Therapeutics - N/V 1
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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
What drugs have a high emetic risk?
- Anthracycline combination (e.g. doxorubicin/cyclophosphamide)
- Dacarbazine/Nitrogen Mustard
What drugs have a moderate emetic risk?
- Most anthracyclines
What drugs have a low emetic risk?
- Topoisomerase inhibitors
What drugs have a minimal emetic risk?
- Vinca Alkaloids
What drug classes are used for CINV treatment?
- Serotonin antagonists
- NK1 receptor antagonists
- DA antagonists
What are the Serotonin (5-HT3) Antagonists?
- Dolasetron (Anzemet)
- Granisetron (Kytril)
- Ondasetron (Zofran)
- Palonosetron (Aloxi)
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
What is the MOA of Serotonin (5-HT3) antagonists?
- Blocks enterochromaffin cells in the GI
- Effects 5-HT receptors in the medulla
Should you give a patient and oral or IV serotonin antagonist?
Either, equally effective for all except palonsetron
What is the transdermal serotonin antagonist?
Sancuso – Granisetron
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
Is granisetron oral or TD more effective?
When should IV Serotonin antagonists be given?
30 minutes prior to chemo
When should Oral Serotonin antagonists be given?
60 minutes prior to chemo
Serotonin antagonists are often given in combination with what other drugs?
Steroid and Aprepitant
How should serotonin antagonists not be given?
What are the adverse effects of Serotonin antagonists?
HA, Somnolence, Sedation, Dizziness, Constipation or Diarrhea (have a bowel regimen upfront), QT-prolongation
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
Corticosteroids have what place in CINV?
- Synergism with 5-HT3 antagonists and metoclopramide
- Acute and delayed N/V
- (Not FDA approved)
When do lower doses of Corticosteroids need to be used in CINV?
When used in combo with Apripitant due to a CYP DDI
What dose of Corticosteroid is appropriate for a highly emetogenic drug?
12-20 mg x 1 dose 30 min prior to chemo
What dose of Corticosteroid is appropriate for a moderately emetogenic drug?
8-12 mg 1 dose 30 min prior to chemo
What are the adverse effects of Corticosteroids?
- Transient perineal, vaginal or anal burning (slow the rate to prevent)
How should you counsel a patient on corticosteroids for CINV?
- Take with food
- Avoid alcohol
- Caution with warfarin or herbals
- Call if black stools
What are the Neurokinin-1 receptor antagonists?
- Aprepitant (Emend) - PO
- Fosaprepitant (Emend) - IV
- Netupitant/palanosetron (Akynzeo)
What is the MOA of Neurokinin-1 receptor antagonists?
Binds Substance P in the CNS and GI
What place in therapy are Neurokinin-1 receptor antagonists used?
Prevention of acute and delayed, mod-highly emetogenic chemo
When should Aprepitant be given?
1 hour before chemo
Aprepitant interacts with what other drugs?
- Docetaxel, Etoposide, Paclitaxel
- OCs – reduces efficacy
- Metabolized by: CYP3A4, 2C9 (induces first 2), and 1A2
What are the AE of Aprepitant?
- Increased liver enzymes
When are DA antagonist used for CINV?
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