QT Prolongation: Medications That Raise Arrhythmia Risk

When your heart beats, it follows a precise electrical pattern. That pattern shows up on an ECG as waves and intervals - one of the most important being the QT interval. This number tells doctors how long it takes your heart’s lower chambers to recharge between beats. If that interval gets too long - a condition called QT prolongation - your heart can slip into a dangerous rhythm called torsades de pointes. And in some cases, that rhythm turns fatal.

QT prolongation isn’t always caused by heart disease. More often, it’s triggered by medications. Hundreds of commonly prescribed drugs - from antibiotics to antidepressants - can stretch that interval, sometimes silently. The risk is real, even if the event is rare. And knowing which drugs to watch for could save your life.

What Exactly Is QT Prolongation?

The QT interval measures the time from when the heart’s ventricles start contracting to when they fully recover. It’s not a fixed number. It changes with your heart rate. That’s why doctors use a corrected version - QTc - which adjusts for how fast or slow your heart is beating. Bazett’s formula is the most common way to calculate it, though it’s not perfect, especially at very slow or fast heart rates.

A normal QTc is under 450 ms for men and under 460 ms for women. Once it hits 500 ms or more, the risk of torsades de pointes jumps significantly. A rise of more than 60 ms from your baseline is also a red flag. That’s why doctors check your ECG before and after starting certain medications - not to scare you, but to catch trouble early.

Most QT-prolonging drugs work by blocking the hERG potassium channel. This channel helps reset the heart’s electrical charge after each beat. When it’s blocked, the heart takes longer to recharge. That delay creates a perfect storm for chaotic rhythms. It’s not the drug’s fault alone - it’s the combination of the drug, your body, and other factors.

High-Risk Medications You Should Know

Some drugs are known to cause QT prolongation more than others. The list is long, but these categories stand out:

• Antiarrhythmics: Drugs like sotalol, dofetilide, and quinidine are designed to treat arrhythmias - but they can cause them too. Sotalol carries a 2-5% risk of torsades in clinical trials. Quinidine? Around 6% of patients develop it.
• Antibiotics: Erythromycin and clarithromycin (macrolides) are common culprits. Moxifloxacin (a fluoroquinolone) can add 6-10 ms to your QTc. Azithromycin is less risky, but still flagged in combination with other drugs.
• Antipsychotics: Haloperidol, ziprasidone, and thioridazine all carry warnings. Ziprasidone even has a black box warning from the FDA. These drugs are often used in emergency settings, making accidental combinations dangerous.
• Antiemetics: Ondansetron (Zofran) is one of the most common causes of drug-induced torsades. It’s given for nausea, especially after surgery or chemo - but it’s also one of the top drugs linked to TdP in FDA reports.
• Antidepressants: Citalopram and escitalopram (Celexa, Lexapro) are dose-dependent. The FDA limits citalopram to 40 mg daily, and 20 mg if you’re over 60. Higher doses? Higher risk.
• Opioid replacement: Methadone is a major concern. Doses over 100 mg daily significantly increase QTc. Many patients on methadone maintenance have no symptoms - until they do.
• Cancer drugs: Tyrosine kinase inhibitors like vandetanib and nilotinib are increasingly common. About 44% of newer oncology drugs carry QT prolongation warnings.

Even drugs you think are safe - like fluconazole (an antifungal) or certain antihistamines - can add to the risk when stacked with others.

Why Some People Are at Higher Risk

Not everyone who takes a QT-prolonging drug develops torsades. But certain factors make it much more likely:

• Female sex: Women make up about 70% of documented torsades cases. Hormonal differences and slower drug clearance play a role.
• Age over 65: Slower metabolism and more medications increase risk.
• Low potassium or magnesium: Electrolyte imbalances make the heart more electrically unstable. This is common in people on diuretics or with eating disorders.
• Heart disease: Prior heart attack, heart failure, or bradycardia (slow heart rate) make the heart more vulnerable.
• Genetics: About 30% of drug-induced torsades cases involve hidden mutations in the hERG gene or related channels. You might not know you’re at risk until it’s too late.
• Drug combinations: Taking two or more QT-prolonging drugs multiplies the risk. A 2020 FDA analysis found 68% of torsades cases involved multiple high-risk drugs. Haloperidol plus ondansetron? That combo has been linked to sudden QT spikes.

One real case from an emergency room: a 65-year-old woman got ondansetron for nausea and azithromycin for a respiratory infection. Her QTc jumped from 440 ms to 530 ms in 24 hours. She developed torsades. She survived - but barely.

How Doctors Manage the Risk

Most hospitals follow a simple three-step approach:

1. Screen before prescribing: Check for electrolyte imbalances, existing heart conditions, and other medications. Ask about family history of sudden cardiac death.
2. Baseline ECG: Recommended for anyone starting a high-risk drug - especially if they’re over 65, female, or on multiple QT-prolonging drugs.
3. Follow-up ECG: Repeat within 3-7 days after starting or increasing the dose. That’s when the drug reaches steady state and the QT effect is strongest.

Some guidelines say: if your QTc goes above 500 ms or increases more than 60 ms from baseline, stop the drug - unless there’s no alternative. That’s what Medsafe (New Zealand’s drug safety agency) recommends. And it’s a standard many U.S. hospitals now follow.

Electronic health records are getting smarter. Systems with built-in QT risk alerts have cut inappropriate prescribing by over 50% in some hospital networks. They flag dangerous combos before the prescription even leaves the computer.

The Bigger Picture: Why This Matters

Drug-induced torsades is rare - less than 1 in 10,000 patient-years for most medications. But when it happens, it’s often sudden and deadly. And unlike heart attacks, there’s rarely warning. No chest pain. No dizziness. Just a flatline.

The pharmaceutical industry is responding. The CiPA initiative - launched by the FDA and global regulators - is replacing old QT testing with more advanced models that look at multiple ion channels, not just one. Since 2016, 22 drug candidates have been scrapped because of proarrhythmia risk. Each failure costs over $2 billion. That’s how seriously this is taken now.

But the real win? Better outcomes. Since 2014, systematic QT risk assessments have reduced drug-induced torsades by about 40%. It’s not perfect - but it’s working.

What You Can Do

If you’re taking any of these medications, here’s what to ask your doctor:

• “Is this drug known to affect the QT interval?”
• “Am I on any other meds that could add to the risk?”
• “Should I have an ECG before or after starting this?”
• “What symptoms should I watch for - like dizziness, palpitations, or fainting?”

Don’t panic if you’re on one of these drugs. Most people take them safely. But awareness matters. If you’ve had unexplained fainting, especially after starting a new medication, get your heart checked. And never stop a medication without talking to your doctor - sudden withdrawal can be just as dangerous.

The goal isn’t to avoid all risky drugs. It’s to use them wisely - with the right checks in place. That’s how medicine keeps getting safer.