What are the benefits of using Benadryl (diphenhydramine) as a mouthwash for mouth sores?

Benadryl (Diphenhydramine) Mouthwash for Oral Mucositis

Diphenhydramine-lidocaine-antacid mouthwash (commonly called "magic mouthwash") provides statistically significant but clinically modest pain relief for oral mucositis, reducing pain by approximately 3 points more than placebo over 4 hours, though this falls short of the minimal clinically important difference of 3.5 points. 1

Evidence-Based Recommendations

When to Use Diphenhydramine-Based Mouthwash

• The NCCN recommends magic mouthwash (containing diphenhydramine/Benadryl, lidocaine, and antacid) as a rinse for symptomatic relief of oral mucositis, swished for 1-2 minutes and either spit out or swallowed depending on formulation. 2

• In a head-to-head randomized trial of 275 patients undergoing head and neck radiotherapy, diphenhydramine-lidocaine-antacid mouthwash reduced mucositis pain by 11.7 points compared to 8.7 points with placebo (difference of 3.0 points, 95% CI 0.1-5.9, P=0.004). 1

• The pain relief effect, while statistically significant, did not reach the pre-specified minimal clinically important difference of 3.5 points, suggesting the benefit is real but modest. 1

Comparative Effectiveness

• A randomized trial of 142 patients with chemotherapy-induced mucositis found no significant difference in time to resolution between magic mouthwash (lidocaine-Benadryl-Maalox), chlorhexidine, or salt-and-soda solution, making the least costly option (salt and soda) equally effective. 3

• Diphenhydramine-lidocaine-antacid mouthwash performed similarly to doxepin mouthwash (both reduced pain by approximately 3 points more than placebo), but doxepin caused more drowsiness (1.5 points higher, P=0.03), unpleasant taste, and stinging/burning. 1

Adverse Effects Profile

• Grade 3 adverse events occurred in only 4% of patients using diphenhydramine-lidocaine-antacid mouthwash, similar to placebo (2%). 1

• Importantly, diphenhydramine-lidocaine-antacid mouthwash did not cause significant drowsiness or fatigue, unlike doxepin mouthwash which caused fatigue in 6% of patients. 1

• One case report documented successful use of Benadryl Elixir mixed with Maalox and 2% viscous lidocaine to treat severe oral mucosal injuries, with improvement within 48 hours. 4

Clinical Algorithm for Use

For cancer patients with oral mucositis pain:

1. First-line symptomatic relief: Use diphenhydramine-lidocaine-antacid mouthwash for immediate pain control, recognizing it provides modest (3-point) pain reduction over 4 hours. 1

2. Cost-conscious alternative: Consider salt-and-soda solution, which has equivalent efficacy at lower cost for chemotherapy-induced mucositis. 3

3. Severe pain requiring stronger intervention: Escalate to morphine-based mouthwash (0.2% morphine) for chemoradiation patients or patient-controlled analgesia with morphine for HSCT patients, as recommended by ESMO. 5, 2

4. Alternative to doxepin: Choose diphenhydramine-based formulation over doxepin if drowsiness or sedation is a concern, as it has similar efficacy without the fatigue profile. 1

Important Caveats

• The evidence for diphenhydramine mouthwash is primarily for symptomatic pain relief, not prevention or treatment of the underlying mucositis. 1

• The 4-hour duration of effect is relatively short, requiring frequent dosing for sustained relief. 1

• While NCCN recommends magic mouthwash, ESMO guidelines do not specifically endorse it, instead recommending morphine-based or doxepin mouthwashes for pain management. 5, 2

• Avoid using undiluted or improperly formulated mouthwashes, as this can cause severe mucosal injury rather than relief. 4