Ambisome (liposomal amphotericin B) is the lipid formulation of amphotericin B that is indicated in the treatment of serious fungal infections.

AmBisome (Liposomal amphotericin B) Uses:

• Cryptococcal meningitis in HIV-infected patients:

  • Treatment of cryptococcal meningitis in patients who are HIV-infected.

• Empiric therapy in fungal infections:

  • As Empiric treatment in febrile neutropenic patients suffering from presumed fungal infection.

• Fungal infections, systemic therapy:

  • Systemic infections caused by Aspergillus sp, Candida sp, and/or Cryptococcus sp in patients refractory to conventional amphotericin B deoxycholate or when renal impairment or unacceptable toxicity cannot allow the use of the deoxycholate formulation.

• Visceral Leishmaniasis:

  • Treatment Visceral leishmaniasis.

• Off Label Use of amBisome (Liposomal Amphotericin B) in Adults:

  • Candidiasis, empiric therapy (non-neutropenic ICU patients)
  • Coccidioidomycosis in HIV patients
  • Fungal meningitis (secondary to contaminated [eg, Exserohilum rostratum] steroid products)
  • Fungal osteoarticular infections (secondary to contaminated [eg, Exserohilum rostratum] steroid products)
  • Histoplasmosis in HIV patients
  • Cutaneous and mucosal Leishmaniasis
  • Cutaneous leishmaniasis in HIV patients
  • Visceral Leishmaniasis in HIV patients
  • Talaromyces marneffei infection in HIV patients

AmBisome (Liposomal amphotericin B) Dose in Adults

Note:

• Lipid-based amphotericin formulations (AmBisome) may cause confusion with conventional formulations (desoxycholate [Amphocin, Fungizone]) or with other lipid-based amphotericin formulations (amphotericin B lipid complex [Abelcet], amphotericin B cholesteryl sulfate complex [Amphotec]).
• Lipid-based and conventional formulations are not interchangeable and are used in different dosages.
• Overdoses have been reported when conventional formulations were dispensed inadvertently for lipid-based products.

Usual dosage range: IV: 3 to 6 mg/kg/day Note:

• Premedication:
  • For patients who develop non-anaphylactic immediate infusion-related reactions, premedicate with nonsteroidal anti-inflammatory agent ± diphenhydramine; or
  • acetaminophen with diphenhydramine; or
  • hydrocortisone 30 to 60 minutes prior to drug administration:
  • Meperidine may be administered, if the patient experiences rigors during the infusion.

Indication-specific dosing:

amBisome dose as alternative therapy in the Aspergillus (systemic infection) (off-label):

• 3 to 5 mg/kg/day.
• doses up to 7.5 mg/kg/day have been recommended for CNS infection.
• The minimum duration of treatment is 6 to 12 weeks and depending upon the site of infection, the severity of the disease, and the level/duration of immunosuppression.

Note: Guidelines recommend amphotericin B lipid formulations should be considered for invasive aspergillosis in cases when triazoles, specifically voriconazole, are contraindicated or not tolerated.

amBisome dose in the  empiric therapy of Aspergillosis (off-label):

• 3 mg/kg/day.

Note: Guidelines recommend amphotericin B lipid formulations be considered for invasive aspergillosis in cases when triazoles, specifically voriconazole, are contraindicated or not tolerated.

amBisome dose in the treatment of Candidiasis:

• Candidemia (non-neutropenic patients) (alternative agent):

  • 3 to 5 mg/kg/day; may shift to fluconazole (usually after 5 to 7 days) in clinically stable patients, with fluconazole-susceptible isolates, and on negative repeat cultures.
  • The total duration of antifungal therapy is at least Two weeks after the documented evidence of Candida from the bloodstream and resolution of candidemia-associated symptoms in patients without metastatic complications.

• Candidemia (neutropenic patients) (alternative agent):

  • 3 to 5 mg/kg/day; may shift to fluconazole during persistent low Absolute neutrophil count in clinically stable patients, with fluconazole-susceptible isolates and negative repeat cultures.
  • The total duration of antifungal therapy is at least two weeks after the documented clearance of Candida from the bloodstream and resolution of neutropenia and candidemia-associated symptoms in patients with no metastatic complications.

• The central nervous system (eg, meningitis):

  • 5 mg/kg/day (with or without oral flucytosine);
  • step-down to fluconazole therapy is advised after initial response to treatment.

• Chronic disseminated (hepatosplenic):

  • 3 to 5 mg/kg/day;
  • after several weeks, changing to oral fluconazole in clinically stable, fluconazole-susceptible patients.

• Empiric therapy in suspected invasive candidiasis (non-neutropenic ICU patients) (alternative agent):

  • 3 to 5 mg/kg/day; treatment should continue for 14 days in patients with clinical and subjective improvement. Consider discontinuing after 4 to 5 days in patients with no clinical improvement.

• Endocarditis (native or prosthetic valve) or infected implantable cardiac devices (eg, pacemaker, ICD, VAD):

  • 3 to 5 mg/kg/day (with or without flucytosine);
  • for native or prosthetic valve endocarditis, therapy should be continued for at least 6 weeks post valve replacement surgery (longer durations in patients with abscesses or other complications);
  • for patients with implantable cardiac devices, therapy should be continued for 4 to 6 weeks post-surgery (4 for infections limited to generator pockets and at least 6 weeks for infections involving the wires).

Note:

• May transition to fluconazole if the patient is clinically stable with fluconazole-susceptible isolates and Candida has been cleared from the bloodstream;
• chronic or long-term suppression with fluconazole may be needed (eg, prosthetic valve, valve replacement not possible).

• Endophthalmitis (with or without vitritis) caused by fluconazole- or voriconazole-resistant isolates:

  • 3 to 5 mg/kg/day (with or without flucytosine) for at least 4 to 6 weeks until examination indicates resolution;
  • for patients with vitritis or with macular involvement (with or without vitritis), an intravitreal injection of voriconazole or amphotericin B deoxycholate is also recommended.

• Intra-abdominal candidiasis (alternative agent):

  • 3 to 5 mg/kg/day; duration of therapy depends upon clinical response and source control.

• Osteomyelitis or septic arthritis due to Candida (alternative agent):

  • 3 to 5 mg/kg/day for at least 14 days, followed by fluconazole.

• Suppurative thrombophlebitis:

  • 3 to 5 mg/kg/day; continue for at least 14 days after candidemia has cleared; consider switching to fluconazole in clinically stable patients with a fluconazole-susceptible isolate who have responded to initial therapy.

• Manufacturer’s labeling:

  • Dosing in the prescribing information may not reflect current clinical practice.
    • Empiric therapy: 3 mg/kg/day;
    • Invasive infection: 3 to 5 mg/kg/day.

amBisome dose in the treatment of Coccidioidomycosis in HIV-infected patients (off-label):

• Severe non-CNS infection (i.e. diffuse pulmonary or severely ill with the extrathoracic or disseminated disease):

  • 3 to 5 mg/kg/day until clinical improvement, then start triazole therapy (eg, fluconazole or itraconazole).

amBisome dose in the treatment of Cryptococcosis:

• Disseminated cryptococcosis (non-CNS or severe pulmonary disease) in HIV-infected patients:

  • IV: 3 to 4 mg/kg/day with flucytosine (preferred) or fluconazole, or without a concomitant agent.

• Meningitis in HIV-infected patients:

  • 3 to 4 mg/kg/day with flucytosine (preferred) or fluconazole, or without a concomitant agent.
  • doses up to 6 mg/kg/dose have been reported for treatment of meningoencephalitis and may be suggested for treatment failure or high fungal burden disease.

• Manufacturer’s labeling:

  • Dosing in the prescribing information may not reflect current clinical practice. 6 mg/kg/day.

amBisome dose in the treatment of fungal sinusitis:

• Limited data in immunosuppressed patients have shown efficacy with 3 to 10 mg/kg/day.

Note: An azole antifungal is recommended if the causative organism is Aspergillus spp or Pseudallescheria boydii (Scedosporium sp).

amBisome dose in the treatment of Histoplasmosis in HIV-infected patients:

• moderately severe to severe disseminated disease:

  • Induction therapy: 3 mg/kg/day for at least 2 weeks, followed by oral itraconazole for maintenance therapy

• Histoplasma meningitis:

  • Induction therapy: 5 mg/kg/day for 4 to 6 weeks, followed by oral itraconazole for maintenance therapy

amBisome dose in the treatment of cutaneous leishmaniasis:

• IV: 3 mg/kg/day on days 1 through 5, and then on day 10 or
• on days 1 through 7.
• The total dose administered should be 18 to 21 mg/kg.

amBisome dose in the treatment of cutaneous Leishmaniasis in HIV-infected patients:

• 2 to 4 mg/kg/day for 10 days or
• an interrupted schedule (eg, 4 mg/kg on days 1 through 5, and then on days 10, 17, 24, 31, 38).
• Total dose given should be 20 to 60 mg/kg.

amBisome dose in the treatment of mucosal Leishmaniasis:

• 3 mg/kg/day IV for a total administered dose of almost 20 to 60 mg/kg.

amBisome Dose in the treatment of visceral Leishmaniasis:

• Immunocompetent:

  • 3 mg/kg/day on days 1 through 5, and 3 mg/kg/day on days 14 and 21;
  • a repeat course may be given in patients who do not achieve parasitic clearance

• Immunocompromised:

  • 4 mg/kg/day on days 1 through 5, and 4 mg/kg/day on days 10, 17, 24, 31, and 38

amBisome Dose in the treatment of visceral leishmaniasis in HIV-infected patients:

• Treatment:

  • 2 to 4 mg/kg/day or
  • an interrupted schedule (eg, 4 mg/kg on days 1 through 5, and then on days 10, 17, 24, 31, and 38).
  • Total dose administered: 20 to 60 mg/kg

• Chronic maintenance therapy (for patients with a CD4 count <200 cells/mm³):

  • 4 mg/kg every 2 to 4 weeks

amBisome Dose in the treatment of Severe Meningitis (secondary to contaminated [eg, Exserohilum rostratum] steroid products) or in patients not improving with voriconazole monotherapy (off-label):

• IV: 5 to 6 mg/kg/day in combination with voriconazole for ≥3 months; a higher dose (7.5 mg/kg/day) may be considered in patients who are not

Note: Consult an infectious disease specialist and current CDC guidelines for specific treatment recommendations.

amBisome Dose in the treatment of severe Osteoarticular infection (secondary to contaminated e.g., Exserohilum rostratum) steroid products:

• IV: 5 mg/kg/day in combination with voriconazole for ≥3 months.

Note: Take the opinion of an infectious disease specialist and current CDC guidelines for specific treatment recommendations.

amBisome Dose in the treatment of Talaromyces marneffei infection in HIV-infected patients (off-label):

• 3 to 5 mg/kg/day for 2 weeks, followed by oral itraconazole for 10 weeks, followed by chronic maintenance therapy

AmBisome (Liposomal amphotericin B) Dose in Childrens

• Medication errors, including deaths, have been reported from confusion between lipid-based forms of amphotericin (Abelcet, Amphotec, AmBisome) and conventional amphotericin B for injection.
• Lipid-based and conventional formulations are not interchangeable and have different dosing recommendations.
• Overdoses have occurred when conventional formulations were dispensed inadvertently for lipid-based products.

Note:

• Premedication: For patients who experience non-anaphylactic infusion-related immediate reactions, pre-medicate with the following drugs 30 to 60 minutes prior to drug administration: NSAID (with or without diphenhydramine) or acetaminophen with diphenhydramine or hydrocortisone.
• If the patient experiences rigors during the infusion, meperidine may be administered.

amBisome (Liposomal amphotericin B) General dosing:

• Empiric therapy:

  • Infants, Children, and Adolescents:

    • IV: 3 mg/kg/dose once a day

• Treatment, susceptible systemic infection:

  • Infants, Children, and Adolescents:

    • IV: 3 to 5 mg/kg/dose once a day

amBisome (Liposomal amphotericin B) dose in the treatment of Aspergillosis:

• Invasive:

  • Infants, Children, and Adolescents:

    • IV: 3 to 5 mg/kg/dose once a day.

• Endocarditis:

  • Children and Adolescents:

    • IV: 3 to 5 mg/kg/dose once a day with or without flucytosine.

amBisome (Liposomal amphotericin B) dose in the treatment of invasive Blastomycosis:

• Infants, Children, and Adolescents:

  • IV: 3 to 5 mg/kg/dose once a day for initial therapy,
  • if CNS infection 4 to 6 weeks may be needed; followed by oral itraconazole for a total of 12 months.

amBisome (Liposomal amphotericin B) dose in the treatment of Candidiasis:

• Invasive (Independent of HIV status):

  • Infant, Children, and Adolescents:

    • IV: 3 to 5 mg/kg/dose once a day.
    • Note: In HIV-exposed/- positive patients, doses at the higher end of the range may be considered (5 mg/kg/day).

• CNS infection:

  • Infants, Children, and Adolescents:

    • IV: 5 mg/kg/dose once a day with or without flucytosine.

• Endocarditis:

  • Infants, Children, and Adolescents:

    • IV: 3 to 5 mg/kg/dose once a day with or without flucytosine.

• Esophageal:

  • HIV-exposed/-positive:

    • Adolescents:

      • IV: 3 to 4 mg/kg/dose once a day for 14 to 21 days.

amBisome (Liposomal amphotericin B) dose in the treatment of invasive Coccidioidomycosis:

• Non-HIV-exposed/ HIV-positive:

  • Disseminated infection, non-pulmonary:

    • Infants, Children, and Adolescents:

      • IV: 2 to 5 mg/kg/dose once a day with or without concomitant azole antifungal.

  • Diffuse Pulmonary infection:

    • Infants, Children, and Adolescents:

      • IV: 2 to 5 mg/kg/dose once a day for several weeks, followed by an oral azole antifungal for a total length of therapy ≥12 months.

• HIV-exposed/ HIV-positive:

  • Severe non-CNS infection (ie, diffuse pulmonary or severely ill with extrathoracic disseminated disease):

    • Infants and Children:

      • IV: 5 mg/kg/dose once a day until clinical improvement (minimum of several weeks of therapy), then initiate triazole therapy (eg, fluconazole or itraconazole);
      • The dose may be increased to as high as 10 mg/kg/dose once a day for life-threatening infection.

    • Adolescents:

      • IV: 3 to 5 mg/kg/dose once a day until clinical improvement, then switch to fluconazole or itraconazole.

amBisome (Liposomal amphotericin B) dose in the treatment of invasive cryptococcosis:

• Disseminated cryptococcosis (non-CNS or severe pulmonary disease):

  • Infants and Children (independent of HIV status):

    • IV: 3 to 5 mg/kg/dose once a day with oral flucytosine;
    • if flucytosine unavailable or not tolerated may administer alone or in combination with high-dose fluconazole in HIV-exposed/-positive patients.

  • Adolescents:

    • Non-HIV-exposed/-positive:

      • IV: 3 to 4 mg/kg/dose once a day for at least 14 days;
      • may consider the addition of oral flucytosine.

    • HIV-exposed/-positive:

      • IV: 3 to 4 mg/kg/dose once a day with or without flucytosine or fluconazole.

amBisome (Liposomal amphotericin B) dose in the treatment of Meningitis:

• Non-HIV-exposed/ HIV-positive:

  • Infants, Children, and Adolescents:

    • IV: 5 mg/kg/dose once a day with flucytosine.

• HIV-exposed/ HIV-positive:

  • Manufacturer’s labeling:

    • Infants, Children, and Adolescents:

      • IV: 6 mg/kg/dose once a day

  • Alternate dosing:

    • Infants and Children:

      • IV: 6 mg/kg/dose once a day with or without oral flucytosine or high dose fluconazole for a minimum 2-week induction;

    • Note:

      • Minimum 2-week induction, followed by consolidation and chronic suppressive therapy;
      • a longer duration of induction therapy may be necessary if CSF is not negative or lack of clinical improvement.

    • Adolescents:

      • IV: 3 to 4 mg/kg/dose once a day with or without oral flucytosine or fluconazole.
      • doses up to 6 mg/kg/dose have been reported for treatment of meningoencephalitis and may be considered for treatment failure or high fungal burden disease.

amBisome (Liposomal amphotericin B) dose in the empiric therapy of Febrile neutropenia:

• Infants, Children, and Adolescents:

  • IV: 3 mg/kg/dose once daily.

amBisome (Liposomal amphotericin B) dose in the treatment of Histoplasmosis:

• Non-HIV-exposed or HIV-positive:

  • Acute pulmonary disease or disseminated (non-CNS):

    • Infants, Children, and Adolescents:

      • IV: 3 mg/kg/dose once a day for 1 to 2 weeks followed by oral itraconazole for a total of 12 weeks; conventional amphotericin B typically preferred.

• HIV-exposed/-positive:

  • Disseminated infection (non-CNS disease):

    • Infants and Children:

      • IV: 3 to 5 mg/kg/dose once a day for at least 2 weeks for induction;
      • if itraconazole not tolerated for consolidation therapy may continue for 4 to 6 weeks.

    • Adolescents:

      • IV: 3 mg/kg/dose once a day for at least 2 weeks for induction.

  • CNS disease:

    • Infants, Children, and Adolescents:

      • IV: 5 mg/kg/dose once a day for 4 to 6 weeks for induction, followed by consolidation therapy.

amBisome (Liposomal amphotericin B) dose in the treatment of Leishmaniasis:

• Visceral infection, treatment:

  • Immunocompetent patients:

    • Infants, Children, and Adolescents:

      • IV: Initial: 3 mg/kg/dose once a day on days 1 to 5 and 3 mg/kg/dose on days 14 and 21.

Note: Repeat course may be given to patients who do not achieve parasitic clearance.

• Immunocompromised patients:

  • Infants, Children, and Adolescents:

    • IV: Initial: 4 mg/kg/dose once a day on days 1 to 5 and 4 mg/kg/dose on days 10, 17, 24, 31, 38

• HIV-exposed/-positive:

  • Treatment:

    • Adolescents:

      • IV: 2 to 4 mg/kg/dose once a day or an interrupted schedule of 4 mg/kg/dose on days 1 to 5, and on days 10, 17, 24, 31, and 38 to achieve a total dose of 20 to 60 mg/kg.

  • Chronic maintenance therapy:

    • Adolescents:

      • IV: 4 mg/kg/dose every 2 to 4 weeks;
      • Note: Use reserved for patients with visceral infection and CD4 count <200 cells/mm

amBisome (Liposomal amphotericin B) dose in the treatment of cutaneous infection in HIV-exposed/-positive:

• Adolescents:

  • 2 to 4 mg/kg/dose IV once a day for 10 days or an interrupted schedule of 4 mg/kg/dose on days 1 to 5, and on days 10, 17, 24, 31, and 38 to achieve a total dose of 20 to 60 mg/kg.

amBisome (Liposomal amphotericin B) Dose in the treatment of Sporotrichosis infection:

• Disseminated, pulmonary, or osteoarticular disease:

  • Adolescents:

    • 3 to 5 mg/kg/dose IV once a day, followed by oral itraconazole after a favorable response is seen with amphotericin initial therapy

• Meningeal:

  • Adolescents:

    • • 5 mg/kg/dose IV once a day for 4 to 6 weeks, followed by oral itraconazole

Pregnancy Risk Factor B

• In animal reproduction studies, adverse events were not reported.
• Amphotericin crosses over the placenta to enter the fetal circulation.
• For serious systemic fungal diseases, pregnant women should be treated with amphotericin B.

Liposomal Amphotericin B Use during Breast-Feeding:

• If amphotericin has been excreted from breast milk, there is no data.
• Because of its poor oral absorption, the systemic exposure to nursing infants is likely to be very low.
• The manufacturer does not recommend breast-feeding due to the risk of toxic effects.

amBisome (liposomal amphotericin B dose in Kidney Disease:

There are no dosage adjustments provided in the manufacturer’s labeling; It has been successfully administered to patients with preexisting renal impairment.

• End-stage renal disease (ESRD) on intermittent hemodialysis (IHD) (administer after hemodialysis on dialysis days):

  • It is poorly dialyzed;
  • No dosage adjustment necessary

• CVVH/CVVHD/CVVHDF:

  • No dosage adjustment necessary

amBisome dose in Liver disease:

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Common Side Effects of amBisome (Liposomal Amphotericin B):

• Cardiovascular:

  • Hypertension
  • Tachycardia
  • Peripheral Edema
  • Edema
  • Hypotension
  • Chest Pain
  • Localized Phlebitis

• Central Nervous System:

  • Chills
  • Insomnia
  • Headache
  • Pain
  • Anxiety
  • Confusion

• Dermatologic:

  • Skin Rash
  • Pruritus

• Endocrine & Metabolic:

  • Hypokalemia
  • Hypomagnesemia
  • Hyperglycemia
  • Hypocalcemia
  • Hyponatremia
  • Hypervolemia

• Gastrointestinal:

  • Nausea
  • Vomiting
  • Diarrhea
  • Abdominal Pain
  • Constipation
  • Anorexia

• Genitourinary:

  • Nephrotoxicity
  • Hematuria

• Hematologic & Oncologic:

  • Anemia
  • Leukopenia
  • Thrombocytopenia

• Hepatic:

  • Increased Serum Alkaline Phosphatase
  • Hyperbilirubinemia
  • Increased Serum ALT
  • Increased Serum AST
  • Abnormal Hepatic Function Tests

• Hypersensitivity:

  • Transfusion Reaction

• Infection:

  • Sepsis
  • Infection

• Neuromuscular & Skeletal:

  • Weakness
  • Back Pain

• Renal:

  • Increased Serum Creatinine
  • Increased Blood Urea Nitrogen

• Respiratory:

  • Dyspnea
  • Pulmonary Disease
  • Cough
  • Epistaxis
  • Pleural Effusion
  • Rhinitis

• Miscellaneous:

  • Infusion Related Reactions

Less Common Side Effects of amBisome (Liposomal Amphotericin B):

• Cardiovascular:

  • Atrial Fibrillation
  • Bradycardia
  • Cardiac Arrest
  • Cardiac Arrhythmia
  • Cardiomegaly
  • Facial Edema
  • Flushing
  • Heart Valve Disease
  • Orthostatic Hypotension
  • Vascular Disorder
  • Vasodilatation

• Central Nervous System:

  • Dizziness
  • Abnormality In Thinking
  • Agitation
  • Coma
  • Depression
  • Drowsiness
  • Dysesthesia
  • Dystonia
  • Hallucination
  • Malaise
  • Nervousness
  • Paresthesia
  • Rigors
  • Seizure

• Dermatologic:

  • Diaphoresis
  • Alopecia
  • Cellulitis
  • Dermal Ulcer
  • Dermatological Reaction
  • Maculopapular Rash
  • Skin Discoloration
  • Urticaria
  • Vesiculobullous Dermatitis
  • Xeroderma

• Endocrine & Metabolic:

  • Hypernatremia
  • Acidosis
  • Hyperchloremia
  • Hyperkalemia
  • Hypermagnesemia
  • Hyperphosphatemia
  • Hypophosphatemia
  • Increased Lactate Dehydrogenase
  • Increased Nonprotein Nitrogen

• Gastrointestinal:

  • Gastrointestinal Hemorrhage
  • Aphthous Stomatitis
  • Dyspepsia
  • Dysphagia
  • Enlargement Of Abdomen
  • Eructation
  • Fecal Incontinence
  • Flatulence
  • Gingival Hemorrhage
  • Hematemesis
  • Hemorrhoids
  • Hiccups
  • Increased Serum Amylase
  • Intestinal Obstruction
  • Mucositis
  • Rectal Disease
  • Stomatitis
  • Xerostomia

• Genitourinary:

  • Dysuria
  • Toxic Nephrosis
  • Urinary incontence
  • Vaginal Hemorrhage

• Hematologic & Oncologic:

  • Blood Coagulation Disorder
  • Bruise
  • Decreased Prothrombin Time
  • Hemophthalmos
  • Hemorrhage
  • Hypoproteinemia
  • Increased Prothrombin Time
  • Oral Hemorrhage
  • Petechia
  • Purpura

• Hepatic:

  • Hepatic Injury
  • Hepatic Sinusoidal Obstruction Syndrome (Formerly Known As Hepatic Veno-Occlusive Disease)
  • Hepatomegaly

• Hypersensitivity:

  • Delayed Hypersensitivity
  • Hypersensitivity Reaction

• Immunologic:

  • Graft Versus Host Disease

• Infection:

  • Herpes Simplex Infection

• Local:

  • Inflammation At Injection Site

• Neuromuscular & Skeletal:

  • Arthralgia
  • Myalgia
  • Neck Pain
  • Ostealgia
  • Tremor

• Ophthalmic:

  • Conjunctivitis
  • Dry Eyes

• Renal:

  • Acute Renal Failure
  • Renal Failure
  • Renal Function Abnormality

• Respiratory:

  • Hypoxia
  • Asthma
  • Atelectasis
  • Dry Nose
  • Flu-Like Symptoms
  • Hemoptysis
  • Hyperventilation
  • Pharyngitis
  • Pneumonia
  • Pulmonary Edema
  • Respiratory Alkalosis
  • Respiratory Failure
  • Respiratory Insufficiency
  • Sinusitis

• Miscellaneous:

  • Procedural Complication

Contraindications to amBisome (Liposomal Amphotericin B):

Hypersensitivity to amphotericinB deoxycholate and any component of the formulation

Warnings and precautions​​​​​​​

• Anaphylaxis

  • It has been reported that amphotericin B-containing drugs were involved in the incident
    • Due to the possibility that anaphylactic reactions may occur, it is important that cardiopulmonary resuscitation facilities are available at all times.
  • If severe anaphylactic reactions occur,
    • The infusion should be stopped immediately
    • The patient should stop receiving further infusions.
  • Administer under close clinical observation during initial dosing.

• Infusion reactions

  • Infusions may cause acute reactions, including fever and chills, within 1 to 3 hours of starting. These reactions are more common in the first few doses but generally decrease with subsequent doses.
  • If severe anaphylactic reactions occur, stop infusion immediately. The patient should not be given any further infusions.

• Heart failure:

  • According to the American Heart Association's scientific statement, amphotericin is a substance that can cause myocardial damage (magnitude: major/moderate).

Liposomal amphotericin B: Drug Interaction

Risk Factor C (Monitor therapy)
Alfuzosin	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Aminoglycosides	Amphotericin B may enhance the nephrotoxic effect of Aminoglycosides.
Antifungal Agents (Azole Derivatives, Systemic)	May diminish the therapeutic effect of Amphotericin B.
Antipsychotic Agents (Second Generation [Atypical])	Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]).
Barbiturates	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Benperidol	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Blood Pressure Lowering Agents	May enhance the hypotensive effect of HypotensionAssociated Agents.
Brimonidine (Topical)	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Cardiac Glycosides	Amphotericin B may enhance the adverse/toxic effect of Cardiac Glycosides.
Corticosteroids (Orally Inhaled)	May enhance the hypokalemic effect of Amphotericin B.
Corticosteroids (Systemic)	May enhance the hypokalemic effect of Amphotericin B.
CycloSPORINE (Systemic)	Amphotericin B may enhance the nephrotoxic effect of CycloSPORINE (Systemic).
Diazoxide	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Dronabinol	May increase the serum concentration of Amphotericin B. Specifically, dronabinol may displace amphotericin B from its protein-binding sites, leading to an increased concentration of active, unbound drug.
DULoxetine	Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine.
Flucytosine	Amphotericin B may enhance the adverse/toxic effect of Flucytosine. This may be related to the adverse effects of amphotericin B on renal function.
Ganciclovir-Valganciclovir	May enhance the nephrotoxic effect of Amphotericin B.
Herbs (Hypotensive Properties)	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Hypotension-Associated Agents	Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents.
Levodopa-Containing Products	Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products.
Lormetazepam	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Molsidomine	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Naftopidil	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Nicergoline	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Nicorandil	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Nitroprusside	Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside.
Pentoxifylline	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Pholcodine	Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine.
Phosphodiesterase 5 Inhibitors	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Prostacyclin Analogues	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Quinagolide	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Risk Factor D (Consider therapy modification)
Amifostine	Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered.
Colistimethate	Amphotericin B may enhance the nephrotoxic effect of Colistimethate.
Obinutuzumab	May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion.
Sodium Stibogluconate	Amphotericin B may enhance the cardiotoxic effect of Sodium Stibogluconate.
Risk Factor X (Avoid combination)
Bromperidol	Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents.
Foscarnet	May enhance the nephrotoxic effect of Amphotericin B.
Methoxyflurane	May enhance the nephrotoxic effect of Amphotericin B.
Saccharomyces boulardii	Antifungal Agents (Systemic, Oral) may diminish the therapeutic effect of Saccharomyces boulardii.

Monitoring parameters:

• Renal function (monitor frequently during therapy),
• electrolytes (especially potassium and magnesium),
• liver function tests,
• temperature,
• hematocrit,
• PT/PTT,
• CBC;
• monitor input and output;
• monitor for signs of hypokalemia (muscle weakness, cramping, drowsiness, ECG changes, etc);
• monitor cardiac function if used concurrently with corticosteroids

How to administer amBisome (Liposomal Amphotericin B)?

• Administer via intravenous infusion, over a period of approximately 2 hours.
• Infusion time may be lower down to approximately 1 hour in patients in whom the treatment is well-tolerated.
• If the patient experiences any problem during infusion, the duration of infusion may be increased.
• An existing intravenous line should be flushed with D/W before and after infusion (if not feasible, administer through a separate line).
• An in-line membrane filter (not less than 1 micron) may be used.
• For a patient who experiences chills, fever, hypotension, nausea, or other non-anaphylactic immediate infusion-related reactions, pre-medicate with the following drugs, 30 to 60 minutes prior to drug administration:
  • A nonsteroidal (eg, ibuprofen, choline magnesium trisalicylate) ± diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone.
• If the patient experiences rigors during the infusion, meperidine may be administered.

Mechanism of Action of Ambisme (Liposomal Amphotericin B):

• Binds to Ergosterol, altering cell membrane permeability for susceptible fungi, and causing cell death through leakage of cell components.
• According to the proposed mechanism, amphotericin stimulates macrophages through an oxidation-dependent process.

Notice:

Nonlinear kinetics: greater than proportional increase of serum concentration with an increasing dose

Half-life elimination:

• 7 to 10 hours (following a single 24-hour dosing interval);
• Terminal half to life: 100 to 153 hours (following multiple dosing up to 49 days)

International Brands of Liposomal Amphotericin B:

• AmBisome
• Ambisome
• Amfostat
• Amphotec
• Fengkesong

Liposomal Amphotericin B Brand Names in Pakistan:

No brands available in Pakistan