Likely due to its sedating nature, hydroxyzine (generic Vistaril) is an antihistamine that may be preferable to newer options like Zyrtec (cetirizine), Claritin (loratadine), Allegra (fexofenadine), and Xyzal (levocetirizine) for the treatment of pruritus (itching), anxiety, and nausea than non-drowsy antihistamines. However, drowsiness can be a big problem, and combining hydroxyzine with other meds that produce sleepiness, like CNS depressants, is particularly risky. Other adverse effects of hydroxyzine can also be additive with other drugs. To keep yourself safe, you should be aware of the prescription drugs, nonprescription medications, and foods that interact with hydroxyzine.
Key takeaways:
- Central nervous system (CNS) depressants are a large umbrella category of medications that can cause drowsiness, making them a hazard in combination with hydroxyzine.
- One of hydroxyzine’s serious adverse effects is a potential effect on electrical conduction in the heart, specifically prolongation of the QT interval. If used along with other QT-prolonging pills, the danger is heightened.
- Hydroxyzine can produce serious side effects via its anticholinergic effect, meaning it inhibits the neurotransmitter acetylcholine, which can be cumulative with other anticholinergic drugs.
- If you are being prescribed hydroxyzine and a drug that interacts with it, immediately bring your concern to the prescribing healthcare professional to have it addressed.
Hydroxyzine drug interactions
The potential for adverse effects with hydroxyzine alone is noteworthy. Drowsiness and dizziness are fairly common, along with anticholinergic effects like dry mouth, urinary retention, and constipation. Less common but much more serious is the potential for cardiac QT-prolongation, which can precipitate serious heart rhythm problems. The risk of these issues is raised by taking medications with similar side effects.
CNS depressants
Drugs that cause drowsiness are termed CNS depressants. Hydroxyzine falls within that broad category, and coupling it with other meds creates more concern for falls and accidents. Some specific examples of drug classes and members are worth pointing out.
- Opiate analgesics, including Oxaydo (oxycodone), morphine, and hydrocodone-acetaminophen
- Benzodiazepines, such as Xanax (alprazolam), Ativan (lorazepam), and Valium (diazepam)
- Muscle relaxants, like Fexmid (cyclobenzaprine), metaxalone, and Robaxin (methocarbamol)
- Anticonvulsants, including Neurontin (gabapentin) and Lyrica (pregabalin)
- Hypnotics, such as Ambien and Lunesta
- Antidepressants, like Prozac and trazodone
Symptoms could range from mild sleepiness to difficulty waking up or unsteadiness with walking. Severe degrees are reasons to seek care immediately. You may need to avoid hydroxyzine if you take another CNS depressant, or the dosing may need to be conservative to avoid over-sedation. Besides dose, your age and other medical conditions could be other factors your healthcare provider will consider.
QT-prolonging drugs
QT prolongation amounts to slowing down the electrical reset after heartbeats. This delay increases the chance of a life-threatening heart arrhythmia developing. Besides hydroxyzine, many different types of medications can prolong the QT interval. We will name a few.
- Macrolide antibiotics, like Zithromax and clarithromycin
- Quinolone antibiotics, such as levofloxacin and moxifloxacin
- Antipsychotics, including Seroquel (quetiapine) and Risperdal (risperidone)
- Antidepressants like Celexa (citalopram), Remeron (mirtazapine), and doxepin
Those examples of QT-prolonging drugs demonstrate how common this issue can be, particularly when mental health medications are often used concurrently. Adding multiple meds that affect cardiac conduction is typically when problems arise. If multiple medications on your list can prolong the QT interval, ask the prescribing healthcare professional to look into it. You may end up getting an electrocardiogram (EKG), a simple in-office test, to measure the QT interval.
Anticholinergics
Inhibiting the action of acetylcholine defines the unifying characteristic of anticholinergics, a category of drugs from an array of different classes. Antihistamines, both sedating (hydroxyzine and diphenhydramine) and non-drowsy (cetirizine and loratadine) varieties can have anticholinergic side effects. A few examples of other anticholinergic drug classes are good to know.
- Antipsychotics, such as Seroquel, Zyprexa (olanzapine), and Risperdal
- Bladder antimuscarinics, like trospium, Ditropan XL (oxybutynin XL), and Detrol (tolterodine)
- Inhaled antimuscarinics, including Spiriva Respimat (tiotropium), Atrovent HFA (ipratropium), and Incruse Ellipta (umeclidinium)
- Tricyclic antidepressants, such as doxepin, amitriptyline, and nortriptyline
While used for different indications, these drug categories all have an anticholinergic effect. Symptoms can include blurred vision, difficulty urinating, constipation, confusion, and agitation. The stronger the doses and the more medications added to the anticholinergic toxicity, the more severe the symptoms may be. Older adults are more susceptible. If you find yourself in a situation where you are having these symptoms and are taking hydroxyzine with or without another anticholinergic, contact your healthcare provider immediately for instructions.
Hydroxyzine food interactions
Fortunately, hydroxyzine hydrochloride does not have serious interactions with most food. You can take it with or without a meal.
Hydroxyzine hydrochloride and grapefruit
As it does with many meds, grapefruit juice can interact with hydroxyzine. Inhibition of the drug’s metabolism results in higher levels of hydroxyzine, leading to more risk of QT-prolongation.
Other hydroxyzine interactions
Drinks are a different story, and unlike foods, certain drinks can have a notable interaction with this antihistamine.
Hydroxyzine and alcohol
Without a doubt, alcohol is a CNS depressant. Put it together with hydroxyzine, and you might be doubly drowsy, making it a dangerous cocktail.
Hydroxyzine and caffeine
Taking hydroxyzine for anxiety and drinking caffeinated beverages is like shooting yourself in the foot. By taking hydroxyzine for its sedating effects, you counter it with the stimulation from caffeine. On the other hand, if you are taking hydroxyzine for itching, caffeine may offset the tiredness side effect well.
Hydroxyzine, cannabis, and illicit drugs
The concern here is akin to the worry with alcohol and CNS depressants. Cannabis and drugs like heroin can combine with hydroxyzine to make for a dangerous medley of sedating substances.
Hydroxyzine and herbal supplements
Plant-based products can fall under CNS depressants like kratom, anticholinergics like Jimson weed, or QT-prolongers like berberine. Just because they are found in nature does not mean that herbs cannot harm you or interact with drugs like hydroxyzine.
How to minimize hydroxyzine interactions
Awareness and communication are your biggest allies in staying safe during medical treatment. Please be aware of the risks of drug interactions anytime you take a new pill, whether prescribed or over-the-counter. Review your complete medication list with your healthcare provider and discuss any concerns about additive side effects.
When to talk to a healthcare provider about hydroxyzine interactions
Asking about drug interactions when you are first prescribed hydroxyzine is wise. You and the prescribing provider can review your medication list for any concerns. If you have been taking hydroxyzine and are about to add in a new prescription or nonprescription pill, stop and ask your healthcare provider or pharmacist for medical advice about any interactions. Your interest and inquisitions will be welcomed, and as a result, you will be safer.
Sources
- Hydroxyzine: drug information, UpToDate (2023)
- Hydroxyzine hydrochloride label, FDA (2014)
- Hydroxyzine hydrochloride drug label, NIH DailyMed (2022)
- Hydroxyzine (oral route), Mayo Clinic (2023)
- Managing anticholinergic side effects, Primary Care Companion Journal Clinical Psychiatry (2004)
- Long QT syndrome, Cleveland Clinic (2023)