This prescription is for topical therapy to manage skin toxicities from anticancer treatments. The pharmacist selected lidocaine jelly 2% and hydrocortisone 1% cream as appropriate first-line options and included fucidin 2% cream as an alternative. Directions for use, quantities dispensed and refill authorization were also included.

1. PAS Conference 2019
May 4, 2019 from 3:45-4:35pm
Lana Dean, BSP
Oncology Pharmacist
Allan Blair Cancer Centre
Saskatchewan Cancer Agency
Regina, SK
Cancer 101: Managing Common Drug
Interactions and External Supportive
Care Medications as well as
Minimizing Mouth Sores

2. Disclosures
 Attended consultant meetings with
and in the past

3. Objectives
 Managing common oral drug interactions in cancer care
 Supportive care medications filled in community from
the cancer centre
 Antibiotic and antiviral prophylaxis
 Nausea and vomiting
 Skin toxicities
 Radiotherapy prescriptions
 SCA’s Using Dexamethasone for Patients with Cancer Involving the
Brain – Patient handout
 Pemetrexed and immunotherapy supportive care
 Oral care
 Prevention and treatment of oral mucositis and stomatitis
 SCA’s Mouth Care during Treatment of Cancer – Patient handout
 Coverage of supportive care prescriptions

4. Objectives
 Managing common oral drug interactions in cancer care
 Supportive care medications filled in community from
the cancer centre
 Antibiotic and antiviral prophylaxis
 Nausea and vomiting
 Skin toxicities
 Radiotherapy prescriptions
 SCA’s Using Dexamethasone for Patients with Cancer Involving the
Brain – Patient handout
 Pemetrexed and immunotherapy supportive care
 Oral care
 Prevention and treatment of oral mucositis and stomatitis
 SCA’s Mouth Care during Treatment of Cancer – Patient handout
 Coverage of supportive care prescriptions

5. Contribution of Drug Interactions to the
Overall Burden of Preventable ADRs1
 Drug interactions represent 3 to 5% of
preventable in-hospital medication errors
 Approximately 3% of all hospital
admissions in the U.S. are caused by drug-
drug interactions
 Drug-drug interactions are estimated to be
the cause of death in 4% of cancer patients

6. Why are cancer patients so
susceptible to drug interactions?1
 Mean age of cancer patients is increasing
 Cancer patients receive multiple
medications
 Cancer patient’s pharmacokinetic
parameters may be altered
 I.e. impaired drug absorption due to
mucositis and malnutrition

7. Drug Interactions in
Oncology1,2
 27% of cancer patients were exposed to potential drug-drug
interactions in an ambulatory cancer setting
 In hospitalized cancer patients, the use of eight or more
drugs and a hospital stay of greater than 6 days were
identified as risk factors for potential drug interactions

8. SCA’s Pharmacists Use These
Drug Interaction Checkers
 Lexi-Comp® and UpToDate®
 Info. in UpToDate® is supplied by Lexi-Comp®
 If find potentially clinically significant drug interaction
with Lexi-comp, check Micromedex®
 +/- Drugs.com
 +/- BC Cancer Agency Cancer Drug Manual
 +/- Ontario Cancer Care Drug Formulary
 Natural Medicines™

9. Case 1: Tamoxifen1
 Renee Taylor, 45 years old
 Adjuvant breast cancer
 Treated with adjuvant chemotherapy
(FEC x 3 then DOC x 3)
 ER/PR+, HER2-
 Started on Tamoxifen post-
chemotherapy x 10 years
 Patient is feeling depressed and feels
she needs some therapy for her
mood
 No other prescriptions/OTCs/herbals

10. Tamoxifen with Antidepressants:
Mechanism and Effect1
 Mechanism:
 Inhibition of activation of Tamoxifen to its major active
metabolite by CYP2D6
 Effect:
 Decreased clinical effectiveness of Tamoxifen
(i.e. decreased disease-free survival)

11. Tamoxifen with Antidepressants:
Management and Evidence1
 Paroxetine/Fluoxetine/Bupropion are strong inhibitors of
CYP2D6 so SHOULD NOT BE USED
 Sertraline/Duloxetine are moderate inhibitors of CYP2D6 so
SHOULD BE AVOIDED if possible
 Citalopram/Escitalopram/Venlafaxine/Desvenlafaxine/
Amitriptyline/Nortriptyline/Trazodone/Mirtazapine are
weak inhibitors of CYP2D6 so CAN BE USED

12. Tamoxifen with Antidepressants:
BC Cancer Drug Monograph3

13. Case 2: Erolitinib1
 David Barnes, 71 years old
 Metastatic non small cell lung
cancer
 Previously treated with
Paclitaxel and Carboplatin
 Disease progression to brain
 Evaluated by Medical
Oncologist and will start on
Erlotinib
 Current 1 ppd smoker x 50 yrs
 Current medications:
 ASA EC 81mg daily
 Rosuvastatin 20mg daily
 Omeprazole 20mg daily

14. Erlotinib (TKI, EGFR inhibitor):
Mechanism of Action4

15. Erlotinib + PPi/H2RA:
Mechanism and Effect1
 Mechanism:
 Erlotinib is metabolized primarily by CYP3A4 and to a
lesser extent by CYP1A2
 The oral absorption of Erlotinib is pH-dependent
 Cigarette smoking induces CYP1A2 (increased clearance)
 Effect:
 Decreases in Erlotinib absorption may occur when given
with H2RAs and PPis so these combinations should be
avoided if possible
 Cigarette smoking can decrease Erlotinib exposure by 50-
60% so smoking cessation should be encouraged

16. Erlotinib + PPi/H2RA:
Management and Evidence1
 Management
 Some options to resolve drug interaction:
 Taper off the PPi +/- Antacids
 Step down PPi to H2RA +/- Antacids
 Erlotinib must be taken once daily
 10 hours after the H2RA dosing and at least 2 hours before
the next dose of the H2RA
 Antacid dose and the Erlotinib dose should be separated by
several hours
 Evidence
 Erlotinib prescribing information states that Erlotinib AUC
was decreased by an average of 46% when co-
administered with Omeprazole
 Lexi-comp:
 Level X with Omeprazole
 Level D with Ranitidine

17. Kinase Inhibitor + PPi: ESMO Guideline5

18. Case 3: Sunitinib1
 Carol Struan, 71 years old
 Metastatic renal cell cancer
 Disease progression to brain
 Will start Sunitinib 50mg daily
for 4 weeks on and 2 weeks off
 Current medications:
 Clarithromycin 500mg BID
x 10 days
 Ranitidine 150mg BID
 Ramipril 10mg daily
 Lorazepam 1mg HS

19. Sunitinib (TKI, VEGF inhibitor):
Mechanism of Action6

20. Sunitinib + Clarithromycin:
Mechanism and Effect1
 Mechanism:
 Sunitinib is primarily metabolized by CYP3A4
 Clarithromycin is a strong inhibitor of CYP3A4 and may
cause QT prolongation
 Sunitinib may also cause dose-dependent QT prolongation
 Effect:
 Using Clarithromycin with Sunitinib may result in increased
plasma concentrations of Sunitinib
 May also cause additive effects on QT prolongation

21. Sunitinib + Clarithromycin:
Evidence and Management1
 Evidence:
 No significant effect on the co-administration of Clarithromycin
or Azithromycin on the pharmacokinetics of Sunitinib in rabbits
was found in a study
 Lexi-Comp (Level D):
 Sunitinib – Metabolism/Transport Effects – Substrate of CYP3A4 (major)
 Clarithromycin – Metabolism/Transport Effects – Inhibits CYP3A4 (strong)
 Management:
 Selection of an alternative to Clarithromycin with no or minimal
enzyme inhibition potential/QT prolongation is advised
 However, if concomitant use is required, consider reducing the
dose of Sunitinib to a minimum of 37.5mg orally daily

22. QT Prolongation of Kinase Inhibitors:
ESMO Guideline7

23. QTc Prolongation: Risk Factors8
Risk Factor Points
Age >/= 68 years 1
Female 1
Loop diuretic 1
Serum potassium </= 3.5 mmol/L 2
QTc interval >/= 450ms 2
Heart failure with reduced ejection fraction 3
1 QTc interval-prolonging drug 3
>/= 2 QTc interval-prolonging drugs 3
Sepsis 3
Maximum score 21
High risk >/= 11 points
Moderate risk 7-10 points
Low risk <7 points

24. How to Avoid QTc Prolongation:
RxFiles9

25. Other examples of common oral drug
interactions at the cancer centre3
 Food interactions
 Ex. Abiraterone + high fat meal
 Ex. Everolimus + grapefruit/Seville
oranges/starfruit
 CAM interactions – UpToDate
 Ex. Immuno-stimulants, probiotics,
antioxidants, estrogenic, antiplatelet effects,
etc.

26. How do I know what anticancer treatment(s)
my patient is taking from the cancer centre?
 Ask the patient
 Review SCA’s Progress Notes on eHealth
Viewer under Clinical Documents
 Call the patient’s cancer centre pharmacy
 Saskatoon Cancer Centre Pharmacy: (306) 655-2680
 Allan Blair Cancer Centre Pharmacy (Regina): (306) 766-2816
 In the future, SCA’s medications will be
integrated with PIP

27. Drug Interactions in Oncology:
Optional Resources and Courses
 BC Cancer Drug Interactions Course (FREE)
 Learninghub.phsa.ca/Courses/5722/bcca-drug-interactions
 Approx. 5 hours
 Essentials of Oncology for Pharmacists ($399 + HST)
 Online through University of Toronto
 12 interactive modules approx. 30-45mins each
 Advanced Oncology for Pharmacists ($1750 + HST)
 Part 1: 19 interactive modules approx. 45-60mins each (Online)
 Part 2: Combination of didactic and case-based discussion (Online or in-person)
 Immunodeficiency Clinic – Toronto General Hospital (FREE)
 Download their app!
 https://hivclinic.ca/drug-information/drug-interaction-tables/
 Oncology Pro – ESMO (FREE)
 Drug-drug interactions with common kinase inhibitors
 https://oncologypro.esmo.org/Oncology-in-Practice/Anti-Cancer-Agents-and-Biological-
Therapy/Drug-Drug-Interactions-with-Kinase-Inhibitors
 UpToDate – CAM Drug Interactions
 https://www.uptodate.com/contents/complementary-and-alternative-therapies-for-
cancer?csi=9b165e65-cd3e-4a11-a9ed-4356aff37c37&source=contentShare

28. Objectives
 Managing common oral drug interactions in cancer care
 Supportive care medications filled in community from
the cancer centre
 Antibiotic and antiviral prophylaxis
 Nausea and vomiting
 Skin toxicities
 Radiotherapy prescriptions
 SCA’s Using Dexamethasone for Patients with Cancer Involving the
Brain – Patient handout
 Pemetrexed and immunotherapy supportive care
 Oral care
 Prevention and treatment of oral mucositis and stomatitis
 SCA’s Mouth Care during Treatment of Cancer – Patient handout
 Coverage of supportive care prescriptions

29. Take Home Prescription:
Post-Chemotherapy Antibiotic Prophylaxis10
 Rationale: Fluoroquinolones prophylaxis is recommended to prevent
life-threatening infections Ex. Febrile neutropenia for high-risk
(sometimes intermediate risk) neutropenic patients and is given with each
cycle of chemotherapy
 Ciprofloxacin 500 mg (First line)
PO BID for 7 days, starting on Day 5 following
chemotherapy to prevent infection during
period of low white blood cell counts
Refill x ____________
Note: Drug Plan EDS criteria for prophylaxis of
prolonged neutropenia
OR
 Clavulin-500 (Cipro allergy)
PO Q8H for 7 days, starting on Day 5 following
chemotherapy to prevent infection during period
of low white blood cell counts
Refill x ____________

30. Take Home Prescription: PJP
(Pneumocystis jirovecii pneumonia) Prophylaxis10
 Trimethoprim/Sulfamethoxazole DS (First line)
1 tablet once daily PO Monday, Wednesday
and Friday each week
Dispense: _________ weeks
OR
 Dapsone 50 mg PO BID (Sulfa allergy)
Dispense: _________ weeks
 Examples of use from UpToDate: Patients receiving some
anticancer treatments (such as Alemtuzumab, TMZ with RT,
Fludarabine + Cyclophosphamide, or Idelalisib), ALL patients,
allogenic HCT recipients, and selected autologous HCT recipients

31. Take Home Prescription:
Post-Chemotherapy Antiviral Prophylaxis10
 Acyclovir 400 mg
400mg PO BID until one month after last
Bortezomib dose
Dispense: 68 x 400mg
Refill x ________
OR
 Valacyclovir 500 mg
500mg PO BID until one month after last
Bortezomib dose
Dispense: 68 x 500mg
Refill x ________
 Rationale: Preventing reactivation of herpes simplex virus
(HSV) and varicella-zoster virus (VZV)

32. Anticancer Treatments are Categorized
Based on Risk of Emesis:
Minimal, Low, Moderate, or High10

33. Take Home Prescription:
High Emetic Risk Chemotherapy10
 Metoclopramide 10 mg
10 mg PO QID regularly for 4½ days, starting before supper on
Day 1 of chemotherapy, then 10mg PO QID PRN to control
nausea/vomiting
Dispense: 60 x 10 mg
Refill: x _____
OR
 Prochlorperazine 10 mg
10 mg PO QID regularly for 4½ days, starting before supper on
Day 1 of chemotherapy, then 10mg PO QID PRN to control
nausea/vomiting
Dispense: 60 x 10 mg
Refill: x ______
+/-
 Ranitidine 150 mg (If not already taking an H2 blocker or PPi)
150mg PO BID for 7 days starting Day 1 of chemotherapy, then
BID PRN to control heartburn symptoms
Dispense: 60 x 150 mg
Refill: x _____

34. Take Home Prescription:
Topical Therapy10
Select all that apply, STRIKEOUT to exclude:
 Lidocaine Jelly 2%
Apply to affected area(s) up to QID as directed
Dispense: 30g, Refill: x _____
 Hydrocortisone 1% Cream (Available OTC now)
Apply to affected area(s) BID as directed
Dispense: 15g, Refill: x ______
 Fucidin 2% Cream
Apply to affected area(s) BID to TID as directed
Dispense: 30g, Refill: x _____
 Flamazine Cream
Apply to affected area(s) once daily
Dispense: 50g, Refill: x _____

35. Take Home Prescription:
Skin Toxicities10
 Rationale: Prevention or treatment of EGFF inhibitor-induced
rash Ex. Cetuximab or Erlotinib
 Doxycycline 100mg
100mg PO BID
Dispense: 60 tablets
Refill: x _____
 Hydrocortisone 1% cream (Available OTC now)
Apply to affected area(s) on face and trunk (chest
and back) BID. Apply lightly and rub in well.
Dispense: 50g
Refill: x ______
Non-prescription items:
Lubriderm Lotion
Apply generously 2 to 3 times daily
Sunscreen SPF greater than or equal to 15
Apply to exposed skin 30 minutes prior to sun exposure

36. Internal Prescription:
Dexamethasone Taper with Radiotherapy10
Dexamethasone _____mg _____times per day for _____days, then
Dexamethasone _____mg _____times per day for _____days, then
Dexamethasone _____mg _____times per day for _____days, then
Dexamethasone _____mg _____times per day for _____days, then
Dexamethasone _____mg _____times per day for _____days, then
Dexamethasone _____mg _____times per day for _____days, then
Stop and reassess.
Notes:
1) Increase the dose to previous level if neurological symptoms
appear after tapering to a lower dose
2) Please consider adding a PPi or H2RA for gastroprotection as
required

37. SCA’s Using Dexamethasone for Patients with
Cancer Involving the Brain – Patient handout10

38. Pemetrexed Preprints: Dexamethasone,
Folic Acid, and Vitamin B12 Indications10
 Rationale: Dexamethasone reduces the risk of rash from
Pemetrexed. Folic acid at least 0.4mg per day + Vitamin
B12 injection every 9 weeks reduces incidence of severe
life-threatening toxicities such as neutropenia,
thrombocytopenia, mucositis, and febrile neutropenia – all
significantly correlated with drug-related death from
Pemetrexed.

39. Immunotherapy Preprints:
DO NOT TREAT if patient is receiving immuno-
suppressive doses of corticosteroids!10
 Rationale: Higher doses of corticosteroids have been shown
to reduce the efficacy of immunotherapy such as reduced
ORR, PFS, and OS.

40. Objectives
 Managing common oral drug interactions in cancer care
 Supportive care medications filled in community from
the cancer centre
 Antibiotic/antiviral prophylaxis
 Nausea and vomiting
 Skin toxicities
 Radiotherapy prescriptions
 SCA’s Using Dexamethasone for Patients with Cancer Involving the
Brain – Patient Handout
 Pemetrexed/Immunotherapy supportive care
 Oral care
 Prevention and treatment of oral mucositis and stomatitis
 SCA’s Mouth Care during Treatment of Cancer Treatment – Patient
handout
 Coverage of supportive care prescriptions

41. WHO’s Oral Toxicity Scale
(We also use CTCAE)

42. 2015 ESMO Clinical Practice Guidelines
for Mucosal Injury – Oral Mucositis11
 Basic oral care is key – education on good oral hygiene!
 Several health professional organizations have reported strategies
for management of oral mucositis caused by high-dose cancer
therapies:
 MASCC/ISOO – focuses on the management of oral mucositis
 ONS
 ASCO
 NCCN
 2015 ESMO Mucosal Injury CPGs represents the current
state-of-the-science in this field at the systematic review level
 2015 ESMO CPG are comprised of three domains:
1) MASCC/ISOO guidelines for management of mucositis caused by
chemotherapy and/or head and neck radiation
2) Recently emergent data relative to systematic enteral nutrition
3) Expert opinion on management of mucosal injury cause by targeted cancer
therapies, in part based on previously reported management of recurrent
aphthous ulceration

43. 2015 ESMO Clinical Practice Guidelines
for Mucosal Injury – Oral Mucositis11

44.  Recommendations IN FAVOUR of an intervention:
 Panel recommends 30 mins of oral cryotherapy be used to
prevent oral mucositis in patients receiving 5-FU bolus
chemotherapy (II)
 Panel recommends recombinant human keratinocyte growth
factor-1 (KGF-1/palifermin) be used to prevent oral mucositis in
patients receiving high-dose chemotherapy and total body
irradiation, followed by autologous stem cell transplantation for a
hematological malignancy (II)
 Panel recommends that low-level laser therapy be used to
prevent oral mucositis in patients receiving HSCT conditioned
with high-dose chemotherapy (II)
 Panel recommends that Benzydamine mouthwash be used to
prevent oral mucositis in patients with head and neck cancer
receiving moderate dose radiation without chemotherapy (I)
2015 ESMO Clinical Practice Guidelines
for Oral Mucositis – Prevention11

45. Oral Mucositis Prophylaxis for
Radiotherapy of Head and Neck Cancers11

46.  Suggestions IN FAVOUR of an intervention:
 Panel suggests that oral care protocols be used to prevent oral
mucositis in all age groups and across all cancer treatment
modalities (III)
 Panel suggests that systemic zinc supplements administered
orally may be of benefit to prevent oral mucositis in oral cancer
patients receiving radiotherapy or chemoradiation (III)
 Panel suggests that oral cryotherapy be used to prevent oral
mucositis in patients receiving high-dose melphalan with or
without total body irradiation as conditioning for HSCT (III)
 Panel suggests low-level laser therapy to prevent oral
mucositis in patients undergoing radiotherapy without
concomitant chemotherapy for head and neck cancer (III)
2015 ESMO Clinical Practice Guidelines
for Oral Mucositis – Prevention11

47. SCA’s Mouth Care during Treatment of Cancer
– Patient handout10, 11

48. SCA’s Mouth Care during Treatment of Cancer
– Patient handout: Rinse mouth10, 11
 Rinse mouth with an alcohol-free mouthwash upon awakening
and at least four times per day (especially after brushing teeth)
 Rinse mouth with ~15ml mouthwash by gargling for ~1 minute
and then spit out. Rinse mouth again with plain water.
 Avoid eating or drinking for around 30 minutes after rinsing

49. SCA’s Mouth Care during Treatment of Cancer
– Patient handout: Avoid painful stimuli10,11
 Smoking
 Alcohol
 Certain foods such as tomatoes, citrus food, “bubbly drinks,”
hot drinks, and spicy, hot, raw, or crusty food

50. Oral Mucositis Prophylaxis for Chemoradiotherapy
or Radiotherapy of Oral Cancers 11, 12

51.  Recommendations AGAINST an intervention:
 Panel recommends that polymyxin, tobramycin, amphotericin B,
bacitracin, clotrimazole, gentamicin antimicrobial lozenges and
paste NOT be used to prevent oral mucositis in patients
receiving radiation therapy for head and neck cancer (II)
 Panel recommends that iseganan antimicrobial mouthwash NOT
be used to prevent oral mucositis in patients receiving high-
dose chemotherapy with or without total body irradiation for
HSCT or in patients receiving radiation therapy or concomitant
chemoradiation for head and neck cancer (II)
 Panel recommends that sucralfate mouthwash NOT be used to
prevent oral mucositis in patients receiving chemotherapy for
cancer (I) or in patients receiving radiation (I) or concomitant
chemoradiation (II)
 Panel recommends that IV glutamine NOT be used to prevent
oral mucositis in patients receiving high-dose chemotherapy with
or without total body irradiation, for HSCT (II)
2015 ESMO Clinical Practice Guidelines
for Oral Mucositis – Prevention11

52.  Suggestions AGAINST an intervention:
 Panel suggests that chlorhexidine mouthwash NOT
be used to prevent oral mucositis in patients receiving
radiation for head and neck cancer (III)
 Panel suggests that GM-CSF mouthwash NOT be
used to prevent oral mucositis in patients receiving
high-dose chemo for HSCT (II)
 Panel suggests misoprostol mouthwash NOT be used
to prevent oral mucositis in patients receiving
radiation for head and neck cancer (III)
 Panel suggests that systemic pentoxifylline orally NOT
be used to prevent oral mucositis in patients
undergoing bone marrow transplantation (III)
 Panel suggests that systemic pilocarpine administered
orally NOT be used to prevent oral mucositis in
patients receiving radiation for head and neck cancer
(III) or patients receiving high-dose chemo with or
without total body irradiation for HSCT (II)
2015 ESMO Clinical Practice Guidelines
for Oral Mucositis – Prevention11

53. Oral Glutamine for Prevention
of Oral Mucositis – Evidence13
 Study done to evaluate the efficacy and safety of oral
glutamine supplementation in head and neck cancer patients
 Patients were assessed once per week to evaluate the onset
and severity of mucositis, pain, use of analgesics and for Ryle
tube feeding
N = 162
• Recruited Dec
2013 – Dec 2014
• Squamous cell
carcinoma of head
and neck
• All patients
received RT (70
Gy in 35 fr) over 7
weeks with
Cisplatin 40mg/m2
once weekly
Arm A:
Orally rinse 15g
Glutamine/240mL water
for ~2min and
swallow BID
Arm B:
Negative control
R
A
N
D
O
M
I
Z
E
D

54. Oral Glutamine for Prevention
of Oral Mucositis – Evidence13
 Results:
 53.1% patients developed oral mucositis toward the fifth
week in the Glutamine arm compared with 55.5% patients
in the control arm at the third week
 None in the Glutamine arm compared with 92.35% of pts
in the control arm developed grade 3 mucositis
 Rates of adverse events like pain, dysphagia, nausea,
edema, and cough, as well as use of analgesics and Ryle
tube feeding were significantly lower in the Glutamine arm
than in the control arm
 57% of patients in the Glutamine arm received 6 cycles of
Cisplatin whereas none of the patients in the control arm
could complete 6 cycles of Cisplatin
 A maximum number of 4 cycles of Cisplatin were
completed by 56% of patients in the control arm

55. Oral Mucositis Prophylaxis for
Chemoradiotherapy of Head and Neck Cancers13

56. Stomatitis Prevention Study:
SWISH14
 US-based, multicenter, single-arm, phase 2 prevention trial
(NCT02069093)
 23 investigational sites
 Enrollment: May 2014 to October 2015
 *At the completion of cycle 2 (day 56), the treating clinician determined whether to
continue the patient’s assigned regimen. Patients can continue to receive their
mouthwash regimen from Novartis for an additional 56 days.
N = 92
•Females ≥ 18 years old
•Postmenopausal locally
advanced or metastatic HR+,
HER2- breast cancer
•Prescribed Everolimus 10mg
+ Exemestane 25mg
•ECOG ≤ 2
Baseline
• Oral pain
assessment
• VAS score
• NDS score
• Good oral care
• EVE 10mg/day
• EXE 25mg/day
• Alcohol-free
Dexamethasone
Mouthwash*
(0.5mg/5mL):
Swish 10mL for 2
minutes and spit QID
Endpoints
Primary: Compare
grade ≥2 stomatitis
incidence at 8 weeks
with BOLERO-2 results
Secondary: Mouthwash
use by average
times/day, EVE/EXE
dose intensity, all-grade
stomatitis incidence,
time to resolution to
grade ≤1, oral pain
scale, and NDS

57. BOLERO-2 vs SWISH Results14
 BOLERO-2 = The Breast Cancer Trials of Oral Everolimus-2
 BOLERO-2 graded stomatitis based on CTCAE v3.0

58. SCA Pharmacy has Coverage Cards for this
Dexamethasone Mouthwash to Prevent Stomatitis for
Everolimus in Advanced Breast Cancer14
Dexamethasone 0.5mg/5mL mouthwash
(alcohol-free)*
Dexamethasone (as sodium phosphate)
injection 4mg/mL: 2.5mL
Ora-Plus®: 50mL
Ora-Sweet® qs to 100mL
Swish 10mL orally for 2 minutes and spit out
(do not swallow) 4 times daily for at least 2
months starting on day 1 of Everolimus
treatment
Notes:
•On Saskatchewan Formulary
•Stomatitis Benefit Program from Novartis
for up to 100% coverage for first 8 weeks of
Afinitor® treatment
*Handbook of Extemporaneous Preparation:
28 days stability

59. Oral Mucositis or Stomatitis Treatment
Using Topical Anesthetics for
ALL Cancer Treatment Modalities10
 Tetracaine 0.5% lollipop or troche
Directions: Use lollipop or troche orally for 30 seconds and repeat prn.
Do not eat or drink until numbness wears off. Store at room temperature.
 Tetracaine 0.5% with 0.05% triamcinolone lollipop or troche
Directions: Use lollipop or troche orally for 30 seconds and repeat prn.
Do not eat or drink until numbness wears off. Store at room temperature.
 Lidocaine viscous 2% (No prescription required)
Directions: Shake well before use. Swish 15mL orally for 30 seconds
and then spit out (do not swallow) every 3 hours prn.
Maximum 8 doses (120mL) in 24 hours.
Do not eat or drink until numbness wears off.
Note: Lollipops/troches must be compounded at a specialty pharmacy

60.  Suggestions IN FAVOUR of an intervention
 The panel suggests that 0.5% Doxepin
mouthwash may be effective to treat pain
due to oral mucositis (IV)
2015 ESMO Clinical Practice Guidelines
for Oral Mucositis – Treatment11

61. Oral Mucositis or Stomatitis Treatment
Using Topical Analgesic
for ALL Cancer Treatment Modalities11

62.  Suggestions IN FAVOUR of an
intervention
 The panel suggests that 0.2% Morphine
mouthwash may be effective to treat pain
due to oral mucositis in patients receiving
chemoradiation therapy for head and neck
cancer (III)
2015 ESMO Clinical Practice Guidelines
for Oral Mucositis – Treatment11

63. Oral Mucositis Treatment for Chemoradiotherapy
of Head and Neck Cancers11
*WARNING: Risk of overdose in opioid naïve patients*

64.  Recommendations AGAINST an
intervention
 The panel recommends that Sucralfate
mouthwash NOT be used to treat oral
mucositis in patients receiving
chemotherapy for cancer (I), or in patients
receiving radiation therapy (II) for head and
neck cancer
2015 ESMO Clinical Practice Guidelines
for Oral Mucositis – Treatment11

65. What about Club Soda?15
 Oral Care Symptom Management Guidelines
from Cancer Care Ontario
 Suggest that club soda SHOULD BE AVOIDED due
to the acidic pH, a result of the carbonic acid content
found in carbonated soft drinks
 Bottom-line: Club soda SHOULD NOT be
recommended for the prevention or treatment of
oral mucositis

66. Rationale for SCA NOT Recommending
“Koolstat” or “Magic/Mucositis Mouthwash”16
1) NOT evidence-based medicine and is INEFFECTIVE for treating
oral thrush and pain associated with oral mucositis
 According to the 2004 Oral Mucositis Guidelines, “Magic Mouthwash” is
no better than normal saline solution in pain relief
 A Cochrane Review found that “Magic Mouthwash” is ineffective for
shortening the healing time of oral mucositis
 The various mouthwash recipes with multi-ingredients use SUB-
THERAPEUTIC levels of Benadryl, Lidocaine, Maalox, Nystatin, etc.
 Lack of controlled studies to evaluate the efficacy of the different
mouthwash recipes
2) Expensive for both the patient and healthcare system
 Can cost upwards of $50 per prescription and only has 14 day shelf life
 As per the 2010 Saskatchewan Drug Formulary Bulletin, no multi-
ingredient mouthwashes are covered for patients in Saskatchewan

67. Rationale for SCA NOT Recommending
“Koolstat” or “Magic/Mucositis Mouthwash”16
3) Risk of Nystatin resistance
 There are various names and formulations of “Koolstat” and
“Magic/Mucositis Mouthwash” but these compounds usually yield
sub-therapeutic levels of Nystatin and thus, our patients are at a
risk of developing Nystatin resistance with time
4) Risk of steroid causing oral thrush
 The formulations of “Koolstat” and “Magic/Mucositis Mouthwash”
that contain steroids such as Cortisone could increase the risk of
causing oral thrush in patients and can be at immunosuppressive
levels in our patients’ bodies
5) Risk of causing harm to our patients
 Health Canada Vigilance Program assigned Magic Mouthwash the
Adverse Reaction Number 000715550 due to the cases at SCA of
causing harm to our patients

68. Oral Mucositis/Stomatitis Prophylaxis
– Mostly based on ESMO 2015 CPGs10

69. Oral Mucositis/Stomatitis Treatment
– Mostly based on ESMO 2015 CPGs10

70. Objectives
 Managing common oral drug interactions in cancer care
 Supportive care medications filled in community from
the cancer centre
 Antibiotic/antiviral prophylaxis
 Nausea and vomiting
 Skin toxicities
 Radiotherapy prescriptions
 SCA’s Using Dexamethasone for Patients with Cancer Involving the
Brain – Patient Handout
 Pemetrexed/Immunotherapy supportive care
 Oral care
 Prevention and treatment of oral mucositis and stomatitis
 SCA’s Mouth Care during Treatment of Cancer Treatment – Patient
handout
 Coverage of supportive care prescriptions

71. Coverage of Supportive Care
Medications10
 Most supportive care medications are NOT COVERED at SCA
 Supportive care prescriptions filled at SCA = “Internal prescriptions:”
 Dexamethasone, Prednisone, Ondansetron, and Nabilone (EDC) – See next slide!
 Acute hypercalcemia: Zoledronic acid, Pamidronate, and Denosumab (EDC)
 Hypomagnesemia treatment: Magnesium sulfate IV
 Hypokalemia treatment: Potassium chloride IV
 Supportive care prescriptions filled at patient’s community pharmacy
= “External prescriptions:”
 Antibiotic prophylaxis (Ciprofloxacin, Clavulin)
 Antiviral prophylaxis (Sulfatrim, Dapsone, Acyclovir, Valcyclovir)
 LMWH (Dalteparin, Enoxaparin, Tinzaparin) and oral anticoagulants
 Anti-emetics (Metoclopramide, Prochlorperazine, Ranitidine, Olanzapine)
 Skin toxicities (Doxycycline, Hydrocortisone 1%, Lubiderm, Sunscreen)
 RT prescriptions (Lidocaine Jelly 2%, HC 1%, Fucidin 2%, Flamazine)
 Oral care/mucositis/stomatitis/pharyngitis/esophagitis: Lidocaine 2% viscous,
H2RAs, PPis, mouthwashes (Benzydamine 0.15%, Dexamethasone
0.5mg/5mL, Doxepin 0.5%, and Morphine 0.2% as per January 2018
Formulary Bulletin – Call NIHB for prior approval)
 Supplements: Calcium, Magnesium, Potassium, etc.

72. SCA Formulary: Coverage of Dexamethasone,
Prednisone, Ondansetron, and Nabilone10
 Prescriptions must be written by one of our physicians for coverage
at SCA and patients must be on active anticancer treatment
 Includes Pain and Symptom Management Physicians
 Dexamethasone and Prednisone per SCA’s Formulary:
 HISTORICAL
 Examples: As part of nausea/vomiting or chemo regimen on PPO, immune-
related adverse events (Ex arthritis, rash, etc.), appetite-stimulation,
inflammation secondary to RT, cerebral edema, etc.
 Ondansetron per SCA’s Formulary:
 Nabilone is also available for refractory cases by EDC

73. Summary
 Drug interactions represent a challenge to health care
professionals. Current knowledge is often inadequate and
constantly changing. Successful management requires
familiarity with available references and vigilant surveillance.
 It’s important that community pharmacists understand the
indications of the supportive care medications from the
cancer centre to help provide seamless care.
 “Magic/Mucositis/Koolstat” (and other multi-ingredient)
Mouthwashes are a thing of the past!
 Please follow the evidence-based prevention and treatment
algorithms from SCA that use ESMO 2015 CPGs
 Most of these supportive care medications ARE NOT
covered by SCA so it’s important to review the coverage
options available to your patient such as Special Support
Form/Palliative Care Coverage Forms from DPEBB or Drug
Company Programs if finances are a concern

74. References
1) Edwards, S. (2016, August). Common Drug Interactions with Oral Anticancer Agents. Lecture conducted during Oncology Essentials for Pharmacists from the
University of Toronto, Canada.
2) Edwards, S. (2017, January). Advanced Drug Interactions. Lecture conducted during Advanced Oncology for Pharmacists from the University of Toronto,
Canada.
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[Accessed 22 Mar. 2019].
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9) Downy, S., Jensen, B. and Rieger, L. (2019). RxFiles. 11th ed. Saskatoon, SK.: RxFiles.
10) SharePoint. (2019). Preprinted Physician Orders. [online] Available at:
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11) Peterson, D. E., Boers-Doets, C. B., Bensadoun, R. J., & Herrstedt, J. (2015). Management of oral and gastrointestinal mucosal injury: ESMO Clinical Practice
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2017].
13) Pattanayak, L., Panda, N., Dash, M. K., Mohanty, S., & Samantaray, S. (2016). Management of Chemoradiation-Induced Mucositis in Head and Neck Cancers
with Oral Glutamine. Journal of Global Oncology, 2(4), 200-206. doi: 10.1200/JGO.2015.000786.
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75. Questions? Ask now or email
lana.dean@saskcancer.ca 