Difflam 0.15% Spray
1
NAME OF THE MEDICINAL PRODUCT
Difflam 0.15% w/v Spray
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each metered dose pump spray delivers Benzydamine hydrochloride 0.15% w/v, approximately 175 microlitres per puff.
Contains methyl parahydroxybenzoate and Ethanol.
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Difflam 0.15% Spray is a metered dose pump throat spray.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Difflam 0.15% Spray is a locally acting analgesic and anti-inflammatory treatment for the throat and mouth.
It is used to treat various painful oropharyngeal conditions such as mouth ulcers, sore throat, sore mouth or gums, dental pain.
4.2 Posology and method of administration
Posology
Adults, adolescents and elderly: 4 to 8 puffs every 1^-3 hourly.
Children(6-12): 4 puffs every 1^-3 hourly.
Children under 6: One puff to be administered per 4 kg body weight, up to a maximum of 4 puffs, 1^-3 hourly.
Elderly: Because of the small amount of drug applied, elderly patients can receive the
Method of administration For oral administration
4.3 Contraindications
Difflam 0.15% w/v Spray is contra-indicated 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
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.
Avoid contact with the eyes.
If the condition is aggravated or not improved use should cease.
This medicinal product contains 10 vol % ethanol.
Methyl hydroxybenzoate may cause allergic reactions (possibly delayed)
4.5 Interaction with other medicinal products and other forms of interaction
None known.
4.6 Fertility, pregnancy and lactation
Pregnancy
Difflam 0.15% w/v Spray 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 0.15% w/v Spray should not be used in lactation unless considered essential
4.7 Effects on ability to drive and use machines
None.
4.8 Undesirable effects
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).
The most common side effects are numbness and a stinging feeling in the mouth.
Respiratory, thoracic and mediastinal disorders Very rare: Laryngospasm or bronchospasm.
Gastrointestinal disorders
Uncommon: Oral numbness and a stinging feeling in the mouth.
The stinging has been reported to disappear upon continuation of the treatment, however if it persists it is recommended that treatment be discontinued.
Skin and subcutaneous tissue disorders
Very rare: Hypersensitivity reactions which may be associated with pruritus, urticaria, photosensitivity reaction and rash
Frequency not known: Angioedema
Immune system disorders
Frequency not known: Anaphylactic reaction which can be potentially life-threatening.
Methyl parahydroxybenzoate may cause allergic reactions (possibly delayed). 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.
4.9 Overdose
Difflam 0.15% Spray 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
Mechanism of action
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-1P (IL-1P) without significantly affecting other proinflammatory (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
Pharmacodynamic effects
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
Clinical efficacy and safety
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 oral administration, Benzydamine is rapidly absorbed from the gastrointestinal tract and maximum plasma levels reached after 2-4 hours. The most important aspect of the tissue distribution of Benzydamine is its tendency to concentrate at the site of inflammation.
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 Ph. Eur.
Saccharin FU
Sodium Bicarbonate Ph. Eur. Ethanol FU
Methylhydroxybenzoate Ph. Eur. Mouthwash Flavour Polysorbate 20 Ph. Eur.
Purified Water Ph. Eur.
6.2 Incompatibilities
None.
6.3 Shelf life
The shelf life expiry date for this product shall not exceed 3 years from the date of its manufacture.
6.4 Special precautions for storage
Do not store above 30°C, do not refrigerate or freeze. Keep out of the reach of children.
6.5 Nature and contents of container
Difflam 0.15% Spray is presented in a 30 ml HDPE bottle with 170 pl valve pump spray.
6.6 Special precautions for disposal
No special requirements
7. MARKETING AUTHORISATION HOLDER
Meda Pharmaceuticals Ltd Skyway House Parsonage Road Takeley
Bishop’s Stortford CM22 6PU
8 MARKETING AUTHORISATION NUMBER(S)
PL 15142/0046
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
30th November 1984 / 05th March 2004
10 DATE OF REVISION OF THE TEXT
06/06/2016