PL Detail-Document #290110 −This PL Detail-Document gives subscribers additional insight related to the Recommendations published in− PHARMACIST’S LETTER / PRESCRIBER’S LETTER January 2013 Treatment of Canker Sores Introduction Aphthous ulcers, or canker sores, are a common annoyance for patients. About one-third of individuals will experience a canker sore in his or her lifetime.1 There isn’t good evidence for many of the treatments used for canker sores. Most of the available data come from very small clinical trials.2 This document reviews common treatments for canker sores. Background on Canker Sores Canker sores generally occur in otherwise healthy patients. They are noninfectious and their cause is unclear.1,3 Canker sores tend to be recurrent and to run in families. They can be triggered by factors such as smoking, stress, trauma, or vitamin and mineral deficiencies. Medications such as beta-blockers, NSAIDs, and antioxidants may also be associated with canker sores.1 Onset of canker sores is more common during the teen years than during adulthood.1,4 Ulcers may have a prodromal phase, with tingling or burning up to two days prior to ulcer appearance.1 In contrast to cold sores, canker sores occur on the inside of the mouth on areas such as the tongue or cheeks. The major problem with canker sores is that they might cause difficulty eating or drinking or performing oral hygeine.4,5 Canker sores tend to heal naturally within one to two weeks.6 There are different classifications of canker sores, but the vast majority are considered minor or simple (fewer, smaller, shorter healing time) as opposed to major or complex (more, larger, longer healing time).4,7 Treatment of canker sores is directed at relieving pain, reducing duration of ulcers, and reducing recurrence of ulcers. In general, the evidence for canker sore treatments is limited. However, the cost of most canker sore treatments is relatively low, at around $20 per course or less.2 Patients may provide input on which treatments they feel are most effective, and pick and choose based on that experience. Prescription Medications Amlexanox 5% oral paste (Aphthasol), available in the U.S., is an anti-inflammatory agent.3 It’s the only prescription product FDAapproved for treating canker sores, and has the best quality of evidence for efficacy compared with other treatments.8 Amlexanox appears to double a patient’s chances of being pain-free and/or having ulcers healed at three days compared with placebo. It can also stop development of a canker sore during the prodromal phase in most instances.2 Amlexanox should be applied to ulcers four times daily. Like other treatments for canker sores, the best time to apply is after eating and brushing the teeth.8 Topical corticosteroids have been shown to reduce pain from canker sores in a number of small clinical trials.1,2,9 Topical steroids may also stop development of ulcers if used in the prodromal phase.1 Compounded clobetasol propionate 0.05% oral paste may be as effective as amlexanox.2,3 Other corticosteroid formulations that have been studied include dexamethasone 0.5 mg/5 mL elixir (commercially available) used as a mouth rinse three to four times daily as well as a variety of other compounded products. Triamcinolone (OraloneU.S., Oracort-Canada, generics) is commercially available as a dental paste. Systemic corticosteroids may be useful for patients with more severe or frequently recurring cases.1 Topical tetracycline regimens may be useful for reducing pain and duration of ulcers.1,3 Formulations that have been studied include various concentrations of tetracycline mouth rinses applied four times daily and minocycline 0.2% mouth rinse applied four times daily.10 The downside of topical antibiotics is that they might increase the risk of thrush.11 Oral doxycycline 20 mg twice daily may reduce ulcer recurrence.12 More. . . Copyright © 2013 by Therapeutic Research Center 3120 W. March Lane, Stockton, CA 95219 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.PharmacistsLetter.com ~ www.PrescribersLetter.com ~ www.PharmacyTechniciansLetter.com (PL Detail-Document #290110: Page 2 of 3) Sucralfate suspension has been studied in a small number of patients with canker sores. It may reduce pain and healing time of ulcers through its effect as a protectant.13 Various regimens are described including 5 to 10 mL swished in the mouth four times daily, or a bit of the suspension applied locally for about one minute at a time, one or two times daily. Note that when sucralfate tabs are used to prepare a slurry, the tabs are not easily crushed. They should be placed in about 10 mL of water per tablet and allowed to dissolve, and then shaken to disperse after about 15 to 20 minutes.14 The results from a number of small trials suggest that chlorhexidine mouthwash used four times daily can speed healing of canker sores.2 Magic mouthwash is an anecdotal remedy for canker sores.2 This compounded product can contain different ingredients depending on the recipe used. Some of the more common ingredients are diphenhydramine, lidocaine, milk of magnesia, and nystatin. However, some recipes include drugs that do have evidence of benefit for canker sores, such as tetracyclines and corticosteroids.15 Magic mouthwash is typically used four times daily. Nonprescription Medications Topical anesthetics such as benzocaine (Anbesol, Kank-A, Zilactin-B, etc), may help reduce pain with canker sores.1 But remember to avoid use of benzocaine in children under the age of two years and advise keeping these products out of their reach due to the risk of methemoglobinemia. Also avoid “caine” anesthetics in patients with a history of allergic reactions to them. Canker Cover is another OTC product that might help reduce discomfort. It has citrus oils and menthol and forms a gel-like protective patch over ulcers.5 Patients may try a number of other simple remedies, although there is not good evidence for their benefit in the treatment of canker sores. Carbamide or hydrogen peroxide might help debride or cleanse ulcers. These can be applied directly to ulcers and allowed to remain for about one minute at a time. Alternately, full-strength solutions mixed with equal amounts of water or commercially available formulations can be used to rinse the mouth. Peroxides can be used up to four times daily for up to seven days, but more frequent or prolonged use might irritate the oral mucosa.5 Salt water rinses (one to three teaspoons of table salt in four to eight ounces [120 to 240 mL] of water) or baking soda pastes may be tried to reduce discomfort. OTC analgesics such as acetaminophen or ibuprofen might also help reduce pain with canker sores. Original Listerine might help reduce healing time.5 Supplements The use of vitamin B12 1000 mcg orally once daily for prophylaxis of canker sores has been studied. This regimen may reduce number, duration, pain, and recurrence of canker sores.2,3 Propolis is a supplement that may have antimicrobial and anti-inflammatory properties. Propolis 500 mg orally once daily might also reduce recurrences of canker sores.16 There are preliminary data that suggest aloe vera or lavender oil applied topically to ulcers might have some utility in reducing pain and healing time.17,18 Non-Drug Strategies Avoidance of certain kinds of food or beverages (e.g., spicy, acidic, sharp) that cause irritation to existing ulcers might help reduce discomfort. Applying ice directly to ulcers for about ten minutes at a time might help reduce pain as well.5 Small studies suggest that avoiding toothpastes with sodium lauryl sulfate might reduce recurrence of canker sores, although data are conflicting.1,2,6 Individuals prone to canker sores may also benefit from preventing contact between the inside of the mouth and sharp dental appliances (e.g., braces, dentures), as well as avoiding toothbrushes with very stiff bristles. Conclusion Amlexanox or topical corticosteroids appear to be the best bets for reducing symptoms and healing time of canker sores. Also consider practical issues, such as patient preference and convenience of application (e.g., a mouth rinse instead of a paste for a patient with many ulcers) when making recommendations for treatments for canker sores. To help maximize the benefits of topical treatment for canker sores, counsel patients to More. . . Copyright © 2013 by Therapeutic Research Center 3120 W. March Lane, Stockton, CA 95219 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.PharmacistsLetter.com ~ www.PrescribersLetter.com ~ www.PharmacyTechniciansLetter.com (PL Detail-Document #290110: Page 3 of 3) avoid eating, drinking, and excessive speaking for 30 minutes after application. In addition, treatments should be started as soon as possible, preferably during the prodromal phase. 7. 8. Users of this PL Detail-Document are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making clinical judgments based on the content of this document. Our editors have researched the information with input from experts, government agencies, and national organizations. Information and internet links in this article were current as of the date of publication. 9. 10. 11. 12. Project Leader in preparation of this PL DetailDocument: Stacy A. Hester, R.Ph., BCPS, Assistant Editor 13. References 14. 1. 2. 3. 4. 5. 6. Chavan M, Jain H, Diwan N, et al. Recurrent aphthous stomatitis: a review. J Oral Pathol Med 2012;41:577-83. Bailey J, McCarthy C, Smith RF. Clinical Inquiry. What is the most effective way to treat recurrent canker sores? J Fam Pract 2011;60:621-32. Baccaglini L, Lalla RV, Bruce AJ, et al. Urban legends: recurrent aphthous stomatitis. Oral Dis 2011;17:755-70. Brocklehurst P, Tickle M, Glenny AM, et al. Systemic interventions for recurrent aphthous stomatitis (mouth ulcers). Cochrane Database Syst Rev 2012;(9):CD005411. Albanese NP. Oral pain and discomfort. In: Krinsky DL, Berardi RR, Ferreri SP, et al, Eds. th Handbook of Nonprescription Drugs. 17 ed. Washington, DC: American Pharmaceutical Association, 2012. Shim YJ, Choi JH, Ahn HJ, Kwon JS. Effect of sodium lauryl sulfate on recurrent aphthous 15. 16. 17. 18. stomatitis: a randomized controlled clinical trial. Oral Dis 2012;18:655-60. Liang MW, Neoh CY. Oral aphthosis: management gaps and recent advances. Ann Acad Med Singapore 2012;41:463-70. Product information for Aphthasol. Access Pharmaceuticals. Dallas, TX 75207. March 2004. Liu C, Zhou Z, Liu G, et al. Efficacy and safety of dexamethasone ointment on recurrent aphthous ulceration. Am J Med 2012;125:292-301. Gorsky M, Epstein JB, Rabenstein S, et al. Topical minocycline and tetracycline rinses in treatment of recurrent aphthous stomatitis: a randomized crossover study. Dermatol Online J 2007;13:1. Mayo Clinic. Canker sore. March 24, 2012. http://www.mayoclinic.com/health/cankersore/DS00354. (Accessed December 10, 2012). Preshaw PM, Grainger P, Bradshaw MH, et al. Subantimicrobial dose doxycycline in the treatment of recurrent oral aphthous ulceration: a pilot study. J Oral Pathol Med 2007;36:236-40. Rattan J, Schneider M, Arber N, et al. Sucralfate suspension as a treatment of recurrent aphthous stomatitis. J Intern Med 1994;236:341-3. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2012. http://www.clinicalpharmacology.com. (Accessed December 11, 2012). PL Detail-Document, Magic Mouthwash Recipes. Pharmacist’s Letter/Prescriber’s Letter. November 2009. Jellin JM, Gregory PJ, et al. Natural Medicines Comprehensive Database. http://www.naturaldatabase.com. (Accessed December 7, 2012). Babaee N, Zabihi E, Mohseni S, Moghadamnia AA. Evaluation of the therapeutic effects of Aloe vera gel on minor recurrent aphthous stomatitis. Dent Res J (Isfahan) 2012;9:381-5. Altaei DT. Topical lavender oil for the treatment of recurrent aphthous ulceration. Am J Dent 2012;25:39-43. Cite this document as follows: PL Detail-Document, Treatment of Canker Sores. Letter/Prescriber’s Letter. January 2013. Pharmacist’s Evidence and Recommendations You Can Trust… 3120 West March Lane, Stockton, CA 95219 ~ TEL (209) 472-2240 ~ FAX (209) 472-2249 Copyright © 2013 by Therapeutic Research Center Subscribers to the Letter can get PL Detail-Documents, like this one, on any topic covered in any issue by going to www.PharmacistsLetter.com, www.PrescribersLetter.com, or www.PharmacyTechniciansLetter.com Detail-Document #251103 −This Detail-Document accompanies the related article published in− PHARMACIST’S LETTER / PRESCRIBER’S LETTER November 2009 ~ Volume 25 ~ Number 251103 Magic Mouthwash Recipes Ingredients1-11,a-e Amount Diphenhydramine 12.5 mg/5 mL 240 mL Hydrocortisone 60 mg Nystatin powder 6 million units Tetracycline 1.5 g Swish and spit 5 mL QID. a.k.a. Mary’s Magic Potion Ingredients1-11,a-e Hydrocortisone Nystatin Diphenhydramine 12.5 mg/5 mL a.k.a. Duke’s Magic Mouthwash4 Amount 60 mg Suspension 30 mL OR Powder 3 million units QS 240 mL Distilled water 160 mL Hydrocortisone 80 mg Maalox 80 mL Swish and spit 5 mL QID. a.k.a. Weisman’s Philadelphia Mouthwash Diphenhydramine 12.5 mg/5 mL Hydrocortisone Nystatin suspension Tetracycline Diphenhydramine 12.5 mg/5 mL Nystatin suspension Maalox Water Diphenhydramine 12.5 mg/5 mL Hydrocortisone Nystatin suspension Tetracycline 100 mL 0.02 g 4.8 mL 200 mg Diphenhydramine 12.5 mg/5 mL Prednisone 5 mg/5 mL Nystatin suspension 1 part 1 part 1 part Nystatin Susp. 100,000 U/mL Lidocaine Viscous 2% Distilled Water Crystal Light-Raspberry with Aspartame crystals8 83.3 mL 83.3 mL 83.3 mL 0.47 g 1 part 1 part 1 part 1 part Diphenhydramine 12.5 mg/5 mL 1 part Viscous lidocaine 2% 1 part Maalox 1 part Swish and swallow 5 mL no more than Q4H. OR For radiation oncology mucositis; palliative care: Swish, hold, and spit or swallow 30 mL Q2H.1 Diphenhydramine 12.5 mg/5 mL 240 mL 120 mg Hydrocortisone powder (wet with 1% CMCf to dissolve) Nystatin Suspension 60 mL Tetracycline 125 mg/5 mL 120 mL (capsule dissolved in flavored syrup) CMCf 1% QS 480 mL Swish and swallow 10 mL TID. Diphenhydramine 12.5 mg/5 mL Mylanta or Maalox Sucralfate Swish and spit or swallow 5 mL meals and PRN.6 30 mL 60 mL 4g TID before 180 mL 0.072 g 36 mL 0.75 g Cherry flavored Kool-Aid mixed 100 mL with 2000 mL distilled water (sugar-free) Viscous lidocaine 2% 100 mL Nystatin suspension 100 mL Swish and spit or swallow 15 mL QID. OR For radiation oncology mucositis; palliative care: Swish, hold, and spit or swallow 30 mL Q4H.1 a.k.a. Koolstat More. . . Copyright © 2009 by Therapeutic Research Center Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com (Detail-Document #251103: Page 2 of 3) Ingredients1-11,a-e Amount Hydrocortisone 100 mg/2 mL 12 mL (Solu-Cortef) Nystatin suspension 7.2 mL Tetracycline 125 mg/5 mL 12 mL (capsule dissolved in syrup) Diphenhydramine 12.5 mg /5 mL 150 mL Swish and swallow 10 mL QID. Viscous lidocaine 2% Hydrocortisone 100 mg/2 mL (Solu-Cortef) Nystatin suspension Mouth rinse Do not swallow. 250 mL 1g 150 mL QS 500 mL Diphenhydramine 12.5 mg /5 mL Dexamethasone 4 mg/mL injection Nystatin suspension Distilled water QS to 200 mL8 Swish and Spit 5 mL QID. 120 mL 0.56 mL 40 mL Viscous lidocaine 2% Cherry flavored Kool-Aid mixed with 1500 mL of sterile water for irrigation (sugar-free) 2000 mL QS 3400 mL Diphenhydramine 12.5 mg/5 mL Prednisone 5 mg/5 mL Nystatin suspension 1 part 1 part 1 part Viscous lidocaine 2% 80 mL Mylanta 80 mL Diphenhydramine 12.5 mg/5 mL 80 mL Nystatin suspension 80 mL Prednisolone 15 mg/5 mL 80 mL Distilled water 80 mL Swish, gargle, and spit 5 mL to 10 mL Q6H PRN. May be swallowed if esophageal involvement.10 Viscous lidocaine 2% 150 mL Diphenhydramine 12.5 mg/5 mL 20 mL Hydrocortisone (Solu-Cortef) 100 mg Tetracycline 2 grams Nystatin suspension 20 mL Swish, hold, and swallow 15 to 30 mL Q4-6H.1 a.k.a. Mile’s Solution Ingredients1-11,a-e Amount Viscous lidocaine 2% 30 mL Maalox 60 mL Diphenhydramine 12.5 mg/5 mL 30 mL Carafate 1 g/10 mL 40 mL Swish, gargle, and spit 5 mL to 10 mL Q6H PRN. May swallow if esophageal involvement.10 Dexamethasone 0.5 mg/5 mL 100 mL Diphenhydramine 12.5 mg/5 mL 100mL Nystatin suspension 60 mL Tetracycline 1500 mg Swish, gargle, and spit 5 mL to 10 mL Q6H PRN. May swallow if esophageal involvement.10 a. Elixirs containing alcohol can cause stinging. Consider using injectable or powder formulation, crushing tablets, or opening capsules in place of elixir formulation to avoid stinging. b. Some U.S. clinicians have found the new formulation of Kaopectate (i.e., containing bismuth) to solidify over a short period of time when mixed with other ingredients. U.S. clinicians should consider this potential problem if utilizing recipes which use Kaopectate in place of Maalox. Canadian Kaopectate formulation does not contain bismuth. c. Nystatin has not been shown to be effective in treating oral fungal infection associated with oral mucositis.11 d. The use of corticosteroids, such as hydrocortisone or dexamethasone, has not been adequately studied to recommend its inclusion in magic mouthwash.11 e. According to USP standards, mixtures containing water should have an expiration not longer than two weeks.12 f. CMC=Carboxymethylcellulose. Users of this document are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making clinical judgments based on the content of this document. Our editors have researched the information with input from experts, government agencies, and national organizations. Information and Internet links in this article were current as of the date of publication. More. . . Copyright © 2009 by Therapeutic Research Center Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com (Detail-Document #251103: Page 3 of 3) Project Leader in preparation of this DetailDocument: Wan-Chih Tom, Pharm.D. References 1. 2. 3. 4. 5. The Erie St. Clair Palliative Care Management Tool. January 2007. http://www.ccacont.ca/Upload/esc/General/Palliative_Care_Manag ment_Tool_v3.2.pdf. (Accessed October 11, 2009). Anon. Slang terms and jargon can cause medication errors. Drugs & Therapy Bulletin. Shands at the University of Florida. November/December 2005. Volume 19, Number 10. http://www.shands.org/professionals/drugInfo/bullet ins/1005.pdf. (Accessed October 11, 2009). Bulletin Board of Oral Pathology. University at Buffalo. 2007. North Carolina Board of Pharmacy. http://www.ncbop.org/faqs/Pharmacist/faq_DukesM agicMouthwash.htm. (Accessed October 11, 2009). Hodgins C, Mosley M, Pola-Strowd M. Recommendations for the diagnosis and management of recurrent aphthous stomatitis. Cite this Detail-Document as follows: 2009;25(11):251103. 2003. University of Texas at Austin, School of Nursing. 6. Tarascon Pharmacopoeia. 2009 Library Edition. Ed. In Chief: Richard J. Hamilton. Jones & Bartlett. Sudbury, MA:164. 7. Department of Pharmacy Services. Mount Sinai Hospital. Toronto, Ontario MSG 1XS. October 2009. 8. Toronto Sunnybrook Regional Cancer Centre Pharmacy. Toronto, Ontario M4N 3M5. October 2009. 9. Drug Information and Research Centre. Ontario Pharmacist’s Association. October 2009. 10. Randy Otterholt, DDS General Dentistry. http://www.drotterholt.com/magicmouthwash.html. (Accessed October 11, 2009). 11. Chan A, Ignoffo RJ. Survey of topical oral solutions for the treatment of chemo-induced oral mucositis. J Oncol Pharm Pract 2005;11:139-43. 12. Chapter 795 Pharmaceutical Compounding-Nonsterile Preparations. The United States Pharmacopeia and The National Formulary (USPNF). http://www.usp.org/pdf/EN/USPNF/generalChapter 795_PF354.pdf. (Accessed October 11, 2009). Magic mouthwash recipes. Pharmacist’s Letter/Prescriber’s Letter Evidence and Advice You Can Trust… 3120 West March Lane, P.O. Box 8190, Stockton, CA 95208 ~ TEL (209) 472-2240 ~ FAX (209) 472-2249 Copyright © 2009 by Therapeutic Research Center Subscribers to Pharmacist’s Letter and Prescriber’s Letter can get Detail-Documents, like this one, on any topic covered in any issue by going to www.pharmacistsletter.com or www.prescribersletter.com
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