CINV Flashcards
Patient risk factors for CINV
- Younger age <50y
- Female
- Anxiety
- Hx of chemo-induced CINV
- Hx of motion sickness
- Hx of emesis w past pregnancy
- Hx of low prior chronic alcohol intake (<1 glass per day)
High emetogenic risk choice of therapy
Acute:
- NK1 antagonist (PO Aprepitant 125mg on D1, followed by 80mg OD on D2, D3) (IV Aprepitant 130mg D1)
- 5-HT3 antagonist (PO/IV Ondansetron 8-16mg OD D1) (PO/IV Granisetron 1mg OD D1)
- Or NK1 + 5-HT3 (PO Akynzeo 1 capsule OD D1) - contains Netupitant 300mg and Palonosetron 0.5mg
- PO/IV Dexamethasone 12mg OD D1, 8mg OD D2-4
- +/- PO Olanzapine 5-10mg OD D1-4 (consider 2.5mg for elderly)
Delayed:
- Dexamethasone 8mg OD D2-4
- Olanzapine 5-10mg OD D2-4
Mod emetogenic risk choice of therapy
Acute:
- 5-HT3 antagonist (PO/IV Ondansetron 8-16mg OD D1) (PO/IV Granisetron 1mg OD D1)
- Dexamethasone IV/PO 12mg D1, 8mg OD D2-4
Delayed:
- Dexamethasone IV/PO 8mg OD D2-4
Low emetogenic risk choice of therapy
Acute:
- 5HT3 antagonist (PO/IV Ondansetron 8-16mg OD D1) (PO/IV Granisetron 1mg OD D1)
OR
- Dexamethasone IV/PO 12mg D1 8mg?
OR
- Dopamine-2 antagonist (PO/IV Metoclopramide 10mg OD-TDS PRN)
Delayed:
NIL
Minimal emetogenic risk choice of therapy
NIL
NK1 antagonist
- Place in therapy
- MOA
- Dosing
- Adverse effects
- DDIs
Place in therapy
- acute and delayed CINV
MOA
- binds to NK-1 receptors, prevents substance P (nociceptive neurotransmitter) from binding to the NK-1 receptor
Dosing
- PO Aprepitant 125mg OD D1, 80mg OD D2-3
- IV Aprepitant 130mg OD D1
- Akynzeo (Netupitant 300mg, Palonosetron 0.5mg) 1 Cap OD, D1
Adverse effects
- Fatigue
- Physical weakness
- Nausea
- Hiccups
- Headache
DDIs
*Aprepitant is a CYP3A4 inhibitor and CYP2C9 inducer
- Steroids (incr conc.)
- Warfarin (dcr conc.)
- BZDs (incr conc.)
- Certain chemotherapy (incr conc. of ifosfamide)
5-HT3 antagonist
- Place in therapy
- MOA
- Dosing
- Adverse effects
- DDIs
Place in therapy
- acute CINV
MOA
- bind to 5-HT3 receptors on vagus afferent nerves, prevent the transmission of signals to the brain, therefore prevent efferent signals that induce N&V
- also have 5-HT3 receptor in CTZ
Dosing
- PO/IV Ondansetron 8-16mg OD D1, 8mg BD D2 onwards
- PO/IV Granisetron 1mg OD D1, 1mg OM D2 onwards
- PO Akynzeo (Netupitant 300mg + Palonosetron 0.5mg) 1 Cap OD, D1
Adverse effects
- Headache
- Constipation
- QTc prolongation
DDIs
- Serotonin syndrome (e.g., w SSRIs)
Dopamine-2 antagonist (Olanzapine)
- Place in therapy
- MOA
- Dosing
- Adverse effects
- DDIs
Place in therapy
- Acute, delayed CINV
MOA
- Block dopamine receptors in CTZ, anticholinergic activity, antagonize of peripheral serotonin receptors in the intestine
Dosing
- PO Olanzapine 5-10mg OD D1-4 (2.5mg OD in elderly)
Adverse effects
- Sedation
- Postural hypotension
- Anticholinergic SEs (dry mouth, constipation)
- EPSE - tremors, restlessness, uncontrolled muscle movements
DDIs
- Not to be used with Metoclopramide due to incr risk of EPSE, neuroleptic malignant syndrome, tardive dyskinesia
Dopamine-2 antagonist (Metoclopramide)
- Place in therapy
- MOA
- Dosing
- Adverse effects
- DDIs
Place in therapy
- Acute, breakthrough
MOA
- Block dopamine receptors in CTZ, stimulate cholinergic activity in the gut to incr gut motility, antagonize of peripheral serotonin receptors in the intestine
Dosing
- Metoclopramide 10mg OD-TDS PRN
Adverse effects
- Sedation
- Diarrhea
- QTc prolongation
- EPSE - tremors, restlessness, uncontrolled muscle movements
DDIs
- Not to be used with Olanzapine due to incr risk of EPSE
Dexamethasone
- Place in therapy
- MOA
- Dosing
- Adverse effects
- DDIs
Place in therapy
- Acute and delayed CINV
MOA
- activity in CNS
Dosing
- PO/IV Dexamethasone 12mg OD D1, 8mg OD D2-4
Adverse effects
- GI upset (stomach pain)
- Insomnia
- Weight gain, water retention
- Easy bruising
- Anxiety
- Elevations in glucose
- (rare) Psychosis, hyperactivity
- (rare) Reactivation of stomach ulcers
*May prescribe Famotidine or Omeprazole (20mg OD)
Benzodiazepines
- Place in therapy
- MOA
- Dosing
- Adverse effects
- DDIs
Place in therapy
- Anticipatory
MOA
- Bind to BZD receptor on postsynaptic GABA neuron, enhance GABA inhibitory effect leading to depression of vomiting center
Dosing
- Lorazepam 0.5-2mg 30min before chemotherapy (or on the night before treatment, then repeated the next day 1-2h before tx)
- Alprazolam 0.5-1mg 30min before chemotherapy
Adverse effects
- Sedation
- Hypotension
- Unstable, clumsy
- Memory loss
- Abnormal sleep behavior
- Paradoxical excitement - excitement, agitation
Other adjuncts
Refractory CINV
E.g.,
- Haloperidol
PO/IV Haloperidol 0.5-2mg q4-6h
- Prochlorperazine/Chlorpromazine/Promethazine
PO Prochlorperazine 10mg TDS/QDS PRN
Non-pharmacological for CINV
- Small frequent meals, avoid heavy meals
- Avoid greasy, spicy, very sweet/salty food, food with strong flavors and smells
- Sip small amounts of fluid
- Avoid caffeinated beverages
- Avoid lying flat for 2h after eating
Non-pharmacological for prevention of anticipatory CINV
- Behavioral therapy (listen to music, relaxation, hypnosis)
- Acupuncture/acupressure
- Ginger
Checkpoint inhibitors
CPIs (e.g., pembrolizumab) have minimal emetogenic risk and do not require routine use of prophylactic antiemetics
If CPI added to chemotherapy, follow emetogenic risk of the other agents administered, Dexamethasone should not be emitted