Mebendazole-«Grindeks»

Therapeutic indications. Enterobiasis, trichuriasis, ascariasis, ankylostomiasis, necatoriasis, and mixed infestations.

Posology and methods of administration. Mebendazoleis administered orally. The tablet may be swallowed, chewed or crushedand mixed with food. No special procedures, such as fasting or purging,are required.
The same dosage schedule applies to children andadults. For treatment of pinworms infestation mebendazole isadministered 100 mg (1 tablet) as a single dose.

In case of otherhelminthic infestation the drug is given 100 mg (1 tablet) twice a day(morning and evening) for three consecutive days. Safety and efficacyof mebendazole has not been established in children under two years.

The treatment shall be repeated after three weeks if re-infection is suspected.

Contraindications. Hypersensitivity to mebendazole or any of excipients.

Special warnings and special precautions for use. To avoid re-infestation and transmission of the infestations patients should observe cleanlines.
In case of severe hepatic impairment increased blood concentration of mebendazole may occur.
Monitoringof hepatic and renal function, as well as blood count is generallyrecommended during prolonged treatment in high dosage.
Mebendazole has not been studied in children under two years. Therefore, it cannot be recommended in this age group.
Tabletsof mebendazole contain lactose. Patients with rare hereditary problemsof galactose intolerance, the Lapp lactase deficiency orglucose-galactose malabsorption should not take this medicine.

Interaction with other medicinal products and other forms of interaction. Interactionwith other medicinal products practically does not occur if the usualdosage of the drug is used and treatment duration is not exceeded.Concomitant treatment with cimetidine may inhibit mebendazolemetabolism and stimulate the drug accumulation in the body.

Pregnancy and lactation. Asmebendazole has shown embryotoxic and teratogenic activity duringseveral studies, mebendazole should be used during pregnancy only ifthe potential benefit justifies the potential risk to the foetus. It isnot known whether mebendazole is excreted in human milk, thereforecaution should be exercised, when medicine is administered to a nursingwoman.

Effects on ability to drive and use machines. Mebendazole has not shown adverse effect on ability to drive and operate machines.

Undesirable effects. Asthe drug in recommended dosage acts locally in gastrointestinal tractundesirable effects are reported rarely and usually manifest asgastrointestinal disturbances. Abdominal pain and diarrhoea have beenreported in cases of massive infestation of worms. Allergic reactions(urticaria, angioedema), very rare – cramps, have been observed.
Granulocytopeniaand anaemia, hepatic impairment followed by the increase of hepatictransaminase in blood, hepatitis, alopecia were reported in patientsreceiving large doses of mebendazole (above 500 mg).

Pharmacodynamic properties
Pharmacotherapeutic group: Anthelmintics.

ATC-CODE: P02 C A01

Mebendazoleis a synthetic broad spectrum anthelmintic of benzimidazole group. Itis most effective against intestinal nematodes, demonstrates efficacyagainst many other helminths, and against various larvae and eggsthereof. Mebendazole most effectively treats the following helminthsinfestations:

Ascaris lumbricoides 98%
Ancylostoma duodenale 96%
Necator americanus 96%
Enterobius vermicularis 95%
Trichuris trichiura 68%

Theefficacy of the drug to inhibit the activity of helminths depends onvarious factors (pre-existing diarrhoea, duration of treatment, and thedegree of helminths infestation).
Sometimes mebendazole is used forthe treatment of capillariasis and strongyloidiasis, while in thesecases longer treatment is needed than in case of treatment withalbendazole.
Mebendazole is effective against Mansonella andTrichinella, and against primary animal parasites – Angiostrongyluscantonensis and Grathostoma spinigerum. There were attempts to usemebendazole for the treatment of opisthorchiasis and echinococcosis,though in case of abenteric helminths larger dosage and prolongedtreatment are needed and the effect is not always satisfactory,therefore, other medicinal preparations are preferred in these cases.
Themechanism of mebendazole anthelminthic activity is a result of aneffect on energy metabolism of helminths. Mebendazole provokesdegeneration of cytoplasmic microtubules, blocking the uptake ofglucose, in a selective and irreversible manner, that appears to leadto endogenous depletion of glycogen stores. Inhibition of livingprocesses leads to decreased synthesis of ATP and to death of helminths.

Pharmacokinetic properties
Onlya small amount of mebendazole (5-10%) is absorbed in gastrointestinaltract because it is practically insoluble in water and organicsolvents. Food enriched with fats may enhance the absorption ofmebendazole.
Peak blood concentration occurs within 2-5 hours.
90-95%of the drug binds with plasma albumin. Absorbed drug enters the serum,liver, fat tissue, cysts fluids and in rather high concentration enterscysts of Trichinella larvae in muscles.
Absorbed portion of the drugundergoes extensive first- pass metabolism in the liver. Metabolitesare inactive. Half-life of mebendazole is 0.93 hours. Metabolites andunchanged drug are excreted in the bile and in the faeces . Only 2% ofa dose (unchanged and in the form of metabolites) is excreted in theurine within 48 hours.
Using a usual therapeutic dose mebendazoleacts locally in intestinal tract because its bioavailability is too lowdue to poor absorption and extensive first- pass metabolism.Nevertheless, upon using high doses (for example, in case oftrichinellosis, opisthorchiasis and echinococcosis) bloodconcentrations of unchanged drug is enough for its systemic effect.

List of excipients
Fillers: Lactose monohydrate,maize starch. Binder: povidone. Disintegrator: sodium starch glycolate,type A (Primojel). Lubricant: magnesium stearate, vegetable grade.Colour: Sunset Yellow Lake, E 110.

Incompatibilities
Not applicable.

Shelf-life.
4 years.

Special precautions for storage
Do not store above 250C.
Do not use after the expiry date stated on the label.

Prescription drug.

Nature and contents of container
tablets per plastic bottle; 1 bottle per cardboard box.

MARKETING AUTHORISATION HOLDER
JSC «Grindeks», 53, Krustpils St., Riga LV-1057, Latvia.
Phone: +371 7083205
Fax: + 371 7083505
E-mail: grindeks@grindeks.lv; www.grindeks.lv

MARKETING AUTHORISATION NUMBER:
EST 114895