases will lower total (but not free) T4 levels.

Use in pregnancy and lactation
Pregnant women
Women on maintenance levothyroxine for hypothyroidism who become pregnant should not need to alter the dose because of the pregnancy so long as they are confirmed to be euthyroid initially, by normal TSH levels. T4 does not cross the placental barrier in the second and third trimester, although it may do so in early pregnancy.
Breast milk
The amount of T4 in breast milk is variable but not sufficient to affect the normal infant.

Contraindications
Levothyroxine is contraindicated in patients with untreated thyrotoxicosis of any etiology or an apparent hypersensitivity to thyroid hormone. It is also contraindicated in the patients with uncorrected adrenal insufficiency. Thyroid hormone should not be used in the treatment of obesity unless there is evidence of hypothyroidism confirmed biochemically.

Drug Interactions
Potentially hazardous interactions
Levothyroxine, when given to hypothyroid patients who are already on anticoagulants, will potentiate the effect of warfarin and other dicoumarin anticoagulants necessitating a marked reduction (50%) in warfarin dosage to prevent excessive prolongation of the prothrombin time and partial thromboplastin time.
Other significant interactions
Cholestyramine may reduce absorption of levothyroxine. Phenylbutazone, carbamazepine and phenytoin may cause a false low total serum T4 levels. Amiodarone commonly produces elevated T4 levels, but triiodothyronine levels are usually normal. Serum T3 and TSH levels rather than T4 should be used to monitor the patient's thyroid status.

Over dosage
A massive acute overdose is fortunately uncommon but potentially lethal. If the patient presents soon after ingestion of an acute overdose then gastric aspiration and lavage are indicated. Other treatment includes propranolol and supportive measures to maintain the circulation.

Commercial Pack
Euthycin : Each bottle contains 100 tablets.