blastomycosis, systemic candidiasis, coccidioidomycosis, histoplasmosis, zygomycosis

(including mucormycosis due to susceptible species of the genera Absidia, Mucor, and
Rhizopus), and infections due to related susceptible species of Conidiobolus, Basidiobolus,
and sporotrichosis.

Leishmaniasis: Alternative treatment in patients with American (New World)

mucocutaneous leishmaniasis

Use: Off-Label: Adult

Candidiasis, endophthalmitis (intravitreal); Candidiasis, esophageal (non-HIV-infected patients);

Candidiasis, esophageal, in patients with HIV; Candidiasis, oropharyngeal (fluconazole-
refractory) (oral); Candidiasis, urinary tract; Leishmaniasis, visceral; Ocular aspergillosis
(ophthalmic); Talaromycosis (formerly penicillosis)

Medication Safety Issues

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its
list of drugs which have a heightened risk of causing significant patient harm when
used in error.

Sound-alike/look-alike issues:

Amphotericin B may be confused with amphotericin B liposomal

Other safety concerns:

Conventional amphotericin formulations (Amphocin, Fungizone) may be confused with

lipid-based formulations (AmBisome, Abelcet, Amphotec).

Large overdoses have occurred when conventional formulations were dispensed

inadvertently for lipid-based products. Single daily doses of conventional amphotericin
formulation never exceed 1.5 mg/kg.

Adverse Reactions
The following adverse drug reactions and incidences are derived from product labeling unless
otherwise specified.

Systemic:

>10%:
 Cardiovascular: Hypotension

Central nervous system: Chills, headache (less frequent with I.T.), malaise, pain (less
frequent with I.T.)

Endocrine & metabolic: Hypokalemia, hypomagnesemia

Gastrointestinal: Anorexia, diarrhea, epigastric pain, heartburn, nausea (less frequent

with I.T.), stomach cramps, vomiting (less frequent with I.T.)

Hematologic & oncologic: Anemia (normochromic-normocytic)

Local: Pain at injection site (with or without phlebitis or thrombophlebitis [incidence

may increase with peripheral infusion of admixtures])

Renal: Renal function abnormality (including azotemia, renal tubular acidosis,

nephrocalcinosis [>0.1 mg/ml]), renal insufficiency

Respiratory: Tachypnea

Miscellaneous: Fever

1% to 10%:

Cardiovascular: Flushing, hypertension

Central nervous system: Arachnoiditis, delirium, neuralgia (lumbar; especially with

intrathecal therapy), paresthesia (especially with intrathecal therapy)

Genitourinary: Urinary retention

Hematologic & oncologic: Leukocytosis

<1% (Limited to important or life-threatening): Acute hepatic failure, agranulocytosis,

anuria, blood coagulation disorder, bone marrow depression, bronchospasm, cardiac
arrest, cardiac arrhythmia, cardiac failure, convulsions, diplopia, dyspnea, eosinophilia,
exfoliation of skin, hearing loss, hemorrhagic gastroenteritis, hepatitis, hypersensitivity
pneumonitis, increased liver enzymes, jaundice, leukoencephalopathy, leukopenia,
maculopapular rash, melena, nephrogenic diabetes insipidus, oliguria, peripheral
neuropathy, pruritus, pulmonary edema, renal failure, renal tubular acidosis, shock,
Stevens-Johnson syndrome, thrombocytopenia, tinnitus, toxic epidermal necrolysis,
ventricular fibrillation, vertigo (transient), visual disturbance, wheezing

Contraindications
Hypersensitivity to amphotericin or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylaxis: Has been reported with amphotericin B-containing drugs; facilities for
cardiopulmonary resuscitation should be available during administration due to the
possibility of anaphylactic reaction. If severe respiratory distress occurs, the infusion
should be immediately discontinued; during the initial dosing, the drug should be
administered under close clinical observation.

• Infusion reactions: Acute reactions (eg, fever, shaking chills, hypotension, anorexia,
nausea, vomiting, headache, tachypnea) may occur 1 to 3 hours after starting an
intravenous infusion. These reactions are usually more common with the first few
doses and generally diminish with subsequent doses. Avoid rapid infusion to prevent
hypotension, hypokalemia, arrhythmias, and shock.

• Leukoencephalopathy: Has been reported following administration of amphotericin.

Total body irradiation has been reported to be a possible predisposition.

• Nephrotoxicity: May cause nephrotoxicity; usual risk factors include underlying renal
disease, concomitant nephrotoxic medications and daily and/or cumulative dosing of
amphotericin. Avoid use with other nephrotoxic drugs; drug-induced renal toxicity
usually improves with interrupting therapy, decreasing dosage, or increasing dosing
interval. However permanent impairment may occur, especially in patients receiving
large cumulative dose (eg, >5 g) and in those also receiving other nephrotoxic drugs.
Hydration and sodium repletion prior to administration may reduce the risk of
developing nephrotoxicity. Frequent monitoring of renal function is recommended.

Disease-related concerns:

• Fungal infections: [US Boxed Warning]: Should be used primarily for treatment of
progressive, potentially life-threatening fungal infections, not noninvasive forms
of infection.

• Heart failure: In a scientific statement from the American Heart Association,

amphotericin has been determined to be an agent that may cause direct myocardial
toxicity (magnitude: moderate/major) (AHA [Page 2016]).

• Renal impairment: Use with caution in patients with renal impairment.

 Special populations:

• Neutropenic patients: Pulmonary reactions may occur in neutropenic patients

receiving leukocyte transfusions; separation of the infusions as much as possible is
advised.

Other warnings/precautions:

• Error prevention: [US Boxed warning]: Verify the product name and dosage if dose
exceeds 1.5 mg/kg.

• Therapy interruption: If therapy is stopped for >7 days, restart at the lowest dose
recommended and increase gradually.

Warnings: Additional Pediatric Considerations

May premedicate patients who experience mild adverse reactions with acetaminophen and
diphenhydramine 30 minutes prior to the amphotericin B infusion; meperidine and ibuprofen
may help to reduce fevers and chills; hydrocortisone can be added to the infusion solution to
reduce febrile and other systemic reactions. If therapy is stopped for >7 days, restart at the
lowest dose recommended and increase gradually. Administer by slow IV infusion; rapid
infusion has been associated with hypotension, hypokalemia, arrhythmias, and shock. Avoid
extravasation; may cause chemical irritation; monitor infusion site; heparin 1 unit/1 mL of
infusion solution can be added to reduce phlebitis. Use caution with intraperitoneal
administration; use associated with irritation to the peritoneum and abdominal pain; not
routinely used unless intolerance to other therapies (ISPD [Warady 2000b]).

Metabolism/Transport Effects
None known.

Drug Interactions
(For additional information: Launch drug interactions program)

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C:
Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of
Amifostine. Management: When used at chemotherapy doses, hold blood pressure
lowering medications for 24 hours before amifostine administration. If blood pressure
lowering therapy cannot be held, do not administer amifostine. Use caution with
radiotherapy doses of amifostine. Risk D: Consider therapy modification