ABELCET
Clinical safety rating: caution
ABELCET (amphotericin B lipid complex) is a polyene antifungal agent used for treatment of invasive fungal infections, including aspergillosis and candidiasis, in patients intolerant to conventional amphotericin B deoxycholate. It is formulated as a lipid complex to reduce nephrotoxicity while maintaining antifungal activity.
Amphotericin B binds to ergosterol in fungal cell membranes, forming pores that increase membrane permeability, leading to leakage of intracellular ions and cell death. The lipid complex formulation (ABELCET) alters pharmacokinetics to reduce nephrotoxicity while retaining antifungal activity.
| Metabolism | Amphotericin B is not significantly metabolized in humans; it is eliminated primarily via biliary excretion with negligible renal metabolism. |
| Excretion | Renal excretion is minimal (<1% unchanged drug); the primary route of elimination is via the hepatobiliary system, with the majority of the dose recovered in feces as unchanged drug and metabolites. Biliary/fecal elimination accounts for >90% of clearance. |
| Half-life | Terminal elimination half-life is approximately 120–180 hours (mean ~153 h) in adults with normal renal and hepatic function. This long half-life reflects slow redistribution from tissues and supports once-daily dosing after a loading regimen. |
| Protein binding | More than 99% bound to plasma proteins, primarily to albumin and lipoproteins (e.g., LDL and HDL). |
| Volume of Distribution | Volume of distribution is approximately 0.5–1.0 L/kg, indicating extensive tissue distribution (e.g., liver, spleen, lung, kidney) with limited penetration into cerebrospinal fluid and vitreous humor. |
| Bioavailability | Not applicable; only administered intravenously. Oral bioavailability is negligible (less than 5%) due to poor gastrointestinal absorption and degradation in the GI tract. |
| Onset of Action | Intravenous administration: clinical response (e.g., defervescence in febrile neutropenia or stabilization in fungal infections) typically observed within 24–48 hours after initiation of therapy; antifungal effect begins with the first dose due to direct membrane disruption. |
| Duration of Action | Duration of antifungal activity persists for several days after a single dose due to prolonged tissue retention; clinical effects may last 2–5 days after drug discontinuation. Dosing is continued until resolution of infection or for a defined course (e.g., 2 weeks post–last positive culture). |
| Molecular Weight | 924.08 |
5 mg/kg IV once daily infused over 2-2.5 hours. For aspergillosis, duration is typically 2-4 weeks total.
| Dosage form | INJECTABLE, LIPID COMPLEX |
| Renal impairment | No dosage adjustment required, but renal function should be monitored; consider dose adjustment if CrCl < 30 mL/min or if significant nephrotoxicity occurs (e.g., doubling of serum creatinine). |
| Liver impairment | No specific adjustment; use with caution in severe hepatic impairment. |
| Pediatric use | Same dosing as adults (5 mg/kg/day IV); safety and efficacy established. |
| Geriatric use | No specific adjustment, but monitor renal function and electrolyte balance due to higher risk of toxicity. |
| 1st trimester | Avoid due to potential fetal toxicity; animal studies show teratogenicity. Use only if clearly needed. |
| 2nd trimester | Use only if benefit outweighs risk; may cause fetal harm. Administer with caution, monitoring for maternal renal function and electrolyte imbalances. |
| 3rd trimester | Use only if benefit outweighs risk; may cause fetal renal impairment or oligohydramnios. Monitor amniotic fluid volume and fetal kidney function. |
Clinical note
Use only if clearly needed; amphotericin B is considered category B (no evidence of risk), but adequate human studies are lacking. Should be reserved for serious systemic infections where benefit outweighs potential fetal risk.
| Placental transfer | Liposomal formulation; amphotericin B is known to cross placenta in animal studies, but limited human data. Likely transfers to fetus. |
| Breastfeeding | Not known whether excreted in human milk. Due to potential for serious adverse reactions in nursing infants, decide to discontinue nursing or drug, considering importance of drug to mother. |
■ FDA Black Box Warning
WARNING: Should be used primarily for treatment of progressive, potentially life-threatening fungal infections in patients intolerant to conventional amphotericin B deoxycholate or whose infection is refractory to that formulation. Not interchangeable with other amphotericin B products. Verify correct product prior to administration. Administer by intravenous infusion only.
| Common Effects | Fever, Chills/rigors, Nausea/vomiting, Headache, Hypokalemia, Hypomagnesemia, Increased serum creatinine, Anemia |
| Serious Effects | Nephrotoxicity (acute renal failure), Hypokalemia, Hypomagnesemia, Cardiac arrest, Anaphylaxis, Hepatotoxicity, Bone marrow suppression |
Hypersensitivity to amphotericin B or any component of the formulation
| Precautions | Nephrotoxicity: monitor renal function closely; may cause azotemia, hypokalemia, hypomagnesemia, Hypersensitivity reactions: anaphylaxis, bronchospasm, flushing, hypotension, Infusion-related reactions: fever, chills, rigors, headache, nausea, vomiting, Cardiotoxicity: arrhythmias, cardiac arrest (especially during rapid infusion), Hepatotoxicity: elevated liver enzymes, bilirubin, Hematologic toxicity: anemia, thrombocytopenia, leukopenia, Electrolyte disturbances: hypokalemia, hypomagnesemia, hyponatremia, Pulmonary toxicity: dyspnea, respiratory failure (rare), Prior to infusion: premedicate with antipyretics, antihistamines, and corticosteroids to reduce infusion reactions |
Loading safety data…
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | Pregnancy Category B. Animal studies with amphotericin B deoxycholate have shown no evidence of fetal harm. There are no adequate and well-controlled studies in pregnant women. However, systemic fungal infections pose significant maternal and fetal risk if untreated. Use only if clearly needed. |
| Fetal Monitoring | Monitor renal function (serum creatinine, BUN), serum electrolytes (especially potassium and magnesium), liver function tests (AST, ALT, alkaline phosphatase), and complete blood count before and during therapy. Assess for signs of infusion-related reactions. In pregnancy, monitor fetal growth and wellbeing via ultrasound as clinically indicated. |
| Fertility Effects | Amphotericin B did not impair fertility in animal studies. No human data on fertility effects. |
| Food/Dietary | No known food interactions. Maintain adequate hydration. |
| Clinical Pearls | Monitor renal function and electrolytes closely; premedicate with diphenhydramine and acetaminophen to reduce infusion-related reactions; do not mix with saline or other electrolytes; administer via in-line filter (5 micron) only; ensure adequate hydration to prevent nephrotoxicity. |
| Patient Advice | This medication is given intravenously and may cause fever, chills, or rigors during infusion. · Report any breathing difficulty, chest pain, or severe reaction immediately. · You may receive pre-medications to reduce side effects. · Stay well hydrated unless instructed otherwise. · Blood tests will be required to monitor kidney function and electrolytes. |