Hydroxyzine and QT Prolongation: What You Need to Know About the Cardiac Risk

Hydroxyzine has been around for decades. It’s the go-to for anxiety, itching, and nausea - especially in older adults and kids. But if you’ve been told it’s "safe" because it’s just an antihistamine, you’re being given outdated advice. Since 2015, regulators in Europe and the U.S. have been warning doctors: hydroxyzine can mess with your heart’s rhythm. And in some people, that can be deadly.

How Hydroxyzine Affects the Heart

Hydroxyzine blocks histamine receptors, which is why it calms itching and anxiety. But it also blocks something else: hERG potassium channels in heart cells. These channels are like tiny gates that let potassium out during the heart’s electrical reset phase. When they’re blocked, the heart takes longer to recharge between beats. That’s called QT prolongation.

On an ECG, that looks like a longer line between the Q and T waves. A normal QTc (corrected QT) is under 450 ms for men and 470 ms for women. If it goes above 500 ms, the risk of a dangerous arrhythmia called Torsade de Pointes spikes. This isn’t theoretical. Between 1955 and 2016, at least 59 cases of QT prolongation or Torsade de Pointes were linked to hydroxyzine. Some happened within 10 minutes of the first dose. Others showed up weeks later.

It’s not just the dose - it’s who’s taking it. People with low potassium, low magnesium, slow heart rates, or existing heart disease are at higher risk. Even more dangerous? Taking hydroxyzine with other QT-prolonging drugs like amiodarone, certain antibiotics, or antidepressants. One case in 2022 involved a 68-year-old woman with no heart history who went into cardiac arrest after taking 50 mg hydroxyzine for anxiety - she was also on amiodarone.

Who’s Most at Risk?

Not everyone who takes hydroxyzine will have a problem. But some groups are far more vulnerable:

• People over 65: Their kidneys and liver clear the drug slower. Hydroxyzine’s half-life can stretch to 25 hours in older adults, meaning it builds up.
• Those with electrolyte imbalances: Low potassium or magnesium - common in diabetics, dialysis patients, or people on diuretics - makes the heart extra sensitive.
• People on multiple QT-prolonging drugs: Even if each drug alone is low risk, together they can push the heart over the edge.
• People with undiagnosed long QT syndrome: Some have genetic mutations that make their hearts extra vulnerable. Hydroxyzine can trigger their first symptom - fainting or sudden cardiac arrest.
• Patients with structural heart disease: Scarred or enlarged hearts don’t handle electrical disruptions well.

Here’s the hard truth: a 2021 survey of 127 hospital pharmacists found 63% had seen hydroxyzine prescribed to patients with two or more of these risk factors - even though guidelines say to avoid it entirely in those cases.

Dosing Rules That Actually Matter

Back in the 1990s, doctors would prescribe up to 200 mg of hydroxyzine a day. That’s not safe anymore. The European Medicines Agency (EMA) tightened the rules in 2015:

• Adults: Max 100 mg per day
• Adults over 65: Max 50 mg per day
• Children: 2 mg per kg, up to 40 kg

Even these doses aren’t risk-free. A 2023 case report showed Torsade de Pointes after just 25 mg in a 45-year-old man with undiagnosed long QT syndrome. That’s why the American Geriatrics Society now lists hydroxyzine as a "Potentially Inappropriate Medication in Older Adults."

And here’s what no one tells you: hydroxyzine isn’t the worst offender among antihistamines - but it’s worse than most. Diphenhydramine (Benadryl) has a similar risk. But cetirizine (Zyrtec) and loratadine (Claritin)? They barely touch the QT interval. If you need an antihistamine for itching or allergies, there are safer options.

What Doctors Should Do Before Prescribing

It’s not enough to just check a box on a form. Proper prescribing means three things:

1. Check the ECG: A 12-lead ECG should be done before starting hydroxyzine, especially if the patient is over 60 or has any heart risk factors. If QTc is over 450 ms (men) or 470 ms (women), don’t prescribe it.
2. Review all medications: Use CredibleMeds.org to check for drug interactions. Hydroxyzine is classified as "Known Risk of TdP." If the patient is on another drug in that category, avoid hydroxyzine entirely.
3. Check electrolytes: A simple blood test for potassium and magnesium can prevent disaster. If potassium is below 4.0 mmol/L or magnesium below 1.8 mg/dL, correct those first.

Many hospitals now have electronic health record systems that block hydroxyzine orders if QTc is over 500 ms or if the patient is on a conflicting drug. That’s a good thing. But it’s not foolproof. If you’re a patient, don’t assume your doctor checked all this. Ask.

What Patients Should Ask Their Doctor

If your doctor prescribes hydroxyzine, ask these questions:

• "Have you checked my ECG? What’s my QTc?"
• "Am I taking any other drugs that could affect my heart rhythm?"
• "Could I use something safer - like cetirizine or a non-sedating option?"
• "What symptoms should I watch for?"

Palpitations, dizziness, fainting, or sudden shortness of breath within hours of taking hydroxyzine? That’s not normal. It’s a red flag. Call your doctor or go to the ER. Don’t wait.

The Bigger Picture: Why This Keeps Happening

Hydroxyzine is cheap. It’s available as a generic. It’s been around since 1956. Many doctors still think of it as "harmless." But the data doesn’t lie. Between 2014 and 2022, U.S. prescriptions dropped from 18.3 million to 12.7 million - a 30% decline - because more doctors are learning the risks.

Still, it’s prescribed too often for chronic anxiety or insomnia. That’s the wrong use. Hydroxyzine isn’t meant for long-term use. It’s a short-term tool - for procedural anxiety, acute itching, or brief sedation. For ongoing anxiety, SSRIs or CBT are better. For chronic itching, gabapentin or mirtazapine are safer alternatives.

And now there’s new hope: a new compound called VH-01 is in early trials. It keeps the antihistamine effect but reduces hERG binding by 87%. That could mean a safer version in the next few years.

Bottom Line

Hydroxyzine isn’t evil. But it’s not harmless either. It’s a drug that needs respect - like blood thinners or heart rhythm meds. If you’re young, healthy, and taking it once in a while for a bad itch or anxiety before a dental visit? The risk is low. But if you’re over 65, on other meds, have low potassium, or a history of heart issues? Avoid it. There are better choices.

The era of treating hydroxyzine like a sleepy-time candy is over. If your doctor prescribes it without checking your heart, ask why. Your heart deserves more than assumptions.