Difflam/Difflam Solution/Difflam-C/Difflam Forte

Benzydamine is 1-Benzyl-3-(3-dimethylaminopropoxy)-1H-indazole is a white crystalline powder with thin bitter taste, soluble in water, ethanol, and chloroform. It is sparingly soluble in ether and petroleum ether.
Cetylpyridinium chloride is 1-hexadecylpyridinium chloride monohydrate. It is a white unctuous powder with a slight characteristic odor, very soluble in alcohol and chloroform and very slightly soluble in ether.
Chlorhexidine is 1,1-hexamethylenebis[5-(4-chlorophenyl)biguanide].
Difflam: Difflam Orange/Difflam Eucalyptus & Menthol contains benzydamine HCl 3 mg and cetylpyridinium chloride 1.33 mg.
Difflam Lemon: Lozenges are flat, bevelled yellow round sweet lemon flavored.
Each lozenge contains 3 mg benzydamine hydrochloride. The other ingredients are anhydrous citric acid, levomenthol, sucralose, lemon flavour, purified water, isomalt.
Difflam Solution: Difflam Solution contains benzydamine HCl 0.15% w/v.
Difflam-C: Each 15-mL solution of Difflam-C contains benzydamine HCl 22.5 mg (0.15% w/v) and chlorhexidine gluconate 18 mg (0.12% w/v).
Difflam Forte: Each spray of Difflam Forte delivers approximately 0.51 mg of benzydamine HCl. It also contains the following ingredients: Ethanol, saccharin sodium and methylhydroxybenzoate. Difflam Forte does not contain gluten, lactose, sugar or coloring agents.

Pharmacology: Benzydamine is an anti-inflammatory and analgesic agent structurally unrelated to the steroid group. Benzydamine differs chemically from other non-steroidal anti-inflammatory agents in that it is a base rather than an acid.
Animal models show that when administered systemically, benzydamine is effective against pain and oedema due to inflammatory conditions. It also inhibits granuloma formation. At concentrations used for topical treatment, benzydamine possesses local anaesthetic action. Benzydamine does not cause erosion of the gastric mucosa when given orally to rats at doses of up to 100 mg/kg.
The analgesic activity of benzydamine was more pronounced in models involving an experimental inflammation rather than in non-inflammatory pain. In common with the aspirin-like drugs, benzydamine possesses an antipyretic activity. Peripheral reflexes were transiently inhibited after intravenous administration to cats.
Isomalt is a sugar-substitute. It is a disaccharide alcohol and is an approximately equimolar mixture of glucose-mannitol and glucose-sorbitol. Isomalt produces no measurable changes in blood glucose levels.
Chlorhexidine is a bisbiguanide antiseptic that helps to reduce the development of plaque and gingivitis when usual oral hygiene measures are interrupted. It is a strong base with affinity for oral structures including hydroxyapatite of tooth enamel, pellicle of tooth surface, bacteria and salivary proteins. Chlorhexidine reduces dental plaque deposition and associated gingivitis as characterized by redness, swelling or bleeding of the gingiva. It also increases the number of days between aphthous ulcers and increases the rate of healing following periodontal surgery.
Pharmacodynamics: The mechanism of anti-inflammatory action is not related to stimulation of the pituitary-adrenal axis. Like other non-steroidal anti-inflammatory agents, benzydamine inhibits the biosynthesis of prostaglandins under certain conditions, but its properties in this respect have not been fully elucidated. The stabilising effect on cellular membranes may also be involved in the mechanism of action.
Following normal topical application of Difflam-C, chlorhexidine produces an immediate bactericidal effect, followed by a prolonged bacteriostatic action. Chlorhexidine is active against a wide range of microorganisms including gram-positive and gram-negative bacteria, yeast, some fungi and viruses. Chlorhexidine appears to delay bacterial growth by a delayed surface action. It is attracted to and absorbed onto microbial cell walls and causes membrane leakage.
Pharmacokinetics: Absorption: Benzydamine is well absorbed following oral administration. Following topical administration of benzydamine hydrochloride in solution form and spray, benzydamine is well absorbed into the inflamed oral mucosa where it exerts anti-inflammatory and local anaesthetic actions. Plasma benzydamine levels following use of benzydamine orally are low and parallel to the amount actually ingested.
Chlorhexidine gluconate is poorly absorbed from the gastrointestinal tract (GIT). No detectable blood levels have been found in humans following oral use and percutaneous absorption, if it occurs at all, is insignificant.
Excretion: Benzydamine and its metabolites are excreted largely in the urine. Metabolism is largely by oxidative pathways, although dealkylation can be shown.
Benzydamine has been detected in blood and urine following gargling with benzydamine hydrochloride (Difflam) solutions. Most of the absorbed dose was eliminated in the first 24 hours. Repeated administration for 7 days did not result in accumulation of benzydamine in plasma.
Approximately 30% of the applied chlorhexidine gluconate is retained in the oral cavity and it is slowly released into the oral fluids for up to 24 hrs. Chlorhexidine is poorly absorbed from the GIT and is primarily excreted in the feces.

Benzydamine hydrochloride is used for temporary relief of painful conditions of the oral cavity including tonsilitis sore throat, radiation mucositis, aphthous ulcers, post-orosurgical and periodontal procedures, pharyngitis, swelling and inflammatory conditions.
Chlorhexidine in Difflam-C helps reduce the development of plaque and gingivitis during the period of treatment when the usual oral hygiene measures are interrupted.

Lozenges: 1 lozenge slowly sucked every one to two hours as required up to a maximum of 12 lozenge per day. Uninterrupted treatment should not exceed 7 days.
Solution: Adults: 15 mL (approximately 1 tbsp) which should be gargled for at least 30 sec at 1½- to 3-hr intervals, as needed.
Rinse for Oral Lesions: 15 mL (approximately 1 tbsp) which should be held in the mouth and swirled for at least 30 sec, with repeat use every 1½-3 hrs throughout the day.
Alternative to Usual Oral Hygiene Procedures: Swirled around the mouth for at least 1 min.
Children 6-12 years: 5-15 mL as a gargle if able to do so, or as an oral rinse.
Uninterrupted treatment should not exceed 7 days.
Spray: Adults and Children >12 years: 2-4 sprays (1-2 mg) directly onto the sore/inflamed area and swallow gently. Repeat every 1½-3 hrs as necessary.
Children 6-12 years: 2 sprays (1 mg) directly onto the sore/inflamed area and swallow gently. Repeat every 1½-3 hrs as necessary.
Uninterrupted treatment should not exceed 7 days, unless under medical supervision.
Administration: Lozenges: Lozenges should not be chewed and should be slowly dissolved in the mouth.
Solution: Difflam solution is indicated for use as a rinse or gargle. It should not be swallowed but rather should be expectorated after each use.
Difflam Solution should generally be used undiluted, but if stinging occurs, it may be diluted with water. The solution should be expelled from the mouth after use.
Difflam-C is best used after brushing the teeth to minimize chlorhexidine-induced discoloration.

There are no known cases of overdosage with Difflam anti-inflammatory lozenges and throat spray.
Adverse CNS effects have been reported following overdosage with high doses of benzydamine hydrochloride in solution form. Difflam is unlikely to cause adverse systemic effects, even if accidental ingestion should occur. There is no specific antidote for benzydamine and should excessive quantities be ingested, the treatment should be symptomatic. Excess consumption of products containing isomalt may have a laxative effect.

Patients with known hypersensitivity to benzydamine HCl, cetylpyridinium chloride, chlorhexidine gluconate or to any of the components of the vehicle.

If a sore throat is either caused or complicated by a bacterial infection, appropriate antibacterial therapy should be considered in addition to the use of Difflam.
The clinical efficacy of an antibacterial agent in lozenges and an antiseptic agent in oral solutions in reducing the severity or duration of throat infections have not been clinically established.
Difflam Solution contains methylhydroxybenzoate as a preservative. This has been known to cause sensitization. Hypersensitivity reactions due to Difflam Solution or any of its components may occur in susceptible individuals.
Excess consumption of products containing isomalt may have a laxative effect.
Difflam-C is not intended for prolonged use except under dental or medical supervision.
Patients with Renal Impairment: Since absorbed benzydamine and metabolites are excreted in the urine, the possibilities of the systemic effects should be considered in patients with severe renal impairment.
Patients with Hepatic Impairment: Since absorbed benzydamine and metabolites are metabolized in the liver, the possibilities of the systemic effects should be considered in patients with severe hepatic impairment.
Use in Pregnancy: See USE IN PREGNANCY & LACTATION section for further information.
Use in Children: Because of the lack of sufficient clinical experience, Difflam is not recommended in children under 6 years of age.

Category B2. Studies in animals are inadequate or may be lacking but available data show no evidence of an increased occurrence of foetal damage. The safety of benzydamine hydrochloride has not been established in pregnant patients. Risk to benefit ratio should be established if benzydamine hydrochloride anti-inflammatory lozenge are to be used in this patients.

Benzydamine hydrochloride in topical oral preparation is generally well tolerated and side-effects are minor. The following adverse reactions have been reported after use of benzydamine hydrochloride in solution form.
Local Adverse Reaction: The most commonly reported reaction is oral numbness (2.6%). Occasional burning or slinging sensation may occur and has been reported in 1.4% of treated cases. Other local adverse effects were less common and included dryness or thirst (0.2%), tingling (0.2%), warm feeling in mouth and altered sense of taste (<0.1%).
Systemic Adverse Reaction: These were very uncommon and never of a serious nature. They consisted mainly of nausea, vomiting, retching, gastro-intestinal disorders (0.4%), dizziness (0.1%), headache and drowsiness (<0.1%). Hypersensitivity reactions occur very rarely but may be associated with pruritus, rash, urticaria, photodermatitis and occasionally laryngospasm or bronchospasm.
The most common adverse reactions associated with chlorhexidine gluconate oral rinses are increased staining of teeth and other oral surfaces, increase in calculus formation and alteration in taste perception. Chlorhexidine tooth staining is harmless and can be minimized by thorough brushing of teeth before administration. No serious systemic adverse reactions associated with its use have been observed in clinical testing.

There are no known drug interactions with benzydamine.

Cleaning Instructions: Spray: After use, wipe the nozzle with a clean tissue to prevent blockage.

Lozenges: Store at temperatures not exceeding 30°C.
Solution: Store below 30°C. Protect from light.
Shelf-Life: 3 years.
Spray: Store at temperatures not exceeding 25°C. Protect from light.
Shelf-Life: 4 years.

Preparations for Oral Ulceration & Inflammation

R02AX03 - benzydamine ; Belongs to the class of other throat preparations.

Non-Rx