Amphotericin B (fungizone ®)

Microbiology
Amphotericin B shows a high order of in vitro activity against many species of fungi.
Histoplasma capsulatum,
Coccidioides immitis,
Candida species,
Blastomyces dermatitidis,
Rhodotorula,
Cryptococcus neoformans,
Sporothrix schenckii,
Mucor mucedo, and
Aspergillus fumigatus

All are inhibited by concentrations of amphotericin B ranging from 0.03 to 1.0 mcg/mL in vitro. While Candida albicans is generally quite susceptible to amphotericin B, non-albicans species may be less susceptible. Pseudallescheria boydii and Fusarium sp. are often resistant to amphotericin B. The antibiotic is without effect on bacteria, rickettsiae, and viruses

FUNGIZONE Intravenous (Amphotericin B for Injection, USP) should be administered primarily to patients with progressive, potentially life-threatening fungal infections. This potent drug should not be used to treat noninvasive fungal infections, such as oral thrush, vaginal candidiasis, and esophageal candidiasis in patients with normal neutrophil counts.

FUNGIZONE Intravenous is specifically intended to treat potentially life-threatening fungal infections: aspergillosis, cryptococcosis (torulosis), North American blastomycosis, systemic candidiasis, coccidioido-mycosis, histoplasmosis, zygomycosis including mucormycosis due to susceptible species of the genera Absidia, Mucor, and Rhizopus, and infections due to related susceptible species of Conidiobolus and Basidiobolus, and sporotrichosis.

Amphotericin B may be useful in the treatment of American mucocutaneous leishmaniasis, but it is not the drug of choice as primary therapy.

General
Amphotericin B should be administered intravenously under close clinical observation by medically trained personnel. It should be reserved for treatment of patients with progressive, potentially life-threatening fungal infections due to susceptible organisms.

Acute reactions including fever, shaking chills, hypotension, anorexia, nausea, vomiting, headache, and tachypnea are common 1 to 3 hours after starting an intravenous infusion. These reactions are usually more severe with the first few doses of amphotericin B and usually diminish with subsequent doses.

Rapid intravenous infusion has been associated with hypotension, hypokalemia, arrhythmias, and shock and should, therefore, be avoided.

Amphotericin B should be used with care in patients with reduced renal function; frequent monitoring of renal function is recommended. In some patients hydration and sodium repletion prior to amphotericin B administration may reduce the risk of developing nephrotoxicity. Supplemental alkali medication may decrease renal tubular acidosis complications.

Since acute pulmonary reactions have been reported in patients given amphotericin B during or shortly after leukocyte transfusions, it is advisable to temporarily separate these infusions as far as possible and to monitor pulmonary function.

Leukoencephalopathy has been reported following use of amphotericin B. Literature reports have suggested that total body irradiation may be a predisposition.

Whenever medication is interrupted for a period longer than 7 days, therapy should be resumed by starting with the lowest dosage level, e.g., 0.25 mg/kg of body weight, and increased gradually as outlined under DOSAGE AND ADMINISTRATION.

DOSAGE AND ADMINISTRATION

CAUTION: Under no circumstances should a total daily dose of 1.5 mg/kg be exceeded. Amphotericin B overdoses can result in potentially fatal cardiac or cardiorespiratory arrest.

FUNGIZONE Intravenous (Amphotericin B for Injection) should be administered by slow intravenous infusion. Intravenous infusion should be given over a period of approximately 2 to 6 hours (depending on the dose) observing the usual precautions for intravenous therapy (see PRECAUTIONS: General). The recommended concentration for intravenous infusion is 0.1 mg/mL (1 mg/10 mL).

Since patient tolerance varies greatly, the dosage of amphotericin B must be individualized and adjusted according to the patient’s clinical status (e.g., site and severity of infection, etiologic agent, cardio-renal function, etc.).

A single intravenous test dose (1 mg in 20 mL of 5% dextrose solution) administered over 20 to 30 minutes may be preferred. The patient’s temperature, pulse, respiration, and blood pressure should be recorded every 30 minutes for 2 to 4 hours.

In patients with good cardio-renal function and a well tolerated test dose, therapy is usually initiated with a daily dose of 0.25 mg/kg of body weight. However, in those patients having severe and rapidly progressive fungal infection, therapy may be initiated with a daily dose of 0.3 mg/kg of body weight. In patients with impaired cardio-renal function or a severe reaction to the test dose, therapy should be initiated with smaller daily doses (i.e., 5 to 10 mg).

Depending on the patient’s cardio-renal status, doses may gradually be increased by 5 to 10 mg per day to final daily dosage of 0.5 to 0.7 mg/kg.

There are insufficient data presently available to define total dosage requirements and duration of treatment necessary for eradication of specific mycoses. The optimal dose is unknown. Total daily dosage may range up to 1.0 mg/kg per day or up to 1.5 mg/kg when given on alternate days.

Sporotrichosis: Therapy with intravenous amphotericin B for sporotrichosis has ranged up to 9 months with a total dose up to 2.5 g.

Aspergillosis: Aspergillosis has been treated with amphotericin B intravenously for a period up to 11 months with a total dose up to 3.6 g.

Rhinocerebral phycomycosis: This fulminating disease generally occurs in association with diabetic ketoacidosis. It is, therefore, imperative that diabetic control be restored in order for treatment with FUNGIZONE Intravenous to be successful. In contradistinction, pulmonary phycomycosis, which is more common in association with hematologic malignancies, is often an incidental finding at autopsy. A cumulative dose of at least 3 g of amphotericin B is recommended to treat rhinocerebral phycomycosis. Although a total dose of 3 to 4 g will infrequently cause lasting renal impairment, this would seem a reasonable minimum where there is clinical evidence of invasion of deep tissue. Since rhinocerebral phycomycosis usually follows a rapidly fatal course, the therapeutic approach must necessarily be more aggressive than that used in more indolent mycoses.