Frozen Premixed Medications

ZOSYN (piperacillin and tazobactam) Injection
Indications and Important Risk Information

Indications

ZOSYN Injection is a combination of piperacillin, a penicillin-class antibacterial and tazobactam, a beta-lactamase inhibitor, indicated for the treatment of:

• Intra-abdominal infections in adult and pediatric patients 2 months of age and older
• Nosocomial pneumonia in adult and pediatric patients 2 months of age and older
• Skin and skin structure infections in adults
• Female pelvic infections in adults
• Community-acquired pneumonia in adults

To reduce the development of drug-resistant bacteria and maintain the effectiveness of ZOSYN Injection and other antibacterial drugs, ZOSYN Injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.

Important Risk Information

• Contraindications: ZOSYN Injection is contraindicated in patients with a history of allergic reactions to any of the penicillins, cephalosporins, or beta-lactamase inhibitors.
• Hypersensitivity Adverse Reactions: Serious and occasionally fatal hypersensitivity (anaphylactic/anaphylactoid) reactions (including shock) have been reported in patients receiving therapy with ZOSYN 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. If an allergic reaction occurs, ZOSYN Injection should be discontinued and appropriate therapy instituted.
• Severe Cutaneous Adverse Reactions: ZOSYN 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 ZOSYN Injection discontinued if lesions progress.
• Hemophagocytic Lymphohistiocytosis (HLH): Cases of HLH have been reported in pediatric and adult patients treated with ZOSYN Injection. Signs and symptoms of HLH may include fever, rash, lymphadenopathy, hepatosplenomegaly and cytopenia. If HLH is suspected, discontinue ZOSYN Injection immediately and institute appropriate management.
• Rhabdomyolysis: Rhabdomyolysis has been reported with the use of piperacillin and tazobactam. If signs or symptoms of rhabdomyolysis such as muscle pain, tenderness or weakness, dark urine, or elevated creatine phosphokinase are observed, discontinue ZOSYN Injection and initiate appropriate therapy.
• 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, ZOSYN Injection should be discontinued and appropriate therapy instituted. The leukopenia/neutropenia associated with ZOSYN Injection administration appears to be reversible and most frequently associated with prolonged administration. Periodic assessment of hematopoietic function should be performed, especially with prolonged therapy, i.e., ≥ 21 days.
• Central Nervous System Adverse Reactions: As with other penicillins, ZOSYN 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. Closely monitor patients with renal impairment or seizure disorders for signs and symptoms of neuromuscular excitability or seizures.
• Nephrotoxicity in Critically Ill Patients: The use of ZOSYN Injection was found to be an independent risk factor for renal failure and was associated with delayed recovery of renal function as compared to other beta-lactam antibacterial drugs in critically ill patients. Alternative treatment options should be considered in the critically ill population. If alternative treatment options are inadequate or unavailable, monitor renal function during treatment with ZOSYN Injection.
• Clostridioides difficile-associated diarrhea (CDAD): CDAD has been reported with use of nearly all antibacterial agents, including ZOSYN Injection, and may range in severity from mild diarrhea to fatal colitis. 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.
• Adverse Reactions: The most common adverse reactions (incidence >5%) are diarrhea, constipation, nausea, headache, and insomnia.
• Renal Impairment: In patients with creatinine clearance ≤ 40 mL/min and dialysis patients (hemodialysis and CAPD), the intravenous dose of ZOSYN Injection should be reduced to the degree of renal function impairment.

• Drug Interactions:

  • ZOSYN Injection administration can significantly reduce tobramycin concentrations in hemodialysis patients. Monitor tobramycin concentrations in these patients.
  • Probenecid prolongs the half-lives of piperacillin and tazobactam and should not be co-administered with ZOSYN Injection unless the benefit outweighs the risk.
  • Co-administration of ZOSYN Injection with vancomycin may increase the incidence of acute kidney injury. Monitor kidney function in patients receiving ZOSYN Injection and vancomycin.
  • Monitor coagulation parameters in patients receiving ZOSYN Injection and heparin or oral anticoagulants.
  • ZOSYN Injection may prolong the neuromuscular blockade of vecuronium and other non-depolarizing neuromuscular blockers. Monitor for adverse reactions related to neuromuscular blockade.

  Please click for accompanying full Prescribing Information for ZOSYN (piperacillin and tazobactam) Injection.

Vancomycin Injection, USP
Indications and Important Risk Information

Indications

Vancomycin Injection is a glycopeptide antibacterial indicated for the treatment of the following infections in adult and pediatric patients for whom appropriate dosing with this formulation can be achieved:  

• Septicemia
• Infective Endocarditis
• Skin and Skin Structure Infections
• Bone Infections
• Lower Respiratory Tract Infections

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Vancomycin Injection and other antibacterial drugs, Vancomycin Injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.

Important Risk Information

• Contraindications:  Vancomycin Injection is contraindicated in patients with known hypersensitivity to vancomycin.  Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products.

• Infusion Reactions:  Hypotension, including shock and cardiac arrest, wheezing, dyspnea, urticaria or pruritus, muscular and chest pain may occur with rapid Vancomycin Injection administration.  The reactions may be more severe in pediatric patients.  Rapid intravenous administration may also be associated with “vancomycin infusion reaction”, which manifests as pruritus and erythema that involves the face, neck and upper body.  There have been reports that the frequency of infusion-related reactions increases with the concomitant administration of anesthetic agents.  Infusion-related adverse reactions are related to both the concentration and rate of administration.

  Administer Vancomycin Injection over a period of 60 minutes or greater prior to administration of anesthetic agents when feasible.  Stopping the infusion usually results in prompt cessation of these reactions.

• Nephrotoxicity:  Vancomycin Injection can result in acute kidney injury (AKI), including acute renal failure.  The risk of AKI increases with higher vancomycin serum levels, prolonged exposure, concomitant administration of other nephrotoxic drugs, concomitant administration of piperacillin-tazobactam, volume depletion, pre-existing renal impairment and in critically ill patients and patients with co-morbid conditions that predispose to renal impairment.  Monitor serum vancomycin concentrations and renal function in all patients.  If AKI occurs, discontinue Vancomycin Injection, or reduce the dose.
• Ototoxicity:  Has occurred in patients receiving Vancomycin Injection.  It may be reversible or permanent.  Ototoxicity manifests as tinnitus, hearing loss, dizziness or vertigo.  The risk is higher in older patients, patients who are receiving higher doses, who have an underlying hearing loss, who are receiving concomitant therapy with another ototoxic agent, or who have underlying renal impairment.  Monitor serum vancomycin concentrations and renal function in all patients.  Discontinue Vancomycin Injection if ototoxicity occurs.  Serial tests of auditory function may be helpful in order to minimize the risk.
• Severe Dermatologic Reactions:  Toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and linear IgA bullous dermatosis (LABD) have been reported. Cutaneous signs or symptoms reported include skin rashes, mucosal lesions, and blisters. Discontinue Vancomycin Injection at the first appearance of signs and symptoms of TEN, SJS, DRESS, AGEP, or LABD.
• Clostridioides difficile associated diarrhea (CDAD):  CDAD has been reported with use of nearly all antibacterial agents, including Vancomycin Injection, and may range in severity from mild diarrhea to fatal colitis.  CDAD must be considered in all patients who present with diarrhea following antibiotic use.  If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued.  Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
• Hemorrhagic Occlusive Retinal Vasculitis (HORV):  HORV, including permanent loss of vision, occurred in patients receiving intracameral or intravitreal administration of vancomycin during or after cataract surgery.  The safety and efficacy of vancomycin administered by the intracameral or the intravitreal route have not been established.
• Neutropenia:  Reversible neutropenia has been reported.  Patients who will undergo prolonged therapy with vancomycin or those who are receiving concomitant drugs that may cause neutropenia should have periodic monitoring of the leukocyte count.  Neutropenia appears to be promptly reversible when vancomycin is discontinued.
• Phlebitis and Other Administration Site Reactions:  Inflammation at the injection site has been reported.  Vancomycin is irritating to tissue and must be given by a secure intravenous route of administration.  Thrombophlebitis may occur, the frequency and severity of which can be minimized by slow infusion of the drug and by rotation of venous access sites.
• Adverse Reactions:  The most common adverse reactions are anaphylaxis, “vancomycin infusion reaction”, acute kidney injury, hearing loss, neutropenia.
• Drug Interactions:
  • Anesthetic Agents: Concomitant administration of vancomycin and anesthetic agents has been associated with erythema and histamine-like flushing.
  • Piperacillin/Tazobactam: Increased incidence of acute kidney injury in patients receiving concomitant piperacillin/tazobactam as compared to vancomycin alone. Monitor kidney function in patients.
• Renal Impairment: Dosage adjustment of VancomycinInjection must be made in patients with impaired renal function. Measure vancomycin serum concentrations to guide intravenous therapy, especially in patients with impaired renal function or fluctuating renal function.

Please click for accompanying full Prescribing Information for Vancomycin Injection, USP.

Daptomycin in 0.9% Sodium Chloride Injection
Indications and Important Risk Information

Indications

Daptomycin in Sodium Chloride Injection is a lipopeptide antibacterial indicated for the treatment of:

• Complicated skin and skin structure infections (cSSSI) in adult and pediatric patients (1 to 17 years of age) for whom appropriate dosing can be achieved
• Staphylococcus aureus bloodstream infections (bacteremia), in adult patients for whom appropriate dosing can be achieved, including those with right-sided infective endocarditis
• Staphylococcus aureus bloodstream infections (bacteremia) in pediatric patients (1 to 17 years of age) for whom appropriate dosing can be achieved

Limitations of use:

• Daptomycin in Sodium Chloride Injection is not indicated for the treatment of pneumonia.
• Daptomycin in Sodium Chloride Injection is not indicated for the treatment of left-sided infective endocarditis due to S. aureus.
• Daptomycin in Sodium Chloride Injection is not recommended in pediatric patients younger than one year of age due to the risk of potential effects on muscular, neuromuscular, and/or nervous systems (either peripheral and/or central) observed in neonatal dogs.
• To reduce the development of drug-resistant bacteria and maintain the effectiveness of Daptomycin in Sodium Chloride Injection and other antibacterial drugs, Daptomycin in Sodium Chloride Injection should be used to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. 

Important Risk Information

Contraindications

• Daptomycin in Sodium Chloride Injection is contraindicated in patients with a known hypersensitivity to daptomycin.

Warnings and precautions

• Anaphylaxis/hypersensitivity reactions: Anaphylaxis/hypersensitivity reactions have been reported with the use of antibacterial agents, including daptomycin for injection, and may be life-threatening. If an allergic reaction occurs, discontinue the drug and institute appropriate therapy.

• Myopathy and rhabdomyolysis: Patients receiving Daptomycin in Sodium Chloride Injection should be monitored for the development of muscle pain or weakness, particularly of the distal extremities. CPK levels should be monitored weekly and more frequently in patients who received recent, prior or concomitant therapy with an HMG-CoA reductase inhibitor or in whom elevations in CPK occur during treatment. In adult patients with renal impairment, both renal function and CPK should be monitored more frequently than once weekly.

  Daptomycin in Sodium Chloride Injection should not be dosed more frequently than once a day.

  Daptomycin in Sodium Chloride Injection should be discontinued in patients with unexplained signs and symptoms of myopathy in conjunction with CPK elevations to levels >1,000 U/L, and in patients without reported symptoms who have marked elevations in CPK, with levels >2,000 U/L.

• Eosinophilic pneumonia: Has been reported in patients receiving daptomycin for injection. In reported cases, patients developed fever, dyspnea with hypoxic respiratory insufficiency and diffuse pulmonary infiltrates or organizing pneumonia. In general, patients developed eosinophilic pneumonia 2 to 4 weeks after starting daptomycin for injection and improved when discontinued and steroid therapy was initiated. Recurrence of eosinophilic pneumonia upon re-exposure has been reported. Patients who develop these signs and symptoms should undergo prompt medical evaluation, and Daptomycin in Sodium Chloride Injection should be discontinued immediately.
• Drug reaction with eosinophilia and systemic symptoms (DRESS): DRESS has been reported in postmarketing experience. Patients who develop skin rash, fever, peripheral eosinophilia and systemic organ (for example, hepatic, renal, pulmonary) impairment while receiving Daptomycin in Sodium Chloride Injection should undergo medical evaluation. If DRESS is suspected, discontinue promptly and institute appropriate treatment.
• Tubulointerstitial nephritis (TIN): TIN has been reported in post-marketing experience. Patients who develop new or worsening renal impairment while receiving Daptomycin in Sodium Chloride Injection should undergo medical evaluation. If TIN is suspected, discontinue promptly and institute appropriate treatment.
• Peripheral neuropathy: Cases have been reported during post-marketing experience. Therefore, physicians should be alert to signs and symptoms of peripheral neuropathy in patients receiving Daptomycin in Sodium Chloride Injection. Monitor for neuropathy and consider discontinuation.
• Potential nervous system and/or muscular system effects in pediatric patients younger than 12 months: Avoid use in pediatric patients younger than 12 months due to the risk of potential effects on muscular, neuromuscular and/or nervous systems (either peripheral and/or central) observed in neonatal dogs with intravenous daptomycin.
• Clostridioides difficile-associated diarrhea (CDAD): CDAD has been reported with the use of nearly all systemic antibacterial agents, including daptomycin for injection, and may range in severity from mild diarrhea to fatal colitis. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibacterial 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.
• Persisting or relapsing S. aureus bacteremia/endocarditis: Patients should have repeat blood cultures. If a blood culture is positive for S. aureus, minimum inhibitory concentration (MIC) susceptibility testing of the isolate should be performed, and diagnostic evaluation of the patient should be performed to rule out sequestered foci of infection. Appropriate surgical intervention and/or consideration of a change in antibacterial regimen may be required. Failure of treatment may be due to reduced daptomycin susceptibility.
• Decreased efficacy was observed in adult patients with moderate baseline renal impairment: Consider these data when selecting antibacterial therapy for use in adult patients with baseline moderate to severe renal impairment.
• Adverse reactions:
  • Adult cSSSI patients: The most common adverse reactions that occurred in ≥2% of adult cSSSI patients receiving daptomycin for injection 4 mg/kg were diarrhea, headache, dizziness, rash, abnormal liver function tests, elevated creatine phosphokinase (CPK), urinary tract infections, hypotension and dyspnea.
  • Pediatric cSSSI patients: The most common adverse reactions that occurred in ≥2% of pediatric patients receiving daptomycin for injection were diarrhea, vomiting, abdominal pain, pruritus, pyrexia, elevated CPK and headache.
  • Adult S. aureus bacteremia/endocarditis patients: The most common adverse reactions that occurred in ≥5% of S. aureus bacteremia/endocarditis patients receiving daptomycin for injection 6 mg/kg were sepsis, bacteremia, abdominal pain, chest pain, edema, pharyngolaryngeal pain, pruritus, increased sweating, insomnia, elevated CPK and hypertension.
  • Pediatric S. aureus bacteremia patients: The most common adverse reactions that occurred in ≥5% of pediatric patients receiving daptomycin for injection were vomiting and elevated CPK.
• Drug interactions:
  • HMG-CoA reductase inhibitors: Inhibitors of HMG-CoA reductase may cause myopathy. Experience with the coadministration of HMG-CoA reductase inhibitors and daptomycin for injection in patients is limited; therefore, consideration should be given to suspending use of HMG-CoA reductase inhibitors temporarily in patients receiving Daptomycin in Sodium Chloride Injection.
  • Drug-lab test interactions: Increased International Normalized Ratio (INR)/Prolonged Prothrombin Time: Clinically relevant plasma concentrations of daptomycin have been observed to cause a significant concentration-dependent false prolongation of prothrombin time (PT) and elevation of International Normalized Ratio (INR) when certain recombinant thromboplastin reagents are utilized for the assay.

Dosage and administration

• If a dose of Daptomycin in Sodium Chloride Injection is required that does not equal 350 mg, 500 mg, 700 mg or 1,000 mg, this product is not recommended for use and an alternative formulation of daptomycin should be considered.

Please click for accompanying full Prescribing Information for Daptomycin in 0.9% Sodium Chloride Injection.