CONTRAINDICATIONS
Tablets and Ophthalmic Solution: Noroxin is contraindicated in patients with a history of
hypersensitivity to norfloxacin or the other members of the quinolone group of antibacterial agents,
or any other component of these medications.
WARNINGS
Tablets
The safety and efficacy of oral norfloxacin in children, adolescents (under the age of 18),
pregnant women, and nursing mothers have not been established. (See PRECAUTIONS,
Pregnancy, Nursing Mothers and Pediatric Use.) The oral administration of single doses of
norfloxacin, 6 times† the recommended human clinical dose (on a mg/kg basis), caused lameness in
immature dogs. Histologic examination of the weight-bearing joints of these dogs revealed
permanent lesions of the cartilage. Other quinolones also produced erosions of the cartilage in
weight-bearing joints and other signs of arthropathy in immature animals of various species. (See
ANIMAL PHARMACOLOGY.)
Norfloxacin has not been shown to be effective in the treatment of syphilis. Antimicrobial
agents used in high doses for short periods of time to treat gonorrhea may mask or delay the
symptoms of incubating syphilis. All patients with gonorrhea should have a serologic test for syphilis
at the time of diagnosis. Patients treated with norfloxacin should have a follow-up serologic test for
syphilis after three months.
Serious and occasionally fatal hypersensitivity (anaphylactoid or anaphylactic) reactions, some
following the first dose, have been reported in patients receiving quinolone therapy. Some reactions
were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial
edema, dyspnea, urticaria and itching. Only a few patients had a history of hypersensitivity
reactions. If an allergic reaction to norfloxacin occurs, discontinue the drug. Serious acute
hypersensitivity reactions may require immediate emergency treatment with epinephrine. Oxygen,
intravenous fluids, antihistamines, corticosteroids, pressor amines, and airway management,
including intubation, should be administered as indicated.
Convulsions have been reported in patients receiving norfloxacin. Convulsions, increased
intracranial pressure, and toxic psychoses have been reported in patients receiving drugs in this
class. Quinolones may also cause central nervous system (CNS) stimulation which may lead to
tremors, restlessness, lightheadedness, confusion, and hallucinations. If these reactions occur in
patients receiving norfloxacin, the drug should be discontinued and appropriate measures instituted.
The effects of norfloxacin on brain function or on the electrical activity of the brain have not been
tested. Therefore, until more information becomes available, norfloxacin, like all other quinolones,
should be used with caution in patients with known or suspected CNS disorders, such as severe
cerebral arteriosclerosis, epilepsy, and other factors which predispose to seizures. (See ADVERSE
REACTIONS.)
†Based on a patient weight of 50 kg.
Ophthalmic Solution
Not For Injection Into The Eye: Serious and occasionally fatal hypersensitivity (anaphylactoid or
anaphylactic) reactions, some following the first dose, have been reported in patients receiving
systemic quinolone therapy. Some reactions were accompanied by cardiovascular collapse, loss of
consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and itching. Only a few
patients had a history of hypersensitivity reactions. Serious anaphylactoid or anaphylactic reactions
require immediate emergency treatment with epinephrine. Oxygen, intravenous steroids and airway
management, including intubation, should be administered as indicated.
PRECAUTIONS
General
Needle-shaped crystals were found in the urine of some volunteers who received either placebo,
800 mg norfloxacin, or 1600 mg norfloxacin (at or twice the recommended daily dose, respectively)
while participating in a double-blind, crossover study comparing single doses of norfloxacin with
placebo. While crystalluria is not expected to occur under usual conditions with a dosage regimen of
400 mg b.i.d., as a precaution, the daily recommended dosage should not be exceeded and the
patient should drink sufficient fluids to ensure a proper state of hydration and adequate urinary
output.
Alteration in dosage regimen is necessary for patients with impaired renal function (see DOSAGE
AND ADMINISTRATION.)
Moderate to severe phototoxicity reactions have been observed in patients who are exposed to
excessive sunlight while receiving some members of this drug class. Excessive sunlight should be
avoided. Therapy should be discontinued if phototoxicity occurs.
Ophthalmic Solution: As with other antibiotic preparations, prolonged use may result in
overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, appropriate
measures should be initiated. Whenever clinical judgment dictates, the patient should be examined
with the aid of magnification, such as slit lamp biomicroscopy and, where appropriate, fluorescein
staining.
Information for the Patient
Tablets: Patients should be advised:
To drink fluids liberally.
That norfloxacin should be taken at least one hour before or at least two hours after a meal.
That multivitamins or other products containing iron or zinc, or antacids should not be taken
within the two-hour period before or within the two-hour period after taking norfloxacin. (See
DRUG INTERACTIONS)
That norfloxacin can cause dizziness and lightheadedness and, therefore, patients should
know how they react to norfloxacin before they operate an automobile or machinery or
engage in activities requiring mental alertness and coordination.
That norfloxacin may be associated with hypersensitivity reactions, even following the first
dose, and to discontinue the drug at the first sign of a skin rash or other allergic reaction.
To avoid undue exposure to excessive sunlight while receiving norfloxacin and to discontinue
therapy if phototoxicity occurs.
That some quinolones may increase the effects of theophylline and/or caffeine. (See DRUG
INTERACTIONS.)
Ophthalmic Solution: Patients should be instructed to avoid allowing the tip of the dispensing
container to contact the eye or surrounding structures.
Patients should be advised that norfloxacin may be associated with hypersensitivity reactions, even
following a single dose, and to discontinue the drug at the first sign of a skin rash or other allergic
reaction.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
No increase in neoplastic changes was observed with norfloxacin as compared to controls in a
study in rats, lasting up to 96 weeks at doses 8 - 9 times† the usual human oral dose (on a mg/kg
basis).
Norfloxacin was tested for mutagenic activity in a number of in vivo and in vitro tests. Norfloxacin
had no mutagenic effect in the dominant lethal test in mice and did not cause chromosomal
aberrations in hamsters or rats at doses 30 - 60 times† the usual human dose (on mg/kg basis).
Norfloxacin had no mutagenic activity in vitro in the Ames microbial mutagen test, Chinese
hamster fibroblasts and V-79 mammalian cell assay. Although norfloxacin was weakly positive in
the Rec-assay for DNA repair, all other mutagenic assays were negative including a more sensitive
test (V-79).
Norfloxacin did not adversely affect the fertility of male and female mice at oral doses up to 30
times† the usual human dose (on a mg/kg basis).
Pregnancy, Teratogenic Effects, Pregnancy Category C
Norfloxacin has been shown to produce embryonic loss in monkeys when given in doses 10 times†
the maximum daily total human dose (on a mg/kg basis). At this dose, peak plasma levels obtained
in monkeys were approximately 2 times those obtained in humans. There has been no evidence of a
teratogenic effect in any of the animal species tested (rat, rabbit, mouse, monkey) at 6 - 50 times†
the maximum daily human dose (on a mg/kg basis). There are, however, no adequate and well
controlled studies in pregnant women. Norfloxacin should be used during pregnancy only if the
potential benefit justifies the potential risk to the fetus.
Nursing Mothers
It is not known whether norfloxacin is excreted in human milk.
When a 200-mg dose of Noroxin was administered to nursing mothers, norfloxacin was not
detected in human milk. However, because the dose studied was low, because other drugs in this
class are secreted in human milk, and because of the potential for serious adverse reactions from
norfloxacin in nursing infants, a decision should be made to discontinue nursing or to discontinue the
drug, taking into account the importance of the drug to the mother.
Pediatric Use
Tablets: The safety and effectiveness of oral norfloxacin in children and adolescents below the age
of 18 years have not been established. Norfloxacin causes arthropathy in juvenile animals of several
animal species. (See WARNINGS and ANIMAL PHARMACOLOGY.)
Ophthalmic Solution: Safety and effectiveness in infants below the age of one year have not been
established.
Although quinolones including norfloxacin have been shown to cause arthropathy in immature
animals after oral administration, topical ocular administration of other quinolones to immature
animals has not shown any arthropathy and there is no evidence that the ophthalmic dosage form of
those quinolones has any effects on the weight bearing joints.