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, take your pill as directed, and never suspect anything’s wrong. But for some drugs, even a normal dose can stretch out the electrical timing of your heart-long enough to trigger a dangerous rhythm called torsades de pointes. This isn’t theoretical. It’s happened to real people. And the list of medications that can do this is longer than most doctors admit.

What QT Prolongation Actually Means

Your heart’s rhythm is controlled by electrical signals. The QT interval on an ECG measures how long it takes your ventricles to charge and reset after each beat. When this interval gets too long, your heart becomes electrically unstable. That’s QT prolongation. It doesn’t cause symptoms on its own. But it sets the stage for torsades de pointes-a wild, chaotic heartbeat that can spiral into cardiac arrest.

Doctors measure the corrected QT interval, or QTc, to account for heart rate. A QTc over 500 milliseconds is a red flag. An increase of more than 60 ms from your baseline is just as concerning. Women are at higher risk-about 70% of reported cases occur in women, especially after childbirth. Why? Hormones, body size, and subtle differences in how heart cells handle electrical currents make female hearts more sensitive to these drug effects.

The Real Culprits: Drugs That Stretch the QT Interval

It’s not just heart meds. Many everyday prescriptions can do this. The biggest offenders fall into three groups.

• Antiarrhythmics: Drugs like sotalol, dofetilide, and quinidine are designed to fix heart rhythms-but they can cause them. Sotalol carries a 2-5% risk of torsades in clinical trials. Quinidine, an older drug, causes it in about 6% of patients.
• Antibiotics and antifungals: Erythromycin and clarithromycin can stretch the QT interval by 15-25 ms. Azithromycin is less risky, but still dangerous when combined with other QT-prolonging drugs. Fluconazole, a common antifungal, is another silent player.
• Antipsychotics and antiemetics: Haloperidol, ziprasidone, and ondansetron (Zofran) are frequently prescribed for nausea, psychosis, or agitation. Ziprasidone has a black box warning for arrhythmia risk. Ondansetron shows up in nearly half of all documented torsades cases, especially when paired with antibiotics or antipsychotics.

Methadone, used for pain and opioid addiction, is another major concern. Doses over 100 mg daily significantly raise risk. Citalopram, an antidepressant, can prolong QTc in a dose-dependent way-so the FDA capped it at 40 mg daily (20 mg if you’re over 60).

Why Some People Are at Higher Risk

Not everyone who takes these drugs has a problem. Risk depends on what else is going on in your body.

• Drug combinations: Taking two or more QT-prolonging drugs multiplies the risk. A 2020 review found 68% of torsades cases involved multiple such drugs. Haloperidol + ondansetron? High risk. Erythromycin + fluconazole? Dangerous combo.
• Low potassium or magnesium: These minerals help your heart reset properly. Low levels make QT prolongation much more likely. Diuretics, vomiting, or poor diet can trigger this.
• Age and sex: People over 65 and women are at higher risk. Postpartum women are especially vulnerable.
• Genetics: About 30% of cases involve hidden genetic variants that make the hERG potassium channel more sensitive to drugs. You won’t know you have it until something goes wrong.
• Heart disease: If you’ve had a heart attack, heart failure, or enlarged heart, your heart is already electrically fragile.

How Doctors Should Respond

Guidelines from Medsafe (New Zealand), the American Heart Association, and the European Society of Cardiology agree: don’t guess. Screen.

1. Check baseline ECG: Before starting high-risk drugs like sotalol, methadone, or ziprasidone, get an ECG. Measure your QTc. Know your starting point.
2. Monitor after starting: Repeat the ECG 3-7 days after beginning treatment or after a dose increase. That’s when drug levels peak and QT changes are most likely.
3. Stop the drug if QTc >500 ms or jumps >60 ms: Unless there’s no alternative, discontinuing the drug is the safest move.
4. Check electrolytes: If you’re on diuretics or have vomiting/diarrhea, test potassium and magnesium. Correct them before prescribing.

Some hospitals use electronic alerts in their systems to flag risky combinations. One study showed this cut dangerous prescribing by 58%. But many clinics still rely on memory or paper charts. That’s a problem.

The Hidden Danger: Over-the-Counter and Newer Drugs

You might think only prescription drugs matter. But even some OTC meds can contribute. Cold remedies with pseudoephedrine, certain herbal supplements, and even high-dose zinc can interfere with heart rhythms. And new drugs are constantly being added to the risk list.

In November 2023, crediblemeds.org added 17 new drugs, including retatrutide-a new obesity medication that showed a 8.2 ms QTc increase in trials. Cancer drugs like vandetanib and nilotinib are now known to carry QT risk. Of the 27 tyrosine kinase inhibitors approved for cancer, 12 (44%) come with QT prolongation warnings.

The pharmaceutical industry is changing too. Since 2016, the FDA and other global agencies use the CiPA framework-testing drugs on multiple heart channels, not just measuring QT. This has led to 22 drug failures between 2016 and 2022, each costing over $2 billion. That’s good for safety, bad for drug development.

What You Can Do

If you’re on any of these medications:

• Ask your doctor: “Could this drug affect my heart rhythm?”
• Ask if you need a baseline ECG.
• Don’t combine multiple drugs that can prolong QT without checking.
• Report unexplained dizziness, fainting, or palpitations immediately.
• Keep a list of all your meds-including supplements-and share it at every visit.

If you’re a caregiver or family member, watch for sudden changes in behavior, energy, or consciousness. Torsades can strike fast. Early recognition saves lives.

Is Routine ECG Screening Worth It?

Some experts argue it’s not cost-effective for low-risk drugs. The chance of torsades from a single, low-risk medication is less than 1 in 10,000 per year. But when you combine risk factors-female, over 65, on two QT drugs, low potassium-the odds shift dramatically.

One case from a Reddit thread tells the story: a 65-year-old woman on ondansetron and azithromycin for stomach flu saw her QTc jump from 440 to 530 ms in 24 hours. She didn’t collapse, but she came close. Her doctor later admitted: “I didn’t think about the combo. I should have checked.”

Systematic screening isn’t perfect. But for high-risk patients, it’s the difference between prevention and tragedy.

The Bigger Picture

QT prolongation isn’t a rare curiosity. It’s a well-documented, preventable cause of sudden death. The good news? We know which drugs cause it. We know who’s at risk. We know how to test for it.

The challenge isn’t science-it’s systems. Too many prescriptions are written without checking ECGs. Too many patients are discharged with new meds and no follow-up. Too many pharmacies don’t flag dangerous combinations.

But change is happening. AI tools are now being tested to predict torsades risk from subtle ECG patterns-not just QTc. Genetic testing may one day identify high-risk patients before they even start a drug.

For now, the safest approach is simple: know your meds. Know your numbers. Ask questions. Your heart is counting on it.