Chemotherapy induced nausea/vomiting

What are the risk factors for chemotherapy induced nausea/vomiting?

§  Female

§  Young age

§  History of morning/motion sickness

§  History of nausea during chemotherapy

§  Anxiety

§  Radiation with chemotherapy

§  Emetogenic potential

Classify the 5 types of CINV:

Type	Definition
Acute	Occurs ≤24 hours after chemotherapy administration; peaks after 5-6 hours
Delayed	Occurs ≥24 hours after chemotherapy administration; often peaks between 48-72 hours
Breakthrough	Post chemotherapy despite optimal antiemetic regimen used; requires rescue therapy
Anticipatory	Triggered by sensory stimuli associated with chemotherapy before administration
Refractory	Occurs in subsequent chemotherapy cycles despite maximum antiemetic usage

What are the non-pharmacological treatment options for chemotherapy nausea/vomiting?

§  Eating small, frequent meals

§  Avoiding foods that cause heartburn/spicy food.

§  Avoiding strong odors

§  Taking antiemetics before food

§  Acupressure

§  Acupuncture

§  Music therapy

§  Support groups

§  Music therapy/relaxation

  What are the pharmacologic treatment options for chemotherapy nausea/vomiting?

-5-HT3 antagonists

-Substance P/NK-1 RA

-Dopamine antagonists

-Atypical antipsychotics

-BZDs

-Corticosteroids

-Cannabinoids

5-HT-3 antagonists:

o   MOA:

§  selectively blocks 5-HT3 peripherally on vagal nerve terminals and centrally in chemoreceptor trigger zone.

o   Adverse Drug Reactions:

§  Headache, constipation, QTc prolongation, fatigue.

o   Medications:

§  Ondansetron (Zofran):IV, PO, ODT.

§  Granisetron (Sancuso): IV, SubQ, PO, Patch.

§  Palonosetron (Aloxi): IV

o   Efficacy:

§  They all have equal efficacy.

§  Corticosteroids increase efficacy by 25%

o   QTC prolongation:

§  The oral medications have less risk than the IV medication for QTc prolongation.

Which type of Chemotherapy Induced Nausea/Vomiting is 5-HT3 used to treat?

  Acute

§  Delayed ( palonosetron)

§  Breakthrough

If no NK1-RA or Olanzapine used:

Palonosetron or granisetron extended release are the preferred agents.

Substance P/NK-1 receptor antagonists:

·         MOA:

o   Selectively inhibits substance P to NK-1 receptors in CNS.

·         Adverse Drug Reactions:

o   Fatigue, diarrhea, hiccups, hypersensitivity ( greater in fosaprepitant).

·         Medications:

o   Aprepitant ( Cimvanti, Emend): PO, IV ; used for Days 1-3

o   Fosaprepitant (Emend): IV ; used for Day 1

o   Netupitant (Akynzeo): PO; used for Day 1

o   Rolapitant (Varubi): PO; used for Day 1

·         Metabolism:

o   It is a CYP3A4 inhibitor , so you will have to decrease the dose of Dexamethasone if given with NK-1 Receptor Antagonists.

Which chemotherapy induced nausea/vomiting are NK-1 antagonist used to prevent?

o   Acute and delayed nausea/vomiting but used in combination with 5-HT3 and Dexamethasone.

  What happens when you give an NK-1 Receptor Antagonist to patients on  Warfarin?

o   It will decrease the INR.

Women who take contraceptives, what will happen to their contraceptives while taking a NK-1 Receptor Antagonist?

o   The NK-1 Receptor Antagonist will decrease the efficacy of contraceptives.

Dopamine receptor antagonists:

·         MOA:

o   Block D2 receptors in the chemoreceptor trigger zone.

·         Adverse Drug Reactions:

o   Drowsiness, anticholinergic effects, EPS, orthostatic hypotension, diarrhea, tardive dyskinesia ( metoclopramide)

·         Medications:

o   Prochlorperazine: PO, IV, PR

o   Promethazine:  PO, IV, PR

o   Metoclopramide: PO ; short-termed use

  What Chemotherapy induced nausea/vomiting are dopamine antagonist used to treat?

o   Breakthrough

Atypical antipsychotics:

·         Olanzapine:

o   MOA:

§  Antagonist of multiple receptors including dopamine, serotonin, histamine, and acetylcholine muscarinic.

o   Dose:

§  2.5 -10 mg once daily at bedtime.

o   Frequency:

§  Daily for 1-4 days.

o   Adverse Drug Reactions:

§  Drowsiness, fatigue, constipation, increased appetite/weight, hyperglycemia, QTc prolongation, EPS.

What chemotherapy induced nausea/vomiting is olanzapine used to treat?

§  Acute and delayed in combination with other drugs, breakthrough.

True/False: drowsiness is the main side effect of olanzapine, so you should take this medication at night/bedtime.

-True

Benzodiazepines:

·         Lorazepam:

o   MOA:

§  GABA receptor modulator; anxiolytic.

o   Dosing:

§  0.5-1 mg

o   Frequency:

§  Q6hrs or right before infusion appointment.

o   Adverse Drug Reactions:

§  Sedation, amnesia, hypotension, respiratory depression.

What chemotherapy nausea/vomiting is lorazepam used to treat?

Anticipatory

Corticosteroids:

·         Dexamethasone:

o   MOA:

§  Unknown

o   Dose if taking with an NK-1 Receptor Antagonist:

§  Day 1: 12 mg

§  Days 2-4: 8 mg

Dose if not taking NK-1 RA:

• Day 1: 20 mg

• Day 2-4: 8 mg

o   Frequency:

§  Can give once daily or twice a day for 4 days.

o   Adverse Drug Reactions:

§  Insomnia, hyperglycemia, mood instability, increased appetite, hypertension, stomach upset.

  Which chemotherapy induced nausea/vomiting is dexamethasone used to treat?

§  Acute and delayed in combination with other agents.

o   If chemotherapy protocol has corticosteroids in plan:

do not need to add additional steroids.

Cannibinoids:

·         Dronabinol:

o   MOA:

§  Unknown , activates CB1 receptor leading to inhibitory effects on cerebral cortex.

o   Dosing:

§  5mg/m^2

o   Frequency:

§  1-3 hours before chemo then 4-6 doses/day.

o   Adverse Drug Reactions:

§  Dysphoria, hallucinations, sedation, disorientation. Vertigo.

What chemotherapy induced nausea/vomiting is dronabinol used to treat?

§  refractory

IV Emetogenic Potential High Risk:

high risk is considered > 90%

IV emetogenic potential moderate risk:

moderate risk is 30-90%

IV emetogenic potential low risk:

low risk is 10-30%

IV emetogenic potential minimal risk:

minimal risk is <10%

IV emetogenicity treatment regimens:

Emetic risk	Treatment options	Examples
High (>90%)	4 drug regimen day 1, 3 drugs day 2-4 Or 3 drug regimen day 1, 1 drug days 2-4 Or 3 drug regimen day 1, 2 drug days 2-4	1-      NK1-RA 2-      5-HT3 RA 3-      Dexamethasone 4-      Olanzapine Followed by: Olanzapine , 5-HT3, NK-1 RA
Moderate (30-90%)	2 drug regimen day 1, 2 drugs day 2-3 Or 3 drug regimen day 1, 1 drug days 2-3 Or 3 drug regimen day 1, 2 drugs day 2-3	1-      NK1 RA 2-      5-HT3 RA 3-      Dexamethasone Followed by: NK-1, dexamethasone
Low (10-30%)	1 drug regimen day 1, breakthrough prn	1-      Dexamethasone Or 1-      5-HT3 RA
Minimal ( < 10%)	No routine prophylaxis	PRN ondansetron

What is the treatment for anticipatory chemotherapy induced nausea/vomiting?

·         Anxiolytic (Lorazepam 0.5-1 mg po evening before anticancer therapy)

What is the treatment for breakthrough chemotherapy induced nausea/vomiting?

·         Re-evaluate current regimen

·         Considered different route: SubQ, topical, Rectal, IV

·         Add one agent from a  different class to current regimen

·         Every patient should have 1-2 meds at home for breakthrough chemotherapy induced nausea/vomiting

Emetogenicity of oral agents:

§  Minimal to Low risk:

·         <30%

§  Moderate to high risk:

·         >30%

Which medications are started before anticancer therapy and continued daily?

·         Minimal to low risk:

o   PRN

o   Metoclopramide

o   5-HT3 RA

o   Prochlorperazine

·         Moderate to high risk:

o   Scheduled

o   5-HT3 RA

Oral agents emetogenic potential moderate to high risk:

-moderate to high risk is >30%

IV Chemotherapy/Oral Chemotherapy emetogenicity treatment: