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.
Dopamine VC Emetic Reflex Substance P Cannabinoids Small Intestine Serotonin
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 Neurokinin-1 Benzamide receptor analogs antagonists Metoclopramide Dopamine Aprepitant fosaprepitant Phenothiazines Prochlorperazine chlorpromazine VC Emetic Reflex Substance P Cannabinoids Small Intestine Cannabinoids Serotonin Dronabinol serotonin (5-HT3) Nabilone receptor antagonists Granisetron ondansetron
1-serotonin (5-HT3) receptor antagonists Granisetron and ondansetron : (5-HT 3 ) serotonin receptor antagonists have equivalent efficacy and safety. Combination with corticosteroids increased their efficacy. (5-HT 3 ) 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 overall (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 , orthostatic 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, once 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
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