QT prolongation isn’t something most people hear about until it’s too late. It’s a silent electrical glitch in the heart that can turn a routine prescription into a life-threatening event. When the QT interval on an ECG stretches too long, it sets the stage for a dangerous rhythm called torsades de pointes - a type of ventricular tachycardia that can spiral into sudden cardiac death. And the scary part? Many of the drugs that cause this aren’t obscure experimental pills. They’re common medications you might already be taking.
What Exactly Is QT Prolongation?
The QT interval measures how long it takes your heart’s lower chambers (ventricles) to recharge after each beat. It’s shown as a spike and dip on an ECG tracing. When that interval gets too long, the heart muscle doesn’t reset properly. That delay creates an electrical imbalance, making the heart vulnerable to chaotic, rapid firing - torsades de pointes. This isn’t theoretical. It’s been documented in thousands of cases since the 1950s, starting with early antiarrhythmics like quinidine. The main culprit? Blockage of the hERG potassium channel. This channel, found in heart cells, helps pump potassium out to reset the electrical charge. When drugs bind to it - often unintentionally - they slow down repolarization. That’s what stretches the QT interval. The hERG channel is surprisingly easy to block. Even small changes in drug concentration can trigger it.Which Medications Are the Biggest Risks?
Not all QT-prolonging drugs are created equal. Some carry high risk even at normal doses. Others only become dangerous when combined with other drugs or in people with underlying conditions. High-risk cardiac drugs:- Sotalol: Used for atrial fibrillation, it prolongs QT by design - but that’s also why it causes torsades in 2-5% of patients.
- Dofetilide and ibutilide: These are used to reset heart rhythm in hospitals. They’re powerful, and the risk is real. Dofetilide requires hospital admission for the first 3 days of treatment - for monitoring.
- Quinidine and procainamide: Older antiarrhythmics. Quinidine causes torsades in up to 6% of users.
- Amiodarone: Yes, it prolongs QT - a lot. But its multi-channel effects make it less likely to cause torsades than sotalol. Still, it’s not safe to ignore.
- Methadone: Used for pain and opioid addiction. Risk spikes above 100 mg/day. TdP cases are well-documented, especially in patients on high doses without ECG monitoring.
- Citalopram and escitalopram: Common antidepressants. The FDA limited citalopram to 40 mg/day (20 mg for those over 60) because of clear QT prolongation at higher doses.
- Antibiotics: Erythromycin and clarithromycin (macrolides) can prolong QT by 15-25 ms. Azithromycin is lower risk, but still flagged. Fluconazole (an antifungal) is another silent player.
- Antipsychotics: Haloperidol, ziprasidone, and thioridazine carry black box warnings. Ziprasidone’s label explicitly mentions ventricular arrhythmia risk.
- Antiemetics: Ondansetron (Zofran) is given to cancer patients and those with nausea. It’s one of the top drugs linked to TdP in FDA reports - especially when paired with other QT-prolonging meds.
Why Some People Are at Higher Risk
It’s not just about the drug. The person matters - a lot. Women are at 70% higher risk. Hormonal differences make their hearts more sensitive to QT prolongation. The risk is highest in the postpartum period. Age over 65. Kidneys and liver slow down. Drugs stick around longer. Blood levels rise. QT prolongation becomes more likely. Electrolyte imbalances. Low potassium, low magnesium, low calcium - these make the heart even more electrically unstable. A simple case of vomiting or diuretic use can tip the scale. Genetics. About 30% of drug-induced TdP cases involve subtle hERG gene variants. People with these variants don’t know they’re at risk until they take a medication that triggers it. Drug combinations. This is where things get dangerous. Taking two QT-prolonging drugs together doesn’t just add risk - it multiplies it. A 2020 FDA analysis found 68% of TdP cases involved two or more such drugs. Common dangerous pairs: ondansetron + azithromycin, haloperidol + citalopram, erythromycin + fluconazole.
When Does QT Prolongation Become Dangerous?
Not every longer QT interval means danger. But there are clear red flags:- QTc over 500 milliseconds - risk of torsades triples to fivefold.
- An increase of more than 60 ms from baseline - even if still under 500 ms, this is a warning sign.
- Flat or notched T-waves on ECG - subtle signs that often precede torsades.
What Doctors Should Do - And Often Don’t
The European Society of Cardiology and the American Heart Association both recommend baseline ECGs before starting high-risk drugs. Repeat ECGs within 3-7 days after starting or increasing the dose. But in practice? Many doctors skip it. Why? Because they think the risk is too low. And for most people, it is. The absolute risk of TdP from a single non-cardiac drug is less than 1 in 10,000 per year. But when you have a 72-year-old woman on citalopram, with low potassium, taking ondansetron for nausea - that’s not a low-risk patient. That’s a ticking time bomb. A 2022 survey of 327 hospital pharmacists found 63% struggled to determine safe combinations of QT-prolonging drugs. Even experienced providers get overwhelmed. That’s why tools like crediblemeds.org - updated quarterly - are essential. It categorizes drugs as “Known Risk,” “Possible Risk,” or “Conditional Risk.” It’s the gold standard.
What You Can Do
If you’re on any of these medications, here’s what matters:- Ask your doctor: “Could this drug affect my heart rhythm?”
- Know your ECG history. If you’ve had a baseline ECG, keep a copy. Bring it to appointments.
- Watch for symptoms. Dizziness, fainting, palpitations, or sudden fatigue - especially after starting a new drug - need immediate attention.
- Don’t combine meds without checking. If you’re prescribed something new, ask your pharmacist if it interacts with your other drugs.
- Check electrolytes. If you’re on diuretics or have had vomiting/diarrhea, get your potassium and magnesium levels checked.