Pharmacy Services Chemotherapy Induced Nausea and Vomiting Haley Gill, BSP VCH-PHC Pharmacy Resident...

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Chemotherapy Induced Nausea and Vomiting

Haley Gill, BSPVCH-PHC Pharmacy Resident 2009-2010


Outline

• Review the pathophysiology of chemotherapy induced nausea and vomiting (CINV)

• Review the different categories of CINV• Review the pharmacologic agents indicated

for CINV• Review the current guidelines for CINV


Consequences of CINV

• medical complications– electrolyte imbalances– dehydration

• quality of life– impact daily functioning

• compliance with chemotherapy


Pathophysiology of CINV


Pathophysiology of CINV


Classification of CINVAcute within 24 hours of chemotherapy

Delayed occurs > 24 hours after chemotherapy

Anticipatory prior to chemotherapy

Breakthrough while receiving prophylactic antiemetics

Refractory Not responsive to therapy


Neurotransmitter Involvement


Risk Factors

• Young age

• Female

• History of low alcohol intake

• Experience of emesis during pregnancy

• Emetogenic potential of chemotherapeutic agent

• History of motion sickness


Antiemetic Agents

• Serotonin 5-HT3 Receptor Antagonists (5-HT3 RA)

• Corticosteroids• Dopamine-Serotonin Receptor Antagonists• Dopamine Receptor Antagonists• Neurokinin-1 Receptor Antagonists (NK-1

RA)• Benzodiazepines• Cannabinoids


Serotonin 5-HT3 RA’s

• Block 5-HT3 receptors in the CNS and GI tract

• Equivalent in efficacy and toxicities

• More effective for acute CINV

• AE’s: headache, constipation, QTc interval prolongation


Serotonin 5-HT3 RA’s

Available Agents Recommended Dose

Ondansetron (Zofran®) IV: 8 mg or 0.15 mg/kg

PO: 8 - 24 mg

dolasetron (Anzemet®) IV: 100 mg or 1.8 mg/kg

PO: 100 mg

granisetron (Kytril®) IV: 1 mg or 0.01 mg/kg

PO: 1 - 2 mg

**single-daily dose schedules are similar in efficacy to multiple-daily dosing**


Corticosteroids

• Dexamethasone (Decadron®)

• Dose: 8 - 20 mg IV or PO

• Effective for both acute and delayed CINV

• MOA: unknown

• AE’s: Insomnia, hyperglycemia, heartburn


Dopamine-Serotonin Receptor Antagonists

• Metoclopramide (Maxeran®) • 10-30 mg IV/PO Q4-6H ac

• Domperidone (Motilium®)• 10-20 mg PO Q4-6H ac

doses = dopamine antagonist effects doses = serotonin antagonist effects

• AE’s: sedation, EPS, diarrhea• Diphenhydramine (Benadryl®) may EPS


Dopamine Receptor Antagonists

• prochlorperazine (Stemetil®)• 5 -10 mg IV/PO Q6H

• haloperidol (Haldol®)• 0.5 – 2 mg PO/SC Q6-12H

• MOA: block dopamine receptors in the CTZ

• AE’s: EPS, disorientation, sedation


Neurokinin-1 Receptor Antagonists• Aprepitant (Emend®), Fosaprepitant (IV)

• Dose: 125 mg PO on day 1 then 80 mg PO daily on days 2 & 3

• MOA: blocks NK-1 receptor in brainstem emetic center & GI tract

• AE’s: fatigue, asthenia, hiccups

• Drug interactions: dose of dexamethasone by 50%


Other AgentsAgent Dose Use

Lorazepam (Ativan ®)

0.5 - 2 mg IV/PO/SL Anticipatory N&V

Cannabinoids• dronabinol (Marinol®)• nabilone (Cesamet®)

2.5 – 10 mg PO TID - QID

Refractory & Breakthrough N&V

Olanzapine (Zyprexa®)

2.5 – 10mg PO hs Acute, Delayed & Refractory N&V

Gabapentin (Neurontin®)

Delayed


Chemotherapy Emetic Risk GroupsHigh Risk in nearly all patients (>90%)

• Cyclophosphamide (high dose), cisplatin

Moderate Risk in 30% to 90% of patients• Daunorubicin, cytarabine (high dose), melphalan (high dose), azacitadine

Low Risk in 10% to 30% of patients• fludarabine, cytarabine (low dose)

Minimal Fewer than 10% at risk• bortezomib, vincristine, hydroxyurea


Guidelines

• Multinational Association of Supportive Care in Cancer (MASCC)

• American Society of Clinical Oncology (ASCO)

• National Comprehensive Cancer Network (NCCN)


Highly Emetogenic ChemotherapyAcute Delayed

MASCC 5-HT3RA + dexamethasone + aprepitant

Dexamethasone + aprepitant

ASCO 5-HT3RA + dexamethasone + aprepitant

Dexamethasone + aprepitant

NCCN 5-HT3RA + dexamethasone + aprepitant ± lorazepam

Dexamethasone + aprepitant ± lorazepam


Moderately Emetogenic Chemotherapy

Acute Delayed

MASCC 5-HT3RA + dexamethasone

Dexamethasone or 5-HT3RA

ASCO 5-HT3RA + dexamethasone

Dexamethasone or 5-HT3RA

NCCN 5-HT3RA + dexamethasone ± lorazepam

Dexamethasone or 5-HT3RA ± lorazepam


Low Emetogenic Chemotherapy

Acute Delayed

MASCC dexamethasone No Routine Prophylaxis

ASCO dexamethasone

NCCN dexamethasone ± lorazepam orprochlorperazine ± lorazepam ormetoclopramide ± lorazepam


Minimal Emetogenic Chemotherapy

Acute Delayed

MASCC No Routine Prophylaxis

No Routine Prophylaxis

ASCO

NCCN


Rescue Therapy

• Add an agent from another class

• phenothiazine, metoclopramide, or dexamethasone

• 5-HT3 RA unlikely to be beneficial if N & V developed with 5-HT3 RA prophylaxis

• Aprepitant NOT for established N & V

• Consider non-chemo causes


Refractory Therapy

• Consider adjusting pre and post chemo regimen

• Little data

• Some evidence for aprepitant & palonosetron (not in Canada)


Patient Education

• Very important!!

• Instruct patients to take their rescue drugs when nausea first begins

• May need to use regularly scheduled rescue drugs

• Additional doses of 5-HT3 RA not more effective than other rescue drugs


CostDrug Cost/day

Aprepitant ~$33.00, $99.60 (tri-pack)

Ondansetron IV $1.80

PO $8.70

Dexamethasone IV $1.52

PO $1.64

Lorazepam IV $0.48

PO $0.05

Metoclopramide IV $11.60

PO $0.72

Prochlorperizine IV $4.68

PO $0.56


Questions?


References1. Kris MG, et al. American Society of Clinical Oncology Guideline for

Antiemetics in Oncology: Update 2006. J Clin Oncol 2006;24(18):2932-47

2. Hesketh PJ. Chemotherapy-Induced Nausea and Vomiting. N Engl J Med 2008;358:2482-94

3. Baker PD, et al. The Pathophysiology of Chemotherapy-Induced Nausea and Vomiting. Gastroenterology Nursing 2005;28(6):469-80

4. Navari RM. Pharmacological Management of Chemotherapy-induced Nausea and Vomiting: Focus on Recent Developments. Drugs 2009;69(5):515-33

5. Jordan K, et al. Guidelines for Antiemetic Treatment of Chemotherapy-Induced Nausea and Vomiting: Past, Present, and Future Recommendations Oncologist 2007;12;1143-1150

6. Multinational Association of Supportive Care in Cancer Antiemetic Guidelines (last update: March 2008). Available at www.mascc.org

7. National Comprehensive Cancer Network Antiemetic Guidelines 2007. Available at www.nccn.com


Emetic Risk

Prophylaxis of acute CINV on day of chemo administration

Prophylaxis of delayed CINV

High 5-HT3RA + dexamethasone + aprepitant Days 2 & 3 after Chemotherapy: dexamethasone + aprepitant

Moderate Anthracycline + Cyclophosphamide:

5-HT3RA + dexamethasone + aprepitant Days 2 & 3 after chemotherapy: aprepitant

All other regimens of moderate emetic risk:

5-HT3RA + dexamethasone Days 2-4 after chemotherapy: dexamethasone or 5-HT3RA

Low Dexamethasone None

Minimal None None

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Pharmacy Services Chemotherapy Induced Nausea and Vomiting Haley Gill, BSP VCH-PHC Pharmacy Resident...

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