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What are the risk factors for CINV?
- Treatment-specific factors: Emetogenicity of drug, dose, infusion rate, cycle and time of infusion
- Patient-specific factors:
- Age = Younger patients <50 years
- Gender = Females
- Alcohol use = Non-alcoholics
- Hx of motion sickness or nausea during pregnancy
- Prior exposure to chemotherapy
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What drugs have a high emetic risk?
- Cisplatin
- Cyclophosphamide
- Anthracycline combination (e.g. doxorubicin/cyclophosphamide)
- Dacarbazine/Nitrogen Mustard
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What drugs have a moderate emetic risk?
- Carboplatin
- Most anthracyclines
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What drugs have a low emetic risk?
- Taxanes
- 5-FU
- Topoisomerase inhibitors
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What drugs have a minimal emetic risk?
- Bevacizumab
- Bleomycin
- Vinca Alkaloids
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What drug classes are used for CINV treatment?
- Serotonin antagonists
- Corticosteroids
- NK1 receptor antagonists
- Antihistamines/Anticholinergics
- DA antagonists
- Benzodiazapines
- Cannabinoids
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What are the Serotonin (5-HT3) Antagonists?
- Dolasetron (Anzemet)
- Granisetron (Kytril)
- Ondasetron (Zofran)
- Palonosetron (Aloxi)
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What role do serotonin (5-HT3) antagonists have in CINV?
Used in the first 24 hours, except Palonosetron, which can be used for delayed NV for a moderately emetogenic chemo therapy
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What is the MOA of Serotonin (5-HT3) antagonists?
- Blocks enterochromaffin cells in the GI
- Effects 5-HT receptors in the medulla
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Should you give a patient and oral or IV serotonin antagonist?
Either, equally effective for all except palonsetron
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What is the transdermal serotonin antagonist?
Sancuso – Granisetron
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How should transdermal serotonin antagonist, Sancuso – Granisetron, be used?
- Prevention of CINV for moderate or highly emetogenic chemo for 5 days
- Apply 24 hours before chemo
- Remove 24 hours after last chemo dose, up to 7 days
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Is granisetron oral or TD more effective?
Neither, same
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When should IV Serotonin antagonists be given?
30 minutes prior to chemo
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When should Oral Serotonin antagonists be given?
60 minutes prior to chemo
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Serotonin antagonists are often given in combination with what other drugs?
Steroid and Aprepitant
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How should serotonin antagonists not be given?
PRN
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What are the adverse effects of Serotonin antagonists?
HA, Somnolence, Sedation, Dizziness, Constipation or Diarrhea (have a bowel regimen upfront), QT-prolongation
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Due to QT prolongation, Ondasetron should not be used in what way?
- No more than 16 mg/dose
- Do not use until K and Mg are corrected
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Corticosteroids have what place in CINV?
- Prevention
- Synergism with 5-HT3 antagonists and metoclopramide
- Acute and delayed N/V
- (Not FDA approved)
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When do lower doses of Corticosteroids need to be used in CINV?
When used in combo with Apripitant due to a CYP DDI
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What dose of Corticosteroid is appropriate for a highly emetogenic drug?
12-20 mg x 1 dose 30 min prior to chemo
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What dose of Corticosteroid is appropriate for a moderately emetogenic drug?
8-12 mg 1 dose 30 min prior to chemo
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What are the adverse effects of Corticosteroids?
- Anxiety
- Insomnia
- Euphoria
- Transient perineal, vaginal or anal burning (slow the rate to prevent)
- Endocrine
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How should you counsel a patient on corticosteroids for CINV?
- Take with food
- Avoid alcohol
- Caution with warfarin or herbals
- Call if black stools
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What are the Neurokinin-1 receptor antagonists?
- Aprepitant (Emend) - PO
- Fosaprepitant (Emend) - IV
- Netupitant/palanosetron (Akynzeo)
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What is the MOA of Neurokinin-1 receptor antagonists?
Binds Substance P in the CNS and GI
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What place in therapy are Neurokinin-1 receptor antagonists used?
Prevention of acute and delayed, mod-highly emetogenic chemo
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When should Aprepitant be given?
1 hour before chemo
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Aprepitant interacts with what other drugs?
- Corticosteroids
- Cyclophosphamide
- Docetaxel, Etoposide, Paclitaxel
- OCs – reduces efficacy
- Warfarin
- Metabolized by: CYP3A4, 2C9 (induces first 2), and 1A2
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What are the AE of Aprepitant?
- Fatigue
- Diarrhea/constipation
- Hiccups
- Increased liver enzymes
- Bradycardia
- HA
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When are DA antagonist used for CINV?
Mild-moderate
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