tobramycin sulfate

tobramycin sulfate

[tō′brəmī′sin]

an aminoglycoside antibiotic.

indications It is prescribed in the treatment of external ocular infection, septicemia, and lower respiratory tract and central nervous system infections caused by gram-negative bacilli, including Pseudomonas.

contraindications Kidney dysfunction, use of potent diuretics, or known hypersensitivity to this or other aminoglycosides prohibits its use.

adverse effects Among the more serious adverse reactions are ototoxicity and nephrotoxicity.

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tobramycin sulfate

Pharmacologic class: Aminoglycoside

Therapeutic class: Anti-infective

Pregnancy risk category B (inhalation, ophthalmic), D (parenteral)

FDA Boxed Warning

The following boxed warnings apply to parenteral administration only:
• When giving drug by injection, observe patient closely for potential ototoxicity and nephrotoxicity. Rarely, nephrotoxicity doesn't emerge until first few days after therapy ends.
• Neurotoxicity, manifested as both auditory and vestibular ototoxicity, can occur. Auditory changes are irreversible and usually bilateral. Eighth-nerve impairment and nephrotoxicity also may develop, mainly in patients with preexisting renal damage and in those with normal renal function who receive drug for longer periods or in higher doses than those recommended. Other neurotoxicity manifestations may include numbness, skin tingling, muscle twitching, and seizures. Risk of drug-induced hearing loss increases with degree of exposure to high peak or high trough drug blood levels. Patients who develop cochlear damage may lack symptoms during therapy to warn of eighth-nerve toxicity, and partial or total irreversible bilateral deafness may continue to develop after withdrawal.
• Monitor renal and eighth-nerve function closely in patients with known or suspected renal impairment and in those whose renal functional initially is normal but who develop signs of renal dysfunction during therapy. Monitor peak and trough drug blood levels periodically during therapy; avoid levels above 12 mcg. Rising trough levels (above 2 mcg) may indicate tissue accumulation. Such accumulation, excessive peak levels, advanced age, and cumulative dose may contribute to ototoxicity and nephrotoxicity. Examine urine for decreased specific gravity and increased protein, cells, and casts. Measure blood urea nitrogen (BUN), serum creatinine, and creatinine clearance periodically. When feasible, obtain serial audiograms. Evidence of impairment of renal, vestibular, or auditory function warrants drug withdrawal or dosage adjustment.
• Avoid concurrent or sequential use of other neurotoxic or nephrotoxic antibiotics, especially other aminoglycosides (such as amikacin, gentamicin, kanamycin, neomycin, and streptomycin), cephaloridine, cisplatin, colistin, polymyxin B, vancomycin, and viomycin. Advanced age and dehydration also increase risk.
• Don't give concurrently with potent diuretics (such as furosemide and ethacrynic acid), because these drugs are also ototoxic. Also, I.V. diuretics may increase tobramycin toxicity by altering antibiotic serum and tissue levels.
• Use drug cautiously in premature infants and neonates.
• Drug may harm fetus when given to pregnant women.

Action

Interferes with protein synthesis in bacterial cell by binding to 30S ribosomal subunit

Availability

Injection: 10 mg/ml, 40 mg/ml, 1.2-g vial

Nebulizer solution: 300 mg/5 ml in 5-ml ampule

Ophthalmic ointment: 0.3%

Ophthalmic solution: 0.3%

Pediatric solution for injection: 20 mg/2 ml

⊘Indications and dosages

➣ Serious infections caused by susceptible organisms

Adults: 3 mg/kg/day I.V. or I.M. in evenly divided doses q 8 hours. For life-threatening infections, may increase up to 5 mg/kg/day I.V. or I.M. in three or four evenly divided doses, then reduce to 3 mg/kg/day as soon as possible.

Children older than 1 week: 6 to 7.5 mg/kg/day in three or four evenly divided doses, such as 2 to 2.5 mg/kg I.V. or I.M. q 8 hours or 1.5 to 1.9 mg/kg I.V. or I.M. q 6 hours

Neonates less than 1 week old: Up to 4 mg/kg/day I.V. or I.M. in evenly divided doses q 12 hours

➣Pseudomonas aeruginosa in cystic fibrosis patients

Adults and children older than age 6: 300 mg inhalation b.i.d. (preferably q 12 hours but no less than 6 hours apart) for 28 days, then off for 28 days; then repeat cycle

➣ Ocular infections caused by susceptible organisms

Adults and children: For mild to moderate infections, apply a ribbon of ophthalmic ointment (approximately 1 cm) to infected eye two or three times daily, or instill one to two drops of ophthalmic solution into infected eye q 4 hours. For severe infections, apply ophthalmic ointment q 3 to 4 hours or instill two drops of ophthalmic solution into infected eye q 30 to 60 minutes; decrease dosing frequency when improvement occurs. Therapy should continue for at least 48 hours after infection is under control.

Dosage adjustment

• Renal impairment

Contraindications

• Hypersensitivity to drug, other aminoglycosides, bisulfites (with some products), or benzyl alcohol (in neonates, with some products)

Precautions

Use cautiously in:
• renal or hearing impairment, neuromuscular diseases, obesity
• elderly patients
• pregnant or breastfeeding patients
• neonates and premature infants.

Administration

• Dilute I.V. dose in 50 to 100 ml of normal saline solution or dextrose 5% in water. For child, smaller volumes are needed.
• Infuse over at least 30 minutes. Flush line after administration.
• Give cephalosporins or penicillin, if ordered, 1 hour before or after tobramycin.
• Give inhalation doses by nebulizer over 10 to 15 minutes.

Route	Onset	Peak	Duration
I.V.	Rapid	15-30 min	Unknown
I.M.	Rapid	30-90 min	Unknown
Inhalation, ophthalmic	Unknown	Unknown	Unknown

Adverse reactions

CNS: confusion, lethargy, headache, delirium, dizziness, vertigo

EENT: eye stinging (with ophthalmic form), ototoxicity, hearing loss, roaring in ears, tinnitus

GI: nausea, vomiting, diarrhea, stomatitis

GU: proteinuria, oliguria, nephrotoxicity

Hematologic: anemia, eosinophilia, leukocytosis, leukopenia, thrombocytopenia, granulocytopenia

Metabolic: hypocalcemia, hyponatremia, hypokalemia, hypomagnesemia

Musculoskeletal: muscle weakness

Respiratory: apnea

Skin: rash, urticaria, itching

Other: superinfection, fever, pain and irritation at injection site

Interactions

Drug-drug. Cephalosporins, vancomycin: increased risk of nephrotoxicity

Dimenhydrinate: masking of ototoxicity symptoms

General anesthetics, neuromuscular blockers: increased neuromuscular blockade and respiratory depression

Indomethacin: increased tobramycin trough and peak levels

Loop diuretics: increased risk of ototoxicity

Penicillins: physical incompatibility, tobramycin inactivation when mixed in same I.V. solution

Polypeptide anti-infectives: increased risk of respiratory paralysis and renal dysfunction

Drug-diagnostic tests. Alanine aminotransferase, aspartate aminotransferase, bilirubin, BUN, creatinine, lactate dehydrogenase, nonprotein nitrogen, urine protein: increased levels

Calcium, granulocytes, hemoglobin, magnesium, platelets, potassium, sodium, white blood cells: decreased levels

Patient monitoring

• Draw sample for peak drug level 1 hour after I.M. or 30 minutes after I.V. administration. Draw sample for trough level just before next dose.
• Assess liver and kidney function tests.
• Monitor CBC with white cell differential.
• Closely monitor patient's hearing.

Patient teaching

• Advise patient to report new signs or symptoms of infection.
• With inhalation form, teach patient how to use nebulizer. Instruct him to administer dose over 10 to 15 minutes by breathing normally through mouthpiece while sitting or standing. Remind him to use only the hand-held nebulizer and compressor originally dispensed with drug. Advise him to use a nose clip to help him breathe through his mouth. If he uses other inhaled drugs, instruct him to take tobramycin last.
• Teach patient proper use of eye drops. Caution him not to touch dropper to eye or any other surface.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.