Amphotericin B (Deoxycholate)
Amphotericin B (Fungizone)
Amphotericin B
(am-foe- TER-ih-sin)
Pregnancy Category: B Fungizone Fungizone Intravenous (Rx)
Amphotericin B Lipid Complex (Amphotericin B Cholesteryl Sulfate Complex)
Amphotericin B Lipid Complex (Abelcet)
Amphotericin B Lipid Complex
(am-foe- TER-ih-sin)
Pregnancy Category: B Abelcet AmBisome Amphotec (Rx)

Classification: Antibiotic, antifungal

See Also: See also Anti-Infectives.

Action/Kinetics: This antibiotic is produced by Streptomyces nodosus; it is fungistatic or fungicidal depending on the concentration of the drug in body fluids and the susceptibility of the fungus. Amphotericin B binds to specific chemical structures--sterols--of the fungal cellular membrane, increasing cellular permeability and promoting loss of potassium and other substances. Liposomal encapsulation or incorporation in a lipid complex can significantly affect the functional properties of the drug compared with those of the unencapsulated or non-lipid-associated drug. The liposomal amphotericin B product causes less nephrotoxicity. Amphotericin B is used either IV or topically. It is highly bound to serum protein (90%) Peak plasma levels: 0.5-2 mcg/mL. t 1/2, initial: 24 hr; second phase: 15 days. Slowly excreted by kidneys.The kinetics of the drug differ in adults and children and are also dependent on the product used.

Uses: The drug is toxic and should be used only for clients under close medical supervision with progressive or potentially fatal fungal infections. Systemic Amphotericin B deoxycholate: Disseminated North American blastomycosis, cryptococcosis, and other systemic fungal infections, including coccidioidomycosis, histoplasmosis, aspergillosis, sporotrichosis, disseminated candidiasis, and monilial overgrowth resulting from oral antibiotic therapy. Zygomycosis, including mucormycosis due to Mucor, Rhizopus and Absidia species. Infections due to susceptible species of Conidiobolus and Basidiobolus. Secondary therapy to treat American mucocutaneous leishmaniasis.
Lipid-based Amphotericin B: The lipid complex (Abelcet) is used in those refractory to amphotericin B deoxycholate or where renal impairment or unacceptable toxicity precludes use of the deoxycholate product for treatment of invasive fungal infections. The cholesteryl product (Amphotec) is used to treat invasive aspergillosis infections. The liposomal product (AmBisome) is used to treat infections caused by Aspergillus, Candida or Cryptococcus species, as well as for empirical treatment in febrile, neutropenic clients with presumed fungal infections.
Investigational: Prophylaxis of fungal infections in clients with bone marrow transplantation. Treatment of primary amoebic meningoencephalitis due to Naegleria fowleri. Subconjunctival or intravitreal injection in ocular aspergillosis. As a bladder irrigation for candidal cystitis. Chemoprophylaxis by low dose IV, intranasal, or nebulized administration in immunocompromised clients at risk of aspergillosis. Intrathecally in those with severe meningitis unresponsive to IV deoxycholate therapy. Intra-articularly or IM for coccidiodal arthritis.
Topical: Cutaneous and mucocutaneous infections of Candida (Monilia) infections, especially in children, adults, and AIDS clients with thrush.

Contraindications: Hypersensitivity to drug unless the condition is life-threatening and amenable only to amphotericin B therapy. Use to treat common forms of fungal diseases showing only positive skin or serologic tests. Use to treat noninvasive forms of fungal disease such as oral thrush, vaginal candidiasis, and esophageal candidiasis in clients with normal neutrophil counts. Lactation.

Special Concerns: The bone marrow depressant effects may result in increased incidence of microbial infection, delayed healing, and gingival bleeding. Although used in children, safety and efficacy have not been determined. Use with caution in clients receiving leukocyte transfusions.

Side Effects: After topical use. Irritation, pruritus, dry skin. Redness, itching, or burning especially in skin folds. After IV use. Most common are listed. General toxic reaction: Fever sometimes with shaking chills usually within 15 to 20 min after treatment, headache, anorexia, malaise, generalized pain (including muscle and joint pain). GI: N&V;, dyspepsia, diarrhea, cramping, epigastric pain, abdominal pain, melena, stomatitis, anorexia. CNS: Confusion, headache, depression, abnormal thinking, insomnia. CV: Hypotension, hypertension, tachycardia, tachypnea, arrhythmias. Dermatologic: Rash, pruritus, maculopapular rash. GU: Hematuria, decreased renal function, renal tubular acidosis, nephrocalcinosis, azotemia, hypokalemia, hyposthenuria. Respiratory: Respiratory failure respiratory disorder, pneumonia, dyspnea, hypoxia, epistaxis, increased cough, lung disorder, hemoptysis, hyperventilation, apnea, pleural effusion, rhinitis. Hematologic: Normochromic, normocytic anemia; increased PT, anemia, coagulation disorder. Metabolic: Bilirubinemia, acidosis, hypovolemia. At site of injection: Venous pain at injection site with phlebitis and thrombophlebitis. Miscellaneous: Weight loss, multiple organ failiure infection, sweating, pain, chest pain, back pain, sepsis facial edema, mucous membrane disorder, asthenia, peripheral edema, eye hemorrhage, blood product transfusion reaction, chills. After intrathecal use: Blurred vision, changes in vision, difficulty in urination, numbness, tingling, pain, or weakness.

Laboratory Test Alterations: AST, ALT, GGT, LDH, alkaline phosphatase, serum creatinine, BUN, bilirubin, BSP retention values, PT. Hypomagnesemia, hyperkalemia, hypocalcemia, hypercalemia, acidosis, hypoglycemia, hyperglycemia, hypermyalesmia, hyperuricemia, hypophosphatemia.

Overdose Management: Symptoms: Cardiopulmonary arrest. Treatment: Discontinue therapy, monitor clinical status, and provide supportive therapy.

Drug Interactions: Aminoglycosides / Additive nephrotoxicity and/or ototoxicity Antineoplastic drugs / Risk for renal toxicity, bronchospasm, and hypotension Corticosteroids, Corticotropin / Potassium depletion caused by amphotericin B cardiac dysfunction Cyclosporine / Renal toxicity Digitalis glycosides / Potassium depletion caused by amphotericin B incidence of digitalis toxicity Flucytosine / Risk of flucytosine toxicity due to cellular uptake or renal excretion Nephrotoxic drugs / Risk of nephrotoxicity Skeletal muscle relaxants, surgical (e.g., succinylcholine, d-tubocurarine ) / Muscle relaxation due to amphotericin B-induced hypokalemia Tacrolimus / Serum creatinine levels Thiazides / Electrolyte depletion, especially potassium AZT / Risk of myelotoxicity and nephrotoxicity

How Supplied: Cream: 3%; Lipid Complex Injection: 50 mg, 100 mg; Lotion: 3%; Powder for injection: 50 mg, 100 mg; Suspension for injection: 100 mg/20 mL

Dosage
?Amphotericin B deoxycholate, IV Test dose by slow IV infusion.
1 mg in 20 mL of 5% dextrose injection should be infused over 20 to 30 min to determine tolerance.
Severe and rapidly progressing fungal infection.
Initial: 0.3 mg/kg over 2 to 6 hr.

Note: In impaired cardiorenal function or if a severe reaction to the test dose, therapy should be initiated with smaller daily doses (e.g., 5-10 mg). Depending on the status of the client, the dose may be increased gradually by 5-10 mg/day to a final daily dose of 0.5-0.7 mg/kg. The total daily dose should not exceed 1.5 mg/kg.
Sporotrichosis.
0.5 mg/kg/day, up to 2.5 g total dose.
Aspergillosis.
1-1.5 mg/kg/day for a total dose of 3.6 g.
Rhinocerebral phycomyosis.
0.25-0.3 mg/kg/day, up to 1-1.5 mg/kg/day, for a total dose of 3 to 4 g.
Prophylaxis of fungal infections in bone marrow transplants.
0.1 mg/kg/day.
Blastomyces, Histoplasmosis.
0.5-0.6 mg/kg/day for 4 to 12 weeks.
Candidiasis, Coccidioidomycosis.
0.5-1 mg/kg/day for 4 to 12 weeks.
Cryptococcus.
0.5-0.7 mg/kg/day for 4 to 12 weeks.
Mucormycosis.
1-1.5 mg/kg/day for 4 to 12 weeks.
Leishmaniasis.
0.5 mg/kg/day given on alternate days for 14 doses (not recommended as primary therapy).
Paracoccidioidomycosis.
0.4-0.5 mg/kg/day by slow IV infusion for 4 to 12 weeks.
?Amphotericin B Deoxycholate Suspension Oral candidiasis.
Swish the suspension in the mouth and then swallow.
?Liposomal Amphotericin B (Ambisome) All uses.
Adults and children, initial: 3-5 mg/kg/day prepared as a 1 to 2 mg/mL infusion and given initially over 120 min; infusion time may be reduced to 60 min if well tolerated or increased if client experiences discomfort. Infusion concentrations of 0.2 to 0.5 mg/mL may be used for infants and small children. An in-line membrane filter of 1 micron or more mean pore diameter may be used. When used to treat leishmaniasis, give 3 mg/kg/day on days 1 through 5, 14 and 21 to immunocompetent clients; a repeat course may be given. Give 4 mg/kg/day on days 1 through 5, 10, 17, 24, 31, and 38 to immunosuppressed clients.
?Amphotericin B cholesteryl (Amphotec) All uses.
Initial: Give a test dose of 1.6-8.3 mg/10 mL infused over 15 to 30 min. Recommended dose: 3-4 mg/kg/day prepared as a 0.6 mg/mL (range of 0.16-0.83 mg/mL) infusion delivered at a rate of 1 mg/kg/hr without an in-line filter.
?Amphotericin B lipid complex (Abelcet) All uses.
5 mg/kg/day prepared as a 1 mg/mL infusion and delivered at a rate of 2.5 mg/kg/hr. For pediatric clients and those with CV disease, the drug may be diluted to a final concentration of 2 mg/mL. Do not use an in-line filter. If the infusion time exceeds 2 hr, mix by shaking the infusion bag q 2 hr.
?Intrathecal Coccidioidal or cryptococcal meningitis.
Initial: 0.025 mg; then increase gradually up to 0.25-1 mg q 48 to 72 hr, up to a maximum total dose of 15 mg.
?Bladder Irritation Candidal cystitis.
50 mcg/mL solution instilled periodically or continuously for 5 to 10 days.
?Topical (Lotion, Cream, Ointment--Each 3%)
Apply liberally to affected areas b.i.d.-q.i.d. Depending on the type of lesion, up to 4 weeks of therapy may be necessary.