Reconstitution of Amphotericin B Eye Drops for Fungal Keratitis
Reconstitute amphotericin B deoxycholate to 0.15% (1.5 mg/mL) by diluting the parenteral formulation (typically Fungizone®) with sterile water, though this extemporaneous preparation is stable for only 7 days refrigerated and causes significant ocular irritation. 1, 2
Standard Reconstitution Protocol
Using Amphotericin B Deoxycholate (Fungizone®)
Start with the parenteral formulation containing 50 mg amphotericin B deoxycholate per vial 2
Reconstitute the vial with 10 mL sterile water for injection (not saline, as it causes precipitation) to create a 5 mg/mL stock solution 2
Further dilute to 0.15% (1.5 mg/mL) by taking 3 mL of the 5 mg/mL stock and adding 7 mL sterile water to achieve a final 10 mL volume at the target concentration 1, 2
Store refrigerated at 2-8°C and discard after 7 days, as stability beyond this period is not guaranteed 2
Administer hourly for the first 24-48 hours if there is no response to initial empirical therapy (econazole 1%), then taper based on clinical response 1
Critical Limitations of Standard Preparation
Deoxycholate causes significant corneal irritation and reduces patient compliance, which is a major drawback of extemporaneous preparations from Fungizone® 3
Short shelf-life of only 1 week refrigerated limits practical use in outpatient settings 3
Particle aggregation can occur, reducing drug availability and potentially causing mechanical irritation 2
Superior Alternative Formulations (When Available)
Gamma-Cyclodextrin Complex
Mix 0.1% amphotericin B with 10% γ-cyclodextrin in sterile water to create a true solution rather than suspension 2
This formulation maintains sterility, acceptable osmolarity, pH, and particle size for ophthalmic use over 30 days at room temperature 2
Antifungal activity is 35% higher against Candida albicans compared to Fungizone®-based preparations 2
Chemical stability is superior to the reference suspension, making this the preferred formulation when cyclodextrin is available 2
Liposomal Amphotericin B (AmBisome®)
Reconstitute AmBisome® to 0.5% (5 mg/mL) by adding sterile water to the vial per manufacturer instructions 3
This preparation remains stable for 6 months at room temperature or refrigerated, with hydrodynamic diameter maintained at 108 ± 30 nm and drug content between 94-107% 3
Liposomal formulation eliminates deoxycholate-related irritation and improves patient tolerance 3
Note: This is a higher concentration (0.5%) than standard (0.15%) but may be diluted if needed, though the 0.5% concentration has been validated for stability 3
Dosing and Administration
Apply 1-2 drops to affected eye(s) every hour around the clock for severe fungal keratitis until clinical improvement, then taper to every 2-4 hours 1, 4
Continue treatment for at least 4-6 weeks with duration dependent on resolution of lesions determined by repeated ophthalmological examinations 5
For severe cases unresponsive to topical therapy alone, consider adjunctive subconjunctival amphotericin B injections (0.5-1.0 mg in 0.5 mL sterile water) to ensure adequate drug penetration 4
Common Pitfalls to Avoid
Never use normal saline as diluent for amphotericin B deoxycholate, as it causes immediate precipitation; only sterile water should be used 2
Do not confuse intravitreal dosing (5-10 μg/0.1 mL) with topical eye drop concentrations (1.5 mg/mL), as intravitreal overdosing causes severe retinal toxicity 5
Warn patients about expected pain and irritation with deoxycholate-based preparations to improve compliance 3, 4
Ensure proper storage and dating of extemporaneous preparations, as expired formulations lose potency and may harbor microbial contamination 2, 3
Consider ophthalmology consultation for all cases of fungal keratitis, as these infections can rapidly progress to corneal perforation and require close monitoring 5