LEVATOA 10%

Indications

• Helminth infections
• Strongyloides infections
• Brugia malayi infections
• Wuchereria bancrofti infections
• Adjunctive therapy in colon cancer with fluorouracil

Dosage

Children: For children aged 1 month to 9 years: Initially 1 mg/kg daily in divided doses on the first day, then increased to 3

Adults: Initially 1 mg/kg daily on the first day, then increased to 6 mg/kg daily in divided doses, with the maximum dose not exceeding 9 mg/kg per day.

Mechanism of action

Levamisole exerts its antiparasitic action by acting as an agonist at L-subtype nicotinic acetylcholine receptors in the muscles of nematodes. This results in paralysis of the worms, preventing their reproductive capabilities. As an immunomodulator, Levamisole restores depressed immune functions, enhances T-cell activation, stimulates antibody formation, and increases macrophage and neutrophil activities.

Pharmacodynamics

Levamisole's pharmacodynamics are characterized by its dual role as an anthelmintic and an immunomodulator. As an anthelmintic, it specifically targets nematodes by agonizing their nicotinic acetylcholine receptors, leading to muscle paralysis. The immunomodulatory effects include activation of natural killer (NK) cells and T-cells, enhancing the host's immune response, and improving macrophage function.

Pharmacokinetics

Levamisole is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It is extensively metabolized in the liver, and its metabolites are excreted in urine. The elimination half-life is approximately 4 to 6 hours. Care should be taken in patients with hepatic impairment, as dose adjustments may be necessary.

Contra-indications

• Blood disorders

Adverse effects

• Arthralgia (long term use)
• Diarrhoea
• Dizziness
• Headache
• Influenza-like illness (long term use)
• Insomnia (long term use)
• Myalgia (long term use)
• Nausea
• Rash (long term use)
• Seizure (long term use)
• Taste altered (long term use)
• Vasculitis (long term use)
• Vomiting

Interactions

• Levamisole moderately decreases exposure to albendazole
• Levamisole increases exposure to ivermectin

Precautions

• Epilepsy
• Sjögren’s syndrome

Pregnancy

Embryotoxic in animal studies, avoid if possible.

Breast-feeding

No information available.

Storage

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

Formulations

• 50 mg chewable tablets

Mechanism of action

Bisulfite functions primarily as a reducing agent in biochemical reactions. It can donate electrons, which is essential in various metabolic processes, including the degradation of cysteine and homocysteine. The compound is involved in pathways related to amino acid metabolism, specifically influencing sulfur amino acid metabolism, which is critical in maintaining cellular redox homeostasis.

Pharmacodynamics

The pharmacodynamic properties of bisulfite include its role in reducing oxidative stress by participating in redox reactions. It helps maintain the balance of thiol groups within proteins, which is vital for their structural integrity and function. Additionally, bisulfite may influence the activity of certain enzymes involved in the metabolism of amino acids.

Pharmacokinetics

Information on the pharmacokinetics of bisulfite is limited. However, it is known to be rapidly absorbed and metabolized in the body. Its primary metabolic pathways involve the degradation of sulfur-containing amino acids. Excretion typically occurs through urine, reflecting its metabolic products.

Pregnancy

Bisulfite is not recommended during pregnancy due to potential risks, consult healthcare professionals for alternatives.

Breast-feeding

Caution is advised when using bisulfite while breastfeeding, consult with healthcare professionals before use.

Storage

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

Indications

• Electrolyte replacement
• Volume expansion in hypovolemic patients
• Management of hyponatremia
• Support in intravenous fluid therapy

Dosage

Children: Refer to the BNF for Children for appropriate dosing in paediatric patients, as dosages may vary based on the formulation and clinical condition.

Adults: Refer to specific product information or clinical guidelines for dosage recommendations, as disodium is often part of combination products.

Mechanism of action

Disodium compounds often function by providing sodium ions that are essential for various physiological processes. Sodium ions play a critical role in maintaining osmotic balance, nerve impulse transmission, and muscle contraction. In the context of intravenous solutions, disodium helps to restore electrolyte balance in patients.

Pharmacodynamics

The pharmacodynamics of disodium is primarily related to its role in electrolyte balance and fluid homeostasis. Sodium ions are vital for the function of excitable tissues, including neurons and muscle cells. Changes in sodium levels can affect blood pressure, hydration status, and overall cellular function.

Pharmacokinetics

The pharmacokinetics of disodium compounds depend on their specific formulation and route of administration. When administered intravenously, disodium is rapidly distributed in the extracellular fluid, where it helps to maintain osmotic pressure. Sodium is primarily excreted by the kidneys, and its levels can be influenced by fluid intake, dietary sodium, and renal function.

Pregnancy

Use with caution. Consult a healthcare provider for specific guidance.

Breast-feeding

Use with caution. Consult a healthcare provider for specific guidance.

Storage

Store at room temperature, away from moisture and direct sunlight.

Indications

• Lead poisoning
• Mercury poisoning
• Calcium overload
• Certain diagnostic procedures involving heavy metals

Dosage

Children: Refer to the BNF for Children for appropriate dosing information tailored for paediatric patients.

Adults: Refer to the BNF for specific dosing guidelines based on the condition being treated, considering factors such as the severity of metal poisoning and renal function.

Mechanism of action

Edetate functions by forming stable complexes with divalent and trivalent metal ions, including lead and calcium, through its multiple carboxylate and amine groups. This chelation renders the metals more soluble and promotes their renal excretion, thereby reducing their toxic effects in the body.

Pharmacodynamics

The chelation of metals by edetate decreases the free metal concentration in the bloodstream, which mitigates the toxic effects associated with heavy metal accumulation. The efficacy of edetate in removing metals such as lead has been well documented, and its ability to bind calcium can influence calcium homeostasis in certain clinical scenarios.

Pharmacokinetics

Edetate is administered intravenously, with rapid distribution throughout the extracellular fluid. It is primarily excreted unchanged by the kidneys. The onset of action occurs quickly after administration, and the duration depends on the dose and the patient's renal function. The elimination half-life is approximately 1 hour but may vary based on renal clearance.

Contra-indications

• Hypersensitivity to edetate or any component of the formulation
• Severe renal impairment
• Active bleeding disorders

Adverse effects

• Hypocalcemia
• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Headache
• Rash
• Fever

Interactions

• May enhance the effects of anticoagulants
• Concurrent use with calcium supplements may reduce effectiveness
• May interfere with the absorption of certain medications due to changes in gastrointestinal motility

Precautions

• Use with caution in patients with renal impairment
• Monitor electrolyte levels, particularly calcium, during treatment
• Assess the patient's hydration status before administration

Pregnancy

Limited data on the use of edetate in pregnancy. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Caution is advised as it is not known whether edetate is excreted in human milk. Weigh the risks and benefits before use.

Storage

Store in a cool, dry place, protected from light. Do not freeze.

Formulations

• Edetate disodium injection
• Edetate calcium disodium injection

Indications

• Pain management
• Vaccination
• Antibiotic therapy
• Hormonal therapies
• Anesthesia
• Nutritional support
• Chemotherapy

Dosage

Children: Refer to specific drug guidelines for paediatric dosing, as it requires careful consideration of weight and age.

Adults: Refer to specific drug guidelines for adult dosing, as it varies widely depending on the medication and clinical condition.

Mechanism of action

The mechanism of action of injected drugs varies widely based on the specific medication being administered. Generally, injected drugs enter the bloodstream directly, allowing them to circulate rapidly throughout the body. For instance, antibiotics may work by inhibiting bacterial cell wall synthesis, while analgesics may modulate pain pathways in the central nervous system. Each drug has unique pathways through which it achieves its therapeutic effects.

Pharmacodynamics

Pharmacodynamics refers to the effects of drugs on the body and their mechanisms of action. For injectable medications, effects can be immediate or delayed, depending on the drug's formulation and route of administration. Factors influencing pharmacodynamics include receptor affinity, drug concentration, and the presence of other substances that may enhance or inhibit the drug's effects. For example, some injectable drugs may require specific receptors to exert their effects, while others may have a broader range of action.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion (ADME) of injected drugs. After administration, drugs are rapidly absorbed into the bloodstream, leading to quick therapeutic effects. The distribution depends on factors such as blood flow, tissue permeability, and protein binding. Drugs are metabolized primarily in the liver and excreted through the kidneys or bile. The pharmacokinetic profile can vary widely based on the drug's chemical nature, dosage, and individual patient factors.

Pregnancy

Safety during pregnancy depends on the specific injection and its active ingredients. It is essential to consult a healthcare professional for guidance.

Breast-feeding

The safety of injections during breastfeeding varies by the specific medication. It is recommended to seek advice from a healthcare provider.

Storage

Store injections as per manufacturer's guidelines, usually in a cool, dry place away from direct sunlight. Some may require refrigeration.

Mechanism of action

The mechanism of action of levamisole as an antiparasitic agent appears to be tied to its agnositic activity towards the L-subtype nicotinic acetylcholine receptors in nematode muscles. This agonistic action reduces the capacity of the males to control their reproductive muscles and limits their ability to copulate. The mechanism of action of Levamisole as an anticancer drug in combination with fluorouracil is unknown. The effects of levamisole on the immune system are complex. The drug appears to restore depressed immune function rather than to stimulate response to above-normal levels. Levamisole can stimulate formation of antibodies to various antigens, enhance T-cell responses by stimulating T-cell activation and proliferation, potentiate monocyte and macrophage functions including phagocytosis and chemotaxis, and increase neutrophil mobility, adherence, and chemotaxis.

Pharmacodynamics

Levamisole is a synthetic imidazothiazole derivative that has been widely used in treatment of worm infestations in both humans and animals. As an anthelmintic, it probably works by targeting the nematode nicotinergic acetylcholine receptor. As an immunomodulator, it appears that Levamisole is an immunostimulant which has been shown to increase NK cells and activated T-cells in patients receiving this adjuvantly along with 5FU for Stage III colon cancer.