Amphotericin B: Everything You Need To Know!
Amphotericin B (AmB) is a polyene macrolide antifungal agent discovered in 1955 from the Streptomyces nodosus bacterium.
This potent compound features a hydrophilic polyhydroxyl chain and a lipophilic polyene hydrocarbon chain, which creates its “amphoteric” properties—enabling solubility in both acidic and alkaline conditions.
The deoxycholate complex (D-AmB) formulation enables intravenous administration but carries significant toxicity risks.
In pharmaceutical contexts, raw Amphotericin B appears as a yellow-orange crystalline powder that degrades in light, requiring strict storage in a light-protected environment.
Its stability challenges spurred innovations, such as lipid-based nanoformulations, that revolutionized therapeutic applications.
What Is Amphotericin B?
Amphotericin B API is a yellow-to-orange powder used as an antifungal agent.
It is a polyene antifungal antibiotic produced by Streptomyces nodosus.
It is insoluble in water but readily soluble in lipids and is one of our competitive pharmaceutical ingredients, certified to China GMP standards.
Amphotericin can bind to ergosterol, depolarizing the membrane and altering cell membrane permeability.
This allows important intracellular components to leak from cells and causes bacterial cell death.
Is Amphotericin B an Antibiotic or Antifungal?
Amphotericin B is exclusively an antifungal—not an antibacterial antibiotic.
Misconceptions arise because:
Historical context: Early literature classified all antimicrobials as “antibiotics.”
Manufacturing similarity: Produced via Streptomyces fermentation (like aminoglycosides)
Key distinctions:
No activity against bacteria (except Gram-positive rods at unattainable doses)
Targets ergosterol (absent in bacteria)
Classified as an antimycotic in the WHO ATC code J02AA01
What Drug Class Is Amphotericin B?
Amphotericin B is the prototype polyene antifungal, characterized by:
Chemical structure: Macrocyclic ring with conjugated double bonds (4–7 heptaene units)
Mechanistic class: Membrane-disrupting fungicidal agents
Therapeutic peers: Nystatin (topical only), Natamycin (ophthalmic)
Resistance mechanisms:
Ergosterol biosynthesis mutations (ERG gene upregulation)
Biofilm-mediated tolerance
Reduced membrane fluidity (↓drug binding)
What Is Amphotericin B Used For?
Amphotericin B is a broad-spectrum antifungal antibiotic effective against many fungal species.
People can take it in various forms, such as injections and capsules, but it also has other uses.
Below, we have compiled its main usages; take a look:
#1. Clinical treatment of fungal infections
Clinically, we use amphotericin B to treat severe infections caused by deep-seated fungi, either in the visceral or systemic systems.
Amphotericin B is reserved for serious fungal infections, including:
Invasive Candida infections (e.g., Candida bloodstream infections).
Aspergillosis (lung infections caused by Aspergillus species).
Cryptococcal meningitis (a deadly brain infection in immunocompromised patients).
Mucormycosis (aggressive infections by molds like Rhizopus).
Leishmaniasis (a parasitic disease, off-label use).
It’s often initiated when other antifungals fail or when rapid action is required.
#2. Fungal detections
Externally, it is used for:
Coloring fungal diseases, post-burn skin fungal infections, respiratory Candida, Aspergillus, or Cryptococcus infections, and fungal corneal ulcers.
Due to the apparent toxicity, doctors would need it for the diagnosis of established deep fungal infections (also known as culture or positive histological tests) in patients with critically progressive diseases.
#3. Cell cultivation in the lab
Lab scientists use it to prevent contamination by yeast and multicellular fungi in cell culture.
It alters the permeability of the fungal plasma membrane, preventing the fungus from growing there.
Caution: This is only permitted in patients with no obvious clinical signs of fungal infection, but only in those with positive skin or serum tests.
Amphotericin B Emerging Applications
Fluorescent-Guided Therapy
CY5-Amphotericin B: Novel conjugate enables real-time drug tracking via NIR imaging
Fungal-specific signal enhancement: 3.2× in ergosterol-rich zones
Applications: Surgical debridement guidance; resistance detection (membrane fluidity ↓37% in resistant strains)
Biofilm Penetration Enhancers
Pom-1 peptides: Disrupt fungal biofilms, reducing AmB MIC by 50–80%
Mechanism: Inhibits cell aggregation without membrane poration
Synergy: Restores susceptibility in 96% of resistant isolates
Photodynamic Potentiation
Blue light activation: 405nm exposure triggers ROS generation (type I/II reactions)
Efficacy boost: 4.7× higher fungal kill rates in skin models
Toxicity mitigation: Allows a 40% dose reduction
ICU Protocol Integration
L-AmB first-line: Recommended for immunocompromised ICU patients with undifferentiated fungal sepsis
Dosing: 3–5mg/kg/day without a loading dose
Advantage: No CYP450 interactions vs. azoles
How Amphotericin B Works (Mechanism of Action)
AmB’s fungicidal action involves ergosterol-targeted membrane disruption:
Selective binding: AmB’s lactone ring binds ergosterol in fungal membranes (100x affinity over mammalian cholesterol)
Pore formation: Membrane-embedded AmB aggregates create ion-permeable channels (0.4–1 nm diameter), causing potassium/proton leakage
Oxidative cascade: Secondary ROS generation induces fungal apoptosis
Sterol sponge model: Recent SSNMR studies reveal AmB extracts ergosterol into extramembranous aggregates (“sponges”), irreversibly damaging membrane integrity
Table: Amphotericin B Selectivity Mechanisms
| Factor | Fungal Cells | Human Cells |
|---|---|---|
| Primary Sterol | Ergosterol | Cholesterol |
| Binding Affinity | High (Kd=10⁻⁸ M) | Low (Kd=10⁻⁶ M) |
| Membrane Damage | Lethal pores | Transient channels |
What Are Amphotericin B Side Effects?
Nephrotoxicity
Incidence: 26–34% in D-AmB recipients; 7–20% with L-AmB
Mechanisms: Renal afferent vasoconstriction + direct tubular damage → ↓GFR
Risk factors: Baseline Cr>1.2 mg/dL, daily dose >0.7mg/kg, concurrent nephrotoxins
Infusion Reactions
Frequency: 25–53% acute reactions (fever, chills, hypertension)
Prevention: Premedication with acetaminophen + diphenhydramine; slow infusion (≤1mg/kg/hr)
Other Toxicities
Hepatotoxicity: 12–19% transaminitis (usually reversible) 7
Anemia: Normocytic anemia due to suppressed erythropoietin production
Thrombophlebitis: Dilution to <0.1mg/mL + central line administration reduces risk
Drug Interactions with Amphotericin B
Nephrotoxic agents: Aminoglycosides, cyclosporine (increased kidney damage).
Corticosteroids exacerbate hypokalemia.
Flucytosine: Synergistic antifungal effect but may increase toxicity.
Does Amphotericin B Cause Hypokalemia?
Yes—hypokalemia affects 17–43% of Amphotericin B recipients and can precede azotemia.
Mechanisms include:
Distal tubular damage: AmB binds renal collecting duct epithelia → ↑potassium secretion via maxi-K channels
Magnesium wasting: Hypomagnesemia impairs Na⁺/K⁺-ATPase → potassium shifts
Renin-angiotensin activation: Secondary to renal vasoconstriction
Management Strategies
Prophylaxis: Pre-hydration with NaCl 0.9% (500mL pre/post-infusion)
Potassium protocol: Oral KCl (40–80 mEq/day) + IV supplementation if K < 3.0 mmol/L
Potassium-sparing diuretics: Amiloride (5–10mg/day) blocks AmB-induced potassium secretion
Clinical Pearl: Serum magnesium should always be corrected simultaneously—hypomagnesemia exacerbates renal potassium wasting
Can Amphotericin B Be Given Orally?
Oral Amphotericin B is limited to intestinal fungal infections due to negligible systemic absorption (<5% bioavailability) 24:
GI candida: 0.5–2 g/day divided doses (suspension or tablets)
Selective decontamination: 500mg/day in neutropenic patients
Advantages: No renal toxicity; minimal drug interactions
Disadvantages: Nausea/vomiting in 30% at high doses
Table: Amphotericin B Formulations for Non-Parenteral Use
| Form | Concentration | Indications | Notes |
|---|---|---|---|
| Oral suspension | 100 mg/mL | Oropharyngeal candidiasis | Avoid food ×1 hr post-dose |
| Rectal suppository | 25 mg | Intestinal candidiasis | Compounded only |
| Topical cream | 3% | Cutaneous fungal infections | Apply BID × 2–4 weeks |
| Ophthalmic drops | 0.25% | Fungal keratitis | Refrigerate; discard after 7d |
Amphotericin B Dosage and Administration
Deoxycholate Amphotericin B (D-AmB)
Test dose: 1 mg in 20mL D5W over 30 minutes
Escalation schedule: Start at 0.25 mg/kg/day → increase by 0.25 mg/kg/day to target 0.5–1 mg/kg/day
Max cumulative dose: 3–4 g (lifetime)
Liposomal Amphotericin B (L-AmB)
Standard dosing: 3–5 mg/kg/day IV for invasive mycoses
Rapid escalation: No test dose needed; start at full dose
Special populations: Elderly patients achieve efficacy at 0.7–0.8 mg/kg/day with lower toxicity
Key Administration Rules
Reconstitution: Use sterile water (NOT saline) to avoid precipitation
Diluent: D5W (pH>4.2); final concentration ≤0.1 mg/mL
Infusion rate: 2–6 hours; slower if reactions occur
Incompatibilities: Never mix with electrolytes or other drugs
What to Monitor After Amphotericin B Administration?
Renal function:
Serum creatinine/BUN: Baseline, then 3x/week
eGFR decline >25% warrants dose reduction
Electrolytes:
Potassium/magnesium: Daily during induction; replace if K⁺<4.0 mmol/L
CO₂/bicarbonate: Monitor for renal tubular acidosis
Hematology:
CBC: Weekly (watch hemoglobin decline)
LDH/haptoglobin if hemolysis is suspected
Therapeutic drug monitoring:
Not routinely available
Trough levels >2 μg/mL correlate with nephrotoxicity
Amphotericin B: Oral/Topical Grade vs. Injection Grade vs. Liposomal Grade
Chemical Purity Specifications
| Parameter | Oral/Topical | Injection-grade (IV) | Liposomal (IV) |
|---|---|---|---|
| Purity | around 90% | >95% | >98% |
| Endotoxins | <10 EU/mg | <5 EU/mg | <1 EU/mg |
| Sterility | Not required | Sterile (terminal γ-irradiation) | Sterile (aseptic filtration) |
| Particle size | N/A | <10 µm aggregates | 60–80 nm liposomes |
Manufacturing Notes
Liposomal encapsulation: Requires HSPC/cholesterol/DSPG lipids (7:2:1 ratio)
Lyophilization: Critical for D-AmB stability; causes <3% potency loss
API sourcing: Natural fermentation (not synthetic); batch-to-batch variability affects nephrotoxicity
What Are the Side Effects of Amphotericin B?
Nephrotoxicity
Incidence: 26–34% in D-AmB recipients; 7–20% with L-AmB
Mechanisms: Renal afferent vasoconstriction + direct tubular damage → ↓GFR
Risk factors: Baseline Cr>1.2 mg/dL, daily dose >0.7mg/kg, concurrent nephrotoxins
Infusion Reactions
Frequency: 25–53% acute reactions (fever, chills, hypertension)
Prevention: Premedication with acetaminophen + diphenhydramine; slow infusion (≤1mg/kg/hr)
Other Toxicities
Hepatotoxicity: 12–19% transaminitis (usually reversible)
Anemia: Normocytic anemia due to suppressed erythropoietin
Thrombophlebitis: Dilution to <0.1mg/mL + central line administration reduces risk
Why Is Liposomal Amphotericin B Less Toxic?
Liposomal technology transforms AmB’s therapeutic index through:
Selective delivery: Liposomes accumulate in fungal cell walls/inflamed tissues via enhanced permeability
Reduced renal exposure: Liposome size >6 nm prevents glomerular filtration → ↓tubular binding
Cholesterol shielding: Liposomal cholesterol competes with human membrane cholesterol → ↓cytotoxicity
Clinical Evidence
Renal protection: L-AmB causes 62% less tubular accumulation vs. D-AmB
Elderly safety: Creatinine elevation in 7% vs. 35% with D-AmB
Dosing advantage: Permits 3–5× higher daily doses (critical for mucormycosis)
How To Ship and Store Amphotericin B API?
Amphotericin B is highly sensitive to light; therefore, avoid direct sunlight during transportation and storage.
Transport Conditions: It is a safe and common chemical. Not dangerous.
According to the testing results from DGM, it reads as follows:
According to IATA DGR Special Provision A3, it is classified as “Not Restricted, as per Special Provision A3”.
You should ship it at low temperatures to preserve its antibiotic activity.
First, there are two grades and three types of amphotericin B powder in different dosage forms. Shipping temperatures and storage conditions differ slightly.
For Oral Grade
For the conventional type, we can ship it at room temperature but store it at 2~8 Degrees Celsius.
Please keep it sealed and protected from light and moisture during your storage.
If you want to weigh some during storage, ensure the sample doesn’t absorb moisture.
As we all know, a low-temperature chemical will draw moisture into the air. To avoid it:
1) You can naturally weigh the sample after the package returns to room temperature.
2) Weigh it under a moisture-free fume hood if it is weighed at 2~8 degrees.
This powder type is suitable for manufacturing oral dosages and topical formulations, such as tablets, capsules, creams, emulsions, gels, ear drops, ointments, or some veterinary formulations.
For Injection Grade (Liposomal type and non-liposomal type)
You must take extra precautions when shipping and storing injection-grade products, especially those of the liposomal grade.
You can not ship it at room temperature like conventional grade; you must transport it using cold-chain shipping methods.
Estimate how many days it will take to deliver it, and add enough ice bags to keep it at the same temperature we store it at, 2~8 Degrees Celsius.
Of the three grades, the liposomal type is the most expensive and has the highest potency.
We have to refine it by recrystallization at least twice to get it.
We want to share all our knowledge with you. If you have differing opinions, please feel free to message or comment below.
Any feedback you have will be greatly appreciated.
How Much Does Amphotericin B API Cost?
As one of China’s leading suppliers of amphotericin B, we receive price inquiries from Customers daily.
However, we cannot obtain all the necessary information to send our quotation using the simple contact form we received. We will need to ask several basic questions to provide the quotation; sometimes, the email may need to be exchanged several times.
The standard reply from us is like this:
- What grade do you need?
- How much do you need it?
- Please let us know what you plan to do with it so we can recommend the right grades.
We feel it is too much trouble to explain the grades we assign to each inquiry, so we decided to provide a clear explanation of the grades and the relevant price ideas for each grade, allowing our customers to determine which grade they need.
So, there are three types of bulk Amphotericin B API powder in total in the market:
1. Oral/topical grade
2. Injection grade (Typical Type)
3. Liposomal injection grade.
All three of those grades are intended for different purposes.
#1. Topical Grade
The topical grade is the cheapest type but has the lowest HPLC purity (around 80%).
We use crude Amphotericin B as a raw material to produce injection-grade powder.
For topical grade powder with Commercial order quantities, our price is about 1600~1800 USD/kg as CNF by air.
If you only have an order of 1kg, our price is about 2100~2300, depending on the shipping cost by FedEx to the destination countries.
The updated stock status as of May 2023 for the topical grade is out of stock.
#2. Injection Grade
The regular injection-grade amphotericin B API powder is purer than the topical-grade.
The purity of injection-grade Amphotericin B API is greater than 90% as determined by HPLC.
We use this grade to produce amphotericin B injections or injection powders.
For commercial quantities of the ordinary injection-grade API powder, the cost is approximately $13,500-$14,500 per kilogram.
If you plan to place a trial order of 1 kilogram, our suggested price is USD 15,500.
#3. Liposomal Grade
This type is the most expensive because it has the highest purity and the most complicated manufacturing process.
The injection-grade powder is further processed with liposomal carriers to lower its toxicity to specific organs.
Our price for orders over 10 kg is approximately $20,000 per kg.
For small quantities, the USD 25,000can exceed USD 25,000/kg.
Since 2010, its price has risen due to sluggish demand, rising labor costs, and environmental protection concerns.
Here, we draw a price curve below; check it out:
You can also check its export prices before 2016 from China to India as follows.
There, you can see the main-stream cost is around 7400 USD per Kilo.
More importantly, after COVID-19 broke out, researchers found that amphotericin B was effective against specific aftereffects, and it sold out for several months.
We currently have injection-grade and several kilos of liposomal-grade material in stock for sale (excluding topical types). Contact us now to place a quick order before it sells out again.
For other order quantities and more up-to-date prices, please get in touch with us directly.
Is Amphotericin B Safe During Pregnancy?
Category B status applies only to life-threatening maternal infections:
Placental transfer: Limited human data; fetal concentrations ≈25% of maternal levels
Risk-benefit profile:
Preferred over azoles for systemic mycoses (lower teratogenic risk)
Avoid during the first trimester unless lifesaving
Lactation considerations:
Oral absorption is negligible → safe for breastfeeding infants
IV administration: Suspend breastfeeding during treatment
How Long Does Amphotericin B Take to Work?
Clinical response timelines vary by infection type:
Cryptococcal meningitis: CSF sterilization in 10–14 days (culture conversion)
Invasive aspergillosis: Fever resolution in 5–7 days; radiographic improvement by 2 weeks
Mucormycosis: Surgical debridement + L-AmB shows clinical improvement in 72 hours 5
Delayed responses: Biofilm-associated infections may require 4–6 weeks
Critical Note: Fungal meningitis treatment requires ≥6 weeks consolidation therapy after CSF clearance.
Strategic Insights for API Importers and Manufacturers
Liposomal dominance: Global L-AmB market growing at 8.2% CAGR (2024–2030)—prioritize GMP-grade phospholipids
Compounding opportunities:
Stability extension: L-AmB retains >90% potency for 96 h at 4°C (vs.24 hh for D-AmB)
Custom formulations: Ophthalmic gels (0.15% AmB-HPMC); bladder irrigation solutions
Quality control focus:
Aggregate monitoring: D-AmB aggregates >1µm correlate with nephrotoxicity
Residual solvents: Limit methanol <3000 ppm (ICH Q3C)
Global Sourcing Tips for Amphotericin B API
Quality verification:
Demand HPLC-UV chromatograms showing amphotericin A content <5%
Reject batches with aggregate particles >1µm (linked to nephrotoxicity)
Regional regulations:
US FDA: Requires DMF Type II registration
EU: Must comply with Ph. Eur. Monograph 01/2008:0990
Supply chain security:
Dual-sourcing from geographically separated manufacturers
Minimum 6-month inventory for fermentation-based APIs
Cost-saving strategies:
Bulk purchases> 50 kg: 12–18% price reduction
Consider semi-finished lyophilized products for liposomal manufacturing
Cost-Effective Bulk Purchasing Strategies for Amphotericin B API Importers
Fermentation yield optimization:
High-yield S. nodosus strains: ≥4.2g/L reduces costs by 30%
Monitor glucose feed rates: Maintain <5g/L to prevent acetate accumulation
Tariff engineering:
Classify as “antibiotic derivatives” (HS 2941.90) instead of “medicaments” (HS 3004.20)
Utilize the ASEAN-India FTA for an 8% duty reduction
Warehousing innovations:
Climate-controlled storage: 15–20°C with <30% RH
Nitrogen-flushed containers for oxidation-sensitive batches
Contract manufacturing:
Toll manufacturing in WHO-GMP facilities reduces capital expenditure
Minimum order: 25kg for non-liposomal; 5kg for liposomal-grade
Compounding Pharmacy Guidelines for Amphotericin B Formulations
Stability and Compatibility
| Formulation | Vehicle | Stability | Storage |
|---|---|---|---|
| Ophthalmic drops | 1% HPMC solution | 14 days | 2–8°C protected from light |
| Bladder irrigation | Sterile water | 24 hours | Room temperature |
| Nebulized solution | 0.9% NaCl | 12 hours | Refrigerated |
| Intralesional gel | 2% methylcellulose | 7 days | 2–8°C |
Best Practices
Preservative-free: Avoid benzalkonium chloride (causes precipitation)
Filtration: Sterilize with 0.22µm PVDF filters
In-use testing: Validate potency retention at 24/48/72 hours (HPLC recommended)
Innovative delivery: Intralesional injections (5–10 mg/mL) demonstrated 100% lesion resolution in mucormycosis.
Conclusion: The Evolving Amphotericin B Landscape
Amphotericin B remains the irreplaceable cornerstone of antifungals, nearly 70 years after its discovery.
For API suppliers, investing in high-purity fermentation technologies and liposomal encapsulation platforms addresses a critical market need — especially with the lipid-based segment projected to grow at an 8.2% CAGR (2024–2030).
Compounding pharmacies play pivotal roles in creating patient-tailored formulations for niche applications, from intralesional mucormycosis treatments 5 to ophthalmic gels with 14-day stability.
Emerging technologies, such as fluorescence-guided surgery and photodynamic activation, are expanding AmB’s clinical utility while mitigating toxicity.
For manufacturers, prioritizing low-aggregate API production and lyophilization excellence directly impacts nephrotoxicity profiles—a key differentiator in competitive markets.
As antifungal resistance escalates, AmB’s fungicidal action and innovative delivery systems ensure its continued relevance in modern medicine.
“Liposomal amphotericin B represents the single most significant advance in systemic antifungal therapy, combining uncompromised efficacy with dramatically improved safety.” – Journal of Antimicrobial Chemotherapy, 2025
Disclaimer:
This content is for informational purposes only and is intended for business-to-business communication within the pharmaceutical industry. It is not intended as medical advice. The manufacture, import, and use of API must comply with all applicable laws and regulations in the relevant country or region.
This blog post is informational only and does not constitute medical advice.
Always consult a healthcare professional before starting any new medication or treatment.
