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
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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
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Consequences of CINV
• medical complications– electrolyte imbalances– dehydration
• quality of life– impact daily functioning
• compliance with chemotherapy
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Pathophysiology of CINV
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Pathophysiology of CINV
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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
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Neurotransmitter Involvement
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Risk Factors
• Young age
• Female
• History of low alcohol intake
• Experience of emesis during pregnancy
• Emetogenic potential of chemotherapeutic agent
• History of motion sickness
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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
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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
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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**
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Corticosteroids
• Dexamethasone (Decadron®)
• Dose: 8 - 20 mg IV or PO
• Effective for both acute and delayed CINV
• MOA: unknown
• AE’s: Insomnia, hyperglycemia, heartburn
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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
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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
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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%
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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
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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
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Guidelines
• Multinational Association of Supportive Care in Cancer (MASCC)
• American Society of Clinical Oncology (ASCO)
• National Comprehensive Cancer Network (NCCN)
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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
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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
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Low Emetogenic Chemotherapy
Acute Delayed
MASCC dexamethasone No Routine Prophylaxis
ASCO dexamethasone
NCCN dexamethasone ± lorazepam orprochlorperazine ± lorazepam ormetoclopramide ± lorazepam
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Minimal Emetogenic Chemotherapy
Acute Delayed
MASCC No Routine Prophylaxis
No Routine Prophylaxis
ASCO
NCCN
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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
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Refractory Therapy
• Consider adjusting pre and post chemo regimen
• Little data
• Some evidence for aprepitant & palonosetron (not in Canada)
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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
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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
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Questions?
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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
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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