Amphotericin B (Conventional)

Name: Amphotericin B (Conventional)

If OVERDOSE is suspected

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Pharmacologic Category

  • Antifungal Agent, Parenteral

Dosing Pediatric

Note: Conventional amphotericin formulations (desoxycholate [Amphocin, Fungizone]) may be confused with lipid-based formulations (AmBisome, Abelcet, Amphotec). Lipid-based and conventional formulations are not interchangeable and have different dosage recommendations. Overdoses have occurred when conventional formulations were dispensed inadvertently for lipid-based products.

Note: Premedication: For patients who experience infusion-related immediate reactions, premedicate with the following drugs 30 to 60 minutes prior to drug administration: NSAID and/or diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone. If the patient experiences rigors during the infusion, meperidine may be administered.

Test dose: IV: Infants and Children: 0.1 mg/kg/dose to a maximum of 1 mg; infuse over 30 to 60 minutes. Many clinicians believe a test dose is unnecessary.

Susceptible fungal infections: IV: Infants and Children: Maintenance dose: 0.25 to 1 mg/kg/day given once daily; infuse over 2 to 6 hours. Once therapy has been established, amphotericin B can be administered on an every-other-day basis at 1 to 1.5 mg/kg/dose; cumulative dose: 1.5 to 2 g over 6 to 10 weeks

Note: Duration of therapy varies with nature of infection: Usual duration is 4 to 12 weeks or cumulative dose of 1 to 4 g.

Indication-specific dosing:

Infants and Children:

Candidiasis (HIV-exposed/-positive):

Invasive: IV: 0.5 to 1.5 mg/kg/day once daily (CDC 2009)

Esophageal: IV: 0.3 to 0.5 mg/kg/day once daily (CDC 2009)

Oropharyngeal, refractory: IV: 0.3 to 0.5 mg/kg/day (CDC 2009)

Coccidioidomycosis (HIV-exposed/-positive): IV: 0.5 to 1 mg/kg/day (CDC 2009)

Cryptococcus, CNS disease (HIV-exposed/-positive): IV: 0.7 to 1 mg/kg/day plus flucytosine; Note: Minimum 2 week induction followed by consolidation and chronic suppressive therapy; may increase amphotericin dose to 1.5 mg/kg/day if flucytosine is not tolerated.

Cryptococcus, disseminated (non-CNS disease) or severe pulmonary disease (HIV-exposed/-positive): IV: 0.7 to 1 mg/kg/day once daily with or without flucytosine

Histoplasma, CNS or severe disseminated: IV: 1 mg/kg/day once daily (CDC 2009)

Adolescents:

Coccidioidomycosis in HIV-infected patients with severe, non-meningeal infection (ie, diffuse pulmonary or severely ill with extrathoracic disseminated disease) (off-label use): IV: Refer to adult dosing.

Dosing Hepatic Impairment

No dosage adjustment provided in manufacturer’s labeling.

Storage

Store intact vials under refrigeration. Protect from light. Reconstituted vials are stable, protected from light, for 24 hours at room temperature and 1 week when refrigerated. Parenteral admixtures in D5W are stable, protected from light, for 24 hours at room temperature and 2 days under refrigeration. Short-term exposure (<24 hours) to light during IV infusion does not appreciably affect potency.

Adverse Reactions

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

ALERT U.S. Boxed Warning

Appropriate use:

This drug should be used primarily for treatment of patients with progressive and potentially life-threatening fungal infections; it should not be used to treat noninvasive forms of fungal disease such as oral thrush, vaginal candidiasis, and esophageal candidiasis in patients with normal neutrophil counts.

Error prevention:

Exercise caution to prevent inadvertent overdose with amphotericin B. Verify the product name and dosage if dose exceeds 1.5 mg/kg.

Pregnancy Risk Factor B Pregnancy Considerations

Adverse events were not observed in animal reproduction studies. Amphotericin crosses the placenta and enters the fetal circulation. Amphotericin B is recommended for the treatment of serious systemic fungal diseases in pregnant women. Refer to current guidelines (IDSA [Pappas 2016]; King 1998; Pilmis 2015).

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