Amikacin Sulfate

Aminoglycoside Antibiotic Antibacterial

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog IM, SC, IV (slow bolus or infusion) 15-20 mg/kg q24h (once daily) or 6-8 mg/kg q8h (traditional dosing) Duration: Usually 5-7 days; monitor renal function and drug levels if prolonged.
Notes: Once-daily dosing is preferred to reduce nephrotoxicity. Adjust dose in renal impairment.
Cat IM, SC, IV 15-20 mg/kg q24h Duration: 5-7 days
Notes: Cats are more sensitive to nephrotoxicity; ensure adequate hydration.
Horse IV, IM 10-15 mg/kg (foals: 20-25 mg/kg) q24h Duration: 5-7 days
Notes: Monitor renal function; avoid concurrent NSAIDs.
Cattle IM, SC, IV 10-15 mg/kg q24h Duration: 3-5 days
Notes: Extra-label; observe withdrawal times. Not recommended for lactating dairy cows.
Small Ruminants (sheep, goats) IM, SC, IV 10-15 mg/kg q24h Duration: 3-5 days
Notes: Extra-label; use with caution in food animals.
Rabbit SC, IM, IV 10-15 mg/kg q24h or divided q12h Duration: 5-7 days
Notes: Monitor renal function; ensure hydration.
Birds (companion) IM, IV 15-20 mg/kg q12h or q24h Duration: 5-7 days
Notes: Dose may vary by species; monitor for nephrotoxicity.
Reptiles IM 2.5-5 mg/kg q24-72h Duration: Variable; based on culture and sensitivity.
Notes: Dosing intervals may be prolonged due to ectothermic metabolism.

Clinical Indications & Species Uses

General Indications
  • Treatment of serious infections caused by susceptible aerobic Gram-negative bacteria when less toxic antibiotics are ineffective or contraindicated.
Dog (Canine)
  • Treatment of serious Gram-negative bacterial infections, including septicemia, pneumonia, urinary tract infections, skin and soft tissue infections, bone and joint infections, and intra-abdominal infections.
  • Often used in combination with beta-lactam antibiotics for synergistic coverage in severe infections.
Cat (Feline)
  • Treatment of serious Gram-negative infections, including septicemia, pneumonia, urinary tract infections, and skin infections.
  • May be used for infections caused by Pseudomonas aeruginosa.
Horse (Equine)
  • Treatment of neonatal septicemia, pneumonia, and other serious Gram-negative infections.
  • Used for respiratory tract infections, joint infections, and peritonitis.
  • Intrauterine infusion for endometritis caused by susceptible bacteria.
Cattle (Bovine)
  • Treatment of respiratory disease complex (e.g., pneumonia) caused by Gram-negative organisms.
  • Treatment of acute mastitis, metritis, and other systemic infections.
Small Ruminants (Sheep / Goat)
  • Treatment of serious Gram-negative infections, including pneumonia, septicemia, and enteritis.
  • Extra-label use; not FDA-approved for food animals.
Rabbit & Small Mammals
  • Treatment of respiratory infections (e.g., Pasteurella multocida) and other Gram-negative infections.
  • May be used for urinary tract infections.
Avian & Poultry
  • Treatment of Gram-negative infections in companion birds (e.g., psittacines) and poultry.
  • Used for respiratory and systemic infections; extra-label in poultry.
Exotic & Other Species
  • Reptiles: Treatment of Gram-negative infections, including abscesses and septicemia.
  • Small mammals (ferrets, guinea pigs): Treatment of respiratory and urinary infections.

Pharmacology & Mechanism of Action

Drug Class: Aminoglycoside Antibiotic | Pharmacological Group: Antibacterial

Mechanism of Action: Amikacin is a semi-synthetic aminoglycoside antibiotic that exerts its bactericidal effect by irreversibly binding to the 30S ribosomal subunit of susceptible bacteria. This binding interferes with the initiation of protein synthesis, leading to misreading of the genetic code and production of nonfunctional or toxic proteins. This disrupts the bacterial cell membrane integrity, causing rapid cell death. Amikacin is particularly effective against aerobic Gram-negative bacteria, including many strains resistant to other aminoglycosides due to its resistance to many aminoglycoside-inactivating enzymes.

Pharmacodynamics: Amikacin exhibits concentration-dependent bactericidal activity. Its efficacy is optimized by achieving high peak concentrations (Cmax) relative to the minimum inhibitory concentration (MIC) of the pathogen, typically aiming for a Cmax/MIC ratio of 8-10. It also exhibits a post-antibiotic effect (PAE), suppressing bacterial growth for several hours after drug levels fall below the MIC. Amikacin is active against many aerobic Gram-negative bacilli (e.g., E. coli, Klebsiella, Pseudomonas, Enterobacter, Serratia, Proteus) and some Gram-positive bacteria (e.g., Staphylococcus aureus, including some penicillinase-producing strains). It has poor activity against anaerobes and streptococci.

⚑ Pharmacokinetics Summary

Absorption: Amikacin is poorly absorbed from the gastrointestinal tract; oral administration is ineffective for systemic infections. It is rapidly and completely absorbed after intramuscular (IM) or subcutaneous (SC) administration, with peak serum concentrations occurring within 30-90 minutes. Topical application to wounds or mucous membranes may result in some systemic absorption, especially if applied to large denuded areas.
Distribution: Amikacin is hydrophilic and distributes primarily into extracellular fluid. It penetrates poorly into the cerebrospinal fluid (CSF), eye, and prostatic fluid, even in the presence of inflammation. It does cross the placenta. Volume of distribution is approximately 0.2-0.3 L/kg in most species. It accumulates in the renal cortex and inner ear, which is the basis for its nephrotoxicity and ototoxicity.
Metabolism: Amikacin undergoes minimal metabolism; it is primarily excreted unchanged by the kidneys. No significant hepatic metabolism occurs.
Excretion: Amikacin is eliminated almost entirely by glomerular filtration, with active tubular secretion playing a minor role. In animals with normal renal function, the elimination half-life is approximately 1-2 hours in dogs and cats, 2-3 hours in horses, and 1.5-2 hours in cattle. Excretion is significantly prolonged in animals with renal impairment.
Half-Life: Dogs: 1-2 hours; Cats: 1-2 hours; Horses: 2-3 hours; Cattle: 1.5-2 hours; Rabbits: 1-2 hours; Birds: 1-2 hours (variable).
Bioavailability: Oral: <5% (not systemically absorbed); IM/SC: ~100% in most species.
Protein Binding: Amikacin has low protein binding, typically less than 10% in most species.

Available Formulations & Strengths

Injectable Solution 50 mg/mL, 250 mg/mL (IM, SC, IV)
Ophthalmic Solution 0.5% (5 mg/mL) (Ophthalmic)
Ointment 0.5% (Ophthalmic)

Contraindications & Clinical Warnings

Contraindications:
  • Hypersensitivity to amikacin or other aminoglycosides.
  • Pre-existing renal disease or severe renal impairment.
  • Dehydration or hypovolemia (increased risk of nephrotoxicity).
  • Concurrent use of other nephrotoxic drugs (e.g., NSAIDs, amphotericin B, other aminoglycosides).
  • Use in animals with myasthenia gravis (may exacerbate neuromuscular blockade).
Warnings & Clinical Precautions:
  • Amikacin is nephrotoxic and ototoxic; monitor renal function (BUN, creatinine, urinalysis) before and during therapy.
  • Use with caution in neonates and geriatric animals due to immature or decreased renal function.
  • Ensure adequate hydration during therapy.
  • Avoid prolonged therapy (>7 days) unless necessary and monitored.
  • In food animals, observe withdrawal times; extra-label use requires veterinary oversight.
  • May cause neuromuscular blockade; use with caution in animals with respiratory compromise or those receiving anesthetics/muscle relaxants.
  • Do not mix with other drugs in the same syringe or infusion line (incompatibility).

Adverse Effects & Reactions

Common:

  • Nephrotoxicity (increased BUN/creatinine, proteinuria, casts)
  • Ototoxicity (vestibular and cochlear damage, hearing loss, ataxia)
  • Pain at injection site
  • Gastrointestinal upset (nausea, diarrhea)

Serious / Severe:

  • Acute renal failure
  • Irreversible hearing loss
  • Neuromuscular blockade leading to respiratory depression
  • Anaphylaxis (rare)

Rare:

  • Allergic reactions (skin rash, urticaria)
  • Eosinophilia
  • Hepatotoxicity (rare)
  • Electrolyte disturbances (hypokalemia, hypocalcemia)

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Furosemide or other loop diuretics Increased risk of ototoxicity and nephrotoxicity. High
Nonsteroidal anti-inflammatory drugs (NSAIDs) Additive nephrotoxicity; reduced renal blood flow. High
Other aminoglycosides (e.g., gentamicin, neomycin) Additive nephrotoxicity and ototoxicity. High
Amphotericin B Increased risk of nephrotoxicity. High
Neuromuscular blocking agents (e.g., atracurium, succinylcholine) Enhanced neuromuscular blockade, respiratory depression. High
Penicillins (e.g., ampicillin, ticarcillin) In vitro inactivation if mixed; synergistic antibacterial effect when administered separately. Moderate
Cephalosporins Additive nephrotoxicity. Moderate
Methoxyflurane or other halogenated anesthetics Increased nephrotoxicity. Moderate

Overdose & Toxicity Management

Signs of Toxicity:

  • Acute renal failure (oliguria, anuria, elevated BUN/creatinine)
  • Ototoxicity (head tilt, ataxia, hearing loss)
  • Neuromuscular blockade (muscle weakness, respiratory depression)
  • Seizures (rare)
  • Cardiovascular collapse (in severe cases)

Emergency Treatment Protocol: There is no specific antidote. Treatment is supportive and symptomatic. Discontinue amikacin immediately. Maintain adequate hydration with intravenous fluids to promote renal excretion. Monitor renal function and electrolytes. In severe cases, hemodialysis or peritoneal dialysis may be considered to remove the drug. For neuromuscular blockade, administer calcium gluconate (10% solution) IV slowly, and consider neostigmine if respiratory depression is severe. Provide respiratory support as needed.

Food Animal Withdrawal Times

πŸ₯© Meat: 18 daysπŸ₯› Milk: 7 days

Withdrawal times are not established for amikacin in food animals; extra-label use requires extended withdrawal periods. The values provided are estimates based on label for cattle (meat 18 days, milk 7 days) but may vary; consult FARAD (Food Animal Residue Avoidance Databank) for specific guidance.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 20-25Β°C (68-77Β°F); protect from freezing.

Handling & Special Conditions: Do not use if solution is discolored or contains particulate matter. Keep container tightly closed.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for use in dogs and cats (injectable solution) and for ophthalmic use in dogs and cats. Not approved for food animals.

Extra-Label (Off-Label) Use: Amikacin is not FDA-approved for food animals; extra-label use is permitted under AMDUCA with veterinary oversight, requiring extended withdrawal times. In companion animals, it is a prescription drug.

Clinical Pearls & Practice Notes

πŸ’‘ Clinical Insights: Amikacin is a potent aminoglycoside reserved for serious Gram-negative infections, especially those resistant to gentamicin. Due to its nephrotoxicity and ototoxicity, it should be used judiciously, with therapeutic drug monitoring (peak and trough levels) when possible. Once-daily dosing is preferred to maximize efficacy and minimize toxicity. Always ensure adequate hydration and monitor renal function. In food animals, use is extra-label and requires careful attention to withdrawal times. Combination therapy with a beta-lactam (e.g., ampicillin, ceftiofur) is often recommended for synergistic coverage and to reduce the risk of resistance. Avoid concurrent use of other nephrotoxic drugs. For ophthalmic use, amikacin is effective against Pseudomonas and other Gram-negative pathogens.

References & Literature

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