In clinical trials of Macrobid, the most frequent
clinical adverse events that were 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:
Gastrointestinal: Diarrhea, dyspepsia, abdominal
pain, constipation, emesis
Neurologic: Dizziness, drowsiness, amblyopia
Respiratory: Acute pulmonary hypersensitivity
reaction (see WARNINGS)
Allergic: Pruritus, urticaria
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. (See WARNINGS.)
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. (See WARNINGS.)
Asthenia, vertigo, and nystagmus also have 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.
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
WHICH 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 IMPAIRED PERMANENTLY,
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
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. (See WARNINGS.)
Changes in EKG (e.g., non-specific ST/T wave changes,
bundle branch block) have been reported in association with pulmonary
Cyanosis has been reported rarely.
Hepatic: Hepatic reactions, including hepatitis,
cholestatic jaundice, chronic active hepatitis, and hepatic necrosis, occur
rarely. (See WARNINGS.)
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
also have been reported with the use of nitrofurantoin: glucose-6- phosphate
dehydrogenase deficiency anemia (see WARNINGS), 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.