Trade Names:Amphotec- Powder for injection 50 mg (as cholesteryl)- Powder for injection 100 mg (as cholesteryl)Amphotericin B Desoxycholate
Trade Names:Amphotericin B- Powder for injection 50 mg (as desoxycholate)Amphotericin B, Lipid-Based
Trade Names:Abelcet- Suspension for injection 100 mg per (as lipid complex)
Trade Names:AmBisome- Powder for injection 50 mg (as liposomal)
Alters fungal cell membrane permeability.
C max is approximately 2.6 to 2.9 mcg/mL.Amphotericin B desoxycholate
C max is 0.5 to 2 mcg/mL.Amphotericin B, lipid-based
C max is approximately 1.7 mcg/mL ( Abelcet ) and approximately 7.3 to 83 mcg/mL ( Ambisome ; 1 to 5 mg/kg/day).
Vd is approximately 3.8 to 4.1 L/kg; distribution half-life is approximately 3.5 min.Amphotericin B desoxycholate
Plasma protein binding is more than 90%. Distributed to inflamed pleura, peritoneum, synovium, and aqueous humor.Amphotericin B, lipid-based
Vd is approximately 131 L/kg ( Abelcet ) and 0.1 to 0.44 L/kg ( Ambisome ; 1 to 5 mg/kg/day).
Not known.Amphotericin B desoxycholate
Metabolic pathways are unknown.
The half-life is approximately 27.5 to 28.2 h; Cl is approximately 0.105 to 0.112 L/h/kg.Amphotericin B desoxycholate
Elimination half-life is approximately 15 days. Plasma t ½ is about 24 h. Excreted slowly over a period of weeks to months by the kidneys, with approximately 40% appearing in the urine over a 7-day period.Amphotericin B, lipid-based
The half-life is approximately 173.4 h ( Abelcet ), approximately 7 to 10 h ( Ambisome ; measured within 24-h dosing interval), and approximately 100 to 153 h ( Ambisome ; measured up to 49 days after dosing). Cl is approximately 436 mL/h/kg ( Abelcet ) and 11 to 51 mL/h/kg ( Ambisome ).
The effects of CrCl outside the range of 35 to 202 mL/min per 70 kg have not been studied.Amphotericin B, lipid-based
Pharmacokinetics have not been studied.Hepatic Function ImpairmentAmphotericin B cholesteryl
The effects of hepatic function outside mean values for AST and total bilirubin of 59.4 units/mL and 3.5 mg/dL, respectively, have not been studied.Amphotericin B, lipid-based
Treatment of progressive, potentially fatal infections caused by certain fungal species.Amphotericin B cholesteryl
Treatment of invasive aspergillosis in patients for whom renal function impairment or unacceptable toxicity precludes use of amphotericin B deoxycholate or in patients with invasive aspergillosis in whom amphotericin deoxycholate has failed.Amphotericin B desoxycholate
Treatment of potentially life-threatening infections caused by certain fungal species. Amphotericin B for injection is specifically intended to treat potentially life-threatening fungal infections: aspergillosis, cryptococcosis (torulosis), North American blastomycosis, systemic candidiasis, coccidioidomycosis, histoplasmosis, zygomycosis including mucormycosis caused by susceptible species of the genera Absidia , Mucor , and Rhizopus , and infections caused by related susceptible species of Conidiobolus , Basidiobolos , and sporotrichosis.Amphotericin B, lipid-based
Treatment of invasive fungal infections in patients refractory to conventional amphotericin B (lipid complex); empirical treatment of febrile, neutropenic patients with presumed fungal infections (liposomal); treatment of visceral leishmaniasis (liposomal); treatment of cryptococcal meningitis in HIV-infected patients (liposomal); treatment of Aspergillus species, Candida species, and Cryptococcus species refractory to amphotericin B deoxycholate, or in patients for whom renal function impairment or unacceptable toxicity precludes use of amphotericin B deoxycholate.
Prophylaxis of fungal infections in patients with bone marrow transplantation; treatment of primary amoebic meningoencephalitis caused by Naegleria fowleri ; subconjunctival or intravitreal treatment of ocular aspergillosis; bladder irrigation for candidal cystitis; chemoprophylaxis of aspergillosis; intrathecal treatment of severe meningitis unresponsive to IV therapy; intra-articular or IM treatment of coccidioidal arthritis; intranasal or nebulized administration in immunocompromised patients at risk of aspergillosis.
IV Test dose advisable (eg, 10 mL containing 1.6 to 8.3 mg infused over 15 to 30 min); recommended treatment dose is 3 to 4 mg/kg once a day.Amphotericin B DesoxycholateAdults
IV Because individual tolerance varies greatly, consider administration of a single IV test dose (1 mg in 20 mL of dextrose 5% in water) administered over 20 to 30 min. Monitor the patient's temperature, pulse, respiration, and BP every 30 min for 2 to 4 h. In patients with healthy cardio-renal function, therapy is usually started with 0.25 mg/kg daily. However, in patients with a severe, rapidly progressing fungal infection, therapy may be started with a dose of 0.3 mg/kg daily. In patients with impaired cardio-renal function or severe reactions to the test dose, start therapy with lower daily doses. Depending on cardio-renal function, doses may be increased in increments of 5 to 10 mg/day to a final daily dose of 0.5 to 0.7 mg/kg. Total daily doses may range up to 1 mg/kg/day or 1.5 mg/kg given on alternate days.Aspergillosis
Treatment has been for a period up to 11 mo with a total dose of up to 3.6 g.Rhinocerebral phycomycosis
Because this fulminating disease generally occurs in association with diabetic ketoacidosis, it is imperative that diabetic control be restored for amphotericin B treatment to be successful. Although a total dose of 3 to 4 g will infrequently cause lasting renal function impairment, a cumulative dose of at least 3 g is recommended. This appears to be a reasonable minimum dose when there is evidence of deep tissue invasion.Sporotrichosis
Treatment has been for a period of up to 9 mo with a total dose of up to 2.5 g.Amphotericin B Lipid ComplexSystemic Fungal Infections Adults and Children
IV 5 mg/kg/day as a single infusion at a rate of 2.5 mg/kg/h. If infusion time exceeds 2 h, mix contents of infusion bag by shaking every 2 h. Dilute to 2 mg/mL for children and patients with CV disease.Amphotericin B LiposomalCryptococcal Meningitis Adults
IV 6 mg/kg/day.Empirical Fungal Infections Adults
IV 3 mg/kg/day.Leishmaniasis Adults
IV 3 mg/kg/day on days 1 through 5 and on days 14 and 21 for immunocompetent patients; administer 4 mg/kg/day on days 1 through 5 and on days 10, 17, 24, 31, and 38 for immunosuppressed patients. For immunocompetent patients who do not achieve parasitic Cl with the recommended dose, a repeat course may be useful.Systemic Fungal Infections Adults
IV 3 to 5 mg/kg/day as a 1 to 2 mg/mL dilution.Children
IV 3 to 5 mg/kg/day as a 0.2 to 0.5 mg/mL dilution.
Store refrigerated at 36° to 46°F. Protect from light. Do not freeze. After reconstitution, store up to 48 h at 36° to 46°F and an additional 6 h at room temperature. Do not freeze. Discard any unused portion.Amphotericin B liposomal
Store unopened vials at temperatures up to 77°F. Store reconstituted product concentrate refrigerated at 36° to 46°F. Do not freeze. Inject within 6 h of dilution with dextrose 5% injection in water.Amphotericin B cholesteryl
Store at 59° to 86°F. After reconstitution, store refrigerated at 36° to 46°F and use within 24 h. Do not freeze. After further dilution with dextrose 5% in water for injection, store refrigerated at 36° to 46°F and use within 24 h. Discard unused portion.Amphotericin B desoxycholate
Store refrigerated at 36° to 46°F. Protect from light. The concentrate, after reconstitution, may be stored in the dark, at room temperature for 24 h or refrigerated for 1 wk. Discard any unused portion. Solution prepared for IV infusion (0.1 mg/mL or less) should be used promptly after preparation and should be protected from light during administration.
Concurrent use may enhance potential for arrhythmias, bronchospasm, renal toxicity, and shock.Azole antifungal agents (eg, fluconazole, ketoconazole)
Antagonism between amphotericin B and the antifungal agent may occur.Corticosteroids and corticotropin
Increased potential for hypokalemia.Cyclosporine, tacrolimus
May increase nephrotoxic effects.Digitalis glycosides
Amphotericin B–induced hypokalemia may potentiate digitalis toxicity.Flucytosine
Increased risk of flucytosine toxicity.Leukocyte transfusions
Acute pulmonary toxicity has been reported in patients receiving IV amphotericin B and leukocyte transfusions. Do not give concurrently.Nephrotoxic agents (eg, aminoglycosides)
Possible synergistic nephrotoxicity.Skeletal muscle relaxants (eg, tubocurarine)
Amphotericin B–induced hypokalemia may enhance curariform effect of skeletal muscle relaxant.Zidovudine
Closely monitor renal and hematologic function if used with amphotericin B.
Do not mix with other IV medications.
None well documented.
Phlebitis (25%); hypertension, tachycardia (23%); hypotension (22%); chest pain (12%); cardiac arrest (6%); vasodilatation (5%); arrhythmia; atrial fibrillation, bradycardia, cardiomegaly, hemorrhage, postural hypotension; valvular heart disease, vascular disorder (2% to 10%); cardiovascular disorder (at least 5%); CHF, supraventricular tachycardia, syncope, ventricular extrasystoles (1% to less than 5%); MI, shock, tachypnea.
Headache, insomnia (21%); anxiety (14%); asthenia, confusion (13%); dizziness (10%); abnormal thinking, agitation, coma, convulsions, depression, dysesthesia, hallucinations, malaise, nervousness, paresthesia, somnolence, tremor (2% to 10%); hypertonia, neuropathy, psychosis, speech disorder, stupor (1% to less than 5%); cerebral vascular accident, diplopia, encephalopathy, extrapyramidal syndrome, peripheral neuropathy, transient vertigo.
Rash (25%); pruritus, sweating (11%); alopecia, dry skin, herpes simplex, maculopapular rash, purpura, skin discoloration, skin disorder, skin ulcer, urticaria, vesiculobullous rash (2% to 10%); acne, petechial rash, skin nodule (1% to less than 5%); erythema multiforme, exfoliative dermatitis, flushing.
Conjunctivitis, dry eyes, eye hemorrhage, pharyngitis (2% to 10%); amblyopia, deafness, ear disorder, tinnitus (1% to less than 5%); visual impairment.
Vomiting (44%); nausea (40%); diarrhea (30%); constipation (21%); anorexia (14%); GI hemorrhage, nausea and vomiting (11%); dry mouth/nose, dyspepsia, dysphagia, eructation, fecal incontinence, flatulence, hemorrhoids, gum/oral hemorrhage, hematemesis, ileus, mucositis, rectal disorder, stomatitis, ulcerative stomatitis (2% to 10%); bloody diarrhea, increased gamma-glutamyl transpeptidase, GI disorder, gingivitis, glossitis, melena, mouth ulceration, oral moniliasis, rectal disorder (1% to less than 5%); cramping, epigastric pain.
Nephrotoxicity (34%); hematuria (14%); kidney failure (5%); abnormal renal function, acute kidney failure, acute renal failure, dysuria, toxic nephropathy, urinary incontinence, vaginal hemorrhage (2% to 10%); albuminuria, glucosuria, oliguria, urinary retention, urinary tract disorder (1% to less than 5%); anuria, azotemia, decreased renal function, hyposthenuria, impotence, nephrocalcinosis, renal tubular acidosis.
Anemia (48%); leukopenia (17%); thrombocytopenia (13%); coagulation disorder, decreased or increased prothrombin, ecchymosis, fluid overload, petechiae (2% to 10%); decreased thromboplastin, hypochromic anemia, increased fibrinogen, leukocytosis (1% to less than 5%); blood dyscrasias including eosinophilia, coagulation defects normochromic, normocytic anemia; agranulocytosis (postmarketing).
Increased ALT (15%); abnormal LFTs, increased AST (13%); hepatocellular damage, hepatomegaly, veno-occlusive liver disease (2% to 10%); liver failure (1% to less than 5%); cholangitis, cholecystitis, hepatitis, jaundice.
Allergic reaction (2% to 10%); anaphylactic and anaphylactoid reactions, bronchospasm, hypersensitivity pneumonitis, wheezing.
Injection-site inflammation (2% to 10%); pain at injection site, phlebitis, thrombophlebitis.
Hypokalemia (51%); hypomagnesemia, increased creatinine (49%); increased BUN (31%); hyperglycemia (28%); increased alkaline phosphatase (22%); hypocalcemia (21%); bilirubinemia (19%); peripheral edema (17%); edema, hypervolemia (15%); hyponatremia (12%); acidosis, hyperchloremia, hyperkalemia, hypermagnesemia, hyperphosphatemia, hypophosphatemia, hypoproteinemia, increased amylase, increased LDH, nonprotein nitrogen, respiratory alkalosis (2% to 10%); generalized edema, weight gain (at least 5%); dehydration, hyperlipidemia, hypernatremia, hypoglycemia; weight loss (1% to less than 5%); hyperamylasemia, hyperuricemia.
Back pain (12%); arthralgia, bone pain, dystonia, myalgia, neck pain, rigors (2% to 10%); myasthenia including bone, joint, and muscle pain.
Dyspnea (29%); increased cough (22%); hypoxia (21%); epistaxis (20%); lung disorder (18%); pleural effusion (13%); rhinitis (11%); respiratory failure (8%); apnea (at least 5%); hyperventilation (5%); asthma, atelectasis, hemoptysis, hiccup, lung edema, pneumonia, respiratory insufficiency, sinusitis (2% to 10%); respiratory disorder (1% to less than 5%); pulmonary edema (postmarketing).
Chills/rigors (90%); chills (77%); fever (58%); abdominal pain (22%); blood product transfusion reaction (19%); pain, sepsis (14%); infection (13%); multiple organ failure (11%); procedural complications (10%); cellulitis, cell-mediated immunological reaction, enlarged abdomen, face edema, graft-versus-host disease, influenza-like symptoms (2% to 10%); mucous membrane disorder (at least 5%); accidental injury, death, hypothermia, immune system disorder (1% to less than 5%); angioedema, cyanosis/hypoventilation, hemorrhagic cystitis (postmarketing).
Do not use to treat noninvasive forms of fungal diseases (eg, esophageal candidiasis, oral thrush, vaginal candidiasis) in patients with normal neutrophil counts. Exercise caution to prevent inadvertent overdose. Use primarily for the treatment of progressive and potentially life-threatening fungal infections.
Monitor pulmonary function in patients receiving leukocyte transfusions.Fungal culture
Ensure that fungal culture (blood or urine, as appropriate) of organism has been obtained before beginning therapy.Infusion-related symptoms
If the patient experiences infusion-related symptoms (eg, chills, fever, hypotension, joint pain), an NSAID, corticosteroid, or other antipyretic may be given before administering drug.Injection site
Monitor IV injection site closely during administration for signs of infiltration.Lab values
Monitor laboratory values, including LFTs, CBC, renal function tests, serum creatinine, and serum electrolytes (particularly magnesium and potassium levels), during therapy.
Category B .
Safety and efficacy in children younger than 1 mo of age not established.Amphotericin B desoxycholate
Safety and efficacy not established.
No serious unexpected adverse reactions have been reported.
Anaphylaxis has been reported.
Drug is toxic; use with caution under close supervision. Renal damage is the most important toxic effect. Despite its dangerous adverse reactions, amphotericin B frequently is the only effective treatment for potentially fatal fungal diseases.
Rapid IV infusion has been associated with arrhythmias, hypokalemia, hypotension, and shock.
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