CARBEN 500

Indications

• Roundworm infections
• Hookworm infections
• Whipworm infections
• Pinworm infections
• Other helminth infections

Dosage

Children: Child 1 month–9 years: Initially 1 mg/kg daily in divided doses on the first day, then increased to 3 mg/kg daily in divided doses, dose to be increased gradually over 3 days. Child 10–17 years: Initially 1 mg/kg daily in divided doses on the first day, then increased to

Adults: 100 mg for 1 dose, if reinfection occurs, a second dose may be needed after 2 weeks.

Mechanism of action

Mebendazole causes degenerative alterations in the tegument and intestinal cells of the worm by binding to the colchicine-sensitive site of tubulin, thus inhibiting its polymerization into microtubules. This leads to impaired glucose uptake and depletion of glycogen stores in the parasites, resulting in decreased ATP production, immobilization, and eventual death of the helminths.

Pharmacodynamics

Mebendazole is a synthetic broad-spectrum anthelmintic. Its principal mode of action is through the inhibition of tubulin polymerization, which results in the loss of cytoplasmic microtubules. This action disrupts organelle movement and interferes with the normal physiological processes of helminths, effectively leading to their death.

Pharmacokinetics

Mebendazole is poorly absorbed from the gastrointestinal tract, which contributes to its effectiveness as an anthelmintic. After oral administration, the drug is primarily metabolized in the liver. Its low solubility limits absorption, but it can still exert its effects on the intestinal parasites present in the gastrointestinal tract. The drug's elimination half-life is variable, and it is not significantly distributed in body tissues.

Contra-indications

• Blood disorders

Adverse effects

• Abnormal sensation in eye
• Anaemia
• Appetite decreased
• Asthenia
• Asthma exacerbated
• Chest discomfort
• Coma
• Confusion
• Conjunctival haemorrhage
• Constipation
• Diarrhoea
• Difficulty standing
• Difficulty swallowing
• Dizziness
• Fever
• Gastrointestinal discomfort
• Headache
• Hepatitis
• Hypotension
• Joint disorders
• Leucopenia
• Lymphatic abnormalities
• Myalgia
• Nausea
• Oedema
• Pain
• Psychiatric disorder
• Seizure
• Severe cutaneous adverse reactions (SCARs)
• Stupor
• Tachycardia
• Tremor
• Urinary incontinence
• Vertigo
• Vomiting

Interactions

• Cimetidine (increases concentration of mebendazole)

Precautions

• Use with caution in patients with epilepsy
• Use with caution in patients with 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 light.

Formulations

• Chewable tablet 100 mg

Mechanism of action

Mebendazole causes degenerative alterations in the tegument and intestinal cells of the worm by binding to the colchicine-sensitive site of tubulin, thus inhibiting its polymerization or assembly into microtubules. The loss of the cytoplasmic microtubules leads to impaired uptake of glucose by the larval and adult stages of the susceptible parasites, and depletes their glycogen stores. 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. Due to diminished energy production, the parasite is immobilized and eventually dies. Although the exact mechanism of anthelmintic activity of mebendazole has not been fully elucidated, the drug appears to cause selective and irreversible inhibition of the uptake of glucose and other low molecular weight nutrients in susceptible helminths; inhibition of glucose uptake appears to result in endogenous depletion of glycogen stores in the helminth. Mebendazole does not inhibit glucose uptake in mammals. Mebendazole appears to cause degenerative changes in the intestine of nematodes and in the absorptive cells of cestodes. The principal anthelmintic effect of the drug appears to be degeneration of cytoplasmic microtubules within these intestinal and absorptive cells. Microtubular deterioration results in inhibition of organelle movement and interferes with the absorptive and secretory function. As a result of excessive accumulation of intracellular transport secretory granules, hydrolytic and proteolytic enzymes are released and cause cellular autolysis. This irreversible damage leads to death of the parasite. Vermicidal; may also be ovicidal for ova or most helminths; mebendazole causes degeneration of parasite's cytoplasmic microtubules and thereby selectively and irreversibly blocks glucose uptake in susceptible adult intestine-dwelling helminths and their tissue-dwelling larvae; inhibition of glucose uptake apparently results in depletion of the parasite's glycogen stores; this, in turn, results in reduced formation of adenosine triphosphate (ATP) required for survival and reproduction of the helminth; corresponding energy levels are gradually reduced until death of the parasite ensues; mebendazole does not appear to affect serum glucose concentrations in humans, however. 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/

Pharmacodynamics

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