Prevention of Antineoplastic Medication induced Nausea and Vomiting - - PowerPoint PPT Presentation

Prevention of Antineoplastic Medication induced Nausea and Vomiting in Pediatric Cancer Patients

Done by :Meznah Zaid Al-Mutairi Pharm.D Candidate PNU University College of Pharmacy

Introduction

 Nausea and vomiting are common side effects for patients treated with systemic chemotherapy (70-80 %).  Prevention and control of nausea and vomiting (N&V) are critical in the treatment of cancer patients.

Important definition

Pathogenesis of Chemotherapy-Induced Nausea and Vomiting

Chemotherapy directly affects the higher neurologic centers in the central nervous system, the vomiting center located in the medulla oblongata, and peripheral neurologic receptors in the small intestine, inducing the release of neurotransmitters such as substance P and serotonin, which in turn signal the vomiting center, with the resultant CINV.

Emetic Reflex Dopamine Serotonin

Cannabinoids

Substance P

VC Small Intestine

Importance of control of nausea and vomiting

 It effects patients’ quality of life.  The compliance of treatment was decreased.  It causes metabolic changes.  It effects functional and intelligence capacity of patients.  It causes anorexia and nutritional deficiency.  Aspiration pneumonia and oesophagus damage might be seen. Effective chemotherapy treatments were discontinued because of this side effect.

Grade of nausea and vomiting

National Cancer Institute Classification of Nausea and Vomiting 2013

Types of AINV

 Acute antineoplastic-induced nausea and vomiting: nausea, vomiting, and/or retching that occurs within 24 hours following the administration of an antineoplastic therapy.  Delayed antineoplastic-induced nausea and vomiting: nausea, vomiting, and/or retching that occur more than 24 hours after and usually within 7 days of administration of an antineoplastic therapy.  Anticipatory antineoplastic-induced nausea and vomiting: nausea, vomiting, and/or retching that occurs within 24 hours prior to administration of antineoplastic therapy (After a negative past experience with chemotherapy).

The POGO Antineoplastic–induced Nausea and Vomiting Guideline 2013

Types of AINV

 Breakthrough antineoplastic-induced nausea and vomiting: Occurs despite patient being treated with preventive therapy.  Refractory antineoplastic-induced nausea and vomiting: Occur during subsequent cycles of chemotherapy when antiemetic prophylaxis has failed in earlier cycles.

The POGO Antineoplastic–induced Nausea and Vomiting Guideline 2013

Antiemetic Agents in Pediatric Cancer Patients

1- Serotonin (5-HT3) receptor antagonists. 2- Corticosteroids. 3- Neurokinin-1 receptor antagonists. 4- Benzamide analogs. 5- Phenothiazines. 6-Cannabinoids

Mechanism of action

Emetic Reflex Dopamine Serotonin

Cannabinoids

Substance P

VC Small Intestine Benzamide analogs Metoclopramide

serotonin (5-HT3) receptor antagonists Granisetron

• ndansetron

Neurokinin-1 receptor antagonists Aprepitant fosaprepitant

Phenothiazines Prochlorperazine chlorpromazine

Cannabinoids Dronabinol Nabilone

1-serotonin (5-HT3) receptor antagonists

Granisetron and ondansetron :

• (5-HT3) serotonin

receptor antagonists have equivalent efficacy and safety.

• Combination

with corticosteroids increased their efficacy.

• (5-HT3) serotonin receptor antagonists are not

effective for preventing delayed emesis.

1-serotonin (5-HT3) receptor antagonists

 Side effects :

• Mild headache.
• -Transient elevation serum aminotreansferases
• Constipation .
• QT prolongation .

 Drug-drug interaction:

• Tramadol.

2-Corticosteroids

Dexamethasone

 MOA: Unkown ,thought to act by inhibiting prostaglandin synthesis in the cortex.  Adverse effect : associated with single doses and short courses of steroids are infrequent , they may include euphoria , anxiety ,insomnia , increased appetite and mild fluid retention.  Drug-drug interaction:

• Doxorubicin.
• Ifosfamide.

3- Neurokinin-1 receptor antagonists

 Aprepitant or fosaprepitant:

• Aprepitant is approved for use in comination with other

antiemetic drugs for preventing acute and delayed nausea and vomiting associated with initial and repeat courses of chemotherapy known to cause these problems ,including high-dose cisplatin .

• Aprepitant improved the overall complete response

(defined as no emetic episodes and no use of rescue therapy )by about 20% when added to a serotonin (5- HT3) receptor antagonists and dexamethasone.

3- Neurokinin-1 receptor antagonists

 Fosaprepitant vs. Aprepitant :

• Intravenous single-day fosaprepitant is now regarded as

equivalent to 3 days of aprepitant for HEC .

• aprepitant (125 mg PO on day 1 then 80 mg on days 2-

3) or fosaprepitant (150 mg IV on day 1) .

• Fosaprepitant was not inferior to aprepitant for CR in the
• verall (71.9% vs. 72.3%) .

3- Neurokinin-1 receptor antagonists

 Adverse effect :

Asthenia ,dizziness and hiccups.

 Drug-drug interaction:

• Dexamethasone.
• Imatinib.

4- Benzamide analogs

Metoclopramide  Adverse effect :

• Mild sedation , diarrhea and extrapyramidal

reactions (eg. Dystonia , akathisia ).

• Given with benztropine (0.02-0.05 mg/kg/dose

1-2 times daily) or Diphenhydramine (0.5-1 mg/kg/dose IV) to avoid extrapyramidal reactions .

5- phenothiazines

Prochlorperazine ,chlorpromazine and promethazine  Chlorpromazine is often preferred in children because it is associated with fewer extrapyramidal reactions than prochlorperazine.  Adverse events : Drowsiness ,hypotension , akathisia and dystonia.

6-Cannabinoids

Dronabinol and Nabilone  Adverse events : Drowsiness , Dizziness , Euphoria ,

• rthostatic hypotension , ataxia and

appetite stimulation.

Non-Pharmacologic Treatment

 Eat the foods smaller and more frequent.  Drink the liquids one hour before or after meals.  Eat the cracker, toast, salty biscuit if the emesis occur in the morning.  Walking short distance outdoors and inhale air deeply and slowly.  Keep away from odors of foods, perfüme and fume.  Do not sleep immediately after dinner.  Begin eating light foods (soup, yoghurt) after control nause and vomitting.

POGO,2013

Emetogenic Potential of Antineoplastic agents  Emetogenicity : the propensity of an agent to cause nausea, vomiting or retching.  Current model includes four level for intravenous chemotherapy and two level for oral chemotherapy.  Level for intravenous chemotherapy (minimal , low, moderate and high emetogenic risk ) and for oral chemotherapy (prophylaxis recommended and as needed).

The POGO Antineoplastic–induced Nausea and Vomiting Guideline 2013

high emetogenic Antineoplastic agents

Classification of Emetogenic Potential of Antineoplastic Medication in Pediatric Cancer Patient  This is a purely synthetic administered via SC injection,

• nce daily .

 It has predictable anticoagulant activity and does not require monitoring.  NO significant drug interactions were reported.  Mechanism of action: it is indirect inhibitors of Xa. Unlike heparin and LMWHs, it has no effect on thrombin.

The POGO Antineoplastic–induced Nausea and Vomiting Guideline 2013

high emetogenic treatment algorithm

The POGO Antineoplastic–induced Nausea and Vomiting Guideline 2013

Antiemetic Dosage Recommendations for children receiving HIGHLY Emetogenic Antineoplastic Therapy

The POGO Antineoplastic–induced Nausea and Vomiting Guideline 2013

Duration of Antiemetic agents for children receiving HIGHLY Emetogenic Antineoplastic Therapy  NK1 receptor antagonist (Aprepitant day 1-3) and  5-HT3 receptor antagonist PO/IV on day 1 only and  dexamethasone PO/IV on days 1-3 or 1-4 .

The POGO Antineoplastic–induced Nausea and Vomiting Guideline 2013 Medscape ,2014

Moderate emetogenic Antineoplastic agents

Classification of Emetogenic Potential of Antineoplastic Medication in Pediatric Cancer Patient

The POGO Antineoplastic–induced Nausea and Vomiting Guideline 2013

Moderate emetogenic treatment algorithm

The POGO Antineoplastic–induced Nausea and Vomiting Guideline 2013

Antiemetic Dosage Recommendations for children receiving Moderately Emetogenic Antineoplastic Therapy

The POGO Antineoplastic–induced Nausea and Vomiting Guideline 2013

Duration of Antiemetic agents for children receiving Moderately Emetogenic Antineoplastic Therapy  5-HT3 receptor antagonist PO/IV on day 1 only and  dexamethasone PO/IV on days 1-3 or 1-4.

The POGO Antineoplastic–induced Nausea and Vomiting Guideline 2013 Medscape ,2014

Low emetogenic Antineoplastic agents

Classification of Emetogenic Potential of Antineoplastic Medication in Pediatric Cancer Patient

The POGO Antineoplastic–induced Nausea and Vomiting Guideline 2013

Low emetogenic treatment algorithm

The POGO Antineoplastic–induced Nausea and Vomiting Guideline 2013

Antiemetic Dosage Recommendations for children receiving LOW Emetogenic Antineoplastic Therapy

The POGO Antineoplastic–induced Nausea and Vomiting Guideline 2013

Minimal emetogenic Antineoplastic agents

Classification of Emetogenic Potential of Antineoplastic Medication in Pediatric Cancer Patient

The POGO Antineoplastic–induced Nausea and Vomiting Guideline 2013

Minimal emetogenic treatment algorithm

For multiple agent and multi-day antineoplastic therapy –refer to recommendations in Low emetic risk table.

The POGO Antineoplastic–induced Nausea and Vomiting Guideline 2013

Lexicomp ,2014

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