Tobramycin

Pronunciation: TOE-bruh-MY-sin
Class: Antibiotic, Aminoglycoside

Trade Names

AK-Tob
- Solution 0.3%

TOBI
- Nebulizer solution 300 mg per 5 mL

Tobramycin
- Injection 10 mg/mL (as sulfate)
- Injection 40 mg/mL (as sulfate)
- Powder for injection 1.2 g (as sulfate)

Tobrex
- Solution, ophthalmic 0.3%
- Ointment, ophthalmic 0.3%

Sandoz Tobramycin (Canada)

Pharmacology

Inhibits bacterial protein synthesis, causing cell death.

Pharmacokinetics

Absorption

Injection (IM)

IM tobramycin is rapidly absorbed. C max is 4 mcg/mL (IM dose 1 mg/kg). T max is 30 to 90 min. Levels persist approximately 8 h. Therapeutic serum levels are about 4 to 6 mcg/mL. The injectable dose form is poorly absorbed in the GI tract.

Inhalation

Bioavailability varies because of individual differences in nebulizer performance and airway pathology. C max is 35 to 7414 mcg/g in sputum.

Distribution

Injection (IM)

Tobramycin can be detected in tissues and body fluids. The drug appears in low concentrations in CSF and concentrations are dose-dependent, dependent on rate of penetration, and degree of meningeal inflammation. Concentrations in the renal cortex are several times higher than usual serum levels.

Inhalation

Tobramycin is concentrated primarily in airways.

Metabolism

Injection (IM)

Little, if any, metabolic transformation occurs.

Elimination

Injection (IM)

Tobramycin is eliminated almost exclusively by glomerular filtration. In healthy renal function, up to 84% of a dose is recoverable from urine in 8 h and up to 93% in 24 h. Tobramycin t ½ is 2 h.

Onset

Inhalation

Onset of action is 10 min.

Duration

Injection (IM)

Duration of action is up to 8 h following an IM dose.

Special Populations

Renal Function Impairment
Injection (IM)

Serum concentrations are usually higher and can be measured for longer periods of time than in healthy adults. Dosage adjustment is recommended. Excretion is slow and accumulation of the drug may cause toxic blood levels.

Dialysis patients

25% to 70% of the administered dose may be removed depending on duration and type of dialysis.

Neonates

Serum concentrations are usually higher and can be measured for longer periods of time than in healthy adults. Dosage adjustment is recommended.

Indications and Usage

Treatment of serious infections caused by susceptible strains of gram-negative bacteria; treatment of serious susceptible staphylococcal infections when other, less toxic drugs are contraindicated.

Ophthalmic

Treatment of superficial ocular infections.

Inhalation

Management of cystic fibrosis patients with Pseudomonas aeruginosa .

Contraindications

Previous reactions to aminoglycosides.

Ophthalmic

Epithelial herpes simplex keratitis; vaccinia; varicella; mycobacterial infections of eye; fungal infections.

Dosage and Administration

Adults

IM / IV 3 to 5 mg/kg/day in 3 to 4 equal doses. Ophthalmic 1.25 cm ribbon of ointment twice daily to 3 times daily (every 3 to 4 h for severe infections) or 1 to 2 gtt 4 to 6 times/day (for severe infections, every h until improvement; then frequency of administration is reduced).

Children

IM / IV 6 to 7.5 mg/kg/day in 3 to 4 equally divided doses. Ophthalmic 1.25 cm ribbon of ointment twice daily to 3 times daily (every 3 to 4 h for severe infections) or 1 to 2 gtt 4 to 6 times/day (for severe infections, every h until improvement; then frequency of administration is reduced).

Premature Or Full-Term Newborns 1 wk old or younger

IM / IV Up to 4 mg/kg/day in 2 divided doses.

General Advice

  • Administer separately. Do not mix with other drugs.
  • For IV administration dilute in 50 to 100 mL of 0.9% sodium chloride injection or 5% dextrose injection. Use less diluent for children. Administer at least 20 min to 60 min.
  • Administer IM injection deep into large muscle.

Storage/Stability

Store ophthalmic preparations at room temperature away from sunlight. Do not freeze. Discard if solution is brown or cloudy or contains particles.

Drug Interactions

Depolarizing and nondepolarizing muscle relaxants

May enhance neuromuscular blocking effects. Protracted respiratory depression may occur.

Loop diuretics

May increase auditory toxicity.

Nephrotoxic drugs (eg, amphotericin B, cephalosporins, enflurane, methoxyflurane, vancomycin)

May increase risk of nephrotoxicity.

Penicillins

Penicillins, particularly carbenicillin and ticarcillin, can inactivate tobramycin in admixture, assay procedures, or patients with renal failure.

Polypeptide antibiotics

May increase risk of respiratory paralysis and renal dysfunction.

Incompatibility

Do not mix with other drugs.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Headache; fever; confusion; lethargy; disorientation; delirium.

Dermatologic

Rash; urticaria; itching; pain and irritation at injection site.

EENT

Tinnitus; vertigo; dizziness; hearing loss. With ophthalmic preparation: localized ocular toxicity and hypersensitivity; lid itching; lid swelling; conjunctival erythema.

GI

Nausea; vomiting; diarrhea.

Genitourinary

Oliguria; proteinuria; increased serum creatinine and BUN.

Hematologic

Anemia; leukopenia; leukocytosis; eosinophilia.

Metabolic

Decreased serum calcium, sodium, potassium, or magnesium; increased LFT results.

Respiratory

Apnea.

Precautions

Warnings

Renal and eight nerve function closely monitored in patients with suspected renal dysfunction. Monitor peak and trough concentration.

Dosage adjustments required in renal impairment.

Nephrotoxicity

Usually reversible.

Neurotoxicity

Manifests as both auditory and vestibular ototoxicity, and primarily occurs in patients with preexisting renal damage or with prolonged therapy. Partial or total irreversible deafness may continue to develop after drug is stopped. Other features of neurotoxicity include paresthesias, twitching, and seizures.

Teratogenic

In pregnancy.


Pregnancy

Category D (parenteral); Category B (ophthalmic).

Lactation

Undetermined.

Children

Use parenteral form cautiously in premature infants and newborns due to renal immaturity.

Burn patients

Pharmacokinetics may be altered; serum levels are important for determining appropriate dosing.

Hypomagnesemia

Occurs often, especially in those with restricted diets or who eat poorly.

Long-term therapy

Generally not indicated; greatly increases risk of toxic reactions.

Neuromuscular blockade

Potential curare-like effects may aggravate muscle weakness or cause neurotoxicity. Use drug with caution in patients with neuromuscular disorders, hypomagnesemia, hypocalcemia, or hypokalemia; with anesthesia or muscle relaxants, and in newborns whose mothers received magnesium sulfate.

Ophthalmic ointment

May retard corneal healing.

Overdosage

Symptoms

Nephrotoxicity, neuromuscular blockade, respiratory paralysis, ototoxicity. With ophthalmic preparation (topical overdose): punctate keratitis, erythema, increased lacrimation, edema, lid itching.

Patient Information

  • Instruct patient how to administer ophthalmic preparation, including need for careful handwashing.
  • Encourage patient to drink plenty of fluids while taking drug.
  • Instruct patient to notify health care provider of headache, fever, confusion, nausea, vomiting, diarrhea, rashes, itching, pain at injection site, ringing or roaring in ears, dizziness, or hearing loss.
  • Inform patient that health care provider will want follow-up blood studies and audiograms.
  • Inform patient that ophthalmic preparations may cause temporary blurring of vision or stinging and instruct patient to report excessive stinging, burning, persistent or increased pain, tearing, lid itching, swelling or redness of eyes to health care provider.
  • Instruct patient not to wear contact lenses during treatment.
  • For patient using ophthalmic solution, stress need for compliance with complete course of therapy.
  • Nebulizer solution
  • Instruct patient to take as close to 12 h apart as possible. Do not take less than 6 h apart.
  • Should be taken over a 10- to 15-min period using a hand-held PARI LC PLUS reusable nebulizer with a DeVilbiss Pulmo-Aide compressor.
  • If patient is on multiple therapies, other therapies should be taken first followed by tobramycin.
  • Inhale while sitting or standing upright and breathing normally through the mouthpiece of the nebulizer. Nose clips may help the patient breathe through the mouth.

Copyright © 2009 Wolters Kluwer Health.

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