Stability data:
|
| Drug |
Stability
Refrigerated |
Stability
Room Temp. |
Reconstituted
Vial/Powder |
Notes |
| Ciprofloxacin |
Store in a refrigerator, 2 to 8°C (36 to 46°F) |
Store at 20 to 25°C (68 to 77°F) |
Solution |
Protect from light, avoid excessive heat, protect from freezing. |
EXP: 14 DAYS (RT/REF).
Cipro 400mg ivpb produces the same levels as 500mg tablet.
DOSAGE AND ADMINISTRATION – ADULTS
Ciprofloxacin injection should be administered to adults by intravenous infusion over a period of 60 minutes at dosages described in the Dosage Guidelines table. Slow infusion of a dilute solution into a larger vein will minimize patient discomfort and reduce the risk of venous irritation. (See Preparation of Ciprofloxacin Injection for Administration section.)
The determination of dosage for any particular patient must take into consideration the severity and nature of the infection, the susceptibility of the causative microorganism, the integrity of the patient’s host-defense mechanisms, and the status of renal and hepatic function.
ADULT DOSAGE GUIDELINES
| Infection* |
Severity |
Dose |
Frequency |
Usual Duration |
| Urinary Tract |
Mild/Moderate |
200 mg |
q12h |
7-14 Days |
| |
Severe/Complicated |
400 mg |
q12h |
7-14 Days |
| Lower Respiratory |
Mild/Moderate |
400 mg |
q12h |
7-14 Days |
| Tract |
Severe/Complicated |
400 mg |
q8h |
7-14 Days |
| Nosocomial |
Mild/Moderate/Severe |
400 mg |
q8h |
10-14 Days |
| Pneumonia |
|
|
|
|
| Skin and Skin |
Mild/Moderate |
400 mg |
q12h |
7-14 Days |
| Structure |
Severe/Complicated |
400 mg |
q8h |
7-14 Days |
| Bone and Joint |
Mild/Moderate |
400 mg |
q12h |
≥4-6 Weeks |
| |
Severe/Complicated |
400 mg |
q8h |
≥4-6 Weeks |
| Intra-Abdominal^ |
Complicated |
400 mg |
q12h |
7-14 Days |
| Acute Sinusitis |
Mild/Moderate |
400 mg |
q12h |
10 Days |
Chronic Bacterial
Prostatitis |
Mild/Moderate |
400 mg |
q12h |
28 Days |
Empirical Therapy in
Febrile |
Severe
Ciprofloxacin |
400 mg |
q8h |
|
| Neutropenic Patients |
+
Piperacillin |
50 mg/kg |
q4h |
7-14 Days |
| |
|
Not to exceed
24 g/day |
|
|
Inhalational Anthrax
(Post-Exposure)^^ |
400 mg |
q12h |
60 Days |
*DUE TO THE DESIGNATED PATHOGENS
^used in conjunction with metronidazole. (See product labeling for prescribing information.)
^^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. Total duration of ciprofloxacin administration (IV or oral) for inhalational anthrax (post-exposure) is 60 days. |
Ciprofloxacin injection should be administered by intravenous infusion over a period of 60 minutes.
Conversion of IV to Oral Dosing in Adults: Ciprofloxacin tablets and oral suspension for oral administration are available. Parenteral therapy may be switched to oral ciprofloxacin when the condition warrants, at the discretion of the physician.
| Equivalent AUC Dosing Regimens |
| Ciprofloxacin Oral Dosage |
Equivalent Ciprofloxacin Injection Dosage |
| 250 mg Tablet q 12 h |
200 mg IV q 12 h |
| 500 mg Tablet q 12 h |
400 mg IV q 12 h |
| 750 mg Tablet q 12 h |
400 mg IV q 8 h |
Adults with Impaired Renal Function: Ciprofloxacin is eliminated primarily by renal excretion; however, the drug is also metabolized and partially cleared through the biliary system of the liver and through the intestine. These alternative pathways of drug elimination appear to compensate for the reduced renal excretion in patients with renal impairment. Nonetheless, some modification of dosage is recommended for patients with severe renal dysfunction. The following table provides dosage guidelines for use in patients with renal impairment:
| RECOMMENDED STARTING AND MAINTENANCE DOSES |
| FOR PATIENTS WITH IMPAIRED RENAL FUNCTION |
| Creatinine Clearance (mL/min) |
Dosage |
| >30 |
See usual dosage |
| 5-29 |
200-400 mg q 18-24 hr |
When only the serum creatinine concentration is known, the following formula may be used to estimate creatinine clearance:
Men: Creatinine clearance (mL/min) = Weight (kg) x (140 – age) / [72 x serum creatinine (mg/dL)]
Women: 0.85 x the value calculated for men.
The serum creatinine should represent a steady state of renal function.
For patients with changing renal function or for patients with renal impairment and hepatic insufficiency, careful monitoring is suggested.
DOSAGE AND ADMINISTRATION – PEDIATRICS
Ciprofloxacin injection should be administered by intravenous infusion as described in the Dosage Guidelines table.
An increased incidence of adverse events compared to controls, including events related to joints and/or surrounding tissues, has been observed. (See package insert for ADVERSE REACTIONS and CLINICAL STUDIES.)
Dosing and initial route of therapy (i.e., IV or oral) for complicated urinary tract infection or pyelonephritis should be determined by the severity of the infection. In the clinical trial, pediatric patients with moderate to severe infection were initiated on 6 to 10 mg/kg IV every 8 hours and allowed to switch to oral therapy (10 to 20 mg/kg every 12 hours), at the discretion of the physician.
PEDIATRIC DOSAGE GUIDELINES
| Infection |
Route of Administration |
Dose (mg/kg) |
Frequency |
Total Duration |
| Complicated Urinary Tract or Pyelonephritis (patients from 1 to 17 years of age) |
Intravenous |
6 to 10 mg/kg (maximum 400 mg per dose; not to be exceeded even in patients weighing > 51 kg) |
Every 8 hours |
10-21 days* |
| Oral |
10 mg/kg to 20 mg/kg (maximum 750 mg per dose; not to be exceeded even in patients weighing > 51 kg) |
Every 12 hours |
| Inhalational Anthrax (Post-Exposure) ** |
Intravenous |
10 mg/kg (maximum 400 mg per dose) |
Every 12 hours |
60 days |
| Oral |
15 mg/kg (maximum 500 mg per dose) |
Every 12 hours |
* The total duration of therapy for complicated urinary tract infection and pyelonephritis in the clinical trial was determined by the physician. The mean duration of treatment was 11 days (range 10 to 21 days).
** Drug administration should begin as soon as possible after suspected or confirmed exposure to Bacillus anthracis spores. 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.
Preparation of Ciprofloxacin Injection for Administration
Vials (Injection Concentrate): THIS PREPARATION MUST BE DILUTED BEFORE USE. The intravenous dose should be prepared by aseptically withdrawing the concentrate from the vial of ciprofloxacin injection. This should be diluted with a suitable intravenous solution to a final concentration of 1 to 2 mg/mL. (See COMPATIBILITY AND STABILITY.) The resulting solution should be infused over a period of 60 minutes by direct infusion or through a Y-type intravenous infusion set which may already be in place.
If the Y-type or “piggyback” method of administration is used, it is advisable to discontinue temporarily the administration of any other solutions during the infusion of ciprofloxacin injection. If the concomitant use of ciprofloxacin injection and another drug is necessary each drug should be given separately in accordance with the recommended dosage and route of administration for each drug.
COMPATIBILITY AND STABILITY
Ciprofloxacin injection 1% (10 mg/mL), when diluted with the following intravenous solutions to concentrations of 0.5 to 2 mg/mL, is stable for up to 14 days at refrigerated or room temperature storage.
0.9% Sodium Chloride Injection
5% Dextrose Injection
Sterile Water for Injection
10% Dextrose for Injection
5% Dextrose and 0.225% Sodium Chloride for Injection
5% Dextrose and 0.45% Sodium Chloride for Injection
Lactated Ringer’s for Injection
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
HOW SUPPLIED
Ciprofloxacin Injection USP is available as a clear, colorless to slightly yellowish solution. Ciprofloxacin Injection is available in 200 mg and 400 mg strengths. The concentrate is supplied in vials as follows:
NDC 55390-197-01 – 200 mg, 1%, 20 mL Vial; individually boxed
NDC 55390-198-01 – 400 mg, 1%, 40 mL Vial; individually boxed
STORAGE
Store between 5° to 30°C (41° to 86°F).
Protect from light, avoid excessive heat, protect from freezing.
| INHALATIONAL ANTHRAX — 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. (See DOSAGE AND ADMINISTRATION .) 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 0.2 mcg/mL. 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 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. (For additional information, see PRECAUTIONS: Pediatric Use.) Ciprofloxacin serum concentrations achieved in humans serve as a surrogate endpoint reasonably likely to predict clinical benefit and provide the basis for this indication.4
A placebo-controlled animal study in rhesus monkeys exposed to an inhaled mean dose of 11 LD50 (~5.5 x 105) spores (range 5 to 30 LD50) of B. anthracis was conducted. The minimal inhibitory concentration (MIC) of ciprofloxacin for the anthrax strain used in this study was 0.08 mcg/mL. In the animals studied, mean serum concentrations of ciprofloxacin achieved at expected Tmax (1 hour post-dose) following oral dosing to steady-state ranged from 0.98 to 1.69 mcg/mL. Mean steady-state trough concentrations at 12 hours post-dose ranged from 0.12 to 0.19 mcg/mL5. Mortality due to anthrax for animals that received a 30-day regimen of oral ciprofloxacin beginning 24 hours post-exposure was significantly lower (1/9), compared to the placebo group (9/10) [p=0.001]. The one ciprofloxacin-treated animal that died of anthrax did so following the 30-day drug administration period6.
More than 9300 persons were recommended to complete a minimum of 60 days of antibiotic prophylaxis against possible inhalational exposure to B. anthracis during 2001. Ciprofloxacin was recommended to most of those individuals for all or part of the prophylaxis regimen. Some persons were also given anthrax vaccine or were switched to alternative antibiotics. No one who received ciprofloxacin or other therapies as prophylactic treatment subsequently developed inhalational anthrax. The number of persons who received ciprofloxacin as all or part of their post-exposure prophylaxis regimen is unknown.
Among the persons surveyed by the Centers for Disease Control and Prevention, over 1000 reported receiving ciprofloxacin as sole post-exposure prophylaxis for inhalational anthrax. Gastrointestinal adverse events (nausea, vomiting, diarrhea, or stomach pain), neurological adverse events (problems sleeping, nightmares, headache, dizziness or lightheadedness) and musculoskeletal adverse events (muscle or tendon pain and joint swelling or pain) were more frequent than had been previously reported in controlled clinical trials. This higher incidence, in the absence of a control group, could be explained by a reporting bias, concurrent medical conditions, other concomitant medications, emotional stress or other confounding factors, and/or a longer treatment period with ciprofloxacin. Because of these factors and limitations in the data collection, it is difficult to evaluate whether the reported symptoms were drug-related. |
Bedford Laboratories™
Bedford, OH 44146
November 2007 CPRO-P02
|
