amphotericin B deoxycholate (amphotericin B (conventional), Fungizone)

Dosing and uses of Amphotericin B (conventional), Fungizone (amphotericin B deoxycholate)

• Adult
• Pediatric

 

Adult dosage forms and strengths

powder for injection

• 50mg/vial

 

Systemic Fungal Infections

Test dose: 1 mg IV x1 infused over 20-30 min

Load: 0.25-0.5 mg/kg IV infused over 2-6 hr

Maintenance: 0.25-1 mg/kg IV qDay OR up to 1.5 mg/kg IV qOD (may increase gradually by 0.25 mg-increments/day)

 

Renal Impairment

CrCl <10 mL/min: 0.5-0.7 mg/kg IV q24-48hr

Consider other antifungal agents that may be less nephrotoxic

Intermittent hemodialysis: 0.5-1 mg/kg IV q24hr after dialysis session

Continuous renal replacement therapy: 0.5-1 mg/kg IV q24hr

 

Other Indications & Uses

Aspergillosis, cryptococcosis, blastomycosis, systemic candidiasis, coccidioidomycosis, histoplasmosis, zygomycosis, sporotrichosis, leishmaniasis (not drug of choice)

Infections of Mucor, Rhizopus, Absidia, Conidiobolus, Basiobolus spp.

Off-label: amoebic meningoencephalitis (Naegleria fowleri); ocular aspergillosis; candidal cystitis; severe meningitis (intrathecal); coccidioidal arthritis (intra-articular or IM)

 

Pediatric dosage forms and strengths

powder for injection

• 50mg/vial

 

Systemic Fungal Infections

Test dose: 0.1 mg/kg IV, not to exceed 1 mg; administer over 20-60 min

Initial dose: 0.25 mg/kg/dose IV qDay/qOd

Maintenance: Increase by 0.25 mg/day increments as tolerated to 1-1.5 mg/kg/day

 

Amphotericin B (conventional), Fungizone (amphotericin B deoxycholate) adverse (side) effects

>10%

Anorexia

Chills

Diarrhea

Fever

Headache

Hypokalemia

Hypomagnesemia

Hypotension

Malaise

Nausea

Pain (generalized)

Pain at injection site

Renal function abnormalities

Tachypnea

Vomiting

 

1-10%

Arachnoiditis

Delerium

Flushing

Hypertension

Leukocytosis

Lumbar nerve pain

Paresthesia

Urinary retention

 

<1%

Agranulocytosis

Anuria

Bone marrow suppression

Cardiac arrest

Coagulation defects

Convulsions

Dyspnea

Hearing loss

Leukopenia

Maculopapular rash

Renal failure

Thrombocytopenia

Vision changes

 

Warnings

Contraindications

Hypersensitivity

 

Cautions

Indicated for patients with progressive and potentially fatal fungal infections

Do not use for noninvasive fungal infections (eg, oral thrush, vaginal candidiasis, esophageal candidiasis) in patients with normal neutrophil counts

Risk of nephrotoxicity, however, do not withhold if risk of infection outweighs renal risk

Risk of acute infusion reactions, especially with first dose

Caution when coadministration with other drugs that cause hypokalemia (eg, corticosteroids, digoxin)

Cases of new-onset dilated cardiomyopathy with subsequent heart failure have been reported; symptoms normalized within 6 months of discontinuation

 

Pregnancy and lactation

Pregnancy category: B

Lactation: Excretion in milk is unknown; due to the potential for serious adverse reactions in breast-fed infants, a decision should be made whether to discontinue nursing or whether to discontinue the drug, taking into account the importance of the drug to the mother

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Amphotericin B (conventional), Fungizone (amphotericin B deoxycholate)

Vd: 4 L/kg

Distribution: CholSO4 & lipid complex show lower kidney concs than conventionaL

Protein Bound: 90%

Half-Life, elimination: 15 days

Half-Life, plasma: 24 hr

Excretion: urine

 

Mechanism of action

Acts by binding to sterols in fungal cell membrane, leading to alterations in cell permeability and cell death

 

Administration

IV Incompatibilities

Solution: D5/LR, D5/NS, LR, Ns

Additive: amikacin, CaCl2, Ca-gluconate, chlorpromazine, cimetidine, ciprofloxacin, diphenhydramine, dopamine, CaNa2EDTA, gentamicin, kanamycin, MgSO4, meropenem, metaraminol, methyldopate, penicillin G Na/K, polymyxin B SO4, KCl, prochlorperazine, ranitidine, streptomycin, verapamiL

Syringe: pantoprazole

Y-site (partial list): allopurinol, amifostine, amsacarine, anidulafungin, aztreonam, bivalirudin, cefepine, cefpirone, cisatracurium(?), dexmedetomidine, docetaxel, doxorubicin liposomal, enalaprilat, etoposide PO4, fenoldopam mesylate, filgrastim, fluconazole, fludarabine, foscarnet, gatifloxacin, gemcitabine, granisetron, Hextend, lansoprazole, linezolid, melphalan, meropenem, ondansetron, paclitaxel, pemetrexed, piperacillin tazobactam, propofol, remifentanil(?), sargramostim(?), vinorelbine

 

IV Compatibilities

Solution: D5W, D10W

Additive: fluconazole, heparin, hydrocortisone Na-PO4; hydrocortisone Na-succinate; NaHCO3

Syringe: heparinY-site: aldesleukin, amiodarone, diltiazem, tacrolimus, teniposide, thiotepa, zidovudine

 

IV Preparation

Reconstitute 50 mg vial contents by adding 10 mL SWI without bacteriostatic agent to obtain a 5 mg/mL solution-add SWI rapidly & shake immediately until the colloidal dispersion is clear

For IV infusion, dilute further (usually to 0.1 mg/mL) with 500 mL D5W (pH >4.2)

Do not use if precipitate or foreign matter present

Store dry form at 36-46°F (2-8°C)

Protect from light

 

IV Administration

Use promptly after dilution

Infuse over 2-6 hr

May use an inline filter provided pore diameter >1 micron

Do not mix or piggyback with amphotericin B

Use IV site in distal vein