When a medication changes the way your heart beats, it’s not always obvious. You might feel fine, but under the surface, something dangerous could be happening. QT prolongation is one of those silent risks - a delay in the heart’s electrical reset that can lead to a life-threatening rhythm called torsades de pointes. It doesn’t happen often, but when it does, it can kill. And the worst part? Many of the drugs that cause it are common prescriptions you’d never suspect.
What Exactly Is QT Prolongation?
On an ECG, the QT interval measures how long it takes your heart’s lower chambers (ventricles) to charge and discharge electrically. If that interval gets too long, your heart can’t reset properly. This creates a window where an extra electrical signal can trigger a chaotic, fast rhythm - torsades de pointes. It looks like a twisting pattern on the monitor, and if it doesn’t stop, it turns into ventricular fibrillation. No heartbeat. No blood flow. Death in minutes.
QT prolongation isn’t always caused by disease. In fact, more than half the cases seen in hospitals are drug-induced. The problem starts with a single ion channel in heart cells - the hERG channel. This channel lets potassium out after each heartbeat, helping the heart relax. Many drugs block it accidentally, or sometimes on purpose. When that happens, the heart takes longer to reset. That’s QT prolongation.
Which Medications Are the Biggest Culprits?
Not all drugs that prolong QT are created equal. Some are high-risk, others are low. The key is knowing which ones to watch for.
Class III antiarrhythmics like sotalol and dofetilide are designed to prolong the QT interval to stop other arrhythmias. But that’s like using a flamethrower to light a candle - it works, but it’s dangerous. Sotalol causes torsades in 2-5% of patients. Dofetilide? Up to 6% in some trials. Even though these are used under close monitoring, mistakes happen.
Then there are the non-heart drugs that sneak in under the radar. Antibiotics like clarithromycin and erythromycin are common culprits. Erythromycin can stretch the QT interval by 15-25 milliseconds. Combine it with a CYP3A4 inhibitor like fluconazole (a common antifungal), and you’re doubling the risk. A 2022 case in the UK saw a 72-year-old woman develop torsades after taking azithromycin and fluconazole together for a chest infection. Her QTc jumped from 440 to 530 ms in under 24 hours.
Antipsychotics like haloperidol and ziprasidone are also on the list. Ziprasidone has a black box warning from the FDA for ventricular arrhythmia. And while sudden death from these drugs is rare, it’s not zero. In fact, haloperidol is one of the top three drugs linked to torsades in FDA reports.
Antiemetics like ondansetron - the go-to drug for nausea after chemo or surgery - are surprisingly risky. In a review of 147 torsades cases, ondansetron appeared in 42% of them. It’s not the drug itself; it’s the combination. Give it with an antipsychotic or an antibiotic? Risk spikes.
And then there’s methadone. Used for pain and opioid addiction, it’s one of the most dangerous. Doses over 100 mg daily are a red flag. The FDA has issued warnings, but many prescribers still don’t check QTc before starting it. In one UK clinic, 18% of patients on methadone had QTc >500 ms - and none were being monitored.
Even antidepressants aren’t safe. Citalopram was limited to 40 mg/day (20 mg for over-60s) in 2011 because of QT risk. Escitalopram is safer, but not risk-free. And newer drugs like the obesity medication retatrutide, approved in late 2023, already show QTc prolongation in early trials.
Who’s Most at Risk?
It’s not just about the drug. It’s about the person taking it.
Women are two to three times more likely to develop torsades than men. Why? Hormones. Estrogen slows down the heart’s repolarization. Postpartum women are especially vulnerable.
Older adults are at higher risk too. Their kidneys and liver clear drugs slower. Their hearts are more sensitive. And they’re more likely to be on multiple meds - a recipe for disaster.
People with low potassium or magnesium are sitting on a time bomb. These electrolytes help the hERG channel work. If levels drop, even a low-risk drug can become dangerous.
Genetics play a role too. About 30% of drug-induced torsades cases happen in people with hidden genetic mutations in the hERG channel. They might never know until a medication triggers a crisis.
When Should You Worry?
Not every QT prolongation is dangerous. But there are clear red flags:
- QTc >500 milliseconds - risk triples to fivefold.
- QTc increase of more than 60 ms from baseline - stop the drug.
- Two or more QT-prolonging drugs taken together - risk multiplies.
- QTc >450 ms in women or >470 ms in men - watch closely.
Doctors use Bazett’s formula to correct QT for heart rate. But it’s flawed. At slow heart rates (under 50 bpm), it overcorrects. At fast rates (over 90 bpm), it undercorrects. That’s why some ECGs get misread. A QTc of 490 ms might actually be 520 ms if the heart rate is low - and no one notices.
How Do You Prevent It?
The best defense is awareness - and action.
Before prescribing: Check for existing heart conditions, electrolyte levels, and other meds. Use crediblemeds.org - it’s free, updated quarterly, and lists every drug with known, possible, or conditional QT risk.
Baseline ECG: Required for anyone starting high-risk drugs like sotalol, methadone, or dofetilide. Also for older patients on multiple meds.
Follow-up ECG: Repeat within 3-7 days after starting or increasing the dose. That’s when drug levels peak and QT changes are most likely.
Electrolytes: Always check potassium and magnesium before and during treatment. Fix them if low.
Drug combinations: Avoid pairing ondansetron with haloperidol. Don’t mix erythromycin with fluconazole. These are not theoretical risks - they’ve caused deaths.
Some hospitals now use electronic health record alerts that flag dangerous combinations. One UK system saw a 58% drop in risky prescriptions after adding these alerts.
The Bigger Picture
The pharmaceutical industry is changing. The FDA, EMA, and Japan’s PMDA launched the CiPA initiative in 2013 to move beyond just measuring QT intervals. Now, new drugs must be tested on multiple ion channels and modeled in computer simulations. Since 2016, 22 drug candidates have been dropped because of proarrhythmia risk. Each failure costs $2.6 billion - but it’s better than a patient dying on the ward.
AI is stepping in too. A 2024 study showed a machine learning model could predict torsades risk with 89% accuracy by analyzing tiny ECG waveform details no human could spot. That’s the future.
Meanwhile, in hospitals across the UK and beyond, pharmacists and cardiologists are pushing for better protocols. The American College of Cardiology says systematic QT screening has cut torsades cases by 40% in the last decade. That’s progress. But it’s not enough.
Because the next person to get torsades might be your patient. Or your parent. Or you.
What If You’re Already on One of These Drugs?
If you’re taking any of the drugs listed above - especially if you’re on more than one - don’t stop abruptly. Talk to your doctor. Ask:
- Is my QTc been checked recently?
- Am I on any other meds that could interact?
- Have my potassium and magnesium levels been checked?
- Is there a safer alternative?
Most people take these drugs without issue. But if you’ve had unexplained fainting, dizziness, or palpitations - especially after starting a new med - tell your doctor. That could be your body’s warning.
Can a normal ECG rule out QT prolongation risk?
No. A normal ECG doesn’t mean you’re safe. QT prolongation can develop after starting a drug, especially if you have other risk factors like low potassium, older age, or drug interactions. That’s why follow-up ECGs are critical - usually within 3-7 days of starting or increasing the dose.
Is QT prolongation always dangerous?
No. Mild prolongation (QTc 450-499 ms) is common and often harmless, especially if there are no other risk factors. The real danger starts when QTc exceeds 500 ms or increases by more than 60 ms from baseline. That’s when torsades becomes likely.
Can I take ondansetron if I’m on an antidepressant?
It’s risky. Ondansetron combined with antidepressants like citalopram or antipsychotics like haloperidol has caused multiple cases of torsades. If you need an anti-nausea drug and are on a QT-prolonging med, ask for alternatives like metoclopramide (with caution) or non-drug options. Always check crediblemeds.org for interaction warnings.
Why are women more at risk than men?
Women naturally have longer QT intervals than men, partly due to estrogen’s effect on heart cell channels. After menopause, the risk remains high, and postpartum women are especially vulnerable. Studies show women make up about 70% of documented torsades cases, even when taking the same dose as men.
Are there any safe alternatives to methadone for pain or addiction?
Yes. Buprenorphine is a much safer option for opioid addiction - it has minimal QT effect. For pain, non-opioid options like gabapentin or physical therapy may help. If methadone is necessary, ensure baseline and regular ECGs, keep doses under 100 mg daily, and avoid combining it with other QT-prolonging drugs.
How often should I get an ECG if I’m on a QT-prolonging drug?
Baseline ECG before starting. Then repeat within 3-7 days after starting or increasing the dose. For high-risk drugs like sotalol or methadone, monthly checks for the first 3 months, then every 3-6 months if stable. If you have other risk factors (elderly, low electrolytes, kidney disease), your doctor may want more frequent monitoring.
What’s Next?
Drug safety is evolving. The FDA’s 2024 draft guidance makes CiPA testing mandatory for all new drugs starting in January 2025. That means fewer dangerous drugs will reach the market. But for now, the responsibility falls on prescribers and patients.
Don’t assume your meds are safe just because they’re approved. Ask questions. Demand ECGs when needed. Know your risk. Because in the case of QT prolongation, the difference between safety and disaster is often just a few milliseconds - and one smart question.
