SANIMIX POWDER FOR SOLUTION FOR INJECTION

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

Indications

• Muscle spasticity
• Muscle spasms
• Pain management in musculoskeletal disorders

Dosage

Children: Refer to specific pediatric guidelines or consult a healthcare professional for appropriate dosing.

Adults: Refer to specific clinical guidelines or consult a healthcare professional for appropriate dosing.

Mechanism of action

Diaceturate acts by inhibiting the presynaptic release of acetylcholine at the neuromuscular junction, thereby reducing muscle contraction. This inhibition leads to decreased excitability of motor neurons and relaxation of skeletal muscles.

Pharmacodynamics

The pharmacodynamic profile of diaceturate indicates its ability to produce muscle relaxation through central and peripheral mechanisms. It alters neurotransmitter release and modulates synaptic transmission, leading to decreased muscle tone and increased ease of movement. Its effects can be observed within a short time frame following administration, making it effective for acute muscle spasm relief.

Pharmacokinetics

Diaceturate is typically absorbed rapidly after administration, with peak plasma concentrations achieved within a few hours. It undergoes hepatic metabolism, with its metabolites being excreted primarily through the kidneys. The drug has a relatively short half-life, necessitating multiple doses for sustained effect in clinical use.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Dizziness
• Rash

Precautions

• Use with caution in patients with liver impairment
• Monitor for allergic reactions
• Caution in patients with renal impairment

Pregnancy

The safety of diaceturate during pregnancy has not been established. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Caution is advised when using diaceturate in breastfeeding women, as it's unknown if it passes into breast milk.

Storage

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

Indications

• Trypanosomiasis (sleeping sickness)
• Nagana in livestock
• Infections caused by Trypanosoma brucei
• Infections caused by Trypanosoma congolense

Dosage

Children: Paediatric dosing of diminazene should be derived from the BNF for Children, taking into account the weight and age of the child. Refer to the BNF for Children for specific dosing recommendations.

Adults: The dosage for adults should be determined based on the specific condition and patient factors. Refer to the BNF for accurate dosing guidelines.

Mechanism of action

Diminazene acts by inhibiting the enzyme dihydrofolate reductase, which is crucial for the synthesis of folate in protozoa. This inhibition disrupts the folate metabolic pathway, leading to a decrease in nucleic acid synthesis and ultimately resulting in the death of the protozoan parasites. Additionally, it may interfere with the mitochondrial function of the parasites, further contributing to its antiparasitic effects.

Pharmacodynamics

The pharmacodynamics of diminazene involve its selective action on trypanosomes, with the drug being less toxic to host cells. It has a high affinity for the target enzyme, allowing for effective suppression of protozoan growth. The drug's therapeutic index is favorable, meaning it can effectively treat infections at doses that are relatively safe for the host.

Pharmacokinetics

Diminazene is well-absorbed following parenteral administration. It is widely distributed throughout the body, with a significant volume of distribution. The drug undergoes hepatic metabolism, and its elimination half-life can vary depending on species and individual health. Excretion is primarily via the urine, with metabolites detected in both urine and feces.

Adverse effects

• Anorexia
• Vomiting
• Diarrhoea
• Lethargy
• Neurological signs (e.g., tremors, ataxia)
• Hypersensitivity reactions

Precautions

• Use with caution in animals with hepatic or renal impairment.
• Monitor for signs of toxicity, especially in cases of overdose.

Pregnancy

Safety during pregnancy has not been established; use only if the benefits outweigh the risks.

Breast-feeding

Safety during breastfeeding has not been established; use with caution.

Storage

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

Formulations

• Injection solution

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.