Included as part of the PRECAUTIONS section.
Tendinopathy and Tendon Rupture
Fluoroquinolones, including Proquin XR (ciprofloxacin hcl) , are associated with an increased risk
of tendinitis and tendon rupture in all ages. This adverse reaction most frequently
involves the Achilles tendon, and rupture of the Achilles tendon may require
surgical repair. Tendinitis and tendon rupture in the rotator cuff (the shoulder),
the hand, the biceps, the thumb, and other tendon sites have also been reported.
The risk of developing fluoroquinolone-associated tendinitis and tendon rupture
is further increased in older patients usually over 60 years of age, in patients
taking corticosteroid drugs, and in patients with kidney, heart or lung transplants.
Factors, in addition to age and corticosteroid use, that may independently increase
the risk of tendon rupture include strenuous physical activity, renal failure,
and previous tendon disorders such as rheumatoid arthritis. Tendinitis and tendon
rupture have also occurred in patients taking fluoroquinolones who do not have
the above risk factors. Tendon rupture can occur during or after completion
of therapy; cases occurring up to several months after completion of therapy
have been reported. Proquin XR (ciprofloxacin hcl) should be discontinued if the patient experiences pain, swelling, inflammation or rupture of a tendon. Patients should be advised
to rest at the first sign of tendinitis or tendon rupture, and to contact their
healthcare provider regarding changing to a non-quinolone antimicrobial drug
[see ADVERSE REACTIONS].
Exacerbation of Myasthenia Gravis
Fluoroquinolones, including Proquin XR (ciprofloxacin hcl) , have neuromuscular blocking activity
and may exacerbate muscle weakness in persons with myasthenia gravis. Postmarketing
serious adverse events, including deaths and requirement for ventilatory support,
have been associated with fluoroquinolone use in persons with myasthenia gravis.
Avoid Proquin XR (ciprofloxacin hcl) in patients with known history of myasthenia gravis.
[See PATIENT INFORMATION and ADVERSE REACTIONS/Reported
Post-Marketing Adverse Events with Other Formulations of Ciprofloxacin].
Serious and occasionally fatal hypersensitivity and/or anaphylactic reactions
have been reported in patients receiving therapy with fluoroquinolones, including
ciprofloxacin. These reactions often occur following the first dose. Some reactions
have been accompanied by cardiovascular collapse, hypotension/shock, seizure,
loss of consciousness, tingling, angioedema (including tongue, laryngeal, throat,
or facial edema/swelling), airway obstruction (including bronchospasm, shortness
of breath, and acute respiratory distress), dyspnea, urticaria, itching, and
other serious skin reactions. Proquin XR (ciprofloxacin hcl) should be discontinued immediately at
the first appearance of a skin rash or any other sign of hypersensitivity. Serious
acute hypersensitivity reactions may require treatment with epinephrine and
other resuscitative measures, including oxygen, intravenous fluids, antihistamines,
corticosteroids, pressor amines, and airway management, as clinically indicated
[see ADVERSE REACTIONS].
Other Serious and Sometimes Fatal Reactions
Other 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, including ciprofloxacin. 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,
- vasculitis; arthralgia; myalgia; serum sickness;
- allergic pneumonitis
- inertstitial nephritis; acute renal insufficiency or failure;
- hepatitis; jaundice; acute hepatic necrosis or failure;
- anemia, including hemolytic and apalstic; thrombocytopenia, including thrombotic
thrombocytopenic purpura; leukopenia; agranulocytosis; pancytopenia; and/or
other hemtologic abnormalities.
- The drug should be discontinued immediately at the first appearance of a
skin rash, jaundice, or any other sign of hypersensitivity and supportive
measures instituted [see ADVERSE REACTIONS].
Serious and fatal reactions have been reported in patients receiving theophylline
concurrently with fluoroquinolones, including ciprofloxacin. These reactions
have included cardiac arrest, seizure, status epilepticus, and respiratory failure.
Although similar adverse effects have been reported in patients receiving theophylline
alone, the possibility that these reactions may be potentiated by Proquin XR (ciprofloxacin hcl)
cannot be eliminated. If concomitant use cannot be avoided, serum concentrations
of theophylline should be monitored and dosage adjustments made as appropriate
[see DRUG INTERACTIONS].
Central Nervous System Effects
Convulsions, increased intracranial pressure, and toxic psychosis have been
reported in patients receiving quinolones, including ciprofloxacin. Ciprofloxacin
may also cause CNS events including: dizziness, confusion, tremors, hallucinations,
depression, and, rarely, suicidal thoughts or acts. The reactions may occur
following the first dose. If these reactions occur in patients receiving ciprofloxacin,
the drug should be discontinued and appropriate measures instituted. As with
all quinolones, ciprofloxacin should be used with caution in patients with known
or suspected CNS disorders 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 ADVERSE REACTIONS,
Clostridium difficile-Associated Diarrhea
Clostridium difficile associated diarrhea (CDAD) has been reported with
use of nearly all antibacterial agents, including Proquin XR (ciprofloxacin hcl) , and may range
in severity from mild diarrhea to fatal colitis. Treatment with antibacterial
agents alters the normal flora of the colon leading to overgrowth of C. difficile.
C. difficile produces toxins A and B which contribute to the development
of CDAD. Hypertoxin producing strains of C. difficile cause increased
morbidity and mortality, as these infections can be refractory to antimicrobial
therapy and may require colectomy. CDAD must be considered in all patients who
represent with diarrhea following antibiotic use. Careful medical history is
necessary since CDAD has been reported to occur over two months after the administration
of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against
C. difficile may need to be discontinued. Appropriate fluid and electrolyte
management, protein supplementation, antibiotic treatment of C. difficile,
and surgical evaluation should be instituted as clinically indicated [see ADVERSE
Rare cases of sensory or sensorimotor axonal polyneuropathy affecting small
and/or large axons resulting in paresthesias, hypoesthesias, dyesthesias, and
weakness have been reported in patients receiving quinolones, including ciprofloxacin.
Ciprofloxacin should be discontinued if the patient experiences symptoms of neuropathy, including pain, burning, tingling, numbness, and/or weakness, or
is found to have deficits in light touch, pain, temperature, position, sense,
vibratory sensation, and/or motor strength in order to prevent the development
of an irreversible condition [see ADVERSE REACTIONS].
Arthropathic Effects in Animals
Ciprofloxacin, as with other members of the quinolone class, causes arthropathy
and/or chondroplasia in immature dogs. Related quinolone-class drugs also produce
erosions of cartilage of weight-bearing joints and other signs of arthropathy
in immature animals of various species. The relevance of these findings to the
clinical use of ciprofloxacin is unknown. [see Use In Specific Populations,
Moderate to severe photosensitivity/phototoxicity reactions, the latter of
which may manifest as exaggerated sunburn reactions (e.g., burning, erythema,
exudation, vesicles, blistering, edema) involving areas exposed to light (typically
the face, “V” area of the neck, extensor surfaces of the forearms,
dorsa of the hands), can be associated with the use of quinolones after sun
or UV light exposure. Therefore, excessive exposure to these sources of light
should be avoided. Drug therapy should be discontinued if phototoxicity occurs
[see ADVERSE REACTIONS].
Development of Drug Resistant Bacteria
Prescribing Proquin XR (ciprofloxacin hcl) in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the
patient and increases the risk of the development of drug-resistant bacteria.
Patient Counseling Information
See FDA-Approved Medication Guide
Use Only for Uncomplicated Urinary Tract Infection
Inform patients that Proquin XR (ciprofloxacin hcl) is only approved to treat uncomplicated urinary
tract infections and to contact their healthcare provider if they do not feel
better or if they develop fever and back pain while or after taking Proquin
Instruct patients to contact their healthcare provider if they experience pain,
swelling, or inflammation of a tendon, or weakness or inability to use one of
their joints; rest and refrain from exercise; and discontinue Proquin XR (ciprofloxacin hcl) treatment.
The risk of severe tendon disorders with fluoroquinolones is higher in older
patients usually over 60 years of age, in patients taking corticosteroid drugs,
and in patients with kidney, heart or lung transplants [see BOXED WARNING
and WARNINGS AND PRECAUTIONS].
Myasthenia Gravis Syndrome
Fluoroquinolones like Proquin XR (ciprofloxacin hcl) may cause worsening of myasthenia gravis symptoms,
including muscle weakness and breathing problems. Patients should call their
healthcare provider right away if you have any worsening muscle weakness or
Inform patients that ciprofloxacin may be associated with hypersensitivity
reactions; even following a single dose. Instruct patients to discontinue Proquin
XR and contact their healthcare provider at the first sign of a skin rash, hives
or other skin reactions, a rapid heartbeat, difficulty in swallowing or breathing,
any swelling suggesting angioedema (e.g., swelling of lips, tongue, face, tightness
of the throat, hoarseness), or other symptoms of an allergic reaction [see WARNINGS
Inform patients that convulsions have been reported in patients taking fluoroquinolones,
including ciprofloxacin and to notify their physician before taking this drug
if they have a history of convulsions [see WARNINGS AND PRECAUTIONS].
Neurologic Adverse Effects (e.g., dizziness, lightheadedness)
Instruct patients to wait to see how they react to Proquin XR (ciprofloxacin hcl) before they operate
an automobile or machinery or engage in other activities requiring mental alertness
and coordination [see WARNINGS AND PRECAUTIONS].
Clostridium difficile-Associated Diarrhea
Inform patients that diarrhea is a common problem caused by antibiotics which
usually ends when the antibiotic is discontinued. Sometimes after starting treatment
with antibiotics, patients can develop watery and bloody stools (with or without
stomach cramps and fever) even as late as two or more months after having taken
the last dose of the antibiotic. If this occurs, instruct patients to contact
their physician as soon as possible [see WARNINGS AND PRECAUTIONS].
Advise patients if symptoms of peripheral neuropathy including pain, burning,
tingling, numbness, and/or weakness develop, they should discontinue treatment
and contact their physician [see WARNINGS AND PRECAUTIONS].
Advise to minimize or avoid exposure to natural or artificial sunlight (tanning
beds or UVA/B treatment) while taking Proquin XR (ciprofloxacin hcl) . If patients need to be outdoors
when taking Proquin XR (ciprofloxacin hcl) , instruct them to wear loose-fitting clothes that protect
skin from sun exposure and discuss other sun protection measures with their
physician. If a sunburn like reaction or skin eruption occurs, instruct patients
to contact their physician [see WARNINGS AND PRECAUTIONS].
Administration with Food, Fluids, and Concomitant Medications
Instruct patients to:
- Take Proquin XR (ciprofloxacin hcl) with a main meal of the day, preferably the evening meal
and not to take more than one Proquin XR (ciprofloxacin hcl) tablet per day, even if a dose is
- Take Proquin XR (ciprofloxacin hcl) tablets whole. Never split, crush, or chew tablets.
- Drink fluids liberally while taking Proquin XR (ciprofloxacin hcl) to avoid formation of a highly
concentrated urine and crystal formation in the urine.
- Take Proquin XR (ciprofloxacin hcl) at least 4 hours before or 2 hours after antacids and other
multivalent cation-containing products. Aluminum or magnesium-containing antacids,
sucralfate, VIDEX® (didanosine) chewable buffered tablets or pediatric
powder, metal cations such as iron and calcium, and multivitamin preparations
containing zinc reduces the absorption of ciprofloxacin.
- Avoid taking Proquin XR (ciprofloxacin hcl) with dairy products (like milk or yogurt) or calcium-fortified
juices alone, since the absorption of ciprofloxacin may be significantly reduced
by these products. However, Proquin XR (ciprofloxacin hcl) may be taken with a meal that contains
Instruct patients to inform their healthcare provider if they are taking theophylline.
Proquin XR (ciprofloxacin hcl) may increase the effects of theophylline and some other prescription
or over-the-counter medications, when taken concurrently with ciprofloxacin.
Instruct patients to inform their healthcare provider if they are taking antacids
and other multivalent cation containing prescription or over-the-counter medications.
Such products can reduce the absorption of ciprofloxacin [see Administration
with Food, Fluids and Concomitant Medications].
Use of Proquin XR (ciprofloxacin hcl) Sample Pack Advise the patient that the sample pack contains
only one dose for the first day of treatment with Proquin® XR (ciprofloxacin hcl) . Complete
treatment requires 3 doses. The patient must fill a prescription for the remaining
Human Milk Feeding
Advise women to avoid feeding their infants with their milk during treatment
with Proquin XR (ciprofloxacin hcl) . Women should either discontinue feeding or pump and discard
their milk during treatment and for 24 hours after the last dose [see Use
in Specific Populations].
Antibacterial drugs including Proquin XR (ciprofloxacin hcl) should only be used to treat bacterial
infections. They do not treat viral infections (e.g., the common cold). When
Proquin XR (ciprofloxacin hcl) is prescribed to treat a bacterial infection, patients should be
told that although it is common to feel better early in the course of therapy,
the medication should be taken exactly as directed. Skipping doses or not completing
the full course of therapy may (1) decrease the effectiveness of the immediate
treatment and (2) increase the likelihood that bacteria will develop resistance
and will not be treatable by Proquin XR (ciprofloxacin hcl) or other antibacterial drugs in the
future [see WARNINGS AND PRECAUTIONS].
Carcinogenesis, Mutagenesis, Impairment of Fertility
Rodent carcinogenicity studies were not required. Two in vitro mutagenicity
tests were conducted with ciprofloxacin:
Bacterial Reverse Mutation Assay; negative for mutagenicity in the presence
and absence of an S9 metabolic activation system.
Chinese Hamster Ovary (CHO) Chromosomal Aberration Assay; positive for inducing
In addition to the in vitro genotoxicity assays, an in vivo rat micronucleus
study with ciprofloxacin was negative.
Fertility studies performed with male and female rats at oral doses of ciprofloxacin
up to 600 mg/kg/day (approximately 10-fold the recommended 500 mg therapeutic
dose based upon body surface area) revealed no evidence of impairment.
Use In Specific Populations
Pregnancy (Teratogenic Effects. Pregnancy Category C)
There are no adequate and well-controlled studies of Proquin XR (ciprofloxacin hcl) in pregnant
women. However, human data on more than 500 infants from two controlled cohort
studies do not show an increased risk for major congenital malformations overall
in infants exposed to ciprofloxacin during the first trimester of pregnancy
or at other times during pregnancy. The risks to a developing musculoskeletal
system were not fully evaluated. Animal studies in rats and rabbits demonstrated
variations or anomalies in fetal skeletal development and increased embryo-fetal
mortality. These effects occurred at clinically relevant doses but also in the
presence of maternal toxicity. Proquin XR (ciprofloxacin hcl) should be used during pregnancy only
if the potential benefit justifies the potential risk to the fetus.
A controlled, prospective observational study followed 200 women exposed to
fluoroquinolones (52.5% exposed to ciprofloxacin and 68% first trimester exposures)
during gestation. Following in-utero exposure to fluoroquinolones during embryogenesis,
there was no associated increased risk of major malformations. The reported
rates of major congenital malformations were 2.2% for the fluoroquinolone group
and 2.6% for the control group. Rates of spontaneous abortions, prematurity
and low birth weight did not differ between the study groups, and there were
no clinically significant musculoskeletal dysfunctions up to one year of age
in ciprofloxacin exposed children.
A controlled, retrospective cohort study of more than 30,000 infants enrolled
in Medicaid included 588 infants exposed to ciprofloxacin during pregnancy (average
8 day exposure), and 439 exposures occurred during the first trimester. Compared
to a control group with no antibiotic exposure and a control group with exposure
to a nonteratogenic antibiotic commonly used during pregnancy, infants exposed
to ciprofloxacin during the first trimester (or other times during pregnancy)
did not demonstrate an increased risk for major congenital malformations overall.
The study was powered to rule out a two fold increased risk for major malformations.
The study was not designed to fully assess abnormal musculoskeletal development.
Another prospective observational study reported on 549 pregnancies with fluoroquinolone
exposure (93% first trimester exposures). There were 70 ciprofloxacin exposures,
all within the first trimester. The malformation rates among live-born babies
exposed to ciprofloxacin and to fluoroquinolones overall were both within the
background rates for congenital malformations in the general population. There
was no specific patterns of congenital abnormalities and no clear adverse reactions
due to in-utero exposure to ciprofloxacin.
Published data do not suggest increased rates of prematurity, spontaneous abortions,
or birth weight in women exposed to ciprofloxacin during pregnancy, but these
data are very limited.
In embryo/fetal developmental toxicity studies, pregnant rats and rabbits received
oral doses of ciprofloxacin up to 600 mg/kg/day in rats and 30 mg/kg/day in
rabbits. In rats, fetal skeletal variations occurred at the maternally toxic
dose of 600 mg/kg/day (approximately 1.8-fold the recommended 500 mg therapeutic
dose based upon plasma AUC measure of systemic exposure). In pregnant rabbits,
the maternally toxic 30 mg/kg/day dose resulted in abortions and reductions
in body weight gain. Embryo/fetal lethality and skeletal developmental effects
also occurred in rabbits at this dose level (approximately 1.2-fold the recommended
therapeutic dose based upon body surface area), while the maternally toxic 10
mg/kg/day dose level did not induce embryo/fetal developmental effects. A peri/postnatal
developmental toxicity study conducted in pregnant/lactating female rats exhibited
no developmental effects in offspring at the highest dose level of 600 mg/kg/day.
Both the 300 and 600 mg/kg/day dose levels were maternally toxic to the pregnant
dams based upon slight body weight gain reduction. There was no evidence of
compound-related fetal malformation in any of the reproductive toxicity studies.
Ciprofloxacin is excreted in human milk. In one study, ten lactating women
received oral ciprofloxacin 750 mg every 12 hours. Peak human milk concentrations
of ciprofloxacin following the third dose averaged 3.79 mcg/mL (S.D. 1.26),
and these levels decreased to a mean of 0.02 mcg/mL at 24 hours after the third
dose. Based on these concentrations, the maximum daily infant dose of ciprofloxacin
through human milk is about 0.569 mg/kg per day, about 2.8% of the approved
20 mg/kg dose in children one year of age or older.
Because of the potential for serious adverse reactions in infants from ciprofloxacin,
a decision should be made whether to discontinue nursing or discontinue the
drug, taking into account the importance of ciprofloxacin to the mother. During
short courses of therapy, nursing mothers may express and discard milk. Human
milk feeding can resume 24 hours after the last dose of Proquin XR (ciprofloxacin hcl) .
The safety and effectiveness of Proquin XR (ciprofloxacin hcl) in pediatric patients and adolescents
less than 18 years of age have not been established. Quinolones, including ciprofloxacin,
cause arthropathy in juvenile animals [see Nonclinical Toxicology]
Geriatric patients are at increased risk for developing severe tendon disorders
including tendon rupture when being treated with a fluoroquinolone such as Proquin
XR. This risk is further increased in patients receiving concomitant corticosteroid
therapy. Tendinitis or tendon rupture can involve the Achilles, hand, shoulder,
or other tendon sites and can occur during or after completion of therapy; cases
occurring up to several months after fluoroquinolone treatment have been reported.
Caution should be used when prescribing Proquin XR (ciprofloxacin hcl) to elderly patients especially
those on corticosteroids. Patients should be informed of this potential side
effect and advised to discontinue Proquin XR (ciprofloxacin hcl) and contact their healthcare provider
if any symptoms of tendinitis or tendon rupture occur [see WARNINGS AND PRECAUTIONS,
Clinical experience with Proquin XR (ciprofloxacin hcl) did not include sufficient number of subjects
65 years of age or older to determine whether they respond differently than
younger subjects. Reported clinical experience with other formulations of ciprofloxacin
has not identified differences in responses between elderly and younger patients,
but greater sensitivity of some older individuals on any drug therapy cannot
be ruled out. Ciprofloxacin is substantially excreted by the kidney and the
risk of adverse reactions may be greater in patients with impaired renal function.
No alteration of dosage is necessary for patients greater than 65 years of age
with normal renal function [see CLINICAL PHARMACOLOGY].
In general, elderly patients may be more susceptible to drug-associated effects
on the QT interval. Therefore, precaution should be taken when using Proquin
XR with concomitant drugs that can result in prolongation of the QT interval
(e.g. class IA or class III antiarrhythmics) or in patients with risk factors
for torsades de pointes (e.g., known QT prolongation, uncorrected hypokalemia).
Ciprofloxacin is eliminated primarily by renal excretion; however, the drug
is also metabolized and partially cleared through the biliary system of the
liver and through the intestine. These alternate pathways of drug elimination
appear to compensate for the reduced renal excretion in patients with renal
impairment. No dosage adjustment is required for patients with mild to moderate
renal impairment. The efficacy of Proquin XR (ciprofloxacin hcl) has not been studied in patients
with severe renal impairment [see CLINICAL PHARMACOLOGY].
No dosage adjustment is required with Proquin XR (ciprofloxacin hcl) in patients with stable chronic
cirrhosis. However, the pharmacokinetics of ciprofloxacin in patients with acute
hepatic impairment has not been fully elucidated [see CLINICAL PHARMACOLOGY].