WHAT ORAL ANTINEOPLASTIC AGENTS MEAN … ORAL ANTINEOPLASTIC AGENTS MEAN FOR YOUR PATIENTS, ... diarrhea 29 Multifaceted and ... ASCO=American Society of Clinical Oncology,

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WHAT ORAL ANTINEOPLASTIC AGENTS MEAN FOR YOUR PATIENTS, YOUR STAFF, AND YOUR PHARMACY: A REVIEW OF COMMON ORAL

AGENTS, PROPER HANDLING, AND

SUPPORTIVE CAREKelsey Mulverhill, PharmD and Ai Thi Nguyen, PharmD Oregon State Pharmacy AssociationPGY2 Oncology Pharmacy Residents Lane County Mid-Winter CE SeminarOregon Health & Science University February 19, 2017

Disclosure

� Kelsey Mulverhill and Ai Thi Nguyen have no actual or potential conflicts of interest in relation to this program.

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Objectives

1. Identify common side effects for the oral oncolytic agents

that are presented.

2. Properly counsel patients on supportive therapies to

reduce complications from oral oncolytic agents.

3. Describe standard precautions every pharmacy staff

member must take when handling an oral oncolytic

medication.

4. Given a patient case, recommend at least two patient

counseling points on how an oncolytic medication should

be handled, stored, and administered by the patient

and/or caregiver.

5. Given a patient case, list at least two resources for references a pharmacist may use to determine if an

oncolytic agent may interact with a patient’s other

medications.

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Presentation outline4

Questions and

introduction

Common side effects

Supportive care

Standard handling

precautions

Pharmacy staff

resources

Break

Question #1

� When preparing agents for dispensing or when handling oral oncolytics, pharmacy staff should wash their hands, then don gloves. After the oral oncolytic agent is placed in its final container for

dispensing, staff should wash hands again and wash any material that touched the oral oncolytic agent.

a) True

b) False

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Question #2

� A patient comes to your pharmacy to fill fluconazole 200 mg PO once daily for 7 days for completion of treatment for Candida albicans pyelonephritis. The patient is also taking imatinib 400 mg PO daily for

chronic myeloid leukemia. What resources would you use to determine if any drug interactions exist?

a) Lexi-Comp or other drug database

b) Imatinib package insert

c) Oncology pharmacist colleague

d) All of the above

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Question #3

� When educating patients/caregivers on oral oncolytic administration, which of the following general recommendations is INCORRECT?

a) Keep away from children and pets

b) Caregivers should wear gloves when handling

c) May be stored in pill boxes, but should be separate

from other medications

d) May chew, crush, cut, or dissolve

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Question #4

� Which of the following is a possible side effect of anti-estrogen therapies for estrogen-receptor positive breast cancer?

a) Hot flashes

b) Hallucinations

c) Neutropenia

d) Arrhythmias

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Question #5

� A patient comes to your pharmacy asking for your recommendation for GERD symptoms. They are currently taking dasatinib. What over-the-counter medication would you recommend?

a) Ranitidine

b) Omeprazole

c) An antacid, such as calcium carbonate

d) None of the above are recommended

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ORAL ONCOLYTICS:COMPLICATIONS AND MANAGEMENT

Introduction

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Oral oncolytic drugs

Common classes of oral

oncolytics12

� Tyrosine kinase inhibitors (TKIs)

� Immunomodulatory drugs (IMiDs)

� Hormone therapy

� Selective estrogen receptor modulators (SERMs)

� Selective estrogen receptor down-regulators (SERDs)

� Aromatase inhibitors

� Non-steroidal anti-androgens

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Major oral oncolytic

complications13

� The most prevalent complications arising from cancer treatments are

� Cutaneous reactions

� Nausea & vomiting

� Gastrointestinal complaints

� Myelosuppression

CUTANEOUS REACTIONS

Major oral oncolytic complications

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Cutaneous reactions15

� Common with TKIs

� Epidermal growth factor receptor (EGFR) TKIs� Afatinib (Giotrif®)

� Erlotinib (Tarceva®)

� Gefitinib (Iressa®)

� Bcr-Abl TKIs� First generation

� Imatinib (Gleevec®)

� Second generation

� Bosutinib (Bosulif®)

� Dasatinib (Sprycel®)

� Nilotinib (Tasigna®)

Drug Des Devel Ther 2008;2:215-219.

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� TKIs for renal cell carcinoma

� Sorafenib (Nexavar®)

� Sunitinib (Sutent®)

� Immunomodulatory drugs

� Lenalidomide (Revlimid®)

� Thalidomide (Thalomid®)

� Antimetabolite

� Capecitabine (Xeloda®)

Drug Des Devel Ther 2008;2:215-219.Arch Dermatol 2006;142(10):1298-1302.


� Rashes can present as acneiform, papulomacular, or pustular

� May affect any part of the body

� Bcr-Abl TKIs

� Milder cutaneous side effects compared to EGFR inhibitors

� Hand-foot syndrome (HFS) is a distinct cutaneous manifestation

� Associated with sorafenib, sunitinib, and

capecitabine

Drug Des Devel Ther 2008;2:215-219.Arch Dermatol 2006;142(10):1298-1302.

http://www.cancernetwork.com/s ites/default/f iles/cn_import/1913258.png

http://jgo.amegroups.com/article/viewFile/1285/html/7174

http://www.oncotherapynetwork.com/


Grade NCI definition2 Management

1 Mild <10% BSA with or without

symptoms (e.g., pruritus, burning, tightness)

Oral antihistamines1,2,3

Topical antipruritics1

2 Moderate 10-30% BSA with or without

symptoms


Topical steroids1,2,3

3 Severe >30% BSA with or without

associated symptoms


Topical steroids1,2,3

Antibiotics1,2,3

4 Life-

threatening

Papules or pustules covering any

part of the body which are associated with extensive super-

infection

Discontinue therapy

Oral steroids3

Antibiotics1,2,3

5 Death Rash resulting in death -1European Society for Medical Oncology.2Curr Oncol 2011;18(3):126-138.3J Natl Compr Canc Netw 2009;7 Suppl 1:S5-21. BSA=body surface area

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Cutaneous reaction

management

� Oral antihistamines

� Topical antihistamines/ antipruritics

� Topical steroids

� Hydrocortisone 1-2.5%

� Beclometasone 0.025-

0.1%

� Clobetasol 0.05%

� Topical antibiotics

� Clindamycin 2%

� Antibiotics

� Doxycycline 100 mg PO BID

� Minocycline 100 mg

PO daily

� Tetracycline 500 mg

PO BID

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Curr Oncol 2009;16(1):16–26.Drugs 2015;75(12):1335-48.

Cutaneous reaction

management20

Use alcohol-free, fragrance-free, hypoallergenic

moisturizer

Drink plenty of fluids (at least 2L

per day) and avoid caffeine

Apply PABA-free sunscreen of at

least SPF 30 and wear protective

clothing

Avoid hot showers, walking

barefoot, and tight-fitting footwear

Wear hypoallergenic

makeup

Use mild detergents and skin cleansers

Don’t use over-the-counter anti-acne medications

NAUSEA & VOMITING (N&V)


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Nausea & vomiting22

� Risk factors

� Female

� Younger age

� History of emesis during pregnancy

� Motion sickness

� High anxiety

� History of alcohol use is protective against chemotherapy-induced N&V

National Comprehensive Cancer Network. Antiemesis (Version 2.2016).

Nausea & vomiting: mechanism of action of neurotransmitters

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Vomiting Center

Serotonin

Histamine

Acetyl-choline

Substance P

Dopamine

N Engl J Med 2008;358:2482-2494.N Engl J Med 2005;352:817-825.

Nausea & vomiting24

Anticipatory Acute Delayed

Chemotherapy

0-24 hours >24 hours

Psychological

Treatment

BehavioralLorazepam

SerotoninSubstance P

DopamineHistamine

Treatment

5-HT3 antagonistNK-1 receptor antagonist

DexamethasoneDopamine antagonist

Substance P

DopamineHistamine

Treatment

NK-1 receptor antagonistDopamine antagonist

Other receptors


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Nausea & vomiting: emetogenic potential of common agents

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Emetogenic

potential

Emetogenic

risk

Examples

Minimal <10% � Most TKIs

� Thioguanine (Tabloid®)� Hydroxyurea (Hydrea®)

Low 10-30% � Some TKIs

� Lenalidomide (Revlimid®)� Thalidomide (Thalomid®)

Moderate 30-90% � Temozolomide

(Temodar®)� Vinorelbine (Navelbine®)

� Bexarotene (Targretin®)

� Lomustine (CeeNU®)

High >90% � Procarbazine (Matulane®)National Comprehensive Cancer Network. Antiemesis (Version 2.2016).

Nausea & vomiting prevention and treatment

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Emetogenicity

Acute N&V prevention Breakthrough N&V

Minimal Treat only if symptoms are presentAdd one agent from a different class� Olanzapine� Lorazepam

� Cannabinoid� Haloperidol� Metoclopramide� Scopolamine� Phenothiazine� 5-HT3 antagonists� Steroids

LowDexamethasone, metoclopramide, prochlorperazine, or 5-HT3

antagonist

Moderate

5-HT3 antagonist� Dolasetron 100 mg IV days 1-3� Granisetron 2 mg or 1 mg IV/PO BID days 1-3� Ondansetron 16-24 mg PO days 1-3

� Palonosetron 0.25 mg IV onceAND

� Dexamethasone 12 mg IV/PO day 1, 8 mg IV/PO days 2-3WITH/WITHOUT NK-1 antagonist

High

5-HT3 antagonist as aboveANDNK-1 antagonist

� Aprepitant 125 mg PO day 1, 80 mg PO day 2-3

� Fosaprepitant 150 mg IV (Day 1 only)� Rolapitant 180 mg PO

AND� Dexamethasone 12 mg IV/PO day 1, 8 mg IV/PO days 2-4

Alternatives� Olanzapine 10 mg

PO days 1-3� Palonosetron 0.25

mg IV once� Dexamethasone 20

mg IV/PO once


EPS

Movement initiation without fine motor

tuning

Nausea & vomiting: antiemetic side effects

� Extrapyramidal symptoms (EPS) are a common side effect of several antiemetics

� Prochlorperazine

� Promethazine

� Chlorpromazine

� Haloperidol

� Droperidol

� Metoclopramide

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� Treatment� Diphenhydramine 25-

50mg PO or IV q4-6h

� Benztropine 1-2mg IV

or IM x1, followed by 1-

2mg PO daily or BID

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GASTROINTESTINAL COMPLICATIONS


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Gastrointestinal complications: diarrhea

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� Multifaceted and complex pathophysiology

� Impaired absorptive and secretory capacity

� Due to chemotherapy-induced damage to rapidly

dividing crypt cells throughout the intestinal epithelium

� Common offending oral agents

� EGFR inhibitors


J Clin Oncol 2004;22(14):2918-2926.


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� Rule out Clostridium difficile associated diarrhea (CDAD), other infections, and other etiologies

� Carcinoid syndrome

� Irritable bowel disease (IBD)

� Malabsorption

� NCCN and MASCC lack guidelines for the management of diarrhea associated with cancer

treatment

� ASCO published guidelines in 2004

J Clin Oncol 2004;22(14):2918-2926.

ASCO=American Society of Clinical Oncology, MASCC=Multinational Association of Supportive Care in Cancer, NCCN=National Comprehensive

Cancer Network

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� Management

� Hold chemotherapy

� Replace fluids and electrolytes

� Anti-diarrheals

� Reduce chemotherapy dose

� Associated with a decreased overall and disease-free survival

J Clin Oncol 2004;22(14):2918-2926.


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J Clin Oncol 2004;22(14):2918-2926.

Agent Mechanism of action Dose

Loperamide(Imodium®)

Opioid agonist: decreases intestinal

motility

4 mg PO x1, then 2 mg PO q2-4h

� No maximum daily dose

Diphenoxylate/atropine (Lomotil®)

Opioid agonist/ anticholinergic:

decreases intestinal motility

2.5 mg/0.025 mg: 2 tablets PO q6h

� Max daily dose = 20 mg

Tincture of opium Opioid agonist: decreases intestinal

motility

10 mg/mL: 0.6 mL PO q6h

Octreotide (SandoSTATIN®)

Synthetic somatostatin analog: decreases

secretion of vasoactive intestinal peptide (VIP),

prolongs intestinal transit time, and

100-150 mcg subcutaneously TID

Gastrointestinal complications: constipation

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� Common offending oral agents

� Hormonal agents� Anastrozole (Arimidex®)

� Letrozole (Femara®)

� Exemestane (Aromasin®)

� Bicalutamide (Casodex®)

� TKIs� Sorafenib (Nexavar®)

� Sunitinib (Sutent®)

� Immunomodulatory Drugs (IMiDs)

� Supportive therapy� Ondansetron (Zofran®)

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Gastrointestinal complications: constipation

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MYELOSUPPRESSION


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Common offending agents

� Antimetabolites


� 6-mercaptopurine

(Purinethol®)

� Methotrexate (Trexall®)

� Thioguanine (Tabloid®)

� EGFR TKIs

� Bcr-Abl TKIs

� Immunomodulatory drugs (IMiDs)

� Everolimus (Afintor®)

� Hydroxyurea (Hydrea®)

� Idelalisib (Zydelig®)

� Temozolomide(Temodar®)

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Myelosuppression37

� Anemia

� Occurs in 30-90% of patients with cancer

� Pathophysiology

� Bone marrow infiltration

� Iron sequestration secondary to upregulation of cytokines

� Chronic blood loss at tumor site

� Chemotherapy-induced depression of erythropoietin

production through the kidneys

� Chemotherapy-induced myelosuppression

National Comprehensive Cancer Network. Cancer- and Chemotherapy-Induced Anemia (Version 2.2016)

Myelosuppression38

� Anemia

� Erythropoiesis-stimulating agents (ESAs)

� Epoetin Alfa (Procrit®)

� 150 units/kg subcutaneously three times weekly

� 40,000 units subcutaneously once weekly

� Darbepoetin Alfa (Aranesp®)

� 300 mcg subcutaneously once weekly


Myelosuppression39

� Anemia

� Iron supplementation

� Ferrous sulfate 325 mg PO TID

� Ferric carboxymaltose (Injectafer®) 750 mg IV x2 doses q7days

� Iron dextran (INFeD®) 100 mg/day IV (usually until 1000 mg

total dose is reached)

� Iron sucrose (Venofer®) 100-400 mg IV (usually until 1000 mg

total dose is reached)

� Sodium ferric gluconate (Ferrlecit®) 125 mg/dose IV


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Myelosuppression40

� Febrile neutropenia

� Temperature >38.3oC (101oF) or >38oC (100.3oF) for

more than one hour

AND

� Absolute neutrophil count (ANC) <500 cells/mcL

OR

� ANC <1000 cells/mcL with expected drop to <500

cells/mcL within 48 hours


Myelosuppression41

Multinational Association of Supportive Care in Cancer (MASCC)

Severity of illness� No symptoms or mild symptoms

� Moderate symptoms

5

3

No hypotension 5

No chronic obstructive pulmonary disease

4

Solid tumor or no fungal infection 4

No dehydration 3

Outpatient at onset of fever 3

Age <60 years old 2


� MASCC score >21 indicates low risk of acute bacterial infection

Myelosuppression42

� Low risk patients can be treated on an outpatient basis:

� Amoxicillin/clavulanate 875 mg PO BID and ciprofloxacin

500 mg PO BID

� Clindamycin 300 mg PO q6h is substituted for penicillin

allergy

� If febrile neutropenia is treated on an outpatient basis:

� Counsel patients that they need to have daily follow-up

and will need to contact their provider immediately if

their condition worsens

� Do not advise patients to go to the ED unless directed

by their provider

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OTHER UNIQUE COMPLICATIONS WITH ORAL ONCOLYTICS


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Venous thromboembolism44

� Risk factors

� Active cancer

� Post-surgical patients

� Indwelling catheters

� Smoking

� Obesity

� Common offending agents

� TKIs

� IMiDs in combination with dexamethasone

� Selective Estrogen Receptor Modulators (SERMs)

National Comprehensive Cancer Network. Cancer-Associated Venous Thromboembolic Disease. (Version 1.2016).

Venous thromboembolism45

National Comprehensive Cancer Network. Cancer-Associated Venous Thromboembolic Disease. (Version 1.2016).

� Mechanical prophylaxis

� Intermittent pneumatic compression (IPC) devices

� Graduated compression stockings (GCS)

Agent Standard dosing Dosing in obesity (BMI ≥40 kg/m2)

Dalteparin 5000 units SC daily Consider 7500 units SC daily

Enoxaparin 40 mg SC daily Consider 40 mg SC q12h

Fondaparinux 2.5 mg SC daily Consider 5 mg SC daily

Unfractionatedheparin

5000 units SC q8-12h Consider 7500 units SC q8h

Aspirin 81-325 mg daily

Warfarin Adjusted to INR 2-3

SC=subcutaneously

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Hormonal agents46

� Selective Estrogen Receptor Modulator (SERMs)

� Tamoxifen citrate (Soltamox®)

� Raloxifene (Evista®)

� Toremifene citrate (Fareston®)

� Selective Estrogen Receptor Down-Regulators (SERDs)

� Fulvestrant (Faslodex®)

� Aromatase inhibitors

� Anastrozole (Arimidex®)

� Letrozole (Femara®)

� Exemestane (Aromasin®)

Lexi-Comp OnlineTM; Accessed January 27, 2017.

Estrogen47

� Primarily produced by the ovaries

� Adrenal glands produce androgens that are converted to estrogen through aromatase

� Aromatase is located in the ovarian tissue, adipose

and skin fibroblasts, bone, and the brain

� Types of Estrogen

� Estradiol: predominant form in premenopausal women

� Estrone: precursor to estradiol, predominant form in

postmenopausal women

� Estriol: estrogen secreted by placenta during pregnancy

FASEB J 2008;22(9):3328-3336.

Estrogen48

FASEB J 2008;22(9):3328-3336.

LH

ACTH

EstradiolAndrostenedione

Estrone

Estradiol

Testosterone

Xaromatase inhibitors

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Estrogen deprivation side

effects49

� Menopausal symptoms

� Hot flashes

� Night sweats

� Changes in mood

� Arthralgia

� Osteoporosis

� Hypertension

Lexi-Comp OnlineTM; Accessed January 27, 2017.

Menopausal-like symptom management

50

� Hot flashes and night sweats

� Dress in layers, temperature control, and avoid triggers

� Regular exercise

� SSRIs/SNRIs or gabapentin

� No hormone replacement therapy

� Arthalgias

� Exercise and/or acupuncture

� Switch to another aromatase inhibitor or SERM if able

� NSAIDs – consider patient’s comorbidities

� Supplement vitamin D if low

Lexi-Comp OnlineTM. Accessed January 27, 2017.Mayo Clin Proc 2010;85(6):560-566.Curr Oncol 2010;17(1):81-86.

NSAID=non-steroidal anti-inflammatory drug, SERM=selective estrogen receptor modulator,

SSRI=selective serotonin reuptake inhibitor, SNRI=serotonin-norepinephrine reuptake inhibitor

Bone health management51

� Cancer causes � bone metastases

� Majority of cancers have the potential to metastasize to

bones

� Most common: prostate, lung, and breast cancers

� Drug causes � treatment-induced bone loss

� Hormone therapy

� Steroid use for more than 6 months

Ann Oncol 2014;25 Suppl 3:iii124-137.

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Bone health management52

� Bisphosphonates� Zoledronic acid (Zometa®)

� 4 mg IV every 3-6 months depending on cancer type and chemotherapy

� Pamidronate (Aredia®)� 90 mg IV every month if used for bone metastases

� 60 mg IV every 3 months if used for prevention of androgen deprivation-induced osteoporosis

� Denosumab (Xgeva®, Prolia®)� Bone metastases from solid tumors: 120 mg

subcutaneously every 4 weeks

� Treatment-induced bone loss in breast and prostate cancer: 60 mg subcutaneously every 6 months

� Calcium 1000 mg PO daily + vitamin D 1000-2000 units PO daily

Ann Oncol 2014;25 Suppl 3:iii124-137.

References53

1. Huang X, Patel S, Ahmed N, et al. Severe toxicity of skin rash, fever and diarrhea associated with imatinib: case report and review of skin toxicities associated with tyrosine kinase inhibitors. Drug Des Devel Ther 2008;2:215-219.

2. Sviggum HP, Davis MD, Rajkumar SV, et al. Dermatologic adverse effects of lenalidomide therapy for amyloidosis and multiple myeloma. Arch Dermatol 2006;142(10):1298-1302.

3. Burtness B, Anadkat M, Basti S, et al. NCCN Task Force Report: management of dermatologic and other toxicities associated with EGFR inhibition in patients with cancer. J Natl Compr Canc Netw 2009;7(Suppl 1):S5-21.

4. Hirsh V. Managing treatment-related adverse events associated with EGFRtyrosine kinase inhibitors in advanced non-small-cell lung cancer. Curr Oncol 2011;18(3):126-138.

5. Melosky B, Anderson H, Burkes RL. Pan Canadian rash trial: a randomized phase III trial evaluating the impact of a prophylactic skin treatment regimen on epidermal growth factor receptor-tyrosine kinase inhibitor-induced skin toxicities in patients with metastatic lung cancer. J Clin Oncol 2016;34(8):810-815.

6. Benson AB, Ajani JA, Catalano RB, et al. Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol 2004;22(14):2918-2926.

7. Antiemesis (Version 2.2016). In: National Comprehensive Cancer Network. Accessed May 2016.8. Cancer- and Chemotherapy-Induced Anemia (Version 2.2016). In: National Comprehensive Cancer

Network. Accessed May 2016.9. Prevention and Treatment of Cancer-Related Infections (Version 1.2016). In: National Comprehensive Cancer

Network. Accessed January 2016.10. Watson CS, Jeng Y, Kochukov M. Nongenomic actions of estradiol compared with estrone and estriol in pituitary

tumor cell signaling and proliferation. FASEB J 2008;22(9):3328-3336.11. Gralow JR, Biermann JS, Farooki A, et al. NCCN Task Force report: bone health in cancer care. J Natl Compr

Canc Netw 2013;11(Suppl 3):S1-50.12. Lexicomp Online®, Lexi-Drugs®, Hudson, Ohio: Lexi-Comp, Inc.; Accessed January 27, 2017.13. Coleman R, Body JJ, Aapro M, et al. Bone health in cancer patients: ESMO Clinical Practice Guidelines. Ann

Oncol 2014;25(Suppl 3):iii124-137. 14. Files JA, Ko MG, Pruthi S. Managing aromatase inhibitors in breast cancer survivors. Mayo Clin Proc

2010;85(6):560-566.

Questions and a short break54

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Oral oncolytics55

� Why do we care about oral oncolytics?

� 25% of the chemo agents in the research pipeline are

oral

� >30 new oral oncolytics approved since 1998

� 80% of patients would prefer oral oncolytics over other

routes

� How many oral oncolytic agents are available?

� A lot!

J Oncol Pract 2014;doi.10.1200/ JOP.2013.001183.

Introduction: oral oncolytics

� Advantages?

� Convenience

� Non-invasive

� Less complex

� Improved quality of life

� Disadvantages?

� Cost

� Detailed counseling

� Decreased follow up

� Unknown adherence

56

Pharmacy Times website. Updated August 15, 2009. Accessed December 23, 2016.

HANDLING AND STORAGE OF ORAL ONCOLYTICS

Standard precautions

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Standard precautions58

� The healthcare setting has the largest and most diverse mix of chemicals that are hazardous to humans

� Exposure can arise from

� Surface contamination

� Inhalation

� Ingestion via hand-to-mouth contact

� Injection

The main vector of exposure is dermal contact with drugs/drug packaging and through indirect contact by contaminated surfaces

The Oncology Nurse 2014;7(4):1-17.


� A 2003 study documented the presence of drugs and metabolites in the urine of exposed healthcare workers

� Even in those not directly involved in compounding

� Associations have been shown between

� Surface contamination presence of drugs in urine

� Exposure genotoxicity

The Oncology Nurse 2014;7(4):1-17.Int Arch Occup Environ Health 2003;76(1):5-10.


� Significance

� Guidelines for safe and appropriate handling are

imperative

� Accidental exposure to oral oncolytics can occur at

various stages during handling

Transport Unpacking Storage Handling Dispensing Administration Disposal

J Oncol Practice 2011;7(1):7-12.

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� United States Pharmacopeia (USP) Chapter <800>

� Proposed by Compounding Expert Committee and

Compounding with Hazardous Drugs Expert Panel

� Created to identify requirements for hazardous drugs

� Aim to protect

USP website. Accessed January 22, 2017.

Receipt StorageMixing, preparing,

compoundingDispensing Administration

PatientsHealthcare personnel

The environment


� USP <800> unpacking and storage

Designate separate areas for unpacking and handling

Hazardous drug (HD) storage

areas and containers should

be labeled as such

Unless in final unit dose

package, store HDs separately

from other inventory

Store, unpack, compound, or manipulate in

negative pressure areas

Do not store HDs on the floor


Unpacking may also occur in neutral pressure

areas


� USP <800> handling and personal protective equipment (PPE)

Activity Gloves Gown Hair, face, and shoe covers

Eye and face protection

Respiratoryprotection

Receiving intact supplies

+

Transportingintact supplies

+

Stocking +

Non-sterile compounding

+ + +

Spills + + + + +

Receiving brokensupplies

+ + + + +

+=required


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� USP <800> handling and personal protective equipment (PPE)

� Gloves

� Disposal of PPE

USP website. Accessed January 22, 2017.MMWR 2002;51(No. RR-16):1-48.

Powder-free

Perform hand hygiene before donning gloves

AND after removing gloves

Two pairs when compounding, disposing, or

managing a spill

Incinerate at regulated medical waste incinerator

Do NOT place in red bag or sharps

container


� USP <800> dispensing

� HDs not requiring alteration before delivery to the patient

may be dispensed without requirements for containment

unless required by manufacturer

Unit of use or unit dose packaging

Transfer from manufacturer’s

package to prescription container

Count HDs carefully, using dedicated, clean

equipment

Do NOT useautomated counting

machines

Counting coated tablets or capsules

does not require compounding hoods or

isolators as long as they are not altered or

brokenUSP website. Accessed January 22, 2017.


� USP <800> deactivation, decontamination, cleaning, and disinfection

� Should be appropriate for the type of HD, location, and

surface material


Cleaning step Purpose Agents

Deactivation Render compound inert or inactive As listed in HD labelingIf none listed, sodium hypochlorite or EPA-registered oxidizer

Decontamination

Remove inactivated residue Sterile alcohol, sterile water, peroxide, or sodium hypochlorite

Cleaning Remove organic and inorganic material

Germicidal detergent and sterile water

Disinfection Destroy microorganisms Sterile alcohol or EPA-registereddisinfectant

EPA=Environmental Protection Agency

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� USP <800> disposal

� Comply with all applicable federal and state regulations

� Train all staff who perform routine custodial waste

removal and cleaning activities appropriately


Goal = protect staff and the environment to prevent contamination

ORAL ONCOLYTICS

Caregiver and patient counseling

68

Caregiver and patient

counseling69

� Important for providers to

� Components of pharmacist counseling

J Oncol Practice 2011;7(1):7-12.

Review all current medications with the

patient and/or caregiver

Provide clear dosing instructions

Include what to do when a dose is skipped

or if vomiting/spillage occurs

Reassess and discuss medication and food interactions during prescription refill

Provide information on required monitoring, disposal, and side effect management

Provide access to written protocol and

treatment plan from the institution where

treatment was initiated

May come from ambulatory clinic pharmacists or oncologists

Obtain patient consent for oral oncolytics

Consult and assess patient ability to take

oral therapy and comply with their treatment plan

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Caregiver and patient counseling: Do’s for oral oncolytics

70

� Review package label, checking medication name and dosage

� Ensure you understand when and how to take the medication

� Administer the medication as instructed

� Transport and store medications as instructed on the label

J Oncol Practice 2011;7(1):7-12.US Pharm 2014;39(8):4-7.


71

� Consider pill boxes

� Use separate boxes for oncolytic and non-oncolytic

medications

� Report all medications and dietary requirements to

healthcare providers

� Inform other healthcare providers that you are on an oral

oncolytic



72

� Use gloves if possible and wash hands thoroughly before and after glove application

� If no gloves, tip tablets and capsules from

container/blister pack directly in disposable medicine

cup

� Caregivers should wear gloves at all times while

handling oral oncolytics and potentially contaminated

items to minimize exposure


2/1/2017

25


73

� Keep a journal of side effects

� Make a list of side effects for which healthcare providers

have to be contacted immediately

� Report any overdosing immediately

� Return wet, damaged, unused, discontinued, or expired medications to the pharmacist or hospital for disposal



74

� Keep information ready for necessary action in events of accidental exposure (ex. vomiting or accidental ingestion)

� Minimize number of people who come in contact

with oral oncolytics

� Double-flush the toilet during use of and for 4-7 days after stopping oral oncolytics


Caregiver and patient counseling: Don’ts for oral oncolytics

75

� Leave in open areas, near water, direct sunlight, or in easy access by children or pets

� Store in areas where food or drinks are stored or consumed

� Crush, break, or chew

� Discard down the toilet or in the garbage


2/1/2017

26

Caregiver and patient counseling: Don’ts for oral oncolytics

76

� Double-up on doses, unless instructed by healthcare provider

� Skip doses unless instructed by healthcare provider

� Share medications

� Assume that oral is safer than intravenous chemotherapy


General patient and caregiver resources

77

� American Cancer Society

� http://www.cancer.org/treatment/treatments-and-side-

effects/treatment-types/chemotherapy/oral-chemotherapy.html

� Dana-Farber Cancer Institute

� http://www.dana-farber.org/Health-Library/Oral-chemotherapy-

fact-sheet.aspx

� OncoLink

� https://www.oncolink.org/cancer-treatment/chemotherapy/ chemotherapy-safety/taking-oral-anti-cancer-medications-at-

home

� Michigan Society of Hematology & Oncology

� http://www.msho.org/aws/MSHO/asset_manager/get_file/45157

FOOD AND DRUG INTERACTIONS

Pharmacy staff resources

78

2/1/2017

27

Drug or food interaction identification

79

1• Is the oral oncolytic agent new to the patient?

2• Has the patient recently started or stopped any new medications?

3• What medications is the patient taking, including prescription, over the counter,

supplements, herbals, or alternative therapies?

4

• Does any medication induce or inhibit CYP enzymes or P-glycoprotein, interfere with GI absorption, affect immune system function or blood counts, or inhibit the conversion to the active drug?

5

• If unsure of any question above, consult a drug database (Natural Medicines, Lexi-Comp, Micromedex, etc.), primary literature, package insert, and/or oncology pharmacist colleague.

Select interaction: TKIs and CYP inhibitors

80

� Strong inhibitors of CYP3A4 decrease the clearance of all TKIs

� Monitor for increased TKI side effects when CYP

inhibitors are used concomitantly

� Anemia, neutropenia, acneiform rash, nausea, vomiting,

and diarrhea may be increased

� Decreased TKI exposure by CYP enzyme induction may cause clinically relevant ineffectiveness of treatment

Lancet Oncol 2014;15:e315-326. TKI=tyrosine kinase inhibitor

Select interaction: TKIs and other QTc-prolonging medications

81

EKG=electrocardiogram, SSRI=selective serotonin reuptake inhibitor, SNRI=serotonin-norepinephrine

reuptake inhibitor, TCA=tricyclic antidepressant, TKI=tyrosine kinase inhibitor

Blood 2010;doi.org/10.1182/blood-2010-07-294330.

� TKIs commonly cause QTc interval prolongation on EKGs

� Review the patient’s medication list for

� Fluoroquinolones

� Macrolides

� Amiodarone and digoxin

� Metoclopramide

� Azole antifungals

� SSRIs, SNRIs, TCAs, and antipsychotics

2/1/2017

28

Select interaction: tamoxifen and antidepressants

82

� Tamoxifen is converted to it’s active metabolite, endoxifen, by CYP2D6

� SSRIs/SNRIs are inhibitors of CYP2D6

� However, weak inhibitors of CYP2D6 have minimal

effects on the conversion to endoxifen

� For hot flashes associated with tamoxifen

� Recommended venlafaxine, escitalopram, or citalopram

� Weak inhibitors of CYP2D6

BMJ 2010;doi:10.1136/bmj.c693.

SSRI=selective serotonin reuptake inhibitor, SNRI=serotonin-norepinephrine reuptake

inhibitor

Select interaction: TKIs and acid suppressants

83

� Most TKIs require an acidic environment for absorption

� Package inserts and drug databases indicate that

TKIs should not be given with

� PPIs and H2RAs – drug levels may be decreased

� Antacids – okay if given 2 hours before or after the TKI

Lexi-Comp OnlineTM. Accessed January 22, 2017.Lancet Oncol 2014;15:e315-326.

H2RA=histamine-2 receptor antagonist, PPI=proton pump inhibitor, TKI=tyrosine kinase

inhibitor

Increased stomach pH can reduce TKI solubility,

bioavailability, and exposure to the TKI

May result in decreased oncolytic efficacy

In clinical practice, H2RAs may be

given 2 hours after or 10 hours before

TKIs

Food interactions

� As with acid suppressants, the intake of food may alter the pH of the

stomach

� Oral oncolytics have

narrow therapeutic

indices

� Changes in absorption

may lead to harmful

levels or result in

decreased efficacy

84

J Oncol Pract 2014;doi:10.1200/JOP.2013.001183.

Take with food Take on an empty stomach

AltretamineBexaroteneBosutinibCapecitabine

CyclophosphamideExemestaneRegorafenibVorinostat

AbirateroneAfatinibCabozantinibChlorambucil

DabrafenibErlotinibEstramustineLapatinibLomustineMelphalan

MercaptopurineNilotinibPazopanibPomalidomideSorafenibTemozolomide

ThalidomideTrametinibIt is always okay to consult a drug reference

for the most up to date recommendations

2/1/2017

29

Herbals and alternative

medicines85

� May use Natural Medicines database or aboutherbs.com for drug interaction identification

� Consider if any unwanted side effects may exist

Be extremely cautious when recommending herbal medications to patients being treated for cancer

Increased bleeding risk

� Dong quai

� Echinacea

� Fenugreek

� Fish oil

� Garlic

� Ginger

� Ginkgo biloba

� Ginseng

� Green tea

� St. John’s wort

� Valerian

� Vitamin E

� Willow bark

86

Recent Pat Food Nutr Agric 2010;2(1):12-55.

Anticoagulant and

antiplatelet effects

Patients may already be

anemic

Antioxidant activity87

� Cat’s claw

� Coenzyme Q10

� Devil’s claw

� Gingko biloba

� Green tea

� Melatonin


May counteract chemotherapy

oxidizing effects

2/1/2017

30

Immune stimulating effects88

� Bee pollen

� Bitter melon

� Blue-green algae

� Cat’s claw

� Echinacea

� Ginseng

� Spirulina


Especially important to avoid in

hematologic malignancies

References89

1. Segal EM, Flood MR, Mancini RS, et al. Oral chemotherapy food and drug interactions: a comprehensive review of the literature. J Oncol Pract 2014;doi:10.1200/JOP.2013.001183.

2. Mahay H. Oral chemotherapy: patient advantages and challenges. Pharmacy Times website: http://www.pharmacytimes.com/publications/issue/2009/august2009/counselingchemotherapy-0809. Updated August 15, 2009. Accessed December 23, 2016.

3. Weingart SN, Brown E, Bach PB, et al. NCCN task force report: oral chemotherapy. JNCCN 2008;6[Suppl 3]:S1-S14.

4. Goodin S, Griffith N, Chen B, et al. Safe handling of oral chemotherapeutic agents in clinical practice: recommendations from an international pharmacy panel. J Oncol Practice 2011;7(1):7-12.

5. Patel S. Safe handling of chemotherapy for pharmacists. US Pharm 2014;39(8):4-7.6. The United States Pharmacopeial Convention. Briefing: <800> Hazardous drugs–handling in healthcare

settings. USP website: http://www.usp.org/sites/default/files/usp_pdf/EN/m7808_pre-post.pdf. Accessed January 22, 2017.

7. Centers for Disease Control and Prevention. Guideline for hand hygiene in health-care settings: recommendations of the Healthcare Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. MMWR 2002;51(No. RR-16):1-48.

8. Roussel C, Connor TH. Chemotherapy: current and emerging issues in safe handling of antineoplastic and other hazardous drugs. The Oncology Nurse 2014;7(4):1-17.

9. Pethran A, Schierl R, Hauff K, Grimm CH, Boos KS, Nowak D. Uptake of antineoplastic agents in pharmacy and hospital personnel. Part I: monitoring of urinary concentrations. Int Arch Occup Environ Health 2003;76(1):5-10.

10. van Leeuwen RWF, van Gelder T, Mathijssen RHJ, Jansman FGA. Drug-drug interactions with tyrosine kinase inhibitors: a clinical perspective. Lancet Oncol 2014;15:e315-e326.

11. Haouala A, Widmer N, Duchosal MA, Montemurro M, Buclin T, Decosterd LA. Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib, and nilotinib. Blood 2010;doi.org/10.1182/blood-2010-07-294330.

12. Kelly CM, Juurlink DN, Gomes T, et al. Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study. BMJ 2010;doi:10.1136/bmj.c693.

13. Yap KY, See CS, Chan A. Clinically relevant chemotherapy interactions with complementary and alternative medicines in patients with cancer. Recent Pat Food Nutr Agric 2010;2(1):12-55.

[email protected]@ohsu.edu

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