Cipro (Ciprofloxacin)

CIPRO® CIPRO® I.V. CIPRO® Oral Suspension

Bayer

Ciprofloxacin HCl

Ciprofloxacin

Ciprofloxacin

Antibacterial

Action And Clinical Pharmacology: Ciprofloxacin, a synthetic fluoroquinolone, has a bactericidal mode of action. This action is achieved through inhibition of DNA gyrase, an essential component of the bacterial DNA replication system. Inhibition of the alpha subunit of the DNA gyrase blocks the resealing of the nicks on the DNA strands induced by this alpha subunit, leading to the degradation of the DNA by exonucleases. This bactericidal activity persists not only during the multiplication phase, but also during the resting phase of the bacterium.

Ciprofloxacin retained some of its bactericidal activity after inhibition of RNA and protein synthesis by rifampin and chloramphenicol, respectively. These observations suggest ciprofloxacin may possess two bactericidal mechanisms, one mechanism resulting from the inhibition of DNA gyrase and a second mechanism which may be independent of RNA and protein synthesis.

Ciprofloxacin and metronidazole have been studied in combination and serum levels of ciprofloxacin are not significantly altered by metronidazole at the doses studied. Serum levels of metronidazole when administered orally at a dose of 500 mg q6h in combination with ciprofloxacin 500 mg po q12h are: AUC0®6 156.3 mg.h/L, Cmax 31.3 mg/L and Tmax 1.71 hours. Serum levels of metronidazole when administered i.v. at a dose of 500 mg i.v. q6h in combination with ciprofloxacin 400 mg i.v. q12h are: AUC0®6 153.0 mg.h/L, Cmax 33.6 mg/L and Tmax 1.0 hours (see Dosage and Pharmacokinetics).

With oral administration, one 500 mg dose is bioequivalent to a 5 mL volume of the 10% ciprofloxacin oral suspension (containing 500 mg ciprofloxacin/5 mL) (see Dosage).

Following infusion of 400 mg i.v. ciprofloxacin every 8 hours in combination with 50 mg/kg i.v. piperacillin sodium every 4 hours, mean serum ciprofloxacin concentrations were 3.02 g/mL at 30 minutes and 1.18 g/mL between 6 and 8 hours after the end of infusion. The mean serum ciprofloxacin concentration given alone at 400 mg i.v. every 8 hours was 3.67 g/mL at 30 minutes and 1.16 g/mL at 6 hours after the end of infusion.

Pharmacokinetics: The relative bioavailability of oral ciprofloxacin given as a tablet, is between 70 and 80% compared to an equivalent dose of i.v. ciprofloxacin.

Following oral administration of single doses of 250, 500 and 750 mg of ciprofloxacin respectively to groups of 3 healthy male volunteers (age: 22.8±3.5 years, weight: 68.5±9.4 kg), ciprofloxacin was absorbed rapidly and extensively from the gastrointestinal tract.

Maximum serum concentrations (Cmax) increased dose-proportionally and were attained 1 to 2 hours after oral dosing. The total areas under the serum concentration time curves (AUC) were also increased in proportion to dose. Mean concentrations 12 hours after dosing with 250, 500 or 750 mg were 0.1, 0.2, and 0.4 mg/L, respectively. The serum elimination half-lives (t1/2) were between 4 and 6 hours.

With oral administration, a 500 mg dose, given as 10 mL of the 5% suspension (containing 250 mg ciprofloxacin/5 mL) is bioequivalent to the 500 mg tablet. A 10 mL volume of the 5% suspension (containing 250 mg ciprofloxacin/5 mL) is bioequivalent to a 5 mL volume of the 10% suspension (containing 500 mg ciprofloxacin/5 mL).

Following a 60-minute i.v. infusion of 200 and 400 mg ciprofloxacin to 13 healthy male volunteers (18 to 40 years), the mean maximum serum concentrations achieved were 2.14 and 4.60 mg/L respectively; the concentrations at 12.0 hours were 0.11, 0.23 mg/L respectively.

The pharmacokinetics of ciprofloxacin were linear over the dose range of 200 and 400 mg administered i.v. At steady-state, the serum elimination half-life was approximately 5 to 6 hours and the total clearance around 35 L/hour was observed. Comparison of the pharmacokinetic parameters following the 1st and 5th i.v. dose on a 12-hour regimen indicated no evidence of drug accumulation.

An i.v. infusion of 400 mg ciprofloxacin given over 60 minutes every 12 hours, for 6 doses, to 12 healthy male volunteers (18 to 40 years) 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. The 400 mg i.v. dose administered over 60 minutes every 12 hours resulted in a Cmax 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 every 12 hours.

Pharmacokinetics were dose proportioned with no significant changes in clearance or half-life occurring over this dose range.

Indications And Clinical Uses: Oral: Treatment of patients with the following infections caused by susceptible strains of the indicated microorganisms:

Respiratory Tract Infections: Acute exacerbation of chronic bronchitis caused by: H. influenzae, M. catarrhalis, S. pneumoniae.

Acute pneumonia caused by: E. cloacae, E. coli, H. influenzae, K. pneumoniae, P. mirabilis, P. aeruginosa, S. aureus, S. pneumoniae.

Acute sinusitis caused by: H. influenza, M. catarrhalis, S. pneumoniae.

Due to the nature of the underlying conditions which usually predispose patients to pseudomonas infections of the respiratory tract, bacterial eradications may not be achieved in patients who display clinical improvement despite evidence of in vitro sensitivity. In patients requiring subsequent courses of therapy, ciprofloxacin should be used alternately with other antipseudomonal agents. Some strains of P. aeruginosa may develop resistance during treatment. Therefore, susceptibility testing should be performed periodically during therapy to detect the emergence of bacterial resistance.

Urinary Tract Infections: Upper and lower urinary tract infections, such as complicated and uncomplicated cystitis, pyelonephritis, and pyelitis, caused by: C. diversus, C. freundii, E. cloacae, E. coli, K. pneumoniae, K. oxytoca, M. morganii, P. mirabilis, P. aeruginosa, S. marcescens, S. aureus, S. epidermidis, S. saprophyticus, S. faecalis.

Chronic Bacterial Prostatitis: caused by: E. coli.

Skin and Soft Tissue Infections: caused by: E. cloacae, E. coli, K. pneumoniae, P. mirabilis, P. vulgaris, P. aeruginosa, S. aureus, S. epidermidis, S. pyogenes.

Bone and Joint Infections: caused by: E. cloacae, P. aeruginosa, S. marcescens, S. aureus,

Infectious Diarrhea (when antibacterial therapy is indicated): caused by: C. jejuni, E. coli (enterotoxigenic strains), S. dysenteriae, S. flexneri, S. sonnei.

Meningococcal Carriers: Treatment of asymptomatic carriers of N. meningitidis to eliminate meningococci from the nasopharynx. An MIC determination on the isolate from the index case should be performed as soon as possible. Ciprofloxacin is not indicated for the treatment of meningococcal meningitis.

Typhoid Fever: (enteric fever) caused by: S. paratyphi, S. typhi.

Uncomplicated Gonorrhea: Cervical/urethral/rectal/pharyngeal infections caused by N. gonorrhoea. Because co-infection with C. trachomatis is common, consideration should be given to treating presumptively with an additional regimen that is effective against C. trachomatis.

I.V.: For the treatment of patients with the following infections caused by susceptible strains of the indicated microorganisms:

Respiratory Tract Infections: Acute pneumonia caused by: E. cloacae, E. coli, H. influenzae, H. parainfluenzae, K. pneumoniae, P. mirabilis, P. aeruginosa, S. aureus, S. pneumoniae.

Due to the nature of the underlying conditions which usually predispose patients to Pseudomonas infections of the respiratory tract, bacterial eradications may not be achieved in patients who display clinical improvement despite evidence of in vitro sensitivity. In patients requiring subsequent courses of therapy, ciprofloxacin should be used alternately with other antipseudomonal agents. Some strains of P. aeruginosa may develop resistance during treatment. Therefore, susceptibility testing should be performed periodically during therapy to detect the emergence of bacterial resistance.

Urinary Tract Infections: Upper and lower complicated urinary tract infections including pyelonephritis caused by: C. diversus, E. coli, K. pneumoniae, P. mirabilis, P. aeruginosa.

Skin or Skin Structure Infections: caused by: E. cloacae, E. coli, K. pneumoniae, M. morganii, P. mirabilis, P. vulgaris, P. aeruginosa, S. aureus, S. pyogenes.

Septicemia: caused by: E. coli, S. typhi.

Bone: caused by: E. cloacae, P. aeruginosa.

Complicated Intra-abdominal infections only when used in combination with metronidazole (see Dosage): caused by: E. coli, P. aeruginosa, K. pneumoniae, B. fragilis.

Note: Most anaerobic bacteria, including B. fragilis, are resistant to ciprofloxacin. Therefore, ciprofloxacin should not be used as single agent therapy for complicated intra-abdominal infections. Efficacy against Enterococcus sp. in clinical trials has been shown to be only 75%.

Empiric Therapy in Febrile Neutropenic Patients (in combination with piperacillin sodium): (see Dosage).

Appropriate culture and susceptibility tests should be performed prior to initiating treatment in order to isolate and identify organisms causing the infection and to determine their susceptibilities to ciprofloxacin. Therapy with ciprofloxacin may be initiated before results of these tests are known. However, modification of this treatment may be required once results become available or if there is no clinical improvement. Culture and susceptibility testing performed periodically during therapy will provide information on the possible emergence of bacterial resistance. If anaerobic organisms are suspected to be contributing to the infection, appropriate therapy should be administered.

Contra-Indications: In patients who have shown hypersensitivity to ciprofloxacin or other quinolone antibacterial agents.

Manufacturers’ Warnings In Clinical States: Children: The safety of ciprofloxacin in children has not yet been established. Damage to juvenile weight-bearing joints and lameness were observed both in rat and dog studies but not in weaned piglets. Histopathological examination of the weight-bearing joints in immature dogs revealed permanent lesions of the cartilage.

Consequently, ciprofloxacin should not be used in prepubertal patients. Experience in pubertal patients below 18 years of age is limited.

Pregnancy: The safety of ciprofloxacin in the treatment of infections in pregnant women has not yet been established (see Precautions).

General: Convulsions have been reported in patients receiving ciprofloxacin. Convulsions, increased intracranial pressure, and toxic psychosis have been reported in patients receiving drugs in this class. Quinolones may also cause CNS stimulation, which may lead to tremors, restlessness, lightheadedness, confusion and hallucinations. 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, such as severe cerebral arteriosclerosis, epilepsy, and other factors that predispose to seizures (see Adverse Effects).

Precautions: General: Anaphylactic reactions including cardiovascular collapse have occurred rarely in patients receiving therapy with ciprofloxacin. These reactions may occur within the first 30 minutes following the first dose and may require epinephrine and other emergency measures.

Serious and fatal reactions have been reported in patients receiving concurrent administration of ciprofloxacin i.v. and theophylline. These reactions include cardiac arrest, seizure, status epilepticus and respiratory failure. Similar serious adverse events have been noted with administration of theophylline alone, however, the possibility that ciprofloxacin may potentiate these reactions cannot be eliminated. If concomitant use cannot be avoided, the plasma levels of theophylline should be monitored and appropriate dosage adjustments should be made.

Severe hypersensitivity reactions characterized by rash, fever, eosinophilia, jaundice and hepatic necrosis with fatal outcome have also been reported to occur very rarely in patients receiving ciprofloxacin in combination with other drugs. The possibility that these reactions were related to ciprofloxacin cannot be excluded. Ciprofloxacin should be withdrawn at the first appearance of a skin rash or other signs of hypersensitivity.

Tendon rupture (predominantly achilles tendon) has been reported predominantly in the elderly on prior systemic treatment with glucocorticoids. At any sign of tendonitis (i.e., painful swelling), the administration of ciprofloxacin should be discontinued, physical exercise avoided, and a physician consulted.

Crystalluria related to ciprofloxacin has been reported only rarely in man because human urine is usually acidic. Crystals have been observed in the urine of laboratory animals, usually from alkaline urine. Patients receiving ciprofloxacin should be well hydrated and alkalinity of the urine should be avoided. The recommended daily dose should not be exceeded.

Pseudomembranous colitis has been reported with virtually all antibacterial agents, including ciprofloxacin, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients with diarrhea subsequent to the administration of antibacterial agents. Subsequent to diagnosis of pseudomembranous colitis, therapeutic measures should be initiated. Mild cases will usually respond to discontinuation of drug alone. In moderate to severe cases, consideration should be given to the management with fluids, electrolytes, protein supplementation and treatment with an antibacterial drug effective against C. difficile.

Ciprofloxacin has been shown to produce photosensitivity reactions. Patients taking ciprofloxacin should avoid direct exposure to excessive sunlight or UV light. Therapy should be discontinued if photosensitization (i.e., sunburn-like skin reactions) occurs.

I.V. infusion should be administered by slow infusion over a period of 60 minutes. Local i.v. reactions have been reported with the i.v. administration of ciprofloxacin. These reactions are more frequent if infusion time is 30 minutes or less, or if small veins of the hand are used.

Prolonged use of ciprofloxacin may result in the overgrowth of nonsusceptible organisms. Careful observation of the patient is therefore essential, and if superinfection should occur during therapy, appropriate measures should be taken.

Pregnancy: The safety of ciprofloxacin in pregnancy has not yet been established. Ciprofloxacin should not be used in pregnant women unless the likely benefits outweigh the possible risk to the fetus. Ciprofloxacin has been shown to be nonembryotoxic and nonteratogenic in animal studies.

Lactation: Ciprofloxacin is excreted in human milk. A decision should be made to discontinue nursing or to discontinue the administration of ciprofloxacin, taking into account the importance of the drug to the mother and the possible risk to the infant.

Drug Interactions: Concurrent administration of ciprofloxacin with theophylline may lead to an elevated plasma concentration and prolongation of elimination half-life of theophylline. This may result in increased risk of theophylline-related adverse reactions. If concomitant use cannot be avoided, plasma concentrations of theophylline should be monitored and dosage adjustments made as appropriate.

Ciprofloxacin has been shown to interfere with the metabolism and pharmacokinetics of caffeine. Excessive caffeine intake should be avoided.

Some quinolones, including ciprofloxacin, have been associated with transient increases in serum creatinine levels in patients who are concomitantly receiving cyclosporine.

Quinolones have been reported to increase the effects of the oral anticoagulant warfarin and its derivatives. During concomitant administration of these drugs, the prothrombin time or other appropriate coagulation tests should be closely monitored.

Probenecid blocks renal tubular secretion of ciprofloxacin and has been shown to produce an increase in the level of ciprofloxacin in the serum.

Concomitant administration of a nonsteroidal anti-inflammatory drug (fenbufen) with a quinolone (enoxacin) has been reported to increase the risk of CNS stimulation and convulsive seizures.

Antacids containing aluminum or magnesium hydroxide have been shown to reduce the absorption of ciprofloxacin. Concurrent administration with these agents should be avoided.

Administration of sucralfate prior to ciprofloxacin resulted in a 30% reduction in absorption of ciprofloxacin. Concurrent administration with ciprofloxacin should be avoided.

Oral ferrous sulfate at therapeutic doses decreases the bioavailability of oral ciprofloxacin, therefore concomitant therapy is not advised.

The use of calcium supplement and highly buffered drugs such as antiretrovirals reduces the absorption of ciprofloxacin, therefore concomitant administration is not advised.

In particular cases, concurrent administration of ciprofloxacin and glyburide can intensify the action of glyburide (hypoglycemia).

Renal Impairment: Since ciprofloxacin is eliminated primarily by the kidney, ciprofloxacin should be used with caution and at a reduced dosage in patients with impaired renal function (see Dosage).

Hepatic Impairment: In preliminary studies in patients with stable chronic liver cirrhosis, no significant changes in ciprofloxacin pharmacokinetics were observed. The kinetics of ciprofloxacin in patients with acute hepatic insufficiency, however, have not been fully elucidated. An increased incidence of nausea, vomiting, headache and diarrhea were observed in this patient population.

Adverse Reactions: Ciprofloxacin is generally well tolerated. During worldwide clinical investigation, 16 580 courses of ciprofloxacin treatment were evaluated for drug safety.

Adverse events, possibly, probably or highly probably related to ciprofloxacin occurred in 1 395 (8.8%) of patients. The adverse reactions according to treatment (oral, i.v. and sequential therapy) show that the incidence of adverse reactions was 8% for the group treated orally, 17% for the group treated with ciprofloxacin i.v. and 15.3% for the group treated sequentially. The difference between the oral and i.v. group relates to adverse vascular reactions which are known to be associated with i.v. administration.

In orally treated patients enrolled in clinical trials, the most frequently reported events, possibly, probably drug-related were: nausea (1.3%) and diarrhea (1%).

In patients treated with ciprofloxacin i.v., the most frequently reported events, possibly, probably drug-related were: rash (1.8%), diarrhea (1%) and injection site pain (1%).

Local i.v. site reactions have been reported. 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 i.v. administration is not contraindicated unless the reactions recur or worsen.

Events possibly, probably drug-related occurring at a frequency of less than 1% with ciprofloxacin oral and i.v. treatment during clinical trials and subsequent postmarketing surveillance are as follows: Gastrointestinal: vomiting, dyspepsia, abdominal pain, flatulence, dysphagia, enlarged abdomen, dry mouth, stomatitis, gastrointestinal moniliasis, anorexia, jaundice. The following have been reported very rarely: constipation, tooth discoloration, ulcerative stomatitis, pseudomembranous colitis, intestinal perforation, esophagitis, increased appetite, gastrointestinal hemorrhage, melena, liver damage, tenesmus, ileus, toxic megacolon, hepatomegaly, glossitis.

Cardiovascular: palpitation, tachycardia, phlebitis. The following have been reported very rarely: hypertension, hot flashes, cerebrovascular disorder, syncope, kidney vasculitis, vasodilation, atrial fibrillation, cardiac arrest, angina pectoris, electrocardiogram abnormality, myocardial infarct, substernal chest pain, pulmonary embolus, pericarditis, hypotension.

Nervous System: increased sweating, dizziness, agitation, tremor, somnolence, insomnia, confusion, hallucinations, convulsion, headache. The following have been reported very rarely: anxiety, depression, nervousness, apathy, depersonalization, abnormal dreams, hemiplegia, sleep disorder, neuritis, paresthesia, polyneuritis, diplopia, meningism, migraine, increase of intracranial pressure. In some instances these reactions occurred after the first administration of ciprofloxacin. In these instances, ciprofloxacin has to be discontinued and the doctor should be informed immediately.

Respiratory: dyspnea. The following have been reported very rarely: hiccup, increased cough, stridor, larynx edema, voice alteration, lung edema, pharyngitis, hyperventilation, lung hemorrhage.

Skin and Appendages: rash, pruritus. The following have been reported very rarely: urticaria, photosensitive dermatitis, angioedema, alopecia.

Special Senses: tinnitus, abnormal vision, taste perversion. The following have been reported very rarely: conjunctivitis, corneal opacity, eye pain, color blindness, chromatopsia, diplopia, ear pain.

Urogenital: albuminuria, hematuria. The following have been reported rarely: leukorrhea, dysuria, urinary retention, acute kidney failure, abnormal kidney function, nephritis, vaginitis.

Hypersensitivity: rash. The following have been reported rarely: pruritus, drug fever, anaphylactic/anaphylactoid reactions including facial, vascular and laryngeal edema, serum sickness, petechiae, hemorrhagic bullae and small nodules (papules) with crust formation showing vascular involvement (vasculitis), Stevens-Johnson syndrome, interstitial nephritis, hepatitis; very rarely, major liver disorders including hepatic necrosis, Lyell’s syndrome, erythema nodosum, erythema multiforme (minor).

Musculoskeletal: The following have been reported rarely: arthralgia (joint pain), joint swelling, achiness, pain in the extremities, tendonitis (predominantly achillotendonitis); partial or complete tendon rupture (achilles tendon) and very rarely back pain,

Blood and Blood Constituents: eosinophilia, leukocytopenia, leukocytosis, anemia, granulocytopenia, pancytopenia, agranulocytosis. Very rarely: hemolytic anemia, thrombocytopenia, thrombocytosis, altered prothrombin levels.

I.V. Infusion Site: thrombophlebitis: very rarely burning, pain, paresthesia, erythema and swelling.

Laboratory Values: increased alkaline phosphatase, Gamma-GT, transaminases, cholestatic parameters, lactic dehydrogenase, BUN, NPN, AST, ALT, decreased creatinine clearance, hypercholesteremia, albuminuria, bilirubinemia, hyperuricemia, increased sedimentation rate. The following have been reported rarely; electrolyte abnormality, hypercalcemia, hypocalcemia, acidosis, crystalluria and hematuria.

Other: very rarely, asthenia, death.

Most of the adverse events reported were described as only mild or moderate in severity.

There have been 54 reports of arthropathies with ciprofloxacin. Ten of these reports involved children. Arthralgia was usually the first symptom which led to rapid assessment and withdrawal of the drug. No irreversible arthropathies have been observed.

Adverse reactions noted during therapy with ciprofloxacin and metronidazole in clinical trials were similar to those already noted during therapy with ciprofloxacin alone with the following additions: Cardiovascular: peripheral edema.

Digestive: tongue discoloration, colitis, gastritis.

Hemic and Lymphatic: coagulation disorder, thrombocythemia.

Skin: fungal dermatitis, pustular rash, sweating.

Metabolic: hypernatremia, healing abnormal.

Nervous: dementia.

Urinary: kidney tumor necrosis, urinary incontinence.

Symptoms And Treatment Of Overdose: Symptoms and Treatment: In the event of acute, excessive oral overdosage, reversible renal toxicity, arthralgia, myalgia and CNS symptoms have been reported. Therefore, apart from routine emergency measures, it is recommended to monitor renal function and to administer magnesium- or calcium-containing antacids which reduce the absorption of ciprofloxacin and to maintain adequate hydration. Based on information obtained from subjects with chronic renal failure, only a small amount of ciprofloxacin (
Dosage And Administration: The determination of dosage for any particular patient must take into consideration the severity and nature of the infection, the susceptibility of the causative organism, the integrity of the patient’s host-defence mechanisms and the status of renal function.

Oral: Ciprofloxacin may be taken before or after meals. Absorption is faster on an empty stomach. Patients should be advised to drink fluids liberally and not take antacids containing magnesium or aluminum.

Oral Suspension: See Table III. One teaspoon (5 mL) of 10% oral ciprofloxacin suspension=500 mg of ciprofloxacin (see Instructions below for Use/Handling).

Depending on the severity of the infections, as well as the clinical and bacteriological responses, the average treatment period should be approximately 7 to 14 days. Generally, treatment should last 3 days beyond the disappearance of clinical symptoms or until cultures are sterile. Patients with osteomyelitis may require treatment for a minimum of 6 to 8 weeks and up to 3 months. With infectious diarrhea, a 5-day treatment may be sufficient. Typhoid fever should be treated for 14 days. Acute sinusitis should be treated for 10 days with 500 mg q12h. With uncomplicated urinary tract infections such as acute cystitis, a 3-day treatment with 100 mg every 12 hours may be sufficient. Chronic bacterial prostatitis should be treated for 28 days with 500 mg every 12 hours.

Instructions to the Pharmacist for Use/Handling of Cipro Oral Suspension: Preparation of the suspension: 1. The small bottle contains the ciprofloxacin microcapsules; the large bottle contains the diluent. 2. Open both bottles. Child-proof cap: Press down according to the instructions on the cap while turning to the left. 3. Pour the microcapsules completely into the large bottle of diluent. Do not add water to the suspension. 4. Close the large bottle completely according to the instructions on the cap and shake vigorously for about 15 seconds. The suspension is ready for use.

Instructions to the Patient for Taking Cipro Oral Suspension: Shake vigorously each time before use for approximately 15 seconds. Swallow the prescribed amount of suspension. Do not chew the microcapsules. Reclose the bottle completely after use according to instruction on the cap. The suspension is stable for 14 days when stored in a refrigerator or at room temperature (5 to 25°C). Store in an upright position. After treatment has been completed, any remaining suspension should not be reused.

I.V.: Ciprofloxacin should be administered by i.v. infusion over a period of 60 minutes. Slow infusion into a large vein will minimize patient discomfort and reduce the risk of venous irritation.

Definitive clinical studies have not been completed for severe infections other than in the respiratory tract.

The duration of treatment depends upon the severity of infection. Generally ciprofloxacin should be continued for at least 3 days after the signs and symptoms of infection have disappeared. The usual duration is 7 to 14 days. However, for severe and complicated infections more prolonged therapy may be required. Bone and joint infections may require treatment for 4 to 6 weeks or longer.

Sequential I.V./Oral Therapy: In patients receiving i.v. ciprofloxacin, oral ciprofloxacin may be considered when clinically indicated at the discretion of the physician. Clinical studies evaluating the use of sequential i.v./oral therapy in septicemia, however, have not been completed.

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 (see Pharmacology). This alternate pathway of drug elimination appears to compensate for the reduced renal excretion of patients with renal impairment. Nonetheless, some modification of dosage is recommended, particularly for patients with severe renal dysfunction. Table V provides a guideline for dosage adjustment. However, monitoring of serum drug levels provides the most reliable basis for dosage adjustments.

Maximum daily dose, not to be exceeded when either creatinine clearance or serum creatinine are in the ranges stated.

When only the serum creatinine concentration is available, the following formulas (based on sex, weight and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine should represent a steady state of renal function:

Creatinine Clearance mL/s

Males: Weight (kg) X (140 – age) / 49 X serum creatinine (mol/L).

Females: 0.85 X the above value.

In traditional units mL/min

Males: Weight (kg) X (140-age) / 72 X serum creatinine (mg/100 mL).

Females: 0.85 X the above value.

Children: The safety and efficacy of ciprofloxacin in children have not been established. Ciprofloxacin should not be used in prepubertal patients (see Warnings).

Parenteral Products: Intermittent I.V. Infusion: Ciprofloxacin injection should be administered only by i.v. infusion over a period of 60 minutes. The drug should not be given by rapid injection. Slow infusion of a dilute solution into a large vein will minimize patient discomfort and reduce the risk of venous irritation.

If ciprofloxacin i.v. is to be given concomitantly with another drug, each drug should be given separately in accordance with the recommended dosage and route of administration for each drug. Only ciprofloxacin injection in the 10 mg/mL vials should be diluted to 1 to 2 mg/mL with the following recommended i.v. solutions. Cipro I.V. Minibags contain ciprofloxacin at 2 mg/mL and should be administered as is.

Recommended I.V. Solutions for Dilution of Vials: Sterile Water for Injection, USP; 0.9% Sodium Chloride Injection, USP; 5% Dextrose Injection, USP; 5% Dextrose in 0.225% Sodium Chloride Injection, USP; 5% Dextrose in 0.45% Sodium Chloride Injection, USP; 5% Dextrose in Electrolyte #75 Injection; 10% Dextrose Injection; 10% Fructose Injection; Ringer’s Injection; Lactated Ringer’s Injection, USP.

Ciprofloxacin injection when diluted with the recommended i.v. solutions should be used within 24 hours at room temperature or 72 hours when refrigerated. Since ciprofloxacin is slightly light sensitive, the solutions should be protected from light during storage.

Vials: The i.v. dose should be prepared by aseptically withdrawing the appropriate volume of concentrate from the vials of Cipro I.V. This should be diluted with the desired volume (80 to 260 mL) of a suitable i.v. solution (see Recommended I.V. Solution). The resulting solution should be infused over a period of 60 minutes by direct infusion or through a Y-type i.v. infusion set which may already be in place. If this method or the piggyback method of administration is used, it is advisable to discontinue temporarily the administration of any other solutions during the infusion of ciprofloxacin i.v.

As with all parenteral drug products, i.v. admixtures should be inspected visually for clarity, particulate matter, precipitate, discoloration and leakage prior to administration, whenever solution and container permit.

Availability And Storage: Cipro: Oral Suspension: 10%: Each 100 mL of oral suspension contains: ciprofloxacin 10 g (10 %). The drug product is composed of 2 components (microcapsules and diluent) which are mixed prior to dispensing (see Dosage, Instructions to the Pharmacist for Use/Handling).

Store at room temperature (15 to 25°C) in an upright position. Protect from freezing. Reconstituted product may be stored in a refrigerator or at room temperature (5 to 25°C) for 14 days. Store in an upright position. A teaspoon is provided for the patient.

Tablets: 100 mg: Each tablet, engraved CIPRO on one side and 100 on the other, contains: ciprofloxacin HCl equivalent to ciprofloxacin 100 mg. Nonmedicinal ingredients: colloidal silicon dioxide, crospovidone, hydroxypropyl methylcellulose 2910-15, magnesium stearate, maize starch, microcrystalline cellulose, polyethylene glycol, purified water, titanium dioxide. Lactose- and tartrazine-free. Unit dose packages of 6. Store below 30°C.

250 mg: Each tablet, engraved CIPRO on one side and 250 on the other, contains: ciprofloxacin HCl equivalent to ciprofloxacin 250 mg. Nonmedicinal ingredients: colloidal silicon dioxide, crospovidone, hydroxypropyl methylcellulose 2910-15, magnesium stearate, maize starch, microcrystalline cellulose, polyethylene glycol, purified water, titanium dioxide. Lactose- and tartrazine-free. Bottles of 100. Store below 30°C.

500 mg: Each tablet, engraved CIPRO on one side and 500 on the other, contains: ciprofloxacin HCl equivalent to ciprofloxacin 500 mg. Nonmedicinal ingredients: colloidal silicon dioxide, crospovidone, hydroxypropyl methylcellulose 2910-15, magnesium stearate, maize starch, microcrystalline cellulose, polyethylene glycol, purified water, titanium dioxide. Lactose- and tartrazine-free. Bottles of 100. Unit dose packages of 100. Store below 30°C.

750 mg: Each tablet, engraved CIPRO on one side and 750 on the other, contains: ciprofloxacin HCl equivalent to ciprofloxacin 750 mg. Nonmedicinal ingredients: colloidal silicon dioxide, crospovidone, hydroxypropyl methylcellulose 2910-15, magnesium stearate, maize starch, microcrystalline cellulose, polyethylene glycol, purified water, titanium dioxide. Lactose- and tartrazine-free. Bottles of 50. Unit dose packages of 100. Store below 30°C.

Cipro I.V.: Injection: Each mL contains: ciprofloxacin 10 mg. Nonmedicinal ingredients: hydrochloric acid, lactic acid and water for injection USP. Vials of 20 and 40 mL. Protect from light. Store at controlled room temperature (15 to 30°C).

Minibags: Each mL contains: ciprofloxacin 2 mg. Ready-to-use minibags of 100 and 200 mL.

CIPRO® CIPRO® I.V. CIPRO® Oral Suspension Bayer Ciprofloxacin HClCiprofloxacinCiprofloxacin Antibacterial

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