Back
Technical Data
ESSENTIAL INFORMATION COMPATIBLE WITH THE SUMMARY OF DRUG CHARACTERISTICS
Euthyrox®
Levothyroxine sodium
1. QUALITATIVE AND QUANTITATIVE COMPOSITION
2. PHARMACEUTICAL FORM
Tablet
3. CLINICAL PARTICULARS
3.1. Indications
3.2. Posology and Method of Administration
The individual daily dose should be determined by laboratory tests and clinical examinations. Particular caution must be exercised when starting treatment with thyroid hormones in elderly patients, patients with coronary heart disease and patients with severe or long-standing hypothyroidism, that is, a small dose should be chosen to start with which can then be increased gradually and at long intervals with frequent thyroid hormone checks.
Experience has shown that a small dose is also sufficient for patients with a low body weight and patients with a large nodular goitre.
| Indications | (Quantity) | Intake |
|---|---|---|
| Goitre (euthyroid goitre) - In adults - In adolescents | (75 - 200 mcg) (50 - 150 mcg) |
once daily once daily |
| Prevention of goitre once daily recurrence after goiter surgery (strumectomy) | (75 - 200 mcg) | once daily |
| Hypothyroidism in adults at the start of therapy (Increase by 25-50 mcg at 2 to 4 weekly intervals) As maintenance therapy - In children At the start of therapy As maintenance therapy | (25 - 50 mcg) (125 – 250 mcg) (12.5 – 50 mcg) (100 – 150mcg) per m2 body surface | once daily
once daily once daily once daily once daily |
| Concomitant therapy with medication against hyperthyroidism | (50 - 100 mcg) | once daily |
| After total surgical removal of the thyroid (thyroidectomy) | (150 - 300 mcg) | once daily |
| Thyroid suppression test | (200 mcg) | once daily |
In children with a sound heart, the therapy may be started with the entire dose, in adults, the therapy has to be started using small initial doses and gradually increasing to optimum amounts.
The entire daily dose of Euthyrox 100mcgshould be taken in the morning on an empty stomach, at least half an hour before breakfast with some liquid (for example, half a glass of water).
The duration of treatment is generally for life in hypothyroidism and after surgical removal of part or all of the thyroid gland, for some months up to life in the treatment of goitre (euthyroid goitre) and in prevention of goitre recurrence (goitre relapse prophylaxis).
In concomitant therapy to treat hyperthyroidism for as long as the drug against hyperthyroidism is taken.
Thyroid suppression test: 14 days before the repeat scan.
3.3. Contraindications
3.4. Special Warnings and Special Precautions for Use
Before starting therapy with thyroid hormones or before performing a thyroid suppression test, the following diseases or medical conditions should be excluded or treated: coronary failure, angina pectoris, arteriosclerosis, hypertension, pituitary insufficiency. Thyroid autonomy should also be excluded or treated before starting therapy with thyroid hormones. In case of adrenocortical dysfunction, this should be treated before starting the therapy with levothyroxine by adequate replacement treatment to prevent acute adrenal insufficiency (see section 3.3. Contraindications).
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 patient is advised. If signs of psychotic disorders occur, adjustment of the dose of levothyroxine should be considered.
Even slight drug-induced hyperthyroidism must be avoided in patients with coronary failure, cardiac insufficiency or tachycardiac arrhythmias. Hence frequent checks of thyroid hormone parameters must be made in these cases.
In the case of secondary hypothyroidism the cause must be determined before replacement therapy is given and if necessary replacement treatment of a compensated adrenal insufficiency must be commenced.
Where thyroid autonomy is suspected a TRH test should be carried out or a suppression scintigram obtained before treatment.
Haemodynamic parameters should be monitored when levothyroxine therapy is initiated in very low birth weight preterm neonates as circulatory collapse may occur due to the immature adrenal function.
In postmenopausal women with hypothyroidism and an increased risk of osteoporosis supra-physiological serum levels of levothyroxine should be avoided, and, therefore, thyroid function should be checked closely.
Levothyroxine should not be given in hyperthyreotic states other than as concomitant supplementation during anti-thyroid drug treatment of hyperthyroidism.
Thyroid hormones should not be given for weight reduction.In euthyroid patients, treatment with levothyroxine does not cause weight reduction.Substantialdoses may cause sever or even life-threatening undesirable effects. Levothyroxine in high doses should not be combined with certain substances for weight reduction, i.e. sympathomimetics (see section 3.9Overdose).
If a switch to another levothyroxine-containing product is required, there is a need to undertake a close monitoring including a clinical and biological monitoring during the transition period due to a potential risk of thyroid imbalance. In some patients, a dose adjustment could be necessary.
Hypothyroidism and/or reduced control of hypothyroidism may occur when orlistat and levothyroxine are co-administered (see section3.5Interaction with other medicinal products and other forms of interaction). 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.
For diabetic patients and patients under anticoagulant therapy, see section 3.5Interaction with other medicinal products and other forms of interaction.
This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, i.e. essentially ‘sodium-free’.
In elderly people Euthyrox should be dosed very carefully. A small dose should be chosen to start with, which can then be increased gradually and at long intervals with frequent thyroid hormone checks. Even mild hyperthyroidism due to Levothyroxine must be avoided by all means, especially in patients with coronary heart disease, heart failure, or heart rhythm disturbances of the rapid type.
Thyroid hormone therapy in patients with concomitant diabetes mellitus or diabetes insipidus or adrenal cortical insufficiency aggravates the intensity of their symptoms. Appropriate adjustments of the various therapeutics measures directed at these concomitant endocrine disease are required. The therapy of myxedema coma may require simultaneous administration of glucocorticoids.
Pediatric use the diagnosis and institution of therapy for creatinism should be done as soon as after birth as possible to prevent developmental deficiency screening tests for serum T4 and TSH will identify this group of newborn patients. In infants, excessive doses of thyroid hormone preparations may produce craniosynostosis.
Drugs with thyroid hormone activity, alone or togetherwith other therapeutic agents, have been used for the treatment of obesity. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for anoretic effects.
Interaction with Other Medicinal Products and Other Forms of Interaction
Anti-diabetic agents
Levothyroxine may reduce the effect of antidiabetic agents. For this reason, blood glucose levels should be checked frequently at the start of thyroid hormone therapy and the dosage of the antidiabetic agent has to be adapted, if necessary.
Coumarin derivates
The effect of anti-coagulant therapy can be intensified as levothyroxine displaces anti-coagulative drugs from plasma proteins, which may increase the risk of haemorrhage, e.g. CNS or gastrointestinal bleeding, especially in elderly patients. Therefore it is necessary for coagulation parameters to be checked regularly at the start of and during concomitant therapy. If necessary, the dosage of the anti-coagulative drug has to be adapted.
Protease inhibitors
Protease inhibitors (e.g. ritonavir, indinavir, lopinavir) may influence the effect of levothyroxine. Close monitoring of thyroid hormone parameters is recommended. If necessary, the levothyroxine dose has to be adjusted.
Phenytoin
Phenytoin may influencethe effect of levothyroxine by displacing levothyroxine from plasma proteins resulting in an elevated fT4 and fT3 fraction. On the other hand phenytoin increases the hepatic metabolisation of levothyroxine. Close monitoring of thyroid hormone parameters is recommended.
Colestyramine, Colestipol
Ingestion of ion exchange resins such as cholestyramine and colestipol inhibits the absorption of levothyroxine sodium. Levothyroxine sodium should therefore be taken 4-5 hours before administration of such products.
Aluminium, iron, and calcium salts
Aluminium-containing medicinal products (antacids, sucralfate) have been reported in literature as potentially decresing the effect of Levothyroxine. It is therefore recommended that Levothyroxine be administered at least 2 hours prior to the administration of aluminium-containing medicinal products. The same applies to medicinal products containing iron and calcium salts.
Salicylates, dicumarol, furosemide, clofibrate
Salicylates, dicumarol, furosemide in high doses (250 mg), clofibrate and other substances can displace levothyroxine sodium from plasma proteins, resulting in an elevated fT4 fraction.
Orlistat
Hypothyroidism and/or reduce control of hypothyroidsm may occur when orlistat and levothyroxineare taken at the same time. This could be due to a decreased absorption of iodine salts and /or levothyroxine.
Sevelamer
Sevelamer may decrease levothyroxine 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. 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.
Propylthiouracil, glucocorticoids, beta-sympatholytics, amiodarone and iodine containing contrast media
These substances inhibit 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 goitre with possibly unrecognized autonomy.
Sertraline, chloroquine/proguanil
These substances decrease the efficacy of levothyroxine and increase the serum TSH level.
Enzyme inducing medicinal products
Enzyme inducing medicinal products such as barbiturates or carbamazepine can increase hepatic clearance of levothyroxine.
Estrogens
Women using oestrogen-containing contraceptives or postmenopausal women under hormone-replacement therapy may have an increased need for levothyroxine.
Soy-containing compounds
Soy-containing compounds can decrease the intestinal absorption of levothyroxine. Therefore, a dosage adjustment of Euthyrox may be necessary, in particular at the beginning or after termination of nutrition with soy supplements.
3.6. Pregnancy and Lactation
Treatment with levothyroxine should be given consistently during pregnancy and breast-feeding 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 the 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
Experience has shown that there is no evidence of drug-induced teratogenicity and/or foeto-toxicity in humans at the recommended therapeutic dose level. Excessively high dose levels of levothyroxine during pregnancy may have a negative effect on foetal and postnatal development.
Combination therapy of hyperthyroidism with levothyroxine and anti-thyroid agents is not indicated in pregnancy. Such combination would require higher doses of anti-thyroid agents, which are known to pass the placenta and to induce hypothyroidism in the infant.
Thyroid suppression diagnostic test should not be carried out during pregnancy, as the application of radioactive substances in pregnant women is contraindicated.
Breast-feeding
Levothyroxineis secreted into breast milk during lactationbut the concentrations achieved at the recommended therapeutic dose level are not sufficient to cause development of hyperthyroidism or suppression of TSH secretion in the infant.
3.7. Effects on 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 Euthyrox has any influence on the ability to drive and usemachines.
3.8. Undesirable Effects
Where the individual tolerance limit for levothyroxine sodium is exceeded or after overdose 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: cardiac arrhythmias (e.g. atrial fibrillation and extrasystoles), tachycardia, palpitations, anginal conditions, cephalalgia, muscular weakness and cramps, flushing, fever, vomiting, disorders of menstruation, pseudotumorcerebri, tremor, restlessness, insomnia, hyperhidrosis, weight loss, diarrhoea.
In such cases the daily dose should be reduced or the medication withdrawn for several days. Therapy may be carefully resumed once the adverse reactions have disappeared.
Incase of hypersensitivity to any of the ingredients of Euthyrox,allergic reactions, particularly of the skin, may occur. Cases of angioedema have been reported
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.
3.9. Overdose
An elevated T3 level is a reliable indicator of overdose, more than elevated T4 or fT4 levels. After overdose the symptoms of a sharp increase in the metabolic rate occur (see section 3.8Undesirable effects).
Depending on the extent of the overdose it is recommended that treatment is interrupted and that tests are carried out.
Symptoms consisting of intense beta-sympathomimetic effects such as tachycardia, anxiety, agitation and hyperkinesia can be relieved by betablockers. After extreme doses plasmapheresis may be of help.
In predisposed patients isolated cases of seizures have been reported when the individual dose tolerance limit was exceeded.
Overdose of levothyroxinemay result in hyperthyroidism and could lead to symptoms of acute psychosis, especially in patients at risk of psychotic disorders.
Several cases of sudden cardiac death have been reported in patients with long years of levothyroxineabuse.
4.PHARMACOLOGICAL PROPERTIES
4.1. Pharmacodynamic properties
Pharmacotherapeutic group: Thyroid hormones
ATC-Code: H03A A01
The synthetic levothyroxine contained in Euthyrox is identical in effect with the naturally occurring major hormone secreted by the thyroid. It is converted to T3 in peripheral organs and, like the endogenous hormone, develops its specific effects at the T3 receptors. The body is not able to differentiate between endogenous and exogenous levothyroxine.
4.2. Pharmacokinetic properties
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 haemodialysis nor haemoperfusion.
The half-lifeof levothyroxine is on average 7 days. In hyperthyroidism it is shorter (3-4 days) and in hypothyroidism it is longer (approx. 9-10 days). The volume of distribution amounts to about 10-12 l. The liver contains 1/3 of the entire extra-thyroidal 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 faeces. The overall metabolic clearance for levothyroxine is about 1.2 Lplasma/day.
5. PHARMACEUTICAL PARTICULARS
5.1. List of excipients
5.2. Shelf-life
The expiry date of this pack is printed on the folding box.
Do not use this pack once the expiry date has elapsed.
5.3. Storage and Stability
Do not store above 30ºC. Protect from light.
5.4. Package Quantities and Registration Number
Euthyrox 50 mcgBox, 4 blisters @ 25 tabletsReg. No. DKI2163401910A1
Euthyrox 100 mcgBox, 4 blisters @ 25 tabletsReg. No. DKI2163401910B1
HARUS DENGAN RESEP DOKTER
Manufactured byMerck Healthcare KGaA, Darmstadt, Germany
Imported byPT Merck Tbk, Jakarta, Indonesia
PI based on CCDS ver 7.0BPOM Approval of the Update 18Jul2022
DW/jt/07May2021