Dosing and uses of AmBisome (amphotericin B liposomal)
Adult dosage forms and strengths
powder for injection
- 50mg/vial
Fungal Infection, Empiric Therapy
Indicated for empiric therapy for presumed fungal infection in febrile, neutropenic patients
3 mg/kg IV qDay
Systemic Fungal Infections
Indicated for treatment of Aspergillus species, Candida species, and/or Cryptococcus species infections refractory to amphotericin B deoxycholate, or if renal impairment or unacceptable toxicity precludes use of amphotericin B deoxycholate
3-5 mg/kg IV qDay
Cryptococcal Meningitis
Indicated for treatment of Cryptococcal meningitis in HIV-infected patients
6 mg/kg IV qDay
Visceral Leishmaniasis
Indicated for treatment of visceral leishmaniasis
Note: relapse rate high with amphotericin B liposomal following initial clearance of parasites in patients who are immunocompromised
Immunocompetent patients
- 3 mg/kg IV qDay on days 1-5, 14, and 21
- May repeat course of therapy if parasitic clearance not achieved
Immunocompromised patients
- 4 mg/kg IV qDay on days 1-5, 10, 17, 24, 31, and 38
- If parasitic clearance not achieved, consult infectious disease specialist for further treatment
Histoplasmosis (Orphan)
Orphan indication sponsor
- Fujisawa USA, Inc; 3 Parkway North Center; Deerfield, IL 60015
Pediatric dosage forms and strengths
powder for injection
- 50mg/vial
Fungal Infection, Empiric Therapy
Indicated for empiric therapy for presumed fungal infection in febrile, neutropenic patients
As adults; 3 mg/kg IV qDay
Systemic Fungal Infections
Indicated for treatment of Aspergillus species, Candida species, and/or Cryptococcus species infections refractory to amphotericin B deoxycholate, or if renal impairment or unacceptable toxicity precludes use of amphotericin B deoxycholate
As adults; 3-5 mg/kg IV qDay
Cryptococcal Meningitis
Indicated for treatment of Cryptococcal meningitis in HIV-infected patients
As adults; 6 mg/kg IV qDay
Visceral Leishmaniasis
Indicated for treatment of visceral leishmaniasis
Note: relapse rate high with amphotericin B liposomal following initial clearance of parasites in patients who are immunocompromised
Immunocompetent patients
- As adults; 3 mg/kg IV qDay on days 1-5, 14, and 21
- May repeat course of therapy if parasitic clearance not achieved
Immunocompromised patients
- As adults; 4 mg/kg IV qDay on days 1-5, 10, 17, 24, 31, and 38
- If parasitic clearance not achieved, consult infectious disease specialist for further treatment
AmBisome (amphotericin B liposomal) adverse (side) effects
>10%
Hypokalemia (31-51%)
Hypomagnesemia (15-50%)
Chills (29-48%)
Anemia (27-48%)
Nephrotoxicity (14-47%)
Nausea (16-40%)
Vomiting (11-32%)
Diarrhea (11-30%)
Rash (5-25%)
Dyspnea (18-23%)
Hyperglycemia (8-23%)
Insomnia (17-22%)
Alkaline phosphatase increase (7-22%)
Infusion reaction (4-21%)
Headache (9-20%)
Hypertension (8-20%)
Abdominal pain (7-20%)
Tachycardia (9-19%)
Lung disorder (14-18%)
Blood transfusion reaction (9-18%)
Hypocalcemia (5-18%)
Cough (2-18%)
Bilirubinemia (<18%)
Leukopenia (15-17%)
ALT increased (15%)
Constipation (15%)
Peripheral edema (15%)
Pain (14%)
Anorexia (10-14%)
Anxiety (7-14%)
Hypotension (7-14%)
Sepsis (7-14%)
AST increased (13%)
Pleural effusion (13%)
Confusion (9-13%)
Thrombocytopenia (6-13%)
Weakness (6-13%)
Back pain (12%)
Edema (10-12%)
Hyponatremia (9-12%)
Chest pain (8-12%)
Hypervolemia (8-12%)
Pruritus (11%)
Rhinitis (11%)
Phlebitis (9-11%)
1-10%
Abnormal thinking
Acidosis
Agitation
Alopecia
Arthralgia
Asthma
Bruising
Cardiovascular abnormalities
Coagulation disorder
Cellulitis
Depression
Dizziness
Electrolyte abnormalities
Fluid overload
Gastrointestinal hemorrhage
Hallucinations
Hyperventilation
Injection site reaction
Malaise
Mucositis
Petechia
Rash
Renal function abnormalities
Respiratory acidosis
Respiratory failure
Seizure
Stomatitis
Warnings
Contraindications
Hypersensitivity
Cautions
Indicated for patients with progressive and potentially fatal fungal infections
Do not use for noninvasive fungal infections (eg, oral thrush, vaginal candidiasis, esophageal candidiasis) in patients with normal neurophil counts
Caution when coadministration with other drugs that cause hypokalemia (eg, corticosteroids, digoxin)
Acute pulmonary toxicity reported with simultaneously leukocyte transfusions
Caution with other nephrotoxic medications
Pregnancy and lactation
Pregnancy category: B
Lactation: Unknown whether distributed in breast milk, caution advised
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of AmBisome (amphotericin B liposomal)
Half-Life: 7-10 hr (at 24 hr); terminal half-life range 10-153 hr
Vd: 0.1-0.4 L/kg
AUC: 27-555 mcg•h/mL
Peak Plasma Concentration: 7.3-83 mcg/mL
Clearance: 11-51 mL/hr/kg
Mechanism of action
Acts by binding to sterols in fungal cell membrane, leading to alterations in cell permeability and cell death
Administration
IV Incompatibilities
Solution: NaCl solutions or electrolyte solutions
IV Compatibilities
Solution: dextrose solutions
Y-site: anidulafungin
IV Preparation
Reconstitute by adding 12 mL sterile water for injection to 50 mg-vial (resulting concentration 4 mg/mL); do not use fluids containing NaCl or bacteriostatic agent
Do not admix with other drugs or electrolytes
Shake vial vigorously for 30 seconds
Dilute further by withdrawing appropriate amount of reconstituted solution and adding to D5W to provide a final concentration of 1-2 mg/mL; lower concentrations (0.2-0.5 mg/mL) may be appropriate for infants and small children
IV Administration
May be infused through in-line filter provided pore diameter >1 micron
May be administered through existing IV line; if doing so, flush line with D5W prior to infusion, otherwise use separate line
Infuse over at least 2 hr using controlled infusion device; if well tolerated, infusion time may be reduced to 1 hr
Infusion time may need to be increase if discomfort during infusion occurs
Withdraw dosage amount into a syringe and inject through a 5-micron filter into appropriate amount of D5W
Use a controlled infusion device and an inline filter (with a mean pore diameter >1 micron)
Storage
Refrigerate unopened drug at 36-46°F (2-8°C)
Do not freeze
