- benzydamine hydrochloride
This information is intended for use by health professionals
Difflam 0.15% w/v Sore Throat Rinse.
Benzydamine Hydrochloride 0.15% w/v.
Contains methyl parahydroxybenzoate and Ethanol.
For a full list of excipients, see section 6.1.
Solution for use as a gargle/oral rinse.
Difflam Sore Throat Rinse is a locally acting analgesic and anti-inflammatory treatment for the relief of painful inflammatory conditions of the throat including pharyngitis.
Rinse or gargle with 15ml (using measuring cup provided) every 1½ to 3 hours as required for pain relief.
Not suitable for children aged 12 years or under.
No special dosage recommendations are made for elderly patients.
Method of administration
Rinse or gargle.
The solution should be expelled from the mouth after use.
Difflam Sore Throat Rinse should generally be used undiluted, but if 'stinging' occurs the rinse may be diluted with water.
Uninterrupted treatment should not exceed seven days, except under medical supervision.
Difflam Sore Throat Rinse 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.
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.
Difflam Sore Throat Rinse should generally be used undiluted, but if 'stinging' occurs the rinse may be diluted with water. Avoid contact with the eyes.
This medicinal product contains 10 vol % ethanol.
Methyl hydroxybenzoate may cause allergic reactions (possibly delayed)
Difflam Sore Throat Rinse 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 Sore Throat Rinse should not be used in lactation unless considered essential by the physician.
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.
Uncommon: Oral numbness (hypoesthesia) and a stinging feeling in the mouth (oral pain).
Skin and subcutaneous tissue disorders
Very rare: pruritus, urticaria, photosensitivity reaction and rash
Frequency not known: Angioedema
Immune system disorders
Frequency not known: Anaphylactic reaction which can be potentially life-threatening. Hypersensitivity reactions.
Methyl parahydroxybenzoate may cause allergic reactions (possibly delayed).
Reporting of suspected adverse reactionsReporting 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.
Difflam Sore Throat Rinse is unlikely to cause adverse systemic effects, even if accidental ingestion should occur. Intoxication is only to be expected if large quantities of Difflam Oral Rinse/ Difflam Sore Throat Rinse are swallowed (> 300mg).
Symptoms associated with ingested overdose of benzydamine are mainly gastrointestinal symptoms and symptoms of the central nervous system. Most frequent gastrointestinal symptoms are nausea, vomiting, abdominal pain, and esophageal irritation. Symptoms of the central nervous system include dizziness, hallucinations, agitation, anxiety, and irritability.
In acute overdose only symptomatic treatment is possible. Patients should be kept under close observation and supportive treatment should be given. Adequate hydration must be maintained.
Pharmacotherapeutic group: Other anti-inflammatory and antrheumatic agents, non-steroids /Anti-inflammatory preparations, non-steroids for topical use,
ATC code: M01AX07/M02AA05
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-α) and Interleukin-1β (IL-1β) 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
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.
Oral doses of benzydamine are well absorbed and plasma drug concentrations reach a peak fairly rapidly and then decline with a half-life of about 13 hours. Less than 20% of the drug is bound to plasma proteins.
Although local drug concentrations are relatively large, the systemic absorption of mouthwash-gargle doses of benzydamine is relatively low compared to oral doses. This low absorption should greatly diminish the potential for any systemic drug side-effects when benzydamine is administered by this route. Benzydamine is metabolized primarily by oxidation, conjugation and dealkylation.
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.
Ethanol (96% v/v) BP Glycerol Ph Eur, Saccharin Sodium BP, Mouthwash Flavour, 52 503/T, Polysorbate 20 Ph Eur, Methyl Hydroxybenzoate Ph Eur, Quinoline Yellow (E104), Patent Blue V (E131), Purified Water Ph Eur.
Store between 5°C and 30°C; do not freeze; do not leave uncartonned bottle in direct sunlight.
Clear glass bottle with screw cap containing 200 ml.
Dose measure included.
Mylan Products Ltd
20 October 1995/ 31 October 2005
Building 4, Trident Place, Mosquito Way, Hatfield, Herts, AL10 9UL, UK
+44 (0) 800 1218 267
+44 (0)1707 853 000