Vermox®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT VЕRMOX® (VERMOX®)

Composition:

Active ingredient: mebendazole;

1 tablet contains 100 mg of mebendazole;

Excipients: microcrystalline cellulose, sodium starch glycolate (type A), talc, corn starch, sodium saccharin, magnesium stearate, hydrogenated cottonseed oil, orange flavor, colloidal anhydrous silicon dioxide, sodium lauryl sulfate, orange-yellow S (E 110).

Pharmaceutical form. Tablets.

Main physicochemical properties: round, flat tablet with bevelled edges, pale orange in color, engraved with "Me" and "100" separated by a break line on one side and engraved with "JANSSEN" on the other side.

Pharmacotherapeutic group. Anthelmintics. Antinematodal agents. Benzimidazole derivatives. ATC code P02CA01.

Pharmacological properties.

Pharmacodynamics.

Mebendazole acts locally within the intestinal lumen, inhibiting the formation of cellular tubulin in helminths, leading to impaired glucose utilization, digestion, and autolysis of the parasite.

There is no evidence of efficacy of Vermox® in the treatment of cysticercosis.

Pharmacokinetics.

Absorption. Less than 10% of the dose reaches systemic circulation after oral administration due to incomplete absorption and extensive presystemic metabolism (first-pass effect). Peak plasma concentrations are observed 2–4 hours after administration. Concomitant administration with a high-calorie meal slightly increases the bioavailability of mebendazole.

Distribution. 90–95% of the drug dose is bound to plasma proteins. The volume of distribution ranges from 1 to 2 L/kg, indicating the ability of mebendazole to penetrate through vascular walls. This is supported by data from patients who received mebendazole for prolonged periods (40 mg/kg/day for 3–21 months).

Metabolism. After oral administration, mebendazole is predominantly metabolized in the liver. Plasma concentrations of its main metabolites significantly exceed that of mebendazole. Impaired liver function, disturbances in metabolism, or biliary excretion may lead to increased plasma levels of mebendazole.

Elimination. Mebendazole, conjugated forms of mebendazole, and its metabolites undergo partial enterohepatic recirculation and are excreted via urine and bile. The apparent elimination half-life after oral administration is 3–6 hours in most patients.

Pharmacokinetics at steady state.

During long-term therapy (40 mg/kg/day for 3–21 months), plasma concentrations of mebendazole and its main metabolites increase, resulting in approximately a threefold increase in drug exposure at steady state compared to single-dose administration.

Clinical characteristics. Indications.

Treatment of parasitic infections such as: enterobiasis, ascariasis, ancylostomiasis, trichuriasis, necatoriasis.

Contraindications.

Hypersensitivity to mebendazole or to any excipient.

Pregnancy, breastfeeding.

Interaction with other medicinal products and other forms of interaction.

Concomitant use with cimetidine may enhance the effect of Vermox® due to inhibition of hepatic metabolism and increased plasma concentration of mebendazole.

Concomitant use of mebendazole and metronidazole should be avoided (see section "Special precautions for use").

Special precautions for use

Not recommended for treatment of children under 2 years of age.

Rare cases of reversible liver function abnormalities, hepatitis, and neutropenia have been reported in patients receiving mebendazole at standard doses for the approved indications (see section "Adverse reactions"). Cases of glomerulonephritis and agranulocytosis have been reported in association with doses significantly exceeding the recommended doses and with prolonged treatment duration.

Clinical data suggest a possible association between the use of mebendazole and metronidazole and the development of Stevens–Johnson syndrome/toxic epidermal necrolysis. Concomitant use of mebendazole and metronidazole should be avoided.

Due to insufficient experience with the use of the drug in children under 2 years of age, and because there have been isolated reports of seizures during treatment in this age group, Vermox® should be prescribed only if helminthic infestation significantly affects the child's nutritional status and physical development.

There is no need to prescribe a special diet or laxatives during treatment with this drug.

Sunset Yellow FCF (E 110) may cause allergic reactions.

This medicinal product contains 48 mg of sodium per dose. Caution is advised when administering to patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding

Vermox® is contraindicated during pregnancy; therefore, it should not be used by pregnant patients or by those who suspect they may be pregnant.

Breastfeeding

Available data indicate that small amounts of mebendazole are excreted in human milk following oral administration. Therefore, breastfeeding is not recommended during treatment with Vermox®.

Fertility

It is known that mebendazole does not affect fertility when administered at doses up to 10 mg/kg daily. Reproductive studies have shown that mebendazole does not impair male fertility at doses up to and including 40 mg/kg daily.

Ability to affect reaction speed when driving or operating machinery

Vermox® does not impair the ability to drive or operate machinery; however, the possibility of adverse reactions affecting the nervous system should be taken into account (see section "Adverse reactions").

Dosage and Administration.

For oral use.

• For enterobiasis, adults and children aged 2 years and older should be given 1 tablet (100 mg) of Vermox® as a single dose. To prevent reinfection, repeat administration of 1 tablet (100 mg) should be carried out after 2 weeks.
• For ascariasis, trichocephalosis, ancylostomiasis, and necatoriasis, adults and children aged 2 years and older should be given 1 tablet (100 mg) twice daily (in the morning and evening) for 3 days.

The tablet may be chewed or swallowed whole. The tablet should be crushed before giving it to a child. Medication administration to a child must be under parental supervision.

Children.

Use for treatment of children aged 2 years and older.

Overdose.

In patients who received doses higher than recommended or were treated for prolonged periods, alopecia, reversible liver function abnormalities, hepatitis, agranulocytosis, neutropenia, and glomerulonephritis have been rarely observed. Except for agranulocytosis and glomerulonephritis, these adverse reactions have also been observed in patients receiving mebendazole at standard doses (see section "Adverse Reactions").

Symptoms. In cases of accidental overdose, abdominal cramps, nausea, vomiting, and diarrhea may occur.

Treatment. There is no specific antidote. Gastric lavage may be performed immediately after oral ingestion of mebendazole. If indicated, activated charcoal may be administered.

Adverse reactions.

Vermox® is generally well tolerated at recommended doses. Diarrhea and abdominal pain were observed in patients with significant parasitic burden during treatment with Vermox®.

The safety of Vermox® was assessed in 6276 patients who participated in 39 clinical studies evaluating the use of the drug for treatment of single or mixed gastrointestinal parasitic infections. During these clinical trials, adverse reactions were observed in less than 1% of patients receiving treatment with Vermox®.

Adverse reactions identified during clinical studies and in the post-marketing period are listed in Table 1.

Table 1.

a Data on the frequency of adverse reactions were obtained during clinical and epidemiological studies.

b Adverse reactions not observed during clinical studies, the frequency of which was determined using the "rule of 3" (frequency = 1/2092).

*Observed with high-dose administration and long-term treatment.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 30 °C. Keep out of reach and sight of children.

Packaging. 6 tablets per blister pack made of PVC film and aluminum foil; 1 blister pack per cardboard box.

Prescription status. Prescription only.

Manufacturer.

Lusomedicamenta Sociedade Técnica Farmacêutica, S.A. /
Lusomedicamenta Sociedade Tecnica Farmaceutica, S.A.

Manufacturer's address.

Estrada Consiglieri Pedroso, 66, 69 – B, Queluz de Baixo, 2730-055 Barcarena, Portugal /
Estrada Consiglieri Pedroso, 66, 69 – B, Queluz de Baixo, 2730-055 Barcarena, Portugal.