Nitrofurantoin, sold under brand names like Macrobid and Macrodantin, is an antibiotic primarily used to treat and prevent uncomplicated urinary tract infections (UTIs) [1.7.1, 1.7.4]. Its effectiveness stems from its ability to concentrate in the lower urinary tract, where it kills infection-causing bacteria [1.7.4]. However, its efficacy and safety can be compromised when taken with certain other medications. It is crucial for patients and healthcare providers to be aware of these potential interactions to ensure proper treatment and avoid adverse effects.
Major Drug Interactions with Nitrofurantoin
Certain medications can significantly interfere with how nitrofurantoin works or increase the risk of side effects. These interactions are categorized based on their mechanism and clinical significance.
Medications That Reduce Nitrofurantoin's Effectiveness
Some drugs can decrease the absorption or antibacterial action of nitrofurantoin, potentially leading to treatment failure.
- Antacids Containing Magnesium Trisilicate: When taken concurrently, antacids that contain magnesium trisilicate can reduce both the rate and extent of nitrofurantoin absorption [1.3.7, 1.4.2]. The mechanism is thought to be the adsorption of nitrofurantoin onto the surface of the magnesium trisilicate, which prevents it from being properly absorbed by the body [1.3.7]. This can lead to lower levels of the antibiotic in the urine, making it less effective at fighting the UTI [1.5.3]. It is recommended to avoid these antacids, such as Gaviscon, while on nitrofurantoin [1.4.6].
- Quinolone Antibiotics: Antibiotics known as quinolones (e.g., ciprofloxacin, levofloxacin, moxifloxacin) should not be taken with nitrofurantoin [1.3.6]. This is because their mechanisms of action can be antagonistic, meaning they may work against each other, reducing the overall antibacterial effect.
- Live Oral Vaccines: Nitrofurantoin can diminish the effectiveness of certain live vaccines that are taken orally, such as the typhoid vaccine (Vivotif) and the cholera vaccine (Vaxchora) [1.2.1, 1.6.2]. The antibiotic can inhibit the activity of the live bacteria in the vaccine, preventing the body from mounting an adequate immune response [1.6.1]. The CDC recommends waiting 3 days after finishing nitrofurantoin to take the oral typhoid vaccine and 14 days for the oral cholera vaccine [1.6.3].
Medications That Increase Nitrofurantoin Toxicity
Other drugs can alter how nitrofurantoin is processed in the body, leading to increased levels in the blood and a higher risk of side effects.
- Gout Medications (Probenecid and Sulfinpyrazone): These medications, known as uricosuric agents, work by inhibiting the renal tubular secretion of certain substances, including nitrofurantoin [1.3.7]. By blocking its excretion into the urine, they cause nitrofurantoin to build up in the bloodstream [1.5.3, 1.4.2]. This not only increases the risk of systemic side effects like lung or liver problems, but it also decreases the concentration of the antibiotic in the urine, where it is needed to treat the infection [1.5.1]. Therefore, concurrent use should be avoided [1.5.4].
- Methotrexate: Taking nitrofurantoin with methotrexate, a drug used for conditions like rheumatoid arthritis and cancer, can increase the risk of methotrexate toxicity [1.2.1].
- Fluconazole: This antifungal medication, when taken with nitrofurantoin, may increase the risk of adverse effects [1.3.2].
Comparison of Major Nitrofurantoin Interactions
| Interacting Medication Class | Example(s) | Primary Risk | Management Recommendation |
|---|---|---|---|
| Antacids with Magnesium | Gaviscon, Genaton [1.3.3, 1.4.4] | Decreased nitrofurantoin absorption and effectiveness [1.3.7] | Avoid concurrent use. Separate doses if necessary [1.4.8]. |
| Gout Medications | Probenecid, Sulfinpyrazone [1.5.3] | Increased nitrofurantoin blood levels (toxicity) and decreased effectiveness in urine [1.5.1] | Avoid concurrent use. Consider alternative antibiotics [1.5.4]. |
| Live Oral Vaccines | Typhoid (Vivotif), Cholera (Vaxchora) [1.6.2] | Reduced vaccine effectiveness [1.6.1] | Wait at least 3-14 days after finishing nitrofurantoin before vaccination [1.6.3]. |
| Quinolone Antibiotics | Ciprofloxacin, Levofloxacin [1.3.6] | Antagonistic effect, reducing antibacterial action [1.3.6] | Avoid concurrent use. |
Other Considerations
- Lab Tests: Nitrofurantoin can cause a false-positive result for glucose in urine tests when using certain methods, such as Benedict's and Fehling's solutions [1.3.7]. Enzymatic glucose tests are not affected [1.3.7].
- Kidney Function: Patients with poor kidney function (renal impairment), anuria (no urine production), or oliguria (low urine output) should not take nitrofurantoin [1.7.5]. The drug may not reach effective concentrations in the urine and can accumulate in the body, increasing toxicity risk [1.7.5].
- Pregnancy: Nitrofurantoin should not be used at term (38-42 weeks of pregnancy) or during labor and delivery because it can interfere with the immature enzyme systems in a newborn's red blood cells, potentially leading to anemia [1.2.5].
Conclusion
To ensure the safe and effective use of nitrofurantoin for treating urinary tract infections, it is vital to manage potential drug interactions. Medications to avoid include antacids with magnesium trisilicate, certain gout medications like probenecid, some live oral vaccines, and quinolone antibiotics [1.3.6, 1.5.3, 1.4.6, 1.6.2]. These interactions can either render the antibiotic ineffective or increase the risk of harmful side effects. Always inform your healthcare provider about all prescription medications, over-the-counter drugs, and supplements you are taking before starting nitrofurantoin to prevent complications [1.2.1].
For more detailed information, one authoritative resource is the U.S. Food and Drug Administration (FDA) label for the medication, such as this one for Macrobid®.
