Dofetilide and Cimetidine Interaction: What You Need to Know

When you take dofetilide, a potent antiarrhythmic drug used to treat irregular heartbeats like atrial fibrillation, and mix it with cimetidine, a common acid reducer once sold as Tagamet, you’re risking a serious, potentially deadly heart rhythm problem called QT prolongation, a delay in the heart’s electrical recovery that can trigger sudden cardiac arrest. This isn’t a theoretical concern — it’s a well-documented, clinically significant interaction that has led to hospitalizations and deaths. The reason? Cimetidine blocks the liver enzyme (CYP3A4 and CYP2D6) that clears dofetilide from your body. When that cleanup system slows down, dofetilide builds up to toxic levels, turning a life-saving drug into a heart-stopping one.

This interaction doesn’t just affect people on high doses. Even standard doses of cimetidine — like 200 mg taken a few times a day — can push dofetilide levels into dangerous territory. Older adults, people with kidney problems, or those already on other QT-prolonging drugs (like certain antibiotics, antidepressants, or antifungals) are at even higher risk. The FDA issued warnings about this combo years ago, and major cardiology guidelines still list it as a strict no-go. If you’re on dofetilide, you need to avoid cimetidine entirely. But here’s the catch: many people don’t realize cimetidine is still in over-the-counter pills, or that it’s sometimes used off-label for things like hiccups or acid reflux. Even a single dose can be enough to trigger trouble.

So what do you take instead? There are safer acid reducers that don’t interfere with dofetilide — like famotidine (Pepcid), ranitidine (though it’s mostly off the market), or proton pump inhibitors like omeprazole. These don’t block the same liver enzymes, so they won’t spike your dofetilide levels. But don’t just switch on your own. Talk to your doctor or pharmacist. They can review every pill you take — including supplements and herbal products — because other things like azithromycin, fluconazole, or even St. John’s wort can also mess with dofetilide. This isn’t about one bad combo; it’s about understanding how your whole medication picture fits together. The posts below give you real-world examples of dangerous drug interactions, how to spot hidden risks in your medicine cabinet, and what to ask your provider before starting anything new. You don’t need to guess. You just need the right info.