Difflam is indicated in adults and children over 6 years of age, for symptomatic local treatment for the relief of pain and irritation of mouth and throat.

Posology

Adults and children over 6 years of age: one lozenge 3 times a day.

The treatment must not exceed 7 days.

Paediatric population

Children 6-11 years of age:

The medicinal product should be administered under adult supervision.

Children below 6 years of age:

Due to the type of the pharmaceutical form, the administration should be restricted to children of more than 6 years of age.

Method of administration

For oropharingeal use.

Lozenge should be dissolved slowly in the mouth.

Do not swallow. Do not chew.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Benzydamine use is not advisable in patient with hypersensitivity to salicylic acid or other NSAIDs.

Bronchospasm may be precipitated in patients suffering from or with a previous history of bronchial asthma. Caution should be exercised in these patients.

In a minority of patients, buccal/pharyngeal ulceration may be caused by serious disease processes. Patients whose symptoms worsen or do not improve within 3 days, or who appear feverish or have other symptoms, must therefore seek the advice of their doctor or dentist as appropriate.

Difflam contains:

- Aspartame: aspartame is hydrolysed in the gastrointestinal tract when orally ingested. One of the major hydrolysis products is phenylalanine that may be harmful for people with phenylketonuria.

- Isomalt: patients with rare hereditary problems of fructose intolerance should not take this medicine.

- Mint Fragrance with Benzyl Alcohol, Citronellol, d- Limonene, Eugenol, Geraniol, Linalool and Lemon Fragrance with Benzyl Alcohol, Citral, Citronellol, d-Limonene, Geraniol, Linalool. These may cause allergic reactions.

- -Butylated hydroxyanisole which is a component of lemon fragrance: It may cause local skin reactions (e.g. contact dermatitis) or irritation to the eyes and mucous membranes.

No interaction studies have been performed.

Pregnancy

There are no or limited amount of data from the use of benzydamine in pregnant womenand animal studies are insufficient with respect to reproductive toxicity (see section 5.3).

Difflam should not be used during pregnancy.

Breast-feeding

There is insufficient information on the excretion of benzydamine in human milk.

Difflam should not be used during breast-feeding.

Difflam has no or negligible influence on the ability to drive and use machines, when it is used at the recommended dose.

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness

The following rate values have been used: Very common (≥ 1/10), Common (≥ 1/100 to <1/10), Uncommon (≥ 1/1,000 to <1/100), Rare (≥ 1/10,000 to <1/1,000) and Very rare (<1/10,000), not known (cannot be estimated from the available data).

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

Symptoms

No overdosage with the lozenge formulation has been reported. However, very rarely in children excitation, convulsions, sweating, ataxia, tremor and vomiting have been reported after the oral administration of benzydamine dosages about 100 times higher than those of the lozenge.

Management

In the event of acute overdosage only symptomatic treatment is possible; the stomach should be emptied by inducing vomiting or by gastric lavage, and the patient carefully observed and given supportive treatment. Adequate hydration must be maintained.

Pharmacotherapeutic group: other throat preparations, ATC code: R02AX03.

Clinical efficacy and safety

Clinical studies demonstrate that benzydamine is effective in relieving suffering from localised irritation processes of the mouth and pharynx. In addition, benzydamine possesses a moderate local anaesthetic effect.

A 7 days non inferiority, phase IV, multicenter, randomized, open label, active-controlled study has compared the efficacy and safety of Benzydamine hydrochloride 0,3% oromucosal spray and Benzydamine hydrochloride 3 mg lozenges in 363 patients with acute sore throat.

The primary objective of the study was to assess the efficacy of benzydamine hydrochloride (spray or lozenges), in sore throat pain relief at 2 minutes (T2 min) after a single dose (one 3 mg benzydamine lozenge vs 4 nebulizations) administration, using a 7 point STRRS (Sore Throat Relief Rating Scale). The secondary objective of the study was to assess the efficacy of benzydamine hydrochloride (spray or lozenges), in sore throat pain relief at 1 minute (T1) after a single dose administration using STRRS. A pain relief at least slight (STRRS score >1), was observed 1 minute after complete dissolution of the lozenge (mean dissolution time 9.12 minutes) in 87% of patients and in 91% of patients after 2 minutes. A pain relief at least moderate (STRRS score >3,) was observed after 15 minutes in approximately 83% of patients.

The improvement in difficulty in swallowing and swollen sensation were also observed. Improvement in swallowing difficulty and throat swelling was observed 5 minutes after complete dissolution of the lozenge (mean dissolution time 9.12 minutes), reaching a 22% and 25% reduction, respectively, that increased to 42% for both parameters after 2 hours.

Safety profile of benzydamine was confirmed

Absorption

The absorption through the mucosa of the mouth and pharynx was demonstrated by the presence of measurable quantities of benzydamine in the human plasma.

Distribution

About 2 hours after the 3 mg lozenge administration, benzydamine peak plasma values of 37.8 ng/ml with an AUC of 367 ng/ml*h were observed. However, these levels are not sufficient to produce pharmacological systemic effects.

When locally applied benzydamine has been shown to accumulate in inflamed tissues where it reaches effective concentrations because of its capacity to penetrate the epithelial lining.

Biotransformation and elimination

The excretion occurs mainly in the urine and mostly in the form of inactive metabolites or conjugation products.

Development and peri-post natal toxicity was seen in reproductive toxicity studies in rats and rabbits at plasma concentration much higher (up to 40 times) than those observed after a single therapeutic oral dose. No teratogenic effects were seen in those studies. Available kinetic data do not allow to establish the clinical relevance of the reproductive toxicity studies. As the preclinical studies had shortcomings and therefore are of restricted value, they do not provide additional information relevant for the prescriber beyond that included in other sections of the SPC.

Isomalt (E 953),

Aspartame (E 951),

Citric acid, monohydrate,

Lemon flavour,

Mint flavour,

Quinoline yellow (E 104),

Indigotin dye (E 132).

Not applicable.

4 years.

Do not store above 25° C.

Store in original package in order to protect from moisture.

Lozenge is wrapped in paraffin paper.

Ten lozenges form one stick, packaged in printed polyethylene-paper-aluminium trilaminated material.

Lozenges can be packaged also in PVC/PE/PVDC – ALU blister.

Pack sizes of 20 or 30 lozenges.

Not all pack size may be marketed.

No special requirements.

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