AmBisome

Half-Life: 7-10 hr (at 24 hr); terminal half-life range 10-153 hr

Vd: 0.1-0.4 L/kg

AUC: 27-555 mcg•h/mL

Peak Plasma Concentration: 7.3-83 mcg/mL

Clearance: 11-51 mL/hr/kg

Mechanism of Action

Acts by binding to sterols in fungal cell membrane, leading to alterations in cell permeability and cell death

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

You should not use this medicine if you are allergic to amphotericin B.

To make sure amphotericin B liposomal is safe for you, tell your doctor if you have:

• kidney disease;

• liver disease; or

• low levels of calcium or potassium in your blood.

FDA pregnancy category B. Amphotericin B liposomal is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether amphotericin B liposomal passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are receiving amphotericin B liposomal.

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.

Use AmBisome as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as an infusion into a vein over a period of time.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Upset stomach or throwing up.
• Loose stools (diarrhea).
• Hard stools (constipation).
• Not hungry.
• Not able to sleep.
• Headache.
• Back pain.
• Belly pain.
• Feeling tired or weak.
• Cough.
• Anxiety.
• Runny nose.
• Sweating a lot.
• Dizziness.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

AmBisome is indicated for the following:

• Empirical therapy for presumed fungal infection in febrile, neutropenic patients.
• Treatment of Cryptococcal Meningitis in HIV infected patients (see DESCRIPTION OF CLINICAL STUDIES).
• Treatment of patients with Aspergillus species, Candida species and/or Cryptococcus species infections (see above for the treatment of Cryptococcal Meningitis) refractory to amphotericin B deoxycholate, or in patients where renal impairment or unacceptable toxicity precludes the use of amphotericin B deoxycholate.
• Treatment of visceral leishmaniasis. In immunocompromised patients with visceral leishmaniasis treated with AmBisome, relapse rates were high following initial clearance of parasites (see DESCRIPTION OF CLINICAL STUDIES).

See DOSAGE AND ADMINISTRATION for recommended doses by indication.

AmBisome is contraindicated in those patients who have demonstrated or have known hypersensitivity to amphotericin B deoxycholate or any other constituents of the product unless, in the opinion of the treating physician, the benefit of therapy outweighs the risk.

Anaphylaxis has been reported with amphotericin B deoxycholate and other amphotericin B-containing drugs, including AmBisome. If a severe anaphylactic reaction occurs, the infusion should be immediately discontinued and the patient should not receive further infusions of AmBisome.

Unopened vials of lyophilized material are to be stored at temperatures up to 25° C (77° F).

Storage of Reconstituted Product Concentrate

The reconstituted product concentrate may be stored for up to 24 hours at 2º-8º C (36º-46º F) following reconstitution with Sterile Water for Injection, USP. Do not freeze.

Storage of Diluted Product

Injection of AmBisome should commence within 6 hours of dilution with 5% Dextrose Injection.

As with all parenteral drug products, the reconstituted AmBisome should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use material if there is any evidence of precipitation or foreign matter. Aseptic technique must be strictly observed in all handling since no preservative or bacteriostatic agent is present in AmBisome or in the materials specified for reconstitution and dilution.

Your doctor or pharmacist can provide more information about amphotericin B liposomal.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

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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.

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.

**VERIFY PRODUCT NAME AND DOSAGE, ESPECIALLY IF DOSE EXCEEDS 1.5 MG/KG**

Test dose: 1 mg in 20 mL dextrose, slow IV over 20 to 30 minutes, with monitoring for 2 to 4 hours afterward.
Initial dose (patients with good cardio-renal function and well tolerated test dose): 0.25 mg/kg slow IV daily
Initial dose (severe and rapidly progressive infection): 0.3 mg/kg slow IV daily
Initial dose (patients with impaired cardio-renal function OR severe reaction to test dose): use smaller doses (e.g. 5 to 10 mg)
-Gradually increase dose by 5 to 10 mg/day to thefinal daily dose depending on cardio-renal status.

Induction dose: 0.7 to 1 mg/kg IV once a day for at least 4 weeks
-Use in combination with flucytosine.
-Consolidation treatment is done with fluconazole.

Maximum dose: 1.5 mg/kg total daily dose - UNDER NO CIRCUMSTANCES SHOULD THIS DOSE BE EXCEEDED

Comments:
-Administer primarily for progressive, potentially life-threatening fungal infections.
-Excess dosage can lead to potentially fatal cardiac or cardiopulmonary arrest.
-Administer by slow IV infusion, over approximately 2 to 6 hours, depending on dose.
-The recommended concentration for infusion is 0.1 mg/mL.
-Patient tolerance varies greatly; individualize dose based on patient clinical status (e.g. site and severity of infection, cardio-renal function).
-A single test dose is preferred; monitor temperature, pulse, respiration, and blood pressure every 30 minutes for 2 to 4 hours.
-Optimal daily doses and ideal treatment durations are unknown.
-Four week induction therapy is reserved for meningoencephalitis without neurological complications and cerebrospinal fluid yeast cultures that are negative after 2 weeks of treatment.
-In patients with neurological complications, consider using 6 weeks of induction therapy.
-If flucytosine is not given or treatment is interrupted, consider lengthening induction treatment at least 2 weeks.
-Patients at low risk of therapeutic failure (e.g. early diagnosis, no uncontrolled underlying disease, not immunocompromised, and excellent clinical response) consider decreasing induction treatment to 2 weeks.

Use(s): Treatment of cryptococcal meningoencephalitis

**VERIFY PRODUCT NAME AND DOSAGE, ESPECIALLY IF DOSE EXCEEDS 1.5 MG/KG**

Test dose: 1 mg in 20 mL dextrose, slow IV over 20 to 30 minutes, with monitoring for 2 to 4 hours afterward.
Initial dose: 1 mg in 50 mL dextrose IV over 30 minutes
-If initial dose is well tolerated, increase over a period of 2 days to:
Maintenance dose: 0.25 to 1 mg/kg slow IV daily
Duration of therapy: 10 to 14 days

Maximum dose: 1.5 mg/kg total daily dose - UNDER NO CIRCUMSTANCES SHOULD THIS DOSE BE EXCEEDED

Comments:
-Administer primarily for progressive, potentially life-threatening fungal infections.
-Excess dosage can lead to potentially fatal cardiac or cardiopulmonary arrest.
-Administer by slow IV infusion, over approximately 2 to 6 hours, depending on dose.
-The recommended concentration for infusion is 0.1 mg/mL.
-Patient tolerance varies greatly; individualize dose based on patient clinical status (e.g. site and severity of infection, cardio-renal function).
-A single test dose is preferred; monitor temperature, pulse, respiration, and blood pressure every 30 minutes for 2 to 4 hours.
-Optimal daily doses and ideal treatment durations are unknown.
-This disease generally occurs in association with diabetic ketoacidosis; it is imperative for diabetic control to be restored for treatment to be successful.

Use(s): Systemic mycosis

US BOXED WARNING(S):
-This drug should be used PRIMARILY for progressive and potentially life-threatening fungal infections.
-Do not use for noninvasive fungal disease such as oral thrush, vaginal candidiasis and esophageal candidiasis in patients with normal neutrophil counts.
-Do not use injectable doses greater than 1.5 mg/kg.
-EXERCISE CAUTION to prevent overdosage, which can lead to potentially fatal cardiac or cardiopulmonary arrest.
-Verify the product name and dosage before administration, especially if dosage exceeds 1.5 mg/kg.

Consult WARNINGS section for additional precautions.

Substance Name

Amphotericin B

CAS Registry Number

1397-89-3

Drug Class

Antifungal Agents