amphotericin B lipid complex
Abelcet

Available forms
Available by prescription only
Suspension for injection: 100 mg/20-ml vial

Indications and dosages
 Invasive fungal infections, including Aspergillus species and Candida species, in patients who are refractory to or intolerant of conventional amphotericin B therapy. Adults and children: 5 mg/kg daily I.V. as a single infusion administered at 2.5 mg/kg/hour.

Pharmacodynamics
Antifungal action: The active component of Abelcet, amphotericin B, binds to sterols in fungal cell membranes, resulting in enhanced cellular permeability and cell damage. Amphotericin B has fungistatic or fungicidal effects depending on fungal susceptibility.

Pharmacokinetics
Absorption: Administered I.V.
Distribution: Well distributed. The distribution volume increases with increasing dose. Abelcet yields measurable amphotericin B levels in spleen, lungs, liver, lymph nodes, kidneys, heart, and brain.
Metabolism: Unknown.
Excretion: Although rapidly cleared from blood, drug has a long terminal half-life (173 hr), probably because of slow elimination from tissues.

Contraindications and precautions
Contraindicated in patients hypersensitive to amphotericin B or its components. Use cautiously in patients with renal impairment.

Interactions
Drug-drug. Antineoplastics: Increase risk of renal toxicity, bronchospasm, and hypotension. Use together cautiously.
Cardiac glycosides: Increase risk of digitalis toxicity from amphotericin B-induced hypokalemia. Monitor serum potassium level closely.
Clotrimazole, fluconazole, itraconazole, ketoconazole, miconazole: May antagonize amphotericin B. Monitor patient closely.
Corticosteroids, corticotropin: Enhance hypokalemia, which may lead to cardiac toxicity. Monitor serum electrolyte levels and cardiac function.
Cyclosporine: Increases renal toxicity. Monitor patient closely.
Flucytosine: Increases risk of flucytosine toxicity from increased cellular uptake or impaired renal excretion. Use together cautiously.
Nephrotoxic drugs (such as aminoglycosides, pentamidine): Increase risk of renal toxicity. Use together cautiously. Monitor renal function closely.
Skeletal muscle relaxants: Enhances effects of skeletal muscle relaxants resulting from amphotericin B-induced hypokalemia. Monitor serum potassium level closely.
Zidovudine: Increases myelotoxicity and nephrotoxicity. Monitor renal and hematologic function.

Adverse reactions
CNS: headache, pain, fever.
CV: chest pain, cardiac arrest, hypertension, hypotension.
GI: abdominal pain, diarrhea, GI hemorrhage, nausea, vomiting.
GU: renal failure.
Hematologic: anemia, leukopenia, thrombocytopenia.
Hepatic: bilirubinemia.
Metabolic: hypokalemia.
Respiratory: dyspnea, respiratory disorder, respiratory failure.
Skin: rash.
Other: chills, infection, MULTIPLE ORGAN FAILURE,sepsis.

Effects on lab test results
• May increase BUN, creatinine, alkaline phosphatase, ALT, AST, bilirubin, GGT, and LDH levels. May decrease potassium levels.
• May decrease hemoglobin and WBC and platelet counts.

Overdose and treatment
Overdose may raise the risk of cardiorespiratory arrest. Doses as high as 7 to 13 mg/kg haven’t produced serious acute toxicity.
 If overdose is suspected, discontinue therapy, monitor patient’s condition, and provide supportive treatment as needed. Drug isn’t removed by hemodialysis.

Special considerations
• Drug has an unlabeled use for empiric therapy in febrile neutropenic patients.
 ALERT Amphotericin B preparations aren’t interchangeable and dosages will vary.
• Premedication with acetaminophen, antihistamines, and corticosteroids can prevent or lessen severity of infusion-related reactions, such as fever, chills, nausea, and vomiting, which occur 1 to 2 hours after start of infusion.
• Leukocyte transfusions shouldn’t be given with drug because acute pulmonary toxicity has been reported with concurrent administration.
• Don’t mix with saline solution or infuse in same I.V. line as other drugs. Don’t use an in-line filter.
• If infusing through an existing I.V. line, flush first with D₅W.
• To prepare, shake vial gently until there’s no yellow sediment. Using aseptic technique, withdraw calculated dose into one or more 20-ml syringes, using an 18-gauge needle. More than one vial will be required. Attach a 5-micron filter needle to the syringe and inject the dose into an I.V. bag of D₅W. One filter needle can be used for up to four vials of amphotericin B lipid complex. The volume of D₅W should be sufficient to yield a final concentration of 1 mg/ml.
• For children and patients with CV disease, recommended final concentration is 2 mg/ml.
• Discard any unused drug; it doesn’t contain a preservative.
• Use an infusion pump and administer by continuous infusion at 2.5 mg/kg/hour. If infusion time exceeds 2 hours, mix contents by shaking infusion bag every 2 hours.
 ALERT If severe respiratory distress occurs, discontinue infusion, and provide supportive therapy for anaphylaxis. Drug shouldn’t be reinstituted in this situation.
• Take vital signs frequently. Fever, shaking chills, and hypotension may appear within 2 hours after starting infusion. Slowing infusion rate may decrease infusion-related reactions.
• Monitor serum creatinine and electrolyte levels (especially magnesium and potassium), liver function, and CBC during therapy.
• The need for dosage adjustment should be based on the overall clinical status of the patient. Renal toxicity is more common at higher doses.
• Infusions are stable for up to 48 hours if refrigerated at 36° to 46° F (2° to 8° C) and up to 6 hours at room temperature.
Breast-feeding patients
• It’s unknown if drug appears in breast milk. The decision to administer Abelcet to a breast-feeding woman should be based on the risk of adverse reactions in the infant compared to the benefits of treatment.
Pediatric patients
• No unexpected adverse reactions have been reported in children age 16 or younger when given 5 mg/kg daily.
Geriatric patients
• No unexpected adverse reactions have been reported when treated with 5 mg/kg daily.

Patient education
• Inform patient that fever, chills, nausea, and vomiting may occur during infusion and that these reactions usually subside with subsequent doses.
• Instruct patient to report any redness or pain at infusion site.
• Teach patient to recognize and report any symptoms of acute hypersensitivity such as respiratory distress.
• Warn patient that therapy may take several months.
• Tell patient to expect frequent laboratory testing to monitor kidney and liver function.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use