Adult: Individualise dosage based on patient's physical condition, age, cardiac risk factors, and clinical severity and duration of myxoedema symptoms. Initially, 300-500 mcg as loading dose, followed by a maintenance dose of 50-100 mcg daily until the patient is stable and can tolerate oral treatment. Doses are given via IV inj at a Max rate of 100 mcg/min. Elderly: Initiate at lower doses.
Oral TSH suppression
Adult: Adjunct to surgery and radioiodine therapy to manage thyrotropin-dependent well-differentiated thyroid cancer: Individualise dosage based on patient’s clinical response, laboratory parameters, age, weight, CV status, concurrent conditions or medications, and nature of disease being treated. Doses >2 mcg/kg daily may be given as a single dose to suppress TSH levels to <0.1 milliunits/L. In patients with high-risk tumours, the target level for TSH suppression may be lower. Dosage and treatment recommendations may vary among individual products or countries (refer to detailed product guidelines).
Adult: Replacement therapy in congenital or acquired cases: Individualise dosage based on patient's clinical response, laboratory parameters, age, weight, CV status, concurrent conditions or medications, and nature of disease being treated. Initially, 50-100 mcg daily, may increase by 25-50 mcg at approx 3- to 4-week intervals until thyroid deficiency is corrected and maintenance dose is established. Usual maintenance: 100-200 mcg daily. Alternatively, initiate at approx 1.6 mcg/kg daily, adjusted by 12.5-25 mcg increments every 4-6 weeks until serum TSH returns to normal and euthyroid state is achieved. >50 years Initially, 12.5-50 mcg daily, may be increased by 12.5-25 mcg increments at intervals ranging from approx 2-8 weeks. Usual maintenance: 50-200 mcg daily. Daily doses are taken as a single dose. Dosage and treatment recommendations may vary among individual products or countries (refer to detailed product guidelines). Child: Replacement therapy in congenital or acquired cases: 0-3 months 10-15 mcg/kg daily; >3-6 months 8-10 mcg/kg daily; >6-12 months 6-8 mcg/kg daily; 1-5 years 5-6 mcg/kg daily; 6-12 years 4-5 mcg/kg daily. >12 years Patients with incomplete growth and puberty: 2-3 mcg/kg daily; Patients with complete growth and puberty: Approx 1.6 mcg/kg daily, adjusted by 12.5-25 mcg increments every 4-6 weeks until serum TSH returns to normal and euthyroid state is achieved. Individually adjust dose based on response and laboratory parameters. Alternative dosing regimens: For congenital cases: Neonates and infants Initially, 10-15 mcg/kg daily for the 1st 3 months, then individually adjust dose according to clinical findings, thyroid hormone and TSH values. For acquired cases: Children Initially, 12.5-50 mcg daily, then increase gradually every 2-4 weeks based on clinical findings, thyroid hormone and TSH values until full replacement dose is achieved. Maintenance: 100-150 mcg/m2 daily. Daily doses are given as a single dose. Dosage and treatment recommendations may vary among individual products or countries (refer to detailed product guidelines). Elderly: Initially, 12.5-50 mcg daily as a single dose, may be increased gradually by 12.5-25 mcg increments at intervals ranging from approx 2-8 weeks. Usual maintenance: 50-200 mcg daily. Dosage and treatment recommendations may vary among individual products or countries (refer to detailed product guidelines).
Oral Severe and chronic hypothyroidism
Adult: Individualise dosage based on patient's clinical response, laboratory parameters, age, weight, CV status, concurrent conditions or medications, and nature of disease being treated. Initially, 12.5-25 mcg daily as a single dose, may be increased gradually by increments of 12.5-25 mcg at 2- to 4-week intervals until serum TSH levels return to normal and euthyroid state is achieved. Dosage and treatment recommendations may vary among individual products or countries (refer to detailed product guidelines).
Special Patient Group
Patients with CV disease: Initially, 12.5-50 mcg daily, may be increased by 12.5-25 mcg increments at intervals of approx 2-8 weeks. Usual maintenance: 50-200 mcg daily. Dosage and treatment recommendations may vary among individual products or countries (refer to detailed product guidelines).
Neonates (0-3 months) at risk of cardiac failure: Lower initial doses may be considered. Increase dose at 4- to 6-week intervals depending on clinical and laboratory response, as necessary.
Older children at risk of hyperactivity: Initiate at 1/4 of the recommended full replacement dose. Increase dose by 1/4 of the full recommended replacement dose at weekly intervals until full replacement dose is achieved.
Patient with underlying CV disease: Initiate at lower doses.
Should be taken on an empty stomach. Take 30 min-1 hr before meals.
Thyrotoxicosis; uncorrected adrenal insufficiency; acute MI, acute myocarditis, acute pancarditis. Contraindications may vary among individual products (refer to specific product labelling for detailed information).
Patient with adrenal insufficiency; CV disease (e.g. coronary artery disease, angina, hypertension); diabetes mellitus, diabetes insipidus; epilepsy. Not indicated for weight loss or treatment of obesity; suppression of benign thyroid nodules in iodine-sufficient patients; hypothyroidism treatment during recovery phase of subacute thyroiditis. IV inj is not recommended as a substitute for oral preparation. Switching between different brands or preparations is not advisable; if the brand or preparation is changed, closely monitor the patient's laboratory parameters (e.g. serum TSH levels). Children and elderly. Pregnancy and lactation.
Significant: Increased heart rate, cardiac wall thickness or contractility, and precipitated angina (during overtreatment, specifically in elderly and patients with CV disease); worsened glycaemic control (in patients with diabetes mellitus); partial hair loss (during the 1st months of treatment, usually transient); increased bone resorption and reduced BMD (during overreplacement, particularly in postmenopausal women). Rarely, seizures. Cardiac disorders: Palpitations. Endocrine disorders: Thyrotoxic crisis. Gastrointestinal disorders: Diarrhoea, vomiting, abdominal cramps. General disorders and administration site conditions: Malaise, pyrexia, heat intolerance, oedema. Immune system disorders: Hypersensitivity reaction. Investigations: Weight loss. Metabolism and nutrition disorders: Increased appetite. Musculoskeletal and connective tissue disorders: Arthralgia, muscle weakness and spasms. Nervous system disorders: Headache, tremors. Psychiatric disorders: Insomnia, restlessness, nervousness, anxiety, irritability. Reproductive system and breast disorders: Irregular menstruation. Respiratory, thoracic and mediastinal disorders: Dyspnoea. Skin and subcutaneous tissue disorders: Rash, pruritus, hyperhidrosis. Vascular disorders: Flushing. Potentially Fatal: IV (overtreatment, particularly in elderly and patients with CV disease): Severe CV effects (e.g. myocardial ischaemia, MI, or worsening of CHF).
Obtain thyroid function tests (e.g. serum TSH, T4, free T4, or T3 levels) periodically during treatment and dose changes. Perform routine clinical examinations at regular intervals in children to assess mental and physical growth, development, and bone maturation. Monitor heart rate, blood pressure, renal function; BMD (particularly with chronic use in postmenopausal women). Perform ECG before initiating treatment especially in patients with known or at-risk of CV disease. Closely assess for new or worsening CV symptoms (in patients with CV disease and the elderly) and signs and symptoms of hypo- or hyperthyroidism.
Symptoms: Headache, muscle cramps, sweating, tremor, flushing, confusion, insomnia, anxiety, agitation, hyperpyrexia, chest pain, tachycardia or arrhythmia, and coma. Management: Symptomatic and supportive treatment. Give oral activated charcoal within 1 hour of ingestion of >10 mg (adult) or >5 mg (child) dose; assess blood concentration of free thyroxine concentration 6-12 hours after ingestion. Gastric lavage or emesis may also be used following recent ingestion. Administer β-blockers (e.g. propranolol) to control symptoms manifesting as β-adrenergic effects (e.g. tachycardia, hyperkinesia, anxiety, agitation). In extreme doses, may consider plasmapheresis.
Enhanced or increased metabolism with carbamazepine, phenytoin, phenobarbital, primidone, and rifampicin. May reduce absorption with antacids, cimetidine, PPIs, sucralfate, oral Fe, Ca salts, phosphate binders (e.g. sevelamer), bile acid sequestrants (e.g. colestyramine, colestipol), ion exchange resins (e.g. sodium polystyrene sulfonate), and orlistat. Risk of marked tachycardia and hypertension with ketamine. May decrease the effects of digitalis glycosides. Increased risk of cardiac arrhythmias and CNS stimulation with TCAs (e.g. amitriptyline). May result in false low plasma concentration when given with anti-inflammatory agents (e.g. aspirin, phenylbutazone). May increase the effects of anticoagulants (e.g. warfarin) and sympathomimetic agents (e.g. phenylephrine, epinephrine). Sertraline, tyrosine kinase inhibitors (e.g. imatinib), and estrogen derivatives may reduce the effects of levothyroxine sodium. Androgens and corticosteroids may decrease the levothyroxine-binding globulins serum levels. Peripheral conversion of levothyroxine sodium to triiodothyronine may be inhibited by amiodarone and β-blockers (e.g. propranolol), resulting in reduced efficacy. May cause an increase in dose requirements of antidiabetic drugs.
Concomitant administration with enteral nutrition may result in decreased bioavailability and serum thyroxine levels. May reduce absorption with certain foods (e.g. soybean flour, cottonseed meal, walnuts, dietary fibre). May delay absorption and reduce bioavailability with grapefruit juice.
Description: Levothyroxine sodium, a synthetic form of thyroxine, is metabolised into triiodothyronine (active metabolite). Both levothyroxine sodium and triiodothyronine diffuse into cell nucleus and bind to thyroid receptor proteins attached to the deoxyribonucleic acid (DNA) and exert their physiologic effects by controlling DNA transcription and protein synthesis. Its main pharmacologic activity is to increase the rate of cell metabolism. Onset: 3-5 days (oral); 6-8 hours (IV). Pharmacokinetics: Absorption: Variably and incompletely absorbed from the gastrointestinal tract. Reduced absorption with certain foods (e.g. soybean flour, dietary fibre, walnuts). Bioavailability: Oral: 79-81% (fasting state). Time to peak plasma concentration: 2-4 hours. Distribution: Enters breast milk (small amounts). Plasma protein binding: >99%, including thyroxine-binding globulin, thyroxine-binding pre-albumin, and albumin. Metabolism: Metabolised in the liver (major site) and kidney via deiodination to active triiodothyronine (T3) and inactive reverse triiodothyronine (rT3), which both undergo further deiodination to diiodothyronine. May also be metabolised via conjugation with glucuronides and sulfates and undergo enterohepatic recirculation. Excretion: Mainly via urine (as free drug, deiodinated metabolites, and conjugates); faeces (approx 20%). Elimination half-life: Approx 6-7 days (euthyroid patient); 9-10 days (hypothyroid patient); 3-4 days (hyperthyroid patient).
Tab/cap/oral solution: Store between 15-30°C. Protect from heat, moisture, and light. IV inj: Store between 20-25°C. Protect from light.
H03AA01 - levothyroxine sodium ; Belongs to the class of thyroid hormones.
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