LETHYROX 50

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

• Constipation
• Dietary fiber supplementation
• Irritable bowel syndrome
• Diverticular disease
• Weight management

Dosage

Children: Refer to appropriate guidelines for specific dosage; generally taken with adequate fluid intake.

Adults: Refer to appropriate guidelines for specific dosage; generally taken with adequate fluid intake.

Mechanism of action

Cellulose acts primarily as a bulk-forming laxative. It absorbs water in the intestines, which increases stool bulk and stimulates peristalsis, thus facilitating bowel movements. Additionally, cellulose is not digestible by human enzymes, leading to fermentation by gut bacteria, which may enhance gut health and alter gut microbiota composition.

Pharmacodynamics

Cellulose increases stool weight and frequency of bowel movements. It works by retaining water in the intestines, leading to softer stools and improved passage through the gastrointestinal tract. The bulking effect of cellulose can help alleviate constipation and promote overall digestive health. It may also play a role in cholesterol reduction and glycemic control through its effects on digestion and absorption of nutrients.

Pharmacokinetics

Cellulose is not absorbed into the bloodstream due to its indigestible nature. Instead, it passes through the gastrointestinal tract, where it adds bulk to the stool. Its fermentation by colonic bacteria produces short-chain fatty acids, which may have beneficial effects on colon health. The onset of action for cellulose as a laxative can vary but is generally within 24 to 72 hours after ingestion.

Adverse effects

• Bloating
• Flatulence
• Diarrhea
• Abdominal discomfort

Precautions

• Use with caution in patients with a history of gastrointestinal disorders.
• Monitor for potential allergic reactions in sensitive individuals.

Pregnancy

Cellulose is generally considered safe during pregnancy as it is a non-toxic, indigestible fiber.

Breast-feeding

Cellulose is also considered safe during breastfeeding; it is excreted in breast milk in negligible amounts.

Storage

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

Formulations

• Powder
• Capsules
• Tablets
• Granules

Dosage

Children: Refer to official dosing guidelines for paediatric indications and dosages.

Adults: Refer to official dosing guidelines for specific indications and dosages.

Mechanism of action

Fumarate acts primarily as an intermediate in the TCA cycle, where it is converted to malate by the enzyme fumarase. This process is essential for the continuation of aerobic respiration, facilitating the conversion of carbohydrates, fats, and proteins into energy. Additionally, fumarate can participate in redox reactions, influencing cellular metabolism and signaling pathways.

Pharmacodynamics

Fumarate influences various metabolic pathways, including the urea cycle and glycolysis, by participating in electron transfer processes. Its role in the TCA cycle is vital for ATP production, and its interaction with other metabolic pathways helps regulate energy homeostasis and the balance of nitrogen in the body.

Pharmacokinetics

The pharmacokinetics of fumarate involve its absorption, distribution, metabolism, and excretion. Fumarate is readily absorbed when introduced into the body and is distributed to various tissues where it participates in metabolic processes. The metabolic conversion of fumarate occurs primarily in the mitochondria through the TCA cycle, and its elimination from the body is facilitated by renal pathways.

Pregnancy

There are no established guidelines regarding the use of fumerate during pregnancy. Consult healthcare professionals for individual risk assessment.

Breast-feeding

The safety of fumerate during breastfeeding has not been established. Caution is advised and consultation with healthcare professionals is recommended.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Dosage

Children: Refer to specific clinical guidelines for dosing in children, as no standard paediatric dosage is specified in the provided resources.

Adults: Refer to specific clinical guidelines for dosing, as no standard adult dosage is specified in the provided resources.

Mechanism of action

Ethylene glycol toxicity results from its metabolism to glycolic acid and other toxic metabolites. Glycolate accumulates in the body and is eliminated more slowly than ethylene glycol itself. The renal excretion of both compounds plays a crucial role in their elimination, accounting for a significant portion of the administered dose.

Pharmacodynamics

The pharmacodynamics of glycolate are closely tied to its role as a metabolite of ethylene glycol. Its accumulation can lead to metabolic acidosis, although minimal clinical effects have been observed at low doses. The relationship between glycolate and ethylene glycol indicates that glycolate may contribute to the overall toxic effects of ethylene glycol ingestion.

Pharmacokinetics

The pharmacokinetics of glycolate indicate that it reaches peak plasma levels between 4-6 hours after the administration of ethylene glycol. The elimination half-life of ethylene glycol is approximately 1.7 hours in rats and 3.4 hours in dogs. Glycolate is predominantly eliminated through renal excretion, with about 5% of the dose being excreted unchanged.

Pregnancy

There is limited data on the safety of glycolate in pregnancy. Caution is advised.

Breast-feeding

Data on the excretion of glycolate in human milk is not available. Caution is advised.

Storage

Store at room temperature, away from light and moisture.

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

• Vision correction
• Phototherapy for skin conditions (e.g., psoriasis, eczema)
• Treatment of seasonal affective disorder (SAD)
• Circadian rhythm disorders
• Wound healing

Dosage

Children: Light therapy for paediatric patients should be approached with caution and always under professional guidance. Specific dosages will depend on the individual treatment protocol and condition being addressed.

Adults: Dosage of light therapy varies based on the condition being treated and should be tailored to individual needs, typically ranging from 15 minutes to 2 hours of exposure per day depending on the specific treatment protocol.

Mechanism of action

Light affects biological systems primarily through phototransduction, which involves the conversion of light into electrical signals within photoreceptor cells in the retina. This process initiates a cascade of biochemical reactions that ultimately lead to visual perception. In addition, specific wavelengths of light can interact with various biological molecules, triggering cellular responses such as the production of vitamin D through skin exposure to UVB radiation.

Pharmacodynamics

The pharmacodynamic effects of light are highly dependent on its wavelength and intensity. Short-wavelength blue light (around 480 nm) is known to influence circadian rhythms by affecting melatonin secretion. In therapeutic settings, light can modulate biological responses, such as promoting wound healing, reducing inflammation, and alleviating symptoms of seasonal affective disorder (SAD) through bright light therapy.

Pharmacokinetics

Light does not undergo traditional pharmacokinetic processes such as absorption, distribution, metabolism, or excretion. Instead, its effects are immediate and localized, depending on the intensity and duration of exposure. The penetration depth of light varies with wavelength; for example, UV light can penetrate the skin and affect deeper tissues, while visible light primarily affects the surface layers.

Pregnancy

There is limited data on the effects of light exposure during pregnancy. However, excessive exposure to bright light can be harmful to both the mother and the developing fetus.

Breast-feeding

Light exposure is generally considered safe while breastfeeding, but excessive exposure should be avoided to prevent potential harm to the infant.

Storage

Light should be properly controlled and managed in environments where it is used, ensuring that exposure levels are safe and effective.

Indications

• Used as an excipient in tablet formulations
• Used as a bulking agent in capsule formulations
• Used in food products as a thickener or stabilizer

Dosage

Children: Refer to specific product guidelines as dosage will depend on the formulation and the active ingredients.

Adults: Refer to specific product guidelines as dosage will depend on the formulation and the active ingredients.

Mechanism of action

Microcrystalline cellulose acts as a non-digestible filler that enhances the flow properties of powders during the manufacturing of tablets and capsules. It does not have a direct pharmacological action on the body but ensures that the active ingredients are effectively delivered to the patient.

Pharmacodynamics

As a non-active ingredient, microcrystalline cellulose does not exert pharmacodynamic effects typical of active pharmaceutical ingredients. Its primary role is to provide a stable and consistent matrix for the drug, facilitating the release of the active compound once ingested.

Pharmacokinetics

Microcrystalline cellulose is not absorbed in the gastrointestinal tract; it passes through the digestive system largely unchanged. It adds bulk to the stool, which may aid in promoting regular bowel movements. The substance is excreted in feces, where it contributes to dietary fiber intake.

Pregnancy

Data regarding the use of microcrystalline cellulose during pregnancy is limited. It is advisable to consult with healthcare professionals before use.

Breast-feeding

Microcrystalline cellulose is considered safe during breastfeeding, as it is not absorbed systemically.

Storage

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

Mechanism of action

Oxides do not have a single mechanism of action as they are a broad category of compounds. However, in general, metal oxides can exhibit catalytic properties, while non-metal oxides may participate in biochemical reactions by forming acids or bases upon dissolution in water.

Pharmacodynamics

The pharmacodynamics of oxides depend on the specific type of oxide and its interaction with biological systems. For instance, metal oxides may have antimicrobial properties, while certain non-metal oxides can influence metabolic pathways through their acid-base chemistry. The effects vary widely, necessitating specific studies for each oxide's role in therapeutic contexts.

Pharmacokinetics

The pharmacokinetics of oxides are also variable. Many metal oxides are poorly soluble and thus have limited absorption when ingested. Non-metal oxides, such as carbon dioxide, can be readily absorbed and utilized in metabolic processes. The distribution, metabolism, and excretion of oxides depend on their chemical form and the biological system in which they are involved.

Pregnancy

Not applicable as oxide is not a drug but a class of chemical compounds.

Breast-feeding

Not applicable as oxide is not a drug but a class of chemical compounds.

Storage

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

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

Indications

• Hyperlipidemia
• Cardiovascular disease prevention
• Nutritional supplementation
• Potential anti-inflammatory conditions

Dosage

Children: For paediatric dosing, consult specialized pediatric guidelines or the BNF for Children, as recommendations may differ based on age and weight.

Adults: For dosing, refer to specific guidelines and clinical judgment, as doses can vary widely based on the condition being treated and the specific steryl compound used.

Mechanism of action

Steryls primarily function by modulating cell membrane properties and influencing the activity of various membrane-bound enzymes and receptors. They can affect the fluidity and permeability of the cell membrane, which in turn can alter signal transduction pathways and cellular responses.

Pharmacodynamics

The pharmacodynamic effects of steryls include their role in cholesterol metabolism and homeostasis, influencing lipid profiles and potentially affecting cardiovascular health. Steryls can also exhibit anti-inflammatory and antioxidant properties, contributing to their overall impact on health.

Pharmacokinetics

Steryls are absorbed primarily in the intestines and are transported via chylomicrons in the lymphatic system. They undergo hepatic metabolism, where they can be converted into various metabolites. The elimination of steryls occurs mainly through the bile and feces. The half-life and clearance can vary depending on dietary intake and individual metabolic factors.

Pregnancy

The safety of Steryl in pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Caution is advised when using Steryl during breastfeeding. Consult a healthcare professional before use.

Storage

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

Mechanism of action

Ethylene glycol toxicity results from its metabolism to glycolic acid and other toxic metabolites. The accumulation of glycolate and the elimination kinetics of ethylene glycol and its metabolites are not well understood, so studies with male Sprague-Dawley rats and mixed breed dogs have been carried out. Ethylene glycol was administered by gavage to rats and dogs which were placed in metabolic cages for urine and blood sample collection at timed intervals. The peak plasma level of ethylene glycol occurred at 2 hr after dosing and that of glycolate between 4-6 hr. The rate of ethylene glycol elimination was somewhat faster in rats with a half-life of 1.7 hr compared to 3.4 hr in dogs. The maximum plasma level of glycolate was greater in rats although the pattern of accumulation was similar to that in dogs. Glycolate disappeared from the plasma at the same time as ethylene glycol, suggesting a slower rate of elimination of the metabolite than that of ethylene glycol. Renal excretion of ethylene glycol was an important route for its elimination accounting for 20-30% of the dose. Renal excretion of glycolate represented about 5% of the dose. Ethylene glycol induced an immediate, but short lived diuresis compared to that in control rats. Minimal clinical effects (mild acidosis with no sedation) were noted at these doses of ethylene glycol (1-2 g/kg) in both rats and dogs. The results indicate that the toxicokinetics of ethylene glycol and glycolate were similar in both species. The effect of 0.35 to 0.8 mmol/kg glycolic acid and 1.0 to 4.4 mmol/kg sodium glycolate on cyclopropane-epinephrine induced cardiac arrhythmias was examined using dogs. Doses of 0.35 to 0.5 mmol/kg glycolic acid increased the duration of arrhythmias in the 13 dogs tested, whereas doses >0.5 mmol/kg decreased or totally eliminated the arrhythmias in each of 11 dogs. Depression was observed for many of the dogs at higher doses. Sodium glycolate was much less effective in decreasing the arrhythmias, with 3 mmol/kg being required and its action being transient.

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.