Names and pronunciation
(am-foe-ter′i-sin) AmBisome
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Drug reference
(am-foe-ter′i-sin) AmBisome
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Func. class.: Antifungal
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Chem. class.: Amphoteric polyene
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Do not confuse: AmBisome/amphotericin B
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ACTION: Increases cell membrane permeability in susceptible fungi by bind- ing to membrane sterols; alters cell membrane, thereby causing leakage of cell components, cell death THERAPEUTIC OUTCOME Resolution of infection
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USES: Empiric therapy for presumed fun- gal infection in febrile neutropenic patients; treatment of cryptococcal meningitis in HIV- infected patients; treatment of Aspergillus sp., Candida sp., and/or Cryptococcus sp. infections refractory to amphotericin B deoxycholate, or in patients where renal impairment or unacceptable toxicity pre- cludes the use of amphotericin B deoxycho- late (Aspergillus flavus, Aspergillus fumig atus, Blastomyces dermatitidis, Candida albicans, Candida krusei, Candida lusita niae, Candida parapsilosis, Candida trop icalis, Cryptococcus neoformans); treat- ment of visceral leishmaniasis
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Unlabeled uses: Coccidioidomycosis, histoplasmosis
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CONTRAINDICATIONS: Hyper sensitivity Precautions: Anemia, breastfeeding, car- diac disease, children, electrolyte imbalance, geriatric patients, hematologic/hepatic/renal disease, hypotension, pregnancy, severe bone marrow depression
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SIDE EFFECTS CNS: Headache, fever, chills, periph- eral nerve pain, insomnia CV: Hypotension, cardiac arrest, tachy- cardia, edema, flushing GI: Nausea, vomiting, anorexia, diarrhea, cramps, GI hemmorrhage, hyperbilirubinemia GU: Nephrotoxicity HEMA: Anemia, thrombocytopenia, agranulocytosis, leukopenia INTEG: Burning, irritation, pain, necrosis at injection site with extravasation, flushing, dermatitis, skin rash (topical route) MS: Arthralgia, myalgia RESP: Dyspnea, cough SYST: Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, anaphylaxis
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INTERACTIONS Increase: nephrotoxicity—other neph- rotoxic antibiotics (aminoglycosides, antineoplastics, CISplatin, vancomycin, cycloSPORINE, polymyxin B) Increase: hypokalemia—corticosteroids, digoxin, skeletal muscle relaxants, thia- zides, loop diuretics Decrease: amphotericin B liposomal— azole antifungals, may be used concur- rently in serious resistant infections
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DOSAGE AND ROUTES Systemic fungal infections • Adults and children: IV 3-6 mg/kg/ dose q24hr Esophageal candidiasis (unlabeled) A in HIV-infected patients • Adults/adolescents: IV 3-4 mg/kg/ dose q24hr for 14 to 21 days Cryptococcal meningitis in HIV patients • Adults/adolescents/children/infants: IV 6 mg/kg/dose q24hr Visceral leishmaniasis • Adult: IV 3 mg/kg q24hr on days 1-5, then 3 mg/kg q24hr on days 14, 21 (im- munocompetent); 4 mg/kg q24hr on days 1-5, then 4 mg/kg q24hr on days 10, 17, 24, 31, 38 (immunosuppressed) Severe disseminated (nonmeningeal) or diffuse pulmonary coccidioido- mycosis (unlabeled) in HIV-infected patients • Adults: IV 3-5 mg/kg/dose q24hr Histoplasmosis (unlabeled) Adults: IV 3 mg/kg/dose daily depending on the type of histoplasmosis and concomitant conditions Infant/child/adolescent: IV 3-5 mg/kg/ dose daily Renal dose • Adult: IV CCr <10 mL/min use 3 mg/kg q24hr
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Available forms: Powder for injection 50-mg vial
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Administer: • Do not confuse the 4 different types; these are not interchangeable: con- ventional amphotericin B, amphotericin B cholesteryl, amphotericin B lipid complex, amphotericin B liposome • May premedicate with acetamino- phen, diphenhydrAMINE IV route • Give after C&S confirms organism and product needed to treat condition • Use for life-threatening infections • Administer by IV infusion only; use aseptic technique, as LAmB does not contain any preservatives • Visually inspect for particulate and discoloration Reconstitution • LAmB must be reconstituted using sterile water for injection (without a bac- teriostatic agent); DO NOT RECONSTITUTE WITH SALINE OR ADD SALINE TO THE RECONSTITUTED SUSPENSION, DO NOT MIX WITH OTHER DRUGS; doing so can cause a precipitate to form • Reconstitute vials containing 50 mg of LAmB/12 mL of sterile water (4 mg/mL) • Immediately after the addition of water, SHAKE VIGOROUSLY; the suspension should be yellow and translucent; visually inspect vial for particulate matter and con- tinue shaking until completely dispersed • Store suspension for up to 24 hr refrigerated if using sterile water for injection; do not freeze Filtration and dilution • Calculate the amount of reconstituted (4 mg/mL) suspension to be further di- luted and withdraw this amount into a sterile syringe • Attach the provided 5-micron filter to the syringe; inject the syringe contents through the filter into the appropriate amount of D5W injection; use only one filter per vial • The suspension must be diluted with D5W injection (1-2 mg/mL) before ad- ministration; for infants and small chil- dren, lower concentrations (0.2-0.5 mg/ mL) may be appropriate to provide suf- ficient volume for infusion • Use injection of LAmB within 6 hr of dilution with D5W IV INFUSION • Flush line with D5W injection before infusion; if this cannot be done, then a separate IV line must be used • An in-line membrane filter may be used with pore diameter if the filter is not less than 1 micron • Administer using a controlled infusion device over a period of 120 min; infusion time may be reduced to 60 min in pa- tients who tolerate the infusion; if dis- comfort occurs, the duration of infusion may be increased • Store protected from moisture and light; diluted solution is stable for 24 hr at room temperature Acetaminophen and diphenhydrAMINE • 30 min before infusion to reduce fe- ver, chills, headache Y-site compatibilities: Acyclovir, amifostine, aminophylline, anidulafungin, atropine, azithromycin, bivalirudin, bumetanide, buprenorphine, busulfan, butorphanol, CARBOplatin, carmustine, ceFAZolin, ceFOXitin, ceftizoxime, cefTRIAXone, cefu- roxime, cimetidine, clindamycin, cyclo- phosphamide, cytarabine, DACTINomycin, DAPTOmycin, dexamethasone, dexme- detomidine, diphenhydrAMINE, doxacu- rium, enalaprilat, ePHEDrine, EPINEPH- rine, eptifibatide, ertapenem, esmolol, etoposide, famotidine, fenoldopam, fen- taNYL, fludarabine, fluorouracil, fosphe- nytoin, furosemide, granisetron, halo- peridol, heparin, hydrocortisone, HYDROmorphone, ifosfamide, isoproter- enol, ketorolac, levorphanol, lidocaine, linezolid, mesna, methotrexate, methyl- PREDNISolone, metoprolol, milrinone, mitoMYcin, nesiritide, nitroglycerin, nitro- prusside, octreotide, oxaliplatin, oxytocin, palonosetron, pancuronium, pantopra- zole, PEMEtrexed, PENTobarbital, PHE- NObarbital, phenylephrine, piperacil- lin/tazobactam, potassium chloride, procainamide, raNITIdine, SUFentanil, ta- crolimus, theophylline, thiopental, thiotepa, ticarcillin/clavulanate, tigecycline, tri methoprim-sulfamethoxazole, vasopressin, vinCRIStine, voriconazole, zidovudine
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Assess: • VS every 15-30 min during first infu- sion; note changes in pulse, B/P • Blood studies: CBC, potassium, so- dium, calcium, magnesium every 2 wk, BUN, creatinine 2-3×/wk • Weight weekly; if weight increases by more than 2 lb/wk, edema is present; renal damage should be considered • For renal toxicity: increasing BUN, se- rum creatinine; if BUN is >40 mg/dL or if serum creatinine is >3 mg/dL, product may be discontinued, dosage reduced; I&O ratio; watch for decreasing urinary output, change in specific gravity; discontinue product to prevent permanent damage to renal tubules • For hepatotoxicity: increasing AST, ALT, alkaline phosphatase, bilirubin, moni- tor LFTs • For allergic reaction: dermatitis, rash; product should be discontinued, an- tihistamines (mild reaction) or EPINEPH- rine (severe reaction) administered • For hypokalemia: anorexia, drowsi- ness, weakness, decreased reflexes, dizzi- ness, increased urinary output, increased thirst, paresthesias • Infusion reaction: chills, fever, pain, swelling at site
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Evaluate: • Therapeutic response: resolution of in- fection, negative C&S for infecting organism
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • That long-term therapy may be needed to clear infection (2 wk-3 mo, depending on type of infection), that frequent blood A draws will be needed • To notify prescriber of bleeding, bruis- ing, or soft tissue swelling, renal, neuro- logic side effects • Pregnancy/breastfeeding: To notify health care professional if preg- nancy is planned or suspected, not to breastfeed
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PHARMACOKINETICS IV: Metabolized in liver; excreted in urine (metabolites), breast milk; protein binding 90%; poorly penetrates CSF, bronchial secretions, aqueous humor, muscle, bone; half-life 4-6 days
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• Adults/adolescents: IV 3-4 mg/kg/ dose q24hr for 14 to 21 days Cryptococcal meningitis in HIV patients
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• Adults/adolescents/children/infants: IV 6 mg/kg/dose q24hr Visceral leishmaniasis
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