Hormone (hormone) replacement therapy or supplementation in patients with hypothyroidism (insufficient hormone production by the thyroid gland)...

drconsulta 08, Jan de 2019 53 minutes to read

• Hormone (hormone) replacement therapy or supplementation in patients with hypothyroidism (insufficient hormone production by the thyroid gland) of any cause (except in transient hypothyroidism, during the recovery phase of subacute thyroiditis – inflammatory disease of the thyroid gland). Included in this category are: cretinism (condition occurring in infancy or breastfeeding due to thyroid hormone deficiency in the fetal stage), myxedema (associated with hypothyroidism, characterized by dry, rough skin, swollen lips, and thickened nose) and hypothyroidism common in patients of any age (children, adults, and elderly) or stage (eg, pregnancy); primary hypothyroidism resulting from reduced thyroid function; primary thyroid decrease; removal of all or part of the thyroid gland, with or without goiter (noticeable enlargement of the thyroid); secondary hypothyroidism (from the pituitary gland) or tertiary hypothyroidism (from the hypothalamus, which is a region of the brain that controls the endocrine system);
• Suppression of pituitary TSH (thyroid-stimulating hormone or thyrotropin) in the treatment or prevention of various types of euthyroid goiters (goiter due to increased TSH), including thyroid nodules, subacute or chronic lymphocytic thyroiditis (Hashimoto's thyroiditis/autoimmune thyroiditis) and carcinomas thyrotropin-dependent follicular and papillary (malignant tumors) of the thyroid;
• Diagnosis in suppression tests, aiding in the diagnosis of suspected mild hyperthyroidism (excessive hormone production by the thyroid gland) or an autonomous thyroid gland.

How does Merck Levothyroxine Sodium work?

This is a medicine that has in its formula a substance called levothyroxine. Levothyroxine is a hormone normally made by the body by the thyroid gland.

Levothyroxine is prescribed by the doctor to supply the deficiency of this hormone in the body.

Contraindication of Levothyroxine Sodium – Merck

Levothyroxine should not be used in case of intolerance to the components of the formula, recent myocardial infarction, untreated thyrotoxicosis (untreated clinical syndrome resulting from elevated levels of thyroid hormone), decompensated adrenal insufficiency (of the gland located over the kidneys) and untreated hyperthyroidism.

There are no contraindications related to age groups.

How to use Levothyroxine Sodium – Merck

You must take the pills with liquid, by mouth.

There are no studies of the effects of levothyroxine given by non-recommended routes. Therefore, for safety and to ensure the effectiveness of this medication, administration should only be orally as recommended by the physician.

Posology

The administered doses of levothyroxine vary according to the degree of hypothyroidism, the patient's age and individual tolerability. In order to adapt the dosage, it is advisable to measure (T3), (T4) and TSH before starting treatment.

Adult use

hypothyroidism

Levothyroxine should be administered in low doses (50mcg/day) that will be increased according to the patient's cardiovascular conditions.

Initial dose

50mcg/day, increasing by 25mcg every 2 to 3 weeks until the desired effect is achieved. In patients with long-standing hypothyroidism, particularly with suspected cardiovascular disorders, the initial dose should be even lower (25mcg/day).

Maintenance

Daily intake of 75 to 125mcg is recommended, and some patients with malabsorption may require up to 200mcg/day. Most patients do not require doses greater than 150mcg/day. Failure to respond to doses of 200mcg/day suggests malabsorption, noncompliance with treatment, or diagnostic error.

TSH suppression (thyroid cancer) / euthyroid nodules / goiters in adults

Mean suppressive dose of levothyroxine (T4): 2.6mcg/kg/day, for 7 to 10 days. This dose is usually sufficient to obtain normalization of T3 and T4 levels in the body and lack of response to the action of TSH. Sodium levothyroxine should be used with caution in patients with suspected independent thyroid gland, considering that the action of exogenous hormones (from outside the body) can be added to endogenous source hormones (originating in the body).

pediatric use

In newborns, the initial dosage should be 5 to 6mcg/kg/day depending on the dosage of circulating hormones. In children, the dosage must be established according to the results of hormonal dosages and is generally 3mcg/kg/day.

Levothyroxine tablets should be taken on an empty stomach (1 hour before or 2 hours after breakfast or food) in order to enhance their absorption.

For children with difficulties swallowing the pills, they should be crushed and dissolved in a small amount of water. This suspension can be administered by spoon or dropper. Crushed tablets can also be taken with small amounts of food (cereals, juices, etc.). This prepared suspension cannot be saved for later use.

elderly patients

In the elderly, the integrity of the cardiovascular system may be compromised. Therefore, in this patient, therapy with levothyroxine should be started with low doses, such as: 25-50mcg/day.

Follow your doctor's advice, always respecting the times, doses and duration of treatment.

Do not stop treatment without your doctor's knowledge.

What should I do when I forget Merck Levothyroxine Sodium?

If you forget to take a dose, take it as soon as possible. However, if it is close to the time of the next dose, wait for this time, always respecting the interval determined by the dosage. Two doses should never be administered at the same time.

If in doubt, seek advice from your pharmacist or doctor.

Levothyroxine Sodium Precautions – Merck

Tell your doctor if you have heart disease (angina, heart attack), high blood pressure, adrenal insufficiency, lack of appetite, tuberculosis, asthma or diabetes.

Levothyroxine should be used with extreme caution in patients with cardiovascular disorders (related to the heart and circulation), including angina pectoris, heart failure, myocardial infarction and high blood pressure. If necessary, lower starting doses, small dose increases and longer intervals between dose increases should be used.

Thyroid hormone replacement therapy may precipitate adrenal or pituitary gland problems if not adequately treated with corticosteroids.

Thyroid hormones should not be used for weight loss. In euthyroid patients (with normal levels of thyroid hormone production), normal dosages are not effective for weight loss; higher dosages can produce severe or even life-threatening manifestations, especially if administered with other specific care for weight reduction.

Effects on bone mineral density

The use of levothyroxine may be associated with a risk of bone loss, with consequent development of osteoporosis (bone weakness) and fractures. This risk has been observed in some studies in postmenopausal women using suppressive doses of TSH after differentiated thyroid carcinoma.

In premature newborns with low birth weight, the initiation of therapy with levothyroxine must be carried out with extreme caution as circulatory collapse may occur (the heart and vessels are not able to irrigate all body tissues with sufficient oxygen) due to immaturity of function adrenal.

Additional care is required when levothyroxine is administered to patients with Diabetes mellitus or Diabetes insipidus .

Dosage should be adapted according to thyroid (thyroid) function tests. Monitoring of patients should be performed according to clinical symptoms, as well as thyroid function tests. It is necessary to monitor patients receiving concomitant administration of levothyroxine and drugs that may affect thyroid function (such as amiodarone and tyrosine kinase inhibitors, salicytates and high-dose furosemide).

During levothyroxine therapy in postmenopausal women at increased risk of osteoporosis (bone weakness), the dosage of levothyroxine sodium should be adjusted to the lowest possible effective level.

Drug interactions

Inform your doctor if you are using other medicines, especially anticoagulants, oral contraceptives, cholestyramine, acetylsalicylic acid, antidiabetics or antidepressants.

Effects of levothyroxine on other drugs

Oral anticoagulants (medicines that prevent blood clots, e.g. dicoumarol and warfarin)

Thyroid hormones enhance the effects of oral anticoagulants. Patients on anticoagulant therapy still require careful monitoring when treatment with thyroid agents is started or changed as needed to adjust the oral anticoagulant dosage (dose reduction).

Oral antidiabetics and insulin

The use of levothyroxine can lead to an increase in blood glucose, and in diabetic patients, it may be necessary to adjust the dose of oral antidiabetics or insulin. This effect occurs because thyroid hormones help regulate hepatic insulin sensitivity, which is important for inhibiting hepatic gluconeogenesis.

Effects of other drugs on levothyroxine

Enzyme-inducing drugs (increase the action of enzymes and their release) (e.g. rifampicin, carbamazepine or phenytoin, barbiturates)

Increased thyroid metabolism resulting in reduced blood concentrations of thyroid hormones. Thus, patients on thyroid hormone replacement therapy may require increased dosages if these drugs are given concomitantly.

Amiodarone

Inhibits peripheral conversion of levothyroxine T4 to T3 resulting in reduced serum T3 concentration and increased serum TSH level.

Glucocorticoids, propylthiouracil, and beta-sympatholytics (especially propranolol)

They inhibit the peripheral conversion of levothyroxine (T4) to T3 and may lead to a reduction in the serum concentration of T3.

Protease inhibitors (class of drugs that slow viral replication)

There have been reports of loss of therapeutic effect of levothyroxine when used concomitantly with lopinavir/ritonavir. Therefore, clinical symptoms as well as thyroid function tests should be carefully monitored in patients receiving levothyroxine and lopinavir/ritonavir concomitantly.

Tyrosine kinase inhibitors such as imatinib, sunitinib or sorafenib

May reduce the effectiveness of levothyroxine. Therefore, clinical symptoms as well as thyroid function should be carefully monitored in patients receiving levothyroxine and tyrosine kinase inhibitors concomitantly. It may be necessary to adjust the dose of levothyroxine.

Estrogens (eg, oral contraceptives)

They increase thyroxine binding, leading to misdiagnosis and treatment.

salicylates

Doses greater than 2g/day can increase free T4 levels and, when at therapeutic levels, salicylates can cause a reduction in total T4 and free T4 levels by 20 – 30%.

Furosemide

High intravenous dose of furosemide (gt; 80mg), associated with alterations in renal function and serum albumin concentration, may promote a transient increase in free T4 and a reduction in total T4. This effect is not observed at the usual doses used in hypertensive patients or patients with heart failure.

Clofibrato

Studies in animal models suggest that clofibrate can act as a microsomal enzyme inducer and alter the metabolism of thyroid hormones with a consequent reduction in T4 and free T3 levels.

Antidiabetics

Levothyroxine may reduce the hypoglycemic (lowering blood sugar) effect of oral antidiabetic agents such as metformin, glimepiride and glibenclamide, as well as insulin. Monitoring of blood glucose levels is recommended, especially when thyroid hormone therapy is started or stopped, and if necessary, the dosage of the antidiabetic should be adjusted.

Iodinated contrast media

Some iodinated contrast media (iopanoic acid, sodium ipodate and some intravenous preparations containing iodine) may interfere temporarily (approximately 10 to 14 days, the time of contrast excretion) in thyroid function. During this period, there may be release of iodine in quantity (14 to 175mg of iodide) capable of reducing the secretion of thyroid hormones and causing hypothyroidism.

Drugs given by mouth that may reduce the absorption of levothyroxine (T4)

Ion exchange resins (e.g. cholestyramine, sevelamer or calcium polystyrene sulfate and sodium salts)

There is reduced absorption of ingested levothyroxine due to binding to thyroid hormones in the gastrointestinal tract. Therefore, the administration of ion exchange resins should be separated from the administration of levothyroxine as much as possible.

Medicines for the gastrointestinal tract (relating to the digestive system) (eg sucralfate, antacids and calcium carbonate)

There is reduced absorption of levothyroxine from the gastrointestinal tract. Therefore, the administration of drugs for the gastrointestinal tract should be separated from the administration of levothyroxine as much as possible.

iron salts

Ferrous sulfate reduces the absorption of levothyroxine from the gastrointestinal tract. Therefore, the administration of iron salts should be separated from the administration of levothyroxine as much as possible.

interaction with food

Food can interfere with the absorption of levothyroxine. Thus, administration of levothyroxine on an empty stomach (1 hour before or 2 hours after breakfast or food intake) is recommended in order to increase its absorption.

Military

In newborns on a soy diet and treated with levothyroxine for congenital hypothyroidism, an increase in the TSH level has been reported. Excessive doses of levothyroxine may be necessary to achieve normal serum T4 and TSH levels. During and after the soy diet, monitoring of T4 and TSH levels in the blood is necessary, with possible dose adjustment.

Tell your doctor if you are taking any other medication.

Do not use medication without the knowledge of your doctor. It can be dangerous for your health.

Levothyroxine Sodium Adverse Reactions – Merck

• Very common reaction (occurs in more than 10% of patients using this medication);
• Common reaction (occurs between 1% and 10% of patients using this medication);
• Unusual reaction (occurs between 0.1% and 1% of patients using this medication);
• Rare reaction (occurs between 0.01% and 0.1% of patients using this medication);
• Very rare reaction (occurs in less than 0.01% of patients using this medication);
• Reaction with unknown frequency (cannot be estimated from the available data).

In general, adverse reactions to levothyroxine are associated with excessive dosage and correspond to the symptoms of hyperthyroidism (excessive hormone production by the thyroid gland).

heart disorders

Very common

Palpitations (awareness of heartbeats).

Common

Tachycardia (fast heart rate).

unknown frequency

Cardiac arrhythmias (heartbeat irregularity) and angina pain (chest pain).

Skin and subcutaneous disorders

unknown frequency

Rash (skin eruptions), urticaria (skin rash, usually of an allergic origin, which causes itching), sweating (excessive sweating).

psychiatric disorders

Very common

Insomnia.

Common

Nervousness.

unknown frequency

Excitability.

Musculoskeletal and connective tissue disorders

unknown frequency

Muscle weakness, cramps and osteoporosis (bone weakness) on suppressive doses of levothyroxine, especially in postmenopausal women, especially when treated for a long time.

vascular disorders

unknown frequency

Hot flushes (sudden, temporary sensation of heat), circulatory collapse (the heart and vessels are not able to supply all body tissues with sufficient oxygen) in low birth weight premature neonates.

Reproductive system and breast disorders

unknown frequency

Menstrual irregularities.

gastrointestinal disorders

unknown frequency

Diarrhea and vomiting.

Investigations

unknown frequency

Weight loss.

Nervous system disorders

Very common

Headache.

unknown frequency

Tremors, intracranial hypertension (increased pressure within the skull characterized by headache, nausea, visual changes and tinnitus) benign particularly in children.

General disorders and administration site changes

unknown frequency

Heat intolerance, fever.

endocrine disorders

Common

Hyperthyroidism.

Such effects usually disappear with a reduction in dosage or temporary withdrawal of treatment.

Inform your doctor or pharmacist of the appearance of undesirable reactions from the use of the medicine. Also inform the company through its customer service.

Composition of Levothyroxine Sodium – Merck

presentations

Pills of 25, 50, 75, 88, 100, 112, 125, 150, 175 or 200mcg – Pack containing 30 pills.

Oral use.

Adult and pediatric use.

Composition

Each 25mcg tablet contains:

25mcg of levothyroxine sodium.

Excipients:

Corn Starch, Croscamellose Sodium, Magnesium Stearate, Gelatin, Lactose Monohydrate.

Each 50mcg tablet contains:

50mcg of levothyroxine sodium.

Excipients:

Corn Starch, Croscamellose Sodium, Magnesium Stearate, Gelatin, Lactose Monohydrate.

Each 75mcg tablet contains:

75mcg of levothyroxine sodium.

Excipients:

Corn Starch, Croscamellose Sodium, Magnesium Stearate, Gelatin, Lactose Monohydrate.

Each 88mcg tablet contains:

88mcg of levothyroxine sodium.

Excipients:

Corn Starch, Croscamellose Sodium, Magnesium Stearate, Gelatin, Lactose Monohydrate.

Each 100mcg tablet contains:

100mcg of levothyroxine sodium.

Excipients:

Corn Starch, Croscamellose Sodium, Magnesium Stearate, Gelatin, Lactose Monohydrate.

Each 112mcg tablet contains:

112mcg of levothyroxine sodium.

Excipients:

Corn Starch, Croscamellose Sodium, Magnesium Stearate, Gelatin, Lactose Monohydrate.

Each 125mcg tablet contains:

125mcg of levothyroxine sodium.

Excipients:

Corn Starch, Croscamellose Sodium, Magnesium Stearate, Gelatin, Lactose Monohydrate.

Each 150mcg tablet contains:

150mcg of levothyroxine sodium.

Excipients:

Corn Starch, Croscamellose Sodium, Magnesium Stearate, Gelatin, Lactose Monohydrate.

Each 175mcg tablet contains:

175mcg of levothyroxine sodium.

Excipients:

Corn Starch, Croscamellose Sodium, Magnesium Stearate, Gelatin, Lactose Monohydrate.

Each 200mcg tablet contains:

200mcg of levothyroxine sodium.

Excipients:

Corn Starch, Croscamellose Sodium, Magnesium Stearate, Gelatin, Lactose Monohydrate.

Overdosage of Levothyroxine Sodium – Merck

If someone uses a larger than recommended amount of this medication,

Thyroid storm (thyroid crisis caused by increased amounts of thyroid hormones in the bloodstream) after massive or chronic intoxication, convulsions, cardiac arrhythmias, reduced cardiac function, coma and death.

In acute overdoses, gastrointestinal absorption may be reduced by activated charcoal. Treatment is often symptomatic and supportive: beta-blockers may be helpful in controlling the symptoms of sympathomimetic hyperactivity. In cases of overdose with high amounts, plasma filtration (a procedure whereby plasma is separated and extracted from non-coagulated whole blood and the red cells are retransferred to the patient) should be considered.

Overdose with levothyroxine requires longer follow-up as symptoms may be prolonged for up to 6 days due to the gradual peripheral conversion of levothyroxine to triiodothyronine.

In case of using a large amount of this medicine, seek medical help quickly and take the package or leaflet of the medicine, if possible. Call 0800 722 6001 if you need further guidance.

Levothyroxine Sodium Drug Interaction – Merck

Many drugs affect thyroid hormone pharmacokinetics and metabolism (eg, absorption, synthesis, secretion, catabolism, protein binding, and target tissue response) and may alter the therapeutic response to Levothyroxine Sodium. In addition, hormones and thyroid status have varying effects on the pharmacokinetics and actions of other drugs. Food can interfere with the absorption of Levothyroxine Sodium (active substance). Thus, it is recommended to administer Levothyroxine Sodium (active substance) on an empty stomach (half to 1 hour before breakfast) in order to increase its absorption. A list of interactions is shown below.

Drug-Drug Interaction

Contraindicated for use together:

Severity: Major

Severity: Moderate

Severity: Minor

Other drug interactions described

The literature also cites the following interactions:

cytokines

Interferon-α, interleucina-2.

growth hormones

Somatrem, somatropin; methylxanthine; bronchodilators (eg, theophylline); chloral hydrate; diazepam; ethionamide; lovastatin; metoclopramide; 6-mecaptopurine; nitroprusside; sodium para-aminosalicylate; resorcinol (topical overuse); thiazide diuretics.

Drug-Laboratory Test Interactions

Changes with increased thyroglobulin concentration should be considered when analyzing serum T ₄ and T ₃ levels in situations such as pregnancy, infectious hepatitis, use of estrogens, oral contraceptives containing estrogens and acute intermittent porphyria. Decreased thyroglobulin may occur in nephrosis, severe hypoproteinemia, severe liver disease, severe hyponatremia, acromegaly, and after therapy with androgens and corticosteroids.

Levothyroxine Sodium Food Interaction – Merck

Soy flour (pediatric formula), cottonseed cereals, nuts and fiber-based diet may bind and decrease the absorption of levothyroxine sodium from the gastrointestinal tract.

Action of the Substance Levothyroxine Sodium – Merck

Efficacy Results

subclinical hypothyroidism

Levothyroxine Sodium (active substance) at a dose of 0.05 mg per day was shown to be effective in improving the symptoms of subclinical hypothyroidism in a controlled clinical study. Symptoms improved in 8 of 14 patients treated with Levothyroxine Sodium compared to 3 of 12 patients treated with placebo.

congenital hypothyroidism

In a long-term evaluation study, including 49 adults previously treated with thyroxine replacement due to congenital hypothyroidism, it was verified that there were no subsequent adverse effects resulting from the treatment in parameters related to memory, attention and behavior, using high doses of thyroxine. In another study evaluating, after a follow-up of 5 years and 9 months, the use of high doses of Levothyroxine Sodium (active substance) in 18 children with congenital hypothyroidism treated with average doses of 12 mcg/kg/day, it was verified that patients treated early with high doses of Levothyroxine Sodium (active substance) had normal overall development and adequate entry into school term.

TSH suppressive therapy by stimulation with Levothyroxine Sodium (active substance) in patients with nodular thyroid disease

TSH suppressive therapy with Levothyroxine Sodium (active substance) has been evaluated in several clinical studies, with mixed results. In three prospective randomized studies including 167 patients treated for 6 months to 1.5 years with Levothyroxine Sodium (active substance) for thyroid nodule size reduction, the final result showed no more effective effect than placebo. In a randomized placebo-controlled study, the use of Levothyroxine Sodium (active substance) in different doses was compared in order to provide TSH suppression at high or low levels in 49 patients.

In the final analysis, after 12 months, reductions greater than 50% in nodule volume were observed in 37.5% of patients who had a high degree of suppression and in 41.6% of those who had a lesser degree of suppression, with no statistically significant differences between groups. In two other studies, using TSH suppression therapy, it was verified, in the first, a significant result in the reduction of the volume of the nodule after 6 months of treatment and, in the other, a decrease greater than 50% in the size of the nodule in 56% of the cases. cases that received Levothyroxine Sodium (active substance) and in 37% of those who did not have TSH suppressed. Although both studies were not placebo-controlled, the percentage of patients where there was a reduction in nodule size was greater than the percentage of 15 to 30% observed in case of spontaneous regression.

non-toxic multinodular goiter

The natural history of non-toxic multinodular goiter is characterized by unpredictable periods of stability and increase in volume, making it difficult to assess the effectiveness of using Levothyroxine Sodium (active substance) in these cases, since 5 to 10% of cases , may present spontaneous reduction in the size of the gland. In a study of 115 patients, a greater than 13% reduction in total thyroid gland volume was achieved in 58% of patients treated with TSH-suppressive doses for 9 months, with thyroid volume increasing again after cessation of therapy. A similar response was obtained in another study with 40 patients, however, it was not necessary to use suppressive doses.

diffuse goiter

In a clinical study, the return to normal levels of serum TSH with the use of Levothyroxine Sodium (active substance), allowed an average decrease of 32% in thyroid volume, with approximately 50% of cases maintaining a normal thyroid size after 2 years of therapy. In another study, the use of Levothyroxine Sodium (active substance) alone or in combination with iodine proved to be as effective as iodine alone in the treatment of endemic goiter. In this study, 166 patients received either Levothyroxine Sodium (active substance) at a dose of 150 mcg/day or iodine 400 mcg/day or a combination of 75 mcg/day of Levothyroxine Sodium (active substance) and 200 mcg of iodine for 8 months, obtaining There was a comparable reduction in goiter volume in all groups.

Patients with a history of thyroid irradiation

In patients who received cervical or cranial irradiation in childhood for benign conditions, prophylactic therapy with Levothyroxine Sodium (active substance) may be effective in reducing recurrence after surgical resection of benign nodules, and the dose used should be sufficient to reduce the serum TSH level to 0.5 to 1.0 µm/l. Patients who received cervical irradiation in childhood to treat conditions such as Hodgkin's disease, neuroblastoma, Wilms tumor and leukemia have a higher incidence of progression to hypothyroidism and the development of thyroid nodules, with a higher risk of radiation-induced thyroid cancer , and therapy with Levothyroxine Sodium (active substance) should be initiated in cases where the TSH concentration exceeds 3 um/l.

thyroid cancer

In differentiated thyroid tumors (papillary and follicular), which account for 90% of all cases of thyroid cancer, due to their natural history characterized by slow growth, clinical monitoring should be done for several decades before cancer is declared as cured and, during such period, the recommended treatment is the use of supraphysiological doses of Levothyroxine Sodium (active substance) to suppress TSH secretion, being accepted, in clinical practice, the maintenance of TSH levels lower than 0 .1 um/l.

In a retrospective study, evaluating the use of thyroid hormone in patients operated on for papillary thyroid cancer, recurrence in those who used hormone suppression was 17% in 10 years, compared to 34% in those not treated with hormones.

primary hypothyroidism

In a comparative randomized clinical study using LEVOID to evaluate efficacy and safety in the control of primary hypothyroidism, the effect of LEVOID and another commercial preparation of L-thyroxine on parameters of thyroid function (TSH and T ₄-free serum) evaluating patients with primary hypothyroidism due to previous total thyroidectomy due to differentiated thyroid carcinoma or multinodular goiter exerting compression on cervical structures. In this study, 61 patients were divided into 2 randomized groups: group I (n=31) receiving 100 micrograms/day of LEVOID daily and group II (n=30) receiving 100 micrograms/day of another approved commercial preparation of Levothyroxine Sodium (substance active). Samples were collected at baseline (without Levothyroxine Sodium (active substance)) and after 15, 30 and 45 days of hormone therapy.

Baseline TSH values ​​(mean ± SD) were 46.26 ± 26.18 μU/ml (group I) and 41.9 ± 23.1 μU/ml (group II). TSH values ​​declined significantly (F=120.3, plt;0.001) with time of use of Levothyroxine Sodium (active substance), with no statistically significant differences between groups I and II. Likewise, the serum T ₄ level increased significantly in both groups, with no significant difference (F=221.9, plt;0.001) between the groups, demonstrating a clear and increasing corrective action in patients with primary hypothyroidism.

References:

Cooper, D.S.; et al: L-thyroxine therapy in subclinical hypothyroidism. Ann Intern Med, 101: 18-24, 1984.

Oerbeck, B.; et al: Congenital hypothyroidism: no adverse effects of high dose thyroxine treatment on adult memory, attention and behaviour. Arch Dis Child, 9092:132-7, 2005.

Simoneau-Roy, J.; et al: Cognition and behaviour at school entry in children with congenital hypothyreoidism treated early with high-dose levothyroxine. J Pediatr, 144(6): 747-52, 2004.

Koc, M.; Ersoz, H; Akpinar, I; et al: Effect of low-dose levothyroxine on thyroid nodule volume: a crossover placebo-controlled trial. Clin Endocrinol 57:621-628,2002.

Mandel, S.J. et al: Levothyroxine therapy in patients with thyroid disease. Ann Intern Med, 119: 492- 502, 1993.

Hintze, G.; Emrich,D.; Kobberling, J.; et al: Treatment of endemic goiter due to iodine defiency with iodine, levothyroxine or both: results of a multicentre trial. Eur J Clin Invest 19:527-534, 1989.

Neves, SC; Seidenberg, K.; LiCS; Say, A; Zanini, AC; Medeiros-Neto, G.: Randomized, open, comparative clinical trial between two formulations of levo-thyroxine to evaluate efficacy and safety in controlling primary hypothyroidism, 2006.

Pharmacological Characteristics

Pharmacodynamic Properties

The thyroid gland produces triiodothyronine (T ₃ ) and thyroxine (T ₄ ) using iodine that is obtained from dietary sources or through the metabolism of thyroid hormones or other iodine components. About 100 mcg of iodine daily are required to generate sufficient amounts of thyroid hormone, with normal individual production being approximately 90 to 100 mcg of T ₄ and 30 to 35 mcg of T ₃ daily. It is estimated that around 80% of T ₃it is derived from peripheral metabolism and only about 20% is produced directly by the thyroid gland. Glandular function and hormone synthesis are regulated by a feedback system, so that the amounts of Levothyroxine Sodium (active substance) released into the circulation by a functioning thyroid gland are regulated by the amount of thyroid-stimulating hormone (TSH) secreted by the thyroid gland. anterior part of the pituitary gland.

The synthesis of TSH is, in turn, regulated both by the levels of Levothyroxine Sodium (active substance) and triiodothyronine in circulation and by thyrotropin-releasing hormone (TRH), secreted by thyrotropic cells located in the anterior portion of the pituitary gland. TSH and TRH secretion is regulated by negative feedback from thyroid hormone, predominantly from circulating T _{3 or T 3} produced from T ₄ conversion . Both T ₄ and T ₃ circulate bound primarily to carrier proteins, with T ₄ binding strongly to thyroxine-binding globulin (TBG) and weakly to thyroxine-binding prealbumin (TBPA) and albumin (~5% ) and the T₃ binds strongly to TBG and weakly to albumin and, to a lesser extent, to TBPA. Hypothyroidism is the most common pathology related to hormone deficiencies, presenting a wide variety of effects on target organs and a wide variety of clinical repercussions.

Hypothyroidism causes a wide spectrum of manifestations leading ultimately to a hypometabolic state characterized mainly by fatigue, lethargy, cold intolerance, slowness of speech and intellectual functions, decreased reflexes, periorbital edema, dryness and thickening of the skin. In children with such a state of deficiency, delay in growth and skeletal maturation may occur, in addition to a failure of ossification of the epiphyses and the development of the central nervous system. The main effect of exogenous thyroid hormones is to increase the metabolic rate of tissues, which are also related to tissue growth and differentiation.

Pharmacokinetic Properties

The absorption of Levothyroxine Sodium (active substance) is variable, ranging from 48% to 80% of the administered doses. This absorption variation is dependent on several factors, such as: vehicles used in its preparation, intestinal content, intestinal flora and dietary factors. Levothyroxine Sodium (active substance) has a greater binding affinity than triiodothyronine, both in circulation and in cells, which explains its longer duration of action. Daily, about 70% of metabolized thyroxine (T ₄ ) is deiodinated, and after deiodination, about 50% of thyroxine is converted into triiodothyronine (T ₃ ). The half-life of Levothyroxine Sodium (active substance) (T ₄) in normal plasma is from 5.3 to 9.5 days and regarding excretion, about 50% is done through the kidneys and 50% is through the faeces.

Mean CI (90%) of LEVOID pharmacokinetic parameters:

Ref.:

Comparative bioavailability study between a formulation containing Levothyroxine Sodium (active substance) produced by Aché Laboratórios Farmacêuticos (150 mcg tablet) versus a commercial reference formulation (150 mcg) in healthy volunteers. UNIFAC, 2005.

The onset of action of Levothyroxine Sodium (active substance) varies depending on the severity of the disease. The estimated mean time for onset of therapeutic action after administration of LEVOID is a few weeks.

Levothyroxine Sodium Storage Precautions – Merck

Levothyroxine should be stored at room temperature (between 15 and 30 ^o C), protected from light and moisture.

Batch number and manufacturing and expiry dates: see packaging.

Do not use medication that has expired. Store it in its original packaging.

All medication must be kept out of the reach of children.

Physical and organoleptic characteristics

Levothyroxine tablets are round, almost white, flat on both sides, scored on both sides, and labeled with each concentration (EM25; EM50; EM75; EM88; EM100; EM112; EM125; EM150; EM175 ; EM200) on one side.

Before use, observe the appearance of the medicine. If it is within its expiry date and you observe any change in appearance, consult your pharmacist to find out if you can use it.

Levothyroxine Sodium Legal Notice – Merck

M.S. 1.0089.0355.

Responsible Pharmacist:

Fernanda P. Rabello
CRF-RJ no. 16979.

Imported and packaged by:

Merck SA
CNPJ 33.069.212/0001-84
Estrada dos Bandeirantes, 1099
Rio de Janeiro – RJ – CEP 22710-571
Indústria Brasileira.

Made by:

Merck KGaA
Darmstadt – Germany

Or

Merck SA de CV

Naucalpan de Juarez
Mexico.

Sale under medical prescription.