GARDAL 1.9%

Indications

• Helminth infections
• Strongyloidiasis
• Hydatid disease
• Tapeworm infections
• Hookworm infections
• Schistosomiasis

Dosage

Children: For children aged 2–17 years: 400 mg twice daily for 3 days. The dose may be repeated after 3 weeks if necessary. Alternatively, for hookworm infections: 7.5 mg/kg twice daily (maximum per dose 400 mg) for 28 days, followed by a 14-day break, repeated for up to 2–3 cycles.

Adults: For Adult patients, the dosage is typically 400 mg taken by mouth as a single dose or as directed by a healthcare professional based on the specific condition being treated.

Mechanism of action

Albendazole works by inhibiting the polymerization of tubulin into microtubules, disrupting the cytoplasmic structure of the helminths, and thereby inhibiting their motility and reproduction.

Pharmacodynamics

Albendazole exhibits its anthelmintic activity through the inhibition of glucose uptake, leading to depletion of glycogen stores in the worms, ultimately resulting in their death. It is effective against a wide range of parasites.

Pharmacokinetics

Albendazole is rapidly absorbed and is metabolized in the liver to its primary active metabolite, albendazole sulfoxide. Its bioavailability is increased when taken with fatty meals. The drug is primarily excreted in the urine and has a half-life that varies based on individual metabolism.

Adverse effects

• Gastro-intestinal upset
• Lightheadedness
• Pruritus

Interactions

• Levamisole may moderately decrease the exposure to albendazole
• Ritonavir may decrease the exposure to albendazole

Precautions

• Treatment must be given under careful patient supervision
• Stop at the first sign of cerebral involvement

Pregnancy

Refer to BNF for specific guidance.

Breast-feeding

Refer to BNF for specific guidance.

Storage

Store in a cool, dry place away from light.

Formulations

• Tablets
• Suspension

Indications

• Ascariasis
• Strongyloidiasis
• Hookworm infections
• Enterobiasis
• Trichuriasis
• Other helminthic infections

Dosage

Children: Refer to the BNF for Children for specific dosing information.

Adults: Refer to the BNF for specific dosing information.

Mechanism of action

Ricobendazole exerts its anthelmintic effect by binding to tubulin, thereby inhibiting microtubule formation. This disrupts the cytoskeleton of the parasite, impairing its ability to absorb glucose and leading to its eventual death. The drug's action interferes with mitosis and other cellular processes critical to the parasite's survival.

Pharmacodynamics

The pharmacodynamics of ricobendazole involve its ability to selectively target parasitic worms while showing minimal toxicity to the host. The drug's effects are dose-dependent, with higher concentrations leading to increased efficacy against a broader range of helminths. It has a rapid onset of action, providing effective relief from symptoms associated with parasitic infections.

Pharmacokinetics

Ricobendazole is absorbed from the gastrointestinal tract after oral administration, with peak plasma concentrations typically occurring within a few hours. It undergoes extensive metabolism in the liver, leading to the formation of active metabolites. The elimination half-life varies but generally supports the dosing regimen for effective therapeutic outcomes. Excretion occurs primarily via the urine and feces.

Pregnancy

There is limited data on the use of ricobendazole in pregnancy. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

There is no information available regarding the excretion of ricobendazole 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.

Formulations

• {'formulation': 'Tablet', 'strength': '100 mg'}
• {'formulation': 'Suspension', 'strength': '50 mg/5 ml'}

Indications

• Insect pest control
• Synergist in pesticide formulations

Mechanism of action

Piperonyl butoxide inhibits hepatic microsomal oxidase enzymes, as well as a related group of enzymes in insects, by acting as a competitive substrate. This inhibition reduces the detoxification of various drugs and chemicals, potentially increasing susceptibility to toxic substances.

Pharmacodynamics

The pharmacodynamic profile of sulphoxide reflects its role as a synergist in enhancing the potency of insecticides. By inhibiting the metabolic pathways that would typically detoxify these substances, sulphoxide facilitates increased insect mortality rates and efficacy in pest control. However, this also poses a risk of increased toxicity to non-target organisms, including humans.

Pharmacokinetics

The pharmacokinetics of sulphoxide involve absorption, distribution, metabolism, and excretion pathways that may vary between species. Generally, the compound is absorbed after oral intake and distributed throughout the body. It undergoes hepatic metabolism, primarily through cytochrome P450 enzymes, followed by excretion through urine. Specific rates of these processes can depend on various factors including dosage, formulation, and individual metabolic differences.

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 this drug 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 and moisture. Keep out of reach of children.

Mechanism of action

Albendazole causes degenerative alterations in the tegument and intestinal cells of the worm by diminishing its energy production, ultimately leading to immobilization and death of the parasite. It works by binding to the colchicine-sensitive site of tubulin, thus inhibiting its polymerization or assembly into microtubules. As cytoplasmic microtubules are critical in promoting glucose uptake in larval and adult stages of the susceptible parasites, the glycogen stores of the parasites are depleted. Degenerative changes in the endoplasmic reticulum, the mitochondria of the germinal layer, and the subsequent release of lysosomes result in decreased production of adenosine triphosphate (ATP), which is the energy required for the survival of the helminth. Benzimidazoles produce many biochemical changes in susceptible nematodes, eg, inhibition of mitochondrial fumarate reductase, reduced glucose transport, and uncoupling of oxidative phosphorylation ... /but/ the primary action ... /should be/ to inhibit microtubule polymerization by binding to beta-tubulin. The selective toxicity of these agents derives from the fact that specific, high-affinity binding to parasite beta-tubulin occurs at much lower concn than does binding to the mammalian protein ... Benzimidazole-resistant Haemonchus contortus display reduced high-affinity drug binding to beta-tubulin and alterations in beta-tubulin isotype gene expression that correlate with drug resistance ... Two identified mechanisms of drug resistance in nematodes involve both a progressive loss of "susceptible" beta-tubulin gene isotypes together with emergence of a "resistant" isotype with a conserved point mutation that encodes a tyrosine instead of phenylalanine at position 200 of beta-tubulin. While this mutation may not be required for benzimidazole resistance in all parasites, eg, Giardia lamblia, benzimidazole resistance in parasitic nematodes is unlikely to be overcome by novel benzimidazole analogs, because tyrosine also is present at position 200 of human beta-tubulin. /Benzimidazoles/ Although the exact mechanism of action of albendazole has not been fully elucidated, the principal anthelmintic effect of benzimidazoles, including albendazole, appears to be the specific, high-affinity binding of the drug to free beta-tubulin in parasite cells, resulting in selective inhibition of parasite microtubule polymerization, and inhibition of microtubule-dependent uptake of glucose. Benzimidazole drugs bind to the beta-tubulin of parasites at much lower concentrations than to mammalian beta-tubulin protein; the drugs do not inhibit glucose uptake in mammals, and do not appear to have any effect on blood glucose concentrations in humans The mode of action of albendazole is by binding strongly with the tubulin in the cells of nematodes. The intestinal cells of the nematode are particularly affected, resulting in a loss of absorptive function which causes the nematodes to starve to death.

Pharmacodynamics

Albendazole is a broad-spectrum anthelmintic. The principal mode of action for albendazole is by its inhibitory effect on tubulin polymerization which results in the loss of cytoplasmic microtubules.

Mechanism of action

Piperonyl butoxide, like other methylenedioxybenzene synergists (eg, sesamex, sulfoxide, n-propyl isome, piperonyl cyclonene, etc), inhibits hepatic microsomal oxidase enzymes in lab rodents & by inference in man; it also inhibits a related group of enzymes in insects apparently by serving as a competitive substrate. Because these enzymes act to detoxify many drugs & other exogenous chemicals, a heavy exposure to one of these insecticidal synergists might make a person temporarily vulnerable to a variety of toxic insults that would normally be tolerated with ease.