Nausea and Vomiting
Nausea and Vomiting
References
- Evaluation and Treatment of Nausea and Vomiting in Adults — American Family Physician (Johns TL, Lawrence E.). Am Fam Physician 2024;109(5):417-425
- Chronic nausea and vomiting: evaluation and treatment — American Journal of Gastroenterology (Lacy BE, Parkman HP, Camilleri M.). Am J Gastroenterol 2018;113(5):647-659
- Guidelines on management of cyclic vomiting syndrome in adults by the American Neurogastroenterology and Motility Society and the Cyclic Vomiting Syndrome Association — Neurogastroenterology & Motility (Venkatesan T, Levinthal DJ, Tarbell SE, et al.). Neurogastroenterol Motil 2019;31(S2):e13604
- ACG Clinical Guideline: Gastroparesis — American Journal of Gastroenterology, American College of Gastroenterology (Camilleri M, Kuo B, Nguyen L, et al.). Am J Gastroenterol 2022;117(8):1197-1220
- PRZ-METOCLOPRAMIDE (metoclopramide) Product Monograph — Health Canada / Pharmaris Canada Inc.. Date of Initial Authorization: June 14, 2024
- Medication related nausea and vomiting in palliative medicine — Annals of Palliative Medicine (Maceira E, Lesar TS, Smith H.). Ann Palliat Med 2012;1(2):161-176
- Drugs for the treatment of nausea and vomiting in adults in the emergency department setting — Cochrane Database of Systematic Reviews (Furyk JS, Meek RA, Egerton-Warburton D.). Cochrane Database Syst Rev 2015;(9):CD010106
- Pharmacology of antiemetics: update and current considerations in anesthesia practice — Anesthesiology Clinics (Kaye AD, Cornett EM, Chalabi J, et al.). Anesthesiol Clin 2017;35(2):e41-e54
- Summary Safety Review - Domperidone - Serious abnormal heart rhythms and sudden death (cardiac arrest) — Health Canada. Health Canada Drug and Health Products Portal, 2015
- Opioid-induced nausea and vomiting — Annals of Palliative Medicine (Smith HS, Smith JM, Seidner P.). Ann Palliat Med 2012;1(2):121-129
- Scopolamine Hydrobromide Transdermal Patch (Transderm-V) Discontinuation — Medication and Drug Information Service, University of Saskatchewan College of Pharmacy and Nutrition. MEDSASK Bulletin, September 15, 2025
Clinical Snapshot
Nausea (the unpleasant sensation of an imminent need to vomit) and vomiting (the forceful oral expulsion of gastric contents through coordinated contraction of the abdominal wall, diaphragm, and stomach) are symptoms, not a diagnosis, generated by afferent input from the vestibular system, the vagal/gastrointestinal tract, the chemoreceptor trigger zone (located outside the blood-brain barrier and directly sensitive to circulating drugs, toxins, and metabolic derangement), and higher cortical/limbic pathways, all converging on the medullary vomiting centre.[1]
The most clinically useful first question is almost never "which antiemetic" but "which major causal category is this" — a gastrointestinal-motility disorder (gastroparesis), a vestibular or central nervous system process, a causative medication, mechanical gastrointestinal obstruction, or a metabolic/endocrine derangement — since identifying and, where possible, treating the underlying cause should usually drive management rather than reflexively layering on antiemetics.[2]
This chapter covers the general approach to nausea and vomiting in adults, outside of chemotherapy- or radiation-induced nausea and vomiting and nausea and vomiting of pregnancy, which are addressed separately.
Recognize the Condition
Definitions
Vomiting must be distinguished from three related phenomena that change the diagnostic approach: regurgitation (effortless retrograde flow of esophageal or gastric contents without abdominal-wall contraction, typical of reflux or an esophageal motility disorder), rumination (voluntary, learned regurgitation and re-chewing of recently swallowed food, typically beginning soon after a meal), and retching (rhythmic, spasmodic respiratory and abdominal-wall movement against a closed glottis, often preceding vomiting but sometimes occurring without it).[1]
Acute versus chronic
Acute nausea and vomiting lasts up to 7 days and is most often infectious, medication-related, or dietary. Chronic nausea and vomiting persists 4 weeks or longer and warrants a more structured diagnostic work-up for gastrointestinal, metabolic, neurologic, or psychiatric causes rather than ongoing empiric symptomatic treatment alone.[1]
Major causal categories
Gastrointestinal / motility
Gastroparesis, gastric outlet or bowel obstruction, gastritis, peptic ulcer disease, cholecystitis, pancreatitis, hepatitis, gastroesophageal reflux disease, constipation, chronic intestinal pseudo-obstruction, and functional gastrointestinal disorders (irritable bowel syndrome, functional dyspepsia).
Vestibular / neurologic
Motion sickness, benign paroxysmal positional vertigo, labyrinthitis, Meniere disease, migraine, increased intracranial pressure, a mass lesion, stroke, head injury, and other central nervous system disease.
Medication- or substance-induced
A wide range of prescription and non-prescription drugs, alcohol, and cannabis — often overlooked as the cause when a new antiemetic is simply added instead of reviewing the regimen. See Non-Pharmacologic Treatment for a detailed medication-review list.
Metabolic / endocrine
Pregnancy, diabetic ketoacidosis, uremia, hypercalcemia, hyponatremia, thyroid or adrenal disease (including Addison disease), severe heart failure, malignancy (including metastatic disease), and other electrolyte or hormonal derangement.
Infectious
Viral or bacterial gastroenteritis, foodborne illness, and, less commonly, a non-gastrointestinal infection (pyelonephritis, pneumonia, meningitis).
Psychiatric / functional
Anxiety, depression, eating disorders, anticipatory nausea, and chronic idiopathic (functional) nausea without an identifiable structural, metabolic, or psychiatric cause.
Symptom pattern can point to the cause
| Pattern | Suggests |
|---|---|
| Vomiting worse with movement, associated vertigo or nystagmus | Vestibular cause |
| Delayed vomiting more than 1 hour after meals, early satiety, bloating, partly digested food | Gastroparesis or gastric outlet obstruction |
| Bilious or feculent vomiting, severe pain, distension | Intestinal obstruction — a red flag, see Red Flags & Refer |
| Regurgitation of undigested food without nausea | Achalasia, esophageal stricture, or Zenker diverticulum — not a primary vomiting disorder |
| Projectile vomiting, worse in the morning or with position change, associated headache | Increased intracranial pressure — a red flag, see Red Flags & Refer |
| Onset clearly linked in time to a new or recently increased-dose medication | Medication-induced nausea |
| Vomiting before breakfast, in a person who could be pregnant | Pregnancy — always confirm with a pregnancy test in a patient of reproductive age |
| Discrete, stereotyped episodes with symptom-free intervals between them | Cyclic vomiting syndrome, see below |
Cyclic vomiting syndrome is a distinct pattern, not a diagnosis made from a single episode — it is defined by discrete, stereotyped episodes of intense nausea and vomiting (each typically lasting under a week) separated by symptom-free intervals of weeks to months, often with a personal or family history of migraine.[3] Cannabinoid hyperemesis syndrome is an important mimic in a patient with heavy, prolonged cannabis use, distinguished by symptom relief with hot showers or bathing and resolution after sustained cannabis cessation. Management of confirmed cyclic vomiting syndrome (prophylactic tricyclic antidepressant therapy between episodes, and abortive therapy with a triptan and/or antiemetic at prodrome onset) is directed by a clinician experienced with the condition and is outside this chapter’s general scope.[3]
Risk Factors
- Current opioid therapy, or recent opioid initiation or dose increase.
- Recent addition of, or dose increase in, another drug commonly associated with nausea (see Non-Pharmacologic Treatment and Common Errors to Avoid).
- Diabetes mellitus, particularly long-standing or poorly controlled disease (gastroparesis risk).
- Prior abdominal surgery (adhesions) or known malignancy (mechanical obstruction risk).
- Migraine history.
- Anxiety, depression, or an eating disorder.
- Heavy, chronic cannabis use (cannabinoid hyperemesis syndrome).
- Alcohol use disorder.
- Known central nervous system disease or recent head injury.
- Susceptibility to motion sickness, or upcoming travel by air, sea, or road.
- Pregnancy or possible pregnancy in a person of reproductive age.
- Recent exposure to a known enteric pathogen or ill contacts (infectious gastroenteritis).
Red Flags & Refer
Screen every patient for features suggesting a surgical abdomen, an intracranial process, or another emergency before treating nausea and vomiting symptomatically — symptomatic relief can delay recognition of a condition that needs urgent intervention.[1]
- Signs of bowel obstruction — severe or progressively worsening abdominal pain, marked distension, absent or high-pitched ("tinkling") bowel sounds, or feculent or bilious vomiting.
- Signs of increased intracranial pressure or another central cause — severe or new headache, altered mental status, papilledema, a focal neurologic deficit, new-onset seizure, or projectile vomiting without preceding nausea.
- Hematemesis or other evidence of gastrointestinal bleeding (melena, coffee-ground emesis).
- Signs of significant dehydration or electrolyte derangement — marked orthostatic hypotension or tachycardia, confusion, very low urine output, or profound weakness.
- Acute abdomen on examination — localized peritoneal signs, rebound tenderness, or a rigid abdomen.
- Unintentional weight loss, progressive dysphagia, or a palpable abdominal mass, particularly in a patient over 55 years of age.
- Chest pain, dyspnea, diaphoresis, or other features suggesting acute coronary syndrome — especially in a woman, an older adult, or a patient with diabetes, in whom nausea and vomiting can be the dominant presenting symptom of myocardial infarction.
- Fever with signs of a systemic or intra-abdominal infection (peritonitis, cholangitis, pyelonephritis with sepsis).
- Suspected diabetic ketoacidosis — altered mental status, a fruity breath odour, or known hyperglycemia with vomiting.
Assessment & Diagnosis
History
- Onset, duration (acute versus chronic), frequency, and timing relative to meals, time of day, and specific triggers.
- Character of vomitus — bilious, feculent, undigested food, or blood — and whether nausea and vomiting are temporally linked.
- Last menstrual period and pregnancy risk in every patient of reproductive age capable of pregnancy.
- Associated symptoms — abdominal pain, headache, vertigo, chest pain, fever, diarrhea, early satiety, postprandial fullness, weight loss, and change in bowel habits.
- Complete medication history, including recent dose changes, new prescriptions, non-prescription and herbal products, cannabis, and alcohol — a new or increased-dose drug is one of the most commonly missed causes.
- Past medical history — diabetes, prior abdominal surgery, migraine, psychiatric illness, malignancy, and known central nervous system disease.
- Recent travel, food exposure, and sick contacts.
- Psychosocial history and the patient’s own concerns and expectations, particularly for chronic or recurrent symptoms.
Physical examination
- Vital signs, including orthostatic blood pressure and heart rate, to assess volume status.
- Hydration assessment — mucous membranes, skin turgor, jugular venous pressure.
- Abdominal examination — distension, tenderness, peritoneal signs, bowel sounds, masses, organomegaly.
- Directed neurologic examination when a central cause is suspected — mental status, nystagmus, focal deficits, fundoscopy for papilledema.
- General examination for jaundice, lymphadenopathy, or other systemic findings.
Investigations
Extensive testing is not required for short-duration nausea and vomiting without a red-flag feature — for example, a classic acute viral gastroenteritis picture (short duration, associated diarrhea, fever, myalgia, sick contacts) can be treated symptomatically without further work-up.[1]
- Basic or comprehensive metabolic panel and complete blood count when metabolic derangement, dehydration, or an infectious/inflammatory cause is suspected.
- Pregnancy test in every patient of reproductive age capable of pregnancy before starting empiric pharmacotherapy.
- Lipase if pancreatitis is suspected; liver enzymes if a hepatobiliary cause is suspected; thyroid-stimulating hormone if an endocrine cause is suspected.
- Urinalysis and, where relevant, a drug/toxicology screen or a specific drug level (e.g., digoxin, an anticonvulsant).
- Abdominal ultrasound for suspected gallbladder or pancreatic disease.
- Abdominal radiography or CT for suspected bowel obstruction.
- Upper endoscopy for suspected mucosal disease, an alarm feature, or symptoms refractory to empiric treatment.
- Brain CT or MRI for a suspected central cause (increased intracranial pressure, mass lesion, stroke).
Gastric emptying testing when gastroparesis is suspected
Reserve gastric emptying testing for a patient with persistent postprandial fullness, early satiety, bloating, or delayed vomiting once mechanical obstruction and mucosal disease have been excluded, typically by endoscopy.[4]
- Scintigraphic gastric emptying of a standardized solid meal, measured over at least 4 hours (or confirmed at least 90% emptied by 3 hours), is the reference standard.
- Interfering medications — opioids, prokinetics, other antiemetics, cannabinoids, and neuromodulators — should be held for at least 48 hours before the study whenever it is safe to do so, since they can falsely alter the result.
- A stable isotope breath test or a wireless motility capsule are validated alternatives to scintigraphy where scintigraphy is not available.
- Radiopaque marker studies are not recommended to evaluate gastroparesis in a patient with upper gastrointestinal symptoms.
Treatment Targets
- Relieve nausea and vomiting to a level acceptable to the patient — nausea itself can be more distressing than vomiting and significantly affects quality of life.
- Correct or prevent dehydration and electrolyte derangement, particularly hypokalemia, hypomagnesemia, hypo- or hypernatremia, and metabolic alkalosis from repeated vomiting.
- Identify and treat the underlying cause whenever one can be found, rather than relying on symptomatic antiemetic therapy alone.
- Prevent complications of prolonged or severe vomiting — esophageal injury (Mallory-Weiss tear or, rarely, rupture), malnutrition, and dental erosion.
- Use the lowest effective antiemetic dose for the shortest duration needed, minimizing sedation, extrapyramidal, and QTc risk.
- Restore normal oral intake and nutrition, and minimize disruption to the patient’s daily functioning.
Choose Initial Treatment
Step 1 — screen before you treat
Do not treat symptomatically first if any red flag from Red Flags & Refer is present — obtain urgent assessment and the appropriate work-up before starting an antiemetic, since symptomatic relief can mask a surgical abdomen, an intracranial process, or another emergency.
Step 2 — treat the cause when one is identified
Cause identified direct treatment at the underlying process whenever possible — deprescribe or switch a causative medication, treat the infection or metabolic derangement, or start a prokinetic for confirmed gastroparesis — rather than layering an antiemetic on top of an untreated cause.
Step 3 — choose the antiemetic by mechanism
Vestibular or motion-related pattern start an antihistamine/anticholinergic — dimenhydrinate, diphenhydramine, or hydroxyzine.
Fullness, early satiety, or delayed-emptying pattern start a dopamine-antagonist prokinetic — metoclopramide or domperidone.
No clear mechanism, or symptoms persist after treating the identified cause start a serotonin 5-HT3 antagonist (ondansetron) or a dopamine antagonist — the two classes with the best general-purpose evidence and the least sedation — chosen by adverse-effect profile, available route, and patient preference rather than a proven superiority of one over the other.
Step 4 — route
Oral intake not tolerated switch to a non-oral route (orally-disintegrating tablet, intramuscular, intravenous, subcutaneous, or rectal, depending on the agent) rather than persisting with an oral dose the patient cannot keep down.
Step 5 — stewardship
Do not continue any dopamine-antagonist antiemetic (metoclopramide, prochlorperazine, promethazine, domperidone, haloperidol, chlorpromazine) beyond the shortest effective duration — for metoclopramide specifically, treatment must not exceed 12 weeks because of a duration- and dose-dependent risk of tardive dyskinesia.[5]
Non-Pharmacologic Treatment
Medication review — often the highest-yield intervention
Before adding an antiemetic, review the full medication list for a drug that could be causing or worsening the patient’s nausea; stopping, switching, or reducing the dose of a causative agent is frequently more effective than treating symptomatically on top of it.[6]
- Opioids — nausea is common when starting or increasing the dose and typically improves with continued, stable dosing (tolerance) within days; see Treatment Failure & Next Steps for a structured approach.
- Antibiotics, particularly macrolides (erythromycin, clarithromycin — a direct motilin-agonist prokinetic effect at antibacterial doses) and metronidazole.
- NSAIDs and ASA, especially at higher or regular dosing.
- Metformin and GLP-1 receptor agonists, particularly at initiation or dose escalation — nausea is dose- and titration-related and often improves with a slower dose titration.
- Digoxin — nausea can be an early sign of digoxin toxicity and warrants a level check, not just an antiemetic.
- Iron supplements and bisphosphonates.
- Levodopa and other dopamine agonists used for Parkinson disease.
- SSRIs and SNRIs, particularly early in treatment.
- Anticonvulsants, especially at supratherapeutic levels.
- Antiarrhythmics.
- Benzodiazepines and other sedating drugs.
- Hormonal contraceptives and other estrogen-containing therapy.
- Colchicine — gastrointestinal upset is often dose-limiting.
- Alcohol and cannabis — see cannabinoid hyperemesis syndrome under Recognize the Condition.
General measures
- Maintain adequate fluid intake — oral rehydration if tolerated, intravenous fluids if oral intake is not possible or dehydration is more than mild.
- For moderate to severe dehydration or ongoing losses, use an oral rehydration solution formulated with an appropriate sodium and potassium content rather than water alone, since water alone does not replace lost electrolytes.[1]
- Recommend small, frequent meals and snacks rather than large, infrequent meals.
- Advise avoidance of specific foods and smells known to trigger the patient’s symptoms.
- Treat pain if nausea and pain coexist — adequately controlling pain often reduces the accompanying nausea.
- Reassure the patient when the underlying cause is self-limited, and discuss watchful waiting as a reasonable option for patients who prefer to avoid medication for mild, self-limited symptoms.
Motion sickness prevention
Prevention is substantially more effective than treating motion sickness once it is established, so counsel patients travelling by car, boat, or air to:
- Avoid a large meal within a few hours of travel, and avoid alcohol, dairy, and foods high in protein, fat, or sodium before travelling.
- Increase ventilation and exposure to cool, fresh air, and avoid smoking or disagreeable odours during travel.
- Minimize head movement by resting the head against a headrest, and avoid reading or watching videos during travel.
- Focus on a stable external reference point (the horizon) rather than nearby moving objects.
- Choose a seat with the best view of the direction of travel and the least motion — the front seat of a car, over the wing of a plane, or a central, lower position on a boat — and drive rather than ride as a passenger when possible.
Acupressure wristbands have not been shown to reduce motion sickness in controlled study.[1]
Psychological approaches
Relaxation therapy and cognitive behavioural therapy can help nausea associated with anticipatory nausea and functional gastrointestinal disorders, and should be considered alongside, not instead of, an organic work-up when a psychiatric or functional cause is suspected.[2]
Aromatherapy
Inhaled isopropyl alcohol — an alcohol prep pad held 1 to 2 cm below the nostrils and inhaled for several breaths, repeated as needed — reduced nausea more effectively than placebo, and in one comparison more effectively than oral ondansetron in the first 30 minutes, in emergency department patients; it is a reasonable low-risk adjunct while a pharmacologic antiemetic takes effect.[7]
Pharmacologic Treatment Options
Selecting an antiemetic by the neurotransmitter pathway most likely driving the patient’s symptoms — dopaminergic, serotonergic, or histaminergic/cholinergic — improves the chance that the first agent tried actually works.[8]
Cause-directed treatment tracks
Vestibular
Start an antihistamine/anticholinergic — dimenhydrinate 50 mg PO/IM/IV/PR every 4-6 hours PRN is the usual first choice; diphenhydramine or hydroxyzine are reasonable alternatives.
GI-motility (gastroparesis)
Start a dopamine-antagonist prokinetic — metoclopramide 10 mg PO before meals and at bedtime, or domperidone 10 mg PO TID before meals (maximum 30 mg/day per Health Canada safety guidance)[9] — for no more than 12 weeks at a time, with objective gastric emptying testing if symptoms persist.
Medication-induced
Deprescribe, switch, or reduce the dose of the causative drug first; add a short-term antiemetic only if the causative drug genuinely cannot be stopped or changed.
Central nervous system
Treat the underlying process (migraine abortive therapy, management of increased intracranial pressure) and use a 5-HT3 antagonist (ondansetron 4-8 mg PO/IV every 8 hours PRN) or a dopamine antagonist for symptomatic relief alongside it.
| Drug / intervention | Role | Dose / use | Important adverse effects | Teaching points |
|---|---|---|---|---|
| Metoclopramide (oral) Preferred | GI-motility/gastroparesis-associated nausea; general empiric use | 10 mg PO TID-QID before meals and at bedtime (max 0.5 mg/kg/day); limit to 12 weeks | Extrapyramidal symptoms, tardive dyskinesia with prolonged use, drowsiness, restlessness | Take before meals. Report any new tremor, stiffness, or unusual movements immediately; do not continue beyond 12 weeks. |
| Domperidone Preferred | GI-motility/gastroparesis-associated nausea, especially when extrapyramidal risk should be avoided | 10 mg PO TID before meals (max 30 mg/day) | QTc prolongation, hyperprolactinemia, diarrhea | Does not cross the blood-brain barrier at usual doses, so extrapyramidal risk is low, but the 30 mg/day ceiling and caution with other QTc-prolonging drugs still apply. |
| Ondansetron Preferred | Empiric use when sedation or extrapyramidal effects should be avoided | 4-8 mg PO/IV every 8 hours PRN | Headache, constipation, QTc prolongation | Least sedating first-line option; check for other QTc-prolonging drugs before use. |
| Dimenhydrinate Preferred | Vestibular/motion-sickness-associated nausea | 50-100 mg PO/IM/IV/PR every 4-6 hours PRN (max 400 mg/day) | Sedation, anticholinergic effects, paradoxical excitation in children | Take 60 minutes before travel for motion-sickness prevention. |
| Prochlorperazine Alternative | General antiemetic when a dopamine antagonist is preferred but metoclopramide/domperidone are not suitable | 5-10 mg PO every 6-8 hours PRN | Sedation, extrapyramidal symptoms, hypotension | More sedating than metoclopramide; monitor for extrapyramidal symptoms, particularly in younger patients. |
| Promethazine Alternative | Vestibular or general nausea, longer duration of action than dimenhydrinate | 12.5-25 mg PO/IM every 4-6 hours PRN | Marked sedation, extrapyramidal symptoms | Reasonable option when dimenhydrinate is ineffective or a longer duration of action is wanted. |
| Hydroxyzine Alternative | Vestibular or general nausea | 25-100 mg PO/IM every 4-6 hours PRN (max 100 mg/day) | Sedation, anticholinergic effects, QTc prolongation | Avoid in early pregnancy; use a lower maximum dose and divided dosing in older adults given QTc risk. |
| Haloperidol Special situation | Refractory or opioid-induced nausea when first-line agents have failed | 0.5-2 mg PO every 12 hours PRN | QTc prolongation, extrapyramidal symptoms | Not recommended specifically for confirmed gastroparesis; reserve for refractory nausea from other causes. |
Special Populations
Pregnancy
Always confirm pregnancy status in a patient of reproductive age before starting empiric pharmacotherapy. Nausea and vomiting of pregnancy is addressed separately, and the antiemetics discussed in this chapter are not the first-line choices for that indication. If a patient within this chapter’s scope happens to be pregnant, note that hydroxyzine is contraindicated in early pregnancy, and safety data for metoclopramide, domperidone, and several other agents in pregnancy are limited — use the lowest effective dose of an agent with more established pregnancy safety data (e.g., dimenhydrinate, diphenhydramine, or ondansetron) and coordinate with the patient’s obstetric provider.
Breastfeeding
Metoclopramide and domperidone are both excreted into breast milk; use only if the benefit outweighs the risk and discuss the feeding plan with the patient. Ondansetron and dimenhydrinate have more reassuring breastfeeding data. Avoid routine, ongoing use of any sedating antihistamine (diphenhydramine, hydroxyzine, promethazine) in a breastfeeding parent given infant sedation risk with regular use.
Pediatrics
This chapter focuses on the adult approach. A few points are specifically important when a pediatric patient is involved: metoclopramide is contraindicated under 1 year of age and, when used at all in an older child, the total daily dose must not exceed 0.5 mg/kg because of a markedly higher extrapyramidal symptom risk in children; domperidone is not approved for pediatric use in Canada; weight-based dimenhydrinate remains a commonly used first-line option for pediatric motion sickness and gastroenteritis-associated nausea; and ondansetron has the most consistent pediatric evidence for reducing vomiting in acute gastroenteritis.[1]
Older adults
Start at the lowest recommended dose and titrate slowly. Older adults carry substantially higher risk of extrapyramidal symptoms and tardive dyskinesia with dopamine antagonists (particularly older women), anticholinergic toxicity and delirium with first-generation antihistamines, QTc prolongation with domperidone, ondansetron, and hydroxyzine, and falls from any sedating agent — review the full medication list for additive anticholinergic, sedative, or QTc-prolonging burden before adding another agent.
Renal impairment
Reduce the metoclopramide dose at a creatinine clearance under 60 mL/min, including patients on hemodialysis or peritoneal dialysis. Reduce the domperidone dosing frequency in significant renal impairment. No significant ondansetron dose adjustment is required for renal impairment.
Hepatic impairment
Reduce the metoclopramide dose in moderate-severe hepatic impairment (Child-Pugh B or C); no adjustment is needed for mild impairment. Avoid domperidone in moderate-severe hepatic impairment. Use caution with any sedating agent given reduced hepatic clearance.
Monitoring & Follow-Up
Reassess symptom response within a few days of starting empiric therapy for acute nausea and vomiting, and sooner if a red-flag feature develops. For any patient started on a dopamine antagonist, set an explicit stop date or review point — metoclopramide specifically must be reassessed by 12 weeks, since continuing past this point substantially increases tardive dyskinesia risk regardless of how well it is controlling symptoms. Review the medication list for other QTc-prolonging drugs, and check an ECG where a cardiac risk factor is present, in a patient started on domperidone, ondansetron, or hydroxyzine. Monitor hydration status and electrolytes (sodium, potassium, bicarbonate) in a patient with more than mild or brief vomiting, and correct deficits before they cause complications. For confirmed gastroparesis, track weight, nutritional status, and glycemic control (in diabetic patients) alongside symptom control, since worsening glycemic control both results from and worsens gastroparesis. Reinforce at every visit that any dopamine-antagonist antiemetic is a short-term therapy, and specifically ask about new tremor, muscle stiffness, restlessness, or involuntary movements at each follow-up while a patient remains on one.
Treatment Failure / Next Step
- Re-screen for a red flag or organic cause that may have been missed on initial assessment — repeat a focused history and examination, and obtain imaging or endoscopy if not already performed.
- Confirm the oral route is actually being tolerated; switch to a non-oral route (orally-disintegrating, intramuscular, intravenous, subcutaneous, or rectal) if oral intake is not reliably kept down.
- If the first agent has failed at an adequate dose, switch to an agent from a different mechanistic class rather than a second agent from the same class, and consider combining two agents from different classes for moderate to severe refractory symptoms.
- For confirmed gastroparesis refractory to an initial prokinetic trial, consider an off-label 5-HT4 agonist (e.g., prucalopride) or a short pulsed course (1-4 weeks) of a motilin-receptor agonist (erythromycin or azithromycin, off-label, low-dose) — pulsed rather than continuous dosing is used specifically because the prokinetic effect is lost with continuous exposure (tachyphylaxis).[4]
- Reconsider whether this is truly gastroparesis versus chronic idiopathic (functional) nausea without confirmed delayed emptying — a low-dose central neuromodulator (a tricyclic antidepressant or mirtazapine, both off-label) may help chronic idiopathic nausea, but has not shown benefit for objectively confirmed gastroparesis specifically and should not substitute for a prokinetic in that setting.[4]
- For refractory opioid-induced nausea, consider adjusting the opioid regimen — reducing the dose, avoiding large dose increases, or rotating to a different opioid at a reduced equivalent dose — before further escalating antiemetic therapy, since tolerance to opioid-induced nausea often develops with continued, stable dosing.[10]
- Refer to a gastroenterology or motility specialist for medically refractory, objectively confirmed gastroparesis — gastric electrical stimulation and pyloric-directed endoscopic therapy are specialist-directed options reserved for refractory cases.[4]
- If no cause is ever identified despite a thorough work-up and symptoms remain disabling, refer for formal evaluation of chronic idiopathic nausea and vomiting syndrome or cyclic vomiting syndrome rather than continuing indefinite empiric antiemetic escalation.
Common Errors to Avoid
- Starting symptomatic antiemetic therapy before screening for red-flag features suggesting a surgical abdomen, an intracranial process, or another emergency.
- Continuing metoclopramide beyond 12 weeks, or not adding up cumulative exposure when more than one prescriber has ordered it.
- Exceeding domperidone’s 30 mg/day ceiling, or starting it in a patient with an unreviewed QTc-prolonging drug or cardiac risk factor.
- Missing a medication as the actual cause of nausea and simply adding another antiemetic on top instead of reviewing and, where possible, adjusting the causative drug.
- Diagnosing gastroparesis from symptoms alone without objective gastric emptying testing.
- Reaching for a central neuromodulator (a tricyclic antidepressant) as a gastroparesis prokinetic — trial evidence has not shown benefit for gastric emptying or global symptoms in confirmed gastroparesis specifically.[4]
- Using continuous, ongoing motilin-agonist therapy (erythromycin) for gastroparesis rather than a short pulsed course — the prokinetic effect is lost with continuous exposure.
- Forgetting to confirm pregnancy status in a patient of reproductive age before starting an antiemetic.
- Missing cannabinoid hyperemesis syndrome in a patient with heavy, prolonged cannabis use and cyclic vomiting that is temporarily relieved by hot showers or bathing.
- Over-escalating antiemetic therapy for early opioid-induced nausea instead of allowing tolerance to develop over the first days of stable dosing, or adjusting the opioid regimen first.
Clinical Decision Algorithm
Drug Tables
This section summarizes every drug discussed in this chapter with full dosing detail. Drugs used specifically for gastroparesis carry the evidence caveats established in the current ACG gastroparesis guideline, and Health Canada-specific dosing ceilings are noted for metoclopramide and domperidone.[5][9][4] Transdermal scopolamine (Transderm-V), previously a first-line motion-sickness option, has been discontinued by its sole Canadian supplier and is no longer an actionable option for new prescriptions — injectable scopolamine hydrobromide remains available but is not a standard outpatient choice for this indication.[11]
Dopamine antagonists
Do not continue beyond the shortest effective duration; metoclopramide specifically must not exceed 12 weeks. Highest tardive dyskinesia risk is in elderly women, patients with diabetes or hepatic/renal failure, and those on concomitant antipsychotics.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Metoclopramide (oral) | Adults: 10 mg PO TID-QID, 30 minutes before meals and, if needed, at bedtime (max 0.5 mg/kg/day) Elderly, or renal/hepatic impairment: Reduce the dose; start at approximately half the usual dose Pediatrics (5-14 years, gastroparesis only): 2.5-5 mg PO TID before meals; contraindicated under 1 year of age | Extrapyramidal symptoms, tardive dyskinesia (risk increases with treatment duration and cumulative dose), drowsiness, restlessness, hyperprolactinemia | Additive sedation with other CNS depressants; avoid combining with other dopamine antagonists/antipsychotics (potentiated extrapyramidal risk); alters absorption of other oral drugs via changed GI transit | Do not exceed 12 weeks of continuous use. Reduce the dose in renal impairment (creatinine clearance under 60 mL/min) or moderate-severe hepatic impairment. Contraindicated with GI obstruction, perforation, or hemorrhage, and in epilepsy. |
| Metoclopramide (parenteral) | Adults: 10 mg IM/IV every 4-6 hours PRN | Extrapyramidal symptoms, tardive dyskinesia with prolonged use, drowsiness, restlessness, hyperprolactinemia | Additive sedation with other CNS depressants; avoid combining with other dopamine antagonists/antipsychotics | A distinct injectable-only monograph, used for parenteral or perioperative indications; see the oral tablet entry above for outpatient dosing. |
| Domperidone | Adults: 10 mg PO TID, 15-30 minutes before meals (max 30 mg/day) Renal impairment: Reduce dosing frequency to once or twice daily depending on severity Hepatic impairment: Avoid in moderate-severe impairment | QTc prolongation, hyperprolactinemia (galactorrhea, menstrual irregularity), diarrhea, abdominal cramping | Avoid with other QTc-prolonging drugs and strong CYP3A4 inhibitors (domperidone is metabolized by CYP3A4) | Maximum 30 mg/day regardless of indication; consider a baseline ECG in a patient with cardiac risk factors. Available by prescription in Canada. |
| Prochlorperazine | Adults: 5-10 mg PO every 6-8 hours PRN | Sedation, extrapyramidal symptoms, hypotension, anticholinergic effects | Additive sedation with other CNS depressants; additive extrapyramidal risk with other dopamine antagonists | More sedating than metoclopramide; use caution in older adults. |
| Promethazine | Adults, oral: 12.5-25 mg PO every 4-6 hours PRN Adults, IM: 12.5-25 mg IM every 4-6 hours PRN | Marked sedation, extrapyramidal symptoms, anticholinergic effects | Additive sedation with other CNS depressants | Longer duration of action than dimenhydrinate; may help when dimenhydrinate is ineffective. |
| Haloperidol | Adults: 0.5-2 mg PO every 12 hours PRN | QTc prolongation, extrapyramidal symptoms | Additive QTc-prolonging and sedative risk with other such drugs | Reserve for refractory nausea from causes other than confirmed gastroparesis; not recommended specifically for gastroparesis management given a lack of supporting evidence in that setting. |
| Chlorpromazine | Adults: 12.5-25 mg PO/IM every 4-6 hours PRN (max 150 mg/day for nausea and vomiting) | Sedation, hypotension (more pronounced than other phenothiazines), extrapyramidal symptoms, anticholinergic effects | Additive sedation and hypotension with other CNS depressants/antihypertensives | More anticholinergic and hypotensive than prochlorperazine; reserve for when other dopamine antagonists are ineffective or unavailable. |
Serotonin 5-HT3 receptor antagonists
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Ondansetron | Adults, oral: 4-8 mg PO every 8 hours PRN (max 24 mg/day divided) Adults, IV: Up to 16 mg IV initially, infused over at least 15 minutes (do not exceed 8 mg if age 75 or older); subsequent doses no more than 8 mg, at least 4 hours apart | Headache, constipation, dizziness, QTc prolongation | Additive QTc-prolonging risk with other such drugs; CYP3A4 inducers (carbamazepine, phenytoin, rifampin) may reduce ondansetron concentrations; may reduce the analgesic effect of tramadol | Least sedating first-line option; evidence in adult acute gastroenteritis specifically is more limited than in pediatric use. |
Antihistamines / anticholinergics
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Dimenhydrinate | Adults: 50-100 mg PO/IM/IV/PR every 4-6 hours PRN (max 400 mg/day) Adults, long-acting: 100 mg PO every 8-12 hours PRN (max 300 mg/day) Children 6-12 years: 25-50 mg PO every 6-8 hours PRN Children 2-6 years: 15-25 mg PO every 6-8 hours PRN | Sedation, anticholinergic effects (dry mouth, constipation, urinary retention, blurred vision), confusion in older adults, paradoxical excitation in children | Additive sedation with other CNS depressants | Take 60 minutes before travel for motion-sickness prevention; a long-acting formulation is available for extended coverage. |
| Diphenhydramine (oral) | Adults: 25-50 mg PO every 4-6 hours PRN (max 200 mg/day) | Sedation, anticholinergic effects, confusion in older adults | Additive sedation with other CNS depressants; inhibits CYP2D6 and can raise levels of drugs cleared by this pathway | Oral tablet/capsule/liquid-gel formulation; a separate injectable product exists for the intramuscular/intravenous route (see below). |
| Diphenhydramine (parenteral) | Adults: 10-50 mg IM/IV every 4-6 hours PRN | Sedation, anticholinergic effects | Additive sedation with other CNS depressants | A distinct injectable-only monograph. |
| Hydroxyzine | Adults: 25-100 mg PO/IM every 4-6 hours PRN, adjusted to response (max 100 mg/day) | Sedation, anticholinergic effects, QTc prolongation | Additive sedation with other CNS depressants; additive QTc-prolonging risk with other such drugs | Not recommended in early pregnancy; use a reduced maximum dose in older adults given QTc risk. |
| Meclizine | Adults: 25-50 mg PO once daily, 1 hour before travel | Sedation, anticholinergic effects | Additive sedation with other CNS depressants | No Health Canada-authorized monograph currently on file for this platform; dosing shown reflects standard Canadian OTC labelling. |
| Scopolamine (transdermal) | Availability: Discontinued in Canada | Sedation, dry mouth, blurred vision, confusion or delirium in older adults | Additive sedation with other CNS depressants | Discontinued in Canada by its sole supplier as of 2025 — not an actionable option for new prescriptions; listed for reference only. |
Natural health product
Evidence for general nausea and vomiting is inconsistent, though it is more consistently supported for acute migraine-associated nausea; not a substitute for an evidence-based agent in moderate-severe symptoms.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Ginger (Zingiber officinale) | Adults: 250 mg PO QID, or 500 mg PO BID | Abdominal discomfort, diarrhea, a peppery irritant effect in the mouth and throat | May inhibit CYP2C19 in vitro; clinical significance unclear | No Health Canada-authorized monograph currently on file for this platform; consult product-specific labelling for the exact preparation used. |
GI prokinetics for gastroparesis beyond dopamine antagonists (off-label)
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Erythromycin | Adults, off-label prokinetic dose: 125-250 mg PO TID, 30 minutes before meals, for 1-4 weeks | GI upset (cramping, diarrhea) often dose-limiting, QTc prolongation | Strong CYP3A4 inhibitor with numerous interactions; additive QTc-prolonging risk with other such drugs | Off-label prokinetic dose, well below antibacterial dosing. Use a short pulsed course rather than continuous therapy, since the prokinetic effect is lost with continuous exposure (tachyphylaxis) within a few weeks. |
| Prucalopride | Adults: 2 mg PO once daily Age 65 or older, or severe renal/hepatic impairment: 1 mg PO once daily | Headache, GI upset (nausea, diarrhea, abdominal pain) | None clinically significant | Used off-label for gastroparesis; the Health Canada-approved indication is chronic idiopathic constipation. |
Central neuromodulators for chronic idiopathic nausea (off-label, not a substitute for a prokinetic in confirmed gastroparesis)
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Nortriptyline | Adults, off-label: 10-25 mg PO once daily at bedtime, titrated to response | Anticholinergic effects, sedation, orthostatic hypotension, QTc prolongation | Additive sedation/anticholinergic burden with other such drugs; avoid with MAO inhibitors | Off-label for chronic idiopathic nausea. A randomized trial found no benefit for global symptom relief in confirmed gastroparesis, with only mild abdominal-symptom benefit; not a substitute for a prokinetic in confirmed gastroparesis. |
| Amitriptyline | Adults, off-label: 10-25 mg PO once daily at bedtime, titrated to response | Anticholinergic effects, sedation, orthostatic hypotension, QTc prolongation | Additive sedation/anticholinergic burden with other such drugs; avoid with MAO inhibitors | Off-label for chronic idiopathic nausea; a low-dose trial did not affect gastric emptying in functional dyspepsia, so reserve for functional/chronic idiopathic nausea rather than confirmed gastroparesis. |
| Mirtazapine | Adults, off-label: 7.5-15 mg PO once daily at bedtime | Sedation, increased appetite and weight gain, dizziness | Additive sedation with other CNS depressants; avoid with MAO inhibitors | Off-label option for chronic nausea with reduced appetite, given its antiemetic and appetite-stimulating receptor profile; evidence specific to confirmed gastroparesis is limited. |
| Buspirone | Adults, off-label: 10 mg PO TID, 15-30 minutes before meals | Dizziness, headache, nausea (paradoxically, at higher doses) | Avoid with MAO inhibitors; strong CYP3A4 inhibitors increase levels | Off-label for functional dyspepsia-associated nausea and early satiety via relaxation of gastric fundic accommodation; distinct from its approved anxiety dosing. |
Adjunct option for refractory nausea (off-label)
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Olanzapine | Adults, off-label: 2.5-5 mg PO once daily or BID | Sedation, weight gain, metabolic effects (hyperglycemia, dyslipidemia) with regular use, QTc prolongation | Additive sedation with other CNS depressants | Off-label, low-dose option for refractory nausea when first-line agents have failed; a broader receptor-binding profile (dopamine, serotonin, histamine, muscarinic) than single-mechanism antiemetics. |
Professional reference only. Apply clinical judgment and verify patient-specific decisions against current authoritative guidance and product information.