Is hydroxyzine (an antihistamine) effective for treating nausea?

Hydroxyzine for Nausea: Limited Evidence but May Be Useful as Adjunctive Therapy

Hydroxyzine has demonstrated antiemetic effects and can be considered for nausea management, particularly as an adjunctive agent for opioid-induced pruritus with concurrent nausea or in persistent nausea cases, though it is not a first-line antiemetic. 1, 2

Evidence for Antiemetic Activity

Pharmacological Basis

• Hydroxyzine has documented antiemetic effects demonstrated through both apomorphine and veriloid testing, with clinical effects typically noted within 15-30 minutes of oral administration 2
• The FDA label confirms hydroxyzine's antiemetic properties as part of its pharmacological profile, though this is not its primary indication 2

Clinical Context in Guidelines

• ASCO and NCCN guidelines specifically recommend hydroxyzine for opioid-induced pruritus management (10-50 mg at night or via intramuscular injection), where it may provide dual benefit if nausea coexists with itching 1
• NCCN guidelines list hydroxyzine among antihistamines that "may be beneficial" for persistent nausea when added to other antiemetics targeting different mechanisms 1

Recent Research Evidence

• A 2024 retrospective cohort study of 647 female surgical patients found that prophylactic hydroxyzine 25 mg significantly reduced postoperative nausea and vomiting incidence on the day of surgery (34.8% vs 57.0% with no prophylaxis, p=0.002) and through postoperative day 2 (47.8% vs 65.3%, p=0.016) 3
• This represents the most recent and highest-quality evidence specifically examining hydroxyzine for nausea prevention 3

Position in Treatment Algorithm

Not a First-Line Agent

• First-line antiemetics for nonspecific nausea should be dopamine receptor antagonists (metoclopramide, prochlorperazine, haloperidol) or ondansetron, which have stronger evidence 1, 4
• Metoclopramide has the strongest evidence for chronic nausea management and is recommended as first-line for opioid-related nausea 1

Appropriate Clinical Scenarios for Hydroxyzine

• As an adjunctive agent when first-line antiemetics provide inadequate relief, particularly when combined with agents targeting different mechanisms 1
• When sedation is desirable alongside nausea control (e.g., anxious patients, nighttime dosing) 1, 4
• For opioid-induced pruritus with concurrent nausea, where hydroxyzine addresses both symptoms simultaneously 1
• Prophylactically in surgical patients at high risk for postoperative nausea and vomiting, based on the 2024 evidence 3

Dosing Recommendations

• Standard dosing: 10-50 mg orally or intramuscularly 1
• For postoperative nausea prevention: 25 mg has demonstrated efficacy 3
• Timing: Administer when sedative effects are acceptable, often at bedtime 1

Critical Safety Considerations

Sedation Profile

• Hydroxyzine is a sedating antihistamine that may cause drowsiness, which limits daytime use but can be advantageous for nighttime administration 1
• Avoid in patients requiring alertness or when operating machinery 1

Renal and Hepatic Impairment

• Halve the dose in moderate renal impairment (creatinine clearance 10-20 mL/min) 1
• Avoid in severe renal impairment (creatinine clearance <10 mL/min) 1
• Avoid in severe liver disease due to inappropriate sedating effects 1

Pregnancy Contraindication

• Hydroxyzine is specifically contraindicated during early pregnancy in current UK manufacturer guidance 1, 5
• This is the only antihistamine with explicit early pregnancy contraindication 1

Potential for Nightmares

• Hydroxyzine can alter sleep architecture and trigger nightmares, particularly with bedtime dosing, by affecting multiple neurotransmitter systems 5
• Consider earlier evening administration or dose reduction if nightmares occur 5
• Elderly patients require lower starting doses due to increased sensitivity to psychomotor impairment and fall risk 5

Comparative Effectiveness

• No evidence demonstrates hydroxyzine superiority over other antihistamines (diphenhydramine, promethazine) for nausea 1
• Ondansetron has better safety profile (no sedation, no akathisia) and should generally be preferred when sedation is undesirable 4
• Hydroxyzine does not significantly prolong QT intervals, making it safer than some alternatives in cardiac disease patients 6

Common Pitfalls to Avoid

• Do not use hydroxyzine as monotherapy for severe or persistent nausea—it should supplement more effective agents 1
• Do not prescribe in early pregnancy unlike other antihistamines that may be cautiously used 1, 5
• Do not overlook renal function—dose adjustment is mandatory in renal impairment 1, 5
• Do not combine with other sedating medications without considering additive CNS depression 1