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

Hydroxyzine has been around for decades - prescribed for anxiety, itching, nausea, and even to help people sleep. For many, it felt like a safe, go-to option. But in recent years, something changed. Doctors and regulators started sounding alarms: hydroxyzine can mess with your heart’s electrical system. Specifically, it can prolong the QT interval - a measure of how long your heart takes to recharge between beats. And when that interval gets too long, it can trigger a dangerous, sometimes deadly, heart rhythm called Torsade de Pointes.

What Exactly Is QT Prolongation?

Your heart doesn’t just beat randomly. It follows a precise electrical pattern. The QT interval on an ECG shows how long it takes for the heart’s lower chambers (ventricles) to recover after each beat. If this recovery time stretches too far, the heart can get confused and start beating erratically. That’s QT prolongation. It’s not always dangerous. But in some people - especially when combined with other factors - it can spiral into Torsade de Pointes. This isn’t just a flutter. It’s a life-threatening arrhythmia that can lead to fainting, seizures, or sudden cardiac death.

How Does Hydroxyzine Cause This?

Hydroxyzine blocks histamine receptors - that’s why it helps with allergies and itching. But it also blocks something else: potassium channels in the heart, specifically the hERG channel. This channel helps the heart reset after each beat. When hydroxyzine blocks it, the heart takes longer to recover. That’s what stretches the QT interval. Studies show this effect kicks in at therapeutic doses. It’s not just a rare fluke. It’s built into the drug’s chemistry. The European Medicines Agency (EMA) confirmed this in 2015 after reviewing decades of data. They found 59 clear cases linking hydroxyzine to QT prolongation or Torsade de Pointes. Some happened within 10 minutes of taking the first dose. Others showed up weeks later. The risk isn’t random - it’s dose-dependent and personal.

Who’s at Highest Risk?

Not everyone who takes hydroxyzine will have problems. But certain people are walking into a minefield. Here’s who needs to be extra careful:

• People over 65 - metabolism slows down, so the drug builds up.
• Those with low potassium or magnesium - common in people on diuretics, with kidney disease, or eating poorly.
• Anyone already on another QT-prolonging drug - like certain antibiotics, antidepressants, or antiarrhythmics.
• People with a history of heart disease, slow heart rate (bradycardia), or inherited long QT syndrome.
• Patients on high doses - anything over 50 mg daily for older adults, or over 100 mg for younger adults.

A 2022 case report described a 68-year-old woman with no prior heart issues who went into Torsade de Pointes after taking 50 mg of hydroxyzine for anxiety. She was also on amiodarone - a known QT-prolonging drug. That combo turned a routine prescription into a cardiac emergency. Another case involved a 45-year-old man with undiagnosed long QT syndrome. He fainted just 15 minutes after taking 25 mg for itching. Neither case had warning signs before the drug was given.

How Does Hydroxyzine Compare to Other Antihistamines?

Not all antihistamines are created equal. Second-generation ones - like cetirizine, loratadine, and fexofenadine - barely touch the heart. They’re designed to stay out of the brain and heart. That’s why they’re called non-sedating. Hydroxyzine? It’s a first-generation antihistamine. It crosses the blood-brain barrier (that’s why it causes drowsiness) - and it also slips into heart cells.

Compared to diphenhydramine (Benadryl), hydroxyzine has a slightly higher risk of QT prolongation. Both are risky. But compared to newer options, hydroxyzine is in a different league. The EMA’s 2015 review specifically called out hydroxyzine for its strong hERG-blocking effect. Even among sedating antihistamines, it stands out as one of the riskiest.

What Are the Current Safety Guidelines?

Since the 2015 EMA review, rules changed. Here’s what’s now recommended:

• Maximum daily dose: 100 mg for adults under 65.
• Maximum daily dose: 50 mg for adults over 65.
• Never use in patients with QTc >500 ms.
• Don’t combine with other drugs that prolong QT - check the CredibleMeds database.
• Check electrolytes: potassium above 4.0 mmol/L, magnesium above 1.8 mg/dL.
• Get a baseline ECG before starting, especially if you’re over 60 or have heart disease.

Many hospitals now have electronic alerts that block hydroxyzine orders if a patient has two or more risk factors. Pharmacists are trained to flag these prescriptions. Still, a 2021 survey found 63% of hospital pharmacists had seen hydroxyzine prescribed to patients with multiple risk factors - even when guidelines said not to.

Why Is This Still Being Prescribed?

It’s a paradox. Hydroxyzine is cheap, widely available, and works fast for anxiety and itching. 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. That’s because awareness grew. The American Geriatrics Society now lists hydroxyzine as a “potentially inappropriate medication” for older adults. The Beers Criteria explicitly warn against it in seniors due to cardiac risk.

But it hasn’t disappeared. Dermatologists still use it for chronic itching. Psychiatrists sometimes prescribe it for short-term anxiety. The problem? It’s often used for months or years - not just a few days. That’s where accumulation and risk spike.

What Should You Do If You’re Taking Hydroxyzine?

If you’re on hydroxyzine, don’t stop cold turkey. Talk to your doctor. Ask these questions:

• Am I on a safe dose? (Under 50 mg if over 65?)
• Have I had an ECG in the last year?
• Am I taking any other drugs that affect the heart’s rhythm?
• Do I have low potassium, low magnesium, or a history of fainting?

If you’ve had unexplained dizziness, palpitations, or fainting after taking hydroxyzine - even once - tell your doctor. That’s not normal. That’s a red flag.

Are There Better Alternatives?

Yes. And they’re safer.

• For anxiety: Buspirone, SSRIs like sertraline, or short-term benzodiazepines (used carefully).
• For itching: Cetirizine or loratadine (non-sedating, no QT risk), or topical corticosteroids.
• For sleep: Melatonin, cognitive behavioral therapy for insomnia (CBT-I), or low-dose mirtazapine (which has its own risks but lower than hydroxyzine).
• For pruritus in kidney disease: Gabapentin - prescriptions for this jumped 62% between 2015 and 2022 as doctors moved away from hydroxyzine.

The key isn’t just avoiding hydroxyzine. It’s replacing it with something that doesn’t carry the same hidden danger.

What’s Changing Now?

Research is moving fast. A 2023 study found people with a genetic variation called CYP2D6 poor metabolizer status are over three times more likely to develop QT prolongation on hydroxyzine. That means your genes might make you more vulnerable - even at low doses.

A 2024 clinical trial is testing whether routine ECG monitoring during hydroxyzine use reduces cardiac events. Early results are promising.

And there’s hope on the horizon: a new drug called VH-01 is in early trials. It’s designed to keep hydroxyzine’s anti-itch and anti-anxiety effects but with 87% less hERG blockade. If it works, it could bring back the benefits without the risk.

The Bottom Line

Hydroxyzine isn’t banned. It’s not poison. But it’s no longer a “safe sedative.” It’s a drug with a known, measurable, and preventable cardiac risk. The era of prescribing it casually - especially to older adults or people with other health issues - is over. If you’re taking it, ask for a cardiac risk check. If you’re a provider, don’t just write the script. Screen for risk. Check the ECG. Review the meds. Your patient’s heart might depend on it.

Next Steps if You’re Concerned

If you’re taking hydroxyzine and have any risk factors, schedule a visit with your doctor or pharmacist. Bring a list of all your medications - including over-the-counter ones. Ask for a basic ECG if you haven’t had one in the last year. If you’re prescribed hydroxyzine again, ask: “Is this the safest option for me?” There are better, safer choices now. You don’t have to accept a drug with a known cardiac risk just because it’s old or cheap.