MEBENDAZOLE TABLETS 100 MG - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Mebendazole Tablets 100mg

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains mebendazole Ph. Eur. 100mg

Excipients with known effect

Sunset yellow (E110)

Lactose

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Tablet

Orange, flat, bevelled edged tablet with a breakline on one side.

4.1 Therapeutic indications

For the treatment of threadworm (Enterobius vermicularis) infestation.

There is no evidence that this is effective in the treatment of cyticercosis.

4.2 Posology and method of administration

Posology

Adults, the elderly and children over 2 years:

Take one tablet.

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. Care should be taken to avoid re-infection and it is strongly recommended that all members of the family are treated at the same time. It is highly recommended that a second tablet is taken after two weeks, if re-infection is suspected.

Children under 2 years:

Not recommended.

Method of administration Oral

4.3 Contraindications

Mebendazole is contraindicated in pregnant women and in patients who have shown hypersensitivity to the active substance or any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Mebendazole is not recommended in the treatment of children under 2 years.

If symptoms do not disappear within a few days, consult your doctor.

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 one year of age, have been reported very rarely during post-marketing experience with Mebendazole. Mebendazole tablets should only be given to very young children if their worm infestation interferes significantly with their nutritional status and physical development.

Glomerulonephritis and agranulocytosis have been very rarely reported with dosages substantially above those recommended and with treatment for prolonged periods of time.

This medicine contains Sunset Yellow (E110) – may cause allergic reactions.

This medicine contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

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 Mebendazole is contra-indicated 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 mebendazole is administered to breast-feeding women.

Fertility

The effect on human fertility has not been evaluated.

4.7 Effects on ability to drive and use machines

Mebendazole does not affect mental alertness or driving ability.

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 Mebendazole based on the comprehensive assessment of the available adverse event information. A causal relationship with Mebendazole 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.

At the recommended dose, Mebendazole is generally well tolerated. However, patients with high parasitic burdens when treated with Mebendazole have manifested diarrhoea and abdominal pain

The safety of mebendazole 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 mebendazole-treated subjects.

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

Very common Common

(> 1/10)

(> 1/100 and < 1/10)

Not known (cannot be estimated from the available date).

Table 1: Adverse drug Reactions

b Adverse reactions reported during post-marketing surveillance.

c Observed in higher and prolonged doses

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

4.9 Overdose

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 mebendazole is effective in the treatment of cysticercosis.

5.2 Pharmacokinetic properties

Absorption

Following oral administration, approximately <10% of the dose reaches the systemic circulation, due to incomplete absorption and to extensive presystemic metabolism (first-pass effect). Maximum plasma concentrations are generally seen 2 to 4 hours after administration. Dosing with a high fat meal leads to a modest increase in the bioavailability of mebendazole.

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.

Biotransformation

Orally administered mebendazole is extensively metabolized primarily by the liver. Plasma concentrations of its major metabolites (amino and hydroxylated amino 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.

5.3 Preclinical safety data

Acute oral toxicity of mebendazole in a number of species is low with a large margin of safety. Chronic oral toxicity studies in rats at 40 mg/kg/day and above, showed altered liver weights with some slight centrilobular swelling and hepatocellular vacuolation, and altered testicular weights with some tubular degeneration, desquamation and marked inhibition of spermatogenic activity.

In genotoxicity studies mebendazole was aneugenic in mammalian somatic cells above a threshold plasma concentration of 115 ng/mL, but had no mutagenic or clastogenic activity. In limited long term studies in mice and rats no carcinogenic effects were seen.

Mebendazole has shown embryotoxic and teratogenic activity in pregnant rats and mice at oral doses of 10 mg/kg/day and above and in rats at a single dose of 10 mg/kg, approximately equivalent to the human dose of 100 mg on a body surface area (mg/m2) basis.

6.1 List of Excipients

Lactose, pregelatinized maize starch, sunset yellow (E110), sodium saccharin, sodium lauryl sulphate, natural orange flavour, sodium starch glycollate, microcrystalline cellulose and magnesium stearate.

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

2 years

6.4 Special precautions for storage

Do not store above 25°C.

6.5 Nature and contents of container

Blister packs

Pack size: 1, 2, 4, 6 and 8 tablets.

6.6 Special precautions for disposal

None stated.

Any unused product or waste material should be disposed of in accordance with local requirements