General

amphotericin b deoxycholate
(am-foe-TER-i-sin)

• Fungizone [Canada]

amphotericin b cholesteryl sulfate

• Amphotec

amphotericin b lipid complex

• Abelcet

amphotericin b liposome

• AmBisome

Pregnancy Category
Category B

Ther. class.
antifungals

Indications

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

• Amphotericin B liposome: Management of suspected fungal infections in febrile neutropenic patients

» Treatment of visceral leishmaniasis

» Treatment of crytococcal 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: Not absorbed orally.

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. Cholesteryl sulfate—28 hr. Lipid complex—174 hr. Liposomal—100–153 hr

TIME/ACTION PROFILE (blood levels)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	end of infusion	24 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 (increased risk of pulmonary toxicity)

• OB: Has been used safely

Adverse Reactions/Side Effects

CNS: anxiety, confusion, headache, insomnia.

Resp: dyspnea, hypoxia, wheezing.

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

GI: diarrhea, hyperbilirubinemia, liver enzyme elevation, nausea, vomiting, abdominal pain.

GU: nephrotoxicity, hematuria.

F and E: hyperglycemia, hypocalcemia, hypokalemia, hypomagnesemia.

Hemat: anemia, leukopenia, thrombocytopenia.

Derm: pruritis, rashes.

Local: phlebitis.

MS: arthralgia, myalgia.

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

*CAPITALS indicates life-threatening.
*italic indicates most frequent.

Interactions

Drug-Drug

• Increased risk of renal toxicity, bronchospasm, and hypotension with antineoplastics

• Concurrent use with corticosteroids risk of hypokalemia

• Concurrent use with zidovudine may increase the risk of myelotoxicity and nephrotoxicity

• Combined use with flucytosine antifungal activity but may the risk of toxicity from flucytosine

• Combined use with azole antifungals may induce fungal resistance

• Increased 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

• Specific dosage and duration of therapy depend on nature of infection being treated

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 q 48–72 hr, to 500 mcg—1 mg as tolerated (maximum total dose = 15 mg).

• IT (Children): 25–100 mcg q 48–72 hr; to 500 mcg as tolerated.

Amphotericin B Cholesteryl Sulfate (Amphotec)

• IV (Adults and Children): 3–4 mg/kg q 24 hr (no test dose needed).

Amphotericin B Lipid Complex (Abelcet)

• IV (Adults and Children): 5 mg/kg q 24 hr (no test dose needed).

Amphotericin B Liposome (AmBisome)

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

Availability

Amphotericin Deoxycholate

• Powder for injection: 50 mg/vial

Amphotericin B Cholesteryl Sulfate

• Powder for injection: 50 mg/vial, 100 mg/vial

Amphotericin B Lipid Complex

• Suspension for injection: 100 mg/20-ml vial

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 administrationMeperidine and dantrolene have been used to prevent and treat rigors. Assess respiratory status (lung sounds, dyspnea) daily. Notify physician of changes. 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 cholesteryl sulfate, lipid complex, or liposomal formulation.

Potential Nursing Diagnoses

• Risk for infection (Indications)

Implementation

Do not confuse amphotericin B cholesteryl sulfate (Amphotec) with amphotericin deoxycholate, 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 Adminstration:

• Test dose:
Diluent: 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. 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:

» amiodarone

» diltiazem

» hydromorphone

» lorazepam

» tacrolimus

• Y-Site Incompatibility:

» acyclovir

» amikacin

» ampicillin

» ampicillin/sulbactam

» anidulafungin

» atropine

» aztreonam

» bivalirudin

» bumetanide

» calcium chloride

» calcium gluconate

» caspofungin

» cefepime

» ceftizoxime

» chloramphenicol

» cimetidine

» clindamycin

» daptomycin

» dexamethasone sodium phosphate

» diazepam

» digoxin

» diphenhydramine

» dobutamine

» dopamine

» doxycycline

» ertapenem

» erythromycin

» esmolol

» famotidine

» fenoldopam

» filgrastim

» fluconazole

» ganciclovir

» gentamicin

» granisetron

» haloperidol

» hydralazine

» hydrocortisone sodium succinate

» hydroxyzine

» isoproterenol

» ketorolac

» labetalol

» lansoprazole

» levofloxacin

» lidocaine

» linezolid

» meperidine

» meropenem

» methylprednisolone sodium succinate

» metoclopramide

» metoprolol

» metronidazole

» midazolam

» morphine

» nafcillin

» nitroprusside

» norepinephrine

» ondansetron

» palonosetron

» pantoprazole

» penicillin G potassium

» phenylephrine

» phenytoin

» piperacillin/tazobactam

» potassium chloride

» prochlorperazine

» promethazine

» propofol

» propranolol

» protamine

» quinupristin/dalfopristin

» sodium bicarbonate

» tigecycline

» tirofiban

» tobramycin

» trimethoprim/sulfamethoxazole

» vancomycin

» vasopressin

» verapamil

» voriconazole

• Solution Incompatibility:

» LR injection

» saline solutions

Amphotericin B Cholesteryl Sulfate

IV Adminstration:

• Test Dose:
Diluent: Reconstitute 50-mg vial with 10 ml and 100-mg vial with 20 ml of sterile water for injection to achieve a concentration of 5 mg/ml. Reconstituted vials are stable for 24 hr if refrigerated. Further dilute with D5W to achieve concentration below. Do not use other diluents. Infusion stable for 24 hr if refrigerated. Protect from light. To obtain test dose, withdraw 10 ml from final preparation.
Concentration: Final concentration of infusion should be approximately 0.6 mg/ml (range 0.16–0.83 mg/ml)

• Rate:
Infuse over 15–30 min

• Intermittent Infusion:
Diluent: Prepare infusion according to directions above.
Concentration: Final concentration of infusion should be approximately 0.6 mg/ml (range 0.16–0.83 mg/ml)

• Rate:
Infuse at a rate of 1 mg/kg/hr. If patient tolerates infusion without adverse reactions, infusion time may be shortened to a minimum of 2 hr. If reactions occur or patient cannot tolerate volume, infusion time may be extended. Rapid infusions may cause hypotension, hypokalemia, arrhythmias, and shock

• Y-Site Compatibility:

» acyclovir

» aminophylline

» cefoxitin

» ceftizoxime

» clindamycin

» dexamethasone sodium phosphate

» fentanyl

» furosemide

» ganciclovir

» granisetron

» hydrocortisone

» lorazepam

» methylprednisolone

» nitroglycerin

» trimethoprim/sulfamethoxazole

• Y-Site Incompatibility:

» amikacin

» ampicillin

» ampicillin/sulbactam

» aztreonam

» calcium chloride

» calcium gluconate

» cefazolin

» cefepime

» ceftazidime

» ceftriaxone

» cimetidine

» cisatracurium

» cyclosporine

» diazepam

» digoxin

» diphenhydramine

» dobutamine

» dopamine

» droperidol

» enalaprilat

» esmolol

» famotidine

» fluconazole

» gentamicin

» haloperidol

» heparin

» hydromorphone

» hydroxyzine

» imipenem/cilastatin

» labetalol

» lidocaine

» magnesium sulfate

» meperidine

» metoclopramide

» metoprolol

» metronidazole

» midazolam

» morphine

» ondansetron

» phenytoin

» piperacillin/tazobactam

» potassium chloride

» prochlorperazine

» promethazine

» propranolol

» ranitidine

» sodium bicarbonate

» ticarcillin-clavulanate

» tobramycin

» vancomycin

» vecuronium

» verapamil

• Solution Incompatibility:

» saline solutions

Amphotericin B Lipid Complex

IV Adminstration:

• 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:

» anidulafungin

» ertapenem

• Y-Site Incompatibility:

» daptomycin

» tigecycline

» tirofiban

• Solution Incompatibility:

» saline solutions

Amphotericin B Liposome

IV Adminstration:

• 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 seconds 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

» anidulafungin

» atropine

» azithromycin

» bumetanide

» cefazolin

» cefoxitin

» ceftizoxime

» ceftriaxone

» cefuroxime

» cimetidine

» clindamycin

» daptomycin

» dexamethasone sodium phosphate

» diphenhydramine

» enalaprilat

» epinephrine

» ertapenem

» esmolol

» famotidine

» fenoldopam

» fentanyl

» furosemide

» haloperidol

» heparin

» hydrocortisone sodium succinate

» hydromorphone

» isoproterenol

» ketorolac

» lidocaine

» linezolid

» methylprednisolone sodium succinate

» metoprolol

» milrinone

» nitroglycerin

» nitroprusside

» palonosetron

» pantoprazole

» phenylephrine

» piperacillin/tazobactam

» potassium chloride

» procainamide

» ranitidine

» tacrolimus

» ticarcillin/clavulanate

» trimethoprim/sulfamethoxazole

» voriconazole

• Y-Site Incompatibility:

» amikacin

» ampicillin

» ampicillin/sulbactam

» aztreonam

» calcium chloride

» calcium gluconate

» caspofungin

» cefepime

» cefotaxime

» ceftazidime

» ciprofloxacin

» cyclosporine

» diazepam

» digoxin

» diltiazem

» dobutamine

» dolasetron

» dopamine

» doxycycline

» droperidol

» erythromycin

» gentamicin

» hydroxyzine

» imipenem/cilastatin

» labetalol

» lorazepam

» magnesium sulfate

» meperidine

» meropenem

» metoclopramide

» metronidazole

» midazolam

» morphine

» nicardipine

» ondansetron

» phenytoin

» potassium phosphate

» prochlorperazine

» promethazine

» propranolol

» quinupristin/dalfopristin

» sodium bicarbonate

» tobramycin

» vancomycin

» verapamil

• 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 or topical 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 weeks to months of therapy may be required to prevent relapse

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