SIDE EFFECTS
Oral
During clinical investigation with the tablet, 2799 patients
received 2868 courses of the drug. Adverse events that
were considered likely to be drug related occurred in
7.3% of patients treated, possibly related in 9.2% (total
of 16.5% thought to be possibly or probably related to
drug therapy), and remotely related in 3.0%. Ciprofloxacin
was discontinued because of an adverse event in 3.5% of
patients treated, primarily involving the gastrointestinal
system (1.5%), skin (0.6%) and central nervous system
(0.4%).
The most frequently reported events, drug related or
not, were nausea (5.2%), diarrhea (2.3%), vomiting (2.0%),
abdominal pain/discomfort (1.7%), headache (1.2%), restlessness
(1.1%) and rash (1.1%).
Additional Events That Occurred in Less Than 1% of Ciprofloxacin
Patients:
Cardiovascular: Palpitation, atrial
flutter, ventricular ectopy, syncope, hypertension, angina
pectoris, myocardial infarction, cardiopulmonary arrest,
cerebral thromobosis.
Central Nervous System: Dizziness, lightheadedness,
insomnia, nightmares, hallucinations, manic reaction,
irritability, tremor, ataxia, convulsive seizures, lethargy,
drowsiness, weakness, malaise, anorexia, phobia, depersonalization,
depression, paresthesia. (See above.) (See PRECAUTIONS.)
Gastrointestinal: Painful oral mucosa,
oral candidiasis, dysphagia, intestinal perforation, gastrointestinal
bleeding. (See above.) Cholestatic jaundice has been reported.
Musculoskeletal: Arthralgia or back
pain, joint stiffness, achiness, neck or chest pain, flare
up of gout.
Renal/Urogenital: Interstitial nephritis,
nephritis, renal failure, polyuria, urinary retention,
urethral bleeding, vaginitis, acidosis.
Respiratory: Dyspnea, epistaxis, laryngeal
or pulmonary edema, hiccough, hemophysis, bronchospasm,
pulmonary embolism.
Skin/Hypersensitivity: Pruritus, urticaria,
photosensitivity, flushing, fever, chills, angioedema,
edema of the face, neck, lips, conjunctivae or hands,
cutaneous candidiasis, hyperpigmentation, erytherna nodosum.
(See above.) Allergic reactions ranging from urticaria
to anaphylactic reactions have been reported. (See WARNINGS.)
Special Senses: Blurred vision, disturbed
vision (change in color perception, overbrightness of
lights), decreased visual acuity, diplopia, eye pain,
tinnitus, hearing loss, bad taste.
Most of the adverse events reported were described as
only mild or moderate in severity, abated soon after the
drug was discontinued, and required no treatment.
In several instances nausea, vomiting, tremor, irritability,
or palpitation were judged by investigators to be related
to elevated serum levels of theophylline possibly as a
result of drug interaction with ciprofloxacin.
In domestic clinical trials involving 214 patients receiving
a single 250-mg oral dose, approximately 5% of patients
reported adverse experiences without reference to drug
relationship. The most common adverse experiences were
vaginitis (2%), headache (1%), and vaginal pruritus (1%).
Additional reactions, occurring in 0.3%-1% of patients,
were abdominal discomfort, lymphadenopathy, foot pain,
dizziness, and breast pain. Less than 20% of these patients
had laboratory values obtained, and these results were
generally consistent with the pattern noted for multi-dose
therapy.
In randomized, double-blind controlled clinical trials
comparing ciprofloxacin HCl tablets (500 mg b.i.d.) to
cefuroxime axetil (250 mg - 500 mg b.i.d.) and to clarithromycin
(500 mg b.i.d.) in patients with respiratory tract infections,
ciprofloxacin demonstrated a CNS adverse event profile
comparable to the control drugs.
I.V.
The most frequently reported events, without regard to
drug relationship, among patients treated with intravenous
ciprofloxacin were nausea, diarrhea, central nervous system
disturbance, local I.V. site reactions, abnormalities
of liver associated enzymes (hepatic enzymes), and eosinophila.
Headache, restlessness, and rash were also noted in greater
than 1% of patients treated with the most common doses
of ciprofloxacin.
Local I.V. site reactions have been reported with the
intravenous administration of ciprofloxacin. These reactions
are more frequent if the infusion time is 30 minutes or
less. These may appear as local skin reactions which resolve
rapidly upon completion of the infusion. Subsequent intravenous
administration is not contraindicated unless the reactions
recur or worsen.
Additional events, without regard to drug relationship
or route of administration, that occurred in 1% or less
of ciprofloxacin patients are listed below.
Cardiovascular: Cardiovascular collapse,
cardiopulmonary arrest, myocardial infarction, arrhythmia,
tachycardia, palpitation, cerebral thrombosis, syncope,
cardiac murmur, hypertension, hypotension, angina pectoris.
Central Nervous System: Convulsive seizures,
paranoia, toxic psychosis, depression, dysphasia, phobia,
depersonalization, manic reaction, unresponsiveness, ataxia,
confusion, hallucinations, dizziness, lightheadedness,
paresthesia, anxiety, tremor, insomnia, nightmares, weakness,
drowsiness, irritability, malaise, lethargy.
Gastrointestinal: Ileus, jaundice, gastrointestinal
bleeding, C. difficle associated diarrhea, pseudomembranous
colitis, pancreatitis, hepatic necrosis, intestinal perforation,
dyspepsia, epigastric or abdominal pain, vomiting, constipation,
oral ulceration, oral candidiasis, mouth dryness, anorexia,
dysphagia, flatulence
I.V. Infusion Site: Thrombophlebitis,
burning, pain, pruritus, paresthesia, erythema, swelling
Musculoskeletal: Arthralgia, jaw, arm
or back pain, joint stiffness, neck and chest pain, achiness,
flare up of gout
Renal/Urogenital: Renal failure, intarstitial
nephritis, hemorrhagic cystitis, renal calcuti, frequent
urination, acidosis, urethral bleeding, polyuria, urinary
retention, gynecomastia, candiduria, vaginitis. Crystalluria,
cylindruria, hematuria, and albuminutia have also been
reported.
Respiratory: Respiratory arrest, pulmonary
embolism, dyspnea, pulmonary edema, respiratory distress,
pleural effusion, hemoptysis, epistaxis, hiccough
Skin/Hypersensitivity: Anaphylactic
reactions, erythema multiforme/Stevens-Johnson syndrome,
exfoliative dermatitis, toxic epidermal necrolysis, vasculitis,
angioedema, edema of the lips, face, neck, conjunctivae,
hands or lower extremities, purpura, fever, chills, flushing,
pruritus, urtigaria, cutaneous candidiasis, vesicles,
increased perspiration, hyperpigmentation, erythema nodosum,
photosensitivity. Allergic reactions ranging from urticaria
to anaphylactic reactions have been reported. (See WARNINGS.)
Special Senses: Decreased visual acuity,
blurred vision, disturbed vision (flashing lights, change
in color perception, overbrightness of lights, diplopia),
eye pain, anosmia, hearing loss, tinnitus, nystagmus,
a bad taste
Also reported were agranulocytosis, prolongation of prothrombin
time, and possible exacerbation of myasthenia gravis.
Many of these events were described as only mild or moderate
in severity, abated soon after the drug was discontinued,
and required no treatment.
In several instances, nausea, vomiting, tremor, irritability,
or palpitation were judged by investigators to be related
to elevated serum levels of theophylline possibly as a
result of drug interaction with ciprofloxacin.
In randomized, double-blind controlled clinical trials
comparing ciprofloxacin (I.V. and I.V. P.Q., sequential)
with intravenous beta-lactam control antibiotics, the
CNS adverse event profile of ciprofloxacin was comparable
to that of the control drugs.
Post-Marketing Adverse Events
Oral and I.V.
Additional adverse events, regardless of relationship
to drug, reported from worldwide marketing experience
with quinolones, including ciprofloxacin, are:
Body as a Whole: Change in serum phenytoin.
Cardiovascular: Postural hypotension,
vasculitis.
Central Nervous System: Agitation, confusion,
delirium, dysphasia, myoclonus, nystagmus, toxic psychosis.
Gastrointestinal: Constipation, dyspepsia,
flatulence, hepatic necrosis, jaundice, pancreatitis,
pseudomembranous colitis. (The onset of pseudomembranous
colitis symptoms may occur during or after antimicrobial
treatment.)
Hemic/Lymphatic: Agranulocytosis, hemolytic
anemia, methemaglobinemia, prolongation of prothrombin
time.
Metabolic/Nutritional: Elevation of
serum triglycerides, cholesterol, blood glucose, serum
potassium.
Musculoskeletal: Myalgia, possible exacerbation
of myasthenia gravis, tendinitis/tendon rupture.
Renal/Urogenital: Albuminuria, candiduria,
renal calculi, vaginal candidiasis.
Skin/Hypersensitivity: Anaphylactic
reactions, erythema multiforme/Stevens-Johnson syndrome,
exfoliative dermatitis, toxic epidermal necrolysis.
Special Senses: Anosmia, taste loss.
(See PRECAUTIONS.)
Adverse Laboratory Changes
Oral
Changes in Laboratory Parameters Listed as Adverse Events
Without Regard to Drug Relationship:
Hepatic: Elevations of ALT (SGPT) (1.9%),
AST (SGOT) (1.7%), alkaline phosphatase (0.8%), LDH (0.4%),
serum bilirubin (0.3%).
Hematologic: Eosinophilia (0.6%), leukopenia
(0.4%), decreased blood platelets (0.1%), elevated blood
platelets (0.1%), pancytopenia (0.1%).
Renal: Elevations of serum creatinine
(1.1%), BUN (0.9%), CRYSTALLURIA, CYLINDRURIA, AND HEMATURIA
HAVE BEEN REPORTED.
Other Changes Occurring in Less than 0.1% of Courses
Were: Elevation of serum gammaglutamyl transferase, elevation
of serum amylase, reduction in blood glucose, elevated
uric acid, decrease in hemoglobin, anemia, bleeding diathesis,
increase in blood monocytes, leukocytosis.
I.V.
The most frequently reported changes in laboratory parameters
with intravenous ciprofloxacin therapy, without regard
to drug relationship are listed below:
Hepatic: Elevations of AST (SGOT), ALT
(SGPT), alkaline phosphatase, LDH, and serum bilirubin.
Hematologic: Elevated eosinophil and
platelet counts, decreased platelet counts, hemoglobin
and/or hematocrit.
Renal: Elevations of serum creatinine,
BUN, and uric acid.
Other: Elevations of serum creatinine,
phosphokinase, serum theophylline (in patients receiving
theophylline concomitantly), blood glucose, and triglycerides.
Other changes occurring infrequently were: decreased
leukocyte count, elevated atypical lymphocyte count, immature
WBCs, elevated serum calcium, elevation of serum gamma-glutamyl
transpeptidose (g GI), decreased BUN, decreased uric acid,
decreased total serum protein, decreased serum albumin,
decreased serum potassium, elevated serum potassium, elevated
serum cholesterol.
Other changes occurring rarely during administration
of ciprofloxacin were: elevation of serum amylase,
decrease of blood glucose, pancytopenia, leukocytosis,
elevated sedimentation rate, change in serum phenytoin,
decreased prothrombin time, hemolytic anemia, and bleeding
diathesis.
DRUG INTERACTIONS
Oral and I.V.
As with some other quinolones, concurrent administration
of ciprofloxacin with theophylline may to elevated serum
concentrations of theophylline and prolongation of its
elimination half-life. This may result in increased risk
of theophylline-related adverse reactions. (See WARNINGS.)
If concomitant use cannot be avoided, serum levels of
theophylline should be monitored and dosage adjustments
made as appropriate.
Some quinolones, including ciprofloxacin, have also been
shown to interfere with the metabolism of caffeine. This
may lead to reduced clearance of caffeine and a prolongation
of its serum half-life.
Quinolones have been reported to enhance the effects
of the oral anticoagulant warfarin or its derivatives.
When these products are administered concomitantly, prothromoin
time or other suitable coagulation tests should be closely
monitored.
Probenecid interferes with renal tubular secretion of
ciprofloxacin and produces an increase in the level of
ciprofloxacin in the serum. This should be considered
if patients are receiving both drugs concomitantly.
As with other broad-spectrum antimicrobial agents, prolonged
use of ciprofloxacin may result in overgrowth of nonsusceptible
organisms. Repeated evaluation of the patient's condition
and microbial susceptibility testing is essential. If
super infection occurs during therapy, appropriate measures
should be taken.
Some quinolones, including ciprofloxacin, have been associated
with transient elevations in serum creatinine in patients
receiving cyclosporine concomitantly.
Altered serum levels of phenytoin (increased and decreased)
have been reported in patients receiving concomitant ciprofloxacin.
Oral
Concurrent administration of ciprofloxacin with antacids
containing magnesium, aluminum, or calcium; with sucratfate
or divalent and trivalent cations such as iron may substantially
interfere with the absorption of ciprofloxacin, resulting
in serum and urine levels considerably lower than desired.
To a lesser extent this effect is demonstrated with zinc-container
multivitamins. (See DOSAGE AND ADMINISTRATION for concurrent
administration of these agents with ciprofloxacin.)
The concomitant administration of ciprofloxacin with the
sulfonylurea glyburide has, on rare occasions, resulted
in severe hypoglycemia.
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