Euthyrox 100

Indications

• Primary hypothyroidism
• Subclinical hypothyroidism
• Secondary hypothyroidism due to pituitary disease
• Congenital hypothyroidism
• Thyroid hormone replacement in patients with thyroidectomy
• Management of myxedema coma (in emergency settings)
• Hypothyroidism in patients with cardiac disease (with caution)

Dosage

Adults: Initially 1.6 micrograms/kg once daily, adjusted according to response, round dose to the nearest 25 micrograms. For the elderly, initially 25–50 micrograms once daily, adjusted in steps of 25 micrograms every 4 weeks

Mechanism of action

Levothyroxine sodium acts as a replacement for endogenous thyroxine, binding to thyroid hormone receptors in the nucleus of cells. This initiates the transcription of genes that regulate various metabolic processes, including protein synthesis, carbohydrate metabolism, and lipid metabolism. The increase in metabolic rate enhances the overall physiological processes in the body, promoting normal growth and development.

Pharmacodynamics

The pharmacodynamic effects of levothyroxine sodium include increased basal metabolic rate, enhancement of gluconeogenesis and glycogenolysis, and promotion of protein synthesis. It also plays a vital role in the development of the central nervous system and regulates the metabolism of carbohydrates and fats. The effects are dose-dependent, with higher doses leading to more pronounced effects on metabolism.

Pharmacokinetics

Levothyroxine sodium is well-absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 2 to 4 hours after oral administration. It has a half-life of approximately 6 to 7 days, allowing for once-daily dosing. The drug is extensively bound to plasma proteins, primarily thyroxine-binding globulin, and is metabolized predominantly in the liver. Renal impairment may prolong its half-life, necessitating dose adjustments in patients with compromised renal function.

Adverse effects

• Hyperthyroidism
• Allergic reactions
• Cardiac arrhythmias
• Osteoporosis
• Weight loss
• Nervousness
• Insomnia
• Menstrual irregularities
• Heat intolerance
• Tremors

Interactions

• Anticoagulants (e.g., warfarin) - increased effect
• Antidiabetic agents - possible alteration in blood glucose control
• Cholestyramine - may reduce levothyroxine absorption
• Calcium and iron supplements - may interfere with absorption
• Certain antidepressants (e.g., sertraline) - may require dose adjustment
• Estrogens - may increase levothyroxine requirements

Precautions

• Cardiac disease - need for careful dose adjustment
• Adrenal insufficiency - should be treated before starting levothyroxine
• Monitoring of thyroid levels is essential to avoid over-treatment
• Caution in patients with impaired hepatic or renal function

Pregnancy

Levothyroxine is considered safe during pregnancy, but dose adjustments may be required to maintain normal thyroid function.

Breast-feeding

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

Storage

Store in a cool, dry place away from light. Do not store above 25 degrees Celsius.

Formulations

• Tablets (various strengths)
• Oral solution

Indications

• Low blood volume
• Hypovolemic shock
• Burns
• Cardiopulmonary bypass

Dosage

Children: Initially 10-20 mL per kilogram. Adjust according to the patient's condition and response, using 3.5-4% solution. Use under specialist supervision to mitigate the risk of fluid overload.

Adults: Dose according to requirements, typically administered intravenously. Consult product literature for specific dosing guidance.

Mechanism of action

Gelatin acts as a plasma expander by increasing the oncotic pressure in the vascular compartment, which helps to retain fluid within the bloodstream and restore circulating blood volume. This mechanism aids in maintaining blood pressure and improving tissue perfusion.

Pharmacodynamics

Gelatin solutions increase blood volume and improve hemodynamic stability in patients experiencing hypovolemic conditions. By drawing water into the vascular space, they help to counteract the effects of low blood volume, such as hypotension and compromised organ perfusion.

Pharmacokinetics

Gelatin is administered intravenously, and its effects can be observed relatively quickly. The half-life and the metabolic clearance depend on the formulation and concentration of the solution. Gelatin is gradually metabolized by macrophages and eliminated by the renal system. Close monitoring of fluid balance is essential, particularly in patients with cardiac or renal impairment.

Contra-indications

• Severe liver disease
• History of circulatory disease
• Severe cardiac disease

Adverse effects

• Fever
• Flushing
• Nausea
• Urticaria
• Rare or very rare shock

Interactions

• Calcium salts

Precautions

• Monitor cardiovascular and respiratory function
• Correct dehydration when administering
• Administer slowly to avoid rapid rise in blood pressure and cardiac failure
• Increased capillary permeability

Pregnancy

Consult product literature for specific guidance regarding use in pregnancy.

Breast-feeding

Consult product literature for specific guidance regarding use in breastfeeding.

Storage

Store at controlled room temperature, protect from light. Refer to product-specific storage instructions.

Formulations

• 5% solution for infusion
• 20% solution for infusion
• Concentrated solution (15-25% protein)
• Isotonic solution (3.5-5% protein)

Indications

• Used as a disintegrant in tablet formulations
• Enhances the bioavailability of active pharmaceutical ingredients

Dosage

Children: Refer to the specific formulation guidelines, as dosage will vary based on the active ingredient and formulation type.

Adults: Refer to the specific formulation guidelines, as dosage will vary based on the active ingredient and formulation type.

Mechanism of action

Croscarmellose sodium works by swelling and absorbing water when it comes into contact with gastrointestinal fluids. This swelling leads to the rapid disintegration of the tablet or capsule matrix, facilitating the release and absorption of the active pharmaceutical ingredients.

Pharmacodynamics

Croscarmellose sodium is classified as a superdisintegrant. Its ability to rapidly disintegrate solid dosage forms can significantly enhance the dissolution rate of the active ingredient, which is crucial for achieving therapeutic effects in a timely manner.

Pharmacokinetics

Croscarmellose sodium is not absorbed in the gastrointestinal tract and does not exert pharmacological effects in the body. It is considered non-toxic and is excreted unchanged. Its main role is as an excipient, influencing the formulation's characteristics rather than the pharmacokinetics of the active ingredients.

Precautions

• Use with caution in patients with known hypersensitivity to croscarmellose or its components.

Pregnancy

Safety in pregnancy has not been established. Use only if clearly needed.

Breast-feeding

Caution is advised when using during breastfeeding, as safety has not been established.

Storage

Store in a cool, dry place, away from moisture and heat.

Formulations

• Powder
• Granules

Indications

• Lactose intolerance
• As a filler or excipient in pharmaceutical formulations

Dosage

Children: Refer to the BNF for Children for specific dosing information based on age and clinical context.

Adults: Refer to the BNF for specific dosing information based on clinical context.

Mechanism of action

Lactose is metabolized in the intestine by the enzyme lactase into its constituent monosaccharides, glucose and galactose. In individuals with lactase deficiency, unabsorbed lactose passes into the colon, where it is fermented by bacteria, leading to gas production and osmotic effects that contribute to diarrhea.

Pharmacodynamics

The pharmacodynamics of lactose are primarily related to its effects on gastrointestinal function. In healthy individuals, lactose is effectively broken down into glucose and galactose, which are absorbed and utilized for energy. In individuals with lactose intolerance, the unabsorbed lactose can cause osmotic diarrhea and colonic fermentation, leading to discomfort and symptoms associated with lactose intolerance.

Pharmacokinetics

Lactose is not absorbed in the gastrointestinal tract until it is hydrolyzed into glucose and galactose by lactase. The absorption of glucose and galactose occurs in the small intestine. The half-life is not applicable as lactose is not typically administered as a medication but is rather ingested as a natural component of food. Its metabolism primarily occurs in the intestine.

Adverse effects

• Bloating
• Diarrhea
• Abdominal pain
• Flatulence

Precautions

• Use with caution in patients with lactose intolerance.
• Consider potential for gastrointestinal upset in sensitive individuals.

Pregnancy

Lactose is generally considered safe for use during pregnancy. However, consult a healthcare professional for individual advice.

Breast-feeding

Lactose is safe to use while breastfeeding, as it is a natural sugar present in breast milk.

Storage

Store in a cool, dry place, away from direct sunlight.

Formulations

• Powder
• Granules
• Tablets
• Syrup

Indications

• Hypothyroidism
• Thyroid hormone replacement therapy
• Goiter (as part of treatment)
• Thyroid cancer (in certain cases)

Dosage

Children: For children, dosing is determined by age and weight, and specific guidance should be referred from the BNF for Children.

Adults: The initial dose for adults varies based on clinical circumstances and should be titrated according to TSH levels. Typically, a starting dose is around 50-100 micrograms daily, adjusted as necessary.

Mechanism of action

Levothyroxine acts as a replacement for the deficient thyroid hormone T4 in conditions like hypothyroidism. It increases metabolic rate by decreasing thyroid-stimulating hormone (TSH) production from the pituitary gland and is converted to triiodothyronine (T3) in peripheral tissues, which has more potent metabolic effects. This hormone regulates numerous biochemical pathways that influence growth, metabolism, and overall energy levels in the body.

Pharmacodynamics

Levothyroxine maintains normal T4 levels in individuals with deficiency, exerting physiological effects similar to endogenous T4. It has a narrow therapeutic index, necessitating careful dose titration to achieve a euthyroid state, typically monitored via TSH levels. Over-treatment can lead to hyperthyroid symptoms, whereas under-treatment can cause symptoms of hypothyroidism. Regular monitoring is essential to avoid adverse effects on growth, cardiac function, and metabolism.

Pharmacokinetics

Levothyroxine is well-absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 2 to 4 hours post-administration. It has a long half-life, allowing for once-daily dosing, and is metabolized in the liver and other tissues, with a significant portion excreted as metabolites in urine. The pharmacokinetics can be affected by various factors including age, weight, gastrointestinal health, and interactions with other medications.

Adverse effects

• Increased heart rate
• Diarrhea
• Tremors
• Hypercalcemia
• Weakness
• Weight loss
• Heat intolerance
• Increased appetite

Interactions

• voxilaprevir with sofosbuvir and velpatasvir: Severe (increases absorption)
• oral antacids: Unknown (decreases absorption)
• apalutamide: Unknown (decreases exposure)
• oral calcium salts: Unknown (decreases absorption)
• ritonavir: Unknown (decreases concentration)
• oral iron: Unknown (decreases absorption)
• sucralfate: Unknown (decreases absorption)

Precautions

• Monitor thyroid-stimulating hormone (TSH) levels regularly to maintain a euthyroid state
• Titration of dose should be done slowly and carefully to avoid over- or under-treatment
• Patients should be monitored for responses to titration to prevent negative effects on growth, cardiovascular function, and metabolism

Pregnancy

Levothyroxine is considered safe during pregnancy; however, dosages may need to be adjusted to maintain normal thyroid hormone levels.

Breast-feeding

Levothyroxine is excreted in breast milk but in amounts that are not expected to harm a nursing infant; monitoring is recommended.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets
• Oral solution

Indications

• Nutritional support
• Source of carbohydrates
• Dietary fiber source
• Animal feed

Dosage

Children: As with adults, there are no specific dosing recommendations for maize for children. It can be introduced into the diet in age-appropriate forms and quantities, keeping in mind the overall dietary balance.

Adults: There are no specific dosing recommendations for maize as it is typically consumed as part of a balanced diet. It can be included in daily meals in various forms such as whole kernels, flour, or as part of dishes.

Mechanism of action

Maize primarily acts as a source of energy due to its high carbohydrate content. The complex carbohydrates in maize are broken down into glucose, which is then utilized by the body for energy production. It also contributes to dietary fiber intake, which can aid in digestive health and regulation of blood sugar levels.

Pharmacodynamics

The consumption of maize influences blood glucose and insulin levels due to its carbohydrate content. It has a relatively low glycemic index when consumed in whole form, which can help in managing blood sugar levels. The dietary fiber present in maize can also promote satiety and aid in weight management.

Pharmacokinetics

The digestion of maize begins in the mouth with salivary amylase breaking down starches into simpler sugars. In the stomach and small intestine, enzymes further break down these carbohydrates. The resultant glucose is absorbed into the bloodstream, where it is transported to cells for energy production. The absorption rate can vary based on the form of maize consumed (e.g., whole kernels versus processed forms).

Pregnancy

Maize is generally considered safe for consumption during pregnancy as it is a staple food and provides essential nutrients.

Breast-feeding

Maize is safe to consume while breastfeeding and can provide important nutrients to both the mother and the infant.

Storage

Store in a cool, dry place, away from moisture and pests. Properly sealed containers can help prolong shelf life.

Formulations

• Whole maize grains
• Maize flour (cornmeal)
• Maize starch
• Maize oil

Indications

• Nutritional supplementation
• Energy source in enteral nutrition
• Excipient in pharmaceutical formulations

Dosage

Children: Refer to specific guidelines or product inserts for dosing information, as it can vary based on the context of use.

Adults: Refer to specific guidelines or product inserts for dosing information, as it can vary based on the context of use.

Mechanism of action

Starch is broken down into glucose units by enzymes such as amylase during digestion. The glucose is then absorbed in the intestines and utilized for energy production in the body's cells. This pathway involves hydrolysis of the glycosidic bonds, converting starch into simpler sugars.

Pharmacodynamics

Starch primarily serves as an energy source. Its digestion and absorption lead to an increase in blood glucose levels, which provides energy for metabolic processes. In this context, it plays a crucial role in maintaining energy homeostasis in the body.

Pharmacokinetics

Starch is not absorbed in its polymeric form; it must first be enzymatically hydrolyzed into simpler sugars such as maltose and glucose. The digestion and absorption of starch occur predominantly in the small intestine, with glucose being readily absorbed into the bloodstream. The rate of absorption can vary depending on the type of starch and its physical form.

Adverse effects

• Allergic reactions
• Gastrointestinal discomfort
• Diarrhea
• Constipation

Precautions

• Use with caution in individuals with known allergies to starch or starch derivatives
• Monitor for gastrointestinal symptoms in patients with a history of digestive disorders

Pregnancy

Starch is generally considered safe for use during pregnancy. However, it should be consumed in moderation as part of a balanced diet.

Breast-feeding

Starch is deemed safe for nursing mothers when used in moderation as part of a balanced diet.

Storage

Store in a cool, dry place away from moisture and direct sunlight.

Formulations

• Powder
• Granules
• Tablets
• Suspensions

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.