What You Need to Know About Nitrofurantoin Interactions

Nitrofurantoin (Macrobid, Macrodantin) is one of the most commonly prescribed antibiotics for urinary tract infections. Compared to many other drugs, it has a relatively short list of significant interactions—but the ones it does have are important to know about. Some can make the drug less effective, while others can increase the risk of side effects.

Here's what to watch for and what to tell your doctor before starting Nitrofurantoin.

How Drug Interactions Work

Drug interactions happen when one substance changes how another substance works in your body. With Nitrofurantoin, interactions generally fall into three categories:

1. Something reduces Nitrofurantoin's absorption — Less drug gets into your system, making it less effective against your UTI.
2. Something changes how quickly your body eliminates Nitrofurantoin — This can either increase blood levels (raising toxicity risk) or decrease urine levels (reducing effectiveness).
3. Two drugs have opposing effects — Taking them together may cancel out the benefit of one or both.

Medications That Interact with Nitrofurantoin

Major Interactions

These interactions are clinically significant and should generally be avoided:

Probenecid

• Probenecid (used for gout) blocks the kidneys from excreting Nitrofurantoin into the urine. This has a double-negative effect: it increases Nitrofurantoin blood levels (raising the risk of systemic side effects and toxicity) while simultaneously decreasing urine concentrations (making the drug less effective at the infection site).
• What to do: Do not take Probenecid and Nitrofurantoin together. Tell your doctor if you're taking Probenecid for gout.

Sulfinpyrazone

• Sulfinpyrazone (another gout medication) works similarly to Probenecid and has the same interaction: reduced urinary excretion of Nitrofurantoin and increased blood levels.
• What to do: Avoid this combination. Your doctor should choose an alternative UTI antibiotic or gout medication.

Magnesium Trisilicate Antacids

• Antacids containing magnesium trisilicate can significantly reduce the absorption of Nitrofurantoin from the GI tract. Less absorption means less drug in your urine and a less effective treatment.
• What to do: Avoid magnesium trisilicate-containing antacids while taking Nitrofurantoin. If you need an antacid, ask your pharmacist about alternatives that don't contain magnesium trisilicate (such as calcium carbonate products like Tums).

Moderate Interactions

These interactions are worth knowing about but may not always require avoiding the combination:

Norfloxacin and Other Quinolone Antibiotics

• In laboratory studies, Nitrofurantoin has shown antagonism (opposing effects) with quinolone antibiotics like Norfloxacin (Noroxin), Ciprofloxacin (Cipro), and Levofloxacin (Levaquin). Taking them together may reduce the effectiveness of one or both drugs.
• What to do: These drugs are rarely prescribed together in practice since they're both used for UTIs. If your doctor is considering adding or switching antibiotics, mention that you're on Nitrofurantoin.

Live Vaccines

• Like most antibiotics, Nitrofurantoin may reduce the effectiveness of certain live vaccines, including the BCG vaccine and oral typhoid vaccine.
• What to do: If you need a live vaccine, discuss timing with your doctor. Ideally, complete your Nitrofurantoin course before vaccination.

Anticholinergic Drugs

• Medications with anticholinergic effects (such as certain antihistamines, bladder medications like Oxybutynin, and some antidepressants) can slow stomach emptying. This may increase Nitrofurantoin absorption somewhat, though this effect is usually not clinically significant.
• What to do: No action typically needed, but mention all medications to your doctor.

Supplements and Over-the-Counter Products to Watch

Nitrofurantoin has fewer supplement interactions than many drugs, but a few are worth noting:

• Magnesium-containing antacids and supplements — As mentioned above, magnesium trisilicate specifically can reduce absorption. Other magnesium forms (like magnesium oxide or citrate) have less data but should be taken at least 2 hours apart from Nitrofurantoin as a precaution.
• Cranberry supplements — Many UTI patients take cranberry products. There's no known interaction with Nitrofurantoin, and cranberry is generally fine to continue.
• Probiotics — No direct interaction. Some people take probiotics during antibiotic courses to support gut health. This is generally safe but take them a few hours apart from your antibiotic dose.
• Iron supplements — No significant known interaction with Nitrofurantoin, but iron can affect absorption of some medications. Take them at separate times if possible.

Food and Drink Interactions

Food: Take It WITH Food

This isn't an interaction to avoid—it's one to embrace. Taking Nitrofurantoin with food or milk increases bioavailability by approximately 40%. Food also significantly reduces nausea. Take every dose with a meal or snack. This is one of the most important things you can do to make your treatment effective.

Alcohol

There's no direct pharmacological interaction between Nitrofurantoin and alcohol—it won't cause a disulfiram-like reaction (unlike Metronidazole). However, alcohol can irritate the bladder and worsen UTI symptoms, and both alcohol and Nitrofurantoin can cause nausea and stomach upset. It's generally best to avoid or minimize alcohol while treating a UTI.

Caffeine

No direct drug interaction, but caffeine can irritate the bladder and make UTI symptoms worse. Consider reducing coffee, tea, and energy drinks while you're treating your infection.

What to Tell Your Doctor Before Starting Nitrofurantoin

Before your doctor prescribes Nitrofurantoin, make sure they know about:

• All prescription medications you take — Especially Probenecid, Sulfinpyrazone, or any quinolone antibiotics.
• Over-the-counter medications — Particularly antacids. Specify the brand so they can check if it contains magnesium trisilicate.
• Supplements and vitamins — Especially magnesium supplements.
• Kidney function — Nitrofurantoin is contraindicated if your creatinine clearance is below 60 mL/min. If you have any history of kidney disease, your doctor needs to check your kidney function first.
• Liver problems — If you've had liver issues, especially any related to previous Nitrofurantoin use, this drug should be avoided.
• G6PD deficiency — This genetic condition increases the risk of hemolytic anemia with Nitrofurantoin.
• Pregnancy status — Nitrofurantoin is generally safe in early pregnancy but is contraindicated at term (38–42 weeks).
• Any upcoming vaccinations — Particularly live vaccines like BCG or oral typhoid.

Final Thoughts

The good news is that Nitrofurantoin has a relatively clean interaction profile compared to many other antibiotics. The main things to avoid are Probenecid, Sulfinpyrazone, and magnesium trisilicate antacids. Beyond that, the most important "interaction" to remember is a positive one: always take it with food.

If you're looking for more information about Nitrofurantoin, check out our guides on how Nitrofurantoin works, side effects to watch for, or how to save money on your prescription. And if you need to fill your prescription, Medfinder can help you find Nitrofurantoin in stock near you.