Yes

Antifungal Agent, Parenteral; Antifungal Agent, Topical

Treatment of severe systemic and central nervous system infections caused by susceptible fungi such as Candida species, Histoplasma capsulatum, Cryptococcus neoformans, Aspergillus species, Blastomyces dermatitidis, Torulopsis glabrata, and Coccidioides immitis; fungal peritonitis; irrigant for bladder fungal infections; and topically for cutaneous and mucocutaneous candidal infections; used in fungal infection in patients with bone marrow transplantation, amebic meningoencephalitis, ocular aspergillosis (intraocular injection), candidal cystitis (bladder irrigation), chemoprophylaxis (low-dose I.V.), immunocompromised patients at risk of aspergillosis (intranasal/nebulized), refractory meningitis (intrathecal), coccidioidal arthritis (intra-articular/I.M.).

B

Hypersensitivity to amphotericin or any component

Anaphylaxis has been reported with other amphotericin B-containing drugs. During the initial dosing, the drug should be administered under close clinical observation. Avoid additive toxicity with other nephrotoxic drugs; drug-induced renal toxicity usually improves with interrupting therapy, decreasing dosage, or increasing dosing interval. I.V. amphotericin is used primarily for the treatment of patients with progressive and potentially fatal fungal infections; topical preparations may stain clothing. Infusion reactions are most common 1-3 hours after starting the infusion and diminish with continued therapy. Use amphotericin B with caution in patients with decreased renal function. Pulmonary reactions may occur in neutropenic patients receiving leukocyte transfusions; separation of the infusions as much as possible is advised.

>10%:

Central nervous system: Fever, chills, headache, malaise, generalized pain

Endocrine & metabolic: Hypokalemia, hypomagnesemia

Gastrointestinal: Anorexia

Hematologic: Anemia

Renal: Nephrotoxicity

1% to 10%:

Cardiovascular: Hypotension, hypertension, flushing

Central nervous system: Delirium, arachnoiditis, pain along lumbar nerves

Gastrointestinal: Nausea, vomiting

Genitourinary: Urinary retention

Hematologic: Leukocytosis

Local: Thrombophlebitis

Neuromuscular & skeletal: Paresthesia (especially with I.T. therapy)

Renal: Renal tubular acidosis, renal failure

<1%: Cardiac arrest, bone marrow suppression, convulsions, maculopapular rash, coagulation defects, thrombocytopenia, agranulocytosis, leukopenia, acute liver failure, vision changes, hearing loss, anuria, dyspnea

Symptoms of overdose include cardiac arrest, renal dysfunction, anemia, thrombocytopenia, granulocytopenia, fever, nausea, and vomiting

Treatment is supportive

Increased nephrotoxicity: Aminoglycosides, cyclosporine, other nephrotoxic drugs

Potentiation of hypokalemia: Corticosteroids, corticotropin

Increased digitalis and neuromuscular-blocking agent toxicity due to hypokalemia

Decreased effect: Pharmacologic antagonism may occur with azole antifungal agents (eg, miconazole, ketoconazole)

Pulmonary toxicity has occurred with concomitant administration of amphotericin B and leukocyte transfusions

Reconstitute only with sterile water without preservatives, not bacteriostatic water. Benzyl alcohol, sodium chloride, or other electrolyte solutions may cause precipitation.

For I.V. infusion, an in-line filter (>1 micron mean pore diameter) may be used

Short-term exposure (<24 hours) to light during I.V. infusion does not appreciably affect potency

Reconstituted solutions with sterile water for injection and kept in the dark remain stable for 24 hours at room temperature and 1 week when refrigerated

Stability of parenteral admixture at room temperature (25°C): 24 hours; at refrigeration (4°C): 2 days

Standard diluent: Dose/250-500 mL D₅W

Binds to ergosterol altering cell membrane permeability in susceptible fungi and causing leakage of cell components with subsequent cell death

Distribution: Minimal amounts enter the aqueous humor, bile, CSF (inflamed or noninflamed meninges), amniotic fluid, pericardial fluid, pleural fluid, and synovial fluid

Protein binding, plasma: 90% infusion

Half-life, biphasic: Initial: 15-48 hours; Terminal: 15 days

Time to peak: Within 1 hour following a 4- to 6-hour dose

Elimination: 2% to 5% of dose eliminated in biologically active form in urine; approximately 40% eliminated over 7-day period and may be detected in urine for at least 7 weeks after discontinued use

I.V.: Premedication: For patients who experience chills, fever, hypotension, nausea, or other nonanaphylactic infusion-related immediate reactions, premedicate with the following drugs, 30-60 minutes prior to drug administration: a nonsteroidal (eg, ibuprofen, choline magnesium trisalicylate, etc) with or without diphenhydramine; or acetaminophen with diphenhydramine; or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered.

Infants and Children:

Test dose: I.V.: 0.1 mg/kg/dose to a maximum of 1 mg; infuse over 30-60 minutes. Many clinicians believe a test dose is unnecessary.

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

Adults:

Test dose: 1 mg infused over 20-30 minutes. Many clinicians believe a test dose is unnecessary.

Maintenance dose: Usual: 0.25-1.5 mg/kg/day; 1-1.5 mg/kg over 4-6 hours every other day may be given once therapy is established; aspergillosis, mucormycosis, rhinocerebral phycomycosis often require 1-1.5 mg/kg/day; do not exceed 1.5 mg/kg/day

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

I.T.: Meningitis, coccidioidal or cryptococcal:

Children.: 25-100 mcg every 48-72 hours; increase to 500 mcg as tolerated

Adults: Initial: 25-300 mcg every 48-72 hours; increase to 500 mcg to 1 mg as tolerated; maximum total dose: 15 mg has been suggested

Oral: 1 mL (100 mg) 4 times/day

Topical: Apply to affected areas 2-4 times/day for 1-4 weeks of therapy depending on nature and severity of infection

Bladder irrigation: Candidal cystitis: Irrigate with 50 mcg/mL solution instilled periodically or continuously for 5-10 days or until cultures are clear

Dosing adjustment in renal impairment: If renal dysfunction is due to the drug, the daily total can be decreased by 50% or the dose can be given every other day; I.V. therapy may take several months

Dialysis: Poorly dialyzed; no supplemental dosage necessary when using hemo- or peritoneal dialysis or CAVH/CAVHD

Administration in dialysate: Children and Adults: 1-2 mg/L of peritoneal dialysis fluid either with or without low-dose I.V. amphotericin B (a total dose of 2-10 mg/kg given over 7-14 days). Precipitate may form in ionic dialysate solutions.

Renal function (monitor frequently during therapy), electrolytes (especially potassium and magnesium), liver function tests, temperature, PT/PTT, CBC; monitor input and output; monitor for signs of hypokalemia (muscle weakness, cramping, drowsiness, EKG changes, etc)

Therapeutic: 1-2 mg/mL (SI: 1-2.2 mmol/L)

Sedation is common; may cause delirium

May cause bone marrow suppression; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

Take/use as directed; complete full regimen of treatment (most skin lesions may take 1-3 weeks of therapy). Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You may experience nausea, vomiting, or anorexia (small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help); generalized muscle or joint paint (mild analgesic may help); hypotension (use caution when rising from sitting or lying position or when climbing stairs). Report severe muscle cramping or weakness, chest pain or palpitations, CNS disturbances, skin rash, change in urinary patterns or difficulty voiding, black stool, or unusual bruising or bleeding; (I.V. report pain at infusion site).

Breast-feeding precautions: Do not breast-feed.

May be infused over 2-6 hours

Cream: 3% (20 g)

Lotion: 3% (30 mL)

Ointment, topical: 3% (20 g)

Powder for injection, lyophilized, as desoxycholate: 50 mg

Suspension, oral: 100 mg/mL (24 mL with dropper)

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