H2 Blocker Comparison: Which One Works Best for Your Stomach?

When your stomach burns too much acid, H2 blockers, a class of medications that reduce stomach acid by blocking histamine receptors in the stomach lining. Also known as histamine H2-receptor antagonists, they’re one of the most common ways people manage heartburn, ulcers, and GERD without reaching for proton pump inhibitors. These drugs don’t shut down all acid production—just dial it back enough to give your stomach lining time to heal.

There are four main H2 blockers you’ll find on shelves or in prescriptions: famotidine, the most widely used today, sold as Pepcid and generics, with fewer drug interactions than older versions, cimetidine, the original H2 blocker, known for causing hormone-related side effects in some men, ranitidine, once the top choice, now pulled from most markets due to contamination concerns, and nizatidine, a less common but fast-acting option with low interaction risk. Each works similarly, but their strength, how long they last, and their side effect profiles vary. Famotidine is usually the go-to because it’s strong, lasts up to 12 hours, and doesn’t mess with liver enzymes like cimetidine does. Cimetidine might cause breast enlargement or confusion in older adults. Ranitidine? Best avoided—FDA removed it over cancer-causing impurities. Nizatidine is clean but harder to find.

People choose H2 blockers for different reasons: maybe they can’t tolerate PPIs, need something for occasional heartburn, or are looking for a cheaper option. If you’re taking other meds—especially blood thinners or antifungals—your choice matters a lot. Famotidine and nizatidine are safer bets with fewer interactions. If you’re on a budget, generic famotidine is often under $5 a month. And if you’ve tried antacids and they don’t last, H2 blockers give you longer relief without the daily commitment of stronger acid reducers.

What you’ll find below is a clear breakdown of how these four H2 blockers stack up against each other—not just in theory, but in real use. You’ll see which one works fastest, which lasts longest, which has the fewest side effects, and which ones to avoid entirely. No fluff. Just facts from real patient experiences, prescribing patterns, and safety data. Whether you’re managing daily reflux or just need something for a bad night, this collection gives you what you need to pick the right one.