Amphotericin B (Liposomal)

Name: Amphotericin B (Liposomal)

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
  • Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
  • Signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
  • Signs of electrolyte problems like mood changes, confusion, muscle pain or weakness, a heartbeat that does not feel normal, seizures, not hungry, or very bad upset stomach or throwing up.
  • Signs of high or low blood pressure like very bad headache or dizziness, passing out, change in eyesight.
  • Chest pain or pressure or a fast heartbeat.
  • Black, tarry, or bloody stools.
  • Throwing up blood or throw up that looks like coffee grounds.
  • Shortness of breath, a big weight gain, or swelling in the arms or legs.
  • Fever or chills.
  • Sore throat.
  • Feeling very tired or weak.
  • Any unexplained bruising or bleeding.

How do I store and/or throw out Amphotericin B?

  • If you need to store this medicine at home, talk with your doctor, nurse, or pharmacist about how to store it.

Brand Names U.S.

  • AmBisome

Reconstitution

Reconstitute with 12 mL SWFI to a concentration of 4 mg/mL. The use of any solution other than those recommended, or the presence of a bacteriostatic agent in the solution, may cause precipitation. Shake the vial vigorously for 30 seconds, until dispersed into a translucent yellow suspension.

Filtration and dilution: Withdraw appropriate amount of reconstituted solution into a syringe, attach a 5-micron filter, and inject contents of syringe through filter needle into an appropriate amount of D5W. Dilute to a final concentration of 1-2 mg/mL (0.2-0.5 mg/mL for infants and small children).

Storage

Store intact vials at ≤25°C (≤77°F). Reconstituted vials are stable at 2°C to 8°C (36°F to 46°F) for 24 hours. Do not freeze. Begin infusion within 6 hours of dilution with D5W. Extended storage information may be available; contact product manufacturer to obtain current recommendations.

What happens if I miss a dose?

Since amphotericin B liposomal is usually given while you are in the hospital, you are not likely to miss a dose.

If you are receiving amphotericin B liposomal in an outpatient clinic, call your doctor if you will miss an appointment for your amphotericin B liposomal injection.

What should I avoid while receiving amphotericin B liposomal?

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Amphotericin B liposomal dosing information

Usual Adult Dose for Aspergillosis -- Invasive:

Systemic fungal infections: 3 to 5 mg/kg IV once a day

Doses as high as 10 mg/kg have been used in patients with documented Aspergillus infection.

The addition of flucytosine 25 to 37.5 mg/kg orally every 6 hours may be considered in HIV-infected patients with invasive candidiasis.

The total dose administered or duration of therapy will vary and depend on the nature and severity of the infection and the patient's tolerance to amphotericin B liposomal.

Usual Adult Dose for Candidemia:

Systemic fungal infections: 3 to 5 mg/kg IV once a day

Doses as high as 10 mg/kg have been used in patients with documented Aspergillus infection.

The addition of flucytosine 25 to 37.5 mg/kg orally every 6 hours may be considered in HIV-infected patients with invasive candidiasis.

The total dose administered or duration of therapy will vary and depend on the nature and severity of the infection and the patient's tolerance to amphotericin B liposomal.

Usual Adult Dose for Cryptococcosis:

Systemic fungal infections: 3 to 5 mg/kg IV once a day

Doses as high as 10 mg/kg have been used in patients with documented Aspergillus infection.

The addition of flucytosine 25 to 37.5 mg/kg orally every 6 hours may be considered in HIV-infected patients with invasive candidiasis.

The total dose administered or duration of therapy will vary and depend on the nature and severity of the infection and the patient's tolerance to amphotericin B liposomal.

Usual Adult Dose for Febrile Neutropenia:

Empirical therapy: 3 mg/kg IV once a day

The total dose administered or duration of therapy will vary and depend on the severity of the infection and the patient's tolerance to amphotericin B liposomal.

Usual Adult Dose for Cryptococcal Meningitis -- Immunosuppressed Host:

HIV-infected patient: 6 mg/kg IV once a day

The addition of flucytosine 25 mg/kg orally every 6 hours may be considered.

The total dose administered or duration of therapy will vary and depend on the nature and severity of the infection and the patient's tolerance to amphotericin B liposomal.

Usual Adult Dose for Leishmaniasis:

Visceral leishmaniasis:
Immunocompetent patient: 3 mg/kg IV once a day on day 1 through 5, day 14, and day 21
Immunocompromised patient: 4 mg/kg IV once a day on day 1 through 5, day 10, day 17, day 24, day 31, and day 38

If the immunocompetent patient does not achieve parasitic clearance, a repeat course of therapy may be effective. If the immunocompromised patient does not achieve parasitic clearance or experiences a relapse, expert advice regarding future treatment is recommended.

Usual Pediatric Dose for Aspergillosis -- Invasive:

1 month or older:
Systemic fungal infections: 3 to 5 mg/kg IV once a day

Doses as high as 10 mg/kg have been used in patients with documented Aspergillus infection.

The addition of flucytosine 25 to 37.5 mg/kg orally every 6 hours may be considered for HIV-infected patients with invasive candidiasis.

The total dose administered or duration of therapy will vary and depend on the nature and severity of the infection and the patient's tolerance to amphotericin B liposomal.

Usual Pediatric Dose for Candidemia:

1 month or older:
Systemic fungal infections: 3 to 5 mg/kg IV once a day

Doses as high as 10 mg/kg have been used in patients with documented Aspergillus infection.

The addition of flucytosine 25 to 37.5 mg/kg orally every 6 hours may be considered for HIV-infected patients with invasive candidiasis.

The total dose administered or duration of therapy will vary and depend on the nature and severity of the infection and the patient's tolerance to amphotericin B liposomal.

Usual Pediatric Dose for Cryptococcosis:

1 month or older:
Systemic fungal infections: 3 to 5 mg/kg IV once a day

Doses as high as 10 mg/kg have been used in patients with documented Aspergillus infection.

The addition of flucytosine 25 to 37.5 mg/kg orally every 6 hours may be considered for HIV-infected patients with invasive candidiasis.

The total dose administered or duration of therapy will vary and depend on the nature and severity of the infection and the patient's tolerance to amphotericin B liposomal.

Usual Pediatric Dose for Febrile Neutropenia:

1 month or older:
Empirical therapy: 3 mg/kg IV once a day

The total dose administered or duration of therapy will vary and depend on the severity of the infection and the patient's tolerance to amphotericin B liposomal.

Usual Pediatric Dose for Cryptococcal Meningitis -- Immunosuppressed Host:

1 month or older:
HIV-infected patient: 6 mg/kg IV once a day

The addition of flucytosine 25 mg/kg orally every 6 hours may be considered.

The total dose administered or duration of therapy will vary and depend on the nature and severity of the infection and the patient's tolerance to amphotericin B liposomal.

Usual Pediatric Dose for Leishmaniasis:

1 month or older:
Visceral leishmaniasis:
Immunocompetent patient: 3 mg/kg IV once a day on day 1 through 5, day 14, and day 21
Immunocompromised patient: 4 mg/kg IV once a day on day 1 through 5, day 10, day 17, day 24, day 31, and day 38

If the immunocompetent patient does not achieve parasitic clearance, a repeat course of therapy may be effective. If the immunocompromised patient does not achieve parasitic clearance or experiences a relapse, expert advice regarding future treatment is recommended.

Precautions

General

As with any amphotericin B-containing product the drug should be administered by medically trained personnel. During the initial dosing period, patients should be under close clinical observation. Am B isome has been shown to be significantly less toxic than amphotericin B deoxycholate; however, adverse events may still occur.

Laboratory Tests

Patient management should include laboratory evaluation of renal, hepatic and hematopoietic function, and serum electrolytes (particularly magnesium and potassium).

Drug Interactions

No formal clinical studies of drug interactions have been conducted with Am B isome. However, the following drugs are known to interact with amphotericin B and may interact with Am B isome.

Antineoplastic agents:   Concurrent use of antineoplastic agents may enhance the potential for renal toxicity, bronchospasm, and hypotension. Antineoplastic agents should be given concomitantly with caution.

Corticosteroids and corticotropin (ACTH):   Concurrent use of corticosteroids and ACTH may potentiate hypokalemia which could predispose the patient to cardiac dysfunction. If used concomitantly, serum electrolytes and cardiac function should be closely monitored.

Digitalis glycosides:   Concurrent use may induce hypokalemia and may potentiate digitalis toxicity. When administered concomitantly, serum potassium levels should be closely monitored.

Flucytosine:   Concurrent use of flucytosine may increase the toxicity of flucytosine by possibly increasing its cellular uptake and/or impairing its renal excretion.

Azoles (e.g. ketoconazole, miconazole, clotrimazole, fluconazole, etc.):  In vitro and in vivo animal studies of the combination of amphotericin B and imidazoles suggest that imidazoles may induce fungal resistance to amphotericin B. Combination therapy should be administered with caution, especially in immunocompromised patients.

Leukocyte transfusions:   Acute pulmonary toxicity has been reported in patients simultaneously receiving intravenous amphotericin B and leukocyte transfusions.

Other nephrotoxic medications:   Concurrent use of amphotericin B and other nephrotoxic medications may enhance the potential for drug-induced renal toxicity. Intensive monitoring of renal function is recommended in patients requiring any combination of nephrotoxic medications.

Skeletal muscle relaxants:   Amphotericin B-induced hypokalemia may enhance the curariform effect of skeletal muscle relaxants (e.g. tubocurarine) due to hypokalemia. When administered concomitantly, serum potassium levels should be closely monitored.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No long term studies in animals have been performed to evaluate carcinogenic potential of Am B isome. Am B isome has not been tested to determine its mutagenic potential. A Segment I Reproductive Study in rats found an abnormal estrous cycle (prolonged diestrus) and decreased number of corpora lutea in the high dose groups (10 and 15 mg/kg, doses equivalent to human doses of 1.6 and 2.4 mg/kg based on body surface area considerations). Am B isome did not affect fertility or days to copulation. There were no effects on male reproductive function.

Pregnancy Category B

There have been no adequate and well-controlled studies of Am B isome in pregnant women. Systemic fungal infections have been successfully treated in pregnant women with amphotericin B deoxycholate, but the number of cases reported has been small.

Segment II studies in both rats and rabbits have concluded that Am B isome had no teratogenic potential in these species. In rats, the maternal non-toxic dose of Am B isome was estimated to be 5 mg/kg (equivalent to 0.16 to 0.8 times the recommended human clinical dose range of 1 to 5 mg/kg) and in rabbits, 3 mg/kg (equivalent to 0.2 to 1 times the recommended human clinical dose range), based on body surface area correction. Rabbits receiving the higher doses, (equivalent to 0.5 to 2 times the recommended human dose) of Am B isome experienced a higher rate of spontaneous abortions than did the control groups. Am B isome should only be used during pregnancy if the possible benefits to be derived outweigh the potential risks involved.

Nursing Mothers

Many drugs are excreted in human milk. However, it is not known whether Am B isome is excreted in human milk. 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.

Pediatric Use

Pediatric patients, age 1 month to 16 years, with presumed fungal infection (empirical therapy), confirmed systemic fungal infections or with visceral leishmaniasis have been successfully treated with Am B isome. In studies which included 302 pediatric patients administered Am B isome there was no evidence of any differences in efficacy or safety of Am B isome compared to adults. Since pediatric patients have received Am B isome at doses comparable to those used in adults on a per kilogram body weight basis, no dosage adjustment is required in this population. Safety and effectiveness in pediatric patients below the age of one month has not been established.

(See DESCRIPTION OF CLINICAL STUDIES -- Empirical Therapy in Febrile Neutropenic Patients and DOSAGE AND ADMINISTRATION .)

Elderly Patients

Experience with Am B isome in the elderly (65 years or older) comprised 72 patients. It has not been necessary to alter the dose of Am B isome for this population. As with most other drugs, elderly patients receiving Am B isome should be carefully monitored.

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