QT Prolongation: Medications That Raise Arrhythmia Risk

When a medication changes the way your heart beats, it’s not always obvious. You might feel fine, but inside, your heart’s electrical system could be on shaky ground. That’s where QT prolongation comes in - a hidden danger in some of the most commonly prescribed drugs. It doesn’t cause symptoms on its own, but it can trigger a deadly rhythm called torsades de pointes, which can lead to sudden cardiac arrest. The good news? You don’t need to panic. You just need to know which drugs to watch for - and when to ask your doctor for an ECG.

What Exactly Is QT Prolongation?

The QT interval on an ECG measures how long it takes your heart’s lower chambers (ventricles) to recharge between beats. When that interval gets too long - usually defined as a corrected QT (QTc) over 500 milliseconds - your heart becomes electrically unstable. This doesn’t mean you’ll suddenly collapse. But it does mean your heart is more likely to slip into a dangerous, chaotic rhythm called torsades de pointes. Once that starts, it can turn into ventricular fibrillation - and that’s when the heart stops pumping blood.

This isn’t rare. In 2013, the FDA found that 22% of the 205 drugs they reviewed caused measurable QT prolongation. By 2018, crediblemeds.org listed 223 drugs with known, possible, or conditional risk of triggering this problem. Most of these drugs block a specific potassium channel in the heart called hERG. That’s the same channel that keeps the heart’s electrical signal moving smoothly. Block it, and the signal drags - leading to a longer QT interval.

Which Medications Are the Biggest Culprits?

Not all QT-prolonging drugs are created equal. Some are high-risk, some are low-risk, and some only become dangerous when mixed with other drugs or in certain patients.

High-risk drugs include:

• Class Ia antiarrhythmics - quinidine and procainamide. These were among the first drugs linked to QT prolongation. Quinidine causes torsades in about 6% of users.
• Class III antiarrhythmics - sotalol, dofetilide, ibutilide. These are designed to slow the heart’s rhythm, but they carry a 2-5% risk of torsades. Sotalol is especially risky at higher doses.
• Methadone - used for pain and opioid addiction. Risk spikes above 100 mg daily. Even at lower doses, it’s dangerous if combined with other QT-prolonging drugs.
• Amiodarone - while it prolongs QT significantly, its actual torsades risk is low (under 1%) because it blocks multiple channels, not just hERG.

Common non-cardiac drugs with QT risk:

• Antibiotics - erythromycin, clarithromycin, azithromycin. Erythromycin can lengthen QT by 15-25 ms, especially if taken with drugs that slow its breakdown (like grapefruit juice or certain antifungals).
• Antifungals - fluconazole. Risk increases with doses over 400 mg daily.
• Antipsychotics - haloperidol, ziprasidone. Ziprasidone has a black box warning for ventricular arrhythmias. Haloperidol is often used in emergency rooms for agitation - but if given with ondansetron, the risk multiplies.
• Antiemetics - ondansetron (Zofran). Used for nausea, especially after chemo or surgery. It’s one of the top drugs involved in documented torsades cases.
• Antidepressants - citalopram and escitalopram. The FDA capped citalopram at 40 mg daily (20 mg if over 60) because of dose-dependent QT prolongation.

Why Are Some People at Higher Risk?

It’s not just about the drug. It’s about the person taking it. The biggest risk factors include:

• Female sex - women make up about 70% of documented torsades cases. Hormonal differences make their hearts more sensitive to hERG blockade.
• Age over 65 - kidneys and liver slow down, so drugs build up in the body longer.
• Low potassium or magnesium - electrolyte imbalances make the heart more excitable. This is common in people on diuretics, with eating disorders, or after vomiting/diarrhea.
• Heart disease - especially heart failure or prior heart attack. Scarred tissue creates electrical shortcuts that can trigger arrhythmias.
• Genetic factors - about 30% of drug-induced torsades cases involve hidden mutations in the hERG gene. You might not know you have it until a drug triggers a crisis.
• Multiple QT-prolonging drugs - taking two or more drugs that prolong QT is the most common scenario in documented cases. One study found 68% of torsades cases involved two or more such drugs.

A real-world example: a 65-year-old woman with gastroenteritis gets azithromycin and ondansetron. Her baseline QTc was 440 ms. Within 24 hours, it jumps to 530 ms. She collapses. That’s not a fluke - it’s a predictable cascade.

When Should You Get an ECG?

You don’t need an ECG for every new prescription. But you should ask for one if:

• You’re starting a high-risk drug like sotalol, methadone, or dofetilide.
• You’re over 65 and starting any new medication with QT risk.
• You’re taking more than one drug that prolongs QT - even if each is low risk on its own.
• You have a history of heart problems, low electrolytes, or unexplained fainting.
• You’re on a high dose of citalopram, fluconazole, or ondansetron.

Guidelines from the European Society of Cardiology and Medsafe (New Zealand) recommend checking QTc within 3-7 days after starting a high-risk drug or increasing the dose. If the QTc goes over 500 ms, or increases by more than 60 ms from baseline, the drug should be stopped - unless there’s no alternative and the benefit outweighs the risk.

What About Newer Drugs?

The drug development world is changing. In 2013, the FDA launched CiPA - a new testing system that doesn’t just measure QT prolongation. It looks at how drugs affect multiple heart ion channels and uses computer models to predict real-world risk. This has already led to 22 drug failures since 2016, costing billions - but it’s saving lives.

New drugs like retatrutide (an obesity treatment approved in late 2023) now come with QT prolongation warnings. Of the 27 tyrosine kinase inhibitors used in cancer treatment, 12 carry QT risk warnings. These aren’t old drugs - they’re cutting-edge therapies with hidden dangers.

How to Stay Safe

Here’s what you can do:

1. Know your meds - Check crediblemeds.org. It’s free, updated quarterly, and ranks drugs by risk level: Known Risk, Possible Risk, Conditional Risk.
2. Ask your pharmacist - When you get a new prescription, ask: “Does this affect my heart rhythm?” Most pharmacists can access drug interaction databases that flag QT risks.
3. Don’t mix drugs - Avoid combining antibiotics like azithromycin with ondansetron or antipsychotics. Even if your doctor didn’t warn you, it’s a known dangerous combo.
4. Get electrolytes checked - If you’re on diuretics or have had vomiting/diarrhea, ask for a blood test for potassium and magnesium.
5. Monitor your symptoms - Dizziness, fainting, palpitations, or sudden fatigue after starting a new drug? Don’t wait. Get an ECG.

Some doctors argue that routine ECGs for low-risk drugs are overkill. After all, the chance of torsades from a single low-risk drug is less than 1 in 10,000 per year. But when you combine risk factors - a woman over 65 on citalopram and azithromycin with low potassium - the risk isn’t theoretical anymore. It’s real.

What’s Next?

Research is moving fast. In 2023, scientists identified 23 genetic variants that explain 18% of why some people are more sensitive to QT prolongation. AI tools are being trained to spot subtle ECG patterns that predict torsades before the QT interval even looks abnormal. One 2024 study showed an AI algorithm predicting risk with 89% accuracy.

Meanwhile, hospitals using electronic health record systems with built-in QT risk alerts have cut dangerous drug combinations by 58%. That’s not magic - it’s smart technology catching what humans miss.

Final Thought

QT prolongation isn’t something you can feel. But it’s something you can prevent. Most cases happen because of simple, avoidable mistakes: combining two safe drugs, ignoring electrolytes, or not checking ECGs in high-risk patients. You don’t need to avoid all medications. You just need to be informed. Ask questions. Get tested when needed. And never assume a drug is safe just because it’s commonly prescribed.