ANDOLEX-C ORAL GEL

Indications

• Painful inflammatory conditions of the oropharynx
• Oral ulceration and inflammation
• Anaesthesia of mucous membranes

Dosage

Children: For children aged 1 month to 5 years: 1-3 sprays every 1.5-3 hours, dependent on body weight and condition; refer to the BNF for Children for precise dosing.

Adults: Refer to the BNF for specific dosing recommendations.

Mechanism of action

Benzydamine hydrochloride exerts its effects by inhibiting the synthesis of prostaglandins, which are mediators of inflammation and pain. It also possesses local anesthetic properties, providing relief from pain upon application to mucous membranes.

Pharmacodynamics

Benzydamine demonstrates anti-inflammatory, analgesic, and local anesthetic effects. It reduces pain and inflammation in the oropharynx, making it beneficial for various inflammatory conditions.

Pharmacokinetics

Benzydamine is rapidly absorbed when administered topically. It is distributed throughout the body, crosses the placenta, and is present in breast milk in small amounts. The drug undergoes hepatic metabolism and is excreted primarily in urine. Caution is advised in patients with hepatic and renal impairment due to potential accumulation.

Contra-indications

• Hypersensitivity to benzydamine or any component of the formulation

Adverse effects

• Oral disorders
• Photosensitivity reaction
• Skin reactions
• Angioedema

Interactions

• Caution with antiarrhythmics
• Caution with NSAIDs

Precautions

• Can damage plastic cuffs of endotracheal tubes
• Caution in hepatic impairment
• Caution in renal impairment

Pregnancy

Crosses the placenta but not known to be harmful in animal studies-use if benefit outweighs risk.

Breast-feeding

Present in milk but amount too small to be harmful.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Oromucosal Spray 0.15% (sugar-free)
• Mouthwash 0.15% (sugar-free)

Indications

• Sore throat
• Mouth ulcers
• Inflammatory conditions of the oral cavity
• Pain relief in conditions causing inflammation in the throat and mouth

Dosage

Children: Refer to the BNF for Children for appropriate dosing information based on the child's age

Adults: The dosage depends on the formulation and the condition being treated. Refer to the specific product information or the BNF for detailed dosing guidelines.

Mechanism of action

Benzydamine acts by inhibiting the synthesis of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β), while exerting minimal effects on other pro-inflammatory and anti-inflammatory cytokines. It is a weak inhibitor of prostaglandin synthesis, primarily affecting cyclooxygenase (COX) and lipoxygenase enzyme activity at high concentrations. Additionally, benzydamine is believed to inhibit the oxidative burst of neutrophils and stabilize lysosomes, contributing to its anti-inflammatory and analgesic effects. Its local anesthetic action is attributed to its ability to stabilize neuronal membranes.

Pharmacodynamics

Benzydamine provides local anesthetic and analgesic effects, focusing on the local mechanisms of inflammation such as pain and edema. It is absorbed through the oral mucosa and intact skin, binding selectively to inflamed tissues to exert its effects. The drug typically reaches peak plasma concentration within 2 to 4 hours, enhancing its localized therapeutic efficacy while minimizing systemic adverse effects.

Pharmacokinetics

Benzydamine is primarily administered topically, resulting in limited systemic absorption. Once applied, it accumulates in inflamed tissues, allowing for effective local action. The pharmacokinetic profile indicates that peak concentrations are achieved within 2 to 4 hours post-application, although specific systemic absorption metrics are not extensively characterized due to its localized use.

Adverse effects

• local irritation
• burning sensation
• dryness of the mouth
• nausea
• dizziness

Precautions

• Caution in patients with hypersensitivity to benzydamine or other NSAIDs
• Use with caution in patients with asthma or history of allergic reactions

Pregnancy

Benzydamine should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult healthcare provider before use.

Breast-feeding

It is unknown whether benzydamine is excreted in human milk. Caution is advised when administering to breastfeeding women.

Storage

Store at room temperature, away from light and moisture. Do not freeze.

Formulations

• oral rinse
• topical gel
• spray

Indications

• Oral hygiene
• Prevention of dental plaque
• Management of minor infections in the oral cavity

Dosage

Children: Refer to BNF for Children for appropriate formulations and guidance on paediatric use.

Adults: Refer to BNF for specific formulations and usage instructions. Typical concentrations in mouthwashes are around 0.05% to 0.1%.

Mechanism of action

Cetylpyridinium chloride functions as a cationic surfactant that interacts with microbial cell surfaces due to its positively charged hydrophilic region. This interaction disrupts bacterial membrane integrity, leading to leakage of cytoplasmic components, interference with cellular metabolism, and ultimately, cell death. Additionally, it inhibits the synthesis of insoluble glucan by streptococcal glucosyltransferase, adsorbs to enamel surfaces, and prevents bacterial co-adhesion, enhancing its effectiveness in oral hygiene.

Pharmacodynamics

Cetylpyridinium chloride exhibits rapid bactericidal effects against gram-positive pathogens and fungicidal activity against yeasts. It is classified as a cationic disinfectant with local effects, making it suitable for managing minor infections. Its surfactant properties contribute to its efficacy in reducing microbial load in oral care applications.

Pharmacokinetics

Cetylpyridinium chloride is characterized by poor systemic absorption when used topically; therefore, its effects are primarily local rather than systemic. This property allows it to exert its antimicrobial action in the mouth without significant absorption into the bloodstream, making it safe for use in oral care products.

Adverse effects

• Mouth irritation
• Taste alteration
• Dryness of the mouth
• Nausea
• Diarrhea

Precautions

• Use with caution in individuals with a history of hypersensitivity to cetylpyridinium chloride or other quaternary ammonium compounds.
• Avoid swallowing the product.
• Not recommended for use in children under a certain age without medical advice.

Pregnancy

Cetylpyridinium chloride should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consultation with a healthcare provider is advised.

Breast-feeding

It is not known whether cetylpyridinium chloride is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

Store at room temperature, away from direct sunlight and moisture. Keep out of reach of children.

Formulations

• Mouthwash
• Toothpaste
• Lozenges
• Mouth sprays

Mechanism of action

Despite being categorized as a non-steroidal anti-inflammatory drug (NSAID), benzydamine demonstrates various mechanisms of action that differ from those of traditional aspirin-like NSAIDs. In particular, benzydamine predominantly acts by inhibiting the synthesis of pro inflammatory cytokines like tumour necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) without largely affecting other pro inflammatory cytokines (ie. such as IL-6 and IL-8) or anti-inflammatory cytokines (ie. like IL-10 or IL-1 receptor antagonist). Moreover, benzydamine is largely a weak inhibitor of prostaglandin synthesis as it has been shown to effectively inhibit cyclooxygenase (COX) and lipoxygenase enzyme activity only at concentrations of 1mM or greater. Considering most contemporary usages of benzydamine are topical applications that are generally not well absorbed through the skin and/or non-specialized mucosae, benzydamine does not often achieve the kind of absorption or blood concentrations necessary to cause any extraneous distant systemic effects or COX inhibition, allowing it to localize its action. Additionally, it is also hypothesized that benzydamine is capable of inhibiting the oxidative burst of neutrophils and membrane stabilization. These actions are exhibited by the substance’s ability to inhibit the release of granules from neutrophils and to stabilize lysosomes. Furthermore, benzydamine is capable of a local anaesthetic effect that may be related to its capability for inhibiting the release of inflammatory mediators like substance P and calcitonin gene related peptide from sensory nerve endings. Since substance P is capable of causing the release of histamine from mast cells, benzydamine’s prevention of substance P release further contributes to an anti-inflammatory effect. Benzydamine also demonstrates a non-specific antibacterial activity against various bacterial strains that are resistant to broad-spectrum antibiotics such as ampicillin, chloramphenicol, and tetracycline at concentrations of about 3 mmol/L. Combinatorial use of benzydamine and other antibiotics like tetracycline and chloramphenicol are also synergistic against antibiotic resistant strains of *Staphylococcus aureus* and *Pseudomonas aeruginosa*.

Pharmacodynamics

Benzydamine is a non-steroidal anti-inflammatory drug (NSAID) designed to elicit local anesthetic and analgesic effects mainly for the mouth and throat. It specifically acts on the local mechanisms of inflammation such as pain, oedema, or granuloma. Typically applied topically, the drug demonstrates anti-inflammatory activity reducing oedema as well as exudate and granuloma formation. Moreover, benzydamine exhibits analgesic properties and local anaesthetic activity if pain is caused by an inflammatory condition. Benzydamine can be absorbed into the oral mucosa and intact skin. Once absorbed in the local area of pain or inflammation, benzydamine binds selectively to local inflamed tissues, usually allowing it to act with few adverse systemic effects. On average a period of 2 to 4 hours is necessary for the substance to reach peak plasma concentration. Benzydamine can be synthesized with the reaction of the N-benzyl derivative from methyl anthranilate with nitrous acid to give N-nitoso derivative. This is next reduced by sodium thiosulfate to give transient hydrazine. This hydrazine can then undergo spontaneous internal hydrazide formation. Treating this resultant enolate with 3-chloro-1-dimethylamkino propane ultimately yields benzydamine.

Mechanism of action

When incorporated into mouthwashes, toothpastes, lozenges, or mouth sprays, cetylpyridinium chloride is expected to elicit a mechanism of action that decreases new dental plaque growth, decreases or removes existing dental plaque, diminishes the growth of pathogenic bacteria, and inhibits the production of virulence factors. Cetylpyridinium chloride is a quaternary ammonium compound that demonstrates a broad spectrum anti-bacterial activity. It possesses a cationic surface active agent surfactant which can absorb readily to oral surfaces. The molecules of this agent have both hydrophilic and hydrophobic groups. In action, the positively charged hydrophilic region of cetylpyridinium chloride molecules enables the compound to interact with microbial cell surfaces and even integrate into the bacterial cytoplasmic membrane. Consequently, there is a resultant disruption of bacterial membrane integrity causing a leakage of bacterial cytoplasmic components, interference with cellular metabolism, inhibition of cell growth, and ultimately - cell death. Moreover, cetylpyridinium chloride can also inhibit the synthesis of insoluble glucan by streptococcal glucosyltransferase, adsorb to pellicle-covered enamel, and inhibit co-adhesion of bacteria, and bind streptococcus mutans biofilms. This ability of cetylpyridinium chloride to be able to adsorb to pellicle covered enamel imparts substantivity to the compound molecules - that is retention in the mouth and continued antimicrobial activity for a period of time after rinsing. Taking these mechanisms into consideration, cetylpyridinium chloride may be considered an active ingredient that is effective in the treatment and prevention of bacterial or fungal disorders of the oropharyngeal cavity.

Pharmacodynamics

Cetylpyridinium chloride is considered a cationic disinfectant with properties and uses similar to other such cationic surfactants. In particular, cetylpyridinium chloride has demonstrated a rapid bactericidal and fungicide effect on gram-positive pathogens and yeasts, respectively. Cetylpyridinium chloride is subsequently utilized in a variety of preparations for the local treatment of minor infections. Despite the variety of formulations in which cetylpyridinium chloride may appear as an active ingredient, it is generally accepted that it only elicits a local effect owing to the compound's relatively poor absorption by route of exposure.