Tobirax

Approved Indications:

• Serious Gram-negative bacterial infections, particularly those caused by Pseudomonas aeruginosa, Klebsiella spp., Escherichia coli, Enterobacter spp., Serratia spp., and Proteus spp.
• Lower respiratory tract infections (including pneumonia and bronchitis)
• Urinary tract infections (including complicated and recurrent UTIs)
• Skin and soft tissue infections
• Bone and joint infections
• Septicemia and bacteremia
• Meningitis (in combination with other antibiotics)
• Intra-abdominal infections, including peritonitis (with other agents)
• Endocarditis (as adjunct therapy)
• Ocular infections (topical Tobramycin) including:
• Bacterial conjunctivitis
• Keratitis
• Blepharitis
• Dacryocystitis
• Post-surgical prophylaxis

Clinically Accepted Off-label Uses:

• Cystic fibrosis-related pulmonary exacerbations (inhaled form)
• Prophylaxis in neutropenic patients with suspected Gram-negative infections
• Hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) (as part of empiric multidrug therapy)

General Guidelines:

• Route of administration: Intravenous (IV), intramuscular (IM), inhalation (via nebulizer), ophthalmic (eye drops/ointment)
• Duration: Typically 7–10 days; varies by indication and clinical response

Adults (IV/IM):

• Typical dose: 1–2.5 mg/kg/dose every 8–12 hours
• Severe infections: 5–7.5 mg/kg/day divided every 8 hours
• Once-daily dosing (extended interval): 5–7 mg/kg IV once daily in select populations

Inhaled (for Cystic Fibrosis):

• Dose: 300 mg twice daily via nebulizer, typically for 28 days on/28 days off cycles

Pediatrics:

• Neonates: 2–2.5 mg/kg every 12–18 hours depending on weight and age
• Infants and children: 2–2.5 mg/kg every 8 hours
  (Adjustments required based on renal function and therapeutic drug monitoring)

Ophthalmic (Eye Drops/Ointment):

• Adults and children: 1–2 drops in affected eye(s) every 4 hours; in severe cases, every hour initially

Renal Impairment:

• Dose adjustment required: Base adjustments on creatinine clearance (CrCl) and monitor serum drug levels (peak and trough)

Hepatic Impairment:

• No adjustment typically required, but monitor for increased toxicity risk if hepatic dysfunction impairs renal clearance indirectly.

Elderly:

• Dose adjustment based on renal function. Monitor creatinine and serum levels carefully.

Tobramycin is an aminoglycoside antibiotic that binds irreversibly to the 30S ribosomal subunit of susceptible bacteria. This interferes with the initiation complex of peptide formation, misreads mRNA, and causes premature termination of protein synthesis. The disruption in protein synthesis leads to defective or nonfunctional proteins and ultimately bacterial cell death. Tobramycin exhibits bactericidal activity, especially against aerobic Gram-negative organisms, by concentrating in the cytoplasm and compromising membrane integrity, further enhancing its lethal effect.

• Absorption: Poor oral bioavailability; administered parenterally or via inhalation/topically
• Distribution: Widely distributed in extracellular fluid; penetrates poorly into CSF unless meninges are inflamed; does not cross blood-brain barrier easily
• Protein Binding: Low (~10%)
• Metabolism: Not metabolized significantly
• Elimination: Primarily renal via glomerular filtration; ~90–100% excreted unchanged in urine
• Half-life:
• Adults with normal renal function: ~2–3 hours
• Prolonged in renal impairment
• Onset of Action: Rapid (within 30–60 minutes IV)
• Peak Levels: IV: within 30–60 minutes after infusion
• Bioavailability (Inhaled): ~10–15% systemic absorption

• Pregnancy: FDA Pregnancy Category D
• Tobramycin may cause fetal harm (ototoxicity and nephrotoxicity). Use only if benefits outweigh risks.
• Lactation:
• Limited data available. Small amounts may be excreted into breast milk. Systemic absorption in the infant is unlikely, especially with topical or inhaled forms.
• Caution advised; monitor for diarrhea, candidiasis, or potential nephro/ototoxicity in the infant.

• Primary Class: Aminoglycoside Antibiotic
• Subclass: Second-generation aminoglycoside
• Related agents: Gentamicin, Amikacin, Streptomycin

• Known hypersensitivity to Tobramycin or other aminoglycosides
• History of aminoglycoside-induced ototoxicity or nephrotoxicity
• Concurrent use with other nephrotoxic or ototoxic agents unless essential and closely monitored
• Myasthenia gravis (risk of neuromuscular blockade)
• Pregnancy (for systemic use unless benefits outweigh risks)

• Nephrotoxicity: Risk increases with high doses, prolonged use, or renal impairment. Monitor renal function regularly.
• Ototoxicity: Both vestibular and auditory toxicity possible, often irreversible. Audiometric monitoring is advised.
• Neuromuscular blockade: Rare but may lead to respiratory paralysis, especially in patients receiving neuromuscular blockers or with neuromuscular disorders.
• Cystic fibrosis patients: Increased risk of bronchospasm with inhaled forms.
• Therapeutic drug monitoring (TDM): Essential to avoid toxicity. Monitor peak and trough serum levels.
• Avoid concurrent use with loop diuretics (e.g., furosemide) or vancomycin without strict monitoring.

Common Side Effects:

• Renal: Increased serum creatinine, proteinuria
• Auditory/Neurological: Tinnitus, hearing loss, vertigo
• Respiratory (Inhaled): Cough, throat irritation, bronchospasm
• Gastrointestinal: Nausea, vomiting (rare with parenteral use)
• Ocular (Topical): Eye irritation, itching, eyelid swelling

Serious or Rare Side Effects:

• Acute tubular necrosis
• Irreversible ototoxicity
• Neuromuscular blockade
• Anaphylaxis or hypersensitivity reactions
• Superinfection with prolonged use

Onset & Dose-dependence:

• Nephrotoxicity and ototoxicity are dose- and duration-dependent and often delayed onset (days to weeks)

• Loop diuretics (e.g., furosemide, ethacrynic acid): Enhanced ototoxicity
• Vancomycin: Increased nephrotoxicity risk
• Amphotericin B, cisplatin, cyclosporine, tacrolimus: Additive nephrotoxic effects
• Neuromuscular blockers: Potentiation of neuromuscular blockade
• Penicillins/β-lactams (in same IV line): Inactivation when mixed directly

Enzyme Systems:

• Not metabolized via CYP450 enzymes
• No CYP450 induction/inhibition expected

• Cystic Fibrosis Foundation (CFF): Continues to support inhaled Tobramycin use in cycles for chronic P. aeruginosa infection.
• 2023 IDSA guidelines: Recommend careful therapeutic monitoring in critically ill patients and use in combination with β-lactams for empiric Gram-negative coverage.
• Updated warnings (FDA): Reinforced ototoxic and nephrotoxic risk monitoring, especially in pediatrics and elderly.

• Injectable Formulations:
• Store at 20°C to 25°C (68°F to 77°F)
• Do not freeze
• Protect from excessive heat
• Ophthalmic Drops/Ointment:
• Store between 2°C to 25°C (36°F to 77°F)
• Do not freeze; discard if discolored or contaminated
• Inhalation Solutions:
• Store refrigerated at 2°C to 8°C (36°F to 46°F)
• Protect from light
• Once opened, use immediately or per manufacturer’s guidance