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

Hydroxyzine has been used for decades to treat anxiety, itching, and nausea. It’s cheap, effective, and widely prescribed. But behind its calming reputation lies a quiet but serious danger: it can mess with your heart’s electrical rhythm and trigger a life-threatening arrhythmia called QT prolongation.

What Is QT Prolongation, and Why Does It Matter?

Your heart beats because of electrical signals that travel through muscle tissue. The QT interval on an ECG measures how long it takes for the heart’s lower chambers to recharge after each beat. If that interval stretches too long, the heart can develop a dangerous rhythm called Torsade de Pointes - a type of ventricular tachycardia that can cause fainting, seizures, or sudden death.

Hydroxyzine interferes with a key ion channel in heart cells called hERG. This channel helps move potassium out of the cell during repolarization. When hydroxyzine blocks it, the heart takes longer to reset. The result? A longer QT interval. It doesn’t happen in everyone. But when it does, it can happen fast - sometimes within minutes of taking the first dose.

Who’s at Risk?

Most healthy adults can take hydroxyzine without issue. But risk skyrockets if you have even one of these factors:

• Age 65 or older
• Low potassium or magnesium levels
• Existing heart disease or prior QT prolongation
• Slow heart rate (below 50 bpm)
• Taking other drugs that prolong QT - like certain antibiotics, antidepressants, or antiarrhythmics

A 2022 case report in Cureus described a 68-year-old woman with no heart history who went into Torsade de Pointes after a single 50 mg dose of hydroxyzine. She was also on amiodarone - a known QT-prolonging drug. That’s the problem: hydroxyzine doesn’t act alone. It teams up with other risks.

Elderly patients are especially vulnerable. Their kidneys and liver clear drugs slower. Hydroxyzine’s half-life can stretch from 14 to 25 hours in older adults, meaning it builds up. That’s why the European Medicines Agency (EMA) cut the max daily dose for seniors to 50 mg - down from 100 mg for younger adults.

How Common Is This Risk?

It’s rare - but not rare enough to ignore.

Between 1955 and 2016, global pharmacovigilance systems recorded 59 confirmed cases linking hydroxyzine to QT prolongation or Torsade de Pointes. That sounds low. But most cases go unreported. Many doctors still don’t connect a sudden fainting spell or palpitations to hydroxyzine, especially if the patient has no prior heart issues.

In one Reddit thread, users reported 37 cardiac-related concerns tied to hydroxyzine between 2018 and 2023. Nearly half described dizziness or heart flutters within an hour of taking it. That’s not coincidence. That’s a red flag.

The FDA added hydroxyzine to its official list of drugs with QT prolongation risk in 2019. The EMA issued a formal warning in 2015. Yet, a 2021 survey of 127 hospital pharmacists found that 63% had seen hydroxyzine prescribed to patients with two or more risk factors - even though guidelines say it’s a hard no in those cases.

How Does Hydroxyzine Compare to Other Antihistamines?

Not all antihistamines are created equal.

Second-generation ones like cetirizine (Zyrtec) and loratadine (Claritin) barely touch the hERG channel. Their QT risk is negligible. That’s why they’re preferred for long-term use, especially in older adults.

Among first-generation antihistamines - the sleepy ones - hydroxyzine sits near the top of the danger list. It’s slightly worse than diphenhydramine (Benadryl), which also blocks hERG but less potently. Both are far riskier than non-sedating options.

Here’s a quick comparison:

QT Prolongation Risk Comparison Among Common Antihistamines

Drug	Generation	QT Prolongation Risk	Typical Max Daily Dose
Hydroxyzine	First	Known Risk (CredibleMeds)	100 mg (adults), 50 mg (elderly)
Diphenhydramine	First	Possible Risk	300 mg
Cetirizine	Second	Minimal Risk	10 mg
Loratadine	Second	Minimal Risk	10 mg

Hydroxyzine’s molecular structure lets it bind tightly to the hERG channel - more so than most other antihistamines. That’s why cardiologists and pharmacologists now treat it like a cardiac drug, not just a sedative.

What Should Doctors Do Before Prescribing It?

It’s not about avoiding hydroxyzine entirely. It’s about using it wisely.

Before writing a prescription, a clinician should:

1. Check the patient’s ECG for QTc interval - it should be under 450 ms for men, under 470 ms for women.
2. Review all medications using the CredibleMeds database. If the patient is on any drug marked "Known Risk," hydroxyzine is off the table.
3. Test potassium and magnesium levels. If either is low, correct it first.
4. Ask about heart disease, syncope, or family history of sudden cardiac death.
5. Use the lowest effective dose for the shortest time possible.

Many hospitals now have electronic health record systems that block hydroxyzine orders if the patient has a QTc over 500 ms or is on conflicting meds. That’s a good thing. But it’s not foolproof. A 2022 JAMA Internal Medicine study found that even with these safeguards, only 78% of providers documented a formal cardiac risk assessment.

What About Alternatives?

If you’re taking hydroxyzine for anxiety or itching, there are safer options.

For anxiety: Buspirone, low-dose SSRIs like sertraline, or even cognitive behavioral therapy (CBT) are better long-term choices. For itching: gabapentin, naltrexone, or topical capsaicin have proven effective with no cardiac risk.

In dermatology, hydroxyzine is still listed as a second-line option for chronic pruritus - but only if cardiac screening is done. Many dermatologists now skip it entirely and go straight to gabapentin, which has seen a 62% rise in prescriptions since 2015.

For insomnia or sedation in the elderly: mirtazapine, trazodone, or non-pharmacological sleep hygiene are safer. The American Geriatrics Society Beers Criteria now lists hydroxyzine as a "Potentially Inappropriate Medication" for older adults.

The Future of Hydroxyzine

Research is moving fast. A 2023 study found that people with a genetic variant called CYP2D6 poor metabolizer status are over three times more likely to experience QT prolongation on hydroxyzine. That means future prescribing might involve genetic testing.

A new compound called VH-01 is in early trials. It keeps the antihistamine effect but cuts hERG binding by 87%. If it works, it could replace hydroxyzine entirely.

The 2025 European Society of Cardiology guidelines are expected to ban chronic hydroxyzine use entirely. It may only be allowed as a single dose for procedural anxiety - like before a dental appointment.

What Should You Do If You’re Taking Hydroxyzine?

If you’re on hydroxyzine and have no heart issues, no electrolyte imbalances, and aren’t on other risky meds - you’re probably fine. But don’t assume safety.

Ask your doctor:

• "Have you checked my QT interval?"
• "Am I on any other meds that could interact?"
• "Is there a safer alternative for my condition?"

If you feel your heart racing, dizzy, or faint after taking it - stop and get help. Don’t wait. Torsade de Pointes doesn’t give warning signs until it’s too late.

Hydroxyzine isn’t evil. It’s just not as safe as we once thought. The era of treating it like a harmless bedtime pill is over. We now know: if it affects your heart, it deserves the same caution as any heart medication.

Use it with eyes wide open. Or don’t use it at all.