RESTRICTED DRUG

CLASSIFICATION

Antifungal antibiotic

ALTERNATE NAMES

AMBISOME, liposomal amphotericin B

INDICATIONS

• treatment of progressive, potentially fatal disseminated mycotic infections in patients who are refractory to or intolerant of conventional amphotericin B therapy
• restricted to consult by Infectious Diseases Service and CSU Pharmaceutical Sciences; BMT, SOT and ICU patients exempt from Infectious Diseases Consult. Orders must be prescribed using amphtericin B infusion protocol pre-printed order (PPO). This PPO contains creatinine clearance thresholds whereupon amphotericin B liposomal may be ordered.
  
  

RECONSTITUTION AND STABILITY

• refrigerate vial; protect vial from light
• reconstitute each 50 mg vial with 12 mL sterile water for injection (without bacteriostat) to yield a concentration of 4 mg amphotericin B/mL (50 mg/12.9 mL)
• reconstituted vials stable for 14 days in refrigerator or 24 hours at room temperature
• dilute to 0.2-2 mg/mL concentration in 250-500 mL D5W; use 5 micron filter to transfer contents of amphotericin B liposomal from vial to D5W infusion solution
• diluted solutions stable x 24 hours in D5W PVC bags in refrigerator
  
  

COMPATIBILITY

• use D5W only for infusion solution
• incompatible with NS
• flush all lines with D5W
• do not administer via in-line filter < 1 micron
• incompatible with other drugs
  

ROUTES OF ADMINISTRATION

• IV intermittent
  • dilute to 0.2-2 mg/mL in 250-500mL D5W
  • infuse dose over 2 hours; infusion time may be reduced to 1 hour in patients who tolerate treatment
  • if patient experiences discomfort during infusion, the duration of infusion may be increased
    
    

VH & HSC ADMINISTRATION POLICY

A - Not to be administered by the direct IV route
H - The IV rate must be controlled by an automated infusion control device.

DOSAGE

• daily dose and duration of therapy should be based on the clinical situation
• dosage range: 3-6 mg/kg/day
• dosage may need to be reduced in renal failure, however there are no guidelines for dosage adjustment based on serum creatinine. The decision about dosage adjustments should be based on the overall clinical condition of the patient.
• in dialysis patients - give dose after dialysis is completed
  
  

POTENTIAL HAZARDS OF PARENTERAL ADMINISTRATION

• acute reactions including chills, rigors, fever may occur 1-2 hours after initiation of the infusion. These reactions occur less frequently than with traditional amphotericin B; if they do occur, they are more common with the first few doses and generally diminish with subsequent doses. Premedication with acetaminophen, diphenhydramine and hydrocortisone may be required.
• anaphylaxis, hypotension, bronchospasm, arrhythmias, and shock are rare
  
  

IMPORTANT IMPLICATIONS

• abnormal liver function enzymes and elevated serum creatinine have been reported
• serum creatinine, BUN, urinalysis, blood counts and electrolytes should be monitored closely
• despite generally less nephrotoxicity with amphotericin B liposomal compared to conventional amphotericin B, dose limiting renal toxicity may still be observed
• concomitant use of nephrotoxic agents should be undertaken with caution
•  may cause hypokalemia, hypomagnesemia, and hypocalcemia