DIFFLAM CREAM, DIFFLAM 3% P CREAM - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Difflam Cream

or

Difflam 3% P Cream

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tube of Difflam 3% Cream/ Difflam-P 3% Cream contains Benzydamine Hydrochloride 3% w/w.

Excipients with known effects

Contains methyl hydroxybenzoate, propyl hydroxybenzoate, cetyl alcohol propylene glycol, benzyl alcohol, benzyl benzoate, citral, citronellol, coumarin, eugenol, farnesol, geraniol, hydroxycitronellal, isoeugenol, limonene and linalool.

For a full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Cream for topical application to skin.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Difflam 3% Cream/ Difflam-P 3% Cream is a topical analgesic and non-steroidal anti-inflammatory agent.

It is recommended as a short-term treatment for the relief of symptoms associated with painful inflammatory conditions of the musculo-skeletal system, including:

Acute inflammatory disorders such as myalgia and bursitis.

Traumatic conditions such as sprains, strains, contusions and the after-effects of fractures.

Difflam 3% Cream/ Difflam-P 3% Cream is well absorbed through the skin and has been shown to have anti-inflammatory and local anaesthetic actions.

4.2 Posology and method of administration

Difflam Cream/ Difflam 3% P Cream should be massaged lightly into the affected area. Depending on the size of the site to be treated, 35 – 85 mm (1 –2 g) should be applied three times daily and at the discretion of the doctor, up to six times daily in more severe conditions. It is recommended that treatment be limited to not more than ten days.

ELDERLY:

No special dosage recommendations are made for elderly patients.

4.3 Contraindications

Difflam 3% Cream/ Difflam-P 3% Cream is contraindicated in patients with known hypersensitivity to the active substance benzydamine hydrochloride or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

This product should not be applied to the eyes or mucosal surfaces.

Cetyl alcohol may cause local skin reactions (e.g. contact dermatitis).

Propylene glycol may cause skin irritation.

Benzydamine use is not advisable in patients with hypersensitivity to acetylsalicylic 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.

Methyl hydroxybenzoate and propyl hydroxybenzoate may cause allergic reactions (possibly delayed).

This medicine contains 0.04mg benzyl alcohol in each 2g dose which is equivalent to 0.02mg/g. Benzyl alcohol may cause allergic reactions and mild local irritation

This medicinal product contains fragrance with benzyl benzoate, citral, citronellol, coumarin, eugenol, farnesol, geraniol, hydroxycitronellal, isoeugenol, limonene and linalool. These substances may cause allergic reactions.

Instruct patients not to smoke or go near naked flames – risk of severe burns. Fabric (clothing, bedding, dressings etc) that has been in contact with this product burns more easily and is a serious fire hazard. Washing clothing and bedding may reduce product build-up but not totally remove it.

4.5 Interaction with other medicinal products and other forms of interaction None.

4.6 Fertility, Pregnancy and lactation

Pregnancy

Difflam 3% Cream/ Difflam-P 3% Cream should not be used in pregnancy unless considered essential by the physician. There is no evidence of a teratogenic effect in animal studies.

Breast-feeding

Difflam 3% Cream/ Difflam-P 3% Cream should not be used in lactation unless considered essential by the physician.

4.7 Effects on ability to drive and use machines None.

4.8 Undesirable effects

Within the system organ classes, adverse reactions are listed under headings of frequency (number of patients expected to experience the reaction), using the following categories:

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 Card in the

Google Play or Apple App Store.

4.9 Overdose

Difflam 3% Cream/ Difflam-P 3% Cream is unlikely to cause adverse systemic effects, even if accidental ingestion should occur. No special measures are required.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Other anti-inflammatory and antrheumatic agents, non-steroids /Anti-inflammatory preparations, non-steroids for topical use, ATC code: M01AX07/M02AA05

The indazole analogue benzydamine has physicochemical properties and pharmacological activities which differ from those of the aspirin-like NSAIDs. Unlike aspirin-like NSAIDs which are acids or metabolised to acids, benzydamine is a weak base. In further contrast, benzydamine is a weak inhibitor of the prostaglandin synthesis. Only at concentration of 1mM and above benzydamine effectively inhibits cyclooxygenase and lipooxygenase enzyme activity. It mostly exerts its effects through inhibition of the synthesis of proinflammatory cytokines including tumour_necrosis factor-alpha (TNF-a) and Interleukin-1ß (IL-1ß) without significantly affecting other pro-inflammatory (IL-6 and 8) or anti-inflammatory cytokines (IL-10, IL-1 receptor antagonist). Further mechanisms of action are hypothesised including the inhibition of the oxidative burst of neutrophils as well as membrane stabilisation as demonstrated by the inhibition of granule release from neutrophils and the stabilization of lysosomes. The local anaesthetic activity of the compound has been related to an interaction with cationic channels

Benzydamine specifically acts on the local mechanisms of inflammation such as pain, oedema or granuloma. Benzydamine topically applied demonstrates anti-inflammatory activity reducing oedema as well as exudate and granuloma formation. Further, it exhibits analgesic properties if pain is caused by an inflammatory condition and local anaesthetic activity. Hyperthermia, which is indicative of systemic functional involvement, is poorly affected by benzydamine

In a clinical study in 24 patients with pharyngitis following tonsillectomy rinsing with Difflam 0.15% 5 times a day for 6 days significantly better and more rapidly relieved throat pain, difficulty in swallowing and improved clinical signs including hyperaemia and oedema versus placebo on day 7. Similar results were found in other studies in patients with tonsillitis or pharyngitis or following dental surgery. The gargling with 30 ml 0.075% benzydamine prior to the induction of anaesthesia in 58 adults undergoing general anaesthesia with endotracheal tube intubation significantly reduced postoperative sore throat versus water control for the first 24 hours whereas aspirin gargles reduced it for 4 hours.

In a clinical study with 48 patients rinsing four times daily with 0.15% benzydamine during a 3 to 5 week radiotherapy of oral cancer provided significant pain relief and reduction of size and severity of mucositis in the oropharynx. Similar effects were seen in a study in patients undergoing chemotherapy for oral cancer. In a study in 67 patients with severe oropharyngeal mucositis following radiotherapy who rinsed with benzydamine solution pain with swallowing, hyperaemia and severity of mucositis were significantly reduced compared to placebo treatment within the first three treatment days.

A higher incidence of transient numbness and stinging was noted among the patients using benzydamine that was attributed to the medication’s local anaesthetic effect.

The topical application of Difflam cream 3% 3 times daily for 6 days in 50 patients with soft tissue injuries significantly better relieved pain, tenderness, erythema, functional impairment and swelling compared to placebo on day 6.

Overall, benzydamine was well tolerated in clinical trials.

5.2 Pharmacokinetic properties

Following topical administration, benzydamine is absorbed through intact skin and reaches peak levels between 24 – 32 hours, amounting to about 20 – 25% of the plasma levels obtained after the oral administration of the same dose.

About half of the benzydamine is excreted unchanged via the kidney at a rate of 10% of the dose within the first 24 hours. The remainder is metabolised, mostly to N-oxide.

5.3 Preclinical safety data

Non-Clinical Data reveal no special hazards for humans based on conventional studies of safety pharmacology, repeated toxicity, genotoxicity, cardiogenic potential, and toxicity to reproduction.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Glycerol stearate ‘Cutina’

Cetyl Alcohol USNF

Decyl oleate ‘Cetiol V’

Macrogol cetostearyl ether ‘Eumulgin B1’

Propylene Glycol Ph Eur

Perfume, ‘Crematest’ 0/064060’

Methyl Hydroxybenzoate Ph Eur

Propyl Hydroxybenzoate Ph Eur

Purified Water Ph Eur

6.2 Incompatibilities

None known.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

Store between 5 – 30°C. Do not freeze.

6.5 Nature and contents of container

Collapsible Aluminium tube closed with plastic screwcap

or

Laminate tube closed with plastic screwcap.

Contents: 35 g, 50 g or 100 g

6.6 Special precautions for disposal Not applicable.

7 MARKETING AUTHORISATION HOLDER

Mylan Products Ltd.,

Station Close,

Potters Bar,

Herts,

EN6 1TL,

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 46302/0158

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

06/03/1980 / 06/09/2002