Liposomal Amphotericin B

Liposomal Amphotericin B is an Antifungal Agent belonging to the pharmacological class of Polyene antifungals.

Liposomal Amphotericin B has been approved to relieve symptoms and also for the treatment and maintenance of Cryptococcosis, Fungal sinusitis, Invasive Fusariosis, Histoplasmosis, Leishmaniasis, Severe meningitis or in patients not responding to voriconPolyene monotherapy, Mucormycosis, Empirical antifungal therapy for neutropenic fever, Severe osteoarticular infection or in patients with clinical instability, Talaromyces in HIV patients.

Liposomal amphotericin B exhibits excellent bioavailability of 100% when administered through intravenous infusion. It is highly bound to plasma proteins, with a binding rate exceeding 90%. The drug is exclusively metabolized through renal processes. Although the exact volume of distribution and route of elimination is not available, its pharmacokinetics show an initial plasma half-life of approximately 24 hours, followed by an elimination half-life of about 15 days.

The common side effects of Liposomal Amphotericin B include Vision changes, Hearing changes (e.g., ringing in the ears), Dark urine, Severe stomach or abdominal pain, Muscle cramping, Changes in the amount of urine, Painful urination, Numbness or tingling of arms or legs, Cold sweats, Blue lips, Yellowing of eyes or skin, Swelling ankles or feet, Fast/slow/irregular heartbeat, Swelling or pain at the injection site.

Liposomal Amphotericin B is available in the form of Powder for Injection.

Liposomal Amphotericin B is approved in Germany, Japan, Malaysia, India, the U.K., the U.S., and China.

Liposomal Amphotericin B, belonging to the pharmacological class of Polyene antifungals, acts as an Antifungal Agent.

Amphotericin B can exhibit fungistatic or fungicidal effects, depending on its concentration in body fluids and the susceptibility of the fungus. The drug's mechanism of action involves binding to sterols, particularly ergosterol, found in the cell membrane of susceptible fungi. This interaction creates a transmembrane channel, leading to a change in membrane permeability and causing intracellular components to leak out. Ergosterol, which is the primary sterol in the fungal cytoplasmic membrane, serves as the target site for both amphotericin B and the Polyenes. As a polyene, amphotericin B forms an irreversible bond with ergosterol, disrupting membrane integrity and ultimately leading to cell death.

Liposomal Amphotericin B has been approved to relieve symptoms and also for the treatment and maintenance of Cryptococcosis, Fungal sinusitis, Invasive Fusariosis, Histoplasmosis, Leishmaniasis, Severe meningitis or in patients not responding to voricon Polyene monotherapy, Mucormycosis, Empirical antifungal therapy for neutropenic fever, Severe osteoarticular infection or in patients with clinical instability, Talaromyces in HIV patients.

The mean half-life of Liposomal Amphotericin B, determined by measuring total amphotericin B concentrations within a dosing interval of 24 hours after administration, was found to be approximately 7-10 hours.

Liposomal Amphotericin B is found to be available in the form of Powder for Injection.

Liposomal Amphotericin B can be used in the following treatment:

• Aspergillus infection
• Candidiasis
• Coccidioidomycosis in HIV patients
• Cryptococcosis
• Fungal sinusitis
• Invasive Fusariosis
• Histoplasmosis
• Leishmaniasis
• Severe meningitis or in patients not responding to voriconPolyene monotherapy
• Mucormycosis
• Empirical antifungal therapy for neutropenic fever
• Severe osteoarticular infection or in patients with clinical instability
• Talaromycosis in HIV patients

Liposomal Amphotericin B can help to relieve symptoms and also for the treatment and maintenance of Aspergillus infection, Candidiasis, Coccidioidomycosis in HIV patients, Cryptococcosis, Fungal sinusitis, Invasive Fusariosis, Histoplasmosis, Leishmaniasis, Severe meningitis or in patients not responding to voriconPolyene monotherapy, Mucormycosis, Empirical antifungal therapy for neutropenic fever, Severe osteoarticular infection or in patients with clinical instability, Talaromyces in HIV patients.

Liposomal Amphotericin B is approved for use in the following clinical indications:

• Aspergillus infection
• Candidiasis
• Coccidioidomycosis in HIV patients
• Cryptococcosis
• Fungal sinusitis
• Invasive Fusariosis
• Histoplasmosis
• Leishmaniasis
• Severe meningitis or in patients not responding to voriconPolyene monotherapy
• Mucormycosis
• Empirical antifungal therapy for neutropenic fever
• Severe osteoarticular infection or in patients with clinical instability
• Talaromycosis in HIV patients

Aspergillus:

Systemic infection (alternative therapy): IV: 3 to 5 mg/kg once daily; doses up to 7.5 mg/kg once daily may be recommended for CNS infection.

The minimum duration of treatment is 6 to 12 weeks, depending on the site of infection, the extent of the disease, and the level/duration of immunosuppression.

Liposomal amphotericin B should be considered for invasive aspergillosis when triPolyenes, especially voriconPolyene, are contraindicated or not tolerated.

Candidiasis:

Candidemia (nonneutropenic patients - alternative agent): IV: 3 to 5 mg/kg once daily; transition to fluconPolyene after clinical improvement and negative repeat cultures.

Candidemia (neutropenic patients - alternative agent): IV: 3 to 5 mg/kg once daily; transition to fluconPolyene during persistent neutropenia.

Central nervous system (CNS) infection (e.g., meningitis): IV: 5 mg/kg once daily (with or without oral flucytosine); switch to fluconPolyene therapy after initial response.

Chronic disseminated (hepatosplenic): IV: 3 to 5 mg/kg once daily; transition to oral fluconPolyene after several weeks.

Empiric therapy suspected invasive candidiasis (nonneutropenic ICU patients - alternative agent - off-label use): IV: 3 to 5 mg/kg once daily.

Endocarditis or infected implantable cardiac devices: IV: 3 to 5 mg/kg once daily (with or without flucytosine); consider transition to fluconPolyene if clinically stable with fluconPolyene-susceptible isolates.

Esophageal, refractory disease (alternative agent - off-label use): IV: 3 mg/kg once daily; transition to an oral antifungal once patient tolerates oral intake.

Intra-abdominal candidiasis (alternative agent): IV: 3 to 5 mg/kg once daily; duration of therapy determined by clinical response and source control.

Osteomyelitis or septic arthritis due to Candida (alternative agent): IV: 3 to 5 mg/kg once daily for at least 2 weeks, followed by fluconPolyene for extended treatment.

Suppurative thrombophlebitis: IV: 3 to 5 mg/kg once daily; continue for at least 2 weeks after candidemia has cleared; consider transition to fluconPolyene in stable patients with fluconPolyene-susceptible isolates.

Coccidioidomycosis in patients with HIV (off-label use):

Non-CNS infection, severe: IV: 3 to 5 mg/kg once daily until clinical improvement, then initiate triPolyene therapy (e.g., fluconPolyene or itraconPolyene).

Cryptococcosis:

Disseminated cryptococcosis (non-CNS or severe pulmonary disease): Induction therapy: IV: 3 to 4 mg/kg once daily with flucytosine (preferred) or fluconPolyene, followed by consolidation and maintenance therapy with fluconPolyene.

Meningitis: Induction therapy: IV: 3 to 4 mg/kg once daily with flucytosine (preferred) or fluconPolyene; doses up to 6 mg/kg/dose have been reported for severe cases.

Meningitis (resource-limited settings - off-label use): IV: 10 mg/kg as a single dose, in combination with fluconPolyene and flucytosine.

Fungal Sinusitis (limited data in immunocompromised patients):

IV: Efficacy observed with 3 to 10 mg/kg once daily; consider a Polyene antifungal if caused by Aspergillus spp or Pseudallescheria boydii (Scedosporium sp).

Invasive Fusariosis (off-label use):

IV: 3 to 5 mg/kg once daily; duration of treatment is often prolonged and depends on the site of infection, severity, immune status, and response to therapy.

CNS infection: Initial: 5 mg/kg once daily in combination with voriconPolyene; dose escalation may be considered for insufficient response.

Histoplasmosis (off-label use):

Acute pulmonary disease, moderately severe to severe: IV: 3 to 5 mg/kg once daily for 1 to 2 weeks, followed by itraconPolyene maintenance therapy.

Disseminated disease, moderately severe to severe: IV: 3 mg/kg once daily for 1 to 2 weeks (patients without HIV) or at least 2 weeks (patients with HIV), followed by itraconPolyene maintenance therapy.

Histoplasma meningitis: IV: 5 mg/kg once daily for 4 to 6 weeks, followed by itraconPolyene maintenance therapy.

Leishmaniasis:

Cutaneous (off-label use):

Patients without HIV: IV: 3 mg/kg once daily 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.

Patients with HIV: IV: 2 to 4 mg/kg once daily for 10 days or an interrupted schedule, with a total dose administered of 20 to 60 mg/kg.

Mucosal (off-label use):

Patients without HIV: IV: ~3 mg/kg once daily for a cumulative total administered dose of ~20 to 60 mg/kg.

Patients with HIV: IV: 2 to 4 mg/kg once daily for 10 days or an interrupted schedule, with a total dose administered of 20 to 60 mg/kg.

Visceral:

Immunocompetent: IV: 3 mg/kg once daily on days 1 through 5 and 3 mg/kg once daily on days 14 and 21; a repeat course may be given if parasitic clearance is not achieved.

Immunocompromised, including patients with HIV:

Monotherapy: IV: 2 to 4 mg/kg once daily or an interrupted schedule, with a total dose administered of 20 to 60 mg/kg.

Combination therapy (for patients with HIV and visceral leishmaniasis from East Africa or Southeast Asia): IV: 5 mg/kg as a single dose on days 1, 3, 5, 7, 9, and 11 (total dose administered: 30 mg/kg) in combination with miltefosine.

Secondary prophylaxis (chronic maintenance therapy) for patients with HIV and high risk of relapse: IV: 4 mg/kg once every 2 to 4 weeks.

Meningitis, severe or in patients not improving with voriconPolyene monotherapy (off-label use):

IV: 5 to 6 mg/kg once daily in combination with voriconPolyene for ≥3 months; a higher dose (7.5 mg/kg once daily) may be considered in patients who are not improving.

Mucormycosis (off-label use):

IV: 5 to 10 mg/kg once daily; 10 mg/kg once daily recommended for patients with CNS disease or solid organ transplant recipients.

Neutropenic fever, empirical antifungal therapy:

IV: 3 to 5 mg/kg once daily.

Osteoarticular infection, severe or in patients with clinical instability (off-label use):

IV: 5 mg/kg once daily in combination with voriconPolyene for ≥3 months.

Talaromycosis (formerly Penicillinosis) in patients with HIV (off-label use):

IV: 3 to 5 mg/kg once daily for 2 weeks, followed by oral itraconazole for 10 weeks, followed by chronic maintenance therapy.

Liposomal Amphotericin B is available in the following dosage forms and strengths:

• Powder for Injection : 50mg /vial

Powder for Injection.

Dosage Adjustments in Pediatric Patients:

Aspergillosis, Treatment:

• Invasive: Infants, Children, and Adolescents: IV: 3 to 5 mg/kg/dose once daily
• Endocarditis: Children and Adolescents: IV: 3 to 5 mg/kg/dose once daily with or without flucytosine

Blastomycosis, Invasive:

• Infants, Children, and Adolescents: IV: 3 to 5 mg/kg/dose once daily for initial therapy, if CNS infection 4 to 6 weeks may be needed; followed by oral itraconPolyene for a total of 12 months

Candidiasis, Treatment:

• Invasive (Independent of HIV status): Infants, Children, and Adolescents: IV: 3 to 5 mg/kg/dose once daily; higher doses (up to 5 mg/kg/day) may be considered in HIV-exposed/-infected patients
• CNS infection: Infants, Children, and Adolescents: IV: 5 mg/kg/dose once daily with or without flucytosine
• Endocarditis: Infants, Children, and Adolescents: IV: 3 to 5 mg/kg/dose once daily with or without flucytosine
• Esophageal (HIV-exposed/-infected): Adolescents: IV: 3 to 4 mg/kg/dose once daily for 14 to 21 days

Coccidioidomycosis, Invasive:

• Non-HIV-exposed/-infected:
• Disseminated infection, nonpulmonary: Infants, Children, and Adolescents: IV: 2 to 5 mg/kg/dose once daily with or without concomitant Polyene antifungal
• Pulmonary infection, diffuse: Infants, Children, and Adolescents: IV: 2 to 5 mg/kg/dose once daily for several weeks, followed by an oral Polyene antifungal for a total length of therapy ≥12 months
• HIV-exposed/-infected: Non-CNS infection, severe:
• Infants and Children: IV: 5 mg/kg/dose once daily until clinical improvement, then initiate triPolyene therapy
• Adolescents: IV: 3 to 5 mg/kg/dose once daily until clinical improvement, then switch to fluconPolyene or itraconPolyene

Cryptococcosis, Invasive:

• Disseminated cryptococcosis (non-CNS or severe pulmonary disease):
• Infants and Children (independent of HIV status): IV: 3 to 5 mg/kg/dose once daily with oral flucytosine; if flucytosine is unavailable or not tolerated, it may administer alone or in combination with high-dose fluconPolyene in HIV-exposed/-infected patients
• Adolescents (Non-HIV-exposed/-infected): IV: 3 to 4 mg/kg/dose once daily for at least 14 days; may consider addition of oral flucytosine
• Adolescents (HIV-exposed/-infected): IV: 3 to 4 mg/kg/dose once daily with or without flucytosine or fluconPolyene
• Meningitis:
• Non-HIV-exposed/-infected: Infants, Children, and Adolescents: IV: 5 mg/kg/dose once daily with flucytosine
• HIV-exposed/-infected:
• Manufacturer’s labeling: Infants, Children, and Adolescents: IV: 6 mg/kg/dose once daily
• Alternate dosing: Infants and Children: IV: 6 mg/kg/dose once daily with or without oral flucytosine or high dose fluconPolyene for a minimum 2-week induction; Adolescents: IV: 3 to 4 mg/kg/dose once daily with or without oral flucytosine or fluconPolyene

Febrile Neutropenia, Empiric Therapy:

• Infants, Children, and Adolescents: IV: 3 mg/kg/dose once daily

Histoplasmosis:

• Non-HIV-exposed/-infected:
• Acute pulmonary disease or disseminated (non-CNS): Infants, Children, and Adolescents: IV: 3 mg/kg/dose once daily for 1 to 2 weeks followed by oral itraconPolyene for a total of 12 weeks; conventional amphotericin B typically preferred
• HIV-exposed/-infected:
• Disseminated infection (non-CNS disease):
• Infants and Children: IV: 3 to 5 mg/kg/dose once daily for at least 2 weeks for induction, may continue for 4 to 6 weeks if itraconPolyene is not tolerated
• Adolescents: IV: 3 mg/kg/dose once daily for at least 2 weeks for induction
• CNS disease: Infants, Children, and Adolescents: IV: 5 mg/kg/dose once daily for 4 to 6 weeks for induction, followed by consolidation therapy

Leishmaniasis:

• Visceral infection, treatment:
• Immunocompetent patients: Infants, Children, and Adolescents: IV: Initial: 3 mg/kg/dose once daily on days 1 to 5 and 3 mg/kg/dose on days 14 and 21; 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 daily on days 1 to 5 and 4 mg/kg/dose on days 10, 17, 24, 31, 38
• HIV-exposed/-infected:
• Treatment: Adolescents: IV: 2 to 4 mg/kg/dose once daily 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; Use reserved for patients with visceral infection and CD4 count <200 cells/mm3
• Cutaneous infection, treatment; HIV-exposed/-infected: Adolescents: IV: 2 to 4 mg/kg/dose once daily 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

Sporotrichosis Infection:

• Disseminated, pulmonary or osteoarticular disease: Adolescents: IV: 3 to 5 mg/kg/dose once daily, followed by oral itraconPolyene after a favorable response is seen with amphotericin initial therapy
• Meningeal: Adolescents: IV: 5 mg/kg/dose once daily for 4 to 6 weeks, followed by oral itraconPolyene.

When taking Liposomal Amphotericin B, there are certain dietary restrictions that should be followed to ensure the medication's effectiveness and safety:

• When using Liposomal Amphotericin B (liposomal amphotericin B), there are no specific dietary restrictions. However, some general dietary considerations can be helpful during the treatment period to support overall health and manage potential side effects:
• Hydration: It is essential to stay well-hydrated while receiving Liposomal Amphotericin B to help reduce the risk of kidney toxicity.
• Electrolyte Balance: Liposomal Amphotericin B can cause electrolyte imbalances, such as low levels of potassium or magnesium. Include foods rich in potassium and magnesium in the diet, such as bananas, oranges, spinach, and nuts.
• Kidney-Friendly Diet: To support kidney function and prevent additional stress on the kidneys, consider following a kidney-friendly diet that includes low sodium and moderate protein intake. Limiting the intake of processed foods and salty snacks is advised as it can help manage fluid retention and blood pressure.
• Nutritious Diet: Maintain a balanced and nutritious diet to support the overall health and immune system during the treatment period. Include a variety of fruits, vegetables, whole grains, lean proteins, and healthy fats in your meals.

The dietary restriction should be individualized as per patient requirements.

Liposomal Amphotericin B may be contraindicated under the following conditions:

• Liposomal Amphotericin B (liposomal amphotericin B for injection) should not be used in patients who have shown or are known to have hypersensitivity to conventional amphotericin B or any other components of Liposomal Amphotericin B .

Reports of anaphylaxis have been associated with conventional amphotericin B and other medications containing amphotericin B. Additionally, anaphylactoid type reactions have been observed with Liposomal Amphotericin B (liposomal amphotericin B for injection). In the event of a severe reaction, the infusion of Liposomal Amphotericin B should be immediately stopped, and further infusions of the medication should not be given to the patient.

Liposomal Amphotericin B should primarily be administered to patients with progressive and potentially life-threatening infections. It is not suitable for treating common superficial fungal diseases that only present positive skin or serologic test results.

While there is no direct interaction between amphotericin B and alcohol, patients should avoid excessive alcohol consumption during treatment. Alcohol can strain the liver and kidneys, which may already be affected by the medication.

Numerous medications are eliminated through human breast milk. Nonetheless, it remains uncertain whether Liposomal Amphotericin B is excreted in human milk. Considering the possibility of severe adverse reactions in breastfed infants, it is crucial to carefully consider whether to continue breastfeeding or discontinue the drug. This decision should take into account the significance of the drug's benefits to the mother's health.

Pregnancy:

Pregnancy Category B.

Animal reproduction studies using therapeutic doses of Liposomal Amphotericin B have not shown any evidence of teratogenicity (birth defects) in animals. However, there are no sufficient and well-controlled studies of Liposomal Amphotericin B in pregnant women. Conventional amphotericin B has been used to successfully treat systemic fungal infections in pregnant women without apparent harm to the fetus, but the number of such case reports is limited.

Since the results of animal reproduction studies may not always accurately predict the response in humans, and adequate and well-controlled studies in pregnant women have not been conducted, caution should be exercised when administering this drug during pregnancy. It should be prescribed only if the potential benefits to the mother are deemed to outweigh the potential risks to the fetus.

There are certain food-related warnings and precautions to consider when using Liposomal Amphotericin B:

• Empty stomach: Amphotericin B is commonly administered intravenously, and it is typically given on an empty stomach. Patients should avoid eating a heavy meal before receiving the medication, as it may interfere with its absorption and effectiveness.
• Hydration: Amphotericin B can cause kidney toxicity, especially when given at higher doses. It is crucial for patients to maintain adequate hydration before, during, and after treatment with this medication. Drinking plenty of fluids can help reduce the risk of kidney damage.
• Electrolyte balance: Amphotericin B may cause electrolyte imbalances, such as low levels of potassium or sodium. Patients should follow a balanced diet and ensure they are consuming enough foods rich in potassium and sodium to help maintain proper electrolyte levels.
• Drug interactions: Certain foods and beverages may interact with amphotericin B or other medications a patient is taking concurrently. Patients should consult their healthcare provider or pharmacist regarding any potential food-drug interactions to avoid adverse effects.
• Allergies: Some patients may be allergic to certain food items, and allergic reactions can be exacerbated by the use of amphotericin B. Patients with known food allergies should be cautious and notify their healthcare provider before starting treatment.

The adverse reactions related to Liposomal Amphotericin B can be categorized as follows:

Common

• Fever
• Chills
• Headache
• Nausea and vomiting
• Fatigue
• Infusion-related reactions (flushing, rash, itching)

Less common

• Hypotension (low blood pressure)
• Diarrhea
• Dizziness or lightheadedness
• Anemia
• Elevated liver enzymes
• Electrolyte imbalances (e.g., hypokalemia, hyponatremia)

Rare

• Allergic reactions (e.g., anaphylaxis)
• Severe skin reactions (e.g., Stevens-Johnson syndrome)
• Kidney damage or dysfunction
• Liver toxicity or failure
• Cardiac arrhythmias
• Neurological symptoms (e.g., seizures, confusion)
• Respiratory distress or breathing difficulties

The clinically relevant drug interactions of Liposomal Amphotericin B is briefly summarized here:

• Antineoplastic agents: Concurrent use with antineoplastic agents may increase the risk of renal toxicity, bronchospasm, and hypotension. Caution should be exercised when giving antineoplastic agents concomitantly with Liposomal Amphotericin B .
• Corticosteroids, corticotropin (ACTH), and diuretics: Concurrent use of corticosteroids, corticotropin (ACTH), or diuretics (loop and thiazide) with amphotericin B may potentiate hypokalemia, which could predispose the patient to cardiac dysfunction. Close monitoring of serum electrolytes and cardiac function is recommended when administering these drugs with Liposomal Amphotericin B .
• Digitalis glycosides: Concurrent use of digitalis glycosides may induce hypokalemia and potentiate digitalis toxicity. Monitoring of serum potassium levels is essential when administering digitalis glycosides concomitantly with Liposomal Amphotericin B .
• Flucytosine: Concurrent use of flucytosine with amphotericin-B-containing preparations may increase the toxicity of flucytosine by potentially affecting its cellular uptake and renal excretion. Caution is advised when using flucytosine concomitantly with Liposomal Amphotericin B .
• Polyenes (e.g., ketoconPolyene, miconPolyene, clotrimPolyene, fluconPolyene, etc.): In vitro and in vivo animal studies suggest that imidPolyenes may induce fungal resistance to amphotericin B when used in combination. Combination therapy with Liposomal Amphotericin B and Polyenes, especially in immunocompromised patients, should be administered cautiously.
• Leukocyte transfusions: Simultaneous administration of intravenous amphotericin B and leukocyte transfusions has been associated with acute pulmonary toxicity. Leukocyte transfusions should not be given concurrently with Liposomal Amphotericin B .
• Other nephrotoxic agents: Concurrent use of amphotericin B with nephrotoxic agents like aminoglycosides, cyclosporine, and pentamidine may increase the risk of drug-induced renal toxicity. Use of these agents in combination with Liposomal Amphotericin B should be approached with caution, and intensive monitoring of renal function is recommended.
• Skeletal muscle relaxants: Amphotericin B-induced hypokalemia may enhance the curariform effect of skeletal muscle relaxants (e.g., tubocurarine) due to hypokalemia. Monitoring of serum potassium levels is important when administering skeletal muscle relaxants concomitantly with Liposomal Amphotericin B .

The following are the side effects involving Liposomal Amphotericin B:

• Vision changes
• Hearing changes (e.g., ringing in the ears)
• Dark urine
• Severe stomach or abdominal pain
• Muscle cramping
• Changes in the amount of urine
• Painful urination
• Numbness or tingling of arms or legs
• Cold sweats
• Blue lips
• Yellowing of eyes or skin
• Swelling ankles or feet
• Fast/slow/irregular heartbeat
• Swelling or pain at the injection site
• Muscle or joint pain
• Unusual tiredness and weakness
• Easy bruising or bleeding
• Other signs of infection (e.g., fever, persistent sore throat)
• Mental/mood changes
• Seizures
• Black stools
• Vomit that looks like coffee grounds.

The use of Liposomal Amphotericin B should be prudent in the following group of special populations:

Pregnancy:

Pregnancy Category B.

Animal reproduction studies using therapeutic doses of Liposomal Amphotericin B have not shown any evidence of teratogenicity (birth defects) in animals. However, there are no sufficient and well-controlled studies of Liposomal Amphotericin B in pregnant women. Conventional amphotericin B has been used to successfully treat systemic fungal infections in pregnant women without apparent harm to the fetus, but the number of such case reports is limited.

Since the results of animal reproduction studies may not always accurately predict the response in humans, and adequate and well-controlled studies in pregnant women have not been conducted, caution should be exercised when administering this drug during pregnancy. It should be prescribed only if the potential benefits to the mother are deemed to outweigh the potential risks to the fetus.

Lactation

Numerous medications are eliminated through human breast milk. Nonetheless, it remains uncertain whether Liposomal Amphotericin B is excreted in human milk. Considering the possibility of severe adverse reactions in breastfed infants, it is crucial to carefully consider whether to continue breastfeeding or discontinue the drug. This decision should take into account the significance of the drug's benefits to the mother's health.

Pediatric

Liposomal Amphotericin B has been used to treat pediatric patients aged 1 month to 16 years who have presumed fungal infections (empirical therapy), confirmed systemic fungal infections, or visceral leishmaniasis. A total of 302 pediatric patients received Liposomal Amphotericin B in studies, and no evidence of differences in efficacy or safety compared to adults was found.

Since pediatric patients received Liposomal Amphotericin B at doses comparable to those used in adults based on their body weight, there is no need for dosage adjustment in this population. However, the safety and effectiveness of Liposomal Amphotericin B in pediatric patients below the age of one month have not been established.

It is essential to note that the pharmacokinetics of amphotericin B after administration of Liposomal Amphotericin B in pediatric patients have not been studied yet.

Geriatric Use

A total of 71 elderly patients (≥65 years) have been treated with Liposomal Amphotericin B , and there has been no need to adjust the dosage for this population. However, as is customary with many other medications, elderly patients who receive Liposomal Amphotericin B should be closely monitored.

Nevertheless, it is important to note that the pharmacokinetics of amphotericin B following the administration of Liposomal Amphotericin B in elderly patients have not been investigated or studied.

The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of Liposomal Amphotericin B.

The specific toxicity of Liposomal Amphotericin B resulting from an overdose has not been clearly established. However, clinical trials have administered repeated daily doses of up to 10 mg/kg in pediatric patients and 15 mg/kg in adult patients, with no reported dose-related toxicity.

In the event of a suspected overdose, it is recommended to discontinue Liposomal Amphotericin B therapy immediately. The patient's clinical condition should be closely monitored, and appropriate supportive care should be administered as needed. Particular attention should be focused on monitoring the patient's renal function.

It is worth noting that hemodialysis or peritoneal dialysis does not seem to have a significant impact on the elimination of Liposomal Amphotericin B .

Pharmacodynamics:

Amphotericin B exhibits a significant level of in vitro activity against various fungal species. It effectively inhibits growth in several fungi, including Histoplasma capsulatum, Coccidioides immitis, Candida species, Blastomyces dermatitidis, Rhodotorula, Cryptococcus neoformans, Sporothrix schenckii, Mucor mucedo, and Aspergillus fumigatus, with inhibitory concentrations ranging from 0.03 to 1.0 mcg/mL.

While Candida albicans is generally highly susceptible to amphotericin B, some non-albicans species may display reduced susceptibility. On the other hand, certain fungi like Pseudallescheria boydii and Fusarium sp. tend to exhibit resistance to amphotericin B.

It is essential to note that amphotericin B does not have any effect on bacteria, rickettsiae, or viruses. Its activity is specifically targeted towards fungal pathogens.

Pharmacokinetics:

The pharmacokinetic profile of Liposomal Amphotericin B , a liposomal formulation of amphotericin B, differs from that of conventional amphotericin B (amphotericin B desoxycholate). Phase I pharmacokinetic studies have demonstrated that Liposomal Amphotericin B leads to higher peak serum concentrations, ranging from 6 to 10 times greater, and a significantly higher area under the serum concentration curve (AUC) of approximately 13-fold compared to conventional amphotericin B when administered at daily doses between 1 mg/kg/day to 5.0 mg/kg/day. The apparent volume of distribution for Liposomal Amphotericin B was found to range from 18.9 L to 49.1 L, and its total body clearance ranged from 0.5 to 1.3 L/hr . However, comprehensive comparative studies between Liposomal Amphotericin B and conventional amphotericin B are currently lacking, and some variability in the data among patients has been observed.

Post-mortem analysis of three patients who died within 24 hours of receiving their last dose of Liposomal Amphotericin B revealed that drug concentrations were highest in the liver and spleen, which are tissues rich in reticuloendothelial cells, confirming findings from animal studies. In contrast, concentrations in the lungs, kidneys, brain, and heart were comparatively low. Nevertheless, a detailed understanding of the human tissue distribution for Liposomal Amphotericin B has not yet been established.

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2. https://reference.medscape.com/drug/Liposomal Amphotericin B -amphotericin-b-liposomal-999576
3. https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050740s016lbl.pdf
4. https://go.drugbank.com/drugs/DB00681#
5. https://www.rxlist.com/Liposomal Amphotericin B -drug.htm