Amphotericin B

Antifungal Polyene macrolide antibiotic

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog IV 0.5-1 mg/kg (test dose 0.1 mg/kg) diluted in 5% dextrose, infused over 4-6 hours q48h or 3 times per week Duration: Until clinical resolution (often weeks to months)
Notes: Pre-hydrate with saline to reduce nephrotoxicity. Monitor renal parameters.
Cat IV 0.25-0.5 mg/kg (test dose 0.1 mg/kg) diluted in 5% dextrose, infused over 4-6 hours q48h or 3 times per week Duration: Until clinical resolution
Notes: Cats are more sensitive to nephrotoxicity; use lower doses and monitor closely.
Horse IV 0.3-0.8 mg/kg diluted in 5% dextrose, infused over 4-6 hours q48h Duration: Variable, based on response
Notes: For systemic mycoses. For topical use (e.g., guttural pouch), 50-100 mg in 500 mL saline as irrigation.
Cattle IV 0.5 mg/kg diluted in 5% dextrose, infused slowly q48h Duration: Variable
Notes: Rarely used; consider extra-label use restrictions.
Rabbit IV 0.5-1 mg/kg diluted in 5% dextrose, infused over 4-6 hours q48h Duration: Variable
Notes: Monitor renal function; may be nephrotoxic.
Bird (companion) IV 1.5 mg/kg diluted in 5% dextrose, infused over 2-4 hours q8h or q12h Duration: Variable
Notes: For aspergillosis; use with caution.
Poultry Oral 100 mg/kg in drinking water or feed q24h Duration: 5-7 days
Notes: For gastrointestinal candidiasis; not absorbed systemically.

Clinical Indications & Species Uses

General Indications
  • Treatment of severe systemic fungal infections caused by susceptible organisms
Dog (Canine)
  • Systemic mycoses (blastomycosis, histoplasmosis, cryptococcosis, coccidioidomycosis)
  • Aspergillosis (especially sinonasal, as topical irrigation)
  • Leishmaniasis (in combination with other agents)
Cat (Feline)
  • Systemic mycoses (cryptococcosis, histoplasmosis, blastomycosis)
  • Nasal aspergillosis (topical)
  • Leishmaniasis (rarely)
Horse (Equine)
  • Systemic mycoses (histoplasmosis, blastomycosis, cryptococcosis)
  • Fungal keratitis (topical)
  • Guttural pouch mycosis (topical)
Cattle (Bovine)
  • Systemic mycoses (rarely used)
  • Mastitis caused by Candida spp. (intramammary, experimental)
Small Ruminants (Sheep / Goat)
  • Systemic mycoses (rarely used)
Rabbit & Small Mammals
  • Systemic mycoses (e.g., cryptococcosis, aspergillosis)
Avian & Poultry
  • Candidiasis (oral, for gastrointestinal decontamination)
  • Aspergillosis (systemic, in companion birds)
Exotic & Other Species
  • Reptiles: systemic mycoses
  • Small mammals (ferrets, guinea pigs): systemic mycoses

Pharmacology & Mechanism of Action

Drug Class: Antifungal | Pharmacological Group: Polyene macrolide antibiotic

Mechanism of Action: Amphotericin B binds to ergosterol, a key component of fungal cell membranes, forming pores that increase membrane permeability, leading to leakage of intracellular ions and small molecules, and ultimately cell death. It has a higher affinity for fungal ergosterol than mammalian cholesterol, but at high doses can also bind to cholesterol in mammalian cells, contributing to toxicity.

Pharmacodynamics: Amphotericin B is fungicidal or fungistatic depending on the concentration and susceptibility of the organism. It has a broad spectrum of activity against most fungi, including Candida spp., Cryptococcus neoformans, Histoplasma capsulatum, Blastomyces dermatitidis, Coccidioides immitis, Aspergillus spp., and some molds. It is also active against Leishmania spp. and Naegleria fowleri. Resistance is uncommon but has been reported in some fungi due to altered ergosterol content.

⚑ Pharmacokinetics Summary

Absorption: Oral absorption is poor; amphotericin B is administered intravenously for systemic infections. The oral formulation is used for topical gastrointestinal decontamination (e.g., in poultry) but is not absorbed systemically.
Distribution: Widely distributed in body tissues, with high concentrations in liver, spleen, and lungs. Penetration into cerebrospinal fluid is poor, but it can be enhanced by intrathecal administration. It crosses the placenta and is distributed into milk.
Metabolism: Metabolism is not well characterized; the drug is believed to be metabolized in the liver to a minor extent.
Excretion: Excretion is primarily via the biliary route, with about 2-5% excreted in urine. Renal excretion is slow, and the drug can be detected in urine for weeks after discontinuation.
Half-Life: Dog: 24-48 hours; Horse: 24-48 hours; Human: 24 hours (terminal half-life can be up to 15 days due to tissue binding).
Bioavailability: Oral: <5% (not systemically absorbed); IV: 100%.
Protein Binding: Approximately 90-95% bound to plasma proteins.

Available Formulations & Strengths

Injectable Solution (lyophilized powder for reconstitution) 50 mg vial (IV)
Liposomal Injection (AmBisome) 50 mg vial (IV)
Oral Suspension (for topical GI use) 100 mg/mL (Oral)
Ophthalmic Solution (extemporaneous) 0.15% (Topical (ophthalmic))

Contraindications & Clinical Warnings

Contraindications:
  • Hypersensitivity to amphotericin B or any component
  • Severe renal impairment (unless life-threatening infection and no alternative)
  • Concurrent use with nephrotoxic drugs (e.g., aminoglycosides, cyclosporine) unless absolutely necessary
Warnings & Clinical Precautions:
  • Nephrotoxicity is dose-limiting; monitor renal function (BUN, creatinine) before and during therapy
  • Hypokalemia and hypomagnesemia may occur; monitor electrolytes and supplement as needed
  • Infusion-related reactions (fever, chills, vomiting) are common; premedicate with antihistamines, antipyretics, or corticosteroids
  • Use with caution in dehydrated or hypovolemic patients; ensure adequate hydration
  • Do not use saline for reconstitution or infusion; use 5% dextrose
  • Avoid rapid infusion; administer over 4-6 hours
  • In cats, monitor for nephrotoxicity closely; consider lipid formulations to reduce toxicity
  • For food animals, observe withdrawal times; extra-label use requires veterinary oversight

Adverse Effects & Reactions

Common:

  • Nephrotoxicity (azotemia, proteinuria)
  • Hypokalemia
  • Hypomagnesemia
  • Infusion-related reactions (fever, chills, vomiting, anorexia)
  • Phlebitis at injection site

Serious / Severe:

  • Acute renal failure
  • Cardiac arrhythmias (due to electrolyte disturbances)
  • Anaphylaxis
  • Bone marrow suppression (rare)
  • Neurotoxicity (with intrathecal use)

Rare:

  • Hepatotoxicity
  • Hemolytic anemia
  • Pulmonary edema
  • Seizures

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Aminoglycosides (e.g., gentamicin) Additive nephrotoxicity High
Cyclosporine Increased risk of nephrotoxicity High
Corticosteroids May exacerbate hypokalemia Moderate
Digitalis glycosides Increased risk of digitalis toxicity due to hypokalemia Moderate
Neuromuscular blocking agents Enhanced neuromuscular blockade due to hypokalemia Moderate
Antineoplastic agents (e.g., nitrogen mustard) Additive nephrotoxicity and bone marrow suppression Moderate

Overdose & Toxicity Management

Signs of Toxicity:

  • Severe nephrotoxicity (acute renal failure)
  • Hypokalemia/hypomagnesemia leading to cardiac arrhythmias
  • Hypotension
  • Respiratory distress
  • Seizures

Emergency Treatment Protocol: Discontinue drug immediately. Provide supportive care: IV fluids to maintain renal perfusion, correct electrolyte imbalances (potassium, magnesium), monitor cardiac function. In severe cases, hemodialysis may be considered. There is no specific antidote.

Food Animal Withdrawal Times

πŸ₯© Meat: 30 daysπŸ₯› Milk: 7 days

Withdrawal times are not officially established for amphotericin B in food animals; these are conservative estimates. Consult regulatory authorities and FARAD for specific guidance.

Storage, Handling & Regulatory Information

Storage Temperature: Store lyophilized powder at 2-8Β°C (refrigerate). Reconstituted solution is stable for 24 hours at room temperature and 7 days if refrigerated and protected from light.

Light Sensitivity: Light-sensitive β€” protect from direct exposure.

Handling & Special Conditions: Protect from light. Do not freeze. Use 5% dextrose for reconstitution; do not use saline.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use; approved for human use.

Extra-Label (Off-Label) Use: In the US, amphotericin B is not FDA-approved for veterinary species; use is extra-label. Must follow AMDUCA regulations: require valid VCPR, and for food animals, ensure extended withdrawal times and no residues.

Clinical Pearls & Practice Notes

πŸ’‘ Clinical Insights: Amphotericin B remains a potent antifungal for severe systemic mycoses in veterinary patients, but its use is limited by nephrotoxicity. Lipid formulations (e.g., liposomal amphotericin B) are less nephrotoxic but more expensive. Pre-treatment with saline diuresis and monitoring of renal function and electrolytes are essential. Infusion reactions can be managed with premedication. For topical use (e.g., nasal aspergillosis in dogs), it can be administered as an irrigation solution. In food animals, use is rare and requires careful consideration of withdrawal times. Always consult current veterinary pharmacology references for updated dosing and safety information.

References & Literature

  • πŸ“š Plumb's Veterinary Drug Handbook
  • πŸ“š Papich Veterinary Pharmacology and Therapeutics
  • πŸ“š Compendium of Veterinary Products (CVP)