Amphotericin B Data - Uses, Dosage, Drug class, Brand name, Warnings, etc

Pharmacology	Amphotericin B, a polyene macrolide antifungal from Streptomyces nodosus, binds to ergosterol in fungal cytoplasmic membranes, disrupting integrity and function. Resistance is rare, with fungal sensitivity tied to ergosterol concentration.
Administration and Adult Dosage	- IV (see Amphotericin B Formulations Comparison Chart): • Test dose: Optional; conventional amphotericin B 1 mg in D5W 20 mL or 2–5% of initial dose, infused over 10–20 min without premedication; monitor 30–60 min for infusion reactions/hypersensitivity. Not recommended for amphotericin B lipid complex • Initiation: Full dose for life-threatening infections; some start with fractional dose, increasing daily to therapeutic level to improve tolerance (uncontrolled data) • Maintenance: Conventional amphotericin B and lipid complex can be given every other day or Monday/Wednesday/Friday • Prophylaxis (post-bone marrow transplant, conventional): 0.1 mg/kg or 5–10 mg daily • Infusion time: 1–2 hr or 4–6 hr (similar reaction frequency); 4–6 hr required for renal failure, hyperkalemia, or reduced potassium clearance to prevent hyperkalemia • Duration: Continue until clinical/microbiologic resolution or unacceptable toxicity; cumulative dose typically 10–20 mg/kg - PO (suspension, oral candidiasis): 1 mL (100 mg) qid, swish/hold for 1 min, swallow; continue ≥2 weeks - Topical: Apply to affected area 2–4 times daily for 1–4 weeks - Alternative routes (extemporaneous, case-based, not standard): • Intra-articular (fungal arthritis): 5–50 mg every 2–7 days, dose by joint size • Intracavitary (pulmonary aspergillomas): 5–50 mg in D5W daily or 2–3 times weekly • Inhalation (Aspergillus prophylaxis, post-transplant): 0.15% in D5W, nebulized 10 mg/day in 2 doses • Intranasal (prophylaxis, transplant): 0.5% in sterile water, 10 mg/day in divided doses • Intraperitoneal (fungal peritonitis): Used in peritoneal dialysis, incompatible with ionic dialysate • Intrathecal (conventional): 0.5–1 mg 2–3 times/week or 0.3 mg/day, start 0.025–0.05 mg/dose, increase by 0.025–0.05 mg/day; preferably via Ommaya reservoir • Bladder irrigation (fungal cystitis): 50 mg/L in sterile water over 24 hr • Topical ocular (keratomycosis): 0.15% (0.1–0.25%) in preservative-free sterile water with atropine drops every 30–60 min for 48–72 hr, then qid for ≥1 month • Intravitreal (keratomycosis): 5 µg/0.1 mL preservative-free sterile water • Subtenonian (postoperative fungal endophthalmitis): 500–750 µg/day for 8 doses - IM or PO administration of injectable amphotericin B not recommended
Special Populations - Pediatric Dosage	- IV: Same as adult dosage for all formulations - IV prophylaxis (post-transplant, liposomal): 1 mg/kg/day - PO (suspension): Same as adult dosage - Topical (cream/lotion/ointment): Same as adult dosage
Special Populations - Geriatric Dosage	- Same as adult dosage for all formulations; renal impairment may limit long-term IV use - Comorbidities may reduce tolerance to ancillary medications (e.g., corticosteroid-induced sodium retention)
Other Conditions	- Chronic renal dysfunction: No dose adjustment, but use 4–6 hr infusion to prevent hyperkalemia - Acute renal dysfunction: Interrupt therapy, extend dosing interval, or reduce dose as clinically feasible - Obesity (≥1.3 × IBW): Calculate dose using IBW or dosing weight: IBW + 0.4 × (TBW − IBW)
Dosage Forms	- Injection: See Amphotericin B Formulations Comparison Chart - Oral Suspension: 100 mg/mL - Topical Cream: 30 mg/g - Topical Lotion: 30 mg/mL - Topical Ointment: 30 mg/g
Patient Instructions	- Injection: Infusion reactions (shaking, chills, fever, nausea) may occur but are transient; premedications help. Kidney effects may require mineral supplements - Oral Suspension: Shake well, swish/hold for 1 min, swallow; stop if mouth irritation occurs - Topical: May stain clothing
Missed Doses	- Take missed oral/topical dose as soon as remembered; if near next dose, skip and do not double dose
Pharmacokinetics - Serum Levels	- No established correlation between serum levels and therapeutic/toxic effects for any formulation
Pharmacokinetics - Fate	- Conventional amphotericin B: • Poor oral/IM absorption • End-infusion serum: 0.984 ± 0.056 mg/L (0.25 mg/kg dose) • Vdss: 0.74 ± 0.13 L/kg (acute), 4 ± 0.3 L/kg (chronic) • Protein binding: >90% to plasma lipoproteins • Accumulates in liver, spleen, lungs, kidneys • Cl: 0.01 ± 0.001 L/hr/kg • Urinary elimination: 3–8% • Metabolites: Not identified - Cholesteryl sulfate (ABCD): • Vdss: 4.2 ± 1.4 L/kg (adults), 4.6 ± 1.7 L/kg (children) • Cl: 0.11 ± 0.03 L/hr/kg (adults), 0.14 ± 0.02 L/hr/kg (children) • AUC: 9.6 ± 2.6 mg/L/hr (adults), 7.1 ± 2.6 mg/L/hr (children) - Lipid complex (ABLC): • Vdss: 3.9 ± 0.3 L/kg • Cl: 0.08 ± 0.02 L/hr/kg • AUC: 2.76 ± 0.25 mg/L/hr - Liposomal (L-AmB): • Vdss: 0.37 L/kg • Cl: 0.023 L/hr/kg • AUC: 423 mg/L/hr
Pharmacokinetics - t¹⁄₂	- Conventional: α phase 24–50 hr; γ phase 15 days - Cholesteryl sulfate: 32 ± 5.6 hr (adults), 32 ± 13 hr (children) - Lipid complex: α phase 45 ± 6.3 hr - Liposomal: α phase 1.74 hr; β phase 23.6 hr
Adverse Reactions & Side Effects	Frequent: - Infusion reactions: Rigors, chills, fever; less common: nausea, tachycardia, tachypnea, hypo-/hypertension, bradycardia, myalgia, arthralgia; occur during/within 60–90 min post-infusion - Nephrotoxicity: Increased BUN/Crs, hypomagnesemia, hypokalemia, renal tubular acidosis; reversible, but permanent impairment possible with high doses (>1 mg/kg/day conventional), pre-existing renal issues, prolonged therapy, sodium depletion, nephrotoxic drugs - Normochromic normocytic anemia: Mild, transient, nephrotoxicity-related - Phlebitis: From chronic peripheral administration (conventional) Rare: - Anorexia, emesis, diarrhea, epigastric pain, PVCs, bradycardia, dilated cardiomyopathy, hypertension, diffuse alveolar hemorrhage, rhabdomyolysis, parkinsonian syndrome Intrathecal-specific: - Headache, nausea, vomiting, abdominal pain, urinary retention, tinnitus, visual changes, ventriculitis, paresthesias, numbness, mono-/paraparesis, arachnoiditis, focal neurologic defects, chemical/bacterial meningitis, brain puncture/hemorrhage (intracisternal) Notes: - Infusion reactions more common with conventional/ABCD than ABLC/L-AmB - Rapid infusion (<60 min) risks hyperkalemia/cardiovascular collapse in anephric/hyperkalemic patients - Lipid formulations less nephrotoxic but not devoid of risk
Contraindications	- Hypersensitivity to amphotericin B
Precautions & Warnings	- Use cautiously in pregnancy, impaired renal function - Avoid rapid infusions (<4 hr) if Clcr <20 mL/min, hyperkalemia, or reduced potassium excretion - Separate from neutrophil infusions by ≥6 hr; complete infusion ≥2 hr before platelet transfusions
Drug Interactions	- Additive nephrotoxicity with cyclosporine, tacrolimus, aminoglycosides, loop diuretics, other nephrotoxic agents - Corticosteroids enhance potassium loss
Parameters to Monitor	- Infusion reactions with first 3 doses, then as needed - Serum Crs, BUN, magnesium, potassium before therapy, ≥2× weekly; daily for high-risk renal dysfunction - Hemoglobin weekly - Microbiologic, radiographic, clinical signs of fungal infection - Note: Hydrocortisone, acetaminophen, aspirin may mask fevers
Class and Drug Brand Names	- Class: Polyene Antifungals - Brand Names: Fungizone (conventional), Amphotec/Amphocil (cholesteryl sulfate, ABCD), Abelcet (lipid complex, ABLC), AmBisome (liposomal, L-AmB)
Notes	- Amphotericin B lipid complex: Invert admixtures several times before and every 2 hr during infusion for even distribution - Avoid admixture/Y-site with non-dextrose IV fluids, other drugs, or blood products; conventional amphotericin B incompatible with lipid emulsion - Ancillary medications for infusion reactions: Meperidine (25–50 mg IV) for rigors/chills; acetaminophen (325–650 mg PO) for fever; diphenhydramine (25–50 mg PO/IV) as premedication; hydrocortisone for refractory reactions; dantrolene (case-based); avoid ibuprofen due to nephrotoxicity/antiplatelet risks - Nephrotoxicity mitigation: 0.9% NaCl 250–1000 mL over 30–45 min pre-/post-infusion, adjusted for body size/cardiovascular status - Phlebitis prevention: Add heparin 1 IU/mL to conventional amphotericin B infusion

References

Hand of Clinical Drug Data