CHRONIC, SUBACUTE, OR ACUTE PULMONARY HYPERSENSITIVITY
REACTIONS MAY OCCUR.
CHRONIC PULMONARY REACTIONS MAY OCCUR GENERALLY 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
DEGREES 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 more severe.
Acute pulmonary reactions are commonly manifested by
fever, chills, cough, chest pain, dyspnea, pulmonary infiltration with
consolidation of 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 reactions, including hepatitis, cholestatic
jaundice, chronic active hepatitis, and hepatic neurosis, occur rarely. (see
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 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.
Exfoliative dermatitis and erythema multiforme (including
Stevens-Johnson syndrome) have been reported rarely. Transient alopecia also
has been reported.
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; and vasculitis (sometimes associated with pulmonary
reactions) have been reported. Hypersensitivity reactions present the most
frequent spontaneously-reported adverse events in world-wide postmarketing
experience with nitrofurantoin formulations.
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)
Cyanosis secondary to methemoglobinemia has been reported
As with other antimicrobial agents, superinfections
caused by resistant organisms, e.g., Pseudomonas species or Candida species,
can occur. There are sporadic reports of Clostridium difficile superinfections,
or pseudomembranous colitis, with the use of nitrofurantoin.
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.