WARNING
Fluoroquinolones, including ciprofloxacin, may exacerbate muscle weakness in persons with myasthenia gravis. Avoid ciprofloxacin in patients with known history of myasthenia gravis (see WARNINGS).
DESCRIPTION
CLINICAL PHARMACOLOGY
Absorption
| 2505007501000 | 1.22.44.35.4 | 4.811.620.230.8 |
| Parameters | 500 mg q12h, P.O. | 400 mg q12h, I.V. | 750 mg q12h, P.O. | 400 mg q8h, I.V. |
| AUC (mcg•hr/mL) Cmax (mcg/mL) | 13.7a 2.97 | 12.7a 4.56 | 31.6b 3.59 | 32.9c 4.07 |
Distribution
Metabolism
Excretion
Drug-drug Interactions
Special Populations
MICROBIOLOGY
Mechanism of Action
The bactericidal action of ciprofloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV (both type II topoisomerases), which are required for bacterial DNA replication, transcription, repair, and recombination.
Mechanism of Resistance
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. Resistance to fluoroquinolones occurs primarily by either mutations in the DNA gyrases, decreased outer membrane permeability, or drug efflux. In vitro resistance to ciprofloxacin develops slowly by multiple step mutations. Resistance to ciprofloxacin due to spontaneous mutations occurs at a general frequency of between < 10-9 to 1x10-6.
Cross Resistance
There is no known cross-resistance between ciprofloxacin and other classes of antimicrobials.
Ciprofloxacin has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section of the package insert for ciprofloxacin tablets.
Gram-positive bacteria
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).
| Campylobacter jejuni Citrobacter diversus Citrobacter freundii Enterobacter cloacae Escherichia coli Haemophilus influenzae Haemophilus parainfluenzae Klebsiella pneumoniae Moraxella catarrhalis Morganella morganii Neisseria gonorrhoeae | Proteus mirabilis Proteus vulgarisProvidencia rettgeriProvidencia stuartiiPseudomonas aeruginosaSalmonella typhiSerratia marcescensShigella boydiiShigella dysenteriaeShigella flexneriShigella sonnei |
| Acinetobacter Iwoffi Aeromonas hydrophila Edwardsiella tarda Enterobacter aerogenes Klebsiella oxytocaLegionella pneumophila | Pasteurella multocidaSalmonella enteritidisVibrio choleraeVibrio parahaemolyticus Vibrio vulnificusYersinia enterocolitica |
Susceptibility Tests
· Diffusion Techniques
Table 1: Susceptibility Test Interpretive Criteria for Ciprofloxacin
· Quality Control
Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures.1,2 For dilution technique, standard ciprofloxacin powder should provide the MIC values according to criteria outlined in Table 2. For diffusion technique, the 5-mcg ciprofloxacin disk should provide the zone diameters outlined in Table 2.
Table 2: Quality Control for Susceptibility Testing of Ciprofloxacin
| MIC (mcg/mL) | Zone Diameter (mm) | |||||
| Species | S | I | R | S | I | R |
| Enterobacteriacae | ≤1 | 2 | ≥4 | ≥21 | 16-20 | ≤15 |
| Enterococcus faecalis | ≤1 | 2 | ≥4 | ≥21 | 16-20 | ≤15 |
| Staphylococcus species | ≤1 | 2 | ≥4 | ≥21 | 16-20 | ≤15 |
| Pseudomonas aeruginosa | ≤1 | 2 | ≥4 | ≥21 | 16-20 | ≤15 |
| Haemophilus influenzaea | ≤1 | ≥21 | ||||
| Haemophilus parainfluenzaea | ≤1 | ≥21 | ||||
| Streptococcus pneumoniae | ≤1 | 2 | ≥4 | ≥21 | 16-20 | ≤15 |
| Streptococcus pyogenes | ≤1 | 2 | ≥4 | ≥21 | 16-20 | ≤15 |
| Neisseria gonorrhoeaeb | ≤0.06 | 0.12 - 0.5 | ≥1 | ≥41 | 28-40 | ≤27 |
| S=Susceptible, I=Intermediate, and R=Resistant. a 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. b This interpretive standard is applicable only to agar dilution test with GC agar base and 1% defined growth supplement. | ||||||
| Strains | MIC Range (mcg/mL) | Zone Diameter (mm) |
| Enterococcus faecalis ATCC 29212 | 0.25–2 | - |
| Escherichia coli ATCC 25922 | 0.004–0.015 | 30–40 |
| Haemophilus influenzae ATCC 49247 | 0.004–0.03 | 34–42 |
| Pseudomonas aeruginosa ATCC 27853 | 0.25–1 | 25–33 |
| Staphylococcus aureus ATCC 29213 | 0.12–0.5 | - |
| Staphylococcus aureus ATCC 25923 | - | 22–30 |
| Neisseria gonorrhoeae ATCC 49226a | 0.001–0.008 | 48–58 |
| C. jejuni ATCC 33560 b | 0.06–0.25 and 0.03–0.12 | - |
| aN. gonorrhoeae ATCC 49226 tested by agar dilution procedure using GC agar and 1% defined growth supplement in a 5% CO2 environment at 35° to 37°C for 20 to 24 hours3.bC. jejuni ATCC 33560 tested by broth microdilution procedure using cation adjusted Mueller Hinton broth with 2.5 to 5% lysed horse blood in a microaerophilic environment at 36° to 37°C for 48 hours and for 42°C at 24 hours,2 respectively. | ||
INDICATIONS AND USAGE
Adult Patients
Urinary Tract Infections caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Proteus mirabilis, Providencia rettgeri, Morganella morganii, Citrobacter diversus, Citrobacter freundii, Pseudomonas aeruginosa, methicillin-susceptible Staphylococcus epidermidis, Staphylococcus saprophyticus, or Enterococcus faecalis.
Acute Uncomplicated Cystitis in females caused by Escherichia coli or Staphylococcus saprophyticus.
*Ciprofloxacin is not a drug of first choice in the treatment of presumed or confirmed pneumonia secondary to Streptococcus pneumoniae.
Acute Sinusitis caused by Haemophilus influenzae, penicillin-susceptible Streptococcus pneumoniae, or Moraxella catarrhalis.
Skin and Skin Structure Infections caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Proteus vulgaris, Providencia stuartii, Morganella morganii, Citrobacter freundii, Pseudomonas aeruginosa, methicillin-susceptible Staphylococcus aureus, methicillin-susceptible Staphylococcus epidermidis, or Streptococcus pyogenes.
Bone and Joint Infections caused by Enterobacter cloacae, Serratia marcescens, or Pseudomonas aeruginosa.
Complicated Intra-Abdominal Infections (used in combination with metronidazole) caused by Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, or Bacteroides fragilis.
Infectious Diarrhea caused by Escherichia coli (enterotoxigenic strains), Campylobacter jejuni, Shigella boydii†, Shigella dysenteriae, Shigella flexneri or Shigella sonnei†when antibacterial therapy is indicated.
†Although treatment of infections due to this organism in this organ system demonstrated a clinically significant outcome, efficacy was studied in fewer than 10 patients.
Uncomplicated cervical and urethral gonorrhea due to Neisseria gonorrhoeae.
Pediatric patients (1 to 17 years of age)
Complicated Urinary Tract Infections and Pyelonephritis due to Escherichia coli.
NOTE: Although effective in clinical trials, ciprofloxacin is not a drug of first choice in the pediatric population due to an increased incidence of adverse events compared to controls, including events related to joints and/or surrounding tissues. (See WARNINGS, PRECAUTIONS, Pediatric Use, ADVERSE REACTIONSand CLINICAL STUDIES.) Ciprofloxacin, like other fluoroquinolones, is associated with arthropathy and histopathological changes in weight-bearing joints of juvenile animals. (See ANIMAL PHARMACOLOGY.)
Adult and Pediatric Patients
CONTRAINDICATIONS
WARNINGS
Tendinopathy and Tendon Rupture
Exacerbation of Myasthenia Gravis
Pregnant Women
Theophylline
Central Nervous System Effects
Convulsions, increased intracranial pressure (including pseudotumor cerebri), and toxic psychosis have been reported in patients receiving fluoroquinolones, including ciprofloxacin. Ciprofloxacin may also cause central nervous system (CNS) events including: dizziness, confusion, tremors, hallucinations, depression, and, rarely, suicidal thoughts or acts. These 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 fluoroquinolones, 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 PRECAUTIONS: General, Information for Patients, Drug Interactionsand ADVERSE REACTIONS).
Clostridium Difficile-Associated Diarrhea
Peripheral neuropathy
Rare cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias 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.
Musculoskeletal Disorders in Pediatric Patients and Arthropathic Effects in Animals
Ciprofloxacin should be used in pediatric patients (less than 18 years of age) only for infections listed in the INDICATIONS AND USAGE section. An increased incidence of adverse events compared to controls, including events related to joints and/or surrounding tissues, has been observed. (See ADVERSE REACTIONS.)
In pre-clinical studies, oral administration of ciprofloxacin caused lameness in immature dogs. Histopathological examination of the weight-bearing joints of these dogs revealed permanent lesions of the cartilage. Related quinolone-class drugs also produce erosions of cartilage of weight-bearing joints and other signs of arthropathy in immature animals of various species. (See ANIMAL PHARMACOLOGY.)
Prolongation of the QT Interval
Some fluoroquinalones, including ciprofloxacin, have been associated with prolongation of the QT interval on the electrocardiogram and infrequent cases of arrhythmia. Rare cases of torsade de pointes have been spontaneously reported during postmarketing surveillance in patients receiving fluoroquinalones, including ciprofloxacin. Ciprofloxacin should be avoided in patients with known prolongation of the QT interval, patients with uncorrected hypokalemia, and patients receiving Class IA (quinidine, procainamide), or Class III (amiodarone, sotalol) antiarrhythmic agents. Elderly patients may be more susceptible to drug-associated effects on the QT interval (See PRECAUTIONS, Drug Interactionsand Geriatric Use ).
Cytochrome P450 (CYP450) Drug Interactions
Ciprofloxacin is an inhibitor of the hepatic CYP1A2 enzyme pathway. Coadministration of ciprofloxacin and other drugs primarily metabolized by CYP1A2 (for example, theophylline, methylxanthines, tizanidine) results in increased plasma concentrations of the coadministered drug and could lead to clinically significant pharmacodynamic side effects of the coadministered drug (see PRECAUTIONS, Drug Interactions).
Syphilis
PRECAUTIONS
General
Central Nervous System
Renal Impairment
Photosensitivity/Phototoxicity
Information for 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 ciprofloxacin treatment. The risk of severe tendon disorder 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.
· that fluoroquinolones like ciprofloxacin may cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems. Patients should call their healthcare provider right away if they have any worsening muscle weakness or breathing problems.
· that antibacterial drugs including ciprofloxacin tablets should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When ciprofloxacin tablets are 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 ciprofloxacin tablets or other antibacterial drugs in the future.
· that ciprofloxacin may be taken with or without meals and to drink fluids liberally. As with other quinolones, concurrent administration of ciprofloxacin with magnesium/aluminum antacids, polymeric phosphate binders (for example, sevelamer, lanthanum carbonate) or sucralfate, didanosine chewable/buffered tablets or pediatric powder, other highly buffered drugs, or with other products containing calcium, iron or zinc should be avoided. Ciprofloxacin may be taken two hours before or six hours after taking these products. Ciprofloxacin should not be taken with dairy products (like milk or yogurt) or calcium-fortified juices alone since absorption of ciprofloxacin may be significantly reduced; however, ciprofloxacin may be taken with a meal that contains these products.
· that ciprofloxacin may be associated with hypersensitivity reactions, even following a single dose, and to discontinue the drug at the first sign of a skin rash or other allergic reaction.
· that photosensitivity/phototoxicity has been reported in patients receiving quinolones. Patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while taking quinolones. If patients need to be outdoors while using quinolones, they should 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, patients should contact their physician.
· that peripheral neuropathies have been associated with ciprofloxacin use. If symptoms of peripheral neuropathy including pain, burning, tingling, numbness and/or weakness develop, they should discontinue treatment and contact their physicians.
· that ciprofloxacin may cause dizziness and lightheadedness; therefore, patients should know how they react to this drug before they operate an automobile or machinery or engage in activities requiring mental alertness or coordination.
· that ciprofloxacin increases the effects of tizanidine. Patients should not use ciprofloxacin if they are already taking tizanidine.
· that ciprofloxacin may increase the effects of theophylline and caffeine. There is a possibility of caffeine accumulation when products containing caffeine are consumed while taking quinolones.
· that convulsions have been reported in patients receiving quinolones, including ciprofloxacin, and to notify their physician before taking this drug if there is a history of this condition.
· that ciprofloxacin has been associated with an increased rate of adverse events involving joints and surrounding tissue structures (like tendons) in pediatric patients (less than 18 years of age). Parents should inform their child’s physician if the child has a history of joint-related problems before taking this drug. Parents of pediatric patients should also notify their child’s physician of any joint-related problems that occur during or following ciprofloxacin therapy. (See WARNINGS, PRECAUTIONS, Pediatric Use and ADVERSE REACTIONS.)
· 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, patients should contact their physician as soon as possible.
Drug Interactions
Tizanidine
In a pharmacokinetic study, systemic exposure of tizanidine (4 mg single dose) was significantly increased (Cmax 7-fold, AUC 10-fold) when the drug was given concomitantly with ciprofloxacin (500 mg bid for 3 days). The hypotensive and sedative effects of tizanidine were also potentiated. Concomitant administration of tizanidine and ciprofloxacin is contraindicated (see CONTRAINDICATIONS).
Theophylline
As with some other quinolones, concurrent administration of ciprofloxacin with theophylline may lead 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.
Other Xanthine Derivatives
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. On concurrent administration of ciprofloxacin and caffeine or pentoxifylline containing products, elevated serum concentrations of these xanthine derivatives were reported.
Chelation Complex Foundation
Concurrent administration of a quinolone, including ciprofloxacin, with multivalent cation-containing products such as magnesium/aluminum antacids, polymeric phosphate binders (for example, sevelamer, lanthanum carbonate), sucralfate, didanosine chewable/buffered tablets or pediatric powder, other highly buffered drugs, or products containing calcium, iron, or zinc may substantially decrease its absorption, resulting in serum and urine levels considerably lower than desired. (See DOSAGE AND ADMINISTRATIONfor concurrent administration of these agents with ciprofloxacin.)
Histamine H2-receptor antagonists appear to have no significant effect on the bioavailability of ciprofloxacin.
Omeprazole
Concomitant administration of a single tablet dose of 500 mg ciprofloxacin and once-daily administration of 20 mg omeprazole pretreatment for 4 days resulted in a 16% reduction of mean Cmax and mean AUC of ciprofloxacin.
Phenytoin
Altered serum levels of phenytoin (increased and decreased) have been reported in patients receiving concomitant ciprofloxacin.
Glyburide
The concomitant administration of ciprofloxacin with the sulfonylurea glyburide has, on rare occasions, resulted in severe hypoglycemia.
Metronidazole
The serum concentrations of ciprofloxacin and metronidazole were not altered when these two drugs were given concomitantly.
Cyclosporine
Some quinolones, including ciprofloxacin, have been associated with transient elevations in serum creatinine in patients receiving cyclosporine concomitantly.
Oral Anti-coagulants
Simultaneous administration of ciprofloxacin with an oral anticoagulant may augment the effect of the anticoagulant. The risk may vary with the underlying infections, age and general status of the patient so that the contribution of ciprofloxacin to the increase in INR (international normalized ratio) is difficult to assess. Prothromin time and INR should be monitored frequently during and shortly after co-administration of ciprofloxacin with an oral anticoagulant (for example, warfarin).
Probenecid
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.
Methotrexate
Renal tubular transport of methotrexate may be inhibited by concomitant administration of ciprofloxacin potentially leading to increased plasma levels of methotrexate. This might increase the risk of methotrexate associated toxic reactions. Therefore, patients under methotrexate therapy should be carefully monitored when concomitant ciprofloxacin therapy is indicated.
Metoclopramide
Metoclopramide significantly accelerates the absorption of oral ciprofloxacin resulting in shorter time to reach maximum plasma concentrations. No significant effect was observed on the bioavailability of ciprofloxacin.
Duloxetine
In clinical studies it was demonstrated that concomitant use of duloxetine with strong inhibitors of the CYP450 1A2 isozyme such as fluvoxamine, may result in a 5-fold increase in mean AUC and a 2.5-fold increase in mean Cmax of duloxetine. Although no clinical data are available on a possible interaction with ciprofloxacin, similar effects can be expected upon concomitant administration.
NSAIDs
Non-steroidal anti-inflammatory drugs (but not acetyl salicylic acid) in combination of very high doses of quinolones have been shown to provoke convulsions in pre-clinical studies.
Ropinirole
In a study conducted in 12 patients with Parkinson’s disease who were administered 6 mg ropinirole once daily with 500 mg ciprofloxacin twice-daily, the mean Cmax and mean AUC of ropinirole were increase by 60% and 84%, respectively. Monitoring for ropinirole-related side effects and appropriate dose adjustment of ropinirole is recommended during and shortly after co-administration with ciprofloxacin (see WARNINGS , Cytochrome P450).
Lidocaine
In a study conducted in 9 healthy volunteers, concomitant use of 1.5 mg/kg IV lidocaine with 500 mg ciprofloxacin twice daily, resulted in an increase of lidocaine Cmax and AUC by 12% and 26%, respectively. Although lidocaine treatment was well tolerated at this elevated exposure, a possible interaction with ciprofloxacin and an increase in side effects related to lidocaine may occur upon concomitant administration.
Clozapine
Following concomitant administration of 250 mg ciprofloxacin with 304 mg clozapine for 7 days, serum concentrations of clozapine and N-desmethylclozapine were increased by 29% and 31%, respectively. Careful monitoring of clozapine associated adverse effects and appropriate adjustment of clozapine dosage during and shortly after co-administration with ciprofloxacin are advised (see WARNINGS ).
Sildenafil
Following concomitant administration of a single oral dose of 50 mg sildenafil with 500 mg ciprofloxacin to healthy subjects, the mean Cmax and mean AUC of sildenafil were both increased approximately two-fold. Therefore, sildenafil should be used with caution when co-administered with ciprofloxacin.
Class IA or III Antiarrhythmics
Precaution should be taken when using ciprofloxacin concomitantly with class IA or III antiarrhythmics as ciprofloxacin may have an additive effect on the QT interval (see WARNINGS AND PRECAUTIONS, Geriatric Use).
Carcinogenesis, Mutagenesis, Impairment of Fertility
Pregnancy
Teratogenic Effects. Pregnancy Category C
Nursing Mothers
Pediatric Use
Inhalational Anthrax (Post-Exposure)
Complicated Urinary Tract Infection and Pyelonephritis
Cystic Fibrosis
Geriatric Use
ADVERSE REACTIONS
Adverse Reactions in Adult Patients
Adverse Reactions in Pediatric Patients
In this trial, the overall incidence rates of adverse events regardless of relationship to study drug and within 6 weeks of treatment initiation were 41% (138/335) in the ciprofloxacin group versus 31% (109/349) in the comparator group. The most frequent events were gastrointestinal: 15% (50/335) of ciprofloxacin patients compared to 9% (31/349) of comparator patients. Serious adverse events were seen in 7.5% (25/335) of ciprofloxacin-treated patients compared to 5.7% (20/349) of control patients. Discontinuation of drug due to an adverse event was observed in 3% (10/335) of ciprofloxacin-treated patients versus 1.4% (5/349) of comparator patients. Other adverse events that occurred in at least 1% of ciprofloxacin patients were diarrhea 4.8%, vomiting 4.8%, abdominal pain 3.3%, accidental injury 3%, rhinitis 3%, dyspepsia 2.7%, nausea 2.7%, fever 2.1%, asthma 1.8% and rash 1.8%.
In addition to the events reported in pediatric patients in clinical trials, it should be expected that events reported in adults during clinical trials or post-marketing experience may also occur in pediatric patients.
| All Patients (within 6 weeks) | 31/335 (9.3%) | 21/349 (6%) |
| 95% Confidence Interval* | (-0.8%, +7.2%) | |
| Age Group | ||
| ≥ 12 months < 24 months ≥ 2 years < 6 years ≥ 6 years < 12 years ≥ 12 years to 17 years | 1/36 (2.8%)5/124 (4%)18/143 (12.6%)7/32 (21.9%) | 0/413/118 (2.5%)12/153 (7.8%)6/37 (16.2 %) |
| All Patients (within 1 year) | 46/335 (13.7%) | 33/349 (9.5%) |
| 95% Confidence Interval* | (-0.6%, + 9.1%) |
Post-Marketing Adverse Event Reports
Adverse Laboratory Changes
OVERDOSAGE
DOSAGE AND ADMINISTRATION
ADULTS
| Urinary Tract | Acute Uncomplicated Mild/Moderate Severe/Complicated | 250 mg250 mg500 mg | q 12 hq 12 hq 12 h | 3 Days 7 to 14 Days 7 to 14 Days |
| Chronic Bacterial Prostatitis | Mild/Moderate | 500 mg | q 12 h | 28 Days |
| Lower Respiratory Tract | Mild/Moderate Severe/Complicated | 500 mg750 mg | q 12 hq 12 h | 7 to 14 days 7 to 14 days |
| Acute Sinusitis | Mild/Moderate | 500 mg | q 12 h | 10 days |
| Skin and Skin Structure | Mild/Moderate Severe/Complicated | 500 mg750 mg | q 12 hq 12 h | 7 to 14 Days 7 to 14 Days |
| Bone and Joint | Mild/Moderate Severe/Complicated | 500 mg750 mg | q 12 hq 12 h | ≥ 4 to 6 weeks ≥ 4 to 6 weeks |
| Intra-Abdominal* | Complicated | 500 mg | q 12 h | 7 to 14 Days |
| Infectious Diarrhea | Mild/Moderate/Severe | 500 mg | q 12 h | 5 to 7 Days |
| Typhoid Fever | Mild/Moderate | 500 mg | q 12 h | 10 Days |
| Urethral and Cervical Gonococcal Infections | Uncomplicated | 250 mg | single dose | single dose |
| Inhalational anthrax (post-exposure)** | 500 mg | q 12 h | 60 Days | |
| * used in conjunction with metronidazole † Generally ciprofloxacin should be continued for at least 2 days after the signs and symptoms of infection have disappeared, except for inhalational anthrax (post-exposure). ** Drug administration should begin as soon as possible after suspected or confirmed exposure. This indication is based on a surrogate endpoint, ciprofloxacin serum concentrations achieved in humans, reasonably likely to predict clinical benefit.4 For a discussion of ciprofloxacin serum concentrations in various human populations, see INHALATIONAL ANTHRAX – ADDITIONAL INFORMATION. |
| 250 mg Tablet q 12 h 500 mg Tablet q 12 h 750 mg Tablet q 12 h | 200 mg I.V. q 12 h 400 mg I.V. q 12 h 400 mg I.V. q 8 h |
| > 5030 – 505 – 29Patients on hemodialysis orPeritoneal dialysis | See Usual Dosage. 250 – 500 mg q 12 h 250 – 500 mg q 18 h 250 – 500 mg q 24 h (after dialysis) |
PEDIATRICS
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/1.73m2).
| PEDIATRIC DOSAGE GUIDELINES | ||||
| Infection | Route of Administration | Dose(mg/kg) | Frequency | Total Duration |
| ComplicatedUrinary TractorPyelonephritis | Intravenous | 6 to 10 mg/kg(maximum 400 mg perdose; not to be exceededeven in patients weighing > 51 kg) | Every 8hours | 10-21 days* |
| (patients from 1 to 17 years of age) | Oral | 10 mg/kg to 20 mg/kg (maximum 750 mg per dose; not to be exceededeven in patients weighing> 51 kg) | Every 12 hours | |
| InhalationalAnthrax(Post-Exposure)** | Intravenous | 10 mg/kg(maximum 400 mg perdose) | Every 12hours | 60 days |
| Oral | 15 mg/kg(maximum 500 mg per dose) | Every 12 hours | ||
HOW SUPPLIED
ANIMAL PHARMACOLOGY
CLINICAL STUDIES
Complicated Urinary Tract Infection and Pyelonephritis – Efficacy in Pediatric Patients
NOTE: Although effective in clinical trials, ciprofloxacin is not a drug of first choice in the pediatric population due to an increased incidence of adverse events compared to controls, including events related to joints and/or surrounding tissues.
Ciprofloxacin, administered I.V. and/or orally, was compared to a cephalosporin for treatment of complicated urinary tract infections (cUTI) and pyelonephritis in pediatric patients 1 to 17 years of age (mean age of 6 ± 4 years). The trial was conducted in the U.S., Canada, Argentina, Peru, Costa Rica, Mexico, South Africa, and Germany. The duration of therapy was 10 to 21 days (mean duration of treatment was 11 days with a range of 1 to 88 days). The primary objective of the study was to assess musculoskeletal and neurological safety.
Patients were evaluated for clinical success and bacteriological eradication of the baseline organism(s) with no new infection or superinfection at 5 to 9 days post-therapy (Test of Cure or TOC). The Per Protocol population had a causative organism(s) with protocol specified colony count(s) at baseline, no protocol violation, and no premature discontinuation or loss to follow-up (among other criteria).
The clinical success and bacteriologic eradication rates in the Per Protocol population were similar between ciprofloxacin and the comparator group as shown below.
*Patients with baseline pathogen(s) eradicated and no new infections or superinfections/total number of patients. There were 5.5% (6/211) ciprofloxacin and 9.5% (22/231) comparator patients with superinfections or new infections.
| Ciprofloxacin | Comparator | |
| Randomized Patients | 337 | 352 |
| Per Protocol Patients | 211 | 231 |
| Clinical Response at 5 to 9 Days Post-Treatment | 95.7% (202/211) | 92.6% (214/231) |
| 95% CI [-1.3%, 7.3%] | ||
| Bacteriologic Eradication by Patient at 5 to 9 Days Post-Treatment* | 84.4% (178/211) | 78.3% (181/231) |
| 95% CI [-1.3%, 13.1%] | ||
| Bacteriologic Eradication of the Baseline Pathogen at 5 to 9 Days Post-Treatment | ||
| Escherichia coli | 156/178 (88%) | 161/179 (90%) |
INHALATIONAL ANTHRAX IN ADULTS AND PEDIATRICS – ADDITIONAL INFORMATION
REFERENCES
Revised: 01/2012
MEDICATION GUIDE
What is the most important information I should know about ciprofloxacin tablets?
Ciprofloxacin tablets belong to a class of antibiotics called fluoroquinalones. Ciprofloxacin tablets can cause side effects that may be serious or even cause death. If you get any of the following serious side effects, get medical help right away. Talk with your heathcare provider about whether you should continue to take ciprofloxacin tablets.
2. Worsening of myasthenia gravis (a disease which causes muscle weakness).
Fluoroquinalones like ciprofloxacin tablets may cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems. Call your healthcare provider right away if you have any worsening muscle weakness or breathing problems.
See the section “What are the possible side effects of ciprofloxacin tablets?”for more information about side effects.
- Tendon problems can happen in people of all ages who take ciprofloxacin tablets. Tendons are tough cords of tissue that connect muscles to bones. Symptoms of tendon problems may include:Pain, swelling, tears and inflammation of tendons including the back of the ankle (Achilles), shoulder, hand, or other tendon sites.
- The risk of getting tendon problems while you take ciprofloxacin tabletsare higher if you: are over 60 years of age are taking steroids (corticosteroids)have had a kidney, heart or lung transplant.
- Tendon problems can happen in people who do not have the above risk factors when they take ciprofloxacin tablets. Other reasons that can increase your risk of tendon problems can include: physical activity or exercise kidney failure tendon problems in the past, such as in people with rheumatoid arthritis (RA)
- Call your healthcare provider right away at the first sign of tendon pain, swelling or inflammation. Stop taking ciprofloxacin tablets until tendinitis or tendon rupture has been ruled out by your healthcare provider. Avoid exercise and using the affected area. The most common area of pain and swelling is the Achilles tendon at the back of your ankle. This can also happen with other tendons.
- Talk to your healthcare provider about the risk of tendon rupture with continued use of ciprofloxacin tablets. You may need a different antibiotic that is not a fluoroquinolone to treat your infection.
- Tendon rupture can happen while you are taking or after you have finished taking ciprofloxacin tablets. Tendon ruptures have happened up to several months after patients have finished taking their fluoroquinolone.
- Get medical help right away if you get any of the following signs or symptoms of a tendon rupture: hear or feel a snap or pop in a tendon area bruising right after an injury in a tendon area unable to move the affected area or bear weight
What are ciprofloxacin tablets?
Sometimes infections are caused by viruses rather than by bacteria. Examples include viral infections in the sinuses and lungs, such as the common cold or flu. Antibiotics, including ciprofloxacin tablets, do not kill viruses.
Call your healthcare provider if you think your condition is not getting better while you are taking ciprofloxacin tablets.
Who should not take ciprofloxacin tablets?
· Have ever had a severe allergic reaction to an antibiotic known as a fluoroquinolone, or are allergic to any of the ingredients in ciprofloxacin tablets. Ask your healthcare provider if you are not sure. See the list of ingredients in ciprofloxacin tablets at the end of this Medication Guide.
· Also take a medicine called tizanidine. Serious side effects from tizanidine are likely to happen.
What should I tell my healthcare provider before taking ciprofloxacin tablets?
SEE “What is the most important information I should know about ciprofloxacin tablets?”
Ask your healthcare provider if you are not sure if any of your medicines are listed above.
Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.
- have tendon problems
- have a disease that causes muscle weakness (myasthenia gravis)
- have central nervous system problems (such as epilepsy)
- have nerve problems
- have or anyone in your family has an irregular heartbeat, especially a condition called “QT prolongation”
- have a history of seizures
- have kidney problems. You may need a lower dose of ciprofloxacin tablets if your kidneys do not work well.
- have rheumatoid arthritis (RA) or other history of joint problems
- have trouble swallowing pills
- are pregnant or planning to become pregnant. It is not known if ciprofloxacin tablets will harm your unborn child.
- are breastfeeding or planning to breastfeed. Ciprofloxacin passes into breast milk. You and your healthcare provider should decide whether you will take ciprofloxacin tablets or breastfeed.
How should I take ciprofloxacin tablets?
If you have been prescribed ciprofloxacin tablets after being exposed to anthrax:
- Take ciprofloxacin tablets exactly as prescribed by your healthcare provider.
- Take ciprofloxacin tablets in the morning and evening at about the same time each day. Swallow the tablet whole. Do not split, crush or chew the tablet. Tell your healthcare provider if you can not swallow the tablet whole.
- Ciprofloxacin tablets can be taken with or without food.
- Ciprofloxacin tablets should not be taken with dairy products (like milk or yogurt) or calcium-fortified juices alone, but may be taken with a meal that contains these products.
- Drink plenty of fluids while taking ciprofloxacin tablets.
- Do not skip any doses, or stop taking ciprofloxacin tablets even if you begin to feel better, until you finish your prescribed treatment, unless: you have tendon effects (see “What is the most important information I should know about ciprofloxacin tablets?”), you have a serious allergic reaction (see “What are the possible side effects of ciprofloxacin tablets?”), or your healthcare provider tells you to stop.
What should I avoid while taking ciprofloxacin tablets?
- Ciprofloxacin tablets can make you feel dizzy and lightheaded. Do not drive, operate machinery, or do other activities that require mental alertness or coordination until you know how ciprofloxacin tablets affects you.
- Avoid sunlamps, tanning beds, and try to limit your time in the sun. Ciprofloxacin tablets can make your skin sensitive to the sun (photosensitivity) and the light from sunlamps and tanning beds. You could get severe sunburn, blisters or swelling of your skin. If you get any of these symptoms while taking ciprofloxacin tablets, call your healthcare provider right away. You should use a sunscreen and wear a hat and clothes that cover your skin if you have to be in sunlight.
What are the possible side effects of ciprofloxacin tablets?
You may have serious seizure and breathing problems when you take theophylline with ciprofloxacin tablets. These problems may lead to death. Get emergency help right away if you have seizures or trouble breathing.
Seizures have been reported in people who take fluoroquinolone antibiotics including ciprofloxacin tablets. Tell your healthcare provider if you have a history of seizures. Ask your healthcare provider whether taking ciprofloxacin tablets will change your risk of having a seizure.
Allergic reactions, including death, can happen in people taking fluoroquinolones, including ciprofloxacin tablets, even after only one dose. Stop taking ciprofloxacin tablets and get emergency medical help right away if you get any of the following symptoms of a severe allergic reaction:
Skin rash may happen in people taking ciprofloxacin tablets even after only one dose. Stop taking ciprofloxacin tablets at the first sign of a skin rash and call your healthcare provider. Skin rash may be a sign of a more serious reaction to ciprofloxacin tablets.
Tell your healthcare provider right away if you have a change in your heart beat (a fast or irregular heartbeat), or if you faint. Ciprofloxacin tablets may cause a rare heart problem known as prolongation of the QT interval. This condition can cause an abnormal heartbeat and can be very dangerous. The chances of this event are higher in people:
· who are elderly· with a family history of prolonged QT interval· with low blood potassium (hypokalemia)· who take certain medicines to control heart rhythm (antiarrhythmics)
Pseudomembranous colitis can happen with most antibiotics, including ciprofloxacin tablets. Call your healthcare provider right away if you get watery diarrhea, diarrhea that doesnot go away, or bloody stools. You may have stomach cramps and a fever. Pseudomembranous colitis can happen 2 or more months after you have finished your antibiotic.
Damage to the nerves in arms, hands, legs, or feet can happen in people who take fluoroquinolones, including ciprofloxacin tablets. Talk with your healthcare provider right away if you get any of the following symptoms of peripheral neuropathy in your arms, hands, legs, or feet:
Ciprofloxacin tablets may need to be stopped to prevent permanent nerve damage.
People who take ciprofloxacin tablets and other fluoroquinolone medicines with the oral anti-diabetes medicine glyburide can get low blood sugar (hypoglycemia) which can sometimes be severe. Tell your healthcare provider if you get low blood sugar with ciprofloxacin tablets. Your antibiotic medicine may need to be changed.
Increased chance of problems with joints and tissues around joints in children under 18 years old. Tell your child’s healthcare provider if your child has any joint problems during or after treatment with ciprofloxacin tablets.
The most common side effects of ciprofloxacin tablets include:
These are not all the possible side effects of ciprofloxacin tablets. Tell your healthcare provider about any side effect that bothers you, or that does not go away.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
- Theophylline
How should I store ciprofloxacin tablets?
Store at 20° to 25°C (68° to 77°F); excursions permitted to 15°to 30°C (59° to 86°F).
Keep ciprofloxacin tablets and all medicines out of the reach of children.
General information about ciprofloxacin tablets
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use ciprofloxacin tablets for a condition for which it is not prescribed. Do not give ciprofloxacin tablets to other people, even if they have the same symptoms that you have. They may harm them.
This Medication Guide summarizes the most important information about ciprofloxacin tablets. If you would like more information about ciprofloxacin tablets, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about ciprofloxacin tablets that is written for healthcare professionals. For more information call 1-866-850-2876.