Management of Nausea and Vomiting

Introduction to Antiemetic Therapy

• The American College of Physicians recommends the use of medication as monotherapy for acute attacks of chemotherapy-induced nausea and vomiting (CINV) 1
• The National Comprehensive Cancer Network recommends the use of medication in combination with other antiemetics for enhanced efficacy in moderate to high emetogenic chemotherapy regimens 2

Management of Chronic Nausea

• The American Society of Clinical Oncology recommends medication as first-line for management of chronic nausea, including opioid-related nausea, due to its effectiveness and both central and peripheral effects 3

Management of Nausea and Vomiting in Specific Populations

• The American College of Obstetricians and Gynecologists recommends medication for prevention and treatment of nausea and vomiting after cesarean delivery 4

Opioid-Induced Nausea

• The National Comprehensive Cancer Network and the American Society of Clinical Oncology recommend medication as first-line therapy for opioid-induced nausea, due to its effectiveness and both central and peripheral effects 3, 5
• The American Gastroenterological Association recommends metoclopramide 5-10mg orally four times daily, 30 minutes before meals and at bedtime for first-line therapy, with a maximum treatment duration of 12 weeks due to the risk of tardive dyskinesia 6, 7

Treatment Options

• Metoclopramide is recommended at a dose of 5-10 mg orally four times daily, 30 minutes before meals and at bedtime, for patients with intractable nausea and vomiting due to gastroparesis, as suggested by the National Comprehensive Cancer Network 8
• 5-HT3 receptor antagonists such as ondansetron 4-8 mg BID or TID, or granisetron 1 mg BID or transdermal patch may be considered for patients who fail metoclopramide or have contraindications, as recommended by the Clinical Gastroenterology and Hepatology society 6
• Phenothiazine antipsychotics such as prochlorperazine 5-10 mg QID, or chlorpromazine 10-25 mg TID or QID may be considered for patients who fail metoclopramide or have contraindications, as suggested by the Clinical Gastroenterology and Hepatology society 6
• Domperidone may be considered for patients who cannot tolerate metoclopramide, but requires FDA investigational drug application in the US, as per the Clinical Gastroenterology and Hepatology society, and is recommended by the American Academy of Pediatrics for its effectiveness with fewer central nervous system side effects than metoclopramide 6, 9
• Prucalopride, a high-affinity selective 5-HT4 receptor agonist, is used primarily for chronic constipation and is safer for cardiac patients as it does not affect the QT interval 7
• Bethanechol, a direct-acting cholinergic agonist, increases lower esophageal sphincter pressure and improves gastric emptying 9
• Baclofen works as a prokinetic by acting on GABA-B receptors, offering a different mechanism than traditional agents 9
• Itopride is effective for GERD (particularly as add-on therapy to PPIs), functional dyspepsia, diabetic gastroparesis, and reduced GI motility in diabetic patients, with a strength of evidence level of moderate 10

Disease-Specific Management

• For diabetic gastroparesis, optimize glycemic control, use itopride 150 mg daily in divided doses, and monitor both GI symptoms and glycemic indices, as recommended by the American Diabetes Association, with a strength of evidence level of high 7, 6, 11, 12, 13
• For systemic sclerosis-related GI motility disorders, experts recommend prokinetics despite limited RCT evidence, and rotating antibiotics may be useful when malabsorption is caused by bacterial overgrowth in systemic sclerosis patients 14
• For GERD, start with PPI therapy, add prokinetic if symptoms persist, and consider itopride as add-on therapy to PPI for refractory cases, as recommended by the American College of Gastroenterology, with a strength of evidence level of moderate 10

Monitoring and Safety

• Monitor for extrapyramidal symptoms, watch for development of tardive dyskinesia, and perform QTc monitoring for long-term use, as recommended by the American Heart Association, with a strength of evidence level of high 7
• Patients on metoclopramide should be monitored for extrapyramidal symptoms and development of tardive dyskinesia, with a risk of approximately 0.1% per 1000 patient-years, as recommended by the FDA, with a strength of evidence level of high 6
• Elderly patients are at higher risk of tardive dyskinesia and should be monitored closely, with a strength of evidence level of moderate, as recommended by the American Geriatrics Society 7, 15
• Metoclopramide is contraindicated in patients with pheochromocytoma, and use with caution when combined with antipsychotics, MAO inhibitors, sedatives, and narcotics, as recommended by the American College of Clinical Pharmacology, with a strength of evidence level of high 16

Dosage and Administration

• The standard dose of metoclopramide is 10 mg three times daily before meals, with a maximum treatment duration of 12 weeks (FDA recommendation), and a strength of evidence level of high 7
• The standard dose of itopride is 50 mg three times daily, with adjusted doses for GERD (100-150 mg daily in divided doses) and diabetic gastroparesis (150 mg daily in divided doses), as recommended by the American Gastroenterological Association 10
• The maximum recommended daily dose of metoclopramide is 40 mg, although the specific guideline society is not mentioned in this context 8