CHRONIC, SUBACUTE, OR ACUTE PULMONARY HYPERSENSITIVITY
REACTIONS MAY OCCUR.
CHRONIC PULMONARY REACTIONS OCCUR GENERALLY IN PATIENTS W
HO 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).
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, nystagmus, dizziness, headache, and
drowsiness 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.
Dermatologic: Exfoliative dermatitis and erythema
multiforme (including Stevens-Johnson syndrome) have been reported rarely.
Transient alopecia also has been reported.
Allergic: A lupus-like syndrome associated with
pulmonary reactions to nitrofurantoin has been reported. Also, angioedema;
maculopapular, erythematous, or eczematous eruptions; pruritus; urticaria;
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.
Gastrointestinal: Nausea, emesis, and anorexia
occur most often. Abdominal pain and diarrhea are less common gastrointestinal
reactions. These dose-related reactions can be minimized by reduction of
dosage. Sialadenitis and pancreatitis have been reported. 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).
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.
Laboratory Adverse Events: The following
laboratory adverse events have been reported with the use of nitrofurantoin:
increased AST (SGOT), increased ALT (SGPT), decreased hemoglobin, increased
serum phosphorus, eosinophilia, 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.