tobramycin

tobramycin ophthalmic
AKTob, Defy, Tobrex

tobramycin sulfate
Nebcin, Nebcin Add-Vantage, Nebcin Pediatric

tobramycin solution for inhalation
TOBI

Available forms
Available by prescription only
Injection: 40 mg/ml, 10 mg/ml (pediatric), 10 mg/ml (adult)
Nebulizer solution for inhalation: Single-use 5-ml (300-mg) ampule
Ophthalmic ointment: 0.3%
Ophthalmic solution: 0.3%

Indications and dosages
 Serious infections caused by Escherichia coli, Staphylococcus aureus, and Proteus, Klebsiella, Enterobacter, Serratia, Pseudomonas, Citrobacter, and Providencia species. Adults and children with normal renal function: 3 mg/kg I.M. or I.V. daily, divided q 8 hours. Up to 5 mg/kg I.M. or I.V. daily, divided q 6 to 8 hours for life-threatening infections.
Neonates younger than age 1 week: Up to 4 mg/kg I.M. or I.V. daily, divided q 12 hours. For I.V. use, dilute in 50 to 100 ml normal saline solution or D₅W for adults and in less volume for children. Infuse over 20 to 60 minutes.
≡ Dosage adjustment. Use ideal body weight for dosing. For obese patients, use calculated ideal body weight plus 40% of excess to calculate dose.
For patients with impaired renal function, initial dosage is same as for those with normal renal function. Subsequent doses and frequency are determined by renal function study results and blood levels; keep peak serum levels between 4 and 8 mcg/ml and trough serum levels between 1 and 2 mcg/ml. Several methods have been used to calculate dosage in renal impairment.
After a 1-mg/kg loading dose, adjust subsequent dosage by reducing doses administered at 8-hour intervals or by prolonging the interval between normal doses. Both of these methods are useful when serum levels of tobramycin can’t be measured directly. They’re based on either creatinine clearance (preferred) or serum creatinine because these values correlate with half-life of drug.
To calculate reduced dosage for 8-hour intervals, use available nomograms; or, if patient’s steady state serum creatinine values are known, divide the normally recommended dose by patient’s serum creatinine value. To determine frequency in hours for normal dosage (if creatinine clearance rate isn’t available), divide the normal dose by patient’s serum creatinine level. Dosage schedules derived from either method require careful clinical and laboratory observations of patient and should be adjusted as appropriate. These methods of calculation may be misleading in geriatric patients and in those with severe wasting; neither should be used when dialysis is performed.
Hemodialysis removes 50% to 75% of a dose in 6 hours. In anephric patients maintained by dialysis, 1.5 to 2 mg/kg after each dialysis usually maintains therapeutic, nontoxic serum levels. Patients receiving peritoneal dialysis twice a week should receive a 1.5 to 2 mg/kg loading dose followed by 1 mg/kg q 3 days. Those receiving dialysis q 2 days should receive a 1.5 mg/kg loading dose after first dialysis and 0.75 mg/kg after each subsequent dialysis.
 Intrathecally or intraventricularly, together with I.M. or I.V. administration ◇. Adults: 3 to 8 mg q 18 to 48 hours.
 Management of cystic fibrosis in patients with Pseudomonas aeruginosa infection. Adults and children older than age 6: 1 single-use ampule (300 mg) administered q 12 hours for 28 days, then off for 28 days, then on for 28 days. There’s no dose adjustment for age or renal impairment.
 Treatment of external ocular infection caused by susceptible gram-negative bacteria. Adults and children: In mild to moderate infections, instill 1 or 2 drops into affected eye q 4 to 6 hours. In severe infections, instill 2 drops into affected eye hourly or apply a small amount of ointment into conjunctival sac t.i.d. or q.i.d.

Pharmacodynamics
Antibiotic action: Tobramycin is bactericidal; it binds directly to the 30S ribosomal subunit, thereby inhibiting bacterial protein synthesis. Its spectrum of activity includes many aerobic gram-negative organisms, including most strains of P. aeruginosa and some aerobic gram-positive organisms. Tobramycin may act against some bacterial strains resistant to other aminoglycosides; many strains resistant to tobramycin are susceptible to amikacin, gentamicin, or netilmicin.

Pharmacokinetics
Absorption: Absorbed poorly after oral administration and usually is given parenterally. Inhaled drug remains concentrated in the airway, with serum level after 20 weeks of therapy being 1.05 mcg/ml 1 hour after dosing.
Distribution: Distributed widely after parenteral administration; intraocular penetration is poor. CSF penetration is low, even in patients with inflamed meninges. Protein-binding is minimal; tobramycin crosses the placental barrier. Inhaled drug remains primarily concentrated in the airway.
Metabolism: Not metabolized.
Excretion: Excreted primarily in urine by glomerular filtration; small amounts may be excreted in bile and breast milk. Elimination half-life in adults is 2 to 3 hours. In severe renal damage, half-life may extend to 24 to 60 hours. With inhalation use, unabsorbed tobramycin is probably eliminated in the sputum.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug or other aminoglycosides. Use injectable form cautiously in elderly patients and those with impaired renal function or neuromuscular disorders.

Interactions
Drug-drug. Aminoglycosides, amphotericin B, capreomycin, cephalosporins, cisplatin, methoxyflurane, polymyxin B, vancomycin: Increases risk of nephrotoxicity, ototoxicity, and neurotoxicity. Monitor patient carefully.
Antiemetics, antivertigo drugs, dimenhydrinate: May mask tobramycin-induced ototoxicity. Monitor patient closely.
Bumetanide, ethacrynic acid, furosemide, mannitol, urea: Increases risk of ototoxicity. Monitor patient closely.
General anesthetics, neuromuscular blockers, succinylcholine, tubocurarine: Potentiates neuromuscular blockade. Monitor patient closely.
Penicillins: Physically and chemically incompatible. Don’t mix in same I.V. line.

Adverse reactions
CNS: fever (ophthalmic administration); headache, lethargy, confusion, seizures, disorientation (injectable form).
EENT: ototoxicity (injectable form); blurred vision (ophthalmic ointment); burning or stinging on instillation, lid itching or swelling, conjunctival erythema (ophthalmic administration).
GI: vomiting, nausea, diarrhea (injectable form).
GU: increased urinary excretion of casts; nephrotoxicity (injectable form).
Hematologic: anemia, eosinophilia, leukopenia, thrombocytopenia, granulocytopenia (injectable form).
Respiratory: bronchospasm (inhaled form).
Skin: rash, urticaria, pruritus (injectable form).
Other: hypersensitivity reactions, overgrowth of nonsusceptible organisms (ophthalmic administration).

Effects on lab test results
• Tobramycin sulfate may increase BUN, creatinine, and nonprotein nitrogen and nitrogenous compound levels. Tobramycin sulfate may decrease calcium, magnesium, and potassium levels.
• Tobramycin sulfate may increase eosinophil count. Tobramycin sulfate may decrease WBC, platelet, and granulocyte counts.

Overdose and treatment
Signs and symptoms of overdose include ototoxicity, nephrotoxicity, and neuromuscular toxicity.
 Remove drug by hemodialysis or peritoneal dialysis. Treatment with calcium salts or anticholinesterases reverses neuromuscular blockade.

Special considerations
 ALERT Don’t confuse tobramycin with Trobicin.
• For I.V. administration, the usual volume of diluent (normal saline solution injection or D₅W injection) for adult doses is 50 to 100 ml. For children, the volume should be proportionately less. Infusion should be over 20 to 60 minutes.
• Don’t premix tobramycin with other drugs; administer separately at least 1 hour apart.
• Discontinue ophthalmic preparation if keratitis, erythema, lacrimation, edema, or lid itching occurs.
• Because tobramycin is dialyzable, patients undergoing hemodialysis may need dose adjustments.
• Inhalation form of tobramycin is an orphan drug used specifically for management of cystic fibrosis patients with P. aeruginosa infection.
• Monitor patient for symptoms of toxicity.
• Monitor peak and trough drug levels; peak shouldn’t exceed 4 to 8 mcg/ml and trough should be below 2 mcg/ml.
Pregnant patients
• Use drug during pregnancy only when clearly indicated.
Breast-feeding patients
• Drug may appear in breast milk. A decision should be made to discontinue either drug or breast-feeding.

Patient education
• Advise patient that inhalation doses should be taken as close to 12 hours apart as possible and no less than 6 hours apart.
• Instruct patient on proper administration (inhalation).

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use