CINV Flashcards
Breakthrough CINV
Nausea and/or vomiting that occurs within 5 days post chemotherapy despite optimal antiemetic regimen used; requires rescue therapy with other antiemetics
Refractory CINV
Nausea and/or vomiting that occurs in subsequent chemotherapy cycles despite maximum antiemetic protocol
What is the importance of VC?
Afferent impulses to VC trigger efferent impulses to salivation, resp, GI muscles
Anticipatory CINV
Nausea and/or vomiting that is triggered by sensory stimuli associated with chemotherapy administration
List key neurotransmitters/drug classes (NT) that mediate CINV
- Histamine antagonist
- Muscarinic antagonist
- Dopamine antagonist
- Cannabinoids
- 5HT3 antagonist
- Substance P (Neurokinin-1)
- Benzodiazepine
What are the risk factors of CINV?
- Females
- h/o motion sickness
- previous CINV
- pregnancy
- younger age
- anxiety (anticipatory)
What is the goal of treatment of CINV?
Complete prevention (0-1 episodes/24 hours) of nausea/vomiting for at least 3 days for high risk (HEC), 2 days for moderate risk (MEC) after the last dose of chemotherapy
What drug classes prevent CINV?
- 5-HT3-RA
- NK-1 inhibitors
- Adrenal corticosteroids = dexamethasone
- Olanzapine
Which 5-HT3 Receptor Antagonist are good for acute HEC, MEC, low risk & breakthrough emesis?
Any of the 3: Granisetron (Kytril), Ondansetron (Zofran)
Which 5-HT3 Receptor Antagonist are good for acute, HEC, MEC, and delayed emesis?
Palonosetron IV that may “last” for 2-3 days
What are the ADE of 5-HT3-RA?
- non-sedating
- no EPS risk
- headache
- constipation most common
What are the counseling points for 5-HT3-RA?
- Route and dose-dependent risk of prolongation of the QT interval
- Most often associated with IV ondansetron when doses exceed 16 mg dose (FDA max)
- Also risk in congenital QTc or acquired QTc prolongation, electrolyte abnormalities
- Palonosetron, granisetron do not contain this warning
NK1 Antagonist
- Preventative for HEC, esp those with delayed nausea and emesis
- Combined with 5-HT3 RA, steroid, +/- olanzapine for HEC
- NOT for breakthrough
What are the ADEs of NK1 antagonist?
- Fosaprepitant, aprepitant, netupitant inhibit metabolism of dexamethasone – must reduce dexamethasone doses by 50%
- Also other important CYP3A4 metabolism effects – check interactions, esp with chemotherapy such as ifosfamide, other medications
Dexamethasone
- Should be continued for 2-3 days for regimens with delayed emesis risks
- Dose reductions when given with aprepitant or FOSaprepitant (inhibition of DXM metab)
- May be modified or omitted when the chemotherapy regimen already includes a steroid (like in ALL)
- NOT used in brain tumors as antiemetic may reduce chemotherapy passage through BBB
- NOT recommended with immunotherapies and cellular therapies
- HEC, MEC, low - acute, delayed, breakthrough
What are some ADE of Dexamethasone?
- HTN
- DM
- GI upset/bleeding
- agitation
- “itching” or “nerves” or even vomiting when given rapid IVP
Olanzapine
- The “newest” preventative, also breakthrough CINV
- Highly effective, latest addition as a 4-drug regimen for HEC, can be used prn, also used for palliative care nausea
- HEC, MEC, breakthrough, refractory - acute, delayed
What are some ADE of Olanzapine?
- Caution incl. when used with metoclopramide or haloperidol – increased EPS
- Risk of prolongation of QT interval
- CNS depression
- Use with caution in patients at risk for falls (e.g., elderly, debilitated, frail), or at risk for orthostatic hypotension
What is the dose of Olanzapine?
5 mg daily pre-chemotherapy, then daily x 2-3 days post-HEC
* can also be prn daily for breakthrough
What are some breakthrough options?
- Benzodiazepine (Lorazepam)
- Metoclopramide
- Cannabinoids
- Phenothiazines or Haloperidol
ADRs of Benzodiazepine
- CNS depression - fall risk for elderly
- Hypotension
ADRs of Metoclopramide
EPS reactions
ADRs of Phenothiazines or Haloperidol
- CNS depression
- Increased EPS risks with concurrent haloperidol or metoclopramide
- QT prolongation risk
Phenothiazines
Promethazine, prochlorperazine - breakthrough, low risk
Antihistamine/anticholinergics
Benadryl, scopalamine - acute, breakthrough
What parenteral anticancer agents have high emetic risk?
- AC with anthracycline and cyclophosphamide
- Carboplatin
- Carmustine
- Cisplatin
- Cyclophosphamide
- Doxorubicin
- Dacarbazine
- Ifosfamide
What is the treatment option A for high emetic risk?
Before chemo:
1. Olanzapine
2. NK1 RA
3. 5-HT3 RA
4. Dexamethasone
Days 2,3,4
1. Olanzapine
2. Aprepitant if it is used before
3. Dexamethasone
What is the treatment option B for high emetic risk?
Before chemo:
1. Olanzapine
2. Palonosetron
3. Dexamethasone
Days 2,3,4
1. Olanzapine
What is the treatment option C for high emetic risk?
Before chemo:
1. NK1 RA
2. 5-HT3 RA
3. Dexamethasone
Days 1, 2, 3:
1. Aprepitant if it was used before
2. Dexamethasone
Which parenteral anticancer agents are moderate emetic risk?
- Busulfan
- Carboplatin
- Carmustine
- Cyclophosphamide
- Cytarabine
- Daunorubicin
- Doxorubicin
- Irinotecan
- Methotrexate
What is the treatment option D for moderate emetic risk?
Before chemo:
1. 5-HT3-RA
2. Dexamethasone
Days 2, 3, 4:
1. Dexamethasone
OR
1. 5-HT3-RA
What is the treatment option E for moderate emetic risk?
Before chemo:
1. Olanzapine
2. Palonosetron
3. Dexamethasone
Days 2,3,4
1. Olanzapine
What is the treatment option F for moderate emetic risk?
Before chemo:
1. NK1 RA
2. 5-HT3 RA
3. Dexamethasone
Days 2, 3, 4:
1. Aprepitant if it was used before
2. Dexamethasone
If multiple CONSECUTIVE Days of chemotherapy
- 5-HT3 RA prior to each day’s doses
- Dexamethasone daily, then continued 2-3 days post chemo
- NK1 RA
