Transcript Document
Chemotherapy Induced Nausea and Vomiting Haley Gill, BSP VCH-PHC Pharmacy Resident 2009-2010 Pharmacy Services 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 Pharmacy Services Consequences of CINV • medical complications – electrolyte imbalances – dehydration • quality of life – impact daily functioning • compliance with chemotherapy Pharmacy Services Pathophysiology of CINV Pharmacy Services Pathophysiology of CINV Pharmacy Services Classification of CINV Acute 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 Pharmacy Services Neurotransmitter Involvement Pharmacy Services Risk Factors • • • • • Young age Female History of low alcohol intake Experience of emesis during pregnancy Emetogenic potential of chemotherapeutic agent • History of motion sickness Pharmacy Services Antiemetic Agents • Serotonin 5-HT3 Receptor Antagonists (5HT3 RA) • Corticosteroids • Dopamine-Serotonin Receptor Antagonists • Dopamine Receptor Antagonists • Neurokinin-1 Receptor Antagonists (NK-1 RA) • Benzodiazepines • Cannabinoids Pharmacy Services 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 Pharmacy Services 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** Pharmacy Services Corticosteroids • Dexamethasone (Decadron®) • Dose: 8 - 20 mg IV or PO • Effective for both acute and delayed CINV • MOA: unknown • AE’s: Insomnia, hyperglycemia, heartburn Pharmacy Services 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 Pharmacy Services 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 Pharmacy Services 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% Pharmacy Services Other Agents Agent Dose Lorazepam (Ativan 0.5 - 2 mg IV/PO/SL ®) Use Anticipatory N&V Cannabinoids • dronabinol (Marinol®) • nabilone (Cesamet®) Olanzapine (Zyprexa®) Refractory & Breakthrough N&V Gabapentin (Neurontin®) Pharmacy Services 2.5 – 10 mg PO TID - QID 2.5 – 10mg PO hs Acute, Delayed & Refractory N&V Delayed Chemotherapy Emetic Risk Groups High 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 Pharmacy Services Guidelines • Multinational Association of Supportive Care in Cancer (MASCC) • American Society of Clinical Oncology (ASCO) • National Comprehensive Cancer Network (NCCN) Pharmacy Services Highly Emetogenic Chemotherapy Acute Delayed MASCC 5-HT3RA + dexamethasone + aprepitant Dexamethasone + aprepitant ASCO 5-HT3RA + dexamethasone + aprepitant Dexamethasone + aprepitant NCCN 5-HT3RA + dexamethasone + aprepitant ± lorazepam Dexamethasone + aprepitant ± lorazepam Pharmacy Services 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 Pharmacy Services Low Emetogenic Chemotherapy Acute MASCC dexamethasone ASCO dexamethasone NCCN dexamethasone ± lorazepam or prochlorperazine ± lorazepam or metoclopramide ± lorazepam Pharmacy Services Delayed No Routine Prophylaxis Minimal Emetogenic Chemotherapy Acute MASCC No Routine Prophylaxis ASCO NCCN Pharmacy Services Delayed No Routine Prophylaxis 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 Pharmacy Services Refractory Therapy • Consider adjusting pre and post chemo regimen • Little data • Some evidence for aprepitant & palonosetron (not in Canada) Pharmacy Services 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 Pharmacy Services Cost Drug 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 Pharmacy Services Questions? Pharmacy Services References 1. 2. 3. 4. 5. 6. 7. Kris MG, et al. American Society of Clinical Oncology Guideline for Antiemetics in Oncology: Update 2006. J Clin Oncol 2006;24(18):2932-47 Hesketh PJ. Chemotherapy-Induced Nausea and Vomiting. N Engl J Med 2008;358:2482-94 Baker PD, et al. The Pathophysiology of Chemotherapy-Induced Nausea and Vomiting. Gastroenterology Nursing 2005;28(6):469-80 Navari RM. Pharmacological Management of Chemotherapy-induced Nausea and Vomiting: Focus on Recent Developments. Drugs 2009;69(5):515-33 Jordan K, et al. Guidelines for Antiemetic Treatment of ChemotherapyInduced Nausea and Vomiting: Past, Present, and Future Recommendations Oncologist 2007;12;1143-1150 Multinational Association of Supportive Care in Cancer Antiemetic Guidelines (last update: March 2008). Available at www.mascc.org National Comprehensive Cancer Network Antiemetic Guidelines 2007. Available at www.nccn.com Pharmacy Services 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 Pharmacy Services