The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of labeling:
Clinical Trials Experience
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.
During clinical investigations with oral and parenteral CIPRO IV, 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 CIPRO IV: 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 |
|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)
|Gastrointestinal|| Ileus |
|Hemic/Lymphatic|| Agranulocytosis |
Prolongation of Prothrombin Time
Petechia cipro 1a pharma 100 mg alkohol
|Metabolic/Nutritional|| Hyperglycemia |
|Musculoskeletal|| Arthralgia |
|Ren al/U rogenital|| Renal Failure |
|Respiratory|| Respiratory Arrest |
|Skin/Hypersensitivity|| Allergic Reactions |
Anaphylactic Reactions including life-threatening anaphylactic shock
Toxic Epidermal Necrolysis
| extremities |
|Special Senses|| Decreased Visual Acuity |
Disturbed Vision (diplopia, chromatopsia, and photopsia)
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 CIPRO (Intravenous and Intravenous/Oral. sequential) with intravenous beta-lactam control antibiotics, the CNS adverse reaction profile of CIPRO was comparable to that of the control drugs.
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 alkohol 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 Reactions1 as Assessed by the IPSC
|All Patients (within 6 weeks)||31/335 (9.3%)||21/349 (6%)|
|95% Confidence Interval2|| |
|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 Interval2|| |
(-0.6%, + 9.1%)
| 1Included: 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) |
2The study was designed to demonstrate that the arthropathy rate for the CIPRO 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.
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 ciprofloxacintreated 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 1.8%.
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 5-17 years). Sixty seven patients received CIPRO IV 10 mg/kg/dose every 8 hours for one week followed by CIPRO tablets 20 mg/kg/dose every 12 hours to complete 10-21 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 10-21 days. Periodic musculoskeletal assessments were conducted by treatment-blinded examiners. Patients were followed for an average of 23 days after completing treatment (range 0- 93 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 CIPRO 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 CIPRO IV. 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
|Central Nervous System|| Hypertonia |
Exacerbation of myasthenia gravis
|Hemic/Lymphatic|| Pancytopenia (life threatening or fatal outcome) |
|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 |
|Psychiatric Disorders|| Agitation |
|Skin/Hypersensitivity|| Acute generalize exanthematous pustulosis (AGEP) |
Fixed eruption Serum sickness-like reaction
|Special Senses|| Anosmia |
Adverse Laboratory Changes
Changes in laboratory parameters while on CIPRO IV therapy are listed below:
- Hepatic-Elevations of AST (SGOT), ALT (SGPT), alkaline phosphatase, LDH, and serum bilirubin
- Hematologic-Elevated eosinophil and platelet counts, decreased platelet counts, hemoglobin and/or hematocrit
- Renal-Elevations of serum creatinine, BUN, and uric acid
- Other elevations of serum creatine phosphokinase, serum theophylline (in patients receiving theophylline concomitantly), blood glucose, and triglycerides
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.
Read the entire FDA prescribing information for Cipro IV (Ciprofloxacin IV)
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