OVERMIX TOTAL TABLETS

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

• Schistosomiasis caused by Schistosoma mansoni
• Schistosomiasis caused by Schistosoma japonicum
• Tapeworm infections, including Taenia solium and Hymenolepis nana

Mechanism of action

Praziquantel is hypothesized to target the β subunits of voltage-gated Ca2+ channels in parasites such as Schistosoma mansoni and Schistosoma japonicum. This action leads to increased calcium influx, causing rapid contraction and paralysis of the worms. The drug also induces tegumental disintegration and vacuolization in schistosomes, significantly affecting adult worms more than juveniles. Secondary effects include inhibition of glucose uptake and depletion of glycogen levels.

Pharmacodynamics

Praziquantel exhibits a rapid onset of action against trematodes and cestodes, causing significant changes in the permeability of the cell membrane of the parasites. This results in muscle contraction, tegumental damage, and eventual death of the worms. It selectively targets schistosomes and is ineffective against nematodes. The drug's efficacy is notably reduced against juvenile schistosomes and may diminish after a few weeks of treatment.

Pharmacokinetics

Praziquantel is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1-3 hours post-administration. It undergoes extensive hepatic metabolism, primarily by CYP450 enzymes, and has a half-life of approximately 1-3 hours. The drug is excreted mainly in urine as metabolites, with a small fraction excreted unchanged. The pharmacokinetics can be affected by co-administration with certain other drugs that alter its metabolism.

Adverse effects

• dizziness
• hepatitis
• neutropenia
• seizure
• severe cutaneous adverse reactions

Interactions

• mitotane+praziquantel: Severe (decreases exposure)
• rifampicin+praziquantel: Severe (decreases exposure)
• chloroquine+praziquantel: Moderate (decreases exposure)
• cobicistat+praziquantel: Unknown (increases exposure)
• dexamethasone+praziquantel: Unknown (decreases exposure)
• grapefruit juice+praziquantel: Unknown (increases exposure)
• cimetidine+praziquantel: Unknown (increases exposure)
• idelalisib+praziquantel: Unknown (increases exposure)

Pregnancy

Manufacturer advises avoiding use due to toxicity observed in animal studies.

Breast-feeding

Amount present in milk is too small to be harmful; however, the manufacturer advises avoiding use.

Storage

Store in a cool, dry place away from light.

Formulations

• tablets
• oral suspension

Indications

• Osteoarthritis
• Rheumatoid arthritis
• Postoperative pain
• Musculoskeletal pain
• Inflammatory conditions

Dosage

Children: Refer to specific guidelines or the BNF for Children for appropriate dosing information.

Adults: Refer to specific guidelines or the BNF for appropriate dosing information.

Mechanism of action

Embonate acts primarily by inhibiting the cyclooxygenase (COX) enzymes, which are crucial in the conversion of arachidonic acid to prostaglandins. By reducing the production of these inflammatory mediators, embonate decreases inflammation and alleviates pain. This mechanism is akin to that of non-steroidal anti-inflammatory drugs (NSAIDs).

Pharmacodynamics

The pharmacodynamic properties of embonate include its ability to reduce pain and inflammation through the inhibition of prostaglandin synthesis. The effectiveness of the drug in managing pain is typically noticeable within a few hours of administration, and its effects can last for several hours, depending on the dosage and formulation.

Pharmacokinetics

Embonate is absorbed well after oral administration, reaching peak plasma concentrations within a few hours. The drug undergoes hepatic metabolism, primarily via conjugation, and is excreted primarily in urine. The elimination half-life can vary, but it generally allows for once or twice daily dosing. The pharmacokinetics may be affected by factors such as liver function and concurrent medications.

Pregnancy

There is limited data on the safety of embonate during pregnancy. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

There is limited data on the excretion of embonate in human milk. Caution is advised when administering to nursing mothers.

Storage

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

Indications

• Ascariasis
• Enterobiasis (pinworm infection)
• Trichuriasis (whipworm infection)
• Strongyloidiasis (in certain cases)

Dosage

Children: Refer to the BNF for Children for specific dosing information, as it varies based on the child's age and weight.

Adults: Refer to the BNF for specific dosing information, as it may vary based on the infection being treated.

Mechanism of action

Oxantel acts as a potent agonist of N-subtype nicotinic acetylcholine receptors (nAChRs) in parasitic nematodes. Specifically, it targets a distinct subtype of ionotropic acetylcholine receptor formed by the ACR-16 subunit or an ACR-16-like ortholog, leading to neuromuscular paralysis of the parasites.

Pharmacodynamics

In parasitic nematodes, oxantel causes depolarization of the neuromuscular junction, resulting in muscle contraction followed by paralysis. Due to its agonistic action on nicotinic receptors, it disrupts normal neuromuscular function, effectively immobilizing the parasites and facilitating their expulsion from the host's gastrointestinal tract.

Pharmacokinetics

The pharmacokinetics of oxantel, including its absorption, distribution, metabolism, and excretion, are not thoroughly detailed in the available literature. However, it is generally expected to be absorbed following oral administration and to exert its effects locally within the gastrointestinal tract. Further studies may be needed for comprehensive pharmacokinetic profiling.

Pregnancy

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

It is not known whether oxantel is excreted in human milk. Caution should be exercised when administering to a nursing mother.

Storage

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

Formulations

• Tablets

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

Although the exact mechanism of action is unknown, praziquantel was hypothesized to target the β subunits of voltage-gated Ca₂₊ channels, particularly in Schistosoma mansoni and Schistosoma japonicum, due to the lack of two conserved serine residues in these subunits. This is supported by the finding that co-administration of calcium channel blockers like nicarpidine and nifedipine renders 50% of Schistosoma mansoni resistant to praziquantel. Increased exposure of antigens on the worm surface was also observed, but little research has been done to elucidate on the mechanism of action.

Pharmacodynamics

In vitro studies on trematodes and cestodes have shown that praziquantel induces a rapid contraction of schistosomas by a specific effect on the permeability of the cell membrane. The drug further causes vacuolization and disintegration of the schistosome tegument. The effect is more marked on adult worms compared to young worms. An increased Ca2⁺-influx may play an important role. Secondary effects are inhibition of glucose uptake, lowering of glycogen levels and stimulation of lactate release. The action of praziquantel is specific to trematodes and cestodes; nematodes (including filariae) are not affected. Praziquantel is active against schistosoma (for example, Schistosoma mekongi, Schistosoma japonicum, Schistosoma mansoni and Schistosoma hematobium), and infections due to the liver flukes, Clonorchis sinensis/Opisthorchis viverrini. Published in vitro data have shown a potential lack of efficacy of praziquantel against migrating schistosomulae. An interesting quirk of praziquantel is that it is relatively ineffective against juvenile schistosomes. While initially effective, effectiveness against schistosomes decreases until it reaches a minimum at 3-4 weeks. Effectiveness then increases again until it is once again fully effective at 6-7 weeks.

Mechanism of action

Oxantel acts as a potent agonist of N-subtype nicotinic acetylcholine receptors (nAChRs) in parasitic nematodes. Specifically, it targets a distinct subtype of ionotropic acetylcholine receptor formed by the ACR-16 subunit (or an ACR-16-like ortholog).

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,.