AMPHOTERICIN B

General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Pronunciation:
am-foe-ter-i-sin bee

amphotericin B deoxycholate

Trade Name(s)

  • Fungizone Canadian Tradename

amphotericin B lipid complex

Trade Name(s)

  • Abelcet

amphotericin B liposome

Trade Name(s)

  • AmBisome

Ther. Class.
antifungals

Indications

  • IV Treatment of progressive, potentially fatal fungal infections. The lipid complex, and liposome formulations should be considered for patients who are intolerant (e.g., renal dysfunction) or refractory to amphotericin B deoxycholate.
  • Amphotericin B liposome:

    Management of suspected fungal infections in febrile neutropenic patients:

    • Treatment of visceral leishmaniasis,
    • Treatment of cryptococcal meningitis in HIV patients.

Action

  • Binds to fungal cell membrane, allowing leakage of cellular contents.
  • Toxicity (especially acute infusion reactions and nephrotoxicity) is less with lipid formulations.

Therapeutic Effect(s):

Can be fungistatic or fungicidal (depends on concentration achieved and susceptibility of organism).

Spectrum:

Active against:

  • Aspergillosis,
  • Blastomycosis,
  • Candidiasis,
  • Coccidioidomycosis,
  • Cryptococcosis,
  • Histoplasmosis,
  • Leishmaniasis (liposomal formulation only),
  • Mucormycosis.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.

Distribution: Extensively distributed to body tissues and fluids. Poor penetration into CSF.

Metabolism and Excretion: Elimination is very prolonged. Detectable in urine up to 7 wk after discontinuation.

Half-life: Biphasic–initial phase, 24–48 hr; terminal phase, 15 days.  Lipid complex– 174 hr.  Liposomal– 100–153 hr.

TIME/ACTION PROFILE (blood levels)

ROUTEONSETPEAKDURATION
IVrapidend of infusion24 hr

Contraindication/Precautions

Contraindicated in:

  • Hypersensitivity;
  • Lactation: Potential for distribution into breast milk and toxicity in infant; discontinue nursing.

Use Cautiously in:

  • Renal impairment or electrolyte abnormalities;
  • Patients receiving concurrent leukocyte transfusions (↑ risk of pulmonary toxicity);
  • OB:  Has been used safely.

Adverse Reactions/Side Effects

Neuro: anxiety, confusion, headache, insomnia

Resp: dyspnea, hypoxia, wheezing

CV: chest pain, hypotension, tachycardia, edema, hypertension

GI: diarrhea, hyperbilirubinemia, ↑ liver enzymes, nausea, vomiting, abdominal pain

GU: nephrotoxicity, hematuria

F and E: hyperglycemia, hypocalcemia, hypokalemia, hypomagnesemia

Hemat: anemia, leukopenia, thrombocytopenia

Derm: pruritus, rashes

Local: phlebitis

MS: arthralgia, myalgia

Misc: HYPERSENSITIVITY REACTIONS, chills, fever, acute infusion reactions

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

  • ↑ risk of nephrotoxicity, bronchospasm, and hypotension with  antineoplastics.
  • Concurrent use with  corticosteroids  ↑ risk of hypokalemia.
  • Concurrent use with  zidovudine  may ↑ the risk of myelotoxicity and nephrotoxicity.
  • Concurrent use with  flucytosine  ↑ antifungal activity but may ↑ the risk of toxicity from flucytosine.
  • Combined use with  azole   antifungals  may induce fungal resistance.
  • ↑ risk of nephrotoxicity with other  nephrotoxic agents  such as  aminoglycosides,  cyclosporine, or  tacrolimus.
  • Hypokalemia from amphotericin ↑ the risk of  digoxin  toxicity.
  • Hypokalemia may enhance the curariform effects of  neuromuscular blocking agents.

Route/Dosage

Conventional and lipid-based formulations are NOT interchangeable

Amphotericin Deoxycholate

IV (Adults): Give test dose of 1 mg. If test dose tolerated, initiate therapy with 0.25 mg/kg/day (doses up to 1.5 mg/kg/day may be used, depending on type of infection) (alternate-day dosing may also be used);  Bladder irrigation– Instill 50 mcg/mL solution into bladder daily for 5–10 days.

IV (Infants  and Children): Give test dose of 0.1 mg/kg (maximum dose 1 mg) or may administer initial dose of 0.25–1 mg/kg/day over 6 hr (without test dose) (some infections may require 1.5 mg/kg/day; alternate-day dosing may be used).

IT (Adults): 25–300 mcg every 48–72 hr, ↑ to 500 mcg–1 mg as tolerated (maximum total dose = 15 mg).

IT Children: 25–100 mcg every 48–72 hr; ↑ to 500 mcg as tolerated.

Amphotericin B Lipid Complex (Abelcet)

IV (Adults and Children): 2.5–5 mg/kg every 24 hr (no test dose needed).

Amphotericin B Liposome (AmBisome)

IV (Adults and Children): Empiric therapy– 3 mg/kg every 24 hr;  Documented infections– 3–5 mg/kg every 24 hr;  Visceral leishmaniasis (immunocompetent patients)– 3 mg/kg every 24 hr on days 1–5, then 3 mg/kg every 24 hr on days 14 and 21;  Visceral leishmaniasis (immunosuppressed patients)– 4 mg/kg every 24 hr on days 1–5, then 4 mg/kg every 24 hr on days 10, 17, 24, 31, and 38;  Cryptococcal meningitis in HIV patients– 6 mg/kg every 24 hr.

Availability (generic available)

Amphotericin Deoxycholate

Powder for injection: 50 mg/vial

Amphotericin B Lipid Complex

Suspension for injection: 5 mg/mL

Amphotericin B Liposome

Powder for injection: 50 mg/vial

Assessment

  • Monitor patient closely during test dose and the first 1–2 hr of each dose for fever, chills, headache, anorexia, nausea, or vomiting. Premedicating with antipyretics, corticosteroids, antihistamines, meperidine, and antiemetics may decrease these reactions. Febrile reaction usually subsides within 4 hr after the infusion is completed.
  • Assess injection site frequently for thrombophlebitis or leakage. Drug is very irritating to tissues.
  • Monitor vital signs every 15 min during test dose and every 30 min for 2–4 hr after administration. Meperidine and dantrolene have been used to prevent and treat rigors. Assess respiratory status (lung sounds, dyspnea) daily. If respiratory distress occurs, discontinue infusion immediately; anaphylaxis may occur. Equipment for cardiopulmonary resuscitation should be readily available.
  • Monitor intake and output and weigh daily. Adequate hydration (2000–3000 mL/day) and maintaining sodium balance may minimize nephrotoxicity.

Lab Test Considerations:

Monitor CBC, BUN and serum creatinine, and potassium and magnesium levels daily. If BUN and serum creatinine ↑ significantly, may need to discontinue or consider switching to lipid complex, or liposomal formulation.

Potential Diagnoses

Implementation

  • Do not confuse amphotericin deoxycholate with amphotericin B lipid complex (Abelcet), or amphotericin B liposome (AmBisome); they are not interchangeable.

    • This drug should be administered IV only to hospitalized patients or those under close supervision. Diagnosis should be confirmed before administration.

Amphotericin B Deoxycholate

IV Administration

  • Test dose: Reconstitute 50-mg vial with 10 mL of sterile water for injection to achieve a concentration of 5 mg/mL. Reconstituted vial stable for 24 hr at room temperature or 1 wk if refrigerated. Diluent:  Further dilute with 500 mL of D5W. May be diluted in 250 mL of D5W if being administered via a central venous catheter. Protect infusion from light. Infusion stable for 24 hr at room temperature or 2 days if refrigerated. To obtain test dose, withdraw 1 mg (10 mL) from 500 mL infusion and further dilute with D5W to a total volume of 20 mL. Concentration: 0.05 mg/mL.
  • Rate: Infuse over 10–30 min to determine patient tolerance. Pedi:  Infuse over 30–60 min.
  • Intermittent Infusion:   Diluent:  Reconstitute and dilute 50-mg vial as per the directions above. Concentration: Final concentration of infusion should not exceed 0.1 mg/mL for peripheral infusion or 0.25 mg/mL for central line administration.
  • Rate: Infuse slowly over 4–6 hr.
  • Y-Site Compatibility:
    • aldesleukin
    • aminocaproic acid
    • argatroban
    • MORE...
      • carmustine
      • dactinomycin
      • diltiazem
      • etoposide
      • hydromorphone
      • ifosfamide
      • lorazepam
      • octreotide
      • oxaliplatin
      • tacrolimus
      • thiotepa
      • zidovudine
      • zoledronic acid
  • Y-Site Incompatibility:
    • acyclovir
    • alemtuzumab
    • alfentanil
    • MORE...
      • allopurinol
      • amifostine
      • amikacin
      • ampicillin
      • ampicillin/sulbactam
      • anidulafungin
      • atropine
      • azithromycin
      • aztreonam
      • benztropine
      • bivalirudin
      • bleomycin
      • bumetanide
      • butorphanol
      • calcium chloride
      • calcium gluconate
      • cangrelor
      • carboplatin
      • caspofungin
      • cefepime
      • cefotetan
      • ceftaroline
      • chloramphenicol
      • chlorpromazine
      • cisplatin
      • clindamycin
      • cyanocobalamin
      • cyclophosphamide
      • cytarabine
      • dacarbazine
      • dantrolene
      • daptomycin
      • daunorubicin
      • dexamethasone
      • dexmedetomidine
      • dexrazoxane
      • diazepam
      • digoxin
      • diphenhydramine
      • dobutamine
      • docetaxel
      • dopamine
      • doxorubicin
      • doxorubicin liposome
      • doxycycline
      • ephedrine
      • epinephrine
      • epirubicin
      • epoetin alfa
      • eptifibatide
      • ertapenem
      • erythromycin
      • esmolol
      • etoposide phosphate
      • famotidine
      • fenoldopam
      • filgrastim
      • fluconazole
      • fludarabine
      • fluorouracil
      • foscarnet
      • fosphenytoin
      • ganciclovir
      • gemcitabine
      • gentamicin
      • glycopyrrolate
      • granisetron
      • haloperidol
      • hetastarch
      • hydralazine
      • hydrocortisone
      • hydroxyzine
      • idarubicin
      • irinotecan
      • isoproterenol
      • ketorolac
      • labetalol
      • leucovorin
      • levofloxacin
      • lidocaine
      • linezolid
      • melphalan
      • meperidine
      • meropenem
      • mesna
      • methotrexate
      • methylprednisolone
      • metoclopramide
      • metoprolol
      • metronidazole
      • midazolam
      • milrinone
      • mitomycin
      • mitoxantrone
      • morphine
      • mycophenolate
      • nafcillin
      • nalbuphine
      • nicardipine
      • nitroprusside
      • norepinephrine
      • ondansetron
      • oxacillin
      • paclitaxel
      • palonosetron
      • pamidronate
      • pancuronium
      • pantoprazole
      • papaverine
      • pemetrexed
      • penicillin G
      • pentamidine
      • phenylephrine
      • phenytoin
      • piperacillin/tazobactam
      • potassium acetate
      • potassium chloride
      • prochlorperazine
      • promethazine
      • propofol
      • propranolol
      • protamine
      • pyridoxine
      • quinupristin/dalfopristin
      • rituximab
      • rocuronium
      • sodium acetate
      • sodium bicarbonate
      • succinylcholine
      • telavancin
      • thiamine
      • tigecycline
      • tirofiban
      • tobramycin
      • topotecan
      • trastuzumab
      • trimethoprim/sulfamethoxazole
      • vancomycin
      • vasopressin
      • vecuronium
      • verapamil
      • vinblastine
      • vincristine
      • vinorelbine
      • voriconazole
  • Solution Incompatibility:  
    • LR injection
    • saline solutions

Amphotericin B Lipid Complex

IV Administration

  • Intermittent Infusion:   Diluent:  Shake vial gently until yellow sediment at bottom has dissolved. Withdraw dose from required number of vials with 18-gauge needle. Replace needle from syringe filled with amphotericin B lipid complex with 5-micron filter needle. Each filter needle may be used to filter the contents of no more than 4 vials. Insert filter needle of syringe into IV bag of D5W and empty contents of syringe into bag. Protect from light. Infusion is stable for 6 hr at room temperature or 48 hr if refrigerated. Concentration: Final concentration of infusion should be 1 mg/mL; a concentration of 2 mg/mL can be used for pediatric patients or patients who cannot tolerate large volumes of fluid.
  • Rate: Do not use an in-line filter. Infuse at a rate of 2.5 mg/kg/hr via infusion pump. If infusion exceeds 2 hr, mix contents by shaking infusion bag every 2 hr. If administering through an existing line, flush line with D5W before infusion or use a separate line.
  • Y-Site Compatibility:
    • acyclovir
    • allopurinol
    • aminocaproic acid
    • MORE...
      • aminophylline
      • amiodarone
      • anidulafungin
      • argatroban
      • azithromycin
      • aztreonam
      • bumetanide
      • buprenorphine
      • busulfan
      • butorphanol
      • carboplatin
      • carmustine
      • cefazolin
      • cefepime
      • cefotaxime
      • cefotetan
      • cefoxitin
      • ceftazidime
      • ceftriaxone
      • cefuroxime
      • chloramphenicol
      • chlorpromazine
      • cisatracurium
      • clindamycin
      • cyclophosphamide
      • cyclosporine
      • cytarabine
      • dactimomycin
      • dexamethasone
      • digoxin
      • diphenhydramine
      • docetaxel
      • doxorubicin liposome
      • enalaprilat
      • ephedrine
      • epinephrine
      • eptifibatide
      • ertapenem
      • etoposide
      • famotidine
      • fentanyl
      • fludarabine
      • fluorouracil
      • fosphenytoin
      • furosemide
      • ganciclovir
      • granisetron
      • heparin
      • hydrocortisone
      • hydromorphone
      • ifosfamide
      • insulin
      • ketorolac
      • lidocaine
      • linezolid
      • lorazepam
      • mannitol
      • melphalan
      • meperidine
      • methotrexate
      • methylprednisolone
      • metoclopramide
      • mitomycin
      • nafcillin
      • nitroglycerin
      • nitroprusside
      • octreotide
      • oxaliplatin
      • paclitaxel
      • pamidronate
      • pantoprazole
      • pemetrexed
      • pentobarbital
      • phenobarbital
      • piperacillin/tazobactam
      • procainamide
      • succinylcholine
      • sufentanil
      • tacrolimus
      • telavancin
      • theophylline
      • thiopental
      • thiotepa
      • verapamil
      • vinblastine
      • vincristine
      • zidovudine
      • zoledronic acid
  • Y-Site Incompatibility:
    • alemtuzumab
    • alfentanil
    • amifostine
    • MORE...
      • amikacin
      • ampicillin
      • ampicillin/sulbactam
      • bivalirudin
      • bleomycin
      • calcium chloride
      • calcium gluconate
      • caspofungin
      • ciprofloxacin
      • cisplatin
      • dacarbazine
      • dantrolene
      • daptomycin
      • daunorubicin
      • dexmedetomidine
      • dexrazoxane
      • diazepam
      • diltiazem
      • dobutamine
      • dopamine
      • doxorubicin
      • doxycycline
      • droperidol
      • epirubicin
      • erythromycin
      • esmolol
      • etoposide phosphate
      • fenoldopam
      • fluconazole
      • foscarnet
      • gemcitabine
      • gentamicin
      • glycopyrrolate
      • haloperidol
      • hydralazine
      • hydroxyzine
      • idarubicin
      • imipenem/cilastatin
      • irinotecan
      • isoproterenol
      • labetalol
      • leucovorin calcium
      • levofloxacin
      • magnesium sulfate
      • meropenem
      • mesna
      • metoprolol
      • metronidazole
      • midazolam
      • milrinone
      • mitoxantrone
      • morphine
      • moxifloxacin
      • mycophenolate
      • nalbuphine
      • naloxone
      • nicardipine
      • norepinephrine
      • ondansetron
      • pancuronium
      • pentamidine
      • phenylephrine
      • phenytoin
      • potassium acetate
      • potassium phosphate
      • prochlorperazine
      • promethazine
      • propranolol
      • quinupristin/dalfopristin
      • remifentanil
      • rocuronium
      • sodium acetate
      • sodium bicarbonate
      • sodium phosphate
      • streptozocin
      • tirofiban
      • tobramycin
      • topotecan
      • trimethoprim/sulfamethoxazole
      • vancomycin
      • vasopressin
      • vecuronium
      • vinorelbine
      • voriconazole
  • Solution Incompatibility:  
    • saline solutions

Amphotericin B Liposome

IV Administration

  • Intermittent Infusion:   Diluent:  Reconstitute each 50–mg vial with 12 mL of sterile water for injection to achieve concentration of 4 mg/mL. Immediately shake vial vigorously for at least 30 sec until all particulate matter is completely dispersed. Reconstituted vials are stable for 24 hr if refrigerated. Withdraw appropriate volume for dilution into a syringe. Attach the 5-micron filter to the syringe and inject syringe contents into an appropriate volume of D5W. Infusion should be administered within 6 hr of dilution. Concentration: Final concentration of infusion should be 1–2 mg/mL; a lower concentration (0.2–0.5 mg/mL) may be used for infants and small children.
  • Rate: Infuse over 2 hr. Infusion time may be shortened to 1 hr if patient tolerates infusion without any adverse reactions. If discomfort occurs during infusion, duration of infusion may be increased. May be administered through an in-line filter with pore diameter of at least 1 micron. If administering through an existing line, flush line with D5W before infusion or use a separate line.
  • Y-Site Compatibility:
    • acyclovir
    • amifostine
    • aminocaproic acid
    • MORE...
      • aminophylline
      • anidulafungin
      • argatroban
      • atropine
      • azithromycin
      • bivalirudin
      • bumetanide
      • buprenorphine
      • busulfan
      • butorphanol
      • carboplatin
      • carmustine
      • cefazolin
      • cefoxitin
      • ceftriaxone
      • cefuroxime
      • clindamycin
      • cyclophosphamide
      • cytarabine
      • dactinomycin
      • daptomycin
      • dexamethasone
      • dexmedetomidine
      • diphenhydramine
      • doxorubicin liposomal
      • enalaprilat
      • ephedrine
      • epinephrine
      • eptifibatide
      • ertapenem
      • esmolol
      • etoposide
      • famotidine
      • fenoldopam
      • fentanyl
      • fludarabine
      • fluorouracil
      • foscarnet
      • fosphenytoin
      • furosemide
      • granisetron
      • haloperidol
      • heparin
      • hydrocortisone
      • hydromorphone
      • ifosfamide
      • isoproterenol
      • ketorolac
      • lidocaine
      • linezolid
      • mesna
      • methotrexate
      • methylprednisolone
      • metoprolol
      • milrinone
      • mitomycin
      • nitroglycerin
      • nitroprusside
      • octreotide
      • oxaliplatin
      • oxytocin
      • palonosetron
      • pamidronate
      • pancuronium
      • pantoprazole
      • pemetrexed
      • pentobarbital
      • phenobarbital
      • phenylephrine
      • piperacillin/tazobactam
      • potassium acetate
      • potassium chloride
      • procainamide
      • sufentanil
      • tacrolimus
      • theophylline
      • thiopental
      • thiotepa
      • tigecycline
      • trimethoprim/sulfamethoxazole
      • vasopressin
      • vincristine
      • voriconazole
      • zidovudine
      • zoledronic acid
  • Y-Site Incompatibility:
    • alemtuzumab
    • alfentanil
    • amikacin
    • MORE...
      • ampicillin
      • ampicillin/sulbactam
      • aztreonam
      • bleomycin
      • calcium chloride
      • calcium gluconate
      • caspofungin
      • cefepime
      • cefotaxime
      • cefotetan
      • ceftazidime
      • chlorpromazine
      • ciprofloxacin
      • cisplatin
      • cyclosporine
      • dacarbazine
      • daunorubicin
      • dexrazoxane
      • diazepam
      • digoxin
      • diltiazem
      • dobutamine
      • docetaxel
      • dopamine
      • doxorubicin
      • doxycycline
      • droperidol
      • epirubicin
      • erythromycin
      • etoposide phosphate
      • gemcitabine
      • gentamicin
      • hetastarch
      • hydroxyzine
      • idarubicin
      • imipenem/cilastatin
      • irinotecan
      • labetalol
      • leucovorin calcium
      • levofloxacin
      • lorazepam
      • magnesium sulfate
      • mannitol
      • meperidine
      • meropenem
      • metoclopramide
      • metronidazole
      • midazolam
      • mitoxantrone
      • morphine
      • mycophenolate
      • nalbuphine
      • naloxone
      • nicardipine
      • ondansetron
      • paclitaxel
      • pentamidine
      • phenytoin
      • potassium phosphate
      • prochlorperazine
      • promethazine
      • propranolol
      • quinupristin/dalfopristin
      • sodium bicarbonate
      • sodium phosphate
      • telavancin
      • tobramycin
      • vancomycin
      • vecuronium
      • verapamil
      • vinblastine
      • vinorelbine
  • Solution Incompatibility:  Do not dilute or admix with saline solutions, other medications, or solutions containing a bacteriostatic agent.

Patient/Family Teaching

  • Explain need for long duration of IV therapy.
  • Rep:  Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breast feeding during therapy.
  • IV Inform patient of potential side effects and discomfort at IV site. Advise patient to notify health care professional if side effects occur.
  • Home Care Issue: Instruct family or caregiver on dilution, rate, and administration of drug and proper care of IV equipment.

Evaluation/Desired Outcomes

Resolution of signs and symptoms of infection. Several wk to mo of therapy may be required to prevent relapse.

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