Benzydamine anti-inflammatory, anesthetic mouthwash: all evidence

What is Benzydamine hydrochloride?

2021 evidence: Benzydamine is a local anti-inflammatory drug with analgesic properties.

Literature findings strongly emphasize and encourage the use of benzydamine in preventing and treating OM in patients undergoing radiotherapy and chemotherapy
Ref: Nicolatou-Galitis, O., Bossi, P., Orlandi, E. et al. The role of benzydamine in prevention and treatment of chemoradiotherapy-induced mucositis. Support Care Cancer 29, 5701–5709 (2021). https://doi.org/10.1007/s00520-021-06048-5
High-quality evidence and international guidelines recommend the use of Benzydamine hydrochloride mouthwash as an anti-inflammatory agent in highly inflammatory conditions, such as oral mucositis resulting from cancer therapy.

Mechanism of Action: Benzydamine HCl

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

Unlike aspirin-like NSAIDs which are acids or metabolized to acids, benzydamine is a weak base. So we use it topically – inside the mouth and throat to act on the mucosa.
In further contrast, benzydamine is a weak inhibitor of prostaglandin synthesis. Only at a concentration of 1mM and above benzydamine effectively inhibits cyclo-oxygenase and lipo-oxygenase enzyme activity. This can be achieved through topical application.
It mostly exerts its effects through inhibition of the synthesis of pro-inflammatory cytokines including tumor 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 hypothesized including the inhibition of the oxidative burst of neutrophils as well as membrane stabilization as demonstrated by the inhibition of granule release from neutrophils and the stabilization of lysosomes. The local anesthetic activity of the compound has been related to an interaction with cationic channels.

Comparing Benzydamine with other NSAID

Benzydamine shows some properties that are common with other nonsteroidal anti-inflammatory drugs (NSAIDs) but also displays properties that are different from other NSAIDs.

It has no inhibiting effect on amino-acid decarboxylases, which are inhibited by various NSAIDs. Also, Benzydamine has no effect on sulphydryl-group reactivity, contrary to most NSAIDs.

It inhibits platelet aggregation and the inhibition of the collagen-induced aggregation appears to be rather selective with respect to other NSAIDs.
It displays a stabilizing effect on erythrocyte membranes which appears related to its high affinity for membranes in general, and it inhibits the respiratory burst of stimulated human monocytes and granule enzyme release by human neutrophils.
Ref: Segre G, Hammarström S. Aspects of the mechanisms of action of benzydamine. Int J Tissue React. 1985;7(3):187-93. PMID: 4044146.

International guidelines and recommendations:

 

International guidelines in the management of oral mucositis were published in 2004 and then updated in 2007 and 2014.

The Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) clinical practice guidelines (2014) recommend that benzydamine mouthwash be used to prevent OM in patients with cancer (level I evidence) – this is in agreement with the latest Bayesian network analysis (2020).

Reference:

Lalla RV, Bowen J, Barasch A, Elting L, Epstein J, Keefe DM, McGuire DB, Migliorati C, Nicolatou-Galitis O, Peterson DE, Raber-Durlacher JE, Sonis ST, Elad S; Mucositis Guidelines Leadership Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO). MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2014 May 15;120(10):1453-61. doi: 10.1002/cncr.28592. Epub 2014 Feb 25. Erratum in: Cancer. 2015 Apr 15;121(8):1339. PMID: 24615748; PMCID: PMC4164022.

Two meta-analyses published in 2020

1. Bayesian network analysis (2020)

Chamomile, honey, curcumin and benzydamine mouthwashes may be the most advantageous in terms of the prevention of intolerable Oral Mucositis.

Ref: Zhang X, Sun D, Qin N, Liu M, Zhang J, Li X. Comparative prevention potential of 10 mouthwashes on intolerable oral mucositis in cancer patients: A Bayesian network analysis. Oral Oncol. 2020 Aug;107:104751. doi: 10.1016/j.oraloncology.2020.104751. Epub 2020 May 7. PMID: 32388411.

Link: https://www.sciencedirect.com/science/article/abs/pii/S1368837520301871

2. Network Meta-analysis (2020)

A total of 28 RCTs involving 1861 patients were included. The results of network meta-analysis showed that chlorhexidine, benzydamine, honey, and curcumin were more effective than placebo (P < .05).

Ref: Yu YT, Deng JL, Jin XR, Zhang ZZ, Zhang XH, Zhou X. Effects of 9 oral care solutions on the prevention of oral mucositis: a network meta-analysis of randomized controlled trials. Medicine (Baltimore). 2020 Apr;99(16):e19661. doi: 10.1097/MD.0000000000019661. PMID: 32311938; PMCID: PMC7220734.

Link: https://journals.lww.com/md-journal/Fulltext/2020/04170/Effects_of_9_oral_care_solutions_on_the_prevention.22.aspx

Latest international guideline (2020):

Elad, Sharon et al. “MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy.” Cancer vol. 126,19 (2020): 4423-4431. doi:10.1002/cncr.33100

Anti-inflammatory agents: A new guideline was added for benzydamine (Link): a suggestion for the prevention of Oral Mucositis (OM) in patients with H&N cancer receiving RT and CT (Table 1).
  1. The panel recommends benzydamine mouthwash for OM prevention in patients with H&N cancer receiving a moderate dose RT (<50 Gy).
  2. The panel suggests the use of benzydamine mouthwash for the prevention of OM in patients with H&N cancer who receive RT‐CT.

Can we use Benzydamine mouthwash in place of a regular analgesic such as ibuprofen after periodontal surgery?

There was no significant difference in VAS scores between the two groups: benzydamine hydrochloride 0.15% group vs ibuprofen 400-mg tablets. Therefore, it is recommended to use benzydamine hydrochloride 0.15% to reduce pain after periodontal surgeries, which has lower side effects and cost as well as the same efficacy. In order to decrease pain after periodontal surgery, benzydamine hydrochloride mouthwash can be widely used as it has fewer side effects, lower price, and similar effects to ibuprofen.
Ref: Comparison of Benzydamine Hydrochloride Mouthwash 0.15% and Ibuprofen in Reducing Postoperative Pain during 24 hours after Crown Lengthening: a Randomized Clinical Trial.
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