amphotericin B phospholipid complex

Action and Spectrum

Actions and spectrum: 

amphotericin B phospholipid complex is a lipid-based formulation of amphotericin B, an antifungal drug. It is used for the treatment of invasive fungal infections, particularly those caused by Aspergillus and Candida species. 

amphotericin B phospholipid complex works by binding to ergosterol, a component of fungal cell membranes, which leads to the formation of pores and, ultimately, cell death.

The complex phospholipid formulation is used because it can decrease the toxicity of the drug, particularly renal toxicity, which can be a major side effect of amphotericin B. 

The spectrum of activity of the amphotericin B phospholipid complex is broad and includes many fungi that are resistant to other antifungal agents. However, it is primarily used as a second-line therapy due to its high cost and potential for adverse effects. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Increased serum creatinine (11%) 

Multiple organ failure (11%) 

Fever (14%) 

Chills (18%)  

1-10% 

Nausea (3%) 

Chest Pain (3%) 

Abdominal Pain (4%) 

Bilirubinemia (4%) 

Leukopenia (4%) 

Respiratory Disorder (4%) 

Anemia (4%) 

Gastrointestinal Hemorrhage (4%) 

Rash (4%) 

Hypertension (5%) 

Infection (5%) 

Pain (5%) 

Hypokalemia (5%) 

Kidney Failure (5%) 

Thrombocytopenia (5%)
Diarrhea (6%) 

Heart Arrest (6%) 

Headache (6%) 

Sepsis (7%) 

Dyspnea (7%) 

Hypotension (8%) 

Vomiting (8%) 

Respiratory Failure (8%) 

Nausea (9%) 

Black Box Warning

Black Box Warning: 

The black box warning for amphotericin B is related to its potential for causing severe and potentially fatal infusion-related reactions, such as fever, chills, rigors, hypotension, and cardiac arrest.

The risk of these reactions can be reduced by pre-treatment with antipyretics, antihistamines, and/or corticosteroids, as well as by slowing the infusion rate. amphotericin B is also associated with a risk of nephrotoxicity and electrolyte imbalances, particularly hypokalemia and hypomagnesemia, which can be minimized by careful monitoring of renal function and electrolyte levels. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

amphotericin B phospholipid complex is contraindicated in patients with a known hypersensitivity to amphotericin B or any component of the formulation. It is also contraindicated in patients with severe renal impairment or in those who are anuric.  

Caution: 

• Renal impairment: amphotericin B phospholipid complex can cause kidney damage and worsen pre-existing kidney problems. Therefore, it should be used under caution in patients with renal impairment. 
• Electrolyte imbalances: amphotericin B phospholipid complex can cause electrolyte imbalances, such as hypokalemia and hypomagnesemia. Close monitoring of electrolyte levels is required during treatment. 
• Cardiac function: amphotericin B phospholipid complex can cause changes in heart function, such as arrhythmias and changes in blood pressure. Patients with pre-existing cardiac conditions should be closely monitored during treatment. 
• Liver function: amphotericin B phospholipid complex can cause liver damage in rare cases. Liver function should be monitored during treatment. 
• Pregnancy and lactation: amphotericin B phospholipid complex is not recommended during pregnancy and lactation due to limited safety data. However, the medication may be used if the potential benefits outweigh the risks. 
• Immunosuppression: amphotericin B phospholipid complex can cause suppression of the immune system. Therefore, caution is advised when using the medication in patients with immunosuppression, as it may increase the risk of infection. 
• Intravenous administration: amphotericin B phospholipid complex is administered intravenously, and caution should be taken to ensure proper administration technique to minimize the risk of infusion reactions and infection at the site of administration.

Comorbidities: 

amphotericin B phospholipid complex is indicated for the treatment of serious fungal infections. It is reserved for patients who are intolerant to or refractory to other antifungal agents due to their significant side effects. As such, comorbidities that may increase the risk of adverse reactions to the medication should be taken into consideration.

Patients with pre-existing renal impairment or electrolyte abnormalities may be at higher risk for nephrotoxicity associated with amphotericin B therapy. Patients with cardiac disease or a history of cardiac disease may be at higher risk for infusion-related reactions, including hypotension and dyspnea.

Patients with liver disease or impairment may require dose adjustments due to the hepatotoxicity associated with amphotericin B therapy. Additionally, patients with anemia or leukopenia may require close monitoring of their blood counts during therapy with amphotericin B. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: Not assigned 

Lactation: It is not known whether the amphotericin B is excreted in human milk  

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women. 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

amphotericin B phospholipid complex is a polyene macrolide antibiotic that binds to the fungal cell membrane and causes cell death. It has a very broad spectrum of activity against fungal pathogens, including Candida and Aspergillus species, Cryptococcus neoformans, and Histoplasma capsulatum. 

amphotericin B works by binding to ergosterol, which is present in fungal cell membranes but not in mammalian cell membranes. This binding disrupts the membrane, leading to the leakage of intracellular components and cell death. 

The complex phospholipid formulation of amphotericin B is a liposomal delivery system that reduces the toxicity associated with the traditional formulation of the drug. The liposomal structure allows for targeted delivery of the drug to the site of infection, reducing the amount of drug that reaches healthy tissues and organs. 

Pharmacodynamics: 

The complex phospholipid formulation of amphotericin B is a liposomal preparation that consists of small unilamellar vesicles composed of phosphatidylcholine and cholesterol. The liposomes serve as a carrier for amphotericin B, allowing for improved drug delivery and reduced toxicity compared to the conventional formulation. 

The pharmacodynamics of amphotericin B phospholipid complex include the dose-dependent killing of fungal cells, with fungicidal activity observed at higher doses. The drug also exhibits a prolonged post-antifungal effect, which means that it continues to inhibit fungal growth even after the drug has been eliminated from the body.  

Pharmacokinetics: 

Absorption 

It is not absorbed orally and must be given intravenously. 

Distribution 

amphotericin B phospholipid complex is distributed to many organs and tissues, including the liver, spleen, kidneys, and lungs. It does not penetrate the blood-brain barrier. 

Metabolism 

It is not metabolized by the liver. 

Elimination and excretion 

The drug is eliminated through the kidneys, primarily in unchanged form, with a half-life of about 15 days. 

Adminstartion

Administration: 

amphotericin B phospholipid complex is administered via intravenous infusion. The infusion is typically given over several hours, and the duration of treatment depends on the severity of the infection being treated.

The dose of the medication is also determined based on the patient’s weight, kidney function, and the specific condition being treated. The medication should be administered under the supervision of a healthcare professional with experience in the use of antifungal agents. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: amphotericin B phospholipid complex 

Pronounced: [ AM-foe-TER-i-sin-B-LIP-id-KOM-plex]  

Why do we use amphotericin B phospholipid complex? 

amphotericin B phospholipid complex is primarily used for the treatment of systemic fungal infections, including aspergillosis, candidiasis, cryptococcosis, histoplasmosis, blastomycosis, and coccidioidomycosis. It may also be used for other serious fungal infections that do not respond to other treatments.

amphotericin B phospholipid complex is typically reserved for patients who cannot tolerate or are unresponsive to other antifungal agents. It is also used in combination with the other drugs for more severe infections or in immunocompromised patients.