This information is intended for use by health professionals

1. Name of the medicinal product

Oroeze Spray 0.15% w/v Oromucosal Spray

Benzydamine 0.15% w/v Oromucosal Spray

2. Qualitative and quantitative composition

Benzydamine hydrochloride 0.15% w/v.

Each spray contains 262.5 micrograms of benzydamine hydrochloride.

Excipients with known effect

Ethanol (96%) 8.1 %w/v

Methyl parahydroxybenzoate 0.1 %w/v

It also contains propylene glycol.

For the full list of excipients, see Section 6.1

3. Pharmaceutical form

Oromucosal spray.

A clear solution with an odour of peppermint in a multidose spray container fitted with a metering pump and nozzle.

4. Clinical particulars
4.1 Therapeutic indications

Oroeze Spray is a locally acting analgesic and anti-inflammatory treatment for the throat and mouth.

It is especially useful for the relief of pain in traumatic conditions such as following tonsillectomy or the use of a naso-gastric tube; dental surgery.

4.2 Posology and method of administration

Posology

ADULTS AND ELDERLY: 4 to 8 sprays, 1½ - 3 hourly.

Paediatric population

CHILDREN (6-12): 4 sprays, 1½ - 3 hourly.

CHILDREN UNDER 6: One spray to be administered per 4 kg body weight, up to a maximum of 4 sprays, 1½ - 3 hourly.

Because of the small amount of drug applied, elderly patients can receive the same dose as adults.

Method of administration

Oromucosal administration.

4.3 Contraindications

Hypersensitivity to active substance 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.

Oroeze Spray/Benzydamine 0.15% w/v Oromucosal Spray contains methyl parahydroxybenzoate which may cause allergic reactions (possibly delayed). It also contains propylene glycol which may cause skin irritation.

Oroeze Spray/Benzydamine 0.15% w/v Oromucosal Spray contains small amounts of ethanol (alcohol), less than 100 mg per dose.

4.5 Interaction with other medicinal products and other forms of interaction

None known.

4.6 Fertility, pregnancy and lactation

Pregnancy

Oroeze Spray/Benzydamine 0.15% Oromucosal Spray should not be used in pregnancy

Breast-feeding

Oroeze Spray/Benzydamine 0.15% Oromucosal Spray should not be used during lactation unless considered essential by the physician.

Fertility

There is no evidence of a teratogenic effect in animal studies.

4.7 Effects on ability to drive and use machines

Oroeze Spray/Benzydamine 0.15% Oromucosal Spray has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

Adverse events are listed by System Organ Class:

Frequencies are defined using the following convention:

Very common (≥1/10), Common (≥1/100, <1/10), Uncommon (≥1/1000, <1/100), Rare (≥1/10000, <1/1000), Very rare (<1/10000), Not known (cannot be estimated from the available data).

The most common side effects are numbness and a stinging feeling in the mouth.

System organ class

Frequency

Undesirable effects

Immune system disorders

Not known

Anaphylactic reaction which can be potentially life-threatening and hypersensitivity reactionsii

Respiratory, thoracic and mediastinal disorders

Very rare

Laryngospasm or bronchospasm

Gastrointestinal disorders

Uncommon

Oral numbness and a stinging feeling in the mouthi

Skin and subcutaneous tissue disorders

Very rare

Pruritus, urticaria, photosensitivity reaction and rash

Not known

Angioedema

i) The stinging has been reported to disappear upon continuation of the treatment, however if it persists it is recommended that treatment be discontinued.

ii) Methyl parahydroxybenzoate may cause allergic reactions (possibly delayed).

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after authorisations 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 Website at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Symptoms

Oroeze Spray/Benzydamine 0.15% Oromucosal Spray is unlikely to cause adverse systemic effects, even if accidental ingestion should occur. No special measures are required. Intoxication is only expected in case of accidental ingestion of large quantities of benzydamine (> 300 mg)

Symptoms associated with overdose of ingested benzydamine are mainly gastrointestinal symptoms and symptoms of the central nervous system. Most frequent gastrointestinal symptoms are nausea, vomiting, abdominal pain and oesophageal irritation. Symptoms of the central nervous system include dizziness, hallucinations, agitation, anxiety and irritability.

Management

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.

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Non-steroidal anti-inflammatory drug.

ATC code: A01AD02 (Other agents for local oral treatment)

Benzydamine exerts an anti-inflammatory and analgesic action by stabilising the cellular membrane and inhibiting prostaglandin synthesis.

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.

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 benzydamine 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 benzydamine 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

Absorption

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.

Elimination

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

Ethanol (96%)

Methyl parahydroxybenzoate

Saccharin sodium

Polysorbate 20

Peppermint flavour

Aniseed flavour

Purified water

6.2 Incompatibilities

None known.

6.3 Shelf life

2 years unopened.

Use within 6 months of opening.

6.4 Special precautions for storage

There are no special requirements for storage.

6.5 Nature and contents of container

White HDPE multidose spray container, fitted with a metering pump and nozzle, containing 30ml Oroeze.

6.6 Special precautions for disposal and other handling

No special requirements for disposal.

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

7. Marketing authorisation holder

Focus Pharmaceuticals Ltd

Capital House,

85 King William Street,

London EC4N 7BL

United Kingdom.

8. Marketing authorisation number(s)

PL 20046/ 0049

9. Date of first authorisation/renewal of the authorisation

29/01/2010

10. Date of revision of the text

14/04/2020