Prevention and Treatment of Oral Mucositis

Transcription

1 PL Detail-Document # This PL Detail-Document gives subscribers additional insight related to the Recommendations published in PHARMACIST S LETTER / PRESCRIBER S LETTER November 2014 Prevention and Treatment of Oral Mucositis Oral mucositis is mucosal ulceration caused by chemotherapy or radiation treatment. Mucositis can affect not only the mouth, but also the pharyngeal, laryngeal, and esophageal areas. 1 Mucositis is usually very painful and can be slow to heal. 1-3 It can reduce an individual s ability to tolerate cancer treatment, maintain nutritional intake (e.g., drink, eat, swallow), or speak. 1,4 Treatment guidelines have been developed for prevention and treatment of oral mucositis by the Multinational Association of Supportive Care in Cancer (MASCC)/International Society of Oral Oncology (ISOO) ( The National Cancer Institute (NCI) also provides recommendations ( /HealthProfessional/page5) as does the National Comprehensive Cancer Network (NCCN, Stomatitis is a term that is sometimes used interchangeably with mucositis, but is actually more general and describes any inflammatory condition of oral tissue. 2 Canker sores are also different from oral mucositis. Their cause is unclear but they tend to be recurrent and triggered by factors such as smoking, stress, etc. For more info on treatment of canker sores, go to our PL Detail-Document, Treatment of Canker Sores. The following chart lists commonly asked questions about the treatment of oral mucositis. Keep in mind that the effectiveness of interventions may depend on factors such as treatments and the type of cancer being treated. How can oral mucositis be prevented? What nondrug therapies can be recommended for patients with oral mucositis? Proper oral hygiene can help minimize severity of oral mucositis. 1,2 Holding ice chips in the mouth, or cryotherapy, during treatment may help prevent mucositis in some situations. 1,3,12 Oral zinc supplements may be helpful in some patients. 1 Rx palifermin (Kepivance) is FDA- and Health Canada-approved for prevention of oral mucositis in certain oncology patients. 1,2 It can reduce severity and duration of mucositis. 5 Maintain proper oral hygiene, such as brushing the teeth with a soft-bristle toothbrush and flossing with gentle irrigation using a water flosser on a low setting. 1,5 Avoid irritating foods or beverages (e.g., dry, salty, acidic, hard, hot). 5 Rinsing frequently, such as every four hours or between medicated mouth rinse doses, with a bland solution, such as one teaspoon of table salt in 32 oz. (1 L) of water (to make 0.9% sodium chloride) with or without one to two tablespoons of sodium bicarbonate, can be tried. 1,2,5,12 This mixture can be used at room temperature or refrigerated. The patient should rinse and swish then spit. 2 (Note that experts suggest that patients who use well water make their salt solution with bottled water instead.)

2 (PL Detail-Document #301105: Page 2 of 5) What are some commercially available treatments for oral mucositis? What are some common ingredients of compounded magic mouthwash? What is the rationale for these? An OTC antacid liquid (e.g., Amphojel) or film-forming agent (e.g., Zilactin) can be tried. 2 Rx oral protectants (e.g., Episil, Gelclair [alcohol-free], and MuGard-all U.S. only) may be more convenient than OTC products. 2 However, they can cost $100/week or more. 5 Commercial kits for compounding magic mouthwash are available in the U.S. These include: o First-Mouthwash BLM (diphenhydramine, lidocaine, aluminum/magnesium hydroxide) o First-BXN Mouthwash (diphenhydramine, lidocaine, nystatin) o First-Duke s Mouthwash (diphenhydramine, hydrocortisone, nystatin) o First-Mary s Mouthwash (diphenhydramine, hydrocortisone, nystatin, tetracycline) Magic mouthwash kits might be easier to e-prescribe and bill for than compounded products. However, kits are typically about three times more expensive than mixing the mouthwash from scratch using individual ingredients (approximately $25 to $40 vs $5 to $15), and kits only come in specific combinations and concentrations. 6 The logic behind magic mouthwash is to combine ingredients with different mechanisms of action. 5 There are numerous magic mouthwash formulations. Most have at least three ingredients. Recipes may contain a combination of an antibiotic (to reduce the bacterial flora around the lesion), antihistamine (for local anesthetic effect), antifungal (to stop any fungal growth), steroid (to reduce inflammation), a local anesthetic/pain reliever, or an antacid (to enhance coating of the ingredients on the mouth). 7 Common ingredients of magic mouthwash recipes include viscous lidocaine, diphenhydramine, milk of magnesia, kaolin with pectin, and aluminum/magnesium hydroxide. 2 The most popular magic mouthwash formulation includes viscous lidocaine and diphenhydramine plus aluminum/magnesium hydroxide to help ingredients coat the mouth. How effective is magic Continued There is a lack of controlled studies to evaluate the efficacy of the many different magic mouthwash recipes. Whether one recipe is more effective than another is unknown. 8,12 The 2004 guidelines for the treatment of oral mucositis suggest that magic mouthwashes (with various combinations of viscous lidocaine, benzocaine, milk of magnesia, kaolin-pectin, chlorhexidine, or diphenhydramine) are no better than normal saline solution in pain relief. 9 In addition, a Cochrane review found magic mouthwash (containing lidocaine, diphenhydramine, and aluminum hydroxide) to be ineffective in shortening the healing time of oral mucositis related to cancer therapies. 10 There is also concern about the absorption of anesthetics such as lidocaine when used on damaged mucosa. 9 Although frequently used as an ingredient of magic mouthwash, nystatin has not been shown to be effective in treating oral fungal infection associated with mucositis. 7 It is also suggested that the high sugar content of nystatin suspension may feed the fungus. 8 Corticosteroids have not been studied adequately to be recommended as an ingredient of magic mouthwash, and

3 (PL Detail-Document #301105: Page 3 of 5) continued How effective is magic there s concern that long-term use may lead to oral candidiasis. Despite the lack of evidence that magic mouthwashes work in decreasing the pain associated with chemotherapy/radiation-induced mucositis, canker sores, or other oral pain conditions, many patients and prescribers continue to use them. There is a need to standardize the ingredients used to compound magic mouthwash in order to fully evaluate efficacy. Where can I find recipes for magic We have a number of different recipes in our PL Chart, Magic Mouthwash Recipes. Most formulations are used every four to six hours with instructions to hold in the mouth for one to two minutes then spit out or swallow. (Those with lidocaine should be spit out.) 12 Patients should be instructed not to eat or drink for 30 minutes after use. 7 Focal application should be used when possible, instead of widespread topical administration. 2 compounding magic billing compounded magic Continued When compounding these mixtures, try to avoid using elixir formulations as the alcohol content can cause stinging. Consider injectable or bulk powder formulations, crushed tablets, or opened capsules if needed. In some cases injectable formulations are used in place of elixirs. 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 the place of Maalox. Canadian Kaopectate formulation does not contain bismuth. The combination of lidocaine and sucralfate in magic mouthwash may not be compatible in some recipes. Some clinicians report the formation of a thick gel when the two ingredients are mixed. Prior to dispensing magic mouthwash, pharmacists should verify the formula and patient allergies. Patients should be counseled regarding the proper use of magic mouthwash (e.g., to shake well before use, hold in mouth for a minute or two, whether to swallow or not, etc). Billing for magic mouthwash is not straightforward and varies among different pharmacies. There is no single NDC number that can be used to bill for magic mouthwash mixed from individual ingredients. In addition, some of the ingredients used in the magic mouthwash are OTC products, which may not be covered by some insurances. Some pharmacists are left with the option of billing for a single prescription ingredient used for the compound and for the full bottle used since billing a partial bottle is not allowed by insurance companies. Some pharmacists have the patient pay cash. In some cases, the dispensing software allows the pharmacist to enter each ingredient used and the cost of each ingredient for billing. In other cases, pharmacists may choose to bill each ingredient separately as separate prescriptions. The magic mouthwash compounding kits each come with a single unique NDC number accounting for all the ingredients, which can make billing less complicated in some cases. It may be easier to compound with these kits

4 (PL Detail-Document #301105: Page 4 of 5) continued billing compounded magic What beyond-use date should be assigned to compounded magic How should pain from oral mucositis be managed? than having to measure and mix each individual ingredient. These compounding kits have also gone through stability testing and have specified stability duration for an expiration date. Lastly, these mouthwashes have added flavors and may be better tasting than mouthwashes compounded from scratch. Check insurance coverage before assembling the kit. Medicare and Medicaid coverage may be spotty because these are compounding kits, not approved drug products. However, some managed plans may still cover the kits. Prescribers should specify mouthwash kits by brand name or specify the magic mouthwash formula. Beyond-use dates of these mixtures can vary depending on the ingredients and their individual expiration dates. In general, per USP standards, if a mixture contains water and is a mucosal liquid, the beyond-use date should not be longer than 30 days (room temperature). 7,11 Oral mixtures containing water should have an expiration not longer than two weeks (refrigerated). 11 Start with topical anesthetics such as topical lidocaine, 0.5% doxepin mouth rinse, or diphenhydramine mouth rinse. 1,2 Keep in mind most magic mouthwash recipes contain a topical anesthetic. If topical anesthetics don t provide relief, consider opioids such as an alcohol-free morphine solution to swish and swallow, transdermal fentanyl, PCA morphine, etc. 1,2,5 What treatments for oral mucositis should actually be avoided? Avoid sucralfate or chlorhexidine, because they aren t likely to help. 1,3,4 Also avoid alcohol-based mouth rinses, which can increase pain. 12 Avoid using hydrogen peroxide solutions (e.g., 3% hydrogen peroxide diluted 1:1 with water or normal saline) for more than two days. These may help remove oral debris, but longer periods of use can slow healing. 2 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.

5 (PL Detail-Document #301105: Page 5 of 5) Project Leader in preparation of this PL Detail- Document: Stacy A. Hester, R.Ph., BCPS, Assistant Editor References 1. Lalla RV, Bowen J, Barasch A, et al. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer 2014;120: NCI. Oral mucositis. are/oralcomplications/healthprofessional/page5. (Accessed October 8, 2014). 3. Worthington HV, Clarkson JE, Bryan G, et al. Interventions for preventing oral mucositis for patients with cancer receiving treatment (Review). Cochrane Database Syst Rev 2011;(4):CD Clarkson JE, Worthington HV, Furness S, et al. Interventions for treating oral mucositis for patients with cancer receiving treatment. Cochrane Database Syst Rev 2010;(4):CD Negrin RS, Bedard J, Toljanic JA. Oral toxicity associated with chemotherapy. Last updated September 12, In UpToDate, Basow DS (ed), UpToDate, Waltham, MA Cutis Pharmaceuticals. (Accessed October 9, 2014). 7. Chan A, Ignoffo RJ. Survey of topical oral solutions for the treatment of chemo-induced oral mucositis. J Oncol Pharm Pract 2005;11: Dodd MJ, Dibble SL, Miaskowski C, et al. Randomized clinical trial of the effectiveness of 3 commonly used mouthwashes to treat chemotherapy-induced mucositis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90: Rubenstein EB, Peterson DE, Schubert M, et al. Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis. Cancer 2004;100(9 Suppl): Clarkson JE, Worthington HV, Eden OB. Interventions for treating oral mucositis for patients with cancer receiving treatment. Cochrane Database Syst Rev 2007;(2):CD <795> Pharmaceutical Compounding--Nonsterile Preparations. The United States Pharmacopeia and The National Formulary (USP-NF) pdf. (Accessed October 9, 2014). 12. Bensinger W, Schubert M, Ang K, et al. NCCN task force report: prevention and management of mucositis in cancer care. January f. (Accessed October 10, 2014). Cite this document as follows: PL Detail-Document, Prevention and Treatment of Oral Mucositis. Pharmacist s Letter/Prescriber s Letter. November Evidence and Recommendations You Can Trust 3120 West March Lane, Stockton, CA ~ TEL (209) ~ FAX (209) Copyright 2014 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 or