What is the recommended approach to treating nausea in adults, including first‑line medications, special considerations (pregnancy, chemotherapy, Parkinson disease, elderly, renal/hepatic impairment), and when to refer?

Treatment of Nausea in Adults

For general nausea in adults, start with metoclopramide 10-20 mg orally as first-line therapy, which has the strongest evidence for nonspecific nausea. 1

First-Line Pharmacologic Approach

Primary Agents

• Metoclopramide 10-20 mg orally is the recommended initial treatment for most causes of nausea, including medication-induced and chronic nausea, due to its dual central and peripheral antiemetic effects 2, 1
• Prochlorperazine 10-20 mg orally every 6 hours serves as an effective alternative dopamine antagonist when metoclopramide is contraindicated or not tolerated 2, 1, 3
• Monitor for dystonic reactions within the first 48 hours when using dopamine antagonists; keep diphenhydramine 25-50 mg available for treatment 3

Rule Out Reversible Causes First

• Always exclude constipation as a primary or contributing cause before escalating antiemetic therapy 2, 1
• Consider gastroesophageal reflux and treat with proton pump inhibitors or H2 receptor antagonists if suspected 1
• Evaluate for metabolic disturbances (electrolyte abnormalities), infection, medication side effects, and gastrointestinal obstruction 2, 4

Escalation Strategy for Persistent Nausea

Second-Line Approach

• Add a 5-HT3 antagonist (ondansetron 8 mg orally every 8-12 hours or granisetron 1-2 mg orally daily) to the dopamine antagonist rather than switching medications 1, 3
• This combination provides synergistic antiemetic effects by targeting different neurotransmitter pathways 1
• Administer antiemetics around the clock for 1 week rather than as-needed dosing for patients with persistent symptoms 1, 3

Third-Line Options

• Haloperidol 0.5-1 mg orally every 6-8 hours for patients not responding to first-line agents 1
• Dexamethasone 4-10 mg orally/IV once daily can be added to the regimen for additional benefit 3

Refractory Nausea Management

• Olanzapine 5-10 mg orally daily acts on multiple receptor sites (dopaminergic, serotonergic, muscarinic, histaminic) and is effective for refractory cases 2, 3
• Scopolamine transdermal patch 1.5 mg every 72 hours provides anticholinergic antiemetic effects 3
• Cannabinoids (dronabinol 2.5-10 mg orally twice daily or nabilone 1-2 mg orally twice daily) can be trialed for persistent symptoms 2, 3

Special Population Considerations

Pregnancy

• Avoid metoclopramide and most antiemetics in first trimester unless benefits clearly outweigh risks 4
• Consider non-pharmacologic measures first: small frequent meals, ginger, vitamin B6 4

Chemotherapy-Induced Nausea

• Prevention is paramount: Use prophylactic antiemetics based on emetogenic potential of chemotherapy regimen 5, 6
• For highly emetogenic chemotherapy: Combine 5-HT3 antagonist + dexamethasone 20 mg IV + NK1 antagonist (aprepitant 125 mg day 1, then 80 mg days 2-3) 2
• For moderately emetogenic chemotherapy: 5-HT3 antagonist + dexamethasone 8 mg IV 2
• Good acute control (first 24 hours) predicts better delayed emesis control 5

Opioid-Induced Nausea

• Metoclopramide is first-line for chronic opioid-related nausea due to its central and peripheral effects 2
• For patients with previous opioid-induced nausea, use prophylactic metoclopramide or prochlorperazine around the clock for first few days, then gradually wean 2
• Rule out constipation as the primary cause before treating nausea directly 2
• Tolerance typically develops within a few days 2

Parkinson Disease

• Avoid metoclopramide and prochlorperazine as they worsen Parkinson symptoms through dopamine antagonism 4
• Use ondansetron 8 mg orally every 8 hours or domperidone 20 mg (where available, as it doesn't cross blood-brain barrier) 2

Elderly Patients

• Start with lower doses due to increased sensitivity to side effects 7
• Be particularly cautious with anticholinergic agents (scopolamine) due to delirium risk 4
• Monitor for QT prolongation with 5-HT3 antagonists, especially dolasetron 7

Renal/Hepatic Impairment

• Ondansetron requires dose adjustment in severe hepatic impairment (maximum 8 mg daily) 7
• Metoclopramide should be dose-reduced in severe renal impairment 4
• Granisetron and dolasetron have more predictable pharmacokinetics in organ dysfunction 7

Anticipatory Nausea

• Best prevention is optimal control of acute and delayed nausea in previous cycles 2
• Lorazepam 1-2 mg orally is the only pharmacologic agent with demonstrated efficacy, though effectiveness decreases with continued chemotherapy 2
• Behavioral therapies (progressive muscle relaxation, systematic desensitization, hypnosis) are effective but require specialized expertise 2

Non-Pharmacologic Adjuncts

• Small, frequent meals with foods at room temperature 3
• Avoid trigger foods and strong odors 4
• Consider dietary consultation for ongoing symptoms 3
• Acupuncture may be beneficial for refractory cases 2, 3

When to Refer

• Persistent symptoms despite maximal medical therapy 4
• Alarm symptoms: severe abdominal pain, hematemesis, weight loss >5%, signs of obstruction 4
• Suspected surgical causes or gastrointestinal malignancy 8
• Severe dehydration or metabolic abnormalities requiring hospitalization 8
• Undiagnosed chronic nausea lasting >4 weeks despite appropriate investigation 4, 8

Critical Pitfalls to Avoid

• Never treat nausea empirically without first ruling out constipation, especially in patients on opioids or with cancer 2, 1
• Do not use as-needed dosing for persistent nausea—scheduled around-the-clock administration is more effective 1, 3
• Avoid switching antiemetics prematurely—add agents from different classes for synergistic effect rather than substituting 1
• Do not use dopamine antagonists in Parkinson disease patients as they will exacerbate motor symptoms 4
• Prophylactic antiemetics are essential for patients with history of medication-induced nausea or receiving emetogenic chemotherapy 1, 5