A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Zagam Warnings, Precautions, Pregnancy, Nursing, Abuse - Sparfloxacin
Zagam Warnings, Precautions, Pregnancy, Nursing, Abuse - Sparfloxacin
WARNINGS
MODERATE TO SEVERE PHOTOTOXIC REACTIONS HAVE OCCURRED IN PATIENTS EXPOSED
TO DIRECT OR INDIRECT SUNLIGHT OR TO ARTIFICIAL ULTRAVIOLET LIGHT (e.g., SUNLAMPS)
DURING OR FOLLOWING TREATMENT. THESE REACTIONS HAVE ALSO OCCURRED IN PATIENTS
EXPOSED TO SHADED OR DIFFUSE LIGHT, INCLUDING EXPOSURE THROUGH GLASS OR DURING
CLOUDY WEATHER. PATIENTS SHOULD BE ADVISED TO DISCONTINUE SPARFLOXACIN THERAPY
AT THE FIRST SIGNS OR SYMPTOMS OF A PHOTOTOXICITY REACTION SUCH AS A SENSATION
OF SKIN BURNING, REDNESS, SWELLING, BLISTERS, RASH, ITCHING, OR DERMATITIS.
The overall incidence of drug related phototoxicity in the 1585 patients who
received sparfloxacin during clinical trials with recommended dosage was 7.9%
(n=126). Phototoxicity ranged from mild 4.1% (n=65) to moderate 3.3% (n=52)
to severe 0.6% (n=9), with severe defined as involving at least significant
curtailment of normal daily activity. The frequency of phototoxicity reactions
characterized by blister formation was 0.8% (n=13) of which 3 were severe. The
discontinuation rate due to phototoxicity independent of drug relationship was
1.1% (n=17).
As with some other types of phototoxicity, there is the potential for exacerbation
of the reaction on re-exposure to sunlight or artificial ultraviolet light prior
to complete recovery from the reaction. In a few cases, recovery from phototoxicity
reactions was prolonged for several weeks. In rare cases, reactions have recurred
up to several weeks after stopping sparfloxacin therapy.
EXPOSURE TO DIRECT AND INDIRECT SUNLIGHT (EVEN WHEN USING SUNSCREENS OR SUNBLOCKS)
SHOULD BE AVOIDED WHILE TAKING SPARFLOXACIN AND FOR FIVE DAYS FOLLOWING THERAPY.
SPARFLOXACIN THERAPY SHOULD BE DISCONTINUED IMMEDIATELY AT THE FIRST SIGNS OR
SYMPTOMS OF PHOTOTOXICITY.
These phototoxic reactions have occurred with and without the use of sunscreens
or sunblocks and have been associated with a single dose of sparfloxacin. However,
a study in healthy volunteers has demonstrated that some sunscreen products,
specifically those active in blocking UVA spectrum wavelengths (those containing
the active ingredients octocrylene or Parsol® 1789), can moderate the photosensitizing
effect of sparfloxacin. However, many over-the-counter sunscreens do not provide
adequate UVA protection.
Increases in the QT c interval have been observed in healthy volunteers
treated with sparfloxacin. After a single loading dose of 400 mg, a mean increase
in QT c interval of 11 msec (2.9%) is seen; at steady-state the mean
increase is 7 msec (1.9%). The magnitude of the QT c effect does
not increase with repeated administration, and the QT c returns to
baseline within 48 hours of the last dose. In clinical trials involving 1489
patients with a baseline QT c measurement, the mean prolongation
at steady-state was 10 msec (2.5%); 0.7% of patients had a QT c interval
greater than 500 msec; however, no arrhythmic effects were seen.
THE SAFETY AND EFFECTIVENESS OF SPARFLOXACIN IN CHILDREN, ADOLESCENTS (UNDER
THE AGE OF 18 YEARS), PREGNANT WOMEN, AND LACTATING WOMEN HAVE NOT BEEN ESTABLISHED.
(See PRECAUTIONS
Pregnancy, Nursing Mothers; and Pediatric
Use. )
Sparfloxacin has been shown to cause arthropathy in immature dogs when given
in oral doses of 25 mg/kg/day (approximately 1.9 times the highest human dose
on a mg/m 2 basis) for seven consecutive days. Examination of the
weight-bearing joints of the dogs revealed small erosive lesions of the cartilage.
Other quinolones also produce erosions of cartilage of weight-bearing joints
and other signs of arthropathy in immature animals of various species.
Convulsions and toxic psychoses have been reported in patients receiving quinolones,
including sparfloxacin. Quinolones may also cause increased intracranial pressure
and central nervous system stimulation which may lead to tremors, restlessness/agitation,
anxiety/nervousness, lightheadedness, confusion, hallucinations, paranoia, depression,
nightmares, insomnia, and, rarely, suicidal thoughts or acts. These reactions
may occur following the first dose. If these reactions occur in patients receiving
sparfloxacin, the drug should be discontinued and appropriate measures instituted.
As with other quinolones, sparfloxacin should be used with caution in patients
with a known or suspected CNS disorder that may predispose to seizures or lower
the seizure threshold (e.g., severe cerebral arteriosclerosis, epilepsy) or
in the presence of other risk factors that may predispose to seizures or lower
the seizure threshold (e.g., certain drug therapy, renal dysfunction). Cases
of seizure associated with hypoglycemia have been reported. (See PRECAUTIONS
: General , Information for Patients , Drug Interactions and ADVERSE
REACTIONS . )
Serious and occasionally fatal hypersensitivity (including anaphylactoid or
anaphylactic) reactions, some following the first dose, have been reported in
patients receiving quinolones. Some reactions were accompanied by cardiovascular
collapse, hypotension/shock, seizure, loss of consciousness, tingling, angioedema
(including tongue, laryngeal, throat, or facial edema), airway obstruction (including
bronchospasm, shortness of breath, and acute respiratory distress), dyspnea,
urticaria, and/or itching. Only a few patients had a history of previous hypersensitivity
reactions. If an allergic reaction to sparfloxacin occurs, the drug should be
discontinued immediately. Serious acute hypersensitivity reactions may require
immediate treatment with epinephrine, and other resuscitative measures including
oxygen, intravenous fluids, antihistamines, corticosteroids, pressor amines,
and airway management, including intubation, as clinically indicated.
Serious and sometimes fatal events, some due to hypersensitivity, and some
due to uncertain etiology, have been reported rarely in patients receiving therapy
with quinolones. These events may be severe and generally occur following the
administration of multiple doses. Clinical manifestations may include one or
more of the following: fever, rash or severe dermatologic reactions (e.g., toxic
epidermal necrolysis, Stevens-Johnson Syndrome); vasculitis; arthralgia; myalgia;
serum sickness; allergic pneumonitis; interstitial nephritis; acute renal insufficiency
or failure; hepatitis; jaundice; acute hepatic necrosis or failure; anemia,
including hemolytic and aplastic; thrombocytopenia, including thrombotic thrombocytopenic
purpura; leukopenia; agranulocytosis; pancytopenia; and/or other hematologic
abnormalities. The drug should be discontinued immediately at the first appearance
of a skin rash or any other sign of hypersensitivity and supportive measures
instituted. (See PRECAUTIONS
: Information for Patients and ADVERSE
REACTIONS . )
Pseudomembranous colitis has been reported with nearly all antibacterial agents,
including sparfloxacin, and may range in severity from mild to life-threatening.
Therefore, it is important to consider this diagnosis in patients who present
with diarrhea subsequent to the administration of antibacterial agents.
Treatment with antibacterial agents alters the normal flora of the colon and
may permit overgrowth of clostridia. Studies indicate that a toxin produced
by Clostridium difficile is one primary cause of "antibiotic-associated
colitis."
After the diagnosis of pseudomembranous colitis has been established, therapeutic
measures should be initiated. Mild cases of pseudomembranous colitis usually
respond to drug discontinuation alone. In moderate to severe cases, consideration
should be given to management with fluids and electrolytes, protein supplementation,
and treatment with an antibacterial drug clinically effective against C.
difficile colitis.
Ruptures of the shoulder, hand, and Achilles tendons that required surgical
repair or resulted in prolonged disability have been reported with sparfloxacin
and other quinolones. Sparfloxacin should be discontinued if the patient experiences
pain, inflammation, or rupture of a tendon. Patients should rest and refrain
from exercise until the diagnosis of tendonitis or tendon rupture has been confidently
excluded. Tendon rupture can occur at any time during or after therapy with
sparfloxacin.
PRECAUTIONS
General: Adequate hydration of patients receiving sparfloxacin
should be maintained to prevent the formation of a highly concentrated urine.
Administer sparfloxacin with caution in the presence of renal insufficiency.
Careful clinical observation and appropriate laboratory studies should be performed
prior to and during therapy since elimination of sparfloxacin may be reduced.
Adjustment of the dosage regimen is necessary for patients with impaired renal
function-creatinine clearance <50 mL/min. (See CLINICAL PHARMACOLOGYand
DOSAGE AND ADMINISTRATION . )
Avoid the concomitant prescription of medications known to prolong the QT c
interval, e.g., erythromycin, terfenadine, astemizole, cisapride, pentamidine,
tricyclic antidepressants, some antipsychotics including phenothiazines. (See
CONTRAINDICATIONS . ) Sparfloxacin is not recommended for use in patients
with pro-arrhythmic conditions (e.g., hypokalemia, significant bradycardia,
congestive heart failure, myocardial ischemia, and atrial fibrillation).
Moderate to severe phototoxicity reactions have been observed in patients exposed
to direct sunlight while receiving drugs in this class. Excessive exposure to
sunlight should be avoided. In clinical trials with sparfloxacin, phototoxicity
was observed in approximately 7% of patients. Therapy should be discontinued
if phototoxicity (e.g., a skin eruption) occurs.
As with other quinolones, sparfloxacin should be used with caution in any patient
with a known or suspected CNS disorder that may predispose to seizures or lower
the seizure threshold (e.g., severe cerebral arteriosclerosis, epilepsy) or
in the presence of other risk factors that may predispose to seizures or lower
the seizure threshold (e.g., certain drug therapy, renal dysfunction). (See
WARNINGS
and Drug Interactions . )
Information for Patients:
Patients should be advised:
- to avoid exposure to direct or indirect sunlight (including through glass,
while using sunscreens and sunblocks, reflected sunlight, and cloudy weather)
and exposure to artificial ultraviolet light (e.g., sunlamps) during treatment
with sparfloxacin and for five days after therapy. If brief exposure to the
sun cannot be avoided, patients should cover as much of their skin as possible
with clothing;
- to discontinue sparfloxacin therapy at the first sign or symptom of phototoxicity
reaction such as a sensation of skin burning, redness, swelling, blisters,
rash, itching or dermatitis;
- that a patient who has experienced a phototoxic reaction with sparfloxacin
should also be advised to avoid further exposure to sunlight and artificial
ultraviolet light until the phototoxicity reaction has resolved and he or
she has completely recovered from the reaction or for five days whichever
is longer. In rare cases, reactions have recurred up to several weeks after
stopping sparfloxacin therapy;
- that sparfloxacin may cause neurologic adverse effects (e.g., dizziness,
lightheadedness) and that patients should know how they react to sparfloxacin
before they operate an automobile or machinery or engage in other activities
requiring mental alertness and coordination (see
WARNINGS
and ADVERSE
REACTIONS);
- to discontinue treatment and inform their physician if they experience pain,
inflammation, or rupture of a tendon, and to rest and refrain from exercise
until the diagnosis of tendonitis or tendon rupture has been confidently excluded;
- that sparfloxacin can be taken with food or milk or caffeine-containing
products;
- that mineral supplements or vitamins with iron, or zinc, or calcium may
be taken 4 hours after sparfloxacin administration;
- that sucralfate or magnesium- and aluminum-containing antacids may be taken
4 hours after sparfloxacin administration (see
PRECAUTIONS
Drug Interactions
);
- that sparfloxacin 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 drink fluids liberally.
Drug Interactions:
Digoxin: Sparfloxacin has no effect on the pharmacokinetics
of digoxin.
Methylxanthines: Sparfloxacin does not increase plasma theophylline
concentrations. Since there is no interaction with theophylline, interaction
with other methylxanthines such as caffeine is unlikely.
Warfarin: Sparfloxacin does not increase the anti-coagulant
effect of warfarin.
Cimetidine: Cimetidine does not affect the pharmacokinetics
of sparfloxacin.
Antacids and Sucralfate: Aluminum and magnesium cations
in antacids and sucralfate form chelation complexes with sparfloxacin. The oral
bioavailability of sparfloxacin is reduced when an aluminum-magnesium suspension
is administered between 2 hours before and 2 hours after sparfloxacin administration.
The oral bioavailability of sparfloxacin is not reduced when the aluminum-magnesium
suspension is administered 4 hours following sparfloxacin administration.
Zinc/iron salts: Absorption of quinolones is reduced significantly
by these preparations. These products may be taken 4 hours after sparfloxacin
administration.
Probenecid: Probenecid does not alter the pharmacokinetics
of sparfloxacin.
Drug/Laboratory Test Interactions:
Sparfloxacin therapy may produce false-negative culture results for Mycobacterium
tuberculosis by suppression of mycobacterial growth.
Carcinogenesis, Mutagenesis, Impairment of Fertility:
Carcinogenesis: Sparfloxacin was not carcinogenic in mice
or rats when administered for 104 weeks at daily oral doses 3.5-6.2 times greater
than the maximum human dose (400 mg), respectively, based upon mg/m 2 .
These doses corresponded to plasma concentrations approximately equal to (mice)
and 2.2 times greater than (rats) maximum human plasma concentrations.
Mutagenesis: Sparfloxacin was not mutagenic in Salmonella
typhimurium TA98, TA100, TA1535, or TA1537, in Escherichia coli strain
WP2 uvrA, nor in Chinese hamster lung cells. Sparfloxacin and other quinolones
have been shown to be mutagenic in Salmonella typhimurium strain TA102
and to induce DNA repair in Escherichia coli , perhaps due to their inhibitory
effect on bacterial DNA gyrase. Sparfloxacin induced chromosomal aberrations
in Chinese hamster lung cells in vitro at cytotoxic concentrations; however,
no increase in chromosomal aberrations or micronuclei in bone marrow cells was
observed after sparfloxacin was administered orally to mice.
Impairment of Fertility: Sparfloxacin had no effect on the
fertility or reproductive performance of male or female rats at oral doses up
to 15.4 times the maximum human dose (400 mg) based upon mg/m 2 (equivalent
to approximately 12 times the maximum human plasma concentration).
Pregnancy: Teratogenic effects: Pregnancy Category C Reproduction
studies performed in rats, rabbits, and monkeys at oral doses 6.2, 4.4, and
2.6 times higher than the maximum human dose, respectively, based upon mg/m
2 (corresponding to plasma concentrations 4.5- and 6.5-fold higher
than in humans in the monkey and rat, respectively) did not reveal any evidence
of teratogenic effects. At these doses, sparfloxacin was clearly maternally
toxic to the rabbit and monkey with evidence of slight maternal toxicity observed
in the rat. When administered to pregnant rats at clearly maternally toxic doses
(>/=9.3 times the maximum human dose based upon mg/m 2 ), sparfloxacin
induced a dose-dependent increase in the incidence of fetuses with ventricular
septal defects. Among the three species tested, this effect was specific to
the rat. There are, however, no adequate and well-controlled studies in pregnant
women. Sparfloxacin should be used during pregnancy only if the potential benefit
justifies the potential risk to the fetus. (See WARNINGS
).
Nursing mothers: Sparfloxacin is excreted in human milk. Because
of the potential for serious adverse reactions in infants nursing from mothers
taking sparfloxacin, a decision should be made whether to discontinue nursing
or to discontinue the drug, taking into account the importance of the drug to
the mother. (See WARNINGS
.)
Pediatric use: Safety and effectiveness have not been established
in patients below the age of 18 years. Quinolones, including sparfloxacin, cause
arthropathy and osteochondrosis in juvenile animals of several species. (See
WARNINGS
.)
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