ELTROXIN TABLETS 100MCG

Mechanism of action

Levothyroxine acts as a replacement for the deficient thyroid hormone in conditions such as hypothyroidism. It increases the metabolic rate and decreases thyroid-stimulating hormone (TSH) production from the anterior pituitary gland. In peripheral tissues, T4 is converted to triiodothyronine (T3), which has a broader range of stimulatory effects on cell metabolism. Thyroid hormones exert both genomic and non-genomic effects, influencing growth and development, particularly in the fetus and newborn, as well as maintaining various metabolic processes in adults.

Pharmacodynamics

Levothyroxine maintains normal T4 levels in patients with hypothyroidism, exerting the same physiological effects as endogenous T4. It has a narrow therapeutic index, necessitating careful titration to achieve a euthyroid state, with TSH levels monitored within a therapeutic range of 0.4–4.0 mIU/L. Over- or under-treatment may lead to significant adverse effects, including impacts on growth, cardiovascular health, metabolic function, and cognitive abilities. Regular monitoring of TSH levels is crucial to prevent complications such as hyperthyroidism, characterized by symptoms like increased heart rate and weight loss.

Pharmacokinetics

Levothyroxine is well absorbed from the gastrointestinal tract, with peak serum concentrations occurring approximately 2 to 4 hours after oral administration. It is highly protein-bound, primarily to thyroxine-binding globulin, and has a long half-life, generally ranging from 7 to 10 days, which allows for once-daily dosing. The metabolism of levothyroxine predominantly occurs in the liver and kidneys, where it is converted to T3. Factors such as age, sex, and concurrent medications can influence its pharmacokinetics and necessitate dosage adjustments.

Contra-indications

• Hypersensitivity to levothyroxine or any of its excipients
• Untreated hyperthyroidism
• Acute myocardial infarction
• Adrenal insufficiency

Adverse effects

• Hyperthyroidism
• Palpitations
• Increased heart rate
• Weight loss
• Nervousness
• Insomnia
• Tremors
• Heat intolerance
• Diarrhea
• Menstrual irregularities
• Osteoporosis (with prolonged use)

Interactions

• Anticoagulants (increased effect)
• Insulin and oral hypoglycemics (increased dose may be needed)
• Calcium and iron supplements (may reduce absorption of levothyroxine)
• Antacids containing aluminum, magnesium, or calcium (may reduce absorption)
• Certain antidepressants (may enhance effects of levothyroxine)

Precautions

• Caution in patients with cardiovascular disease
• Caution in patients with diabetes mellitus
• Monitor thyroid function tests regularly
• Adjust dose carefully in elderly patients

Pregnancy

Levothyroxine is considered safe during pregnancy. It is important to maintain adequate thyroid hormone levels throughout pregnancy to support fetal development.

Breast-feeding

Levothyroxine is excreted in breast milk in small amounts, but is generally considered safe for use during breastfeeding.

Storage

Store at room temperature, away from moisture and heat. Keep the container tightly closed.

Formulations

• Tablets (various strengths)
• Oral solution

Mechanism of action

Levothyroxine is a synthetically prepared levo-isomer of the thyroid hormone thyroxine (T₄, a tetra-iodinated tyrosine derivative) that acts as a replacement in deficiency syndromes such as hypothyroidism. T₄ is the major hormone secreted from the thyroid gland and is chemically identical to the naturally secreted T₄: it increases metabolic rate, decreases thyroid-stimulating hormone (TSH) production from the anterior lobe of the pituitary gland, and, in peripheral tissues, is converted to T₃. Thyroxine is released from its precursor protein thyroglobulin through proteolysis and secreted into the blood where is it then peripherally deiodinated to form triiodothyronine (T₃) which exerts a broad spectrum of stimulatory effects on cell metabolism. T₄ and T₃ have a relative potency of ~1:4. Thyroid hormone increases the metabolic rate of cells of all tissues in the body. In the fetus and newborn, thyroid hormone is important for the growth and development of all tissues including bones and the brain. In adults, thyroid hormone helps to maintain brain function, food metabolism, and body temperature, among other effects. The symptoms of thyroid deficiency relieved by levothyroxine include slow speech, lack of energy, weight gain, hair loss, dry thick skin and unusual sensitivity to cold. The thyroid hormones have been shown to exert both genomic and non-genomic effects. They exert their genomic effects by diffusing into the cell nucleus and binding to thyroid hormone receptors in DNA regions called thyroid hormone response elements (TREs) near genes. This complex of T₄, T₃, DNA, and other coregulatory proteins causes a conformational change and a resulting shift in transcriptional regulation of nearby genes, synthesis of messenger RNA, and cytoplasmic protein production. For example, in cardiac tissues T₃ has been shown to regulate the genes for α- and β-myosin heavy chains, production of the sarcoplasmic reticulum proteins calcium-activated ATPase (Ca2+-ATPase) and phospholamban, β-adrenergic receptors, guanine-nucleotide regulatory proteins, and adenylyl cyclase types V and VI as well as several plasma-membrane ion transporters, such as Na+/K+–ATPase, Na+/Ca2+ exchanger, and voltage-gated potassium channels, including Kv1.5, Kv4.2, and Kv4.3. As a result, many cardiac functions including heart rate, cardiac output, and systemic vascular resistance are closely linked to thyroid status. The non-genomic actions of the thyroid hormones have been shown to occur through binding to a plasma membrane receptor integrin aVb3 at the Arg-Gly-Asp recognition site. From the cell-surface, T₄ binding to integrin results in down-stream effects including activation of mitogen-activated protein kinase (MAPK; ERK1/2) and causes subsequent effects on cellular/nuclear events including angiogenesis and tumor cell proliferation.

Pharmacodynamics

Oral levothyroxine is a synthetic hormone that exerts the same physiologic effect as endogenous T₄, thereby maintaining normal T₄ levels when a deficiency is present. Levothyroxine has a narrow therapeutic index and is titrated to maintain a euthyroid state with TSH (thyroid stimulating hormone) within a therapeutic range of 0.4–4.0 mIU/L. Over- or under-treatment with levothyroxine may have negative effects on growth and development, cardiovascular function, bone metabolism, reproductive function, cognitive function, emotional state, gastrointestinal function and glucose and lipid metabolism. The dose of levothyroxine should be titrated slowly and carefully and patients should be monitored for their response to titration to avoid these effects. TSH levels should be monitored at least yearly to avoid over-treating with levothyroxine which can result in hyperthyroidism (TSH <0.1mIU/L) and symptoms of increased heart rate, diarrhea, tremor, hypercalcemia, and weakness to name a few. As many cardiac functions including heart rate, cardiac output, and systemic vascular resistance are closely linked to thyroid status, over-treatment with levothyroxine may result in increases in heart rate, cardiac wall thickness, and cardiac contractility and may precipitate angina or arrhythmias, particularly in patients with cardiovascular disease and in elderly patients. In populations with any cardiac concerns, levothyroxine should be initiated at lower doses than those recommended in younger individuals or in patients without cardiac disease. Patients receiving concomitant levothyroxine and sympathomimetic agents should be monitored for signs and symptoms of coronary insufficiency. If cardiac symptoms develop or worsen, reduce the levothyroxine dose or withhold for one week and restart at a lower dose. Increased bone resorption and decreased bone mineral density may occur as a result of levothyroxine over-replacement, particularly in post-menopausal women. The increased bone resorption may be associated with increased serum levels and urinary excretion of calcium and phosphorous, elevations in bone alkaline phosphatase and suppressed serum parathyroid hormone levels. Administer the minimum dose of levothyroxine that achieves the desired clinical and biochemical response to mitigate this risk. Addition of levothyroxine therapy in patients with diabetes mellitus may worsen glycemic control and result in increased antidiabetic agent or insulin requirements. Carefully monitor glycemic control after starting, changing or discontinuing levothyroxine.