CIPROFLOXACIN- ciprofloxacin_injection, solution

Ciprofloxacin is a member of the fluoroquinolone class of antibacterial agents [see Microbiology (12. 4) Absorption Following 60-minute intravenous infusions of 200 mg and 400 mg ciprofloxacin to normal volunteers, the mean maximum serum concentrations achieved were 2. 6 mcg/mL, respectively; the concentrations at 12 hours were 0. 2 mcg/mL, respectively (Table 9). Table 9: Steady-state Ciprofloxacin Serum Concentrations (mcg/mL) After 60-minute INTRAVENOUS Infusions every 12 hours. Time after starting the infusion Dose 30 minutes 1 hour 3 hour 6 hour 8 hour 12 hour 200 mg 1. 2 The pharmacokinetics of ciprofloxacin are linear over the dose range of 200 mg to 400 mg administered intravenously. Comparison of the pharmacokinetic parameters following the 1st and 5th intravenous dose on an every 12 hour regimen indicates no evidence of drug accumulation. The absolute bioavailability of oral ciprofloxacin is within a range of 70en dash80% 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 intravenous dose results in a C max Table 10: Steady-state Pharmacokinetic Parameters Following Multiple Oral and Intravenous Doses (adults) Parameters 500 mg 400 mg 750 mg 400 mg every 12 every 12 hours, intravenously every 12 every 8 hours, intravenously AUC (0en dash24h),ss 27. 4 AUC 0en dash12h 25. 9 AUC 0en dash8h C max ,ss 2. 07 Distribution After intravenous administration, ciprofloxacin is widely distributed throughout the body. Tissue concentrations often exceed serum concentrations in both men and women, particularly in genital tissue including the prostate. Ciprofloxacin is present in active form in the saliva, nasal and bronchial secretions, mucosa of the sinuses, sputum, skin blister fluid, lymph, peritoneal fluid, bile, and prostatic secretions. Ciprofloxacin has also been detected in lung, skin, fat, muscle, cartilage, and bone. The drug diffuses into the cerebrospinal fluid (CSF); however, CSF concentrations are generally less than 10% of peak serum concentrations. Low levels of the drug have been detected in the aqueous and vitreous humors of the eye. Metabolism After intravenous administration, three metabolites of ciprofloxacin have been identified in human urine which together account for approximately 10% of the intravenous dose. The metabolites have antimicrobial activity, but are less active than unchanged. Ciprofloxacin is an inhibitor of human cytochrome P450 1A2 (CYP1A2) mediated metabolism. Co-administration of ciprofloxacin with other drugs primarily metabolized by CYP1A2 results in increased plasma concentrations of these drugs and could lead to clinically significant adverse events of the co-administered drug [see Contraindications (4. 2) Warnings and Precautions (5. 16) Drug Interactions (7) Excretion The serum elimination half-life is approximately 5 to 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 intravenous dose, concentrations in the urine usually exceed 200 mcg/mL 0 to 2 hours after dosing and are generally greater than 15 mcg/mL 8 to 12 hours after dosing. Following a 400 mg intravenous dose, urine concentrations generally exceed 400 mcg/mL 0 to 2 hours after dosing and are usually greater than 30 mcg/mL 8 to 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 (

Ciprofloxacin Injection (in 5% Dextrose Injection) is a fluoroquinolone antibacterial indicated in adults (>=18 years of age) with the following infections caused by designated, susceptible bacteria and in pediatric patients where indicated: 1. 1) 1. 9 o 1. 10 o o 1. 11 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of ciprofloxacin and other antibacterial drugs, ciprofloxacin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. 12 Ciprofloxacin Injection (in 5% Dextrose Injection) is indicated in adult patients for treatment of 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, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes. Ciprofloxacin Injection (in 5% Dextrose Injection) is indicated in adult patients for treatment of bone and joint infections caused by Enterobacter cloacae, Serratia marcescens, Pseudomonas aeruginosa. Ciprofloxacin Injection (in 5% Dextrose Injection) is indicated in adult patients for treatment of complicated intra-abdominal infections (used in combination with metronidazole) caused by Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, Bacteroides fragilis. Ciprofloxacin Injection (in 5% Dextrose Injection) is indicated in adult patients for treatment of nosocomial pneumonia caused by Haemophilus influenzae Klebsiella pneumoniae. Ciprofloxacin Injection (in 5% Dextrose Injection) is indicated in adult patients for the treatment of febrile neutropenia in combination with piperacillin sodium [see Clinical Studies (14. 1) Ciprofloxacin Injection (in 5% Dextrose Injection) is indicated in adults and pediatric patients from birth to 17 years of age for treatment of inhalational anthrax (post-exposure) to reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis. Ciprofloxacin serum concentrations achieved in humans served as a surrogate endpoint reasonably likely to predict clinical benefit and provided the initial basis for approval of this indication. 1 [see Clinical Studies (14. 3) Ciprofloxacin Injection (in 5% Dextrose Injection) is indicated for treatment of plague, including pneumonic and septicemic plague, due to Yersinia pestis (Y. pestis) [see Clinical Studies (14. 4) Ciprofloxacin Injection (in 5% Dextrose Injection) is indicated in adult patients for treatment of chronic bacterial prostatitis caused by Escherichia coli Proteus mirabilis. Ciprofloxacin Injection (in 5% Dextrose Injection) is indicated in adult patients for treatment of lower respiratory tract infections caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Pseudomonas aeruginosa, Haemophilus influenzae, Haemophilus parainfluenzae, Streptococcus pneumoniae. Streptococcus pneumonia Ciprofloxacin Injection (in 5% Dextrose Injection) is indicated for the treatment of acute exacerbations of chronic bronchitis (AECB) caused by Moraxella catarrhalis Because fluoroquinolones, including ciprofloxacin, have been associated with serious adverse reactions [see Warnings and Precautions (5. 1 en dash 5. 16)] Urinary Tract Infection in Adults Ciprofloxacin Injection (in 5% Dextrose Injection) is indicated in adult patients for treatment of urinary tract infections caused by Escherichia coli Klebsiella pneumoniae Enterobacter cloacae Serratia marcescens Proteus mirabilis Providencia rettgeri Morganella morganii Citrobacter koseri Citrobacter freundii Pseudomonas aeruginosa Staphylococcus epidermidis Staphylococcus saprophyticus Enterococcus faecalis Complicated Urinary Tract Infections and Pyelonephritis in Pediatric Patients Ciprofloxacin Injection (in 5% Dextrose Injection) is indicated in pediatric patients one to 17 years of age for treatment of complicated urinary tract infections (cUTI) and pyelonephritis due to Escherichia coli [see Use in Specific Populations (8. 4) Although effective in clinical trials, Ciprofloxacin Injection (in 5% Dextrose Injection), is not a drug of first choice in the pediatric population due to an increased incidence of adverse reactions compared to controls, including reactions related to joints and/or surrounding tissues. Ciprofloxacin Injection (in 5% Dextrose Injection), like other fluoroquinolones, is associated with arthropathy and histopathological changes in weight-bearing joints of juvenile animals [see Warnings and Precautions (5. 13) Adverse Reactions (6. 1) Use in Specific Populations (8. 4) Nonclinical Toxicology (13. 2) Ciprofloxacin Injection (in 5% Dextrose Injection) is indicated in adult patients for treatment of acute sinusitis caused by Haemophilus influenzae Streptococcus pneumoniae, Moraxella catarrhalis Because fluoroquinolones, including Ciprofloxacin Injection (in 5% Dextrose Injection), have been associated with serious adverse reactions [see Warnings and Precautions (5. 16)] To reduce the development of drug-resistant bacteria and maintain the effectiveness of Ciprofloxacin Injection (in 5% Dextrose Injection) and other antibacterial drugs, Ciprofloxacin Injection (in 5% Dextrose Injection) should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. If anaerobic organisms are suspected of contributing to the infection, appropriate therapy should be administered. Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing infection and to determine their susceptibility to ciprofloxacin. Therapy with Ciprofloxacin Injection (in 5% Dextrose Injection) may be initiated before results of these tests are known; once results become available appropriate therapy should be continued. As with other drugs, some isolates of Pseudomonas aeruginosa.

Ciprofloxacin should be administered intravenously at dosages described in the appropriate Dosage Guidelines tables. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Adult Dosage Guidelines Infection Dose Frequency Duration Skin and Skin Structure 400 mg every 8 to 12 hours 7 to 14 days Bone and Joint 400 mg every 8 to 12 hours 4 to 8 weeks Complicated Intra-Abdominal 400 mg every 12 hours 7 to 14 days Nosocomial Pneumonia 400 mg every 8 hours 10 to 14 days Empirical Therapy In Febrile Neutropenic Patients Ciprofloxacin 400 mg and Piperacillin 50 mg/kg every 8 hours 7 to 14 days Inhalational anthrax (post-exposure) 400 mg every 12 hours 60 days Plague 400 mg every 8 to 12 hours 14 days Chronic Bacterial Prostatitis 400 mg every 12 hours 28 days Lower Respiratory Tract 400 mg every 8 to 12 hours 7 to 14 days Urinary Tract 200 to 400 mg every 8 to 12 hours 7 to 14 days Acute Sinusitis 400 mg every 12 hours 10 days 2. 3 Pediatric Dosage Guidelines Infection Dose Frequency Duration Complicated UTI and Pyelonephritis (patients from 1 to 17 years of age) 6 mg/kg to 10 mg/kg (maximum 400 mg per dose) Every 8 hours 10 to 21 days 1 Inhalational Anthrax 10 mg/kg (maximum 400 mg per dose) Every 12 hours 60 days Plague 10 mg/kg (maximum 400 mg per dose) Every 8 to 12 hours 14 days The determination of dosage and duration 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. Table 1: Adult Dosage Guidelines Infection Due to the designated pathogens (see Indications and Usage Dose Frequency Usual Duration Skin and Skin Structure 400 mg every 8 to 12 hours 7 to 14 days Bone and Joint 400 mg every 8 to 12 hours 4 to 8 weeks Complicated Intra-Abdominal Used in conjunction with metronidazole. 400 mg every 12 hours 7 to 14 days Nosocomial Pneumonia 400 mg every 8 hours 10 to 14 days Empirical Therapy In Febrile Neutropenic Patients Ciprofloxacin every 8 hours 7 to 14 days Inhalational Anthrax (Post-Exposure) Begin administration as soon as possible after suspected or confirmed exposure. 400 mg every 12 hours 60 days Plague 400 mg every 8 to 12 hours 14 days Chronic Bacterial Prostatitis 400 mg every 12 hours 28 days Lower Respiratory Tract Infections 400 mg every 8 to 12 hours 7 to 14 days Urinary Tract Infections 200 mg to 400 mg every 8 to 12 hours 7 to 14 days Acute Sinusitis 400 mg every 12 hours 10 days Conversion of Intravenous to Oral Dosing in Adults Patients whose therapy is started with ciprofloxacin injection may be switched to Ciprofloxacin tablets when clinically indicated at the discretion of the physician (Table 2) [see Clinical Pharmacology (12. 3) Table 2: Equivalent AUC Dosing Regimens Ciprofloxacin Oral Dosage Equivalent Ciprofloxacin Injection Dosage 250 mg Tablet every 12 hours 200 mg intravenous every 12 hours 500 mg Tablet every 12 hours 400 mg intravenous every 12 hours 750 mg Tablet every 12 hours 400 mg intravenous every 8 hours Dosing and initial route of therapy (that is, IV or oral) for cUTI or pyelonephritis should be determined by the severity of the infection. Table 3: Pediatric Dosage Guidelines Infection Dose (mg/kg) Frequency Total Duration Complicated Urinary Tract or Pyelonephritis The total duration of therapy for cUTI and pyelonephritis in the clinical trial was determined by the physician. The mean duration of treatment was 11 days (range 10 to 21 days). 6 mg/kg to 10 mg/kg (maximum 400 mg per dose; not to be exceeded even in patients weighing more than 51 kg) Every 8 hours 10 to 21 days Inhalational Anthrax Begin drug administration as soon as possible after suspected or confirmed exposure. 10 mg/kg Every 12 hours 60 days Plague , Begin drug administration as soon as possible after suspected or confirmed exposure to Y. pestis 10 mg/kg Every 8 to 12 hours 14 days 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, particularly for patients with severe renal dysfunction. Dosage guidelines for use in patients with renal impairment are shown in Table 4. Table 4: Recommended Starting and Maintenance Doses for Adult Patients with Impaired Renal Function Creatinine Clearance (mL/min) Dose >30 See Usual Dosage. 5 to 29 200 to 400 mg every 18 to 24 hours When only the serum creatinine concentration is known, the following formulas may be used to estimate creatinine clearance: Men = Weight (kg) × (140 − age) Women The serum creatinine should represent a steady state of renal function. In patients with severe infections and severe renal impairment and hepatic insufficiency, careful monitoring is suggested. Pediatric patients with moderate to severe renal insufficiency were excluded from the clinical trial of cUTI and pyelonephritis. No information is available on dosing adjustments necessary for pediatric patients with moderate to severe renal insufficiency (that is, creatinine clearance of < 50 mL/min/1. 73 m 2 The 2 mg/mL infusion solution in 5% dextrose is available 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 below. 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 ciprofloxacin. If the concomitant use of ciprofloxacin and another drug is necessary each drug should be given separately in accordance with the recommended dosage and route of administration for each drug. Intravenous Infusion Ciprofloxacin Injection, USP (in 5% Dextrose Injection) should be administered by intravenous infusion over a period of 60 minutes. Slow infusion of a dilute solution into a larger vein will minimize patient discomfort and reduce the risk of venous irritation. Hydration of Patients Receiving Ciprofloxacin Adequate hydration of patients receiving Ciprofloxacin Injection, USP (in 5% Dextrose Injection) should be maintained to prevent the formation of highly concentrated urine. Crystalluria has been reported with quinolones [see Warnings and Precautions (5. 17) Adverse Reactions (6. 1) Nonclinical Toxicology (13. 2) Patient Counseling Information (17).

The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of labeling: [see Warnings and Precautions (5. 1) [see Warnings and Precautions (5. 2) [see Warnings and Precautions (5. 3) [see Warnings and Precautions (5. 4) [see Warnings and Precautions (5. 5) [see Warnings and Precautions (5. 6) [see Warnings and Precautions (5. 7) [see Warnings and Precautions (5. 8) [see Warnings and Precautions (5. 9) [see Warnings and Precautions (5. 10) Clostridioides difficile [see Warnings and Precautions (5. 11) [see Warnings and Precautions (5. 12) [see Warnings and Precautions (5. 13) [see Warnings and Precautions (5. 14) [see Warnings and Precautions (5. 15) The most common adverse reactions >=1% were nausea, diarrhea, liver function tests abnormal, vomiting, central nervous system disturbance, local intravenous site reactions eosinophilia, headache, restlessness, and rash. ( 6 To report SUSPECTED ADVERSE REACTIONS, contact Hospira, Inc. at 1-800-441-4100, or FDA at 1-800-FDA-1088 or www. gov/medwatch Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adult Patients During clinical investigations with oral and parenteral ciprofloxacin, 49,038 patients received courses of the drug. The most frequently reported adverse reactions, from clinical trials of all formulations, all dosages, all drug-therapy durations, and for all indications of ciprofloxacin therapy were nausea (2. 5%), diarrhea (1. 6%), liver function tests abnormal (1. 3%), vomiting (1%), and rash (1%). In clinical trials the following adverse reactions were reported in greater than 1% of patients treated with intravenous ciprofloxacin: nausea, diarrhea, central nervous system disturbance, local intravenous site reactions, liver function tests abnormal, eosinophilia, headache, restlessness, and rash. Local intravenous site reactions are more frequent if the infusion time is 30 minutes or less. These may appear as local skin reactions that resolve rapidly upon completion of the infusion. Subsequent intravenous administration is not contraindicated unless the reactions recur or worsen. Table 5: Medically Important Adverse Reactions That Occurred in less than 1% Ciprofloxacin Patients System Organ Class Adverse Reactions Body as a Whole Abdominal Pain/Discomfort Pain Cardiovascular Cardiopulmonary Arrest Myocardial Infarction Tachycardia Syncope Hypertension Angina Pectoris Vasodilation Central Nervous System Restlessness Seizures (including Status Epilepticus) Paranoia Psychosis (toxic) Depression (potentially culminating in self-injurious behavior, such as suicidal ideations/thoughts and attempted or completed suicide) Phobia Depersonalization Manic Reaction Unresponsiveness Ataxia Hallucinations Dizziness Paresthesia Tremor Insomnia Nightmares Irritability Malaise Abnormal Gait Migraine Gastrointestinal Ileus Gastrointestinal Bleeding Pancreatitis Hepatic Necrosis Intestinal Perforation Dyspepsia Constipation Oral Ulceration Mouth Dryness Anorexia Flatulence Hepatitis Hemic/Lymphatic Agranulocytosis Prolongation of Prothrombin Time Petechia Metabolic/Nutritional Hyperglycemia Hypoglycemia Musculoskeletal Arthralgia Joint Stiffness Muscle Weakness Renal/Urogenital Renal Failure Interstitial Nephritis Hemorrhagic Cystitis Renal Calculi Frequent Urination Gynecomastia Crystalluria Cylindruria Hematuria Albuminuria Respiratory Respiratory Arrest Dyspnea Laryngeal Edema Hemoptysis Bronchospasm Skin/Hypersensitivity Allergic Reactions Anaphylactic Reactions including life-threatening anaphylactic shock Erythema Multiforme/Stevens-Johnson Syndrome Exfoliative Dermatitis Toxic Epidermal Necrolysis Vasculitis Angioedema Extremities Purpura Fever Pruritus Urticaria Increased Perspiration Erythema Nodosum Thrombophlebitis Burning Photosensitivity/Phototoxicity Reaction Special Senses Decreased Visual Acuity Blurred Vision Disturbed Vision (diplopia, chromatopsia, and photopsia) Anosmia Hearing Loss Tinnitus Nystagmus Bad Taste In several instances, nausea, vomiting, tremor, irritability, or palpitation were judged by investigators to be related to elevated serum levels of theophylline possibly as a result of drug interaction with ciprofloxacin. In randomized, double-blind controlled clinical trials comparing ciprofloxacin (Intravenous and Intravenous/Oral sequential) with intravenous beta-lactam control antibiotics, the CNS adverse reaction profile of ciprofloxacin was comparable to that of the control drugs. Pediatric Patients Short (6 weeks) and long term (1 year) musculoskeletal and neurological safety of oral/intravenous ciprofloxacin was compared to a cephalosporin for treatment of cUTI or pyelonephritis in pediatric patients 1 to 17 years of age (mean age of 6 +/- 4 years) in an international multicenter trial. The duration of therapy was 10 to 21 days (mean duration of treatment was 11 days with a range of 1 to 88 days). A total of 335 ciprofloxacin- and 349 comparator-treated patients were enrolled. An Independent Pediatric Safety Committee (IPSC) reviewed all cases of musculoskeletal adverse reactions including abnormal gait or abnormal joint exam (baseline or treatment-emergent). Within 6 weeks of treatment initiation, the rates of musculoskeletal adverse reactions were 9. 3% (31/335) in the ciprofloxacin-treated group versus 6% (21/349) in comparator-treated patients. All musculoskeletal adverse reactions occurring by 6 weeks resolved (clinical resolution of signs and symptoms), usually within 30 days of end of treatment. Radiological evaluations were not routinely used to confirm resolution of the adverse reactions. Ciprofloxacin-treated patients were more likely to report more than one adverse reaction and on more than one occasion compared to control patients. The rate of musculoskeletal adverse reactions was consistently higher in the ciprofloxacin group compared to the control group across all age subgroups. At the end of 1 year, the rate of these adverse reactions reported at any time during that period was 13. 7% (46/335) in the ciprofloxacin-treated group versus 9. 5% (33/349) in the comparator-treated patients (Table 6). Table 6: Musculoskeletal Adverse Reactions Included: arthralgia, abnormal gait, abnormal joint exam, joint sprains, leg pain, back pain, arthrosis, bone pain, pain, myalgia, arm pain, and decreased range of motion in a joint (knee, elbow, ankle, hip, wrist, and shoulder) Ciprofloxacin Comparator All Patients (within 6 weeks) 31/335 (9. 3%) 21/349 (6%) 95% Confidence Interval The study was designed to demonstrate that the arthropathy rate for the ciprofloxacin group did not exceed that of the control group by more than + 6%. At both the 6 week and 1 year evaluations, the 95% confidence interval indicated that it could not be concluded that the ciprofloxacin group had findings comparable to the control group. 2%) Age Group 12 months to 24 months 1/36 (2. 8%) 0/41 2 years to <6 years 5/124 (4%) 3/118 (2. 5%) 6 years to <12 years 18/143 (12. 6%) 12/153 (7. 8%) 12 years to 17 years 7/32 (21. 9%) 6/37 (16. 2%) All Patients (within 1 year) 46/335 (13. 7%) 33/349 (9. 5%) 95% Confidence Interval (-0. 1%) The incidence rates of neurological adverse reactions within 6 weeks of treatment initiation were 3% (9/335) in the ciprofloxacin group versus 2% (7/349) in the comparator group and included dizziness, nervousness, insomnia, and somnolence. In this trial, the overall incidence rates of adverse reactions 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 adverse reactions were gastrointestinal: 15% (50/335) of ciprofloxacin patients compared to 9% (31/349) of comparator patients. Serious adverse reactions 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 reaction 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%, dyspepsia 2. 7%, nausea 2. 7%, fever 2. 1%, asthma 1. 8% and rash 1. Short-term safety data for ciprofloxacin was also collected in a randomized, double-blind clinical trial for the treatment of acute pulmonary exacerbations in cystic fibrosis patients (ages 5en dash17 years). Sixty-seven patients received ciprofloxacin 10 mg/kg/dose every 8 hours for one week followed by ciprofloxacin tablets 20 mg/kg/dose every 12 hours to complete 10en dash21 days treatment and 62 patients received the combination of ceftazidime intravenous 50 mg/kg/dose every 8 hours and tobramycin intravenous 3 mg/kg/dose every 8 hours for a total of 10en dash21 days. Periodic musculoskeletal assessments were conducted by treatment-blinded examiners. Patients were followed for an average of 23 days after completing treatment (range 0en dash93 days). Musculoskeletal adverse reactions were reported in 22% of the patients in the ciprofloxacin group and 21% in the comparison group. Decreased range of motion was reported in 12% of the subjects in the ciprofloxacin group and 16% in the comparison group. Arthralgia was reported in 10% of the patients in the ciprofloxacin group and 11% in the comparison group. Other adverse reactions were similar in nature and frequency between treatment arms. The efficacy of ciprofloxacin for the treatment of acute pulmonary exacerbations in pediatric cystic fibrosis patients has not been established. In addition to the adverse reactions reported in pediatric patients in clinical trials, it should be expected that adverse reactions reported in adults during clinical trials or postmarketing experience may also occur in pediatric patients. The following adverse reactions have been reported from worldwide marketing experience with fluoroquinolones, including ciprofloxacin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure (Table 7). Table 7: Postmarketing Reports of Adverse Drug Reactions System Organ Class Adverse Reactions Cardiovascular QT prolongation Torsade de Pointes Vasculitis and ventricular arrhythmia Acute myocardial ischemia with or without myocardial infarction occurring as part of an allergic reaction Central Nervous System Hypertonia Myasthenia Exacerbation of myasthenia gravis Peripheral neuropathy Polyneuropathy Twitching Gastrointestinal Pseudomembranous colitis Hemic/Lymphatic Pancytopenia (life threatening or fatal outcome) Methemoglobinemia Hepatobiliary Hepatic failure (including fatal cases) Infections and Infestations Candidiasis (oral, gastrointestinal, vaginal) Investigations Prothrombin time prolongation or decrease Cholesterol elevation (serum) Potassium elevation (serum) Musculoskeletal Myalgia Myoclonus Tendinitis Tendon rupture Psychiatric Disorders Agitation Confusion Delirium Skin/Hypersensitivity Acute generalize exanthematous pustulosis (AGEP) Fixed eruption Serum sickness-like reaction Special Senses Anosmia Hyperesthesia Hypesthesia Nystagmus Taste loss Changes in laboratory parameters while on ciprofloxacin therapy are listed below: Other changes occurring were: decreased leukocyte count, elevated atypical lymphocyte count, immature WBCs, elevated serum calcium, elevation of serum gamma-glutamyl transpeptidase (gGT), decreased BUN, decreased uric acid, decreased total serum protein, decreased serum albumin, decreased serum potassium, elevated serum potassium, elevated serum cholesterol. Other changes occurring during administration of ciprofloxacin were: elevation of serum amylase, decrease of blood glucose, pancytopenia, leukocytosis, elevated sedimentation rate, change in serum phenytoin, decreased prothrombin time, hemolytic anemia, and bleeding diathesis.

2 Ciprofloxacin Injection (in 5% Dextrose Injection) is contraindicated in persons with a history of hypersensitivity to ciprofloxacin, any member of the quinolone class of antibacterials, or any of the product components [see Warnings and Precautions (5. 7) Concomitant administration with tizanidine is contraindicated [see Drug Interactions (7).

Lactation: See full prescribing information for 8. 5 Risk Summary Prolonged experience with ciprofloxacin in pregnant women over several decades, based on available published information from case reports, case control studies and observational studies on ciprofloxacin administered during pregnancy, have not identified any drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes (see Data (see Data The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Human Data While available studies cannot definitively establish the absence of risk, published data from prospective observational studies over several decades have not established an association with ciprofloxacin use during pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes. Available studies have methodological limitations including small sample size and some of them are not specific for ciprofloxacin. A controlled prospective observational study followed 200 women exposed to fluoroquinolones (52. 5% exposed to ciprofloxacin and 68% first trimester exposures) during gestation. In utero exposure to fluoroquinolones during embryogenesis was not associated with increased risk of major malformations. The reported rates of major congenital malformations were 2. 2% for the fluoroquinolone group and 2. 6% for the control group (background incidence of major malformations is 1en dash5%). Rates of spontaneous abortions, prematurity and low birth weight did not differ between the groups and there were no clinically significant musculoskeletal dysfunctions up to one year of age in the ciprofloxacin exposed children. Another prospective follow-up study reported on 549 pregnancies with fluoroquinolone exposure (93% first trimester exposures). There were 70 ciprofloxacin exposures, all within the first trimester. The malformation rates among live-born babies exposed to ciprofloxacin and to fluoroquinolones overall were both within background incidence ranges. No specific patterns of congenital abnormalities were found. The study did not reveal any clear adverse reactions due to in utero exposure to ciprofloxacin. No differences in the rates of prematurity, spontaneous abortions, or birth weight were seen in women exposed to ciprofloxacin during pregnancy. However, these small postmarketing epidemiology studies, of which most experience is from short term, first trimester exposure, are insufficient to evaluate the risk for less common defects or to permit reliable and definitive conclusions regarding the safety of ciprofloxacin in pregnant women and their developing fetuses. Animal Data Developmental toxicology studies have been performed with ciprofloxacin in rats, mice, and rabbits. In rats and mice, oral doses up to 100 mg/kg administered during organogenesis (Gestation Days, GD, 6en dash17) were not associated with adverse developmental outcomes, including embryofetal toxicity or malformations. In rats and mice, a 100 mg/kg dose is approximately 0. 3 times the maximum daily human oral dose (1500 mg/day) based upon body surface area, respectively. In a series of rabbit developmental toxicology studies, does received oral or intravenous ciprofloxacin for one of the following 5 day periods: GD 6 to 10, GD 10 to 14, or GD 14 to 18, intended to cover the period of organogenesis. This was an attempt to mitigate the gastrointestinal intolerance observed in rabbits that receive antibacterials manifested by reduced maternal food consumption and weight loss, that can lead to embryofetal resorption or spontaneous abortion. An oral ciprofloxacin dose of 100 mg/kg (approximately 1. 3 times the highest recommended clinical oral dose based on body surface area) caused excessive maternal toxicity confounding evaluation of the fetuses. A 30 mg/kg oral dose (approximately 0. 4 times the highest recommended clinical oral dose) was associated with suppression of maternal and fetal body weight gain, but fetal malformations were not observed. Intravenous administration of doses up to 20 mg/kg (approximately 0. 3 times the highest recommended clinical oral dose based upon body surface area) to pregnant rabbits was not maternally toxic and neither embryofetal toxicity nor fetal malformations were observed. In peri- and post-natal studies, rats received ciprofloxacin doses up to 200 mg/kg/day (oral) or up to 30 mg/kg/day (subcutaneous) from GD 16 to 22 days postpartum. The 200 mg/kg dose is approximately 1. 3-times the maximum recommended clinical oral dose based on body surface area. Neither maternal toxicity nor adverse effects on growth and development of the pups were observed, including no sign of arthropathy on the rear leg joints of the pups. Ciprofloxacin and other quinolones have been shown to cause arthropathy in immature animals of most species tested when administered directly [see Warnings and Precautions (5. 13) Nonclinical Toxicology 13. 2 Risk Summary Published literature reports that ciprofloxacin is present in human milk following intravenous and oral administration. There is no information regarding effects of ciprofloxacin on milk production or the breastfed infant. Because of the potential risk of serious adverse reactions in breastfed infants, including arthropathy shown in juvenile animal studies [see Use in Specific Populations (8. 4) Clinical Considerations However, for inhalation anthrax (post exposure), during an incident resulting in exposure to anthrax, the risk-benefit assessment of continuing breastfeeding while the mother (and potentially the infant) is (are) on ciprofloxacin may be acceptable [see Dosage and Administration (2. 2) Pediatric Use (8. 4) Clinical Studies (14. 2) Clinical Considerations Ciprofloxacin may cause intestinal flora alteration of the breastfeeding infant. Advise a woman to monitor the breastfed infant for loose or bloody stools and candidiasis (thrush, diaper rash). Although effective in clinical trials, ciprofloxacin is not a drug of first choice in the pediatric population due to an increased incidence of adverse reactions compared to controls. Quinolones, including ciprofloxacin, cause arthropathy (arthralgia, arthritis), in juvenile animals [see Warnings and Precautions (5. 12) Nonclinical Toxicology (13. 2) Complicated Urinary Tract Infection and Pyelonephritis Ciprofloxacin is indicated for the treatment of cUTI and pyelonephritis due to Escherichia coli. [see Adverse Reactions (6. 1) Clinical Studies (14. 2) Inhalational Anthrax (Post-Exposure) Ciprofloxacin is indicated in pediatric patients from birth to 17 years of age for inhalational anthrax (post-exposure). The risk-benefit assessment indicates that administration of ciprofloxacin to pediatric patients is appropriate [see Dosage and Administration (2. 2) Clinical Studies (14. 3) Plague Ciprofloxacin is indicated in pediatric patients from birth to 17 years of age, for treatment of plague, including pneumonic and septicemic plague due to Yersinia pestis (Y. pestis) [see Indications and Usage (1. 7) Dosage and Administration (2. 4) Geriatric patients are at increased risk for developing severe tendon disorders including tendon rupture when being treated with a fluoroquinolone such as ciprofloxacin. This risk is further increased in patients receiving concomitant corticosteroid therapy. Tendinitis or tendon rupture can involve the Achilles, hand, shoulder, or other tendon sites and can occur during or after completion of therapy; cases occurring up to several months after fluoroquinolone treatment have been reported. Caution should be used when prescribing ciprofloxacin to elderly patients especially those on corticosteroids. Patients should be informed of this potential adverse reaction and advised to discontinue ciprofloxacin and contact their healthcare provider if any symptoms of tendinitis or tendon rupture occur [see Boxed Warning Warnings and Precautions (5. 2) Adverse Reactions (6. 2) Epidemiologic studies report an increased rate of aortic aneurysm and dissection within two months following use of fluoroquinolones, particularly in elderly patients [see Warnings and Precautions (5. 9) In a retrospective analysis of 23 multiple-dose controlled clinical trials of ciprofloxacin encompassing over 3500 ciprofloxacin-treated patients, 25% of patients were greater than or equal to 65 years of age and 10% were greater than or equal to 75 years of age. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals on any drug therapy cannot be ruled out. Ciprofloxacin is known to be substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function. No alteration of dosage is necessary for patients greater than 65 years of age with normal renal function. However, since some older individuals experience reduced renal function by virtue of their advanced age, care should be taken in dose selection for elderly patients, and renal function monitoring may be useful in these patients [see Dosage and Administration (2. 3) Clinical Pharmacology (12. 3) In general, elderly patients may be more susceptible to drug-associated effects on the QT interval. Therefore, precaution should be taken when using ciprofloxacin with concomitant drugs that can result in prolongation of the QT interval (for example, class IA or class III antiarrhythmics) or in patients with risk factors for torsade de pointes (for example, known QT prolongation, uncorrected hypokalemia) [see Warnings and Precautions (5. 12) 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, particularly for patients with severe renal dysfunction [see Dosage and Administration (2. 3) In preliminary studies in patients with stable chronic liver cirrhosis, no significant changes in ciprofloxacin pharmacokinetics have been observed. The pharmacokinetics of ciprofloxacin in patients with acute hepatic insufficiency, have not been studied.

Ciprofloxacin is an inhibitor of human cytochrome P450 1A2 (CYP1A2) mediated metabolism. Co-administration of Ciprofloxacin Injection (in 5% Dextrose Injection) with other drugs primarily metabolized by CYP1A2 results in increased plasma concentrations of these drugs and could lead to clinically significant adverse events of the co-administered drug. Table 8: Drugs That are Affected by and Affecting Ciprofloxacin Drugs That are Affected by Ciprofloxacin Drug(s) Recommendation Comments Tizanidine Contraindicated Concomitant administration of tizanidine and ciprofloxacin is contraindicated due to the potentiation of hypotensive and sedative effects of tizanidine [see Contraindications (4. 2) Theophylline Avoid Use Concurrent administration of ciprofloxacin with theophylline may result in increased risk of a patient developing central nervous system (CNS) or other adverse reactions. If concomitant use cannot be avoided, monitor serum levels of theophylline and adjust dosage as appropriate [see Warnings and Precautions (5. 10) Drugs Known to Prolong QT Interval Avoid Use Ciprofloxacin may further prolong the QT interval in patients receiving drugs known to prolong the QT interval (for example, class IA or III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics) [see Warnings and Precautions (5. 12) Use in Specific Populations (8. 5) Oral antidiabetic drugs Use with caution Hypoglycemia sometimes severe has been reported when ciprofloxacin and oral antidiabetic agents, mainly sulfonylureas (for example, glyburide, glimepiride), were co-administered, presumably by intensifying the action of the oral antidiabetic agent. Fatalities have been reported. [see Adverse Reactions (6. 1) Phenytoin Use with caution To avoid the loss of seizure control associated with decreased phenytoin levels and to prevent phenytoin overdose-related adverse reactions upon ciprofloxacin discontinuation in patients receiving both agents, monitor phenytoin therapy, including phenytoin serum concentration during and shortly after co-administration of ciprofloxacin with phenytoin. Cyclosporine Use with caution Monitor renal function (in particular serum creatinine) when ciprofloxacin is co-administered with cyclosporine. Anti-coagulant drugs Use with caution The risk may vary with the underlying infection, 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. Monitor prothrombin time and INR frequently during and shortly after co-administration of ciprofloxacin with an oral anti-coagulant (for example, warfarin). Methotrexate Use with caution Potential increase in the risk of methotrexate associated toxic reactions. Therefore, carefully monitor patients under methotrexate therapy when concomitant ciprofloxacin therapy is indicated. Ropinirole Use with caution Monitoring for ropinirole-related adverse reactions and appropriate dose adjustment of ropinirole is recommended during and shortly after co-administration with ciprofloxacin [see Warnings and Precautions (5. 16) Clozapine Use with caution Careful monitoring of clozapine associated adverse reactions and appropriate adjustment of clozapine dosage during and shortly after co-administration with ciprofloxacin are advised. NSAIDs Use with caution 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 and in postmarketing. Sildenafil Use with caution Monitor for sildenafil toxicity [see Clinical Pharmacology (12. 3) Duloxetine Avoid Use If unavoidable, monitor for duloxetine toxicity. Caffeine/Xanthine Derivatives Use with caution Ciprofloxacin inhibits the formation of paraxanthine after caffeine administration (or pentoxifylline containing products). Monitor for xanthine toxicity and adjust dose as necessary. Zolpidem Avoid Use Co-administration with ciprofloxacin may increase blood levels of zolpidem, concurrent use is not recommended. Drug(s) Affecting Pharmacokinetics of Ciprofloxacin Probenecid Use with caution (interferes with renal tubular secretion of ciprofloxacin and increases ciprofloxacin serum levels) Potentiation of ciprofloxacin toxicity may occur. Interacting Drug Interaction Theophylline Serious and fatal reactions. Avoid concomitant use. Monitor serum level ( 7 Warfarin Anticoagulant effect enhanced. Monitor prothrombin time, INR, and bleeding ( 7 Antidiabetic agents Hypoglycemia including fatal outcomes have been reported. Monitor blood glucose ( 7 Phenytoin Monitor phenytoin level ( 7 Methotrexate Monitor for methotrexate toxicity ( 7 Cyclosporine May increase serum creatinine. Monitor serum creatinine ( 7.

OVERDOSAGE
In the event of acute overdosage, reversible renal toxicity has been reported in some cases. Observe the patient carefully and give supportive treatment, including monitoring of renal function, urinary pH and acidify, if required, to prevent crystalluria. Adequate hydration must be maintained. Only a small amount of ciprofloxacin (less than 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 mg/kg and 300 mg/kg.
NONCLINICAL TOXICOLOGY
Eight in vitro E. coli 79 Saccharomyces cerevisiae Saccharomyces cerevisiae Thus, 2 of the 8 tests were positive, but results of the following 3 in vivo Long-term carcinogenicity studies in rats and mice resulted in no carcinogenic or tumorigenic effects due to ciprofloxacin at daily oral dose levels up to 250 mg/kg and 750 mg/kg to rats and mice, respectively (approximately 1. 7- times and 2. 5- times the highest recommended therapeutic dose based upon body surface area, respectively). Results from photo co-carcinogenicity testing indicate that ciprofloxacin does not reduce the time to appearance of UV-induced skin tumors as compared to vehicle control. Hairless (Skh-1) mice were exposed to UVA light for 3. 5 hours five times every two weeks for up to 78 weeks while concurrently being administered ciprofloxacin. The time to development of the first skin tumors was 50 weeks in mice treated concomitantly with UVA and ciprofloxacin (mouse dose approximately equal to maximum recommended human dose based upon body surface area), as opposed to 34 weeks when animals were treated with both UVA and vehicle. The times to development of skin tumors ranged from 16 to 32 weeks in mice treated concomitantly with UVA and other quinolones. 5 In this model, mice treated with ciprofloxacin alone did not develop skin or systemic tumors. There are no data from similar models using pigmented mice and/or fully haired mice. The clinical significance of these findings to humans is unknown. Fertility studies performed in male and female rats at oral doses of ciprofloxacin up to 100 mg/kg (approximately 0. 6-times the highest recommended therapeutic oral dose based upon body surface area) revealed no evidence of impairment. Male rats received oral ciprofloxacin for 10 weeks prior to mating and females were dosed for 3 weeks prior to mating through Gestation Day 7. Ciprofloxacin and other quinolones have been shown to cause arthropathy in immature animals of most species tested [see Warnings and Precautions (5. 13) Damage of weight-bearing joints was observed in juvenile dogs and rats. In young beagles, 100 mg/kg ciprofloxacin, given daily for 4 weeks, caused degenerative articular changes of the knee joint. At 30 mg/kg, the effect on the joint was minimal. In a subsequent study in young beagle dogs, oral ciprofloxacin doses of 30 mg/kg and 90 mg/kg ciprofloxacin (approximately 1. 3- times and 3. 5- times the pediatric dose based upon comparative plasma AUCs) given daily for 2 weeks caused articular changes which were still observed by histopathology after a treatment-free period of 5 months. At 10 mg/kg (approximately 0. 6-times the pediatric dose based upon comparative plasma AUCs), no effects on joints were observed. This dose was also not associated with arthrotoxicity after an additional treatment-free period of 5 months. In another study, removal of weight bearing from the joint reduced the lesions but did not totally prevent them. Crystalluria, sometimes associated with secondary nephropathy, occurs in laboratory animals dosed with ciprofloxacin. This is primarily related to the reduced solubility of ciprofloxacin under alkaline conditions, which predominate in the urine of test animals; in man, crystalluria is rare since human urine is typically acidic. In rhesus monkeys, crystalluria without nephropathy was noted after single oral doses as low as 5 mg/kg (approximately 0. 07-times the highest recommended therapeutic dose based upon body surface area). After 6 months of intravenous dosing at 10 mg/kg/day, no nephropathological changes were noted; however, nephropathy was observed after dosing at 20 mg/kg/day for the same duration (approximately 0. 2-times the highest recommended therapeutic dose based upon body surface area). In dogs, ciprofloxacin at 3 mg/kg and 10 mg/kg by rapid intravenous injection (15 sec. ) produces pronounced hypotensive effects. These effects are considered to be related to histamine release, since they are partially antagonized by pyrilamine, an antihistamine. In rhesus monkeys, rapid intravenous injection also produces hypotension but the effect in this species is inconsistent and less pronounced. In mice, concomitant administration of nonsteroidal anti-inflammatory drugs such as phenylbutazone and indomethacin with quinolones has been reported to enhance the CNS stimulatory effect of quinolones. Ocular toxicity seen with some related drugs has not been observed in ciprofloxacin-treated animals.
CLINICAL STUDIES
The safety and efficacy of ciprofloxacin, 400 mg intravenously every 8 hours, in combination with piperacillin sodium, 50 mg/kg intravenously every 4 hours, for the empirical therapy of febrile neutropenic patients were studied in one large pivotal multicenter, randomized trial and were compared to those of tobramycin, 2 mg/kg intravenously every 8 hours, in combination with piperacillin sodium, 50 mg/kg intravenously every 4 hours. Clinical response rates observed in this study were as follows: The clinical success and bacteriologic eradication rates in the Per Protocol population were similar between ciprofloxacin and the comparator group as shown in Table 12. Table 12: Clinical Response Rates Outcomes Ciprofloxacin/Piperacillin N = 233 Success (%) Tobramycin/Piperacillin N = 237 Success (%) Clinical Resolution of Initial Febrile Episode with No Modifications of Empirical Regimen To be evaluated as a clinical resolution, patients had to have: (1) resolution of fever; (2) microbiological eradication of infection (if an infection was microbiologically documented); (3) resolution of signs/symptoms of infection; and (4) no modification of empirical antibiotic regimen. 63 (27%) 52 (21. 9%) Clinical Resolution of Initial Febrile Episode Including Patients with Modifications of Empirical Regimen 187 (80. 3%) 185 (78. 1%) Overall Survival 224 (96. 1%) 223 (94. 1%) Ciprofloxacin, administered IV 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 US, 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 in Table 13. Table 13: Clinical Success and Bacteriologic Eradication at Test of Cure (5 to 9 Days Post-Therapy) 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%] Bacteriologic Eradication by Patient at 5 to 9 Days Post-Treatment 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. 4% (178/211) 78. 3% (181/231) 95% CI [-1. 1%] Bacteriologic Eradication of the Baseline Pathogen at 5 to 9 Days Post-Treatment Escherichia coli 156/178 (88%) 161/179 (90%) Additional information The mean serum concentrations of ciprofloxacin associated with a statistically significant improvement in survival in the rhesus monkey model of inhalational anthrax are reached or exceeded in adult and pediatric patients receiving oral and intravenous regimens. Ciprofloxacin pharmacokinetics have been evaluated in various human populations. The mean peak serum concentration achieved at steady-state in human adults receiving 500 mg orally every 12 hours is 2. 97 mcg/mL, and 4. 56 mcg/mL following 400 mg intravenously every 12 hours. The mean trough serum concentration at steady-state for both of these regimens is 0. In a study of 10 pediatric patients between 6 and 16 years of age, the mean peak plasma concentration achieved is 8. 3 mcg/mL and trough concentrations range from 0. 09 mcg/mL to 0. 26 mcg/mL, following two 30-minute intravenous infusions of 10 mg/kg administered 12 hours apart. After the second intravenous infusion patients switched to 15 mg/kg orally every 12 hours achieve a mean peak concentration of 3. 6 mcg/mL after the initial oral dose. Long-term safety data, including effects on cartilage, following the administration of ciprofloxacin to pediatric patients are limited. Ciprofloxacin serum concentrations achieved in humans serve as a surrogate endpoint reasonably likely to predict clinical benefit and provide the basis for this indication. 1 A placebo-controlled animal study in rhesus monkeys exposed to an inhaled mean dose of 11 LD 50 5 50 B. anthracis max 6 7 More than 9,300 persons were recommended to complete a minimum of 60 days of antibacterial prophylaxis against possible inhalational exposure to B. anthracis A placebo-controlled animal study in African green monkeys exposed to an inhaled mean dose of 110 LD 50 50 Yersinia pestis Y.
REFERENCES
1. 2. 3. 4. 5. 6. 7. 8.
MEDICATION GUIDE
Ciprofloxacin (sip-row-FLOX-a-sin) Injection, USP in 5% Dextrose for Intravenous Infusion Read this Medication Guide before you start taking ciprofloxacin and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment. What is the most important information I should know about ciprofloxacin? Ciprofloxacin, a fluoroquinolone antibacterial medicine, can cause serious side effects. Some of these serious side effects can happen at the same time and could result in death. If you get any of the following serious side effects while you take ciprofloxacin, you should stop taking ciprofloxacin immediately and get medical help right away. Tendon rupture or swelling of the tendon (tendinitis). Tendon problems can happen in people of all ages who take ciprofloxacin. Symptoms of tendon problems may include: o o o The risk of getting tendon problems while you take ciprofloxacin is higher if you: o o o Tendon problems can happen in people who do not have the above risk factors when they take ciprofloxacin. Other reasons that can increase your risk of tendon problems can include: o o o Stop taking ciprofloxacin immediately and get medical help right away at the first sign of tendon pain, swelling or inflammation. Tendon rupture can happen while you are taking or after you have finished taking ciprofloxacin. Stop taking ciprofloxacin immediately and get medical help right away if you get any of the following signs or symptoms of a tendon rupture: o o o 2. Changes in sensation and possible nerve damage (Peripheral Neuropathy). 3. Central Nervous System (CNS) effects. 4. Worsening of myasthenia gravis (a problem that causes muscle weakness). What is ciprofloxacin? Ciprofloxacin is a fluoroquinolone antibacterial medicine used in adults age 18 years and older to treat certain infections caused by certain germs called bacteria. These bacterial infections include: Streptococcus pneumoniae. Ciprofloxacin is also used in children younger than 18 years of age Who should not take ciprofloxacin? Do not take ciprofloxacin if you: registered What should I tell my healthcare provider before taking ciprofloxacin? Before you take ciprofloxacin, tell your healthcare provider about all your medical conditions, including if you: o o Tell your healthcare provider about all the medicines you take, Ciprofloxacin and other medicines can affect each other causing side effects. Especially tell your healthcare provider if you take: registered registered registered registered registered registered registered registered registered registered registered registered registered registered registered registered registered registered registered registered registered registered registered registered registered registered registered Ask your healthcare provider for a list of these medicines if you are not sure. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. How should I take ciprofloxacin? o " What is the most important information I should know about ciprofloxacin? o What is the most important information I should know about ciprofloxacin? o " What is the most important information I should know about ciprofloxacin? o " What are the possible side effects of ciprofloxacin? o What should I avoid while taking ciprofloxacin? Do not What are the possible side effects of ciprofloxacin? Ciprofloxacin may cause serious side effects, including: " What is the most important information I should know about ciprofloxacin? Serious allergic reactions. o o o o o o o Liver damage (hepatotoxicity). o o o o o o o o o o o Aortic aneurysm and dissection. Intestine infection ( Clostridioides difficile Clostridioides difficile Serious heart rhythm changes (QT prolongation and torsade de pointes). o o o o Joint Problems. Sensitivity to sunlight (photosensitivity). " What should I avoid while taking ciprofloxacin? Changes in blood sugar. The most common side effects of ciprofloxacin include: Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all the possible side effects of ciprofloxacin. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store ciprofloxacin? Keep ciprofloxacin and all medicines out of the reach of children. General Information about the safe and effective use of ciprofloxacin. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use ciprofloxacin for a condition for which it is not prescribed. Do not give ciprofloxacin to other people, even if they have the same symptoms that you have. It may harm them. This Medication Guide summarizes the most important information about ciprofloxacin. If you would like more information about ciprofloxacin, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about ciprofloxacin that is written for healthcare professionals. For more information go to www. com What are the ingredients in ciprofloxacin? Active ingredient Inactive ingredients This Medication Guide has been approved by the U. Food and Drug Administration. Distributed by Hospira, Inc. , Lake Forest, IL 60045 USA LAB-1196-8. 0 Revised: 8/2022 Logo.

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