Treatment - Topical Anesthetics

Transcription

1 Treatment - Topical Anesthetics Lidocaine products (viscous, gel or solution) can be used for mucositis pain and discomfort - Apply locally or gargle and spit the solution out 1. It can reduce the gag reflex 2. Lack of safety evidence on systemic uptake Any topical anesthetic agent that would not compromise mucosal surface could be used, e.g. lidocaine, benzocaine, diphenhydramine

2 Treatment Oral Mouthwash Antibiotic - To reduce the bacterial flora around the lesion Antihistamine - For local anesthetic effect Antifungal - To stop any fungal growth Steroid - To reduce inflammation Local anesthetic To reduce any pain Antacid - To enhance coating of the ingredients on the mouth

3 Treatment - Magic Mouthwash No specific recipes and numerous formulations available Usually contains at least 3 ingredients Formulas may contain a combination of an antibiotic, antihistamine, antifungal, steroid, a local anesthetic/pain reliever, or an antacid Most of these formulas are used every 4-6 hrs Swish for 1-2 minutes then spit or swallow Shake well before use No eating or drinking for 30 minutes after use (best to advise patients to use it after meals

4 Recipes of Magic Mouthwash (from pharmacist s letter): Magic Mouthwash. Pharmacist s Letter/Prescriber s Letter 2007;23(7):230703

5 Other Mouthwash Formulas Magic Mouthwash. Pharmacist s Letter/Prescriber s Letter2007;23(7): Formula of Daniel s Mouthwash (at Norris): Hydrocortisone (125mg/mL) 12.8 ml Diphenhydramine (12.5mg/5mL) 640 ml Tetracycline Syrup (125mg/5mL) 64 ml Amphoterican B injection (5mg/mL) 32 ml Sterile Water for Irrigation qs ad 1000 ml Shake well and Refrigerate should be affixed to the bottle Expiration: 30 days after date of preparation

6 Efficacy of Magic Mouthwash Lack of evidence to prove that magic mouthwash is effective in treating mucositis Variations of different formulations among institutions NCCN Task Force Recommendations: Included Magic Mouthwash as part of treatment strategies No one agent or formula is shown to be superior to the other Choice is based on clinical assessment and patient s symptoms and preference

7 Efficacy of Magic Mouthwash Mouth rinses containing Amphotericin B have been used to treat oral candidiasis Nystatin suspension has not been shown to be useful in preventing oral candida colonization Sucralfate suspension (cytoprotective for oral mucosa) has not been shown to be effective in preventing and treating mucositis PHARMACIST S LETTER / PRESCRIBER S LETTER July 2007;23(7): CA Cancer J Clin 2001; 51: Dodd et.al. Cancer Investigation 2003;21: Nottage et.al. eds. Support Care Cancer 2003; 11:41-47

8 What should we do with magic mouthwash? There may be a need to standardize the magic mouthwash formula in order to evaluate its effectiveness Despite the lack of evidence of magic mouthwash s efficacy in treating mucositis, patients and prescribers continue to use it with some success in alleviating symptoms As pharmacists, we should verify the formula and patient allergies prior to dispensing, and provide proper counseling (shake well, swish then spit or swallow, best to take after meals)

9 Xerostomia

10 Xerostomia Salivary gland dysfunction well documented side effect with head and neck radiotherapy Some studies reported that oral dryness may contribute to oral mucositis MOA: Increase trauma and irritation caused by loss of surface lubrication of tissues Unfavorable influences on microbial colonization Dehydration of mucosal surfaces NCCN Task Force Report. JNCCN 2008;6[Supp1]:S1-S21

11 Treatment of Xerostomia Sialagogues agents that stimulates the secretion of saliva Sugarless candy or mints Pilocarpine (cholinergic agonist) Dosage: 5 mg 3 times/day, titration up to 10 mg 3 times/day may be considered for patients who have not responded adequately; do not exceed 2 tablets/dose Amifostine (Chemo-protective agent) NCCN Task Force Report. JNCCN 2008;6[Supp1]:S1-S21

12 Amifostine (Ethyol ) Indications (FDA): To reduce moderate to severe xerostomia (a risk factor) in patients who undergo post-op radiation treatment for head and neck cancer, where the radiation area includes a substantial portion of the parotid glands To reduce the cumulative renal toxicity associated with repeated use of cisplatin in patients with advanced ovarian cancer MOA (Mucositis): An organic thiophosphate that functions as a free radical scavenger and has been investigated for use as a radioprotectant ASCO guidelines (2008): Recommended for use to decrease the incidence of acute and delayed radiation therapy-induced xerostomia No recommendation from NCCN or MASCC for use of Amifostine as treatment strategies for mucositis Usage varies depending on different institutions Ref: JNCCN 2008;6[Supp1]:S1-S21. Amifostine Lexi-Comp Online. Amifostine Prescribing Package Insert

13 Amifostine (Ethyol ) Dosage Recommendation for reduction of Xerostomia from head and neck cancer: IV: 200 mg/m 2 over 3 minutes daily minutes prior to radiation therapy or SubQ (unlabeled route): 500 mg once daily prior to radiation therapy Contraindication: Patients with known hypersensitivity to aminothiol compounds Amifostine Lexi-Comp Online. Amifostine Prescribing Package Insert

14 Amifostine - Precautions Dosage for use in Xerostomia relatively low, generally well tolerated Monitoring Consideration: Hypotension: risk increase in patients on antihypertensives or are dehydrated. Monitor blood pressure during treatment. Advise patients to hold antihypertensive at least 24 hours prior to receiving Amifostine Cutaneous reactions: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, toxoderma, and exfoliative dermatitis have been reported May be delayed, developing up to weeks after treatment initiation Discontinue treatment for severe/serious cutaneous reaction, or with fever. Reinitiate only after careful evaluation Nausea/Vomiting (dose-dependent, mildly emetogenic 300 mg/m 2 ) - Antiemetic can be administered prior to and in conjunction with amifostine if patients developed nausea and vomiting with treatment Hypocalcemia (rare - 1%) - Monitor serum calcium periodically Ref: Amifostine. Lexi-Comp Online. Prescribing Package Insert

15 Treatment of Mucositis with Palifermin

16 Palifermin (Kepivance ) Indication - Decrease the incidence and duration of severe oral mucositis in patients with hematologic malignancies receiving myelotoxic therapy requiring hematopoietic stem cell support MOA - Keratinocyte Growth Factor (KGF) that binds to KGF receptor stimulating proliferation, differentitation and migration of epithelial cells in multiple tissues MASCC, NCCN Task Force Recommendations - Use of Palifermin (at the FDA-approved dose) for prevention of mucosits in patients with hematologic malignancies receiving Total Body Irradiation with autologous stem cell transplantation NCCN Task Force Report. JNCCN 2008;6[Supp1]:S1-S21

17 Palifermin- Administration For Oral mucositis: IV bolus: 60 mcg/kg/day for 3 consecutive days before and after myelotoxic therapy; total of 6 doses Note: Administer first 3 doses prior to myelotoxic therapy, with the 3rd dose given hours before chemotherapy begins. The last 3 doses should be administered after myelotoxic therapy, with the first of these doses after but on the same day as hematopoietic stem cell infusion and at least 4 days after the most recent dose of palifermin *** Pharmacists can assist with the proper schedule and administration of doses *** Palifermin Prescribing Package Insert

18 Palifermin - Precautions Mucositis: Observed if administered within 24 hours of chemotherapy, Palifermin may increase the severity and duration of mucositis due to the increased sensitivity of rapidly-dividing epithelial cells Best be given prior to and following, but not during or within 24 hours of (before or after) chemotherapy Mucocutaneous effects: Edema, erythema, pruritus, rash, oral/perioral dysesthesia, taste alteration, tongue discoloration, and tongue thickening have been reported Advise patients to report symptoms to health care providers Palifermin Prescribing Package insert

19 Palifermin - Precautions Incompatible with heparin: if heparin is used to maintain IV line, flush IV line with NS before and after Palifermin administration Contraindication in patients who has hypersensitivity to E. coli-derived proteins Palifermin Prescribing Package insert

20 Agents NOT Recommended by Guidelines for Mucositis Chlorhexidine (Peridex ) best used for oral hygiene protocols to reduce bacterial colonization of mucosal and periodontal tissues Oral Zinc Sulfate supplementation (weak data) Mucosal coating agents (i.e. Zilactin or Orabase) useful for occasional oral ulcers, limited effectiveness for management of oral mucositis NCCN Task Force Report. JNCCN 2008;6[Supp1]:S1-S21

21 Agents with FDA Approval but NOT Recommended by Guidelines Glutamine topical preparation Precursor for glutathione Reduces the production of proinflammatory cytokines Showed to be effective in treating mucositis in phase 3 trial, pending full FDA approval based on results of data Gelclair (Mucosal barrier gel), Mucotrol (Oral chewable wafer), Caphosol (Saliva substitute) Approved by FDA as devices to manage oral mucositis Lack sufficient studies in well-designed clinical trials to support recommendation for use in management of oral mucositis NCCN Task Force Report. JNCCN 2008;6[Supp1]:S1-S21

22 Summary of Mucositis Management Required multidisciplinary approach to ensure adequate reporting between patients and health care providers Educate patients to monitor symptoms of mucositis Identify patients at high risk for developing mucositis Considered a stepwise approach in prevention and management of mucositis: Good oral hygiene, daily self-assessment, compliant with preventive measures and mouth rinses Current management focus more on Palliative Care

23 Questions?