Chemotherapy induced nausea and vomiting

Pharmacotherapeutics of CINV

1. Chemotherapy induced Nausea and Vomiting Dr. V. S. Swathi Assistant Professor

2. Definition It is the one of the most common side effect of chemotherapy drugs which is used in treatment of cancer. 80% of the patients with cancer will experience chemotherapy induced nausea and vomiting

3. Types Acute : Here patient will experience nausea and vomiting within 24 hours of chemotherapy Delayed : Here patient will experience nausea and vomiting after 24 hours of chemotherapy Anticipated : Here patient will experience nausea and vomiting before starting of chemotherapy Break through: Even after giving prophylactic drugs to prevent chemotherapy induced nausea and vomiting, patients will have episodes of nausea and vomiting, which requires rescue antiemetics Refractory: Nausea and vomiting occurs when there is a poor response to multiple antiemetic regimens

4. Risk factors Less than 50 years Females History of motion sickness History of pregnancy related nausea and vomiting Alcohol use Emesis prior to chemotherapy Failure to adhere treatment guidelines Type of antineoplastic regimen ( Drug, Dose, Route, Schedule, Combination drug)

5. Etiology Emetic risk Agent High (>90%) Cisplatin Cyclophosphamide ≥1500mg/m2 Carmustine Dacarbazine Dactinomycin Moderate (30–90%) Oxaliplatin Cytarabine >1000mg/m2 Carboplatin Ifosfamide Cyclophosphamide Doxorubicin Daunorubicin Epirubicin Low (10–30%) Paclitaxel Docetaxel Mitoxantrone Topotecan Etoposide Pemetrexed Methotrexate Gemcitabine Cytarabine ≤1000mg/m2 Fluorouracil Trastuzumab Minimal (<10%) Bevacizumab Bleomycin Busulfan Fludarabine Rituximab Vincristine

6. Pathogenesis of Vomiting

7. Pathogenesis

8. Pathogenesis

9. Pathogenesis

10. Clinical Presentation Nausea Vomiting Sweating Paleness of skin Palpitations

11. Complications Dehydration Electrolyte imbalance Metabolic alkalosis Oesophageal tear Under nutrition Weight loss Aspiration pneumonitis

12. Diagnosis Patient history Clinical presentation

13. Non Pharmacological Treatment Hypnosis Relaxation techniques Acupuncture Music therapy Systemic desensitization Guided imagery Biofeedback

14. Treatment options for Chemotherapy induced Nausea and Vomiting For high risk of Emesis Acute CINV Delayed CINV DAY 1 DAY 2 DAY 3 DAY 4 Aprepitant 125mg-PO-1 Aprepitant 80mg-PO-1 Aprepitant 80mg-PO-1 - Dolasetron 100mg-PO-1/ Granisetron 2mg-PO-1 - - - Dexamethasone 12mg-PO/IV-1 Dexamethasone 8mg-PO/IV-1 Dexamethasone 8mg-PO/IV-1 Dexamethasone 8mg-PO/IV-1

15. Treatment options for Chemotherapy induced Nausea and Vomiting For high risk of Emesis Acute CINV Delayed CINV DAY 1 DAY 2 DAY 3 DAY 4 Fosaprepitant 150mg-IV-1 - - - Dolasetron 100mg-PO-1/ Granisetron 2mg-PO-1 - - - - Dexamethasone 8mg-PO/IV-1 Dexamethasone 8mg-PO/IV-1 Dexamethasone 8mg-PO/IV-1

16. Treatment options for Chemotherapy induced Nausea and Vomiting For high risk of Emesis Acute CINV Delayed CINV DAY 1 DAY 2 DAY 3 DAY 4 Rolapitant 180mg-PO-1 - - - Ondansetron 16-24mg-PO-1 - - - Dexamethasone 20mg-PO/IV-1 Dexamethasone 8mg-PO/IV-1 Dexamethasone 8mg-PO/IV-1 Dexamethasone 8mg-PO/IV-1

17. Treatment options for Chemotherapy induced Nausea and Vomiting Acute CINV Delayed CINV DAY 1 DAY 2 DAY 3 DAY 4 Netupitant 300mg-PO-1 - - - Palasetron 0.5mg-PO-1 - - - Dexamethasone 8mg-PO/IV-1 Dexamethasone 8mg-PO/IV-1 Dexamethasone 8mg-PO/IV-1 Dexamethasone 8mg-PO/IV-1 For high risk of Emesis

18. Treatment options for Chemotherapy induced Nausea and Vomiting Acute CINV Delayed CINV DAY 1 DAY 2 DAY 3 Netupitant 300mg-PO-1 - - Palasetron 0.5mg-PO-1 Dolasetron-100mg-PO/ Granisetron 1-2mg-PO/ Ondansetron-16mg-PO Dolasetron-100mg-PO/ Granisetron 1-2mg-PO/ Ondansetron-16mg-PO Dexamethasone 8mg-PO/IV-1 - - For moderate risk of Emesis

19. Treatment options for Chemotherapy induced Nausea and Vomiting Acute CINV DAY 1 Dexamethasone 12mg-IV/PO-1/ Dolasetron-100mg-PO-1/ Granisetron-1-2mg-PO-1/ Ondansetron-8-16mg-PO-1 For low risk of Emesis

20. Treatment options for Chemotherapy induced Nausea and Vomiting For minimal risk of Emesis- No treatment required Anticipatory CINV Non pharmacological treatment Alprazolam or Lorazepam Refractory CINV Use different combinations of anti emetics Add rescue anti emetics

21. Treatment options for Chemotherapy induced Nausea and Vomiting Breakthrough CINV Adults Prochlorperazine Promethazine Lorazepam Metaclopromide Haloperidol Dexamethasone One dose in the evening of day before chemotherapy Next dose 1-2 hours prior to chemotherapy Children Chlorpromazine Lorazepam Dexamethasone

22. Drugs used in treatment of Chemotherapy induced Nausea and Vomiting (CINV ) Drug Category Mode of action Adverse effects Aprepitant NK 1 receptor antagonist Antagonises the actions of substance P/ Neurokinin 1 receptors Head ache Asthenia Anorexia GI disturbances Alopecia Fosaprepitant NK 1 receptor antagonist Antagonises the actions of substance P/ Neurokinin 1 receptors Head ache Asthenia Anorexia GI disturbances Alopecia Rotapitant NK 1 receptor antagonist Antagonises the actions of substance P/ Neurokinin 1 receptors Neutropenia Loss of appetite Dizziness Dyspepsia Urinary tract infection

23. Drugs used in treatment of Chemotherapy induced Nausea and Vomiting (CINV) Netupitant NK 1 receptor antagonist Antagonises the actions of substance P/ Neurokinin 1 receptors Head ache Asthenia Dyspepsia Hepatotoxicity Erythema Palanosetron 5 HT3 receptor antagonist Antagonises the actions of serotonin QT prolongation Anxiety GI disturbances Hyperkaelemia Hepatotoxicity Granisetron 5 HT3 receptor antagonist Antagonises the actions of serotonin Head ache GI disturbances Asthenia Somnolenance Sedation

24. Drugs used in treatment of Chemotherapy induced Nausea and Vomiting (CINV) Ondansetron 5 HT3 receptor antagonist Antagonises the actions of serotonin Head ache Malaise Hypoxia Anxiety Urinary retention Dolasetron 5 HT3 receptor antagonist Antagonises the actions of serotonin Head ache Diarrhea Hypertension Arrhythmia GI disturbance s Alprazolam Benzodiazepine Decreased anxiety related to chemotherapy Drowsiness Depression Head ache GI disturbances Dry mouth Lorazepam Benzodiazepine Decreased anxiety related to chemotherapy Sedation Amnesia Vertigo Asthenia Tremor

25. Resources https ://www.ncbi.nlm.nih.gov/pmc/articles/PMC3938333/pdf/nihms454621.pdf http://www.ijmpo.org/article.asp?issn=0971-5851;year=2017;volume=38;issue=3;spage=334;epage=339;aulast=Baburaj https://www.frontiersin.org/articles/10.3389/fphar.2017.00019/full https://www.ons.org/sites/default/files/hawkins.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188425/pdf/nihms-261834.pdf