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

Hydroxyzine has been used for over 60 years to treat anxiety, itching, and nausea. It’s cheap, widely available, and often prescribed because it works fast - usually within 15 to 60 minutes. But here’s the thing: hydroxyzine isn’t as safe as most doctors or patients think. Behind its calming effects lies a hidden danger: it can mess with your heart’s electrical rhythm and trigger a life-threatening arrhythmia called Torsade de Pointes. This isn’t a rare outlier. It’s a documented, predictable risk - and it’s getting worse because so many people are still being prescribed it without proper checks.

How Hydroxyzine Affects Your Heart

Hydroxyzine blocks a specific ion channel in your heart called hERG. This channel controls the flow of potassium out of heart cells during the repolarization phase - the part of the heartbeat that lets the muscle reset after contracting. When hERG gets blocked, that reset gets delayed. The result? A longer QT interval on an ECG. That’s not just a number on a graph. It means your heart is taking longer than normal to recharge between beats. When this delay gets too long, it can spiral into Torsade de Pointes - a chaotic, twisting rhythm that can cause fainting, seizures, or sudden death.

The science is clear. Studies show hydroxyzine binds tightly to the inner part of the hERG channel at concentrations you reach with normal doses. It doesn’t need a massive overdose. Even 25 mg - half the usual starting dose - has been linked to cardiac events in vulnerable people. The European Medicines Agency confirmed this in 2015 after reviewing 59 reported cases of QT prolongation or Torsade de Pointes tied to hydroxyzine. That’s not a fluke. That’s a pattern.

Who’s at Risk? It’s Not Just the Elderly

You might assume only older adults are at risk. That’s partly true - but it’s not the whole story. The real danger comes from combinations. Someone taking hydroxyzine for anxiety might also be on amiodarone for arrhythmia, or a diuretic that lowers potassium, or an antidepressant like citalopram. All of these drugs prolong the QT interval. Together, they stack up. One study found 63% of pharmacists had seen hydroxyzine prescribed to patients with two or more risk factors - even though guidelines say that’s a hard no.

Other risk factors include:

• Low potassium (under 4.0 mmol/L)
• Low magnesium (under 1.8 mg/dL)
• Heart disease or previous heart attack
• Slow heart rate (under 50 bpm)
• Being female (women naturally have longer QT intervals)
• Genetic variants like CYP2D6 poor metabolizer status - which means your body clears hydroxyzine slowly, letting it build up

There was a 68-year-old woman in a 2022 case report with no prior heart issues. She took 50 mg of hydroxyzine for anxiety. Within hours, she went into Torsade de Pointes. She needed emergency cardioversion. She had no warning signs. No chest pain. No dizziness before it happened. Just sudden collapse.

What’s Changed Since 2015?

After the EMA review in 2015, things started to shift. The maximum daily dose was cut from 150 mg to 100 mg for adults. For anyone over 65, it’s capped at 50 mg. In children, it’s limited to 2 mg per kg of body weight. These aren’t suggestions. They’re hard limits now.

Electronic health records have been updated to block prescriptions if the patient’s QTc interval is above 500 ms - or if they’re on another drug known to prolong QT. The CredibleMeds database, which classifies drugs by arrhythmia risk, now lists hydroxyzine as “Known Risk of TdP.” That’s the highest warning level. It’s the same category as dofetilide and sotalol - drugs designed to treat arrhythmias, not sedate anxiety.

Prescribing habits are changing. In the U.S., hydroxyzine prescriptions dropped from 18.3 million in 2014 to 12.7 million in 2022. That’s a 30% decline. But it’s still one of the most commonly used antihistamines for anxiety - especially in primary care. Why? Because many providers still think of it as “just an antihistamine.” They forget it’s a cardiac drug in disguise.

How Does It Compare to Other Antihistamines?

Not all antihistamines are created equal. Second-generation ones like cetirizine, loratadine, and fexofenadine barely touch the hERG channel. They’re safe for the heart. Even diphenhydramine (Benadryl) - another first-gen antihistamine - has a lower risk than hydroxyzine.

Here’s a quick comparison:

The bottom line? If you need an antihistamine for anxiety or itching, there are safer options. Hydroxyzine should only be considered when others fail - and even then, only if your heart is checked first.

What Should You Do If You’re Taking Hydroxyzine?

If you’re currently on hydroxyzine, here’s what to do:

1. Check your dose. Are you taking more than 50 mg a day? If you’re over 65, you shouldn’t be. If you’re under 65, 100 mg is the max - but even that’s pushing it.
2. Review your other meds. Look at every pill you take. Use the CredibleMeds website (or ask your pharmacist) to see if any of them are on the “Known Risk” list. Common ones include antibiotics like azithromycin, antidepressants like citalopram, antifungals like fluconazole, and antiarrhythmics like amiodarone.
3. Get an ECG. If you’ve been on hydroxyzine for more than a few weeks, ask for a 12-lead ECG. Look for QTc longer than 450 ms (men) or 470 ms (women). Anything over 500 ms is an absolute red flag.
4. Watch for symptoms. Dizziness, palpitations, lightheadedness, or fainting within hours of taking it? Stop it immediately and call your doctor.

Don’t wait for a crisis. A 2019 case report described a 45-year-old man with undiagnosed long QT syndrome. He took 25 mg of hydroxyzine for itching. Fifteen minutes later, he passed out. He had no family history. No prior symptoms. Just a genetic flaw and a routine prescription.

The Future of Hydroxyzine

Experts agree: hydroxyzine isn’t going away. But its role is shrinking. The American Geriatrics Society now lists it as a “Potentially Inappropriate Medication” for older adults. The European Society of Cardiology is expected to ban chronic use by 2025 - limiting it to single doses for procedural anxiety only.

New drugs are coming. A compound called VH-01 is in early trials and shows 87% less hERG blockade than hydroxyzine - while keeping the same antihistamine effect. That could be a game-changer.

For now, the message is simple: hydroxyzine isn’t a harmless sedative. It’s a drug that needs cardiac screening like a blood thinner or a heart medication. If your doctor prescribes it without asking about your ECG, your meds, or your risk factors - push back. Your heart might depend on it.