Macrobid (Nitrofurantoin) Side Effects, Warnings, and Interactions

Macrobid, Macrodantin, and Furadantin (nitrofurantoin) are antibiotics used to treat urinary tract infections (UTIs) caused by E. Coli, Enterobacter cystitis, Enterococcus, Klebsiella, and Staphylococcus aureus bacteria.

Macrobid is a sustained release form of macrocrystalline used twice daily, while Macrodantin is a macrocrystalline form, and Furadantin is a microcrystalline form. The macrocrystalline form is absorbed slower than the microcrystalline form and is useful when patients can’t tolerate the latter. Common side effects of Macrobid, Macrodantin, and Furadantin include:

Serious side effects of Macrobid, Macrodantin, and Furadantin include:

• lung injury (symptoms: difficulty breathing, chills, fever, chest pain, cough),
• anemia,
• liver damage leading to jaundice or hepatitis,
• exfoliative dermatitis,
• Clostridium difficile (C. diff) colitis,
• vasculitis, and
• tingling in the extremities.

Drug interactions of Macrobid, Macrodantin, and Furadantin include probenecid, sulfinpyrazone, magnesium trisilicate antacids, live tuberculosis vaccines (BCG vaccine) and live typhoid vaccines, and quinolone antibiotics.

There are no adequate studies of Macrobid, Macrodantin, and Furadantin in pregnant women, but it is generally considered safe. However, they should not be used near the time of delivery (38-42 weeks gestation) since it interferes with the immature enzyme systems in the red blood cells of newborns, potentially damaging the cells and resulting in anemia. Macrobid, Macrodantin, and Furadantin are distributed into breast milk and should be used with caution in breastfeeding women.

What are the important side effects of Macrobid (nitrofurantoin)?

Common side effects of nitrofurantoin include:

The macrocrystalline form (Macrodantin) causes less stomach upset. Stomach upset can also be minimized by using a lower dose or by taking nitrofurantoin with food or milk.

Possible serious side effects include:

• Lung injury
• Anemia
• Liver damage
• Exfoliative dermatitis
• Clostridium difficilecolitis
• Vasculitis

Nitrofurantoin can cause serious lung injury. The reaction can occur within hours of the start of treatment if the patient has previously received nitrofurantoin, or within a few days of starting nitrofurantoin for the first time. Symptoms include:

In other people, lung injury may occur after approximately a month of treatment. Symptoms include:

• Difficulty breathing
• Rapid breathing
• Cough

Fortunately, the symptoms usually resolve within a week if the medication is stopped. In other individuals, lung injury may not develop until after several months or years of therapy. Unless recognized and treated, this delayed lung injury can result in permanent lung damage that remains even after the drug is stopped.

Nitrofurantoin can also cause damage to the sensory nerves of the arms and legs (peripheral neuropathy), resulting in tingling in the extremities. The condition can become severe and is more likely to occur in people with diabetes, vitamin B deficiency, or general debilitation.

Reduced red blood cell count (anemia) can occur from nitrofurantoin by breaking red blood cells (hemolytic anemia). This reaction occurs most frequently in persons with a deficiency of an enzyme called glucose-6-phosphate dehydrogenase that is crucial to the survival of red blood cells.

Nitrofurantoin can also cause liver damage leading to jaundice or hepatitis. Elevated liver enzymes indicate liver damage and are a reason to stop the drug.

Treatment with nitrofurantoin can cause urine to change color to a dark yellow or brown.

Macrobid (nitrofurantoin) side effects list for healthcare professionals

In clinical trials of Macrobid, common clinical adverse events reported as possibly or probably drug-related were nausea (8%), headache (6%), and flatulence (1.5%). Additional clinical adverse events reported as possibly or probably drug-related occurred in less than 1% of patients studied and are listed below within each body system in order of decreasing frequency:

Respiratory: Acute pulmonary hypersensitivity reaction

Miscellaneous: Fever, chills, malaise

The following additional clinical adverse events have been reported with the use of nitrofurantoin:

Gastrointestinal: Sialadenitis, pancreatitis. There have been sporadic reports of pseudomembranous colitis with the use of nitrofurantoin. The onset of pseudomembranous colitis symptoms may occur during or after antimicrobial treatment.

Neurologic: Peripheral neuropathy, which may become severe or irreversible, has occurred. Fatalities have been reported. Conditions such as renal impairment (creatinine clearance under 60 mL per minute or clinically significant elevated serum creatinine), anemia, diabetes mellitus, electrolyte imbalance, vitamin B deficiency, and debilitating diseases may increase the possibility of peripheral neuropathy.

Asthenia, vertigo, and nystagmus have also been reported with the use of nitrofurantoin.

Benign intracranial hypertension (pseudotumor cerebri), confusion, depression, optic neuritis, and psychotic reactions have been reported rarely. Bulging fontanels, as a sign of benign intracranial hypertension in infants, have been reported rarely.

Respiratory

CHRONIC, SUBACUTE, OR ACUTE PULMONARY HYPERSENSITIVITY REACTIONS MAY OCCUR WITH THE USE OF NITROFURANTOIN.

CHRONIC PULMONARY REACTIONS GENERALLY OCCUR IN PATIENTS WHO HAVE RECEIVED CONTINUOUS TREATMENT FOR SIX MONTHS OR LONGER. MALAISE, DYSPNEA ON EXERTION, COUGH, AND ALTERED PULMONARY FUNCTION ARE COMMON MANIFESTATIONS THAT CAN OCCUR INSIDIOUSLY. RADIOLOGIC AND HISTOLOGIC FINDINGS OF DIFFUSE INTERSTITIAL PNEUMONITIS OR FIBROSIS, OR BOTH, ARE ALSO COMMON MANIFESTATIONS OF THE CHRONIC PULMONARY REACTION. FEVER IS RARELY PROMINENT.

THE SEVERITY OF CHRONIC PULMONARY REACTIONS AND THEIR DEGREE OF RESOLUTION APPEAR TO BE RELATED TO THE DURATION OF THERAPY AFTER THE FIRST CLINICAL SIGNS APPEAR. PULMONARY FUNCTION MAY BE PERMANENTLY IMPAIRED, EVEN AFTER CESSATION OF THERAPY. THE RISK IS GREATER WHEN CHRONIC PULMONARY REACTIONS ARE NOT RECOGNIZED EARLY.

In subacute pulmonary reactions, fever and eosinophilia occur less often than in the acute form. Upon cessation of therapy, recovery may require several months. If the symptoms are not recognized as being drug-related and nitrofurantoin therapy is not stopped, the symptoms may become more severe.

Acute pulmonary reactions are commonly manifested by fever, chills, cough, chest pain, dyspnea, pulmonary infiltration with consolidation or pleural effusion on x-ray, and eosinophilia. Acute reactions usually occur within the first week of treatment and are reversible with cessation of therapy. Resolution often is dramatic.

Changes in EKG (e.g., non-specific ST/T wave changes, bundle branch block) have been reported in association with pulmonary reactions.

Cyanosis has been reported rarely.

Hepatic: Hepatic reactions, including hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis, occur rarely.

Allergic: Lupus-like syndrome associated with pulmonary reaction to nitrofurantoin has been reported. Also, angioedema; maculopapular, erythematous, or eczematous eruptions; anaphylaxis; arthralgia; myalgia; drug fever; chills; and vasculitis (sometimes associated with pulmonary reactions) have been reported. Hypersensitivity reactions represent the most frequent spontaneously-reported adverse events in worldwide postmarketing experience with nitrofurantoin formulations.

Dermatologic: Exfoliative dermatitis and erythema multiforme (including Stevens-Johnson syndrome) have been reported rarely.

Hematologic: Cyanosis secondary to methemoglobinemia has been reported rarely.

Miscellaneous: As with other antimicrobial agents, superinfections caused by resistant organisms, e.g., Pseudomonas species or Candida species, can occur.

In clinical trials of Macrobid, the most frequent laboratory adverse events (1-5%), without regard to drug relationship, were as follows: eosinophilia, increased AST (SGOT), increased ALT (SGPT), decreased hemoglobin, increased serum phosphorus. The following laboratory adverse events have also been reported with the use of nitrofurantoin: glucose-6-phosphate dehydrogenase deficiency anemia, agranulocytosis, leukopenia, granulocytopenia, hemolytic anemia, thrombocytopenia, megaloblastic anemia. In most cases, these hematologic abnormalities resolved following cessation of therapy. Aplastic anemia has been reported rarely.

What drugs interact with Macrobid (nitrofurantoin)?

Antacids containing magnesium trisilicate, when administered concomitantly with nitrofurantoin, reduce both the rate and extent of absorption. The mechanism for this interaction is probably the adsorption of nitrofurantoin onto the surface of magnesium trisilicate.

Uricosuric drugs, such as probenecid and sulfinpyrazone, can inhibit renal tubular secretion of nitrofurantoin. The resulting increase in nitrofurantoin serum levels may increase toxicity, and the decreased urinary levels could lessen its efficacy as a urinary tract antibacterial.

Drug/Laboratory Test Interactions

As a result of the presence of nitrofurantoin, a false-positive reaction for glucose in the urine may occur. This has been observed with Benedict’s and Fehling’s solutions, but not with the glucose enzymatic test.

Summary

Macrobid, Macrodantin, and Furadantin (nitrofurantoin) are antibiotics used to treat urinary tract infections (UTIs) caused by E. Coli, Enterobacter cystitis, Enterococcus, Klebsiella, and Staphylococcus aureus bacteria. Side effects include headache, rash, itching, nausea, vomiting, and others.