Euthyrox

Euthyrox

levothyroxine sodium

Manufacturer:

Merck

Distributor:

Zuellig
Full Prescribing Info
Contents
Levothyroxine sodium.
Description
Each Euthyrox 25 mcg Tablet contains 25 mcg Levothyroxine sodium.
Each Euthyrox 50 mcg Tablet contains 50 mcg Levothyroxine sodium.
Each Euthyrox 100 mcg Tablet contains 100 mcg Levothyroxine sodium.
Each Euthyrox 150 mcg Tablet contains 150 mcg Levothyroxine sodium.
Excipients/Inactive Ingredients: Lactose monohydrate, maize starch, gelatin, croscarmellose sodium, magnesium stearate.
Action
Pharmacology: Pharmacodynamics: Levothyroxine, the active ingredient in Euthyrox, is a synthetic thyroid hormone, which is identical to the natural thyroid hormone thyroxine (T4). The human organism does not differentiate between natural T4 hormone and synthetic levothyroxine because of their identical effects.
Levothyroxine is converted to tri-iodo-thyronine (T3) in the peripheral organs and develops its specific effect at the T3-receptor.
Pharmacokinetics: Orally given levothyroxine is absorbed almost exclusively in the upper small intestine. Depending on the galenical formulation, absorption amounts up to 80%. Tmax is approximately 5 to 6 hours.
Following oral administration the onset of action is seen after 3-5 days. Levothyroxine exhibits an extremely high binding to specific transport proteins of about 99.97%. This protein hormone binding is not covalent and so the bound hormone in plasma is in continuous and very rapid exchange with the fraction of the free hormone.
Due to its high protein binding, levothyroxine undergoes neither hemodialysis nor hemoperfusion.
The half-life of levothyroxine is on average 7 days. In hyperthyroidism, it is shorter (3-4 days) and in hypothyroidism, it is longer (approximately 9-10 days). The volume of distribution amounts to about 10-12 L. The liver contains 1/3 of the entire extrathyroidal levothyroxine which is rapidly exchangeable with the levothyroxine in serum. Thyroid hormones are metabolized mainly in the liver, kidneys, brain and muscles. The metabolites are excreted with urine and feces. The overall metabolic clearance for levothyroxine is about 1.2 L plasma/day.
Toxicology: Preclinical Safety Data: Acute Toxicity: Levothyroxine has a very slight acute toxicity. In incidents of poisoning (attempts at suicide) in humans, doses of 10 mg levothyroxine were tolerated without complications. In general, serious complications, such as threat to vital functions (respiration and circulation) need not be expected unless coronary heart disease is present.
Chronic Toxicity: The chronic toxicity of levothyroxine was studied in various animal species (rat, dog). At high doses, signs of hepatopathy, increased occurrence of spontaneous nephroses as well as changes in organ weights were observed in rats. No substantial adverse reactions occurred in dogs. Several cases of sudden cardiac death have been reported in patients with long years of levothyroxine abuse.
Reproduction Toxicity: Thyroid hormones pass the placenta only in slight, ineffective amounts. Ample experience in humans is available on therapy with levothyroxine in all phases of pregnancy: there is no evidence of any toxic effect on the fetuses or of drug-induced malformations.
No information is available on harmful effects on male or female fertility.
There have been no indications of any kind in this connection.
Mutagenicity: No information is available on this subject. So far no indications of any kind have become known suggesting damage to the progeny due to changes in the genome caused by thyroid hormones.
Carcinogenicity: No long-term animal studies have been carried out with levothyroxine.
Indications/Uses
Treatment of benign euthyroid goiter in patients with normal thyroid function.
Prophylaxis of relapse after surgery for euthyroid goiter, depending on the postoperative hormone status.
Substitution therapy in hypothyroidism (to replace natural thyroid hormones, when the thyroid gland does not produce enough).
Suppression therapy in thyroid cancer (to suppress tumor growth in patients with thyroid cancer).
Applies only to 25 mcg, 50 mcg and 100 mcg Tablets: Concomitant therapy during anti-thyroid medicinal treatment of hyperthyroidism (to balance thyroid hormone levels when overproduction of thyroid hormones is treated with antithyroid medicines).
Applies only to 100 mcg and 150 mcg Tablets: Diagnostic use for thyroid suppression testing (testing of thyroid function).
Dosage/Direction for Use
In order to treat each patient according to individual needs, tablets are available with a levothyroxine sodium content ranging from 25 to 150 mcg. Patients, therefore, usually need to take only one tablet per day.
The dosage recommendations given are only guidelines.
The individual daily dose should be determined on the basis of laboratory tests and clinical examinations. As a number of patients show elevated concentrations of T4 and fT4, basal serum concentration of thyroid-stimulating hormone provides a more reliable basis for subsequent treatment. In elderly patients, in patients with coronary heart disease, and in patients with severe or long-existing hypothyroidism, special caution is required when initiating therapy with thyroid hormones, that is, a low initial dose should be given which should then be increased slowly and at lengthy intervals with frequent monitoring of thyroid hormones. A maintenance dose lower than that required for complete correction of TSH levels may be considered. Experience has shown that a lower dose is sufficient in low-weight patients and in patients with a large nodular goiter. Treatment generally starts with a low dose which is increased every 2-4 weeks, until full individual dose is reached. During the initial weeks of treatment, laboratory tests have to be done in order to adjust the dose.
For neonates and infants with congenital hypothyroidism, where rapid replacement is important, the initial recommended dosage is 10 to 15 mcg per Kg body weight per day for the first 3 months. Thereafter, the dose should be adjusted individually according to the clinical findings and thyroid hormone and TSH values.
The usual dose range is shown in the following table. A lower individualized dose may be sufficient if a patient is an elderly, has heart problems, has severe or long-standing thyroid sub-function or has a low body weight or a large goiter. (See table.)

Click on icon to see table/diagram/image

The daily doses can be given in a single administration. Take a single daily dose in the morning on an empty stomach, half an hour before breakfast, preferably with a little liquid (for example, half a glass of water).
Infants receive the entire daily dose at least 30 minutes before the first meal of the day. Immediately before use, the tablet can be crushed and mixed with some water and then given to the child with some more liquid. Always prepare the mixture freshly, as required.
Duration of treatment may vary depending on the condition for which levothyroxine (Euthyrox) is used. For benign euthyroid goiter, a treatment duration of 6 months up to 2 years is necessary. If the medical treatment is not sufficient within this time, surgery or radioiodine therapy of the goiter should be considered. In the case of substitution in hypothyroidism and after strumectomy or thyroidectomy as well as for relapse prophylaxis after euthyroid goiter removal, treatment is usually continued for life.
Concomitant therapy of hyperthyroidism after achieving euthyroid status is indicated for the period in which the anti-thyroid agent is given.
The dose should not be doubled to make up for a forgotten tablet. The normal dose should be taken the following day.
Overdosage
Symptoms: Overdose may cause symptoms of a significant increase in the metabolic rate. If a higher dose than prescribed is taken, symptoms such as rapid heart rate (tachycardia), anxiety, agitation or unintended movements (hyperkinesia) may occur. In patients with a neurological disorder (e.g. epilepsy), seizures may occur in isolated cases. If any of this happens, the patient should contact the doctor immediately.
Several cases of sudden cardiac death have been reported in patients with long years of levothyroxine abuse.
In predisposed patients isolated cases of seizures have been reported when the individual dose tolerance limit was exceeded. Overdose of levothyroxine may result in hyperthyroidism and could lead to symptoms of acute psychosis, especially in patients at risk of psychotic disorders.
Management: An elevated T3 level is a reliable indicator of overdose, more than elevated T4 or fT4 levels. Depending on the extent of the overdosage, it is recommended that treatment is interrupted and that tests are carried out.
Beta-sympathomimetic effects such as tachycardia, anxiety, agitation or hyperkinesia can be relieved by beta-blockers. After extreme doses, plasmapheresis may be indicated.
Contraindications
Levothyroxine (Euthyrox) must not be used in patients with: untreated adrenal insufficiency (dysfunction of the adrenal gland); untreated pituitary insufficiency (dysfunction of the pituitary gland); untreated thyrotoxicosis (excessive overproduction of thyroid hormones); acute myocardial infarction (heart disease); acute myocarditis or acute pancarditis (heart inflammation); hypersensitivity to any of the excipients of the product.
Combination therapy of levothyroxine (Euthyrox) and an anti-thyroid agent for hyperthyroidism is not indicated during pregnancy.
Special Precautions
Thyroid hormones should not be given for weight reduction. In euthyroid patients, treatment with levothyroxine does not cause weight reduction. Substantial doses may cause serious or even life-threatening undesirable effects, particularly in combination with certain substances for weight reduction, and especially with sympathomimetic amines.
Before starting therapy with thyroid hormones or before performing a thyroid suppression test, the following diseases or medical conditions must be excluded or treated: coronary insufficiency, angina pectoris, arteriosclerosis, hypertension.
When initiating levothyroxine therapy in patients at risk of psychotic disorders, it is recommended to start at a low levothyroxine dose and to slowly increase the dosage at the beginning of the therapy. Monitoring of the patients is advised. If signs of psychotic disorders occur, adjustment of the dose of levothyroxine should be considered.
Thyroid autonomy (dysfunction of the thyroid gland with uncontrolled overproduction of thyroid hormones) must also be excluded or treated before starting therapy with thyroid hormones. Where thyroid autonomy is suspected, a TRH test or a suppression scintigram is recommended before initiation of treatment.
Even slight drug-induced hyperthyroidism must be avoided in patients with coronary insufficiency, heart failure and tachycardiac arrhythmias. Hence, frequent checks of thyroid hormone parameters must be made in these cases.
Levothyroxine (Euthyrox) is not recommended in hyperthyroid metabolic states. An exception is the concomitant supplementation during anti-thyroid drug treatment of hyperthyroidism.
The etiology of secondary hypothyroidism must be determined before thyroid hormone replacement therapy is given. If necessary, replacement treatment of a compensated adrenal insufficiency must be commenced.
In postmenopausal women with hypothyroidism and an increased risk of osteoporosis, supra-physiological serum levels of levothyroxine have to be avoided. Therefore, close monitoring of the thyroid function is recommended.
Once a levothyroxine (Euthyrox) treatment has been established, it is recommended to adjust the dosage following the patient's clinical response and laboratory test.
Levothyroxine (Euthyrox) contains lactose; therefore its use is not recommended in patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
Hypothyroidism and/or reduced control of hypothyroidism may occur when orlistat and levothyroxine are co-administered. Patients taking levothyroxine should consult a doctor before starting treatment with orlistat, as orlistat and levothyroxine may need to be taken at different times and the dose of levothyroxine may need to be adjusted. Further, it is recommended to monitor the patient by checking the hormone levels in the serum.
Effects on the Ability to Drive and Use Machines: No studies on the effects on the ability to drive and use machines have been performed. However, since levothyroxine is identical to the naturally occurring thyroid hormone, it is not expected that levothyroxine (Euthyrox) has any influence on the ability to drive and use machines, if used as recommended.
Use In Pregnancy & Lactation
Treatment with thyroid hormones should be given consistently during pregnancy and breastfeeding in particular. Dosage requirements may even increase during pregnancy. Since elevations in serum TSH may occur as early as 4 weeks of gestation, pregnant women taking levothyroxine should have their TSH measured during each trimester, in order to confirm that maternal serum TSH values lie within the trimester-specific pregnancy reference range. An elevated serum TSH level should be corrected by an increase in the dose of levothyroxine. Since postpartum TSH levels are similar to preconception values, the levothyroxine dosage should return to the pre-pregnancy dose immediately after delivery. A serum TSH level should be obtained 6-8 weeks postpartum.
Pregnancy: Thyroid suppression diagnostic tests must be avoided during pregnancy, as the application of radioactive substance in pregnant women is contraindicated. There is no evidence of drug-induced teratogenicity and/or feto-toxicity in humans at the recommended therapeutic dose level. Excessively high dose levels of levothyroxine during pregnancy may have a negative effect on fetal and postnatal development.
Combination therapy of hyperthyroidism with levothyroxine and anti-thyroid agents is not indicated during pregnancy. Such combination would require higher dose of anti-thyroid agents, which are known to pass the placenta and to induce hypothyroidism in the infant.
Lactation: Levothyroxine is secreted into breast milk during lactation but the concentrations achieve at the recommended therapeutic dose level are not sufficient to cause development of hyperthyroidism or suppression of TSH secretion in the infant.
Adverse Reactions
Where the individual tolerance limit for levothyroxine is exceeded or in the case of overdosage, it is possible for the following clinical symptoms typical of hyperthyroidism to occur, especially if the dose is increased too quickly at the start of treatment: irregular or rapid heart rate (tachycardia, palpitations, arrhythmias such as atrial fibrillation and extrasystoles), chest pain (angina pectoris), headache, muscle weakness or cramps, warmth and redness of the face (flushing), fever, vomiting, disorders of menstruation, pseudotumor cerebri (increased pressure in the head with eye swelling), trembling, restlessness, sleep disturbances, sweating (hyperhidrosis), weight loss, diarrhea. In such cases the daily dose should be reduced or the medication withdrawn for several days.
Therapy may carefully be resumed once the adverse effects have disappeared. In case of hypersensitivity to any of the ingredients of levothyroxine (Euthyrox), allergic reactions, particularly of the skin, may occur. Cases of angioedema (swelling of the face or throat) have been reported.
At the first sign of any adverse drug reaction, patient must seek medical attention immediately.
Drug Interactions
Antidiabetic drugs: Levothyroxine (Euthyrox) may reduce the effect of antidiabetics. Therefore, it is necessary to check blood glucose levels frequently at the start of thyroid hormone therapy. If necessary, the dose of the antidiabetic drug has to be adjusted.
Coumarin derivatives: Levothyroxine (Euthyrox) may intensify the effect of anticoagulants as levothyroxine displaces anticoagulants from plasma protein bounds which may increase the risk of hemorrhage, e.g. CNS or gastrointestinal bleeding, especially in elderly patients. Therefore it is necessary to check the coagulation parameters regularly at the start of and during concomitant therapy. If necessary, the dose of the anticoagulant has to be adjusted.
Protease inhibitors: The doctor should be informed if the patient is taking protease inhibitors (e.g. ritonavir, indinavir, lopinavir) because these substances may influence the effect of levothyroxine (Euthyrox). Close monitoring of thyroid hormone parameters is recommended. If necessary, the levothyroxine (Euthyrox) dose has to be adjusted.
Phenytoin: Phenytoin may influence the effect of levothyroxine (Euthyrox) by displacing levothyroxine from plasma proteins resulting in an elevated fT4 and fT3 fraction. On the other hand, phenytoin increases the hepatic metabolization of levothyroxine. Close monitoring of thyroid hormone parameters is recommended.
Salicylates, dicoumarol, furosemide (in high doses of 250 mg), clofibrate: These drugs may intensify the effect of levothyroxine (Euthyrox). These drugs and other substances can displace levothyroxine (Euthyrox) from plasma proteins, resulting in an elevated fT4 fraction.
Orlistat: Hypothyroidism and/or reduced control of hypothyroidism may occur when orlistat and levothyroxine are taken at the same time. This could be due to a decreased absorption of iodine salts and/or levothyroxine.
Sevelamer: Sevelamer may decrease levothyroxine (Euthyrox) absorption. Therefore, it is recommended that patients are monitored for changes in thyroid function at the start or end of concomitant treatment. If necessary, the levothyroxine dose has to be adjusted.
Tyrosine-kinase inhibitors: Tyrosine-kinase inhibitors (e.g. imatinib, sunitinib) may decrease the efficacy of levothyroxine (Euthyrox). Therefore, it is recommended that patients are monitored for changes in thyroid function at the start or end of concomitant treatment. If necessary, the levothyroxine dose has to be adjusted.
Ion exchange resins (e.g. cholestyramine, cholestipol): Ion exchange resins inhibit the absorption of levothyroxine (Euthyrox). It is therefore recommended that levothyroxine (Euthyrox) be taken 4-5 hours before administration of ion exchange resins.
Aluminum containing drugs, iron-containing drugs, calcium salts: Aluminum-containing drugs (antacids, sucralfate), iron-containing drugs and calcium salts have been reported in literature as potentially decreasing the effect of levothyroxine. Drugs containing levothyroxine should therefore be administered at least 2 hours prior to the administration of aluminum-containing drugs, iron-containing drugs and calcium salts.
Propylthiouracil, glucocorticoids, beta-sympatholytics and iodine-containing contrast media: These substances inhibit the peripheral conversion of T4 to T3.
Amiodarone: This substance inhibits the peripheral conversion of T4 to T3. Due to its high iodine content, amiodarone can trigger hyperthyroidism as well as hypothyroidism. Particular caution is advised in the case of nodular goiter with possibly unrecognized autonomy.
Sertraline, chloroquine/proguanil: These substances decrease the efficacy of levothyroxine (Euthyrox) and increase the serum TSH level.
Drugs leading to hepatic enzyme induction (e.g. barbiturates, carbamazepine): These substances can increase the hepatic clearance of levothyroxine (Euthyrox).
Estrogen: Women using estrogen-containing contraceptives or postmenopausal women under hormone-replacement therapy may have an increased need for levothyroxine (Euthyrox).
Soy products: Soy products may lower the uptake of levothyroxine (Euthyrox) from the intestine and therefore, an adjustment of the levothyroxine (Euthyrox) dose may be necessary, in particular at the beginning or after termination of nutrition with soy supplements.
Storage
Euthyrox 25 mcg Tablet: Store at temperatures not exceeding 30°C.
Euthyrox 50 mcg Tablet: Store at temperatures not exceeding 30°C.
Euthyrox 100 mcg Tablet: Store at temperatures not exceeding 30°C.
Euthyrox 150 mcg Tablet: Store at temperatures not exceeding 30°C.
Protect from light.
MIMS Class
Thyroid Hormones
ATC Classification
H03AA01 - levothyroxine sodium ; Belongs to the class of thyroid hormones.
Presentation/Packing
Tab 25 mcg x 100's. 50 mcg x 100's. 100 mcg x 100's. 150 mcg x 100's.
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