Ambisome

Action

😶🤠😮 Binds to sterols in fungal cell membrane, increasing permeability. This allows potassium to exit the cell, causing fungal impairment or death.

Availability

😶🤠😮 Amphotericin B cholesteryl sulfate-

😶🤠😮 Injection: 50 mg, 100 mg

😶🤠😮 Amphotericin B desoxycholate-

😶🤠😮 Injection: 50-mg vial

😶🤠😮 Oral suspension: 100 mg/ml in 24-ml bottles

😶🤠😮 Amphotericin B lipid complex-

😶🤠😮 Suspension for injection: 100 mg/20-ml vials

😶🤠😮 Amphotericin B liposome-

😶🤠😮 Injection: 50 mg

Indications and dosages

😶🤠😮 ➣ Invasive aspergillosis

😶🤠😮 Adults:Amphotericin B desoxycholate-For patients with good cardiorenal function who tolerate test dose, give 0.25 to 0.3 mg/kg daily by slow I.V. infusion (0.1 mg/ml over 2 to 6 hours). Gradually increase to 0.5 to 0.6 mg/kg daily. Patients with neutropenia or rapidly progressing, potentially fatal infections may require higher dosages (1 to 1.5 mg/kg daily).

😶🤠😮 Adults and children ages 1 month and older:Amphotericin B liposome-3 to 5 mg/kg I.V. daily

😶🤠😮 ➣ Invasive aspergillosis in patients with renal impairment or unacceptable toxicity who can't tolerate or don't respond to amphotericin B desoxycholate in effective doses

😶🤠😮 Adults and children:Amphotericin B cholesteryl sulfate-3 to 4 mg/kg daily reconstituted in sterile water for injection and diluted in dextrose 5% in water (D₅W) and give by continuous infusion at 1 mg/kg/hour. Amphotericin B lipid complex-5 mg/kg daily I.V. prepared as 1-mg/ml infusion and delivered at a rate of 2.5 mg/kg/hour.

😶🤠😮 ➣ Systemic histoplasmosis

😶🤠😮 Adults:Amphotericin B desoxycholate-If patient tolerates test dose, gradually increase from initial recommended dosage of 0.25 to 0.3 mg/kg daily by slow I.V. infusion (0.1 mg/ml over 2 to 6 hours) to usual dosage of 0.5 to 0.6 mg/kg daily I.V. for 4 to 8 weeks; higher dosages (0.7 to 1 mg) may be necessary for rapidly progressing, potentially fatal infections.

😶🤠😮 ➣ Systemic coccidioidomycosis and blastomycosis

😶🤠😮 Adults:Amphotericin B desoxycholate-If patient tolerates test dose, gradually increase from initial recommended dosage of 0.25 to 0.3 mg/kg daily by slow I.V. infusion (0.1 mg/ml over 2 to 6 hours) to usual dosage of 0.5 to 1 mg/kg daily I.V. for 4 to 12 weeks.

😶🤠😮 ➣ Systemic cryptococcosis

😶🤠😮 Adults:Amphotericin B desoxycholate-If patient tolerates test dose, gradually increase from initial recommended dosage of 0.25 to 0.3 mg/kg daily by slow I.V. infusion (0.1 mg/ml over 2 to 6 hours) to usual dosage of 0.3 to 1 mg/kg daily I.V. (with or without flucytosine) for 2 weeks to several months. For patients with human immunodeficiency virus (HIV) infection, usual dosage is 0.7 mg/kg daily I.V. for 4 weeks, followed by 0.7 mg/kg I.V. given on alternate days for 4 additional weeks. If patient can't tolerate or doesn't respond to amphotericin B desoxycholate, give amphotericin B cholesteryl sulfate at a dosage of 3 to 6 mg/kg daily I.V.

😶🤠😮 Adults and children ages 1 month and older:Amphotericin B liposome-3 to 5 mg/kg daily I.V.

😶🤠😮 ➣ Cryptococcal meningitis in HIV-infected patients

😶🤠😮 Adults:Amphotericin B desoxycholate-If patient tolerates test dose, gradually increase from initial recommended dosage of 0.25 to 0.3 mg/kg daily by slow I.V. infusion (0.1 mg/ml over 2 to 6 hours) to usual dosage of 0.3 to 1 mg/kg daily I.V. (with or without flucytosine) for 2 weeks to several months. Amphotericin B lipid complex-5 mg/kg I.V. infusion daily for 6 weeks, followed by 12 weeks of oral fluconazole therapy. Amphotericin B liposome-6 mg/kg I.V. infusion daily.

😶🤠😮 ➣ Disseminated candidiasis

😶🤠😮 Adults:Amphotericin B desoxycholate-If patient tolerates test dose, gradually increase from initial recommended dosage of 0.25 to 0.3 mg/kg daily by slow I.V. infusion (0.1 mg/ml over 2 to 6 hours) to usual dosage of 0.4 to 0.6 mg/kg daily by slow I.V. infusion for 7 to 14 days (low-risk patients) or for 6 weeks (high-risk patients). For hepatosplenic candidiasis, 1 mg/kg daily I.V. given with oral flucytosine; for severe or refractory esophageal candidiasis in HIV-infected patients, 0.3 mg/kg daily I.V. for at least 5 to 7 days; for candiduria, 0.3 mg/kg daily I.V. for 3 to 5 days.

😶🤠😮 Adults and children ages 1 month and older:Amphotericin B liposome-3 to 5 mg/kg/day I.V. for 5 to 7 days

😶🤠😮 ➣ Systemic zygomycosis, including mucormycosis

😶🤠😮 Adults:Amphotericin B desoxycholate-If patient tolerates test dose, gradually increase from initial recommended dosage of 0.25 to 0.3 mg/kg daily by slow I.V. infusion (0.1 mg/ml over 2 to 6 hours) to usual dosage of 1 to 1.5 mg/kg daily I.V. for 2 to 3 months. For rhinocerebral phycomycosis form, total dosage is 3 g I.V.

😶🤠😮 ➣ Systemic disseminated sporotrichosis

😶🤠😮 Adults:Amphotericin B desoxycholate-If patient tolerates test dose, gradually increase from initial recommended dosage of 0.25 to 0.3 mg/kg daily by slow I.V. infusion (0.1 mg/ml over 2 to 6 hours) to usual dosage of 0.4 to 0.5 mg/kg daily I.V. for 2 to 3 months.

😶🤠😮 ➣ Cutaneous leishmaniasis

😶🤠😮 Adults and children:Amphotericin B desoxycholate-If patient tolerates test dose, gradually increase from initial recommended dosage of 0.25 to 0.5 mg/kg/day given by slow I.V. infusion (0.1 mg/ml over 2 to 6 hours) until 0.5 to 1 mg/kg/day is reached; then give every other day. Usual duration is 3 to 12 weeks.

😶🤠😮 ➣ Visceral leishmaniasis in immunocompetent patients

😶🤠😮 Adults and children ages 1 month and older:Amphotericin B liposome-3 mg/kg given I.V. over 2 hours on days 1 through 5, 14, and 21. Repeat course if initial treatment fails to clear parasites.

😶🤠😮 ➣ Visceral leishmaniasis in immunocompromised patients

😶🤠😮 Adults and children ages 1 month and older:Amphotericin B liposome-4 mg/kg given I.V. over 2 hours on days 1 through 5, 10, 17, 24, 31, and 38

😶🤠😮 ➣ Empiric therapy for presumed fungal infection in febrile, neutropenic patients

😶🤠😮 Adults:Amphotericin B desoxycholate-If patient tolerates test dose, gradually increase from initial recommended dosage of 0.25 to 0.3 mg/kg daily by slow I.V. infusion (0.1 mg/ml over 2 to 6 hours) to usual dosage of 0.25 to 1 mg/kg daily I.V. Amphotericin B liposome-3 mg/kg daily given I.V. over 120 minutes for 2 weeks.

Off-label uses

😶🤠😮 • Chemoprophylaxis in immunocompromised patients

😶🤠😮 • Coccidioidal arthritis

😶🤠😮 • Prophylaxis of fungal infections in bone-marrow transplant recipients, patients with primary amoebic meningoencephalitis caused by Naegleria fowleri, and patients with ocular aspergillosis

Contraindications

😶🤠😮 • Hypersensitivity to drug and its components

😶🤠😮 • Severe respiratory distress

Precautions

😶🤠😮 Use cautiously in:

😶🤠😮 • renal impairment, electrolyte abnormalities

😶🤠😮 • pregnant or breastfeeding patients

😶🤠😮 • children.

Administration

😶🤠😮 • Know that amphotericin B should be given only by health care professionals thoroughly familiar with drug, its administration, and adverse reactions.

😶🤠😮 ☞ Before giving first dose of conventional amphotericin B (desoxycholate form), test dose may be ordered (due to widely varying tolerance and clinical status) as follows: 1 mg in 20 ml of D₅W over 20 to 30 minutes; monitor vital signs every 30 minutes for next 2 hours.

😶🤠😮 • Know that if desoxycholate form is discontinued for 1 week or longer, drug should be restarted at 0.25 mg/kg daily, with dosage then increased gradually.

😶🤠😮 • Pretreat with antihistamines, antipyretics, or corticosteroids, as prescribed.

😶🤠😮 • Give through separate I.V. line, using infusion pump and in-line filter with pores larger than 1 micron.

😶🤠😮 • Choose distal vein for I.V. site. Alternate sites regularly.

😶🤠😮 • Mix with sterile water to reconstitute. Don't mix with sodium chloride, other electrolytes, or bacteriostatic products.

😶🤠😮 • Flush I.V. line with 5% dextrose injection before and after infusion.

😶🤠😮 • Keep dry form of drug away from light. Once mixed with fluid, solution can be kept in light for up to 8 hours.

😶🤠😮 ☞ Know that total daily dosage of amphotericin B desoxycholate form should never exceed 1.5 mg/kg.

Adverse reactions

😶🤠😮 CNS: anxiety, confusion, headache, insomnia, weakness, depression, dizziness, drowsiness, hallucinations, speech difficulty, ataxia, vertigo, stupor, psychosis, seizures

😶🤠😮 CV: hypotension, hypertension, tachycardia, phlebitis, chest pain, orthostatic hypotension, vasodilation, asystole, atrial fibrillation, bradycardia, cardiac arrest, shock, supraventricular tachycardia

😶🤠😮 EENT: double or blurred vision, amblyopia, eye hemorrhage, hearing loss, tinnitus, epistaxis, rhinitis, sinusitis, pharyngitis

😶🤠😮 GI: nausea, vomiting, diarrhea, melena, abdominal pain, abdominal distention, dry mouth, oral inflammation, oral candidiasis, anorexia, GI hemorrhage

😶🤠😮 GU: painful urination, hematuria, albuminuria, glycosuria, excessive urea buildup, urine of low specific gravity, nephrocalcinosis, renal failure, renal tubular acidosis, oliguria, anuria

😶🤠😮 Hematologic: eosinophilia; normochromic, normocytic, or hypochromic anemia; leukocytosis; thrombocytopenia; leukopenia; agranulocytosis; coagulation disorders

😶🤠😮 Hepatic: jaundice, acute hepatic failure, hepatitis

😶🤠😮 Metabolic: hypomagnesemia, hypokalemia, hypocalcemia, hypernatremia, hyperglycemia, dehydration, hypoproteinemia, hypervolemia, hyperlipidemia, acidosis

😶🤠😮 Musculoskeletal: muscle, joint, neck, or back pain

😶🤠😮 Respiratory: increased cough, hypoxia, lung disorders, hyperventilation, wheezing, dyspnea, hemoptysis, tachypnea, asthma, bronchospasm, respiratory failure, pulmonary edema, pleural effusion

😶🤠😮 Skin: discoloration, bruising, flushing, pruritus, urticaria, acne, rash, sweating, nodules, skin ulcers, alopecia, maculopapular rash

😶🤠😮 Other: gingivitis, fever, infection, peripheral or facial edema, weight changes, pain or reaction at injection site, tissue damage with extravasation, hypersensitivity reactions including anaphylaxis

Interactions

😶🤠😮 Drug-drug.Antineoplastics (such as mechlorethamine): renal toxicity, bronchospasm, hypotension

😶🤠😮 Cardiac glycosides: increased risk of digitalis toxicity (in potassium-depleted patients)

😶🤠😮 Corticosteroids: increased potassium depletion

😶🤠😮 Cyclosporine, tacrolimus: increased creatinine levels

😶🤠😮 Flucytosine: increased flucytosine toxicity

😶🤠😮 Imidazoles (clotrimazole, fluconazole, ketoconazole, miconazole): antagonism of amphotericin B effects

😶🤠😮 Leukocyte transfusion: pulmonary reactions

😶🤠😮 Nephrotoxic drugs (such as antibiotics, pentamidine): increased risk of renal toxicity

😶🤠😮 Thiazides: increased electrolyte depletion Skeletal muscle relaxants: increased skeletal muscle relaxation

😶🤠😮 Zidovudine: increased myelotoxicity and nephrotoxicity

😶🤠😮 Drug-diagnostic tests.Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, bilirubin, blood urea nitrogen, creatinine, gamma-glutamyltransferase, lactate dehydrogenase, nitrogenous compounds (urea), uric acid: increased levels

😶🤠😮 Calcium, hemoglobin, magnesium, platelets, potassium, protein: decreased levels

😶🤠😮 Eosinophils, glucose, white blood cells: increased or decreased levels

😶🤠😮 Liver function tests: abnormal results Prothrombin time: prolonged

😶🤠😮 Drug-herbs.Gossypol: increased risk of renal toxicity

Patient monitoring

😶🤠😮 ☞ Monitor for infusion-related reactions (fever, chills, hypotension, GI symptoms, breathing difficulties, and headache). Stop infusion and notify prescriber immediately if reaction occurs.

😶🤠😮 ☞ After giving test dose, monitor vital signs and temperature every 30 minutes for 2 to 4 hours, as ordered.

😶🤠😮 • Assess fluid intake and output.

😶🤠😮 • Monitor kidney and liver function test results and serum electrolyte levels.

😶🤠😮 • Assess for signs and symptoms of ototoxicity (hearing loss, tinnitus, ataxia, and vertigo).

Patient teaching

😶🤠😮 ☞ Advise patient to contact prescriber immediately if he has fever, chills, headache, vomiting, diarrhea, cough, or breathing problems.

😶🤠😮 • Instruct patient to report hearing loss, dizziness, or unsteady gait.

😶🤠😮 • Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration, alertness, and vision.

😶🤠😮 • Instruct patient to drink plenty of fluids.

😶🤠😮 • Tell patient to monitor urine output and report significant changes.

😶🤠😮 • Advise patient to minimize GI upset by eating small, frequent servings of food and drinking plenty of fluids.

😶🤠😮 • As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and herbs mentioned above.