Kanamycin - Drug Monograph

Introduction

Kanamycin is an aminoglycoside antibiotic derived from Streptomyces kanamyceticus. First isolated in 1957, it has been used clinically for decades to treat serious Gram-negative bacterial infections. As a bactericidal antibiotic, kanamycin remains relevant in specific clinical scenarios despite the development of newer antimicrobial agents.

Mechanism of Action

Kanamycin exerts its bactericidal effect by binding irreversibly to the 30S ribosomal subunit of susceptible bacteria. This binding:

• Interferes with the initiation complex formation
• Causes misreading of mRNA codons, leading to incorporation of incorrect amino acids into polypeptide chains
• Results in the production of nonfunctional proteins
• Ultimately causes bacterial cell death through disruption of essential cellular processes

The drug requires oxygen-dependent transport across bacterial cell membranes, making it ineffective against anaerobic bacteria.

Indications

FDA-approved indications include:

• Serious infections caused by susceptible strains of E. coli, Proteus species, Enterobacter aerogenes, Klebsiella pneumoniae, Serratia marcescens, and Acinetobacter species
• Adjuvant therapy in Mycobacterium tuberculosis infections (when first-line drugs cannot be used)
• Hepatic coma (to reduce ammonia-forming bacteria in the GI tract)

Off-label uses may include:

• Treatment of multidrug-resistant tuberculosis
• Certain mycobacterial infections
• Plague (Yersinia pestis) when preferred agents are contraindicated

Dosage and Administration

• IM/IV: 5-7.5 mg/kg/day divided every 8-12 hours
• Maximum daily dose: 1.5 g (15 mg/kg)
• Duration: 7-14 days depending on infection severity

• IM/IV: 5-7.5 mg/kg/day divided every 8-12 hours
• Neonates: 7.5 mg/kg every 12 hours

Dosage must be adjusted based on creatinine clearance:

• CrCl 50-80 mL/min: 60-90% of normal dose
• CrCl 10-50 mL/min: 30-70% of normal dose
• CrCl <10 mL/min: 20-30% of normal dose

• IV infusion: Dilute in 50-200 mL of compatible fluid (NS or D5W) and infuse over 30-60 minutes
• IM injection: Administer deep into large muscle mass

Pharmacokinetics

Contraindications

• Hypersensitivity to kanamycin or other aminoglycosides
• History of serious toxic reactions to other aminoglycosides
• Cross-sensitivity with other aminoglycosides may occur

Warnings and Precautions

• Nephrotoxicity: Risk of acute renal tubular necrosis
• Ototoxicity: Both vestibular and auditory toxicity can occur, potentially permanent
• Neuromuscular blockade: Especially with concurrent anesthesia or neuromuscular blocking agents

• Use with caution in patients with renal impairment, dehydration, or preexisting hearing loss
• Elderly patients at increased risk of toxicity
• Monitor for superinfection and fungal overgrowth
• Use during pregnancy only if potential benefit justifies potential fetal risk (Category D)

Drug Interactions

• Other nephrotoxic drugs: Vancomycin, amphotericin B, cisplatin - increased nephrotoxicity
• Other ototoxic drugs: Loop diuretics, platinum-based chemotherapy - increased ototoxicity
• Neuromuscular blocking agents: Enhanced neuromuscular blockade
• Penicillins: Physically incompatible when mixed; may inactivate kanamycin

Adverse Effects

• Pain at injection site
• Skin rash
• Fever
• Eosinophilia

• Nephrotoxicity (elevated BUN, creatinine, oliguria)
• Ototoxicity (tinnitus, hearing loss, vertigo, ataxia)
• Neuromuscular blockade (respiratory depression)
• Peripheral neuropathy
• Electrolyte disturbances (hypokalemia, hypomagnesemia, hypocalcemia)
• Blood dyscrasias (rare)

Monitoring Parameters

• Renal function tests (BUN, creatinine, creatinine clearance)
• Audiogram (baseline and serial)
• Vestibular function assessment
• Serum electrolytes

• Serum creatinine every 2-3 days
• Peak and trough levels (target peak: 15-30 mcg/mL; trough: <5-10 mcg/mL)
• Daily assessment of hearing and balance
• Urinalysis for casts, cells, and protein
• Input/output monitoring
• Signs of neuromuscular blockade

Patient Education

• Report any hearing changes, ringing in ears, dizziness, or balance problems immediately
• Maintain adequate hydration unless contraindicated
• Inform all healthcare providers of kanamycin use
• Complete full course of therapy unless instructed otherwise
• Be aware of potential side effects and report any unusual symptoms
• Do not take other medications without consulting healthcare provider
• Regular follow-up appointments are essential for monitoring

References

1. Gilbert DN, Chambers HF, Eliopoulos GM, et al. The Sanford Guide to Antimicrobial Therapy. 52nd ed.; 2022. 2. Lexicomp Online. Kanamycin monograph. Wolters Kluwer Clinical Drug Information. Accessed 2023. 3. FDA Prescribing Information: Kanamycin Injection. Revised 2019. 4. Bartlett JG. Johns Hopkins ABX Guide. 2023 edition. 5. Nelson RW, Couto CG. Small Animal Internal Medicine. 6th ed. Elsevier; 2020. 6. Blumenthal KG, Peter JG, Trubiano JA, Phillips EJ. Antibiotic allergy. Lancet. 2019;393(10167):183-198. 7. Rybak MJ, Le J, Lodise TP, et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm. 2020;77(11):835-864.