Ready-to-Use 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.

Norepinephrine Bitartrate in 5% Dextrose Injection 
Indication and Important Risk Information

Indication

• Norepinephrine Bitartrate in Dextrose Injection is indicated to raise blood pressure in adult patients with severe, acute hypotension.

Important Risk Information

• Contraindications: None.

• Tissue Ischemia: Administration of Norepinephrine Bitartrate in Dextrose Injection to patients who are hypotensive from hypovolemia can result in severe peripheral and visceral vasoconstriction, decreased renal perfusion and reduced urine output, tissue hypoxia, lactic acidosis, and reduced systemic blood flow despite “normal” blood pressure. Address hypovolemia prior to initiating Norepinephrine Bitartrate in Dextrose Injection. Avoid use in patients with mesenteric or peripheral vascular thrombosis, as this may increase ischemia and extend the area of infarction.

  Gangrene of the extremities has occurred in patients with occlusive or thrombotic vascular disease or who received prolonged or high dose infusions. Monitor for changes to the skin of the extremities in susceptible patients.

  Extravasation of Norepinephrine Bitartrate in Dextrose Injection may cause necrosis and sloughing of surrounding tissue. To reduce the risk of extravasation, infuse into a large vein, check the infusion site frequently for free flow, and monitor for signs of extravasation.

  Avoid administration into the veins in the leg in elderly patients.

  Emergency Treatment of Extravasation: Infiltrate the ischemic area as soon as possible, using a syringe with a fine hypodermic needle with 5 to 10 mg of phentolamine mesylate in 10 to 15 mL of 0.9% Sodium Chloride Injection in adults.

• Hypotension after Abrupt Discontinuation: Sudden cessation of the infusion rate may result in marked hypotension. When discontinuing the infusion, gradually reduce the infusion rate while expanding blood volume with intravenous fluids.
• Cardiac Arrhythmias: Norepinephrine Bitartrate in Dextrose Injection elevates intracellular calcium concentrations and may cause arrhythmias, particularly in the setting of hypoxia or hypercarbia. Perform continuous cardiac monitoring of patients with arrhythmias.
• Elderly Patients: May be at a greater risk of developing adverse reactions.
• Adverse Reactions: Most common adverse reactions are hypertension and bradycardia.

• Drug Interactions:

  • Co-administration of Norepinephrine Bitartrate in Dextrose Injection with monoamine oxidase (MAO) inhibitors or other drugs with MAO-inhibiting properties (e.g., linezolid) or with tricyclic antidepressants can cause severe, prolonged hypertension.
  • Anti-diabetics: Norepinephrine Bitartrate in Dextrose Injection can decrease insulin sensitivity and raise blood glucose.
  • Concomitant use of Norepinephrine Bitartrate in Dextrose Injection with halogenated anesthetics may lead to ventricular tachycardia or ventricular fibrillation. Monitor cardiac rhythm in patients receiving concomitant halogenated anesthetics. 

  Please click for accompanying full Prescribing Information for Norepinephrine Bitartrate in 5% Dextrose Injection.

MYXREDLIN (Insulin Human) in 0.9% Sodium Chloride Injection
Indication and Important Risk Information

Indication

MYXREDLIN is a short-acting human insulin indicated to improve glycemic control in adults and pediatric patients with diabetes mellitus.

Important Risk Information

Contraindications

• During episodes of hypoglycemia
• Hypersensitivity to insulin human or any of the excipients in MYXREDLIN

Warnings and Precautions

• Hyper- or Hypoglycemia with Changes in Insulin Regimen: Carry out under close medical supervision and increase frequency of blood glucose monitoring.
• Administer MYXREDLIN intravenously ONLY under medical supervision with close monitoring of blood glucose and potassium levels. Hypokalemia may be life-threatening if not treated.
• Individualize dose based on metabolic needs, blood glucose monitoring results, and glycemic control goal. Dosage adjustments may be needed with changes in nutrition, renal, or hepatic function or during acute illness.
• Adverse reactions observed with insulin human injection include hypoglycemia, allergic reactions, weight gain and edema.
• Fluid Retention and Heart Failure with Concomitant Use of Thiazolidinediones (TZDs): Observe for signs and symptoms of heart failure; such as shortness of breath, swelling of your ankles or feet, or sudden weight gain. 

Dosage and Administration

• Inspect MYXREDLIN visually before use. It should appear clear and colorless. Do not use MYXREDLIN if particulate matter or coloration is seen.
• Do not add supplementary medication or additives.
• Do not use in series connections.
• Do not shake or freeze. Discard unused portion. 

Please click for full Prescribing Information for MYXREDLIN (Insulin Human) in 0.9% Sodium Chloride Injection.

NEXTERONE (amiodarone HCl) Premixed Injection
Indication and Important Risk Information

Indications

NEXTERONE Premixed Injection 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 Premixed Injection is contraindicated in patients with:
  • Known hypersensitivity to any of the components of NEXTERONE Premixed Injection, including iodine
  • Cardiogenic shock
  • Marked sinus bradycardia
  • Second- or third-degree atrioventricular (AV) block unless a functioning pacemaker is available
• 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.
• Primary Graft Dysfunction (PGD) Post Cardiac Transplant: In retrospective studies, amiodarone use in transplant recipients prior to heart transplants has been associated with an increased risk of PGD. Severe PGD may be irreversible. For patients who are on the heart transplant waiting list, consideration should be given to use an alternative antiarrhythmic drug as early as possible before transplant.
• Bradycardia and Atrioventricular Block: May require slowing the infusion rate or discontinuing NEXTERONE Premixed Injection. 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 Premixed Injection for evidence of progressive hepatic injury. Consider reducing the rate of administration or withdrawing NEXTERONE Premixed Injection if hepatic injury occurs.
• Proarrhythmia: NEXTERONE Premixed Injection 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. 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.
• 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 Premixed Injection 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 Premixed Injection is administered during pregnancy or if the patient becomes pregnant while taking.
• 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 click for accompanying full Prescribing Information for NEXTERONE (amiodarone HCI) Premixed Injection.

CARDENE I.V. (nicardipine hydrochloride) Injection
Indication and Important Risk Information

Indication

CARDENE I.V. is a calcium channel blocker indicated for the short-term treatment of hypertension when oral therapy is not feasible or not desirable. For prolonged control of blood pressure, transfer patients to oral medication as soon as their clinical condition permits.

Important Risk Information

Contraindications  

Do not use in patients with advanced aortic stenosis. 

Warnings and Precautions  

• Exacerbation of Angina
  Increases in frequency, duration, or severity of angina have been seen in chronic therapy with oral nicardipine. Induction or exacerbation of angina has been seen in less than 1% of coronary artery disease patients treated with CARDENE I.V. The mechanism of this effect has not been established.
• Exacerbation of Heart Failure
  Titrate slowly when using CARDENE I.V., particularly in combination with a beta-blocker, in patients with heart failure or significant left ventricular dysfunction because of possible negative inotropic effects.
• Increased effect with Impaired Hepatic Function
  Since nicardipine is metabolized in the liver, consider lower dosages and closely monitor responses in patients with impaired liver function or reduced hepatic blood flow.
• Prolonged effect with Impaired Renal Function
  When CARDENE I.V. was given to mild to moderate hypertensive patients with moderate renal impairment, a significantly lower systemic clearance and higher area under the curve (AUC) was observed. Titrate gradually in patients with renal impairment.
• Local Irritation
  To reduce the possibility of venous thrombosis, phlebitis, local irritation, swelling, extravasation, and the occurrence of vascular impairment, administer drug through large peripheral veins or central veins rather than arteries or small peripheral veins, such as those on the dorsum of the hand or wrist. To minimize the risk of peripheral venous irritation, change the site of the drug infusion every 12 hours. 
• Adverse Reactions: Most common adverse reactions are headache (15%), hypotension (6%), tachycardia (4%) and nausea/vomiting (5%).
• Drug Interactions:  
• Cimetidine has been shown to increase nicardipine plasma concentrations with oral nicardipine administration. Frequently monitor response in patients receiving both drugs.
• Oral or intravenous nicardipine may increase cyclosporine and tacrolimus plasma levels. Frequent monitoring of trough blood levels of cyclosporine and tacrolimus is recommended when co-administering CARDENE I.V.
• Pregnancy: Based on animal data may cause fetal harm. CARDENE I.V. should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Dosage and Administration

• If unacceptable hypotension or tachycardia occurs, discontinue the CARDENE I.V. infusion. When blood pressure and heart rate stabilize, restart the infusion at low doses.

Please click for accompanying full Prescribing Information for CARDENE I.V.

Vasopressin in 0.9% Sodium Chloride Injection
Indication and Important Risk Information

Indication

Vasopressin in Sodium Chloride Injection is indicated to increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines.

Important Risk Information

• Contraindications: Vasopressin in Sodium Chloride Injection is contraindicated in patients with a known allergy or hypersensitivity to 8-L-arginine vasopressin.
• Worsening Cardiac Function: A decrease in cardiac index may be observed with the use of vasopressin.
• Reversible Diabetes Insipidus: Patients may experience reversible diabetes insipidus, manifested by the development of polyuria, a dilute urine, and hypernatremia, after cessation of treatment with vasopressin. Monitor serum electrolytes, fluid status, and urine output after vasopressin discontinuation. Some patients may require readministration of vasopressin or administration of desmopressin to correct fluid and electrolyte shifts.

• Adverse Reactions:    

  – The most common adverse reactions include decreased cardiac output, bradycardia, tachyarrhythmias, hyponatremia, and ischemia (coronary, mesenteric, skin, digital).

• Drug Interactions:  

  – Pressor effects of catecholamines and Vasopressin in Sodium Chloride Injection are expected to be additive.  

  – Indomethacin may prolong effects of Vasopressin in Sodium Chloride Injection.  

  – Co-administration of ganglionic blockers or drugs causing SIADH (syndrome of inappropriate antidiuretic hormone secretion) may increase the pressor response.  

  – Co-administration of drugs causing diabetes insipidus may decrease the pressor response.  

• Pregnancy: May induce tonic uterine contractions that could threaten the continuation of pregnancy. 

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

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.