Cipro I.V.

Ciprofloxacin injection may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• nausea
• vomiting
• stomach pain
• heartburn
• diarrhea
• pale skin
• unusual tiredness
• sleepiness
• irritation, pain, tenderness, redness, warmth, or swelling at the injection spot

If you experience any of the following symptoms, or any of the symptoms described in the IMPORTANT WARNING section, stop using ciprofloxacin injection and call your doctor immediately or get emergency medical help:

• severe diarrhea (watery or bloody stools) that may occur with or without fever and stomach cramps (may occur up to 2 months or more after your treatment)
• rash
• hives
• itching
• peeling or blistering of the skin
• fever
• swelling of the eyes, face, mouth, lips, tongue, throat, hands, feet, ankles or lower legs
• hoarseness
• difficulty breathing or swallowing
• ongoing or worsening cough
• fast or fluttering heartbeat
• fainting
• loss of consciousness
• yellowing of the skin or eyes
• dark urine
• light colored stool
• decreased urination
• unusual bruising or bleeding
• joint or muscle pain

Ciprofloxacin injection may cause problems with bones, joints, and tissues around joints in children. Ciprofloxacin injection should not normally be given to children younger than 18 years of age unless they have certain serious infections that cannot be treated with other antibiotics or they have been exposed to plague or anthrax in the air. If your doctor prescribes ciprofloxacin injection for your child, be sure to tell the doctor if your child has or has ever had joint-related problems. Call your doctor if your child develops joint problems, such as pain or swelling, while using ciprofloxacin injection or after treatment with ciprofloxacin injection.

Talk to your doctor about the risks of using ciprofloxacin injection or giving ciprofloxacin injection to your child.

Ciprofloxacin injection may cause other side effects. Call your doctor if you have any unusual problems while using this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Ciprofloxacin is injected into a vein through an IV. You may be shown how to use an IV at home. Do not self-inject this medicine if you do not understand how to give the injection and properly dispose of used needles, IV tubing, and other items used to inject the medicine.

Ciprofloxacin must be injected slowly, over at least 60 minutes.

Drink plenty of liquids while you are using ciprofloxacin.

Ciprofloxacin is usually given every 8 to 12 hours for up to 14 days. Some infections may need to be treated for 4 to 6 weeks. Anthrax exposure is usually treated for 60 days.

Follow your doctor's dosing instructions very carefully.

Use this medicine for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Skipping doses may also increase your risk of further infection that is resistant to antibiotics. Ciprofloxacin will not treat a viral infection such as the flu or a common cold.

If you use this medicine long-term, you may need frequent medical tests at your doctor's office.

Store at room temperature away from moisture, heat, and light. Do not freeze.

Do not use ciprofloxacin if it has changed colors or has particles in it. Call your pharmacist for new medication.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how Cipro I.V. affects you.
• Have your blood work checked if you are on this medicine for a long time. Talk with your doctor.
• If you have high blood sugar (diabetes), you will need to watch your blood sugar closely.
• Tell your doctor if you have signs of high or low blood sugar like breath that smells like fruit, dizziness, fast breathing, fast heartbeat, feeling confused, feeling sleepy, feeling weak, flushing, headache, more thirsty or hungry, passing urine more often, shaking, or sweating.
• This medicine may affect how much of some other drugs are in your body. If you are taking other drugs, talk with your doctor. You may need to have your blood work checked more closely while taking Cipro I.V. with your other drugs.
• Do not use longer than you have been told. A second infection may happen.
• Tell your doctor if you take a drug that has caffeine, or you eat or drink products that have caffeine, like tea, coffee, cola, or chocolate.
• You may get sunburned more easily. Avoid sun, sunlamps, and tanning beds. Use sunscreen and wear clothing and eyewear that protects you from the sun.
• Drink lots of noncaffeine liquids unless told to drink less liquid by your doctor.
• Very bad and sometimes deadly allergic side effects have rarely happened. Talk with your doctor.
• Rarely, very bad and sometimes deadly effects have happened with this medicine. These include muscle or joint, kidney, liver, blood, and other problems. Talk with the doctor if you have questions.
• A type of abnormal heartbeat (prolonged QT interval) can happen with Cipro I.V.. Call your doctor right away if you have a fast heartbeat, a heartbeat that does not feel normal, or if you pass out.
• If you are over the age of 60, use this medicine with care. You could have more side effects.
• Use care in children younger than 18 years of age. Talk with the doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using Cipro I.V. (ciprofloxacin injection) while you are pregnant.

IV: 400 mg IV every 12 hours
Oral: 500 mg orally every 12 hours

Duration of therapy: 60 days

Comments:
-Therapy should be started as soon as possible after suspected/confirmed exposure.
-Indication based on efficacy studies in animals.

Use: For treatment of inhalational anthrax (postexposure) to reduce incidence/progression of disease after exposure to aerosolized Bacillus anthracis

US CDC recommendations:
-IV: 400 mg IV every 8 hours
-Oral: 500 mg orally every 12 hours

Duration of Therapy:
Postexposure prophylaxis for B anthracis infection: 60 days

Systemic anthrax:
-With possible/confirmed meningitis: At least 2 to 3 weeks or until patient is clinically stable (whichever is longer)
-When meningitis has been excluded: At least 2 weeks or until patient is clinically stable (whichever is longer)
-Patients exposed to aerosolized spores will require prophylaxis to complete an antimicrobial regimen of 60 days from onset of illness.

Cutaneous anthrax without systemic involvement:
-Bioterrorism-related cases: 60 days
-Naturally acquired cases: 7 to 10 days

Comments:
-The preferred drug for pregnant women
-Recommended as a preferred oral drug for postexposure prophylaxis and for the treatment of cutaneous anthrax without systemic involvement
-Recommended as the preferred IV drug for the treatment of systemic anthrax
-Recommended for all strains (regardless of penicillin susceptibility or if susceptibility unknown) when used for postexposure prophylaxis, systemic anthrax when meningitis has been excluded, or cutaneous anthrax without systemic involvement
-Recommended for use with a protein synthesis inhibitor when used for systemic anthrax; the addition of a bactericidal beta-lactam is recommended with possible/confirmed meningitis.
-Systemic anthrax includes anthrax meningitis, inhalation anthrax, injection anthrax, gastrointestinal anthrax, and cutaneous anthrax with systemic involvement, extensive edema, or lesions of the head or neck.
-Current guidelines should be consulted for additional information.

IV: 400 mg IV every 12 hours
Oral: 500 mg orally every 12 hours

Duration of therapy: 7 to 14 days

Use: In combination with metronidazole, for treatment of complicated intraabdominal infections due to Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, or Bacteroides fragilis

IV: 400 mg IV every 8 to 12 hours
Oral: 500 to 750 mg orally every 12 hours

Duration of therapy: 14 days

Comments:
-Therapy should be started as soon as possible after suspected/confirmed exposure.
-Indication based on efficacy study in animals only.

Uses: For treatment of plague (including pneumonic and septicemic plague) due to Yersinia pestis; for prophylaxis of plague

Working Group on Civilian Biodefense recommendations for management of plague used as a biological weapon:
-IV: 400 mg IV twice a day
-Oral: 500 mg orally twice a day

Duration of therapy:
-Treatment, contained or mass casualty setting: 10 days
-Postexposure prophylaxis: 7 days

Comments:
-May switch to oral therapy when clinically indicated
-Recommended as an alternative IV drug for treatment of pneumonic plague in a contained casualty setting
-Recommended as a preferred oral drug for treatment of pneumonic plague in a mass casualty setting and for postexposure prophylaxis
-Current guidelines should be consulted for additional information.

500 mg orally every 12 hours for 10 days

Comments:
-Efficacy in eradicating the chronic typhoid carrier state has not been established.

Use: For treatment of typhoid fever (enteric fever) due to Salmonella typhi

IDSA Recommendations:
-Non-typhi species of Salmonella: 500 mg orally twice a day

Duration of Therapy:
-Immunocompetent patients: 5 to 7 days
-Immunocompromised patients: Up to 14 days (or longer if relapsing) may be required

US CDC, NIH, and HIVMA/IDSA Recommendations for HIV-infected Patients:
-IV: 400 mg IV every 12 hours
-Oral: 500 to 750 mg orally every 12 hours

Duration of Salmonellosis Therapy:
For gastroenteritis without bacteremia:
-If CD4 count at least 200 cells/mm3: 7 to 14 days
-If CD4 count less than 200 cells/mm3: 2 to 6 weeks

For gastroenteritis with bacteremia:
-If CD4 count at least 200 cells/mm3: 14 days; longer if persistent bacteremia or complicated infection (e.g., metastatic foci of infection present)
-If CD4 count less than 200 cells/mm3: 2 to 6 weeks

Comments:
-Recommended as preferred empiric therapy for bacterial enteric infections (pending diagnostic studies) and as preferred therapy for salmonella gastroenteritis with or without bacteremia
-Empiric therapy for bacterial enteric infections recommended for patients with advanced HIV (CD4 count less than 200 cells/mm3 or concomitant AIDS-defining illnesses) and clinically severe diarrhea (at least 6 stools/day or bloody stool) and/or associated fever/chills. Fecal samples should be obtained for diagnostic testing before starting therapy; therapy should be adjusted based on those results.
-All HIV-infected patients with salmonellosis should receive antibiotic therapy; increased risk of bacteremia (by 20- to 100-fold) and mortality (by up to 7-fold) compared to HIV-negative subjects.
-Current guidelines should be consulted for additional information.

IDSA recommendations: 1 g orally once

Comments:
-For use as an adjunct to fluid and electrolyte replacement
-Current guidelines should be consulted for additional information.

US CDC recommendations: 750 mg orally twice a day
Duration of therapy: At least 3 weeks and until all lesions have completely healed

Comments:
-Recommended as an alternative regimen
-The patient's sexual partner(s) should also be evaluated/treated.
-Current guidelines should be consulted for additional information.

1 year or older:
IV: 6 to 10 mg/kg IV every 8 hours
Maximum dose: 400 mg/dose

Oral: 10 to 20 mg/kg orally every 12 hours
Maximum dose: 750 mg/dose

Total duration of therapy: 10 to 21 days

Comments:
-Dose and initial route of therapy should be based on severity of infection.
-Due to an increased incidence of side effects compared to controls (including those related to joints and/or surrounding tissues), this drug is not a drug of first choice in pediatric patients.

Uses: For treatment of complicated UTIs and pyelonephritis due to E coli

US BOXED WARNING:
SERIOUS SIDE EFFECTS INCLUDING TENDINITIS, TENDON RUPTURE, PERIPHERAL NEUROPATHY, CNS EFFECTS, AND EXACERBATION OF MYASTHENIA GRAVIS:
-Fluoroquinolones (including this drug) have been associated with disabling and potentially irreversible serious side effects that have occurred together (including tendinitis and tendon rupture, peripheral neuropathy, CNS effects). This drug should be discontinued immediately and use of fluoroquinolones (including this drug) should be avoided in patients with any of these serious side effects.
-Fluoroquinolones (including this drug) may exacerbate muscle weakness in patients with myasthenia gravis. This drug should be avoided in patients with known history of myasthenia gravis.
-Since fluoroquinolones (including this drug) have been associated with serious side effects, this drug should be reserved for use in patients with no alternative treatment options for acute exacerbation of chronic bronchitis, acute uncomplicated cystitis/uncomplicated urinary tract infections (acute cystitis), or acute sinusitis.

Extended-release tablets: Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Absorption

Following 60-minute intravenous infusions of 200 mg and 400 mg ciprofloxacin to normal volunteers, the mean maximum serum concentrations achieved were 2.1 and 4.6 mg/mL, respectively; the concentrations at 12 hours were 0.1 and 0.2 mg/mL, respectively.

The pharmacokinetics of ciprofloxacin are linear over the dose range of 200 to 400 mg administered intravenously. Comparison of the pharmacokinetic parameters following the 1st and 5th I.V. dose on a q 12 h regimen indicates no evidence of drug accumulation.

The absolute bioavailability of oral ciprofloxacin is within a range of 70-80% with no substantial loss by first pass metabolism. An intravenous infusion of 400-mg ciprofloxacin given over 60 minutes every 12 hours has been shown to produce an area under the serum concentration time curve (AUC) equivalent to that produced by a 500-mg oral dose given every 12 hours. An intravenous infusion of 400 mg ciprofloxacin given over 60 minutes every 8 hours has been shown to produce an AUC at steady-state equivalent to that produced by a 750-mg oral dose given every 12 hours. A 400-mg I.V. dose results in a C max similar to that observed with a 750-mg oral dose. An infusion of 200 mg ciprofloxacin given every 12 hours produces an AUC equivalent to that produced by a 250-mg oral dose given every 12 hours.

Distribution

After intravenous administration, ciprofloxacin is present in saliva, nasal and bronchial secretions, sputum, skin blister fluid, lymph, peritoneal fluid, bile, and prostatic secretions. It has also been detected in the lung, skin, fat, muscle, cartilage, and bone. Although the drug diffuses into cerebrospinal fluid (CSF), CSF concentrations are generally less than 10% of peak serum concentrations. Levels of the drug in the aqueous and vitreous chambers of the eye are lower than in serum.

Metabolism

After I.V. administration, three metabolites of ciprofloxacin have been identified in human urine which together account for approximately 10% of the intravenous dose. The binding of ciprofloxacin to serum proteins is 20 to 40%.

Excretion

The serum elimination half-life is approximately 5-6 hours and the total clearance is around 35 L/hr. After intravenous administration, approximately 50% to 70% of the dose is excreted in the urine as unchanged drug. Following a 200-mg I.V. dose, concentrations in the urine usually exceed 200 mg/mL 0-2 hours after dosing and are generally greater than 15 mg/mL 8-12 hours after dosing. Following a 400-mg I.V. dose, urine concentrations generally exceed 400 mg/mL 0-2 hours after dosing and are usually greater than 30 ug/mL 8-12 hours after dosing. The renal clearance is approximately 22 L/hr. The urinary excretion of ciprofloxacin is virtually complete by 24 hours after dosing.

Although bile concentrations of ciprofloxacin are several fold higher than serum concentrations after intravenous dosing, only a small amount of the administered dose (< 1%) is recovered from the bile as unchanged drug. Approximately 15% of an I.V. dose is recovered from the feces within 5 days after dosing.

Special Populations

Pharmacokinetic studies of the oral (single dose) and intravenous (single and multiple dose) forms of ciprofloxacin indicate that plasma concentrations of ciprofloxacin are higher in elderly subjects (> 65 years) as compared to young adults. Although the C max is increased 16-40%, the increase in mean AUC is approximately 30%, and can be at least partially attributed to decreased renal clearance in the elderly. Elimination half-life is only slightly (~20%) prolonged in the elderly. These differences are not considered clinically significant. (See PRECAUTIONS: Geriatric Use .)

In patients with reduced renal function, the half-life of ciprofloxacin is slightly prolonged and dosage adjust-ments may be required. (See DOSAGE AND ADMINISTRATION .)

In preliminary studies in patients with stable chronic liver cirrhosis, no significant changes in ciprofloxacin pharmacokinetics have been observed. However, the kinetics of ciprofloxacin in patients with acute hepatic insufficiency have not been fully elucidated.

Following a single oral dose of 10 mg/kg ciprofloxacin suspension to 16 children ranging in age from 4 months to 7 years, the mean C max was 2.4 mg/mL (range: 1.5 - 3.4 mg/mL) and the mean AUC was 9.2 ug*h/mL (range: 5.8 - 14.9 ug*h/mL). There was no apparent age-dependence, and no notable increase in C max or AUC upon multiple dosing (10 ug/kg TID). In children with severe sepsis who were given intravenous ciprofloxacin (10 mg/kg as a 1-hour infusion), the mean C max was 6.1 ug/mL (range: 4.6 - 8.3 ug/mL) in 10 children less than 1 year of age; and 7.2 ug/mL (range: 4.7 - 11.8 ug/mL) in 10 children between 1 and 5 years of age. The AUC values were 17.4 ug*h/mL (range: 11.8 - 32.0 ug*h/mL) and 16.5 ug*h/mL (range: 11.0 - 23.8 ug*h/mL) in the respective age groups. These values are within the range reported for adults at therapeutic doses. Based on population pharmacokinetic analysis of pediatric patients with various infections, the predicted mean half-life in children is approximately 4 - 5 hours, and the bioavailability of the oral suspension is approximately 60%.

Drug-drug Interactions:   The potential for pharmacokinetic drug interactions between ciprofloxacin and theophylline, caffeine, cyclosporins, phenytoin, sulfonylurea glyburide, metronidazole, warfarin, probenecid, and piperacillin sodium has been evaluated. (See PRECAUTIONS: Drug Interactions .)

MICROBIOLOGY

Ciprofloxacin has in vitro activity against a wide range of gram-negative and gram-positive microorganisms. The bactericidal action of ciprofloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and recombination. The mechanism of action of fluoroquinolones, including ciprofloxacin, is different from that of penicillins, cephalosporins, aminoglycosides, macrolides, and tetracyclines; therefore, microorganisms resistant to these classes of drugs may be susceptible to ciprofloxacin and other quinolones. There is no known cross-resistance between ciprofloxacin and other classes of antimicrobials. In vitro resistance to ciprofloxacin develops slowly by multiple step mutations.

Ciprofloxacin is slightly less active when tested at acidic pH. The inoculum size has little effect when tested in vitro . The minimal bactericidal concentration (MBC) generally does not exceed the minimal inhibitory concentration (MIC) by more than a factor of 2.

Ciprofloxacin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section of the package insert for CIPRO I.V. (ciprofloxacin for intravenous infusion).

Aerobic gram-positive microorganisms

Enterococcus faecalis (Many strains are only moderately susceptible.)

Staphylococcus aureus (methicillin-susceptible strains only)

Staphylococcus epidermidis (methicillin-susceptible strains only)

Staphylococcus saprophyticus

Streptococcus pneumoniae (penicillin-susceptible strains)

Streptococcus pyogenes

Aerobic gram-negative microorganisms

Citrobacter diversus

Citrobacter freundii

Enterobacter cloacae

Escherichia coli

Haemophilus influenzae

Haemophilus parainfluenzae

Klebsiella pneumoniae

Moraxella catarrhalis

Morganella morganii

Proteus mirabilis

Proteus vulgaris

Providencia rettgeri

Providencia stuartii

Pseudomonas aeruginosa

Serratia marcescens

Ciprofloxacin has been shown to be active against Bacillus anthracis both in vitro and by use of serum levels as a surrogate marker (see INDICATIONS AND USAGE and INHALATIONAL ANTHRAX - ADDITIONAL INFORMATION ).

The following in vitro data are available, but their clinical significance is unknown.

Ciprofloxacin exhibits in vitro minimum inhibitory concentrations (MICs) of 1 ug/mL or less against most (>/= 90%) strains of the following microorganisms; however, the safety and effectiveness of ciprofloxacin intravenous formulations in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.

Aerobic gram-positive microorganisms

Staphylococcus haemolyticus

Staphylococcus hominis

Streptococcus pneumoniae (penicillin-resistant strains)

Aerobic gram-negative microorganisms

Acinetobacter Iwoffi

Aeromonas hydrophila

Campylobacter jejuni

Edwardsiella tarda

Enterobacter aerogenes

Klebsiella oxytoca

Legionella pneumophila

Neisseria gonorrhoeae

Pasteurella multocida

Salmonella enteritidis

Salmonella typhi

Shigella boydii

Shigella dysenteriae

Shigella flexneri

Shigella sonnei

Vibrio cholerae

Vibrio parahaemolyticus

Vibrio vulnificus

Yersinia enterocolitica

Most strains of Burkholderia cepacia and some strains of Stenotrophomonas maltophilia are resistant to ciprofloxacin as are most anaerobic bacteria, including Bacteroides fragilis and Clostridium difficile.

Susceptibility Tests

Dilution Techniques:   Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure. Standardized procedures are based on a dilution method 1 (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of ciprofloxacin powder. The MIC values should be interpreted according to the following criteria:

For testing aerobic microorganisms other than Haemophilus influenzae , and Haemophilus parainfluenzae a :

For testing Haemophilus influenzae and Haemophilus parainfluenzae b :

The current absence of data on resistant strains precludes defining any results other than "Susceptible". Strains yielding MIC results suggestive of a "nonsusceptible" category should be submitted to a reference laboratory for further testing.

A report of "Susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of "Intermediate" indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone, which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of "Resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.

Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard ciprofloxacin powder should provide the following MIC values:

Diffusion Techniques:   Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure 2 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 5-mg ciprofloxacin to test the susceptibility of microorganisms to ciprofloxacin.

Reports from the laboratory providing results of the standard single-disk susceptibility test with a 5-ug ciprofloxacin disk should be interpreted according to the following criteria:

For testing aerobic microorganisms other than Haemophilus influenzae , and Haemophilus parainfluenzae a :

For testing Haemophilus influenzae and Haemophilus parainfluenzae b :

The current absence of data on resistant strains precludes defining any results other than "Susceptible". Strains yielding zone diameter results suggestive of a "nonsusceptible" category should be submitted to a reference laboratory for further testing.

Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for ciprofloxacin.

As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 5-ug ciprofloxacin disk should provide the following zone diameters in these laboratory test quality control strains:

In the event of acute overdosage, the patient should be carefully observed and given supportive treatment, including monitoring of renal function. Adequate hydration must be maintained. Only a small amount of ciprofloxacin (< 10%) is removed from the body after hemodialysis or peritoneal dialysis.

In mice, rats, rabbits and dogs, significant toxicity including tonic/clonic convulsions was observed at intravenous doses of ciprofloxacin between 125 and 300 mg/kg.

DOSAGE AND ADMINISTRATION - ADULTS

CIPRO I.V. should be administered to adults by intravenous infusion over a period of 60 minutes at dosages described in the Dosage Guidelines table. Slow infusion of a dilute solution into a larger vein will minimize patient discomfort and reduce the risk of venous irritation. (See Preparation of CIPRO I.V. for Administration section.)

The determination of dosage for any particular patient must take into consideration the severity and nature of the infection, the susceptibility of the causative microorganism, the integrity of the patient's host-defense mechanisms, and the status of renal and hepatic function.

CIPRO I.V. should be administered by intravenous infusion over a period of 60 minutes.

Conversion of I.V. to Oral Dosing in Adults:   CIPRO Tablets and CIPRO Oral Suspension for oral administration are available. Parenteral therapy may be switched to oral CIPRO when the condition warrants, at the discretion of the physician. (See CLINICAL PHARMACOLOGY and table below for the equivalent dosing regimens.)

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.

Adults with Impaired Renal Function:   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 alternative pathways of drug elimination appear to compensate for the reduced renal excretion in patients with renal impairment. Nonetheless, some modification of dosage is recommended for patients with severe renal dysfunction. The following table provides dosage guidelines for use in patients with renal impairment:

When only the serum creatinine concentration is known, the following formula may be used to estimate creatinine clearance:

The serum creatinine should represent a steady state of renal function.

For patients with changing renal function or for patients with renal impairment and hepatic insufficiency, careful monitoring is suggested.

DOSAGE AND ADMINISTRATION - PEDIATRICS

CIPRO I.V. should be administered as described in the Dosage Guidelines table. An increased incidence of adverse events compared to controls, including events related to joints and/or surrounding tissues, has been observed. (See ADVERSE REACTIONS and CLINICAL STUDIES .)

Dosing and initial route of therapy (i.e., I.V. or oral) for complicated urinary tract infection or pyelonephritis should be determined by the severity of the infection. In the clinical trial, pediatric patients with moderate to severe infection were initiated on 6 to 10 mg/kg I.V. every 8 hours and allowed to switch to oral therapy (10 to 20 mg/kg every 12 hours), at the discretion of the physician.

Pediatric patients with moderate to severe renal insufficiency were excluded from the clinical trial of complicated urinary tract infection and pyelonephritis. No information is available on dosing adjustments necessary for pediatric patients with moderate to severe renal insufficiency (i.e., creatinine clearance of < 50 mL/min/1.73m 2 ).

Preparation of CIPRO I.V. for Administration

Vials (Injection Concentrate): THIS PREPARATION MUST BE DILUTED BEFORE USE. The intravenous dose should be prepared by aseptically withdrawing the concentrate from the vial of CIPRO I.V. This should be diluted with a suitable intravenous solution to a final concentration of 1-2mg/mL. (See COMPATIBILITY AND STABILITY .) The resulting solution should be infused over a period of 60 minutes by direct infusion or through a Y-type intravenous infusion set which may already be in place.

If the Y-type or "piggyback" method of administration is used, it is advisable to discontinue temporarily the administration of any other solutions during the infusion of CIPRO I.V. If the concomitant use of CIPRO I.V. and another drug is necessary each drug should be given separately in accordance with the recommended dosage and route of administration for each drug.

Flexible Containers: CIPRO I.V. is also available as a 0.2% premixed solution in 5% dextrose in flexible containers of 100 mL or 200 mL. The solutions in flexible containers do not need to be diluted and may be infused as described above.

COMPATIBILITY AND STABILITY

Ciprofloxacin injection 1% (10 mg/mL), when diluted with the following intravenous solutions to concentrations of 0.5 to 2.0 mg/mL, is stable for up to 14 days at refrigerated or room temperature storage.

0.9% Sodium Chloride Injection, USP

5% Dextrose Injection, USP

Sterile Water for Injection

10% Dextrose for Injection

5% Dextrose and 0.225% Sodium Chloride for Injection

5% Dextrose and 0.45% Sodium Chloride for Injection

Lactated Ringer's for Injection