Dofetilide and Cimetidine Interaction: Why This Combination Can Be Deadly

Two medications, taken separately, are safe. Taken together? They can stop your heart.

The Quiet Killer in Your Medicine Cabinet

Dofetilide, sold under the brand name Tikosyn, is a powerful drug used to reset and keep the heart beating normally in people with atrial fibrillation or flutter. It works by blocking specific electrical signals in the heart. But it’s not forgiving. Even a small rise in its blood levels can push the heart into a dangerous rhythm called torsades de pointes - a type of ventricular arrhythmia that can lead to sudden death.

Cimetidine, known as Tagamet, is an old-school acid reducer. For decades, it was the go-to for heartburn and ulcers. It’s cheap, available over the counter, and many older adults still take it without thinking twice. But here’s the problem: cimetidine doesn’t just calm stomach acid. It also shuts down a key kidney pump that clears dofetilide from your body.

This isn’t a theoretical risk. It’s a documented killer.

How One Pill Can Double the Danger

Dofetilide leaves the body mostly through the kidneys - about 80% of it is excreted unchanged. It doesn’t rely on liver enzymes like many other drugs. Instead, it uses a specific transport system in the kidney tubules called a cation exchange pump. That’s where cimetidine steps in.

Cimetidine blocks that pump. Hard. When you take cimetidine with dofetilide, the drug can’t get out. Plasma levels of dofetilide jump by 50% to 100% within 24 hours. That’s not a minor bump. That’s a tsunami.

The result? QT interval prolongation. The QT interval is the time it takes for the heart to recharge between beats. When it stretches too long, the heart becomes electrically unstable. That’s when torsades de pointes can strike - a chaotic, twisting rhythm that often leads to fainting, seizures, or cardiac arrest.

The FDA-approved prescribing information for Tikosyn says that about 3-5% of people on dofetilide alone develop dangerous QT prolongation. With cimetidine? That number jumps to 12-18%. That’s a fourfold increase in risk.

Why Cimetidine Is the Only H2 Blocker That Matters

Not all acid reducers are the same. Famotidine (Pepcid) and ranitidine (Zantac) don’t touch the kidney pump that clears dofetilide. Studies show they cause no meaningful change in dofetilide levels. But cimetidine? It’s uniquely dangerous.

The difference isn’t subtle. In clinical trials, cimetidine increased dofetilide exposure by 40-50%. Famotidine? Zero effect. That’s why the original Tikosyn label, updated as recently as September 2022, explicitly warns: do not use cimetidine with dofetilide.

This isn’t just a warning - it’s a hard contraindication. The American College of Cardiology and the European Heart Rhythm Association both classify this combination as Level 1: Contraindicated. That’s the highest risk category. No exceptions. No "just a little bit." Even a single 300 mg dose of cimetidine for heartburn has triggered torsades de pointes in patients already on stable dofetilide.

Real Cases, Real Consequences

A 72-year-old man with atrial fibrillation was on dofetilide 500 mcg twice daily. His heart was stable. Then he started taking cimetidine 400 mg twice daily for acid reflux. Three days later, he went into torsades de pointes. He needed emergency cardioversion and ICU care.

A 65-year-old woman took one 300 mg tablet of cimetidine for a sudden bout of heartburn. She didn’t even tell her doctor. Within hours, she collapsed. Her ECG showed polymorphic ventricular tachycardia - a direct result of the interaction. She survived, but barely.

These aren’t rare anomalies. Between 2010 and 2022, the FDA received 87 reports of QT prolongation and 23 cases of torsades de pointes linked to this combination. In a 2022 survey of 47 academic medical centers, cardiologists reported that 12-15% of unexpected torsades cases in dofetilide patients involved hidden cimetidine use.

What Should You Do Instead?

If you’re on dofetilide and need acid suppression, you have safe options.

• Famotidine (Pepcid): The preferred choice. No interaction. Safe at doses up to 40 mg twice daily.
• Proton pump inhibitors (PPIs): Omeprazole, esomeprazole, pantoprazole - all fine. No effect on dofetilide levels.

And if you’re already taking cimetidine? Don’t stop cold turkey without talking to your doctor. But do stop - immediately. And tell your cardiologist. They’ll need to check your QT interval and possibly hold dofetilide for 10 days (five half-lives) before restarting it safely.

How Hospitals Are Stopping This Before It Happens

This interaction used to be more common. In 2015, nearly 9% of patients on dofetilide were accidentally prescribed cimetidine. Today? That number is under 1.5%.

Why? Because electronic health records now block it.

Epic, Cerner, and other major systems have built in mandatory alerts. If a doctor tries to prescribe cimetidine to someone on dofetilide, the system shuts it down. It won’t let them proceed unless they override it with a cardiologist’s signature. That override? It requires documenting why the risk is worth it - and there almost never is a good reason.

AI tools are now predicting this interaction before it happens. By analyzing a patient’s medication list and lab results, these systems can flag potential conflicts 72 hours in advance. That’s not science fiction - it’s happening in hospitals right now.

It’s Not Just About the Heart

Low potassium makes this interaction even worse. If your potassium is below 3.6 mmol/L, your risk of torsades skyrockets. That’s why doctors check electrolytes before starting dofetilide - and again if you’re on any new meds.

The goal? Keep potassium between 4.0 and 5.0 mmol/L. Magnesium levels matter too. Both are simple blood tests. Both are non-negotiable.

Why This Interaction Still Matters in 2026

Cimetidine prescriptions have dropped from 28 million a year in 1990 to about 1.2 million today. That’s good. But it’s still out there. In nursing homes. In VA clinics. In the hands of elderly patients who’ve been taking it for 30 years and never thought to ask if it was safe with their heart meds.

The American Geriatrics Society lists this combo as one of the most inappropriate drug pairs for older adults. Why? Because older people often have reduced kidney function - and that makes dofetilide clearance even slower. Add cimetidine? The risk isn’t just higher. It’s catastrophic.

Even if you’re young and healthy, this interaction doesn’t care. It’s a pharmacokinetic law - not a suggestion.

The Bigger Picture

This isn’t just about two drugs. It’s about how easily dangerous interactions slip through the cracks.

People with atrial fibrillation take an average of nearly seven medications. One of them - a simple antacid - can undo all the careful planning behind their heart treatment.

Every time a patient gets a new prescription, someone should ask: "Is this safe with my other meds?" But in busy clinics, that question gets lost. That’s why automated systems and pharmacist-led reviews are now standard in top hospitals.

The cost of getting this wrong? Around $47,500 per avoidable hospitalization - not counting the human toll.

What You Need to Do Today

• If you’re on dofetilide, check your medicine cabinet right now. Is cimetidine (Tagamet) in it? If yes, stop taking it. Call your doctor before switching.
• If you’re prescribed cimetidine and you’re on any heart rhythm medication, ask: "Is this safe with my other drugs?" Don’t assume it is.
• Ask for a copy of your latest ECG. Make sure your QTc is below 440 ms (or 500 ms if you have bundle branch block).
• Ask your pharmacist to run a full drug interaction check every time you get a new prescription.
• If you’re a caregiver for an elderly person on dofetilide, review all their medications - including OTCs - with their cardiologist.

This interaction is preventable. It’s not complicated. It’s not rare. And it’s not a guess. It’s a fact - backed by decades of data, clinical trials, and real patient deaths.

Don’t let a simple acid reducer become your heart’s undoing.