VERMOX 100 MG TABLETS - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Vermox® 100 mg tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 100 mg of mebendazole.

Excipients: Each tablet also contains 0.06 mg of sunset yellow (E110).

This medicine contains sodium.

For a full list of excipients, see section 6.1

3 PHARMACEUTICAL FORM

Tablet.

Flat, circular, pale orange tablets with “Me/100” on one side and “JANSSEN” on the other.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

For the treatment of Trichuris trichuria (whipworm), Enterobius vermicularis (pinworm or threadworm), Ascaris lumbricoides (roundworm), Ancylostoma duodenale (common hookworm), Necator americanus (American hookworm) in single or mixed gastrointestinal infestations.

There is no evidence that Vermox Tablets are effective in the treatment of cysticercosis.

4.2 Posology and method of administration

Adults and children over 2 years:

For the control of trichuriasis, ascariasis and hookworm infections, one tablet twice a day for three consecutive days.

For the control of enterobiasis a single tablet is administered. It is highly recommended that a second tablet is taken after two weeks, if re-infection is suspected.

Tablets may be chewed or swallowed whole. Crush the tablet before giving it to a young child. Always supervise a child while they are taking this medicine.

Vermox oral suspension should be considered for patients such as young children who are unable to swallow the tablet.

Children under 2 years:

Vermox has not been extensively studied in children below the age of 2 years. Currently available data are described in section 4.4, 4.8 and 5.2, but no recommendations on a posology can be made.

Because of the lack of sufficient safety data, Vermox should not be used in children below the age of 1 year (see section 4.4, 4.8 and 5.2).

Method of Administration

Oral use.

Vermox oral suspension should be considered for patients such as young children who are unable to swallow the tablet.

4.3 Contraindications

Vermox is contra-indicated in pregnancy and in patients who have shown hypersensitivity to the product or any components.

4.4 Special warnings and precautions for use

Not recommended in the treatment of children under 2 years

There have been rare reports of reversible liver function disturbances, hepatitis and neutropenia described in patients who were treated with mebendazole at standard dosages for indicated conditions (see section 4.8 ‘Undesirable effects’). These events, along with glomerulonephritis and agranulocytosis, have also been reported with dosages substantially above those recommended and with treatment for prolonged periods of time.

A case-control study of a single outbreak of Stevens-Johnson syndrome /toxic epidermal necrolysis (SJS/TEN) suggested a possible association with the concomitant use of metronidazole with mebendazole. Although there are no additional data on this potential interaction, concomitant use of mebendazole and metronidazole should be avoided.

Convulsions in children, including in infants below 1 year of age, have been reported very rarely during post-marketing experience (see section 4.8 ‘Undesirable effects’). Vermox has not been extensively studied in children below the age of 2 years.

Therefore, Vermox should be used in children aged 1–2 years only if the potential benefit justifies the potential risk.

Because of the lack of sufficient safety data, Vermox should not be used in

children below the age of 1 year.

Vermox should only be given to very young children if their worm infestation interferes significantly with their nutritional status and physical development.

This medicinal product contains 3.8 mg sodium per tablet, equivalent to 0.19% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

4.5 Interaction with other medicinal products and other forms of interaction Concomitant treatment with cimetidine may inhibit the metabolism of mebendazole in the liver, resulting in increased plasma concentrations of the drug.

Concomitant use of mebendazole and metronidazole should be avoided (see section 4.4).

4.6 Fertility, pregnancy and lactation

Pregnancy

Since Vermox is contraindicated in pregnancy, patients who think they are, or may be, pregnant should not take this preparation.

Breast-feeding

Limited data from case reports demonstrate that a small amount of mebendazole is present in human milk following oral administration. Therefore, caution should be exercised when Vermox is administered to breast-feeding women.

4.7 Effects on ability to drive and use machines

Vermox has no influence on the ability to drive and use machines.

4.8 Undesirable effects

Throughout this section adverse reactions are reported. Adverse reactions are adverse events that were considered to be reasonably associated with the use of Vermox based on the comprehensive assessment of the available adverse event information. A causal relationship with Vermox cannot be reliably established in individual cases. Further, because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The safety of Vermox was evaluated in 6276 subjects who participated in 39 clinical trials for the treatment of single or mixed parasitic infestations of the gastrointestinal tract. In these 39 clinical trials, no adverse drug reactions (ADRs) occurred in >1% of Vermox-treated subjects.

ADRs identified from clinical trials and post-marketing experience with Vermox are included in Table 1. The displayed frequency categories use the following convention:

Very common (>1/10); Common (>1/100 to <1/10); Uncommon (>1/1000 to <1/100); Rare (>1/10,000 to <1/1000); Very rare (<1/10,000), Not known (cannot be estimated from the available data).

Table 1: Adverse Drug Reactions Reported in Clinical Trials and Post-marketing Experience for Vermox

a ADR frequency data derived from Clinical Trials or Epidemiological Studies

b ADRs not observed in clinical trials and frequency calculated based on 6276 patients exposed in clinical trials and epidemiological studies, divided by 3 (Frequency = 1/2092).

Observed in higher and prolonged doses

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

In patients treated at dosages substantially higher than recommended or for prolonged periods of time, the following adverse reactions have been reported rarely: alopecia, reversible liver function disturbances, hepatitis, agranulocytosis, neutropenia and glomerulonephritis. With the exception of agranulocytosis and glomerulonephritis, these also have been reported in patients who were treated with mebendazole at standard dosages (see section 4.8).

Signs and symptoms

In the event of accidental overdosage, abdominal cramps, nausea, vomiting and diarrhoea may occur.

Treatment

There is no specific antidote. Activated charcoal may be given if considered appropriate.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: anthelmintic for oral administration, benzimidazole derivatives; ATC code: P02CA01.

In vitro and in vivo work suggests that mebendazole blocks the uptake of glucose by adult and larval forms of helminths, in a selective and irreversible manner. Inhibition of glucose uptake appears to lead to endogenous depletion of glycogen stores within the helminth. Lack of glycogen leads to decreased formation of ATP and ultrastructural changes in the cells.

There is no evidence that Vermox is effective in the treatment of cysticercosis.

5.2 Pharmacokinetic properties

Absorption

Following oral administration, < 10% of the dose reaches the systemic circulation, due to incomplete absorption and pre-systemic metabolism (first-pass effect). The majority of an orally administered dose remains in the gastrointesti­nal tract.

Maximum plasma concentrations are generally seen 2 to 4 hours after administration. Administration with a high fat meal increases the bioavailability of mebendazole, but the overall effect of food on the amount of drug remaining in the gastrointestinal tract is not expected to be substantial.

Distribution

The plasma protein binding of mebendazole is 90 to 95%. The volume of distribution is 1 to 2 L/kg, indicating that mebendazole penetrates areas outside the vascular space. This is supported by data in patients on chronic mebendazole therapy (e.g., 40 mg/kg/day for 3–21 months) that show drug levels in tissue.

Metabolism

Orally administered mebendazole is extensively metabolised primarily by the liver. Plasma concentrations of its major metabolites (hydrolysed and reduced forms of mebendazole) are substantially higher than those of mebendazole. Impaired hepatic function, impaired metabolism, or impaired biliary elimination may lead to higher plasma levels of mebendazole.

Elimination

Mebendazole, the conjugated forms of mebendazole, and its metabolites likely undergo some degree of enterohepatic recirculation and are excreted in the urine and bile. The apparent elimination half-life after an oral dose ranges from 3 to 6 hours in most patients.

Steady-state pharmacokinetics

During chronic dosing (e.g., 40 mg/kg/day for 3–21 months), plasma concentrations of mebendazole and its major metabolites increase, resulting in approximately 3-fold higher exposure at steady-state compared to single dosing.

Paediatric population

Limited data of the mebendazole concentrations in plasma are available in children and adolescents 1 to 16 years of age. These data do not indicate substantially higher systemic exposure to mebendazole in subjects 3 to 16 years of age compared to adults. In subjects 1 to <3 years of age, systemic exposure is higher than in adults due to higher mg/kg dose relative to adults.

5.3 Preclinical safety data

In animal reproduction studies, adverse developmental effects (i.e., skeletal malformations, soft tissue malformations, decreased pup weight, embryolethality) were observed when mebendazole was administered to pregnant rats and mice throughout the period of organogenesis or as a single oral dose as low as 10 mg/kg in rats (approximately 0.2-fold the maximum recommended human dose (MRHD)). Maternal toxicity was present at the highest of these doses. Dosing of hamsters and rabbits did not result in embryotoxicity or teratogenicity. Doses up to 40 mg/kg in rats (0.8-fold the MRHD, based on mg/m2), given to males for 60 days and to females for 14 days prior to gestation, had no effect upon fetuses and offspring.

No mutagenic activity was observed with mebendazole in bacterial reverse mutation tests. Mebendazole was mutagenic when tested in the mouse lymphoma thymidine kinase assay and aneugenic in vitro in mammalian somatic cells. In the in vivo mouse micronucleus assay, orally administered mebendazole induced an increased frequency of micronucleated polychromatic erythrocytes with evidence suggestive of aneugenicity.

Mebendazole had no carcinogenic effects at doses as high as 40 mg/kg/day when administered daily in the diet over 2 years in carcinogenicity tests in mice and rats (0.4 to 0.8-fold the MRHD, based on mg/m2).

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Microcrystalline cellulose

Sodium starch glycolate

Talc

Maize starch

Sodium saccharin

Magnesium stearate

Cottonseed oil hydrogenated

Orange flavour

Colloidal anhydrous silica

Sodium laurilsulfate

Sunset yellow (E110)

Purified water

2-propanol

* Not present in the final product.

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

Blister strips of PVC genotherm glass clear aluminium foil coated on the inside with a heat seal lacquer.

Pack sizes: 1 and 6 tablet packs.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

7 MARKETING AUTHORISATION HOLDER

Janssen-Cilag Ltd

50–100 Holmers Farm Way,

High Wycombe,

Bucks,

HP12 4EG,

UK

8 MARKETING AUTHORISATION NUMBER(S)

PL 00242/0011

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THEAUTHORISATION

Date of First Authorisation: 9 April 1975

Date of Renewal of Authorisation: 30 September 2003