Vermox 100 Mg/5 Ml Oral Suspension

SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Vermox® 100 mg/5 ml oral suspension

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 5 ml of suspension contains 100 mg of mebendazole.

Excipients: Each 5 ml also contains 500 mg of sucrose, 9 mg of methyl parahydroxybenzoate (E218) and 1 mg of propyl parahydroxybenzoate (E216).

For a full list of excipients, see section 6.1

3 PHARMACEUTICAL FORM

Oral suspension.

White homogeneous oral suspension.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Broad spectrum gastrointestinal anthelmintic indicated for the treatment of: Enterobius vermicularis (threadworm/pinworm)

Oxyuris vermicularis Trichuris trichuria (whipworm)

Ascaris lumbricoides (large roundworm)

Ancylostoma duodenale (common hookworm)

Necator americanus (American hookworm)

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

4.2 Posology and method of administration

Method of administration.

Oral Use

Adults and children over 2 years:

Enterobiasis:

1 x 5 ml (1 dosing cup).

It is highly recommended that a second dose is taken after 2 weeks, if reinfection is suspected.

Ascariasis, trichuriasis, ancylostomiasis, necatoriasis and mixed infections: 1 x 5 ml (1 dosing cup) bd for three days.

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.

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.

Vermox oral suspension contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

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 Pregnancy and lactation

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

As it is not known whether mebendazole is excreted in human milk, it is not advisable to breast-feed following administration of Vermox.

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

System Organ Class	Adverse Drug Reactions
	Frequency Category
	Common (> 1/100 to < 1/10)	Uncommon (> 1/1000 to < 1/100)	Rare (>1/10,000 to <1/1000)
Blood and lymphatic system disorders			Neutropenia^b
Immune system disorders			Hypersensitivity including anaphylactic reaction and anaphylactoid reaction^b
Nervous system disorders			Convulsions^b Dizziness^a
Gastrointestinal disorders	Abdominal pain^a	Abdominal discomfort^a; Diarrhoea^a; Flatulence^a
Hepatobiliary disorders			Hepatitis^b; Abnormal liver function tests^b
Skin and subcutaneous tissue disorders			Rash^a Toxic epidermal necrolysis^b; Stevens-Johnson syndrome^b; Exanthema^b; Angioedema^b; Urticaria^b; Alopecia^b

^a ADR frequency data derived from Clinical Trials or Epidemiological Studies

^b ADRs not observed in clinical trials and frequency calculated using “Rule of 3”, as detailed in SmPC guideline 2009. 6276 patients exposed in clinical trials and epidemiological studies, divided by 3 (Frequency = 1/2092). Note: frequencies differ from those reported in the August 2009 CCDS, as these were not calculated using the formula detailed in the SmPC guideline 2009.

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:

United Kingdom

Yellow Card Scheme

Website: www.mhra.gov .uk/yellowcard

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 to extensive pre-systemic 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.

Metabolism

Orally administered mebendazole is extensively metabolised 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

No relevant information additional to that contained elsewhere in the Summary of Product Characteristics.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sucrose

Microcrystalline cellulose and carmellose sodium

Methylcellulose 15 mPa.s

Methyl parahydroxybenzoate (E218)

Propyl parahydroxybenzoate (E216)

Sodium laurilsulfate Banana flavour Citric acid, monohydrate Purified water

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

Shake well before use.

Keep out of reach and sight of children.

6.5 Nature and contents of container

Amber glass flask containing 30 ml suspension, with either:

• Pilfer-proof screw cap. Cork insert in cap is coated on both sides with polyvinylchloride

• Child-resistant polypropylene screw cap, lined inside with a LDPE insert.

A 5 ml natural polypropylene (food-grade) dosing cup is also provided, graduated for

2.5 ml and 5 ml.

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,

8 MARKETING AUTHORISATION NUMBER(S)

PL 00242/0050

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of First Authorisation: 17 November 1977 Date of Renewal of Authorisation: 15 December 2002

10 DATE OF REVISION OF THE TEXT

14/07/2016