Amphotericin B is a broad-spectrum antifungal agent widely used to treat life-threatening systemic fungal infections such as cryptococcosis, histoplasmosis, mucormycosis, and aspergillosis. It is often considered the “gold standard” antifungal for severe infections.
Despite its effectiveness, Amphotericin B is notorious for its serious toxicities, earning the nickname “Ampho-terrible” among clinicians. Adverse effects can range from infusion-related reactions (fever, chills, muscle spasms) to severe organ toxicities like nephrotoxicity and bone marrow suppression.
To simplify learning, the toxicities of Amphotericin B can be remembered with the mnemonic AMPHOTERICIN.
Mechanism of Action
- Amphotericin B binds to ergosterol in fungal cell membranes.
- This creates pores, leading to leakage of intracellular contents and fungal cell death.
- Unfortunately, it also interacts with cholesterol in human cell membranes, contributing to its toxicity profile.
Amphotericin B Toxicities – Mnemonic: AMPHOTERICIN
A – Anemia
- Caused by suppression of erythropoietin production in the kidneys.
- Patients may present with pallor, fatigue, weakness.
- Long-term therapy requires monitoring hemoglobin levels.
M – Muscle Spasms
- Infusion-related effect due to electrolyte disturbances (hypokalemia, hypomagnesemia).
- May cause cramps and generalized weakness.
- Managed by slowing infusion rate and correcting electrolytes.
P – Phlebitis
- Inflammation of veins at the infusion site.
- Causes pain, swelling, and erythema.
- Can be reduced by using central venous catheters or rotating infusion sites.
H – Headache / Hypotension
- Infusion reactions often cause headaches, dizziness, and low blood pressure.
- Severe hypotension can be dangerous, especially in critically ill patients.
T – Thrombocytopenia
- Reduction in platelet count may occur due to bone marrow suppression.
- Leads to increased bleeding risk.
- Requires regular blood count monitoring.
E – Emesis / Encephalopathy
- Nausea, vomiting, and gastrointestinal upset are common side effects.
- Rarely, neurotoxicity may manifest as confusion or encephalopathy.
R – Respiratory Stridor
- Some patients experience bronchospasm and airway narrowing during infusion.
- May require oxygen supplementation or pre-treatment with bronchodilators.
I – Increased Temperature (Fever)
- High fever is a hallmark of infusion-related reaction.
- Typically occurs within 1–3 hours of administration.
- Pre-medication with antipyretics or steroids can reduce severity.
C – Chills
- Severe rigors and shaking are classic signs of amphotericin infusion reactions.
- Usually managed with meperidine (pethidine) during infusion.
I – Immediate Anaphylaxis
- Rare but life-threatening allergic reaction.
- Symptoms: rash, swelling, hypotension, difficulty breathing.
- Requires immediate discontinuation and emergency management.
N – Nephrotoxicity
- The most serious and dose-limiting toxicity of Amphotericin B.
- Mechanism: direct damage to renal tubular cells → electrolyte wasting (K⁺, Mg²⁺) → renal failure.
- Clinical signs: elevated serum creatinine, reduced urine output, electrolyte imbalances.
- Risk increases with cumulative dose.
- Liposomal formulations of Amphotericin B significantly reduce nephrotoxicity.
Clinical Features of Amphotericin B Toxicities
| Toxicity | Clinical Manifestations | Notes |
|---|---|---|
| Anemia | Fatigue, pallor, weakness | Due to reduced erythropoietin |
| Muscle spasms | Cramps, twitching | Linked to hypokalemia, hypomagnesemia |
| Phlebitis | Pain, swelling at infusion site | Reduced with central lines |
| Headache/Hypotension | Dizziness, low BP during infusion | Infusion-related |
| Thrombocytopenia | Easy bruising, bleeding | Rare but serious |
| Emesis/Encephalopathy | Nausea, vomiting, confusion | GI and CNS side effects |
| Respiratory Stridor | Difficulty breathing, wheezing | Infusion reaction |
| Increased Temperature | Fever within hours of infusion | Common reaction |
| Chills | Severe rigors | Managed with meperidine |
| Immediate Anaphylaxis | Rash, hypotension, airway obstruction | Rare, emergency |
| Nephrotoxicity | Increased creatinine, electrolyte imbalance | Dose-limiting toxicity |
Management of Amphotericin B Toxicities
1. Infusion-related reactions
- Pre-medicate with antihistamines, acetaminophen, corticosteroids.
- Administer slowly over several hours.
- Meperidine for rigors and chills.
2. Nephrotoxicity
- Ensure adequate hydration before infusion.
- Monitor renal function (serum creatinine, electrolytes).
- Prefer liposomal Amphotericin B formulations.
3. Hematologic toxicity
- Monitor hemoglobin and platelet counts regularly.
- Provide transfusions or erythropoietin if required.
4. Electrolyte disturbances
- Replace potassium and magnesium as needed.
Safer Alternatives and Formulations
- Liposomal Amphotericin B and Amphotericin B lipid complex are designed to reduce renal toxicity and infusion reactions.
- However, they are more expensive and usually reserved for patients at higher risk of toxicity.
Frequently Asked Questions (FAQ)
Q1. Why is Amphotericin B called “Ampho-terrible”?
Because of its high rate of severe toxicities, especially nephrotoxicity and infusion-related reactions.
Q2. Which toxicity of Amphotericin B is most dangerous?
Nephrotoxicity is the most serious and dose-limiting side effect.
Q3. How can infusion-related chills and fever be prevented?
By premedicating with acetaminophen, antihistamines, and administering meperidine during infusion.
Q4. Are liposomal formulations safer than conventional Amphotericin B?
Yes, liposomal formulations are significantly safer for kidneys and cause fewer infusion-related reactions.
Q5. Is Amphotericin B safe in pregnancy?
Yes, it is considered the drug of choice for systemic fungal infections in pregnancy, despite its toxicities, because alternatives are more harmful to the fetus.
