Nitrofurantoin, sold under common brand names like Macrobid or Macrodantin, is an antibiotic medication prescribed primarily to treat and prevent urinary tract infections (UTIs). It functions by targeting and killing the bacteria responsible for the infection, concentrating its action specifically in the urine. Understanding what substances or conditions can interfere with its action is important for patient safety and to ensure the medication is effective. Avoiding certain drugs, supplements, and recognizing specific health conditions that prevent its use are necessary steps to guarantee successful treatment.
Dangerous Drug Interactions
A number of prescription and over-the-counter (OTC) medications can negatively affect how nitrofurantoin works in the body or increase the risk of serious side effects.
Probenecid
Medications used to treat gout, specifically Probenecid, interfere with the drug’s excretion. Probenecid inhibits the renal tubular secretion of nitrofurantoin, which is the process by which the kidney actively moves the drug into the urine. This action results in higher concentrations of the antibiotic remaining in the bloodstream, increasing the risk of toxicity, such as peripheral neuropathy. Simultaneously, the lower concentration of the drug reaching the urine means it is less effective at fighting the urinary tract infection.
Antacids
Certain antacids, particularly those containing magnesium trisilicate, are also contraindicated when taking nitrofurantoin because they drastically reduce its absorption. The magnesium trisilicate compound physically binds to the nitrofurantoin molecules in the gastrointestinal tract, preventing the body from absorbing the drug. This physical binding significantly lowers the amount of antibiotic that enters the bloodstream. The result is a sub-therapeutic drug level, meaning the antibiotic is not strong enough to clear the infection, potentially leading to treatment failure.
Quinolone Antibiotics
The concurrent use of nitrofurantoin with some quinolone antibiotics, such as ciprofloxacin, should be approached with caution due to the potential for an antagonistic effect. Laboratory studies have shown that nitrofurantoin can suppress the bactericidal effect of quinolones against specific Gram-negative bacteria, like Proteus mirabilis. This pharmacodynamic interference may reduce the overall effectiveness of the quinolone antibiotic, increasing the risk of treatment failure.
Increased Toxicity Risk
Other medications also carry a heightened risk of toxicity when combined with nitrofurantoin. Drugs like methotrexate, used for autoimmune diseases and cancer, are known to have a risk of lung and liver toxicity. Since nitrofurantoin also carries a rare but serious risk of pulmonary and hepatic damage, taking both medications concurrently can significantly increase the likelihood of developing severe lung or liver problems. Furthermore, live vaccines, such as the oral cholera or oral typhoid vaccine, may not be as effective if taken while on nitrofurantoin.
Health Conditions Preventing Nitrofurantoin Use
Nitrofurantoin is not appropriate for individuals with certain underlying health conditions because the risk of harm outweighs the therapeutic benefit.
Severe Kidney Impairment
The most critical contraindication is severe kidney impairment, generally defined as a creatinine clearance (CrCl) of less than 30 mL/min. For nitrofurantoin to work, it must be filtered by the kidneys and concentrated in the urine to achieve an effective antibacterial level. When kidney function is significantly reduced, the drug cannot be cleared efficiently. This leads to two problems: accumulation in the bloodstream, increasing the risk of severe side effects like peripheral neuropathy; and failure to reach the necessary concentration in the urine, rendering the treatment ineffective.
G6PD Deficiency
Patients diagnosed with Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency, a hereditary condition, should never take this antibiotic. Nitrofurantoin is an oxidant drug, and in people with this enzyme deficiency, it can trigger the rapid breakdown of red blood cells, a dangerous condition called hemolytic anemia. This risk of blood cell destruction makes it an absolute contraindication.
Pregnancy and Infants
Nitrofurantoin is strictly contraindicated in late-term pregnancy, specifically between 38 to 42 weeks gestation, during labor and delivery, or when labor is imminent. Exposure during this time, or in infants under one month of age, carries a risk of hemolytic anemia in the newborn. This is due to the infant’s immature red blood cell enzyme systems.
Prior Organ Damage
A prior history of liver or lung damage associated with nitrofurantoin use also prevents further treatment. Because the drug can cause rare but severe hepatotoxicity (liver damage) or pulmonary hypersensitivity reactions (lung damage), a history of such events means the patient is at a high risk for recurrence.
Food, Supplements, and Alcohol Restrictions
While there are no severe, life-threatening interactions between nitrofurantoin and alcohol, its consumption is generally discouraged while taking the antibiotic. Alcohol can worsen the common side effects of nitrofurantoin, such as nausea, dizziness, and headaches. Moreover, alcohol is known to irritate the bladder and urinary tract, which can aggravate the existing symptoms of a urinary tract infection and potentially delay recovery.
Unlike many other antibiotics, nitrofurantoin must be taken with food or milk to ensure optimal absorption and to minimize common gastrointestinal side effects. Taking the drug with a meal or snack helps increase its bioavailability, ensuring that a sufficient amount of the medication is absorbed into the system to be effective. Although no known foods react with nitrofurantoin, highly acidic or spicy foods may irritate the bladder and worsen UTI symptoms.
Patients should also be cautious about taking certain mineral supplements concurrently with their dose of nitrofurantoin. Supplements containing high levels of divalent or trivalent cations, such as magnesium, calcium, or iron, may interfere with the absorption of the antibiotic. Similar to the antacid interaction, these minerals can bind to the drug in the gut, reducing its effectiveness. To prevent this interference, separate the dose of nitrofurantoin from any mineral supplements by at least two hours.