Vistaril Drug Interactions: What to Avoid and What to Tell Your Doctor

Vistaril (hydroxyzine) has moderate interactions with over 200 different drugs according to available clinical data. Most interactions fall into two main categories: drugs that enhance its sedative effects, and drugs that increase the risk of a dangerous heart rhythm problem called QT prolongation. Here's what you need to know before starting hydroxyzine.

Category 1: CNS Depressants (Enhanced Sedation)

Hydroxyzine enhances the effect of other central nervous system (CNS) depressants. When taken together, the combined sedation can be significantly greater than either drug alone. This is not always dangerous — but you must be aware of it, especially for activities requiring alertness.

CNS depressants to discuss with your doctor include:

Opioid pain medications (morphine, oxycodone, hydrocodone, tramadol): Significant sedation enhancement. When hydroxyzine is used with opioids (such as for preoperative sedation), opioid doses are typically reduced. FDA labels warn of respiratory depression risk when opioids and CNS depressants are combined.

Benzodiazepines (alprazolam/Xanax, lorazepam/Ativan, diazepam/Valium, clonazepam/Klonopin): Combining hydroxyzine and benzodiazepines greatly increases sedation. Your doctor may still prescribe both in some situations but at reduced doses.

Barbiturates (phenobarbital): FDA labeling explicitly warns about the potentiating action of hydroxyzine with barbiturates.

Sleep medications (zolpidem/Ambien, eszopiclone/Lunesta, zaleplon): Enhanced sedation.

Muscle relaxants (cyclobenzaprine, methocarbamol): Increased sedation.

Alcohol: Alcohol is a CNS depressant. Combining with hydroxyzine significantly worsens sedation. Avoid alcohol entirely while taking Vistaril.

Category 2: QT-Prolonging Medications (Heart Rhythm Risk)

Hydroxyzine can prolong the QT interval on an electrocardiogram (ECG). The QT interval represents the time it takes the heart to electrically reset between beats. When it's prolonged beyond normal, there is a risk of a dangerous arrhythmia called Torsade de Pointes, which can cause fainting, cardiac arrest, or death. Combining hydroxyzine with other QT-prolonging drugs multiplies this risk.

QT-prolonging medications to discuss with your doctor:

Antiarrhythmics (quinidine, procainamide — Class IA; amiodarone, sotalol — Class III): High risk of QT prolongation when combined.

Antipsychotics (ziprasidone, iloperidone, clozapine, quetiapine, chlorpromazine): Significant QT risk; caution recommended.

Antidepressants (citalopram/Celexa, escitalopram/Lexapro in high doses, fluoxetine/Prozac): Higher doses of citalopram are associated with QT prolongation; discuss with your prescriber.

Antibiotics (azithromycin/Z-Pack, clarithromycin, erythromycin, gatifloxacin, moxifloxacin): Well-known QT-prolonging antibiotics. Tell your prescriber you take hydroxyzine if they're considering one of these.

Other notable QT-prolongers: methadone, ondansetron (Zofran), pentamidine, certain cancer medications, HIV medications.

Category 3: Anticholinergic Drugs

Hydroxyzine has anticholinergic properties. When combined with other anticholinergic medications, the combined effect can lead to significant dry mouth, urinary retention, constipation, confusion, and in severe cases, anticholinergic toxicity. Common anticholinergic drugs include:

Tricyclic antidepressants (amitriptyline, nortriptyline, imipramine)

Bladder medications (oxybutynin/Ditropan, tolterodine/Detrol)

Certain antipsychotics (chlorpromazine, promethazine)

Some GI medications (dicyclomine, propantheline)

Allergy Interaction: Cetirizine and Levocetirizine

Hydroxyzine is chemically related to cetirizine (Zyrtec) and levocetirizine (Xyzal) — they are actually metabolites or close chemical relatives of hydroxyzine. Because of this, patients who experience a hypersensitivity reaction (including AGEP) to hydroxyzine should avoid cetirizine and levocetirizine due to cross-sensitivity risk.

What to Tell Your Doctor Before Starting Vistaril

Give your prescriber a complete list of all medications you take, including:

All prescription medications

Over-the-counter drugs (antihistamines, sleep aids, cold medications)

Vitamins and supplements (especially valerian, kava, melatonin — which are sedating)

Any history of heart rhythm problems

Any history of reaction to Zyrtec (cetirizine) or Xyzal (levocetirizine)

For a full review of Vistaril side effects, see our companion guide: Vistaril Side Effects: What to Expect and When to Call Your Doctor.