Usage
Liposomal Amphotericin B is prescribed for the treatment of severe systemic fungal infections, including aspergillosis, candidiasis, cryptococcosis, and mucormycosis. It’s also used for visceral leishmaniasis (kala-azar) and as empirical therapy in febrile neutropenia where a fungal infection is suspected. Its pharmacological classification is antifungal and antiprotozoal.
The mechanism of action involves binding to ergosterol, a key component of fungal cell membranes. This binding disrupts membrane integrity, leading to cell death.
Alternate Names
The most common alternate name is “L-AmB.” A popular brand name under which it is marketed is AmBisome.
How It Works
Pharmacodynamics: Liposomal Amphotericin B targets ergosterol in fungal cell membranes. This leads to increased membrane permeability, ion leakage, and ultimately fungal cell death. It also exhibits some activity against certain protozoa, such as Leishmania.
Pharmacokinetics: The drug is administered intravenously. The liposomal formulation alters the distribution and elimination compared to conventional amphotericin B. It exhibits non-linear pharmacokinetics. It’s taken up by the mononuclear phagocyte system (MPS), particularly in the liver and spleen, resulting in higher concentrations in these organs. Elimination is primarily through biliary excretion, with a small amount excreted renally. Metabolism is minimal.
Mode of Action: The primary mode of action is through binding to ergosterol in fungal cell membranes.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Liposomal Amphotericin B’s primary effect is membrane disruption via ergosterol binding. It does not significantly interact with receptors, enzymes, or neurotransmitters in the way that some other drugs do.
Elimination Pathways: Primarily eliminated through biliary excretion, with a small amount excreted renally.
Dosage
Standard Dosage
Adults: 3-5 mg/kg/day IV infused over 30-60 minutes. For mucormycosis, 5-10 mg/kg/day is recommended, potentially up to 15mg/kg/day as tolerated. For empirical therapy in febrile neutropenia, 3 mg/kg/day is typical.
Children (over 1 month): Similar to adult dosing (mg/kg basis). Safety and efficacy in children younger than one month have not been established.
Special Cases:
- Elderly Patients: No specific dose adjustments, but close monitoring is recommended.
- Patients with Renal Impairment: No dose adjustment is typically required.
- Patients with Hepatic Dysfunction: No dose adjustment is typically required.
- Patients with Comorbid Conditions: Consider individual patient factors and monitor closely.
Clinical Use Cases
Dosing in specific clinical settings generally follows the standard recommendations outlined above. Individualized dosing may be necessary depending on the specific infection and patient factors. Consult infectious diseases specialists for guidance.
Dosage Adjustments: Dose adjustments might be considered based on patient response, adverse effects, and clinical condition.
Side Effects
Rare but Serious Side Effects: Anaphylaxis, acute respiratory distress syndrome, nephrotoxicity (especially at higher doses), hepatotoxicity, and cardiac arrhythmias.
Long-Term Effects: Renal impairment can occur with prolonged use, especially at higher doses.
Contraindications
- Known hypersensitivity to amphotericin B or any component of the formulation.
Drug Interactions
Liposomal Amphotericin B can interact with other nephrotoxic drugs (e.g., aminoglycosides, cyclosporine), drugs that can cause hypokalemia (e.g., loop diuretics, corticosteroids), and some antineoplastic agents. Interactions with other antifungals (e.g., azoles) should be monitored closely.
Pregnancy and Breastfeeding
Although considered relatively safe during pregnancy (category B), data is limited. Use only if benefits clearly outweigh risks. It’s unknown if the drug is excreted in breast milk. Use with caution during breastfeeding and consider potential risks to the neonate.
Drug Profile Summary
- Mechanism of Action: Binds to ergosterol in fungal cell membranes, causing cell death.
- Side Effects: Infusion reactions, nephrotoxicity, electrolyte abnormalities.
- Contraindications: Hypersensitivity to amphotericin B.
- Drug Interactions: Nephrotoxic drugs, hypokalemia-inducing drugs.
- Pregnancy & Breastfeeding: Use with caution if benefits outweigh risks.
- Dosage: 3-5 mg/kg/day IV; higher doses in certain cases.
- Monitoring Parameters: Renal function, electrolytes (potassium, magnesium), liver function tests, complete blood count, and signs of infusion reactions.
Popular Combinations
Often used as monotherapy. Combination therapy may be considered in certain cases, like cryptococcal meningitis (with flucytosine and fluconazole).
Precautions
Careful monitoring of renal function and electrolyte levels is crucial. Premedication with antipyretics, antihistamines, and/or corticosteroids may be used to reduce infusion-related reactions.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Liposomal Amphotericin B?
A: The usual dosage is 3-5 mg/kg/day IV. Higher doses (5-10 mg/kg/day, even up to 15 mg/kg/day as tolerated) may be used for mucormycosis.
Q2: How is Liposomal Amphotericin B administered?
A: It is administered intravenously, usually over 30-60 minutes.
Q3: What are the common side effects of Liposomal Amphotericin B?
A: Common side effects include fever, chills, rigors, nausea, vomiting, headache, hypotension, and electrolyte abnormalities.
Q4: What are the serious side effects of Liposomal Amphotericin B?
A: Serious side effects include anaphylaxis, nephrotoxicity, hepatotoxicity, and cardiac arrhythmias.
Q5: What are the contraindications for Liposomal Amphotericin B?
A: The main contraindication is known hypersensitivity to amphotericin B.
Q6: Can Liposomal Amphotericin B be used in pregnant or breastfeeding women?
A: It can be used with caution if the benefits outweigh the risks. Consult with specialists for careful risk-benefit assessment.
A: The liposomal formulation reduces toxicity, particularly nephrotoxicity, and allows for higher doses. It also alters the pharmacokinetics, leading to different distribution and elimination profiles.
Q8: What monitoring is required during Liposomal Amphotericin B therapy?
A: Close monitoring of renal function, electrolytes, and signs of infusion reactions is essential.
Q9: What are the key drug interactions to be aware of with Liposomal Amphotericin B?
A: Interactions with other nephrotoxic drugs and drugs that can cause hypokalemia are important considerations.
This information is current as of February 16, 2025, and is intended for use by qualified medical professionals. Always consult the latest medical references and guidelines for the most up-to-date information.
