Benzydamine is a nonsteroidal anti-inflammatory drug that has been used in an oral rinse. It has some local anesthetic and analgesic properties. Benzydamine has been evaluated in patients with cancer for the prevention and management of mucositis.
Kwong, K.K. (2004). Prevention and treatment of oropharyngeal mucositis following cancer therapy: Are there new approaches? Cancer Nursing, 27(3), 183–205.
Database searched was MEDLINE (1993–2003) for randomized, controlled trials evaluating mucositis interventions.
A total of 50 randomized controlled trials were presented. Other trials and papers were referenced.
The author concluded that most agents require more study.
The author noted the problem of variation in study protocols, insufficient sample sizes, and a lack of consensus regarding the scoring system for mucositis.
The author noted the need to include psychotherapeutic interventions and management and pointed out the lack of a quality-of-life tool for mucositis.
Shih, A., Miaskowski, C., Dodd, M. J., Stotts, N.A., & MacPhail, L. (2002). A research review of the current treatments for radiation-induced oral mucositis in patients with head and neck cancer. Oncology Nursing Forum, 29, 1063–1078.
Database searched was MEDLINE (1966–2001). Additional papers were found from reference lists.
Studies were included in the review if they were aimed at prevention, palliation, or reduction of radiation-induced oral mucositis in patients with head and neck cancer.
Studies were excluded if they were not in English.
More than 50 studies were included. Most were randomized, controlled trials; some were pilot or descriptive studies.
Sample sizes ranged from 10 to more than 200.
Based on the findings of studies conducted to date, no conclusions regarding the agents and their ability to decrease the severity of radiation-induced oral mucositis were possible. Results were inconsistent. The most effective measure to treat radiation-induced mucositis was frequent oral rinsing with a bland mouthwash such as saline or sodium bicarbonate. Consistent oral care, dental care, oral assessment, and standardized oral hygiene were the suggested approaches to managing oral mucositis. Sodium bicarbonate reduces the acidity of the oral fluids immediately; it also dilutes accumulating mucus and discourages yeast colonization.
Findings related to benzydamine were inconsistent. In a trial of chlorhexidine versus benzydamine, patients reported more discomfort with benzydamine and were more likely to discontinue participation in the trial. Chlorhexidine was not effective in reducing the severity of mucositis in three double-blind, placebo-controlled trials. Two trials that examined antimicrobial activity failed to show any significant effects on the suppression of any type of oral flora using chlorhexidine.
Dose variations in granulocyte macrophage colony-stimulating factor (subcutaneous) trials make it impossible to determine whether this agent has a role in the radiation setting.
Four studies investigated the effectiveness of using topical antibiotics with a more specific spectrum for gram-negative bacteria and yeast. Two placebo-controlled, randomized clinical trials, both with fewer than 100 patients, and one case-controlled study investigated the efficacy of amphotericin B (polymyxis E, tobramycin, and amphotericin B [PTA] lozenge) to reduce the severity of radiation-induced mucositis. One study examined tetracaine and antibiotics. Additional work is warranted to determine the effects of the PTA lozenge on mucositis severity, pain severity, and dysphagia. Results for the trial were promising; however, conclusions cannot be drawn because only one study examined tetracaine.
Additional investigation of immunoglobulin and povidone-iodine are recommended.
Epstein, J.B., Silverman, S., Paggiarino, D.A., Crockett, S., Schubert, M.M., Senzer, N.N., … Leveque, F.G. (2001). Benzydamine HCl for prophylaxis of radiation-induced oral mucositis: Results from a multicenter, randomized, double-blind, placebo-controlled clinical trial. Cancer, 92, 875–885.
Participants were randomized to receive either benzydamine HCl oral rinse, containing 0.15% benzydamine oral rinse (1.5 mg/ml benzydamine) or placebo, which identical in appearance and taste consisting of the vehicle only (approximately 10% alcohol by volume, menthol, peppermint oil, clove oil, and other flavoring agents).
Patients were to rinse with 15 ml of solution for two minutes, 4–8 times daily, before and during radiation therapy (RT) and for two weeks after completion of RT. If burning or stinging occurred, dilution of the rinse with water at 1:1 or 1:2 was allowed.
Patients were evaluated before RT, twice weekly during RT, at the end of RT, and 2–3 weeks after RT.
The study was conducted at 16 centers in North America (15 in the United States and 1 in Canada).
Benzydamine produced a 26.3% reduction in mean mucositis area under the curve (AUC) compared with placebo for overall 0–5000 cGy (p = 0.009).
Pain also decreased as evidenced by a delay in use of concomitant systemic analgesics. Mouth pain showed a 25.8% reduction in AUC (p = 0.064) versus placebo, and throat pain showed a 22.5% reduction in AUC (p = 0.064).
Pain during meals was not effectively reduced.
Benzydamine was not effective in reducing more severe mucositis in patients receiving high, single, daily RT regimens of 220 cGy per day or more.
Hadjieva, T., Cavallin-Stahl, E., Linden, M., & Tiberg, F. (2014). Treatment of oral mucositis pain following radiation therapy for head-and-neck cancer using a bioadhesive barrier-forming lipid solution. Supportive Care in Cancer, 22, 1557–1562.
To test the analgesic effect of CAM2028 with benzydamine compared with CAM2028 without benzydamine (the FDA-approved prescription formula of episil) over an eight-hour period. During treatment with CAM2028, phospholipid and triglceride lipid components self-assemble with a volume of water (saliva) to form a bioadhesive and protective liquid crystalline lining of the oral mucosa. Additional objective of the study was to assess the safety and tolerability of a single-dose of the combined formulation.
Crossover, double-blind, placebo-controlled, single-dose, randomized, proof of concept trial
All patients completed the trial. With both treatments, patients experienced a mean 40% decrease in pain intensity at six hours. Both treatments resulted in significant pain relief within five minutes of application that was evident during the entire eight-hour assessment period. At no time did mean pain ratings or pain intensity difference differ statistically between the two treatments. The mean AUC of pain intensity over time did not differ between the two treatments. All of the analyses of pain intensity outcomes showed a statistically significant clinical center effect, with one center reporting larger pain intensity difference values than others. No reason was offered for this difference.
The similar treatment effects of CAM2028 with or without benzydamine suggest that benzydamine did not contribute additionally to the reduction of oral mucositis pain compared with the unmedicated CAM2028 control. CAM2028 resulted in immediate and significant pain relief with a duration that was maintained for up to eight hours.
Kazemian, A., Kamian, S., Aghili, M., Hashemi, F. A., & Haddad, P. (2009). Benzydamine for prophylaxis of radiation-induced oral mucositis in head and neck cancers: A double-blind placebo-controlled randomized clinical trial. European Journal of Cancer Care, 18(2), 174–178.
To evaluate the efficacy of benzydamine oral rinse for prevention of radiation-induced mucositis
Patients rinsed for 2 minutes four times a day with 15 mL study medication (0.15% benzydamine oral rinse) or identical placebo (in appearance and taste) from the first day of radiation therapy (RT) to the end of treatment. Patients were encouraged to brush their teeth at least twice daily and rinse as necessary with normal saline or sodium bicarbonate. Commercial mouthwashes were prohibited.
The study was conducted at the Radiation Oncology Department of the Cancer Institute at Tehran University of Medical Sciences in 2004-2005.
This was a double-blind, randomized, placebo-controlled trial.
Benzydamine 0.15% oral rinse was safe and well tolerated. It significantly reduced RT-induced mucositis, which also decreased the interruption of treatment.
Nurses will need to know how to effectively teach patients to use the oral rinse. This study also highlights the importance of daily oral hygiene, which is another good teaching point.
Rastogi, M., Khurana, R., Revannasiddaiah, S., Jaiswal, I., Nanda, S.S., Gupta, P., . . . Bhatt, M.L. (2016). Role of benzydamine hydrochloride in the prevention of oral mucositis in head and neck cancer patients treated with radiotherapy (> 50 Gy) with or without chemotherapy. Supportive Care in Cancer. Advance online publication.
To evaluate the role of benzydamine in the prevention of mucositis in patients receiving more than 50 Gy of radiation therapy
Patients were stratified according to receiving radiotherapy or radiotherapy and chemotherapy, and then randomly assigned to control or treatment with benzydamine. All patients were advised to use saline mouth rinses, and those in the treatment group also used 0.15% benzydamine hydrochloride rinse. Both groups were to rinse and gargle with the mixture four to six times daily. Patients were examined weekly until four weeks after completion of the treatment.
PHASE OF CARE: Active antitumor treatment
Randomized, controlled trial
Patients receiving radiotherapy alone who used benzydamine had a lower prevalence of grade 3 mucositis compared to controls (p = 0.038); however, control patients receiving only radiotherapy also had a longer duration of radiation treatment (p = 0.042, 56 versus 44 days). No significant difference in mucositis outcomes occurred among those receiving both chemotherapy and radiation. Control patients in this group had a longer duration of radiation therapy.
Benzydamine prophylaxis appears to be effective to reduce the severity of oral mucositis among patients receiving radiotherapy alone for head and neck cancer. Effects for patients receiving both chemotherapy and radiation therapy were not seen.
Oral rinses with benzydamine were helpful to reduce the prevalence of severe mucositis among patients receiving radiation therapy for head and neck cancer. It is unclear if benzydamine can also be helpful for patients receiving combination chemotherapy and radiation therapy.
Roopashri, G., Jayanthi, K., & Guruprasad, R. (2011). Efficacy of benzydamine hydrochloride, chlorhexidine, and povidone iodine in the treatment of oral mucositis among patients undergoing radiotherapy in head and neck malignancies: A drug trail. Contemporary Clinical Dentistry, 2, 8–12.
To manage oral mucositis induced by radiotherapy and to reduce pain by using benzydamine hydrochloride, chlorhexidine, and povidone iodine
Selected patients were divided into study and control groups. The study groups were further subdivided into group 1, group 2, and group 3. Each study group consisted of 25 patients, and the control group also consisted of 25 patients; the three study groups and the control group were given benzydamine hydrochloride, chlorhexidine, povidone iodine, and distilled water, respectively. These rinses were given after two weeks of radiation therapy (RT) at the onset of oral mucositis.
Patients in the study groups as well as the control group were instructed to rinse the oral cavity with 15 ml of their respective rinses for at least 30 seconds, 4 times a day at six-hour intervals. The mouth-rinsing regimen was performed under professional supervision. The samples of mouth rinses were given to the patients without dilution for one week use, one at a time, for convenience. Patients also were given measuring cups to measure the quantity of oral rinses. All patients were examined at the end of every week during the RT for about a six-week period.
The study was conducted at the Radiotherapy Department of Kidwai Memorial Institute of Oncology in Bangalore, Karanataka, India.
Patients were undergoing the active treatment phase of care.
The study did not involve blinding.
This study was oorly designed, and the report was confusing and difficult to understand.
Several studies have pointed in the direction that benzydamine hydrochloride is effective in the management of oral mucositis. Further well-designed, randomized placebo controlled studies are needed for verification.
Sheibani, K.M., Mafi, A.R., Moghaddam, S., Taslimi, F., Amiran, A., & Ameri, A. (2015). Efficacy of benzydamine oral rinse in prevention and management of radiation-induced oral mucositis: A double-blind placebo-controlled randomized clinical trial. Asia-Pacific Journal of Clinical Oncology, 11, 22–27.
To assess the efficacy of prophylactic benzydamine in an oral solution for reducing the signs and symptoms of oral mucositis in patients receiving radiation therapy (RT) with or without chemotherapy for head and neck cancers
A 0.15% benzydamine or placebo oral rinse of 15 ml was used for two minutes four to eight times daily starting the day before RT and continuing till two weeks RT completion.
Randomized, double-blinded, placebo-controlled trial stratified according to KPS and treatment schedule (once- or twice-daily fraction) and then randomized
No difference in the severity of mucositis was found during weeks 1–3. By week 4, the placebo arm had significantly more mucositis than the treatment arm (p = 0.01), and this trend continued until the end of treatment. The difference in the mean score at one and two weeks after treatment continued to show lower scores in the treatment group, but this was nonsignificant.
An oral rinse of benzydamine 0.15% was safe and well-tolerated with no noticeable side effects reported by patients. It reduced the incidence and severity of radiation-induced oral mucositis.
Benzydamine was well-tolerated, easy to administer, and may be an appropriate prophylactic treatment for oral mucositis in patients receiving RT for head and neck cancer.
Nicolatou-Galitis, O., Sarri, T., Bowen, J., Di Palma, M., Kouloulias, V.E., Niscola, P., . . . Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). (2013). Systematic review of anti-inflammatory agents for the management of oral mucositis in cancer patients. Supportive Care in Cancer , 21(11), 3179–3189.
PURPOSE: Systematically review literature and define updated clinical practice guidelines regarding use of anti-inflammatory agents
TYPES OF PATIENTS ADDRESSED: Patients receiving chemotherapy or radiation therapy
RESOURCE TYPE: Evidence-based guideline
PROCESS OF DEVELOPMENT: Studies evaluated using Hadorn criteria and assigned levels of evidence on Somerfield criteria by independent reviewers. Findings were integrated into guidelines based on overall level of evidence for each intervention.
DATABASES USED: MEDLINE (1966–December 31, 2010)
KEYWORDS: aminosalicylic acid, amifostine, amlexanox, anti-inflammatory, anti-TNF, anti-tumor necrosis factor, aspirin, Benadryl®, benzydamine, betamethasone, celecoxib, corticosteroid, dexamethasone, diphenhydramine, Ethyol®, flurbiprofen, histamine, hydrocortisone, ibuprofen, indomethacin, infliximab, irsogladine, lactoferrin, mesalazine, misoprostol, N-acetylcysteine, non-steroidal anti-inflammatory agents, NSAIDS, orgotein, prednisone, prostaglandin, RK-02-02, salicylic acid, steroid, thalidomide, TNF antibody, TNF inhibitor, and tumor necrosis factor/TNF
INCLUSION CRITERIA: Articles involving anti-inflammatory agents for prevention or treatment of oral mucositis
PHASE OF CARE: Active antitumor treatment
Forty-one studies were included in the review involving use of multiple anti-inflammatory agents.
Two new guidelines were identified by this systemic review. The panel suggests that misoprostol mouthwash should not be used for the prevention of radiation-induced oral mucositis in patients with head and neck cancer. The other new guideline the panel recommends is benzydamine mouthwash for the prevention of oral mucositis in patients with head and neck cancer receiving moderate-dose radiation therapy (up to 50 Gy) without concomitant chemotherapy. In addition to this, the lack of clear evidence supporting the use of any anti-inflammatory agent other than benzydamine, the use of anti-inflammatory agents continues to be a promising strategy for the prevention and treatment of oral mucositis. More well-designed studies are needed to examine the use of anti-inflammatory agents for oral mucositis in various cancer care settings.