Project Description

Levothyroxine sodium

tablets 0.0001 g in blister –Levothyroxinesodium 0.0001 g

international nonproprietary name

Levothyroxine sodium.

Ref

BP-0072

Pharmacotherapeutic group

Drugs for the treatment of thyroid gland.

Composition of the preparation

Activesubstance – levothyroxinesodium – 0.0001 g

Вauxiliary substances: lactose, starch, sucrose, calcium stearate

Pharmacological action

Pharmacodynamics

The drug stimulates deficiency recovery of thyroid gland hormones. In low doses it is anabolic, in moderate doses it stimulates growth and development, increases tissue demand in oxygen, regulates protein, fat and carbon metabolism, increases cardiovascular and CNS activity, in high doses inhibits generation of thyrotropin-release and thyrotrophic hormones.

Metabolism mechanism intends receptor binding with genes, alteration of oxidation in mitochondrions and regulation of substrate and cation streams outside and inside the cells.

Clinical effect in hypertensia is revealed in 3-5 days. Early diffusion hyperplastic diffuse goiter decreases or disappears in 3-6 months, if later nodular phase, significant reduction of thyroid gland is manifested in 30% of cases, practically in all the patients there is evidence of the prevention of its further growth.

Pharmacokinetics

After oral intake the drug is easily absorbed in gastrointestinal tract. Theabsorptionis48-79%. Fasting intake increases the absorption of the active substance. Max.plasma concentration is evident in 6 h. plasma protein binding is more than 99%. Metabolic clearance os 1.2 l of plasma a day. Half-excretion is about 8 days. Biotransformation is a gradual deiodizing (inclusive T3 generation) mainly in liver, muscles, brain and is liver conjugation with glycoronate and sulphateof.

Indications 

Hyperthyroid condition of various ethiology (caused by intervention and medicamental effect inclusive), suppressive thyroid therapy of simple (nontoxic) goiter, autoimmune Hashimoto’s thyroiditis, multinodular goiter, thyroid-static therapy of hyperthyrosis (complex therapy after euthyroid phase), thyroid-tropin-dependent high differentiated papillary or follicular carcinoma of thyroid gland (complex therapy), prevention of goiter recurrence after resection, suppressive scintigraphic test of thyroid gland.

special indication

It is recommended to control regularly blood thyrotrophic hormone content, the higher level indicates insufficient drug dose. Suppressive thyroid therapy is evaluated also by radioactive iodine capture. In ancient multinodular goiter perform stimulating test with thyroid-tropin-releasing-hormone before treatment.

Mainly in hyperthyrosis restore metabolism gradually, in particular in elderly patients with cardiovascular pathology. In elderly patients the initial dose is NMT 50 mg.

Administer with care in stenocardia, hypertenisa, tachyarrythmia, epilepsy, insufficient adrenal cortex and hypophysis function, diabetes. In differentiated diagnostic test of thyroid suppression in patients with diabetes increase antidiabetic dose.

In children a very high initial dose may cause hepatic disorder. In children with convulsion attack possible increase of the attack recurrence.

In II and III pregnancy term the dose is usually increased by 25%. Administer with care in severe ancient hypo-function of thyroid gland. Eliminate eventual hypo-phase or hypothalamic hyperthyrosis before treatment.

In pregnancy and lactation drug intake is medically controlled. It is contraindicated in combination with thyroid static agents in pregnancy.

special warning

Not established

Dosage and method of administration

Oral fasting intake with small quantity of water. In hypotensia the initial dose is 25-100 mg a day, with gradual increase (by 25-50 mg every 2-3 weeks) to maintaining dose 125-250 mg a day, after malignant neoplasm of thyroid gland intervention up to 300 mg a day. In children the initial dose is 12.5-50 mg, the maintaining dose is 100-150 mg a day. Incomplextherapyofhyperthyrosis5-100 mgaday. For suppressive test: during 14 days 200 mg a day or 3 mg 1 time within 7 days before the repeated scintigram. Euthyroid goiter and prevention of its recurrence after resection: in adults 75-200 mg a day, in children 12.5-150 mg a day.

overdosage

Symptoms: thyreotoxic attack, sometimes delayed for several days high dose intake of the drug.

Treatmentе: administration of beta-adrenoblocators, i.v. corticosteroids, plasmapheresis.

Dosageform

safety measures

Not established

Side effects

Tachycardia, rhythmdisturbance, posteriorbreastbonepain, tremor, anxiety, insomnia, hyperhidrosis, reducedbodyweight, diarrhea, alopecia, adrenaldysfunction (hypophysicalorhypothalamichyperthyrosis), renalfailureinchildren. In certain cases eventual body weigh increase cause by appetite increase.

Contraindications

Hypersensitivity, untreated thyrotoxicosis, acute myocardial infarction, stenocardia, myocarditis, tachysystolic rhythm disturbanc, heart failure, severe hypertensia, non-corrected adrenal cortex dysfunction, elderly age (after 65).

Interactions with other medicinal preparations

The drug enhances the activity of antidepressants, anticoagulants, reduces insulin, oral hypoglycemic and cardiac glycoside agent action. Colestiramin, colestipol, aluminum hydrate decreases drug absorption. Concurrent administration of estrogen-containing contraceptives for oral intake may require drug dose increase. Phenobarbital and phenotoin increases metabolic clearance maintaining unaltered the ratio of free T3 and T4 in blood. Protein binding is modified by anabolic steroids, asparaginase, clofibrate, furosemide, salicylate, tamoxiphen. Synthesis, distribution and metabolism is subject to amiodaron, aminoglytetimid, paraaminosalicylic acid, ethionamide, antithyreodic agents, beta-adrenoblocators, carbamasepin, chloralhydrate, diazepam, lovodop, dophamin, methoclopramyde, lovostatin, somatostatin and others.

The form of release

Tablets 0.0001 g of levothyroxine sodium in tablets.