LIVHART-M

Indications

• Onchocerciasis (river blindness)
• Strongyloidiasis
• Scabies (especially hyperkeratotic or crusted scabies)
• Lymphatic filariasis
• Other helminth infections

Dosage

Children: Child 6 months–17 years: 100 mg for 1 dose;

Adults: Adult: Initially 1 mg/kg daily on the first day, then increased to 6 mg/kg daily in divided doses, gradually increased over 3 days. Maximum 9 mg/kg per day. For scabies, 100 mg for 1 dose; if reinfection occurs, a second dose may be given after 2 weeks.

Mechanism of action

Ivermectin binds selectively to glutamate-gated chloride channels, leading to increased permeability of the cell membrane to chloride ions. This results in hyperpolarization of the nerve or muscle cells in the parasites, causing paralysis and death. It also interacts with other chloride channels, which may contribute to its antiparasitic effects.

Pharmacodynamics

Ivermectin exhibits broad-spectrum activity against a variety of parasites, including nematodes and arthropods. Its effectiveness is attributed to its ability to paralyze and kill parasites, thus facilitating their expulsion from the host. The drug has a long half-life, allowing for effective dosing regimens, and it is generally well-tolerated in patients.

Pharmacokinetics

Ivermectin is rapidly absorbed following oral administration, with peak plasma concentrations occurring within 4 to 6 hours. It is extensively distributed throughout the body, including the central nervous system. The drug undergoes hepatic metabolism, primarily via cytochrome P450, and is eliminated with a half-life of approximately 18 hours. Excretion occurs mainly in the feces, with a smaller proportion eliminated in urine.

Contra-indications

• Blood disorders
• Epilepsy
• Sjögren’s syndrome

Adverse effects

• Diarrhoea
• Dizziness
• Headache
• Influenza-like illness
• Insomnia
• Myalgia
• Nausea
• Rash
• Seizure
• Taste alteration
• Vomiting
• Skin reactions
• Abnormal sensation in eye
• Anaemia
• Appetite decrease
• Asthenia
• Asthma exacerbated
• Chest discomfort
• Confusion
• Conjunctival haemorrhage
• Constipation
• Gastrointestinal discomfort
• Headache
• Hepatitis
• Hypotension
• Joint disorders
• Leukopenia
• Myalgia
• Nausea
• Oedema
• Pain
• Psychiatric disorder
• Severe cutaneous adverse reactions
• Stupor
• Tachycardia
• Tremor
• Urinary incontinence
• Vertigo

Interactions

• Coumarins: Unknown (increases anticoagulant effect)
• Levamisole: Unknown (increases exposure)

Precautions

• Use with caution in hepatic impairment
• Avoid sun exposure when using topical formulations

Pregnancy

Embryotoxic in animal studies, avoid if possible.

Breast-feeding

Manufacturer advises avoid-limited information available; ensure infant does not come in contact with treated areas.

Storage

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

Formulations

• Tablets
• Topical formulation

Indications

• Enterobiasis (pinworm infection)
• Ascariasis (roundworm infection)
• Other intestinal helminth infections

Dosage

Children: Refer to the BNF for Children for appropriate dosing information based on the child's age and weight.

Adults: Refer to specific guidelines or the BNF for dosing recommendations, as doses may vary based on the type of helminthic infection.

Mechanism of action

Pamoate works by depolarizing the neuromuscular junctions of the parasites, leading to paralysis. It binds to nicotinic acetylcholine receptors on the parasite's muscle cells, causing sustained muscle contraction followed by paralysis. This mechanism prevents the parasites from maintaining their grip on the intestinal wall, resulting in their expulsion from the host.

Pharmacodynamics

The pharmacodynamic profile of pamoate highlights its specific action on the neuromuscular system of parasites. Unlike some other anthelmintics, pamoate does not have systemic absorption, which limits its effects to the intestinal lumen. This targeted action minimizes potential side effects in the host while effectively eliminating the parasites.

Pharmacokinetics

Pamoate is poorly absorbed from the gastrointestinal tract, with minimal systemic circulation. The drug remains predominantly in the intestinal lumen, where it exerts its anthelmintic effects. Its elimination half-life is relatively short, and it is primarily excreted unchanged in the feces. Due to its limited absorption, pamoate does not typically require dose adjustments in renal impairment.

Contra-indications

• Hypersensitivity to pamoate or any of its components
• Severe liver disease
• Severe renal impairment

Adverse effects

• Gastrointestinal disturbances (nausea, vomiting, diarrhea)
• Dizziness
• Headache
• Fatigue
• Allergic reactions (rash, itching)
• Abdominal pain

Interactions

• May interact with other medications that affect liver enzymes
• Potential for increased toxicity when used with other hepatotoxic agents

Precautions

• Caution in patients with a history of liver or renal disease
• Monitor for signs of toxicity
• Use with caution in elderly patients

Pregnancy

The safety of pamoate during pregnancy has not been established. Use only if clearly needed and the benefits outweigh the risks.

Breast-feeding

There is limited information on the excretion of pamoate in human milk. A decision should be made to discontinue nursing or discontinue the drug, considering the importance of the drug to the mother.

Storage

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

Formulations

• Oral tablets
• Suspensions
• Powders for reconstitution

Indications

• Ascariasis
• Enterobiasis (pinworm infection)
• Hookworm infections
• Strongyloidiasis (off-label use)

Dosage

Children: For children aged 2 years and older, the recommended dose is usually 10 mg/kg (up to a maximum of 1 g) given as a single dose. For children under 2 years, refer to the BNF for Children for specific dosing guidance.

Adults: The standard adult dose for treating pinworm or roundworm infections is typically 10 mg/kg (up to a maximum of 1 g) as a single dose.

Mechanism of action

Pyrantel promotes the release of acetylcholine, inhibits cholinesterase, and stimulates ganglionic neurons, acting as a depolarizing neuromuscular blocking agent in helminths. This leads to extensive depolarization of the helminth muscle membrane, causing muscle tension and subsequent paralysis, which facilitates the expulsion of the parasites from the intestine.

Pharmacodynamics

Pyrantel exhibits properties akin to both competitive and depolarizing neuromuscular blocking agents, leading to spastic paralysis of the helminths. The drug induces marked and persistent activation of nicotinic receptors in the parasites, which results in their inability to maintain attachment to the intestinal walls.

Pharmacokinetics

Pyrantel is administered orally and is minimally absorbed from the gastrointestinal tract, which enhances its effectiveness against intestinal parasites. The majority of the drug remains in the gut, where it acts on the parasites directly. The metabolites and unabsorbed drug are excreted in the feces, primarily through normal peristalsis.

Adverse effects

• Nausea
• Vomiting
• Abdominal cramps
• Diarrhea
• Dizziness
• Headache
• Rash

Precautions

• Use with caution in patients with liver disease
• Not recommended for use in cases of known hypersensitivity to pyrantel or its components
• Monitor for signs of allergic reactions

Pregnancy

Pyrantel is classified as pregnancy category C. Animal studies have shown an adverse effect, and there are no adequate and well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Pyrantel is excreted in breast milk. Caution is advised when administering to nursing mothers, as the effects on the nursing infant are not well studied.

Storage

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

Formulations

• Pyrantel pamoate oral suspension
• Pyrantel pamoate tablets

Mechanism of action

By promoting the release of acetylcholine, inhibiting cholinesterase, and stimulating ganglionic neurons, pyrantel serves as a depolarizing neuromuscular blocking agent in helminths. This causes extensive depolarization of the helminth muscle membrane, resulting in tension to the helminth's muscles, leading to paralysis and release of their attachment to the host organism intestinal walls. This action is unlike piperazine, which is a hyperpolarizing neuromuscular blocking agent that causes relaxation of the helminth muscles, leading to a subsequent detachment from the intestinal wall. Excretion of the parasites in the feces occurs by normal peristalsis. PYRANTEL & ITS ANALOGS ARE DEPOLARIZING NEUROMUSCULAR BLOCKING AGENTS. THEY INDUCE MARKED, PERSISTENT ACTIVATION OF NICOTINIC RECEPTORS, WHICH RESULTS IN SPASTIC PARALYSIS OF THE WORM. PYRANTEL ALSO INHIBITS CHOLINESTERASES. /PYRANTEL PAMOATE AND ANALOGS/ PYRANTEL ... CAUSES A SLOWLY DEVELOPING CONTRACTURE OF PREPARATIONS OF ASCARIS AT 1% OF THE CONCENTRATION OF ACETYLCHOLINE REQUIRED TO PRODUCE THE SAME EFFECT. IN SINGLE MUSCLE CELLS OF THIS HELMINTH, PYRANTEL CAUSES DEPOLARIZATION & INCREASED SPIKE-DISCHARGE FREQUENCY, ACCOMPANIED BY INCREASE IN TENSION.

Pharmacodynamics

It has similar properties to both competitive and depolarizing neuromuscular blocking agents, which leads to the understanding of the paralytic effect of the drug has on parasites, ultimately resulting in the death of the parasite,.