Tobramycin
From DrugPedia: A Wikipedia for Drug discovery
Pronouncation: (TOE-bruh-MY-sin)
Class: Antibiotic, Aminoglycoside
Trade Names:
AK-Tob
- Solution 0.3%
Trade Names:
TOBI
- Nebulizer solution 300 mg per 5 mL
Trade Names:
Tobramycin
- Injection 10 mg/mL (as sulfate)
- Injection 40ߙmg/mL (as sulfate)
- Powder for injection 1.2 g (as sulfate)
Trade Names:
Tobrex
- Solution, ophthalmic 0.3%
- Ointment, ophthalmic 0.3%
PMS-Tobramycin (Canada)
Scheinpharm Tobramycin (Canada)
Contents |
[edit] Pharmacology
Inhibits bacterial protein synthesis, causing cell death.
[edit] Pharmacokinetics
Absorption
Injection (IM)
IM tobramycin is rapidly absorbed. C max is 4 mcg/mL (IM dose 1ߙmg/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.
[edit] 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.
[edit] Contraindications
Previous reactions to aminoglycosides.
Ophthalmic
Epithelial herpes simplex keratitis; vaccinia; varicella; mycobacterial infections of eye; fungal infections.
[edit] Dosage and Administration
Adults
IM/IV 3 to 5 mg/kg/day in 3 to 4ߙequal 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 1ߙwk 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 100ߙmL 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.
[edit] Storage/Stability
Store ophthalmic preparations at room temperature away from sunlight. Do not freeze. Discard if solution is brown or cloudy or contains particles.
[edit] 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.
[edit] 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.
[edit] 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.
[edit] Overdosage
Symptoms
Nephrotoxicity, neuromuscular blockade, respiratory paralysis, ototoxicity. With ophthalmic preparation (topical overdose): punctate keratitis, erythema, increased lacrimation, edema, lid itching.
[edit] 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 12ߙh apart as possible. Do not take less than 6ߙh 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.
