AMBISOME
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AMBISOME (AMBISOME).
Amphotericin B binds to ergosterol in fungal cell membranes, forming pores that disrupt membrane integrity, leading to leakage of intracellular contents and fungal cell death.
| Metabolism | Amphotericin B is predominantly cleared via the reticuloendothelial system and is excreted slowly in urine and feces. Metabolism is not well characterized, but it is not extensively metabolized by liver enzymes. |
| Excretion | Renal: negligible (<1% unchanged); Biliary/fecal: primary route, approximately 90% of dose recovered in feces as parent drug and metabolites; Urinary: minimal (less than 1% as unchanged drug). |
| Half-life | Terminal elimination half-life: approximately 7–10 hours (initial phase), with a prolonged terminal half-life of 100–153 hours due to slow redistribution from tissues; clinically, this supports once-daily dosing after initial accumulation. |
| Protein binding | Highly bound (>90%), primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd: 0.4–0.6 L/kg; reflects extensive tissue distribution, particularly into organs of the reticuloendothelial system (liver, spleen). |
| Bioavailability | Intravenous: 100% (only route of administration). |
| Onset of Action | Intravenous: clinical effects (fever resolution, fungal clearance) typically observed within 24–72 hours after initiation of therapy. |
| Duration of Action | Duration: effects persist for 24 hours after a single dose, but therapeutic concentrations in tissues (liver, spleen) may last weeks; dosing interval is 24 hours. |
| Action Class | Fungal cell membrane active agent |
| Brand Substitutes | Sporotar 50mg Injection, Abhope 50mg Injection, Amphogard 50mg Injection, Lambin Injection, Fungsome 50mg Injection |
3-5 mg/kg/day intravenously for systemic fungal infections; for visceral leishmaniasis: 3 mg/kg/day IV on days 1-5, 14, and 21.
| Dosage form | INJECTABLE, LIPOSOMAL |
| Renal impairment | No dose adjustment required for renal impairment; use caution in patients with pre-existing renal disease and monitor renal function. |
| Liver impairment | No specific dose adjustment for Child-Pugh class A or B; for Child-Pugh class C, consider dose reduction or increased monitoring due to potential hepatotoxicity. |
| Pediatric use | For systemic fungal infections: 3-5 mg/kg/day IV; for visceral leishmaniasis: 3 mg/kg/day IV on days 1-5, 14, and 21; weight-based dosing with no maximum daily dose specified. |
| Geriatric use | No specific dose adjustment; monitor renal function closely due to age-related decreased GFR and potential nephrotoxicity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AMBISOME (AMBISOME).
| Breastfeeding | Excretion in human milk unknown; caution advised. M/P ratio not available. |
| Teratogenic Risk | Pregnancy Category A. No evidence of teratogenicity in animal studies; no adequate human studies in first trimester. In second and third trimesters, use only if clearly needed; no known fetal risks. |
| Fetal Monitoring | Monitor renal function, hepatic function, and electrolytes monthly. Fetal growth and amniotic fluid volume by ultrasound if prolonged use. |
■ FDA Black Box Warning
Amphotericin B products should be used primarily for treatment of severe fungal infections in immunocompromised patients where significant toxicity is justified. Amphotericin B is associated with severe nephrotoxicity, especially when used at higher doses or with other nephrotoxic agents. Infusion-related reactions (fever, chills, rigors, hypotension) are common and may be severe.
| Serious Effects |
["Hypersensitivity to amphotericin B or any component of the formulation (unless the condition is life-threatening and amenable only to amphotericin B therapy)"]
| Precautions | ["Nephrotoxicity: Monitor renal function closely; avoid concomitant nephrotoxic drugs when possible.","Infusion reactions: Premedication (e.g., acetaminophen, antihistamines, corticosteroids) may reduce severity.","Electrolyte disturbances: Hypokalemia, hypomagnesemia may occur; monitor and replace as needed.","Hepatotoxicity: Monitor liver function tests.","Cardiotoxicity: Rarely associated with arrhythmias; caution in patients with cardiac disease.","Pancreatitis: Has been reported; consider in patients with abdominal pain."] |
| Food/Dietary |
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| Fertility Effects | No known adverse effects on fertility in animal studies. |
| No known significant food interactions. Grapefruit juice does not affect liposomal amphotericin B metabolism. |
| Clinical Pearls | AmBisome (liposomal amphotericin B) is preferred over conventional amphotericin B due to reduced nephrotoxicity and infusion-related reactions. Dose adjustment not required in renal impairment, but monitor renal function closely. Premedication with acetaminophen, diphenhydramine, and hydrocortisone may reduce infusion reactions. For cryptococcal meningitis in HIV, combination with flucytosine is recommended. Not interchangeable with other amphotericin B formulations; verify dose and product before administration. |
| Patient Advice | Take exactly as prescribed; do not skip doses or stop early. · Infusion reactions (fever, chills, nausea) may occur; report these to your healthcare provider. · Drink plenty of fluids unless advised otherwise by your doctor. · Contact your doctor immediately if you experience signs of allergic reaction (rash, itching, swelling, severe dizziness, trouble breathing). · Tell your doctor about all medications you are taking, including over-the-counter drugs and herbal supplements. · This medication can cause kidney problems; you will need regular blood tests. |