QT Prolongation: Medications That Raise Arrhythmia Risk

When your heart beats, it follows a precise electrical rhythm. That rhythm shows up on an ECG as a series of waves - P, Q, R, S, T. The time between the start of the Q wave and the end of the T wave is called the QT interval. It’s the heartbeat’s reset button: the time it takes for the lower chambers of the heart to charge and discharge. When that interval gets too long - a condition called QT prolongation - your heart can slip into a dangerous rhythm called torsades de pointes. It’s rare, but it can kill you in seconds.

What Causes QT Prolongation?

Most people think of heart rhythm problems as something you’re born with. But the biggest threat today comes from something you can control: medications. Over 200 prescription and over-the-counter drugs are known to stretch the QT interval. They don’t do it on purpose. They’re just side effects - often silent ones.

The main culprit is a single ion channel in heart cells: the hERG channel. This channel lets potassium out of the cell after each beat, helping the heart reset. Many drugs accidentally block it. Antibiotics, antipsychotics, antidepressants, even some stomach meds can do it. When potassium can’t leave the cell, the heart stays charged longer. That’s QT prolongation.

The FDA reviewed 205 drugs in 2013 and found that nearly one in five - 46 of them - clearly prolonged the QT interval. By 2018, the independent database CredibleMeds listed 223 drugs with confirmed or possible risk. That’s not a small number. It’s a hidden danger in medicine cabinets everywhere.

Which Medications Are the Most Dangerous?

Not all QT-prolonging drugs are created equal. Some carry a much higher risk than others.

Class III antiarrhythmics like sotalol and dofetilide are designed to prolong the QT interval - that’s how they stop dangerous rhythms. But they’re also the most likely to cause torsades. Sotalol, for example, triggers torsades in 2-5% of patients. Amiodarone, another Class III drug, prolongs QT even more, but its risk is lower - under 1% - because it blocks multiple channels, not just one.

Then there are the non-heart drugs that sneak under the radar:

• Methadone: Used for pain and opioid addiction. Risk spikes above 100 mg/day. TdP cases are well-documented.
• Citalopram and escitalopram: Antidepressants. The FDA capped citalopram at 40 mg/day (20 mg for people over 60) after studies showed clear QT dose-response.
• Antibiotics: Erythromycin and clarithromycin can prolong QT by 15-25 ms. Azithromycin is less risky but still dangerous in high doses or with other triggers.
• Antifungals: Fluconazole, especially at doses over 400 mg/day.
• Antiemetics: Ondansetron (Zofran) - common for nausea - was involved in 42% of TdP cases in one FDA analysis.
• Antipsychotics: Haloperidol and ziprasidone carry black box warnings for sudden cardiac death. Ziprasidone’s risk is real, even if actual TdP events are rare.

Who’s at Highest Risk?

It’s not just about the drug. It’s about the person taking it.

Women are at far greater risk - about 70% of documented torsades cases occur in women. Why? Hormones. Estrogen slows potassium flow naturally. After menopause, that effect drops, but the risk remains higher than in men. Postpartum women are especially vulnerable.

Age matters too. People over 65 have slower drug clearance, weaker hearts, and often take multiple meds. That’s a perfect storm.

Genetics play a role. About 30% of drug-induced torsades cases happen in people with subtle hERG gene mutations they didn’t know they had. You might be fine on one drug. Add another? Boom.

Low potassium, low magnesium, or low calcium - common in people with eating disorders, kidney disease, or on diuretics - make the heart even more sensitive to QT-prolonging drugs.

And here’s the biggest hidden risk: combining drugs. Taking two QT-prolonging meds doubles your risk. Taking three? It’s not linear - it’s exponential. A 2020 FDA analysis found that 68% of TdP cases involved two or more risky drugs. One case? A 65-year-old woman on ondansetron for nausea and azithromycin for infection. Her QTc jumped from 440 ms to 530 ms in 24 hours. She went into torsades. She survived - barely.

What’s a Dangerous QTc Number?

Doctors measure the corrected QT interval - QTc - to account for heart rate. The standard formula is Bazett’s: QT divided by the square root of the RR interval. It’s imperfect, especially at slow or fast heart rates, but it’s what we use.

Here’s the hard line:

• QTc over 500 ms = high risk. Torsades risk triples to fivefold.
• QTc increase of more than 60 ms from baseline = dangerous, even if still under 500.

A QTc of 470 ms in a man or 480 ms in a woman is borderline. A QTc of 510 ms? That’s a red flag. Many hospitals now have protocols to stop the drug immediately if QTc hits 500 ms or rises 60 ms from baseline.

How Do Doctors Manage This Risk?

The smartest hospitals don’t guess. They screen.

• Baseline ECG: Before starting a high-risk drug, get an ECG. It’s cheap. It’s quick. It saves lives.
• Repeat ECG: Within 3-7 days of starting or increasing the dose. That’s when drug levels peak.
• Check electrolytes: Potassium and magnesium should be in normal range. Fix them before giving the drug.
• Check drug interactions: Use tools like CredibleMeds.org. It’s free. It’s updated quarterly. It lists every drug with QT risk and how serious it is.
• Use EHR alerts: Hospitals with smart electronic records that flag dangerous combinations have cut inappropriate prescribing by over 50%.

Some doctors argue that screening everyone is overkill. After all, the absolute risk of torsades from a single non-cardiac drug is less than 1 in 10,000 patient-years. But when you’re the one patient who gets it, the statistics don’t matter. One death is too many.

What’s Changing in Drug Development?

The old way of testing for QT risk - just measuring QTc in healthy volunteers - is outdated. The FDA, EMA, and other regulators launched the CiPA initiative in 2013. Now, new drugs must be tested on multiple ion channels, not just hERG. They use computer models to simulate how the drug affects the whole heart, not just one channel.

The result? More drug failures. Between 2016 and 2022, 22 drugs were pulled from development because of proarrhythmia risk. Each failure cost over $2 billion. But it’s better than a drug hitting the market and killing people.

New drugs like retatrutide (an obesity medication approved in 2023) now come with QT prolongation warnings from day one. That’s progress.

What Should You Do?

If you’re on any medication - especially antibiotics, antidepressants, antipsychotics, or pain meds - ask your doctor:

• Is this drug on the CredibleMeds list for QT prolongation?
• Am I taking any other drugs that could add to the risk?
• Should I get an ECG before or after starting this?
• What are my electrolyte levels?

Don’t assume your doctor knows. Many don’t. A 2022 survey of hospital pharmacists found that 63% struggled to determine safe combinations of QT-prolonging drugs.

If you’re prescribed a drug with a QT warning, don’t panic. But do pay attention. Watch for dizziness, fainting, palpitations. Report them. Don’t wait.

Final Thought

QT prolongation isn’t a rare genetic disorder. It’s a preventable side effect of modern medicine. We’ve gotten better at spotting it. We’ve got tools. We’ve got guidelines. The problem isn’t ignorance - it’s complacency.

A simple ECG. A quick check of your meds. A conversation with your doctor. That’s all it takes to stop a silent killer before it strikes.