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Drugs reference index «Amphotericin B»

Amphotericin B


Amphotericin B

Pronunciation: (am-foe-TER-i-sin)Class: Polyene antifungal Amphotericin B Cholesteryl

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)

Pharmacology

Alters fungal cell membrane permeability.

Pharmacokinetics

Absorption

Amphotericin B cholesteryl

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).

Distribution

Amphotericin B cholesteryl

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).

Metabolism

Not known.

Amphotericin B desoxycholate

Metabolic pathways are unknown.

Elimination

Amphotericin B cholesteryl

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 ).

Special Populations

Renal Function ImpairmentAmphotericin B cholesteryl

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

Not known.

Indications and Usage

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.

Unlabeled Uses

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.

Contraindications

Standard considerations.

Dosage and Administration

Amphotericin B CholesterylSystemic Fungal Infections Adults and Children

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.

General Advice

  • Amphotericin B cholesteryl
  • Administer diluted in dextrose 5% injection by IV infusion rate of 1 mg/kg/h.
  • Follow manufacturer's instructions for reconstitution and administration. Reconstitute by using sterile water for injection. Do not reconstitute with saline or dextrose solutions or admix with saline or electrolytes.
  • Do not filter or use an in-line filter.
  • Do not mix with other IV medications.
  • Amphotericin B desoxycholate
  • Do not use a filter less than 1 micron
  • Whenever therapy is interrupted for more than 7 days, resume treatment by starting with the lowest dosage level and gradually increasing the dose.
  • Under no circumstances should the daily dose exceed 1.5 mg/kg.
  • Follow the manufacturer's instructions for reconstitution and administration. Reconstitute by using sterile water for injection without a bacteriostatic agent.
  • Shake the vial immediately until the colloidal solution is clear.
  • Use solution prepared for IV infusion (0.1 mg/mL or less) promptly after preparation, and protect from light during administration.
  • Amphotericin B, lipid-based
  • Follow manufacturer's instructions for reconstitution and administration. Use dextrose 5% injection for reconstitution. Do not reconstitute with other drugs or electrolytes because compatibility of lipid-based amphotericin B has not been established. Flush an existing IV line with dextrose 5% injection before infusion of lipid-based amphotericin B, or use a separate infusion line.
  • Amphotericin B liposomal
  • Shake the vial gently until there is no yellow sediment at the bottom.
  • Do not use an in-line filter less than 5 microns.
  • Amphotericin B liposomal must be reconstituted using sterile water for injection (without a bacteriostatic agent)
  • Do not reconstitute with saline or add saline to the reconstituted concentration, or mix with other drugs. The use of solution other than those recommended may cause precipitation.
  • Do not use a filter less than 1 micron.

Storage/Stability

Amphotericin B, lipid-based

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.

Drug Interactions

Antineoplastic agents

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.

Incompatibility

Do not mix with other IV medications.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

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.

CNS

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.

Dermatologic

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.

EENT

Conjunctivitis, dry eyes, eye hemorrhage, pharyngitis (2% to 10%); amblyopia, deafness, ear disorder, tinnitus (1% to less than 5%); visual impairment.

GI

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.

Genitourinary

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.

Hematologic-Lymphatic

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).

Hepatic

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.

Hypersensitivity

Allergic reaction (2% to 10%); anaphylactic and anaphylactoid reactions, bronchospasm, hypersensitivity pneumonitis, wheezing.

Local

Injection-site inflammation (2% to 10%); pain at injection site, phlebitis, thrombophlebitis.

Metabolic-Nutritional

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.

Musculoskeletal

Back pain (12%); arthralgia, bone pain, dystonia, myalgia, neck pain, rigors (2% to 10%); myasthenia including bone, joint, and muscle pain.

Respiratory

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).

Miscellaneous

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).

Precautions

Warnings

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

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.

Pregnancy

Category B .

Lactation

Undetermined.

Children

Amphotericin B, lipid-based, amphotericin B cholesteryl

Safety and efficacy in children younger than 1 mo of age not established.

Amphotericin B desoxycholate

Safety and efficacy not established.

Elderly

No serious unexpected adverse reactions have been reported.

Hypersensitivity

Anaphylaxis has been reported.

Nephrotoxicity

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 infusion

Rapid IV infusion has been associated with arrhythmias, hypokalemia, hypotension, and shock.

Overdosage

Symptoms

Cardiorespiratory arrest.

Patient Information

  • Explain need for prolonged therapy and for close monitoring during course of therapy.
  • Encourage patient to increase fluid intake to 2,000 to 3,000 mL/day, if allowed.
  • Inform patient to report any discomfort at injection site immediately.
  • Instruct patient to report symptoms of chills, fever, or malaise.

Copyright © 2009 Wolters Kluwer Health.

  • Amphotericin B Prescribing Information (FDA)
  • Amphotericin B MedFacts Consumer Leaflet (Wolters Kluwer)
  • Fungizone Prescribing Information (FDA)
  • amphotericin B Concise Consumer Information (Cerner Multum)
  • amphotericin b Intravenous, Injection Advanced Consumer (Micromedex) - Includes Dosage Information

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