This information is intended for use by healthcare professionals.
1. Name of the drug
Difflam Aerosol 0,15% p/v
2. Qualitative and quantitative composition
Each puff (175 microliters) contains 262.5 micrograms of benzydamine hydrochloride (0.15% w/v).
Excipient(s) with known effects:
methyl parahydroxybenzoate
Ethanol
Mint aroma with benzyl alcohol, cinnamyl alcohol, citral, citronellol, eugenol, geraniol, isoeugenol, limonene and linalool.
For the complete list of excipients, see section 6.1.
3. Pharmaceutical form
Difflam Spray is a metered dose pump throat spray.
4. Clinical data
4.1 Therapeutic indications
Difflam Spray is a locally acting anti-inflammatory and analgesic treatment for the throat and mouth. It is especially useful for pain relief in traumatic conditions, such as after tonsillectomy or use of a nasogastric tube; dental surgery.
4.2 Posology and method of administration
Posology
Adults, teenagers and seniors:4 to 8 puffs every 1½-3 hours.
Children (6-12):4 puffs every 1½-3 hours.
Children under 6 years old:One inhalation should be administered for every 4 kg of body weight, up to a maximum of 4 inhalations, every 1½-3 hours.
Geezer:Due to the small amount of medicine applied, elderly patients can receive the same dose as adults.
administration method
for oral administration
4.3 Contraindications
Difflam Spray 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
The use of benzydamine is not recommended in patients who are hypersensitive to aspirin or other NSAIDs.
Bronchospasm may be precipitated in patients with or with a history of bronchial asthma. Caution should be exercised in these patients.
Avoid eye contact.
If the condition worsens or does not improve, use should be discontinued.
This medicine contains 14 mg of alcohol (ethanol) in each puff. The amount of 1 inhalation of this medicine is equivalent to less than 1 ml of beer or 1 ml of wine. The small amount of alcohol in this medicine will have no noticeable effect.
Methyl parahydroxybenzoate may cause allergic reactions (possibly delayed)
This medicine contains 0.025 mg of benzyl alcohol in each 175 microliter dose, which is equivalent to 0.14 mg/ml. Benzyl alcohol can cause allergic reactions and mild local irritation.
This medication contains mint flavor with benzyl alcohol, cinnamyl alcohol, citral, citronellol, eugenol, geraniol, isoeugenol, limonene and linalool. These substances can cause allergic reactions.
This medicinal product contains less than 1 mmol sodium (23 mg) per 8 inhalation doses; that is, essentially "sodium free".
4.5 Interaction with other drugs and other forms of interaction
None known.
4.6 Fertility, pregnancy and lactation
the pregnancy
Diffflam Spray should not be used during pregnancy unless considered essential by your doctor. There is no evidence of a teratogenic effect in animal studies.
Breast-feeding
Diffflam Spray should not be used during lactation unless considered essential by a physician.
4.7 Effects on ability to drive and use machines
No.
4.8 Undesirable Effects
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
The following frequency values were used: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/100) , 10,000 to <1/1,000) and very rare (<1/10,000), frequency not known (cannot be estimated from available data).
The most common side effects are numbness and a burning sensation in the mouth.
Organ class system | Frequency | adverse reaction |
Immune system disorders | not known | Anaphylactic reactions, Hypersensitivity reactions [20]. |
Respiratory, thoracic and mediastinal disorders | Very strange | Laryngospasm or bronchospasm |
gastrointestinal problems | uncommon | Oral numbness and burning sensation in the mouth. Itching has been reported to disappear with continued treatment; however, if it persists, discontinuation of treatment is recommended. |
Skin and subcutaneous tissue disorders | Very strange | Pruritus, hives, photosensitivity reaction and rash |
not known | angioedema |
Notification of suspected adverse reactions
It is important to report suspected adverse drug reactions after authorization. Allows continuous monitoring of the benefit/risk ratio of the drug. 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 is unlikely to cause adverse systemic effects, even if accidentally ingested. No special measures are required. Intoxication is only expected in case of accidental ingestion of large amounts of benzydamine (> 300 mg)
Symptoms associated with ingested benzydamine overdose are primarily gastrointestinal symptoms and central nervous system symptoms. The most common gastrointestinal symptoms are nausea, vomiting, abdominal pain and esophageal irritation. Central nervous system symptoms include dizziness, hallucinations, agitation, anxiety, and irritability.
In case of acute overdose, only symptomatic treatment is possible. Patients should be kept under close observation and supportive care given. Adequate hydration must be maintained.
5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Other anti-inflammatory and anrheumatic agents, non-steroidal/Anti-inflammatory preparations, non-steroidal for topical use, ATC code: M01AX07
Mechanism of action
The indazole analogue benzydamine has physicochemical properties and pharmacological activities that differ from aspirin-like NSAIDs. Unlike aspirin-like NSAIDs, which are acidic or metabolized to acids, benzydamine is a weak base. In further contrast, benzydamine is a weak inhibitor of prostaglandin synthesis. Only at a concentration of 1 mM and above, benzydamine effectively inhibits the activity of cyclooxygenase and lipoxygenase enzymes. It exerts its effects primarily by inhibiting the synthesis of pro-inflammatory cytokines, including tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β), without significantly affecting other pro-inflammatory cytokines (IL-6 and 8) or anti-inflammatory cytokines (IL-10, IL-1 receptor antagonist). Other mechanisms of action are postulated, including inhibition of neutrophil oxidative burst, as well as membrane stabilization, as demonstrated by inhibition of granule release from neutrophils and stabilization of lysosomes. The local anesthetic activity of the compound has been linked to an interaction with cation channels.
pharmacodynamic effects
Benzidamine acts specifically on local inflammatory mechanisms such as pain, edema or granuloma. Topically applied benzydamine demonstrates anti-inflammatory activity that reduces edema as well as exudate and granuloma formation. Furthermore, it exhibits analgesic properties if the pain is caused by an inflammatory condition and local anesthetic activity. Hyperthermia, indicative of systemic functional impairment, is little affected by benzydamine.
Clinical efficacy and safety
In a clinical study in 24 patients with pharyngitis after tonsillectomy, Difflam 0.15%, 5 times daily for 6 days, provided significantly better and faster relief of sore throat, difficulty swallowing, and improvement in clinical signs including hyperemia and edema compared to placebo on day 7. Similar results were found in other studies in patients with tonsillitis or pharyngitis or after dental surgery. Gargling with 30 mL of 0.075% benzydamine before induction of anesthesia in 58 adults undergoing general anesthesia with endotracheal intubation significantly reduced postoperative sore throat compared to water control in the first 24 hours, while gargling with aspirin reduced for 4 hours.
In a clinical study of 48 patients, 4 times daily 0.15% benzydamine for 3 to 5 weeks of radiotherapy for oral cancer provided significant pain relief and a reduction in the 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 of 67 patients with severe oropharyngeal mucositis after radiotherapy who rinsed with benzydamine solution, pain on swallowing, hyperemia and severity of mucositis were significantly reduced compared to placebo treatment in the first three months.
A higher incidence of transient numbness and burning was observed among patients using benzydamine, which was attributed to the local anesthetic effect of the drug.
Topical application of Difflam 3% cream 3 times daily for 6 days in 50 patients with soft tissue injuries provided significantly better relief of pain, tenderness, erythema, functional impairment and swelling compared to placebo on day 6.
In general, benzydamine was well tolerated in clinical trials.
5.2 Pharmacokinetic properties
After oral administration, benzydamine is rapidly absorbed from the gastrointestinal tract, with peak plasma levels achieved after 2 to 4 hours. The most important aspect of the tissue distribution of benzydamine is its tendency to concentrate at the site of inflammation. Approximately half of benzydamine is excreted unchanged by the kidneys at a rate of 10% of the dose in the first 24 hours. The rest is metabolized mainly to N-oxide.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated toxicity, genotoxicity, cardiogenic potential, and reproductive toxicity.
6. Pharmaceutical data
6.1 List of excipients
Glycerol Ph. EUR.
saccharin FU
Sodium Bicarbonate Ph. eur.
Ethanol FU
Metilhidroxibenzoato Ph. Eur.
Mouthwash Polysorbate Flavor 20 Ph. EUR.
Purified Water Ph. eur.
6.2 Incompatibilities
No.
6.3 Useful life
The expiry date of this product should not exceed 3 years from the date of manufacture.
6.4 Special storage precautions
Do not store above 30°C, refrigerate or freeze. Keep out of the reach of children.
6.5 Nature and contents of container
Difflam Spray is presented in a 30 ml HDPE bottle with a 170 l spray pump.
6.6 Special precautions for disposal and other handling
The patient must read the instruction leaflet before use.
7. Marketing Authorization Holder
Mylan Products Ltd, Station Close, Potters Bar, Hertfordshire, EN6 1TL, Reino Unido.
8. Marketing authorization number(s)
PL 46302/0160
9. Date of first authorization/renewal of authorization
30aNovember 1984/05aMarch 2004
10. Text revision date
December 2020.