QT Prolongation: Medications That Raise Arrhythmia Risk

When you take a new medication, you expect it to help - not to put your heart at risk. But some common drugs, even those prescribed for everyday issues like nausea, depression, or infection, can quietly stretch the heart’s electrical cycle in a way that could trigger a life-threatening rhythm. This is called QT prolongation, and it’s not rare. It’s happening right now in hospitals, clinics, and homes across the UK and beyond.

What Exactly Is QT Prolongation?

On an ECG, the QT interval measures how long it takes your heart’s lower chambers (ventricles) to recharge after each beat. If that interval gets too long - usually defined as a corrected QT (QTc) over 500 milliseconds - the heart’s electrical system becomes unstable. That’s when a dangerous rhythm called torsades de pointes can start. It’s a type of ventricular tachycardia that looks like a twisting pattern on the monitor. Left untreated, it can flip into ventricular fibrillation and cause sudden death.

This isn’t just theoretical. In 2013, the U.S. FDA found that 22% of the 205 drugs they reviewed caused measurable QT prolongation. By 2018, crediblemeds.org listed 223 medications with known, possible, or conditional risk of triggering this rhythm. Many of these are drugs you’ve likely heard of: antibiotics like azithromycin, antidepressants like citalopram, antipsychotics like haloperidol, and even anti-nausea pills like ondansetron.

Why Do Some Drugs Cause This?

The culprit is usually the hERG potassium channel - a tiny protein in heart cells that helps reset the electrical charge after each beat. Many drugs accidentally block this channel, slowing down repolarization. The result? A longer QT interval.

Some drugs do this on purpose. Class III antiarrhythmics like sotalol and dofetilide are designed to prolong repolarization to stop fast heart rhythms. But here’s the irony: they carry their own risk of causing the very arrhythmia they’re meant to treat. Sotalol, for example, causes torsades in 2-5% of patients. Amiodarone also prolongs QT, but its risk is lower - under 1% - because it blocks multiple channels, not just hERG.

But the real danger comes from combinations. Taking two QT-prolonging drugs together can push the interval past the danger line. A 2020 analysis of FDA reports found that 68% of torsades cases involved multiple such drugs. One common, avoidable combo: ondansetron (for nausea) plus azithromycin (for infection). In one documented case, a woman’s QTc jumped from 440 ms to 530 ms within 24 hours after receiving both.

Who’s Most at Risk?

Not everyone who takes these drugs will have problems. But certain factors stack the deck:

• Women are 2 to 3 times more likely than men to develop torsades - especially after menopause or childbirth.
• Older adults (over 65) have slower drug clearance and often take multiple medications.
• People with low potassium or magnesium - common in those on diuretics or with eating disorders - are more vulnerable.
• Those with heart disease or a history of arrhythmias face higher baseline risk.
• Genetics play a role too. About 30% of drug-induced torsades cases involve hidden mutations in the hERG gene or related channels.

One study found that 23 genetic variants together explain nearly 18% of why some people’s QT intervals stretch more than others’ on the same drug. This isn’t just luck - it’s biology.

Which Medications Are the Biggest Culprits?

Not all QT-prolonging drugs are equal. Here’s how they break down by risk level:

Even newer drugs aren’t safe. Retatrutide, a 2023 obesity drug, showed an 8.2 ms QTc increase in trials. The FDA now requires all new drug applications to include multi-channel safety data under the CiPA initiative - a major shift from just measuring QT intervals.

How Do Doctors Spot This Before It’s Too Late?

Screening isn’t always routine - but it should be. The European Society of Cardiology and Medsafe (New Zealand) both recommend a baseline ECG before starting high-risk drugs. Repeat the ECG within 3-7 days after starting or increasing the dose. That’s when the drug reaches steady state and the QT effect peaks.

Key thresholds:

• QTc >500 ms = high risk. Stop the drug unless absolutely necessary.
• QTc increase >60 ms from baseline = warning sign. Reassess therapy.

But ECGs aren’t foolproof. Bazett’s formula - the most common way to correct QT for heart rate - overcorrects at slow rates and undercorrects at fast ones. That’s why some clinicians now use Fridericia’s formula (QTc = QT / RR^1/3) or rely on automated ECG machines with built-in algorithms.

Hospitals using EHR systems with built-in QT alerts have cut dangerous prescribing by 58%. These systems flag combinations like haloperidol + ondansetron or citalopram + clarithromycin before the prescription is even filled.

What Should You Do If You’re Taking One of These Drugs?

If you’re on a medication known to prolong QT, here’s what to do:

1. Ask your doctor or pharmacist: "Is this drug on the crediblemeds.org list?" (It’s free and updated quarterly.)
2. Check if you’re taking more than one QT-prolonging drug. Even if each is "low risk," together they can be dangerous.
3. Get a baseline ECG if you’re over 65, female, have heart disease, or are on high-dose methadone or citalopram.
4. Watch for symptoms: dizziness, fainting, palpitations, or unexplained seizures. These could be early signs of torsades.
5. Don’t stop your medication abruptly - but do report any new symptoms immediately.

For patients on methadone or antipsychotics, regular monitoring (every 30 days and quarterly) has proven safe and effective - even when QTc stays above 470 ms.

The Bigger Picture: Why This Matters

Each case of torsades costs the NHS or Medicare an estimated $38,600 in hospital care. But prevention is cheaper. ECG monitoring costs about $187 per patient - far less than the price of a cardiac arrest.

And the problem is growing. As more drugs enter the market - especially for cancer, obesity, and mental health - the number of QT-prolonging agents keeps rising. The 2024 FDA draft guidance makes it harder for new drugs to get approved without proving they don’t trigger arrhythmias. That’s good news for patients, even if it slows drug development.

What’s clear: QT prolongation isn’t a rare side effect. It’s a preventable one. With better screening, smarter prescribing, and awareness, we can stop many of these deaths before they happen.

Final Thoughts

QT prolongation isn’t something you can feel. There’s no pain, no swelling, no obvious warning. That’s why it’s so dangerous. But it’s also why it’s so preventable. With a simple ECG, a quick check of your medication list, and a conversation with your pharmacist, you can avoid a life-threatening rhythm. The science is clear. The tools exist. What’s needed now is awareness - and action.