Framycetin

Pharmacotherapeutic group: Stomatological preparations; other agents for local oral treatment, ATC code: A01AD02. Mechanism of action Benzydamine, an indazole analogue, possesses physicochemical properties and pharmacological activity distinct from acetylsalicylic acid-type NSAIDs. Unlike NSAIDs related to acetylsalicylic acid—which are acids or are metabolised to acids—benzydamine is a weak base. It also differs in its only weak inhibitory effect on prostaglandin synthesis. Benzydamine effectively inhibits the enzymatic activity of cyclooxygenases and lipoxygenases only at concentrations of 1 mmol/L and above. Its action consists predominantly of inhibiting the synthesis of pro-inflammatory cytokines, including tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), without significantly affecting other pro-inflammatory cytokines (IL-6 and IL-8) or anti-inflammatory cytokines (IL-10, IL-1 receptor antagonist). Additional mechanisms are thought to contribute, including inhibition of the neutrophil oxidative burst and membrane stabilisation, as evidenced by inhibition of granule release from neutrophils and stabilisation of lysosomes. The local anaesthetic effect of the substance has been attributed to interaction with cation channels. Pharmacodynamic effects Benzydamine acts specifically on local inflammatory manifestations such as pain, oedema and granuloma formation. Topically applied benzydamine exhibits anti-inflammatory activity, reducing oedema and the formation of exudate and granulomas. It also has analgesic effects when pain is inflammatory in origin, together with a local anaesthetic action. Benzydamine has virtually no effect on hyperthermia arising from systemic functional activation. Clinical efficacy and safety In a clinical study involving 24 patients with pharyngitis following tonsillectomy, rinsing with 0.15% benzydamine solution five times daily for 6 days produced marked clinical improvement and more rapid relief of oral and throat pain and swallowing difficulties; by day 7, improvements in clinical signs—including hyperaemia and oedema—were also evident compared with placebo. Similar results have been observed in other studies in patients with tonsillitis or pharyngitis and in patients following oral surgical procedures. Gargling with 30 mL of 0.075% benzydamine solution prior to induction of anaesthesia in 58 adult patients undergoing general anaesthesia with endotracheal intubation significantly reduced postoperative sore throat (compared with a water control) for the first 24 hours, whereas an acetylsalicylic acid-containing gargle reduced it for 4 hours. In a clinical study involving 48 patients who performed mouth rinses with 0.15% benzydamine solution four times daily during weeks 3 to 5 of radiotherapy for oral cavity cancer, significant pain relief and a lower extent and severity of oropharyngeal mucositis were observed. Similar effects were reported in patients undergoing chemotherapy for oral cavity cancer. In a study of 67 patients with severe oropharyngeal mucositis following radiotherapy who were treated with benzydamine mouth rinses, significant reductions in painful swallowing, hyperaemia and mucositis were achieved within the first three days of treatment compared with placebo. In patients using benzydamine, a higher incidence of transient numbness and stinging was observed, attributed to the local anaesthetic effect of the product. Overall, benzydamine was well tolerated in clinical trials.