Frozen Premix Products

Vancomycin Injection, USP

Vancomycin Injection, USP in 5% Dextrose

500 mg/100 mL (5 mg/mL) in single dose GALAXY container

750 mg/150 mL (5 mg/mL) in single dose GALAXY container

1 g/200 mL (5 mg/mL) in single dose GALAXY container

1.25 g/250 mL (5 mg/mL) in single dose GALAXY container

1.5 g/300 mL (5 mg/mL) in single dose GALAXY container

Vancomycin Injection, USP in 0.9% Sodium Chloride

500 mg/100 mL (5 mg/mL) in single dose GALAXY container

750 mg/150 mL (5 mg/mL) in single dose GALAXY container

1 g/200 mL (5 mg/mL) in single dose GALAXY container

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 Infection
• 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 Vancomycin Injection 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 see accompanying full Prescribing Information for Vancomycin Injection, USP.

Daptomycin in 0.9% Sodium Chloride Injection

350 mg/50 mL, 500 mg/50 mL, 700 mg/100 mL, 1,000 mg/100 mL

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 and,
• 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 see accompanying full Prescribing Information for Daptomycin in 0.9% Sodium Chloride Injection.

Cefazolin in Dextrose Injection, USP

1 gram/50 mL

2 grams/100 mL

3 grams/150 mL

Indications and Important Risk Information

Indications

Cefazolin in Dextrose Injection is a cephalosporin antibacterial indicated for:

• Treatment of respiratory tract infections in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved.
  Limitations of Use: Injectable benzathine penicillin is considered the drug of choice in treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever.
• Treatment of the following infections caused by susceptible isolates of the designated microorganisms in adult and pediatric patients for whom appropriate dosing with this formulation can be achieved: Urinary tract infections; Skin and skin structure infections; Biliary tract infections; Bone and joint infections; Genital infections; Septicemia; Endocarditis.
• Perioperative prophylaxis in adults and pediatric patients aged 10 – 17 years old for whom appropriate dosing with this formulation can be achieved.

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

Important Risk Information

• Contraindications: Hypersensitivity to cefazolin or other cephalosporin class antibacterial drugs, penicillins, or other beta-lactams.
• Hypersensitivity Reactions to Cefazolin, Cephalosporins, Penicillins, or Other Beta-lactams: Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterial drugs. Before therapy with Cefazolin in Dextrose Injection, careful inquiry should be made to determine whether the patient has had previous immediate hypersensitivity reactions to cefazolin, cephalosporins, penicillins, or carbapenems. Exercise caution if this product is to be given to penicillin-sensitive patients because cross-hypersensitivity among beta-lactam antibacterial drugs may occur in up to 10% of patients with a history of penicillin allergy. If an allergic reaction occurs, discontinue the drug.
• Seizures in Patients with Renal Impairment: Seizures may occur particularly in patients with renal impairment when the dosage is not reduced appropriately. Discontinue Cefazolin in Dextrose Injection if seizures occur or make appropriate dosage adjustments in patients with renal impairment. Anticonvulsant therapy should be continued in patients with known seizure disorders.
• Clostridioides difficile-associated Diarrhea (CDAD): 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.
• Prothrombin Activity: Cefazolin in Dextrose Injection may be associated with a fall in prothrombin activity. Those at risk include patients with renal or hepatic impairment or poor nutritional state, as well as patients receiving a protracted course of antimicrobial therapy, and patients previously stabilized on anticoagulant therapy. Prothrombin time should be monitored in patients at risk and exogenous vitamin K administered as indicated.
• Adverse Reactions: Adult and Pediatric Patients: Most common adverse reactions: gastrointestinal (nausea, vomiting, diarrhea), and allergic reactions (anaphylaxis, urticaria, skin rash).
• Pediatric Patients with Perioperative Prophylaxis: The most frequently reported adverse reactions (incidence ≥ 5%) were nausea, infusion site pain, and headache.
• Drug Interactions:
  • • Probenecid: The renal excretion of cefazolin is inhibited by probenecid. Co-administration of probenecid with Cefazolin in Dextrose Injection is not recommended.

Please see accompanying full Prescribing Information for Cefazolin in Dextrose Injection, USP.

NEXTERONE (amiodarone HCl) Premixed Injection

150 mg/100 mL and 360 mg/200 mL

Indication and Important Risk Information

Indication

NEXTERONE is indicated for initiation of treatment and prophylaxis of frequently recurring ventricular fibrillation (VF) and hemodynamically unstable ventricular tachycardia (VT) in patients refractory to other therapy.

Important Risk Information

Contraindications

NEXTERONE is contraindicated in patients with:

• Known hypersensitivity to any of the components of NEXTERONE, including iodine

• Cardiogenic shock

• Marked sinus bradycardia

• Second- or third-degree atrioventricular (AV) block unless a functioning pacemaker is available

Warnings and Precautions

• Persistence of Adverse Effects: Because of the long half-life of amiodarone (9 to 36 days) and its metabolite desethylamiodarone (9 to 30 days), adverse reactions or interactions, as well as observed adverse effects, can persist following amiodarone withdrawal.

• Hypotension: Most often seen in the first several hours of treatment and likely related to the rate of infusion. In some cases, hypotension may be refractory and result in a fatal outcome. To treat: Slow the infusion; as needed, add vasopressor drugs, positive inotropic agents, and volume expansion.

• Bradycardia and Atrioventricular Block: May require slowing the infusion rate or discontinuing NEXTERONE. In some patients, inserting a pacemaker is required. Have a temporary pacemaker available when treating a patient predisposed to bradycardia or AV block.

• Hepatic Injury: Acute hepatocellular necrosis leading to hepatic coma, acute renal failure, and death has been associated. Intravenous infusions at much higher concentrations and rates of infusion than those recommended appear to increase this risk. Carefully monitor patients receiving NEXTERONE for evidence of progressive hepatic injury. Consider reducing the rate of administration or withdrawing NEXTERONE if hepatic injury occurs.

• Proarrhythmia: NEXTERONE may cause a worsening of existing arrhythmias or precipitate a new arrhythmia, sometimes leading to fatal outcomes. Proarrhythmia, primarily torsade de pointes (TdP), has been associated with prolongation by intravenous amiodarone. Monitor patients for QTc prolongation during infusion with NEXTERONE. Reserve the combination of amiodarone with other antiarrhythmic therapies that prolong the QTc to patients with life-threatening ventricular arrhythmias who are incompletely responsive to a single agent. Correct hypokalemia, hypomagnesemia or hypocalcemia whenever possible before initiating treatment with NEXTERONE.

• Pulmonary Injury: There have been post-marketing reports of acute-onset (days to weeks) pulmonary injury. Some cases have progressed to respiratory failure or death. Monitor for new respiratory symptoms and evaluate appropriately. Obtain a baseline chest X-ray and pulmonary function tests in patients who are expected to be receiving amiodarone chronically.

• Loss of Vision: Cases of optic neuropathy and optic neuritis, usually resulting in visual impairment, have been reported. In some cases, visual impairment has progressed to permanent blindness. Optic neuropathy and neuritis may occur at any time following initiation of therapy. Perform an ophthalmic examination if symptoms of visual impairment appear. Reevaluate the necessity of amiodarone therapy if optic neuropathy or neuritis is suspected.

• Thyroid Abnormalities: NEXTERONE inhibits peripheral conversion of thyroxine (T4) to triiodothyronine (T3) and may cause increased T3 levels, and increased levels of inactive reverse T3 (rT3) in clinically euthyroid patients. Monitor thyroid function prior to treatment and periodically thereafter, particularly in elderly patients, and in any patient with a history of thyroid nodules, goiter, or other thyroid dysfunction. Hyperthyroidism may induce arrhythmia breakthrough. If any new signs of arrhythmia appear, the possibility of hyperthyroidism should be considered.

• Neonatal Injury: Amiodarone can cause fetal harm when administered to a pregnant woman. Fetal exposure may increase the potential for adverse experiences including cardiac, thyroid, neurodevelopmental, neurological and growth effects in neonate. Inform the patient of the potential hazard to the fetus if NEXTERONE is administered during pregnancy or if the patient becomes pregnant while taking NEXTERONE.

• Hypersensitivity Reactions: Anaphylactic/anaphylactoid reactions have been reported including shock (sometimes fatal), cardiac arrest, and the following manifestations: hypotension, tachycardia, hypoxia, cyanosis, rash, Stevens-Johnson syndrome, flushing, hyperhidrosis and cold sweat.

• Adverse Reactions: The most common adverse reactions (1-2%) leading to discontinuation of intravenous amiodarone therapy are hypotension, asystole/cardiac arrest/pulseless electrical activity, VT, and cardiogenic shock. Other important adverse reactions are torsade de pointes, congestive heart failure, and liver function test abnormalities.

• Drug Interactions: Amiodarone is a substrate for CYP3A and CYP2C8, so inhibitors and inducers affect amiodarone exposure. Amiodarone inhibits p-glycoprotein and CYP1A2, CYP2C9, CYP2D6, and CYP3A, increasing exposure to other drugs.

Please see accompanying full Prescribing Information for NEXTERONE (amiodarone HCl) Premixed Injection.