Piperacillin And Tazobactam

Use entire contents of pharmacy bulk package bottle promptly. Discard unused portion after 24 hours if stored at room temperature (20°C to 25°C [68°F to 77°F]), or after 48 hours if stored at refrigerated temperature (2°C to 8°C [36°F to 46°F]).

Reconstitute the pharmacy bulk package bottle with exactly 152 mL of a compatible reconstitution diluent, listed below, to a concentration of 200 mg/mL of piperacillin and 25 mg/mL of tazobactam. Shake well until dissolved. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to and during administration whenever solution and container permit.

9% sodium chloride for injection Sterile water for injection ‡ Dextrose 5% Bacteriostatic saline/parabens Bacteriostatic water/parabens Bacteriostatic saline/benzyl alcohol Bacteriostatic water/benzyl alcohol Dilution of the Reconstituted Piperacillin and Tazobactam for Injection Solution for Adult Patients and Pediatric Patients Weighing over 40 kg Reconstituted piperacillin and tazobactam for injection solutions in pharmacy bulk bottles should be further diluted (recommended volume per dose of 50 mL to 150 mL) in a compatible intravenous solution listed below.

Administer by infusion over a period of at least 30 minutes. During the infusion it is desirable to discontinue the primary infusion solution. 9% sodium chloride for injection Sterile water for injection ‡ (Maximum recommended volume per dose of sterile water for injection is 50 mL) Dextran 6% in saline Dextrose 5% Lactated Ringer’s Solution is not compatible with Piperacillin and Tazobactam.

Piperacillin and tazobactam for injection should not be mixed with other drugs in a syringe or infusion bottle since compatibility has not been established. Piperacillin and tazobactam for injection is not chemically stable in solutions that contain only sodium bicarbonate and solutions that significantly alter the pH.

Piperacillin and tazobactam for injection should not be added to blood products or albumin hydrolysates. Parenteral drug products should be inspected visually for particulate matter or discoloration prior to administration, whenever solution and container permit.

4)]. Reconstituted piperacillin and tazobactam for injection solutions for bulk bottles should be further diluted in a compatible intravenous solution listed above. 1. 4 )] . 2. Reconstitute bottle with a compatible reconstitution diluent, as listed above under the subheading “Compatible Reconstitution Diluents for Pharmacy Bulk Bottles,” using the appropriate volume of diluent, as listed in table 4 below.

Following the addition of the diluent, shake the pharmacy bulk bottle until the powder is completely dissolved. 5 g tazobactam) 152 mL 225 mg/mL (200 mg/mL piperacillin and 25 mg/mL tazobactam) 3. Calculate the required volume (mL) of reconstituted piperacillin and tazobactam for injection solution based on the required dose.

4. Aseptically withdraw the required volume of reconstituted piperacillin and tazobactam for injection solution from the pharmacy bulk bottle. 5 mg/mL to 10 mg/mL) in a compatible intravenous solution (as listed above) in an appropriately sized syringe or IV bag.

5. Administer the diluted piperacillin and tazobactam for injection solution by infusion over a period of at least 30 minutes (a programmable syringe or infusion pump is recommended). During the infusion it is desirable to discontinue the primary infusion solution.

Stability of Piperacillin and Tazobactam for Injection Following Reconstitution and Dilution Piperacillin and tazobactam for injection reconstituted from pharmacy bulk package bottles is stable in glass and plastic contain-ers (plastic syringes, IV bags and tubing) when used with compatible diluents.

The pharmacy bulk package bottle should NOT be frozen after reconstitution. Pharmacy bulk package bottles should be used immediately after reconstitution. Discard any unused portion after storage for 24 hours at room temperature (20°C to 25°C [68°F to 77°F]), or after storage for 48 hours at refrigerated temperature (2°C to 8°C [36°F to 46°F]).

Stability studies in the IV bags have demonstrated chemical stability (potency, pH of reconstituted solution and clarity of solution) for up to 24 hours at room temperature and up to one week at refrigerated temperature. Piperacillin and tazobactam for injection contains no preservatives.

Appropriate consideration of aseptic technique should be used. Piperacillin and tazobactam for injection reconstituted from pharmacy bulk package bottles can be used in ambulatory intravenous infusion pumps. Stability of piperacillin and tazobactam for injection in an ambulatory intravenous infusion pump has been demonstrated for a period of 12 hours at room temperature.

5 mL or 25 mL. One-day supply of dosing solution were aseptically transferred into the medication reservoir (IV bags or cartridge). The reservoir was fitted to a preprogrammed ambulatory intravenous infusion pump per the manufacturer's instructions.

Stability of piperacillin and tazobactam for injection is not affected when administered using an ambulatory intravenous infusion pump. 6 Compatibility with Aminoglycosides Due to the in vitro inactivation of aminoglycosides by piperacillin, piperacillin and tazobactam for injection and aminoglycosides are recommended for separate administration.

1 )] . 9% sodium chloride or 5% dextrose a Diluent volumes apply only to bulk pharmacy containers b The concentration ranges in Table 5 are based on administration of the aminoglycoside in divided doses (10 to 15 mg/kg/day in two daily doses for amikacin and 3 to 5 mg/kg/day in three daily doses for gentamicin).

Administration of amikacin or gentamicin in a single daily dose or in doses exceeding those stated above via Y-site with piperacillin and tazobactam for injection has not been evaluated. See package insert for each aminoglycoside for complete Dosage and Administration instructions.

Only the concentration and diluents for amikacin or gentamicin with the dosages of piperacillin and tazobactam for injection listed above have been established as compatible for co-administration via Y-site infusion. Simultaneous co-administration via Y-site infusion in any manner other than listed above may result in inactivation of the aminoglycoside by piperacillin and tazobactam for injection.

Piperacillin and tazobactam for injection is not compatible with tobramycin for simultaneous coadministration via Y-site infusion. Compatibility of piperacillin and tazobactam for injection with other aminoglycosides has not been established.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Clinical Trials in Pediatric Patients Clinical studies of piperacillin and tazobactam in pediatric patients suggest a similar safety profile to that seen in adults. 5 mg/kg) every 8 hours. 1%) in the cefotaxime/metronidazole group. 9%) in the cefotaxime/metronidazole group discontinued due to an adverse event.

In a retrospective, cohort study, 140 pediatric patients 2 months to less than 18 years of age with nosocomial pneumonia were treated with piperacillin and tazobactam and 267 patients were treated with comparators (which included ticarcillin-clavulanate, carbapenems, ceftazidime, cefepime, or ciprofloxacin).

5 mg/kg IV every 6 hours. 2 Postmarketing Experience In addition to the adverse drug reactions identified in clinical trials in Table 6 and Table 7, the following adverse reactions have been identified during post-approval use of piperacillin and tazobactam.

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. Hepatobiliary —hepatitis, jaundice Hematologic —hemolytic anemia, agranulocytosis, pancytopenia Immune —hypersensitivity reactions, anaphylactic/anaphylactoid reactions (including shock), hemophagocytic lymphohistiocytosis (HLH), acute myocardial ischemia with or without myocardial infarction may occur as part of an allergic reaction Renal —interstitial nephritis Nervous system disorders - seizures Psychiatric disorders —delirium Respiratory —eosinophilic pneumonia Skin and Appendages —erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), dermatitis exfoliative, and linear IgA bullous dermatosis Musculoskeletal —rhabdomyolysis Postmarketing experience with piperacillin and tazobactam in pediatric patients suggests a similar safety profile to that seen in adults.

5 )].

7 ) • Clostridioides difficile associated diarrhea: evaluate patients if diarrhea occurs. 1 Hypersensitivity Adverse Reactions Serious and occasionally fatal hypersensitivity (anaphylactic/anaphylactoid) reactions (including shock) have been reported in patients receiving therapy with piperacillin and tazobactam for injection.

These reactions are more likely to occur in individuals with a history of penicillin, cephalosporin, or carbapenem hypersensitivity or a history of sensitivity to multiple allergens. Before initiating therapy with piperacillin and tazobactam for injection, careful inquiry should be made concerning previous hypersensitivity reactions.

If an allergic reaction occurs, piperacillin and tazobactam for injection should be discontinued and appropriate therapy instituted. 2 Severe Cutaneous Adverse Reactions Piperacillin and tazobactam for injection may cause severe cutaneous adverse reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis.

If patients develop a skin rash they should be monitored closely and piperacillin and tazobactam for injection discontinued if lesions progress. 3 Hemophagocytic Lymphohistiocytosis Cases of hemophagocytic lymphohistiocytosis (HLH) have been reported in pediatric and adult patients treated with piperacillin and tazobactam for injection.

Signs and symptoms of HLH may include fever, rash, lymphadenopathy, hepatosplenomegaly and cytopenia. If HLH is suspected, discontinue piperacillin and tazobactam for injection immediately and institute appropriate management. 2) ]. If signs or symptoms of rhabdomyolysis such as muscle pain, tenderness or weakness, dark urine, or elevated creatine phosphokinase are observed, discontinue Piperacillin and tazobactam for injection and initiate appropriate therapy.

5 Hematologic Adverse Reactions Bleeding manifestations have occurred in some patients receiving beta-lactam drugs, including piperacillin. These reactions have sometimes been associated with abnormalities of coagulation tests such as clotting time, platelet aggregation and prothrombin time, and are more likely to occur in patients with renal failure.

If bleeding manifestations occur, piperacillin and tazobactam for injection should be discontinued and appropriate therapy instituted. The leukopenia/neutropenia associated with piperacillin and tazobactam for injection administration appears to be reversible and most frequently associated with prolonged administration.

1 )] . 6 Central Nervous System Adverse Reactions As with other penicillins, piperacillin and tazobactam for injection may cause neuromuscular excitability or seizures. Patients receiving higher doses, especially patients with renal impairment may be at greater risk for central nervous system adverse reactions.

2 ) ]. 1 )]. Based on this study, alternative treatment options should be considered in the critically ill population. 3 )]. 3 )]. 35 mEq (54 mg) of Na + (sodium) per gram of piperacillin in the combination product. This should be considered when treating patients requiring restricted salt intake.

Periodic electrolyte determinations should be performed in patients with low potassium reserves, and the possibility of hypokalemia should be kept in mind with patients who have potentially low potassium reserves and who are receiving cytotoxic therapy or diuretics.

9 Clostridioides difficile Associated Diarrhea Clostridioides difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including piperacillin and tazobactam, and may range in severity from mild diarrhea to fatal colitis.

Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile . C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy.

CDAD must be considered in all patients who present with diarrhea following antibacterial drug use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated.

10 Development of Drug-Resistant Bacteria Prescribing piperacillin and tazobactam in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of development of drug-resistant bacteria.