"The U.S. Food and Drug Administration today approved Zerbaxa (ceftolozane/tazobactam), a new antibacterial drug product, to treat adults with complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI).
The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of labeling:
- Tendon Effects [see WARNINGS AND PRECAUTIONS]
- Exacerbation of Myasthenia Gravis [see WARNINGS AND PRECAUTIONS]
- Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
- Other Serious and Sometimes Fatal Reactions [see WARNINGS AND PRECAUTIONS]
- Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
- Serious Adverse Reactions with Concomitant Theophylline [see WARNINGS AND PRECAUTIONS]
- Central Nervous System Effects [see WARNINGS AND PRECAUTIONS]
- Clostridium Difficile-Associated Diarrhea [see WARNINGS AND PRECAUTIONS]
- Peripheral Neuropathy [see WARNINGS AND PRECAUTIONS]
- Prolongation of the QT Interval [see WARNINGS AND PRECAUTIONS]
- Musculoskeletal Disorders in Pediatric Patients [see WARNINGS AND PRECAUTIONS]
- Photosensitivity/Phototoxicity [see WARNINGS AND PRECAUTIONS]
- Development of Drug Resistant Bacteria [see WARNINGS AND PRECAUTIONS]
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.
Clinical trials in patients with urinary tract infections enrolled 961 patients treated with 500 mg or 1000 mg CIPRO XR. The overall incidence, type and distribution of adverse reactions were similar in patients receiving both 500 mg and 1000 mg of CIPRO XR. The adverse reaction information from clinical studies does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.
In the clinical trial of uncomplicated UTIs, CIPRO XR (500 mg once daily) in 444 patients was compared to ciprofloxacin immediate-release tablets (250 mg twice daily) in 447 patients for 3 days. Discontinuations due to adverse reactions thought to be drug-related occurred in 0.2% (1/444) of patients in the CIPRO XR arm and in 0% (0/447) of patients in the control arm.
In the clinical trial of cUTI and acute uncomplicated pyelonephritis (AUP) defined as infections occurring in premenopausal, non-pregnant women with no known urological abnormalities or comorbidities, CIPRO XR (1000 mg once daily) in 517 patients was compared to ciprofloxacin immediate-release tablets (500 mg twice daily) in 518 patients for 7 to 14 days. Discontinuations due to adverse reactions thought to be drug-related occurred in 3.1% (16/517) of patients in the CIPRO XR arm and in 2.3% (12/518) of patients in the control arm. The most common reasons for discontinuation in the CIPRO XR arm were nausea/vomiting (4 patients) and dizziness (3 patients). In the control arm the most common reason for discontinuation was nausea/vomiting (3 patients).
In these clinical trials, the following events occurred in ≥ 2% of all CIPRO XR patients: nausea (4%), headache (3%), dizziness (2%), diarrhea (2%), vomiting (2%) and vaginal moniliasis (2%).
Adverse reactions, judged by investigators to be at least possibly drug-related, occurring in greater than or equal to 1% of all CIPRO XR treated patients were: nausea (3%), diarrhea (2%), headache (1%), dyspepsia (1%), dizziness (1%), and vaginal moniliasis (1%). Vomiting (1%) occurred in the 1000 mg group.
Table 2: Medically Important Adverse Reactions That
Occurred In < 1% of CIPRO XR Patients
|System Organ Class||Adverse Reactions|
|Body as a Whole||Abdominal pain
|Central Nervous System||Abnormal dreams
Convulsive seizures (including status epilepticus)
Depression (potentially culminating in self-injurious behavior, such as suicidal ideations/thoughts and attempted or completed suicide)
|Hepatobiliary Disorders||Liver function tests abnormal|
Kidney function abnormal
The following adverse reactions have been reported from worldwide marketing experience with fluoroquinolones, including CIPRO XR. 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 3).
Table 3: Postmarketing
Reports of Adverse Drug Reactions
|System Organ Class||Adverse Reactions|
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)
|Skin/Hypersensitivity||Acute generalized exanthematous pustulosis (AGEP)
Serum sickness-like reaction
Adverse Laboratory Changes
Changes in laboratory parameters while on CIPRO are listed below:
Other changes occurring were: elevation of serum gammaglutamyl transferase, elevation of serum amylase, reduction in blood glucose, elevated uric acid, decrease in hemoglobin, anemia, bleeding diathesis, increase in blood monocytes, and leukocytosis.
Read the Cipro XR (ciprofloxacin extended-release) Side Effects Center for a complete guide to possible side effects
Ciprofloxacin is an inhibitor of human cytochrome P450 1A2 (CYP1A2) mediated metabolism. Coadministration of CIPRO XR 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 coadministered drug.
Table 4: Drugs That are Affected by and Affecting
|Drugs That are Affected by CIPRO|
|Tizanidine||Contraindicated||Concomitant administration of tizanidine and CIPRO XR is contraindicated due to the potentiation of hypotensive and sedative effects of tizanidine [see CONTRAINDICATIONS].|
|Theophylline||Avoid Use (Plasma Exposure Likely to be Increased and Prolonged)||Concurrent administration of CIPRO XR 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]|
|Drugs Known to Prolong QT Interval||Avoid Use||Cipro XR 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 and Use in Specific Populations].|
|Oral antidiabetic drugs||Use with caution Glucose-lowering effect potentiated||Hypoglycemia sometimes severe has been reported when CIPRO XR 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. Monitor blood glucose when CIPRO XR is co-administered with oral antidiabetic drugs. [See ADVERSE REACTIONS]|
|Phenytoin||Use with caution Altered serum levels of phenytoin (increased and decreased)||To avoid the loss of seizure control associated with decreased phenytoin levels and to prevent phenytoin overdose-related adverse reactions upon CIPRO XR discontinuation in patients receiving both agents, monitor phenytoin therapy, including phenytoin serum concentration during and shortly after coadministration of CIPRO XR with phenytoin.|
|Cyclosporine||Use with caution (transient elevations in serum creatinine)||Monitor renal function (in particular serum creatinine) when CIPRO XR is co-administered with cyclosporine.|
|Anti-coagulant drugs||Use with caution (Increase in anticoagulant effect)||The risk may vary with the underlying infection, age and general status of the patient so that the contribution of CIPRO XR 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 CIPRO XR with an oral anti-coagulant (for example, warfarin).|
|Methotrexate||Use with caution Inhibition of methotrexate renal tubular transport potentially leading to increased methotrexate plasma levels||Potential increase in the risk of methotrexate associated toxic reactions. Therefore, carefully monitor patients under methotrexate therapy when concomitant CIPRO XR 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 coadministration with CIPRO XR [see WARNINGS AND PRECAUTIONS].|
|Clozapine||Use with caution||Careful monitoring of clozapine associated adverse reactions and appropriate adjustment of clozapine dosage during and shortly after co-administration with CIPRO XR 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 Two-fold increase in exposure||Monitor for sildenafil toxicity [see Pharmacokinetics].|
|Duloxetine||Avoid Use Five-fold increase in duloxetine exposure||If unavoidable monitor, for duloxetine toxicity|
|Caffeine/Xanthine Derivatives||Use with caution Reduced clearance resulting in elevated levels and prolongation of serum half-life||CIPRO XR inhibits the formation of paraxanthine after caffeine administration (or pentoxifylline containing products). Monitor for xanthine toxicity and adjust dose as necessary.|
|Drug(s) Affecting Pharmacokinetics of CIPRO XR|
|Antacids, Sucralfate, Multivitamins and Other Products Containing Multivalent||CIPRO XR should be taken at least two hours before or six hours after Multivalent cation-containing products||Decrease CIPRO XR absorption, resulting in lower serum and urine levels considerably lower than desired for concurrent administration of these agents with CIPRO XR|
|Cations (magnesium/aluminum antacids; polymeric phosphate binders (for example, sevelamer, lanthanum carbonate); sucralfate; Videx® (didanosine) chewable/buffered tablets or pediatric powder; other highly buffered drugs; or products containing calcium, iron, or zinc and dairy products)||administration. [See DOSAGE AND ADMINISTRATION]|
|Probenecid||Use with caution (interferes with renal tubular secretion of CIPRO XR and increases CIPRO XR serum levels)||Potentiation of CIPRO XR toxicity may occur.|
Read the Cipro XR Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 2/12/2015
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