Liothyronine Sodium 25 mcg

Liothyronine Sodium 25 mcg (Liothyronine (as liothyronine sodium)) · ATC H03AA02

Thyroid hormone · triiodothyronine (T3) replacement

Each tablet contains Liothyronine Sodium 25 micrograms.

For the full list of excipients, see section 6.1.

Tablet for oral administration.

Therapeutic indications

Thyroid hormone replacement in hypothyroid states, as determined by a physician.

Posology and method of administration

Take orally as directed by a physician. Swallow whole with water. Do not exceed the prescribed dose.

Contraindications

Known hypersensitivity to the active substance. Untreated thyrotoxicosis, uncorrected adrenal insufficiency and acute myocardial infarction. Use with caution in cardiovascular disease. Under medical supervision only.

Special warnings and precautions for use

Keep out of the reach and sight of children.

Interaction with other medicinal products

Coumarin anticoagulants (warfarin, acenocoumarol)

Thyroid hormone accelerates the catabolism of vitamin K-dependent clotting factors, potentiating the anticoagulant effect and raising INR with a real risk of bleeding; INR requires close monitoring and anticoagulant dose review by the prescriber on any change in thyroid status.

Insulin and oral antidiabetic agents

Restoration of the euthyroid state increases metabolic rate and insulin requirement; initiation, dose increase or withdrawal of liothyronine can destabilise glycaemic control in either direction and warrants closer blood glucose monitoring.

Bile acid sequestrants (cholestyramine, colestipol, colesevelam) and ion-exchange resins

Bind thyroid hormone in the gut and interrupt enterohepatic recycling, markedly reducing absorption; administration must be separated by an interval of several hours as directed by the prescriber.

Polyvalent cations — oral calcium salts, ferrous sulphate, aluminium- and magnesium-containing antacids, sucralfate, sevelamer

Form insoluble complexes that impair absorption and may precipitate loss of biochemical control; dosing should be separated in time.

Sympathomimetic amines and catecholamines

Thyroid hormone sensitises the myocardium to catecholamines; combined use increases the risk of coronary insufficiency and arrhythmia, particularly in patients with coronary artery disease.

Amiodarone, oestrogens, androgens, glucocorticoids, propylthiouracil, propranolol and phenytoin

Alter thyroid hormone binding, deiodination or clearance — oestrogens raise and androgens or glucocorticoids lower thyroxine-binding globulin, while amiodarone, propylthiouracil, propranolol and glucocorticoids inhibit peripheral T4-to-T3 conversion — so thyroid function tests should be reassessed when these are started or stopped.

Use in special populations

Pregnancy and breastfeeding

Thyroid hormone replacement should be continued in pregnancy, as maternal hypothyroidism carries risk to foetal neurodevelopment; however, levothyroxine is generally preferred because T3 crosses the placenta poorly and standard maternal targets are defined in terms of T4 and TSH. Thyroid function requires monitoring each trimester and dosage adjustment by the prescriber. Minimal quantities pass into breast milk and breastfeeding is not contraindicated at replacement exposure.

Paediatric population

Thyroid hormone is essential to skeletal growth and central nervous system maturation, and congenital hypothyroidism requires prompt treatment. Liothyronine is not the agent of choice in children, in whom levothyroxine gives more stable exposure; where used, growth, bone maturation and thyroid function require close monitoring, and transient hair loss and pseudotumour cerebri have been reported.

Elderly

Initiate at reduced exposure and increase gradually as determined by the prescriber. Older patients, and any patient with coronary artery disease, are at risk of precipitating angina, arrhythmia or myocardial infarction; the rapid onset and marked peaks characteristic of T3 make this agent less suitable than levothyroxine where cardiac risk is present.

Renal impairment

No specific dose adjustment is established, as elimination is predominantly by deiodination and hepatobiliary routes; nevertheless thyroid function and clinical response should be monitored, and the altered protein binding seen in nephrotic syndrome may complicate interpretation of thyroid function tests.

Hepatic impairment

Hepatic deiodination and conjugation contribute substantially to clearance and may be reduced in significant impairment; monitoring of thyroid function with cautious dose titration is advised, and results should be interpreted alongside any change in binding-protein concentrations.

Adrenal insufficiency and untreated cardiovascular disease

Contraindicated in untreated thyrotoxicosis, untreated adrenal insufficiency and acute myocardial infarction. Where adrenal insufficiency coexists with hypothyroidism, corticosteroid replacement must be established before thyroid hormone is introduced, since accelerated cortisol metabolism may otherwise precipitate an adrenal crisis.

Athletes

Thyroid hormones, including liothyronine, are not currently prohibited under the WADA Prohibited List, and this substance may be used therapeutically by athletes under medical supervision. Its status is nevertheless kept under review by WADA; non-therapeutic use for body composition purposes carries substantial cardiac and skeletal risk and is not supported.

Undesirable effects

Cardiac

Tachycardia, palpitations, atrial fibrillation and other arrhythmias, angina pectoris, increased cardiac workload and, in overtreatment, myocardial infarction or cardiac failure; risk is greatest in pre-existing coronary disease

Endocrine and metabolic

Features of iatrogenic thyrotoxicosis with suppressed TSH — heat intolerance, hyperhidrosis, weight loss despite increased appetite, increased metabolic rate; unmasking of latent adrenal insufficiency

Nervous system and psychiatric

Tremor, headache, insomnia, restlessness, anxiety, irritability, emotional lability; in children, pseudotumour cerebri has been reported

Musculoskeletal and connective tissue

Muscle weakness and cramp; prolonged suppressive exposure is associated with reduced bone mineral density and increased fracture risk, particularly in postmenopausal women

Gastrointestinal

Diarrhoea, increased stool frequency, vomiting, abdominal cramp

General

Fatigue, fever, flushing, weight change; menstrual irregularity and impaired fertility with over- or under-treatment

Skin and subcutaneous tissue and hair

Rash, urticaria, pruritus, hyperhidrosis, partial and usually transient hair loss (most often reported in children during the early months of treatment)

Immune system

Hypersensitivity reactions to excipients rather than to the hormone itself, including rash, angioedema and, rarely, anaphylaxis

Overdose

Overdosage produces the clinical picture of thyrotoxicosis, with tachycardia, arrhythmia including atrial fibrillation, tremor, agitation, hyperpyrexia, sweating, diarrhoea, weight loss and, in severe cases, features of thyroid storm with cardiac failure or seizure; because liothyronine acts directly and rapidly, symptoms may appear within hours rather than over days as with levothyroxine. There is no specific antidote; management is symptomatic and supportive, comprising withdrawal of the medicine, cardiac monitoring, cooling, fluid and electrolyte replacement and a beta-blocker for adrenergic features, with activated charcoal considered in recent large ingestion. Given the short half-life the disturbance is usually self-limiting once the drug is withdrawn.

Pharmacodynamic properties

Liothyronine sodium is the synthetic sodium salt of L-tri-iodothyronine (T3), the biologically active thyroid hormone (ATC H03AA02). Whereas levothyroxine (T4) is essentially a prohormone requiring peripheral deiodination by types 1 and 2 iodothyronine deiodinase, liothyronine acts directly: it enters the cell, binds nuclear thyroid hormone receptors TR-alpha and TR-beta with roughly ten times the affinity of T4, and the ligand–receptor complex regulates transcription of thyroid-responsive genes. The consequences are increased basal metabolic rate and oxygen consumption, stimulation of carbohydrate, protein and lipid metabolism, upregulation of myocardial beta-adrenoceptors with increased heart rate and contractility, and — during development — essential effects on skeletal growth and central nervous system maturation. Relative to levothyroxine, onset is faster, potency is approximately three- to four-fold greater on a weight basis, and effects are correspondingly shorter-lived, producing more pronounced peaks in serum T3.

Pharmacokinetic properties

Liothyronine is almost completely absorbed from the gastrointestinal tract, with oral bioavailability of approximately 95% and peak serum concentrations at about 2 to 4 hours; absorption is reduced by food and by calcium, iron and other polyvalent cations. It is extensively bound to plasma proteins — chiefly thyroxine-binding globulin, transthyretin and albumin — though its affinity is substantially lower than that of thyroxine, which accounts for its larger free fraction and more rapid tissue availability. Elimination proceeds by sequential deiodination to di-iodothyronine and further inactive iodothyronines, together with hepatic glucuronide and sulphate conjugation and biliary excretion with enterohepatic recycling. The serum half-life is approximately 1 to 2 days in the euthyroid state — markedly shorter than the 6 to 7 days of levothyroxine — and is shortened in hyperthyroidism and prolonged in hypothyroidism; steady state is reached within a few days.

List of excipients

Sucrose, maize starch, gelatin, colloidal anhydrous silica, talc, magnesium stearate. Uncoated tablet, lactose-free. At 25 micrograms the active is a very small fraction of the tablet mass, so liothyronine sodium is granulated with the gelatin binder onto a sucrose–starch diluent base by geometric dilution and low-shear ordered mixing; blend uniformity is sampled at defined bin positions and every batch is tested for content uniformity (Ph. Eur. 2.9.40 / USP <905>), assay and dissolution. Compression is performed under controlled room humidity to protect the hormone.

Excipient warnings

Contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicinal product.

Incompatibilities

Not applicable to this dosage form.

Shelf life

24 months from the date of manufacture in the unopened container.

After first opening

No special in-use storage requirements beyond those in section 6.4. Keep the tablets in the intact blister until immediately before administration and retain the desiccant sachet in the carton; the product is moisture- and light-sensitive, and a tablet removed from its blister should be taken at once or discarded.

Storage

Store below 25 °C in a dry place. Keep tablets in the outer carton until use.

Container

50 uncoated tablets in cold-form OPA/aluminium/PVC–aluminium blisters (10 tablets per blister, 5 blisters per carton) with a silica-gel desiccant sachet, in a tamper-evident, GS1-serialised outer carton with the patient leaflet. The high-barrier cold-form blister is used in preference to a clear film to limit moisture and light ingress at this strength. Primary packaging materials are qualified to ISO 15378. Not all pack sizes may be marketed.

Disposal

No special requirements for handling. Any unused medicinal product or waste material, including partially used blisters, the desiccant sachet and the outer carton, should be disposed of in accordance with local requirements; do not dispose of via wastewater or household waste.

Pack

50 Tablets

GTIN

05012345678924

Serial

7630 5418 3296 24

LOT

LT2710K

MFG

12 / 2027

EXP

12 / 2030

Every carton carries a GS1 DataMatrix and a verification code; a pack can be checked at ergopharm.net/verify.

Ergopharm Advanced Research Centre, Tandalja, Vadodara, Gujarat 390012, India. For Export Only.

Report a suspected adverse reaction or quality defect to pv@ergopharm.net.