Can You Take Zofran and Atarax Together?
Yes, you can take Zofran (ondansetron) and Atarax (hydroxyzine) together, but this combination requires careful cardiac monitoring due to additive QT-interval prolongation risk. 1
Primary Safety Concern: QT Prolongation
Both medications independently prolong the QT interval, and their combination increases the risk of torsades de pointes, a potentially fatal cardiac arrhythmia. 2, 1
Specific Risk Factors to Assess Before Combining
Before using these medications together, evaluate for:
- Pre-existing heart disease, recent myocardial infarction, uncompensated heart failure, or bradyarrhythmias 1
- Congenital long QT syndrome or family history of long QT syndrome 1
- Electrolyte abnormalities, particularly hypokalemia or hypomagnesemia 2, 1
- Concurrent use of other QT-prolonging medications (see list below) 2, 1
Mandatory Precautions When Using Together
Obtain a baseline electrocardiogram before initiating combination therapy to assess the QT interval, especially if any cardiac risk factors are present. 2
Check and correct serum potassium and magnesium levels prior to starting treatment, as electrolyte deficiencies significantly heighten cardiac toxicity risk. 2
Limit ondansetron to a maximum of 8 mg per dose to minimize QT prolongation risk. 2, 3
Medications That Further Increase Risk
The FDA label for hydroxyzine specifically warns about combining it with ondansetron and other QT-prolonging drugs. 1 Additional medications that compound this risk include:
- Antiarrhythmics: quinidine, procainamide, amiodarone, sotalol 1
- Antipsychotics: ziprasidone, iloperidone, clozapine, quetiapine, chlorpromazine 2, 1
- Antidepressants: citalopram, fluoxetine 1
- Antibiotics: azithromycin, erythromycin, clarithromycin, moxifloxacin 2, 1
- Other antihistamines: diphenhydramine, loratadine 2
Central Nervous System Depression
Hydroxyzine potentiates the effects of other CNS depressants, requiring dose reduction when combined with narcotics, non-narcotic analgesics, or barbiturates. 1
- Warn patients about increased drowsiness and caution against driving or operating machinery 1
- Advise against alcohol use, as hydroxyzine increases alcohol's effects 1
- Start elderly patients on low doses of hydroxyzine due to increased risk of confusion and over-sedation 1
Clinical Context for Combined Use
This combination is most commonly used when ondansetron alone fails to control nausea. 2 The NCCN guidelines note that hydroxyzine may be useful for opioid-induced pruritus when administered with ondansetron for nausea control. 2
Ondansetron combined with dexamethasone remains the gold-standard regimen for chemotherapy-induced nausea and vomiting, and should be considered before adding hydroxyzine. 2, 3
Safer Alternative Combinations
If additional antiemetic effect is needed beyond ondansetron alone:
- Add dexamethasone (4-12 mg) for synergistic antiemetic benefit without QT-prolongation concerns 2, 3
- Consider metoclopramide (10-20 mg) or prochlorperazine as alternatives to hydroxyzine 2
- Lorazepam (0.5-2 mg every 4-6 hours) can be added for anticipatory nausea without cardiac risk 2
Special Populations
In elderly patients, start hydroxyzine at the low end of the dosing range due to greater frequency of decreased hepatic, renal, or cardiac function. 1
In pregnant patients with hyperemesis gravidarum, ondansetron should only be used as second-line therapy after 10 weeks of gestation due to potential cardiac defect risk in the first trimester. 2
Common Pitfall to Avoid
Do not assume therapeutic doses are automatically safe together—the QT prolongation risk exists even at standard dosing of both medications when combined. 1 The interaction is dose-dependent and cumulative, making cardiac monitoring essential rather than optional.