Amphotericin B (AmB) is a key agent in the management of serious systemic fungal infections. It was introduced in the mid- 1950s as the first effective anti-fungal drug for systemic mycoses and it has been used as the ‘‘gold standard’’ anti-fungal drug since the 1960s. AmB is a natural antibiotic belonging to the polyene group, isolated in 1955 from a strain of the Actinomycete streptomycesnodosus on soil collected in the Orinoco River region of Venezuela.
AmB has been a main stay of anti-fungal therapy for treating disseminated, life-threatening fungal infections. Perhaps the major reasons for lasting acceptance of AmB are its broad spectrum of activity and the relatively few examples of mycological resistance to the drug.
In its pure form it has very little solubility in aqueous solutions at physiological pH, requiring complexing with some other agent for clinical administration; the first such agent was sodium deoxycholate. AmB can be administered in travenously, intrathecally, intralesionally, intraarticularly, and infused into surgical sites.
In spite of its proven track record, the requirement for parenteral administration for long periods is inconvenient, frequently necessitating hospitalization and prolonged intravenous (IV) access. Furthermore, its well-known side effects and toxicity will sometimes require discontinuation of therapy despite a life-threatening systemic fungal infection.
Class: Antifungal Agent, Parenteral
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;
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.)
Recommended Neonatal, Dose, Route, and Interval. Dose: 0.5 – 1 mg/kg/24hr IV infusion over 2 – 6 hours
Dosage modification for renal dysfunction is only necessary if serum creatinine increases above 0.4 mg/dl during therapy- hold dose for 2 to 5 days.
Possible Adverse Reactions
1. Cardiovascular: hypotension, hypertension, cardiac arrhythmias, flushing
2. CNS: fever, chills, and headache are the most common adverse effects reported with amphotericin B infusion; seizures, malaise
3. Endocrine and metabolic: hypokalemia, hypomagnesemia
4. Gastrointestinal: vomiting, diarrhea
5. Hematologic: anemia, leukopenia, and thrombocytopenia
6. Hepatic: acute hepatic failure, jaundice
7. Local: phlebitis
8. Renal: renal tubular acidosis, renal failure (oliguria, azotemia, elevated serum creatinine)
9. Respiratory: wheezing, hypoxemia
10. Miscellaneous: anaphylactoid reaction
Contraindications and Precautions
1. Hypersensitivity to amphotericin
2. CAUTION in hepatic/renal dysfunction – caution use with other nephrotoxic drugs
3. CAUTION use with steroids: can aggravate hypokalemia caused by amphotericin
1. Monitor for adverse reactions particularly with initial doses. Cardiovascular collapse has been reported after rapid amphotericin injection
2. Follow serum electrolytes (esp. K, Mg, Phos), Hct, liver and renal studies
3. Monitor I and O
4. Infuse alone
5. Observe IV site for signs of phlebitis
6. Monitor for signs of hypokalemia (muscle weakness, drowsiness, EKG changes, etc), blood pressure, temperature, pulse, and respiration
Special Considerations and Calculations
1. Dilute in D5W or D10W DO NOT use NS or Sterile H20 as precipitate may result. Dilute to 0.1 mg/ml for peripheral infusion and 0.2 – 0.5 mg/ml for central infusion in infants who cannot tolerate large fluid volume (done in pharmacy)
2. Reconstitute vial (50mg) with 10 ml D5W for injection to make a concentration of 5mg/ml. Stable for 7 days refrigerated, 24 hours at room temperature. Further dilute 1ml (5mg) in 49ml D5W to make a final dilution of 0.1mg/ml unless otherwise indicated by physician. However, more concentrated solutions increase the likelihood of phlebitis. Stable for 5 days refrigerated and 10 days at room temperature.
3. Therapy can be interrupted for 2 – 5 days in case of renal/hepatic impairment
4. Half-life increased in small neonates, initial: 15 – 48 hours, terminal: 15 days; excreted very slowly by the kidney, may be detected in the urine up to 7 weeks after discontinuation
5. Do NOT mix with any other medications
6. Solution compatibility: D5W, D10W, D15W. Not compatible with TPN; TPN must be shut off during infusion of Amphotericin, or additional IV access utilized. Terminal injection site compatibility with Heparin therefore may be given through central line.
7. Treat with antipyretics, antihistamines, corticosteroids for adverse reactions
8. Monitor weekly hematologic, renal, and hepatic function; at least biweekly serum electrolytes (potassium, magnesium).