Yes

Antibiotic, Aminoglycoside; Antibiotic, Ophthalmic

Treatment of documented or suspected infections caused by susceptible gram-negative bacilli including Pseudomonas aeruginosa; topically used to treat superficial ophthalmic infections caused by susceptible bacteria. Tobramycin solution for inhalation is indicated for the management of cystic fibrosis patients (>6 years of age) with Pseudomonas aeruginosa.

C

Hypersensitivity to tobramycin or other aminoglycosides or components

Use with caution in patients with renal impairment; pre-existing auditory or vestibular impairment; and in patients with neuromuscular disorders; dosage modification required in patients with impaired renal function; (I.M. & I.V.) Aminoglycosides are associated with significant nephrotoxicity or ototoxicity; the ototoxicity is directly proportional to the amount of drug given and the duration of treatment; tinnitus or vertigo are indications of vestibular injury; ototoxicity is often irreversible; renal damage is usually reversible

1% to 10%:

Renal: Nephrotoxicity

Neuromuscular & skeletal: Neurotoxicity (neuromuscular blockade)

Otic: Ototoxicity (auditory), ototoxicity (vestibular)

<1%: Hypotension, drug fever, headache, drowsiness, rash, nausea, vomiting, eosinophilia, anemia, paresthesia, tremor, arthralgia, weakness, lacrimation, itching eyes, edema of the eyelid, keratitis, dyspnea

Symptoms of overdose include ototoxicity, nephrotoxicity, and neuromuscular toxicity

The treatment of choice following a single acute overdose appears to be the maintenance of good urine output of at least 3 mL/kg/hour. Dialysis is of questionable value in the enhancement of aminoglycoside elimination. If required, hemodialysis is preferred over peritoneal dialysis in patients with normal renal function. Careful hydration may be all that is required to promote diuresis and therefore the enhancement of the drug's elimination.

Increased effect: Extended spectrum penicillins (synergistic)

Increased toxicity:

Neuromuscular blockers increase neuromuscular blockade

Amphotericin B, cephalosporins, loop diuretics, and vancomycin may increase risk of nephrotoxicity

Tobramycin is stable at room temperature both as the clear, colorless solution and as the dry powder; reconstituted solutions remain stable for 24 hours at room temperature and 96 hours when refrigerated

Stability of parenteral admixture at room temperature (25°C) and at refrigeration temperature (4°C): 48 hours

Standard diluent: Dose/100 mL NS

Minimum volume: 50 mL NS

Incompatible with penicillins

Interferes with bacterial protein synthesis by binding to 30S and 50S ribosomal subunits resulting in a defective bacterial cell membrane

Absorption: I.M.: Rapid and complete

Time to peak serum concentration: I.M.: Within 30-60 minutes; I.V.: Within 30 minutes

Distribution: To extracellular fluid including serum, abscesses, ascitic, pericardial, pleural, synovial, lymphatic, and peritoneal fluids; crosses the placenta; poor penetration into CSF, eye, bone, prostate

V_d: 0.2-0.3 L/kg; Pediatric patients: 0.2-0.7 L/kg

Protein binding: <30%

Half-life:

Neonates: less than or equal to 1200 g: 11 hours; >1200 g: 2-9 hours

Adults: 2-3 hours, directly dependent upon glomerular filtration rate

Adults with impaired renal function: 5-70 hours

Elimination: With normal renal function, about 90% to 95% of a dose is excreted in the urine within 24 hours

Individualization is critical because of the low therapeutic index

In morbid obesity, dosage requirement may best be estimated using a dosing weight of IBW + 0.4 (TBW - IBW)

Initial and periodic peak and trough plasma drug levels should be determined, particularly in critically ill patients with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery). Two to three serum level measurements should be obtained after the initial dose to measure the half-life in order to determine the frequency of subsequent doses.

Once daily dosing: Higher peak serum drug concentration to MIC ratios, demonstrated aminoglycoside postantibiotic effect, decreased renal cortex drug uptake, and improved cost-time efficiency are supportive reasons for the use of once daily dosing regimens for aminoglycosides. Current research indicates these regimens to be as effective for nonlife-threatening infections, with no higher incidence of nephrotoxicity, than those requiring multiple daily doses. Doses are determined by calculating the entire day's dose via usual multiple dose calculation techniques and administering this quantity as a single dose. Doses are then adjusted to maintain mean serum concentrations above the MIC(s) of the causative organism(s). (Example: 2.5-5 mg/kg as a single dose; expected Cp_max: 10-20 mcg/mL and Cp_min: <1 mcg/mL). Further research is needed for universal recommendation in all patient populations and gram-negative disease; exceptions may include those with known high clearance (eg, children, patients with cystic fibrosis, or burns who may require shorter dosage intervals) and patients with renal function impairment for whom longer than conventional dosage intervals are usually required.

Some clinicians suggest a daily dose of 4-7 mg/kg for all patients with normal renal function. This dose is at least as efficacious with similar, if not less, toxicity than conventional dosing.

Infants and Children <5 years: I.M., I.V.: 2.5 mg/kg/dose every 8 hours

Children >5 years: 1.5-2.5 mg/kg/dose every 8 hours

Note: Some patients may require larger or more frequent doses if serum levels document the need (ie, cystic fibrosis or febrile granulocytopenic patients).

Adults: I.M., I.V.:

Severe life-threatening infections: 2-2.5 mg/kg/dose

Urinary tract infection: 1.5 mg/kg/dose

Synergy (for gram-positive infections): 1 mg/kg/dose

Children and Adults: Ophthalmic: Instill 1-2 drops of solution every 4 hours; apply ointment 2-3 times/day; for severe infections apply ointment every 3-4 hours, or solution 2 drops every 30-60 minutes initially, then reduce to less frequent intervals

Inhalation:

Standard aerosolized tobramycin:

Children: 40-80 mg 2-3 times/day

Adults: 60-80 mg 3 times/day

High-dose regimen: Children greater than or equal to 6 years and Adults: 300 mg every 12 hours (do not administer doses less than 6 hours apart); administer in repeated cycles of 28 days on drug followed by 28 days off drug

Dosing interval in renal impairment:

Cl_cr greater than or equal to 60 mL/minute: Administer every 8 hours

Cl_cr 40-60 mL/minute: Administer every 12 hours

Cl_cr 20-40 mL/minute: Administer every 24 hours

Cl_cr 10-20 mL/minute: Administer every 48 hours

Cl_cr <10 mL/minute: Administer every 72 hours

Hemodialysis: Dialyzable; 30% removal of aminoglycosides occurs during 4 hours of HD - administer dose after dialysis and follow levels

Continuous arteriovenous or venovenous hemofiltration (CAVH/CAVHD): Dose as for Cl_cr of 10-40 mL/minute and follow levels

Administration in CAPD fluid:

Gram-negative infection: 4-8 mg/L (4-8 mcg/mL) of CAPD fluid

Gram-positive infection (ie, synergy): 3-4 mg/L (3-4 mcg/mL) of CAPD fluid

Administration IVPB/I.M.: Dose as for Cl_cr <10 mL/minute and follow levels

Dosing adjustment/comments in hepatic disease: Monitor plasma concentrations

Calcium, magnesium, potassium: Renal wasting may cause hypocalcemia, hypomagnesemia, and/or hypokalemia

Urinalysis, urine output, BUN, serum creatinine, peak and trough plasma tobramycin levels; be alert to ototoxicity; hearing should be tested before and during treatment

Timing of serum samples: Draw peak 30 minutes after 30-minute infusion has been completed or 1 hour following I.M. injection or beginning of infusion; draw trough immediately before next dose

Therapeutic levels:

Peak:

Serious infections: 6-8 mg/mL (SI: 12-17 mg/L)

Life-threatening infections: 8-10 mg/mL (SI: 17-21 mg/L)

Urinary tract infections: 4-6 mg/mL (SI: 7-12 mg/L)

Synergy against gram-positive organisms: 3-5 mg/mL

Trough:

Serious infections: 0.5-1 mg/mL

Life-threatening infections: 1-2 mg/mL

Monitor serum creatinine and urine output; obtain drug levels after the third dose unless otherwise directed

May cause drowsiness

None reported

No information available to require special precautions

No effects or complications reported

Systemic: Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). Report decreased urine output, swelling of extremities, difficulty breathing, vaginal itching or discharge, rash, diarrhea, oral thrush, unhealed wounds, dizziness, change in hearing acuity or ringing in ears, or worsening of condition. Pregnancy precautions: Inform prescriber if you are pregnant.

Ophthalmic: Use as frequently as recommended; do not overuse. Sit down, tilt head back, instill solution or drops inside lower eyelid, and roll eyeball in all directions. Close eye and apply gentle pressure to inner corner of eye for 30 seconds. Do not touch tip of applicator to eye or any contaminated surface. May experience temporary stinging or blurred vision. Do not use any other eye preparation for 10 minutes. Inform prescriber if condition worsens or does not improve in 3-4 days.

Eye solutions: Allow 5 minutes between application of "multiple-drop" therapy; obtain drug levels after the third dose; peak levels are drawn 30 minutes after the end of a 30-minute infusion or 1 hour after initiation of infusion or I.M. injection; the trough is drawn just before the next dose; administer penicillins or cephalosporins at least 1 hour apart from tobramycin

Injection, as sulfate (Nebcin®): 10 mg/mL (2 mL); 40 mg/mL (1.5 mL, 2 mL)

Ointment, ophthalmic (Tobrex®): 0.3% (3.5 g)

Powder for injection (Nebcin®): 40 mg/mL (1.2 g vials)

Solution, inhalation (TOBI™): 60 mg/mL (5 mL)

Solution, ophthalmic: 0.3% (5 mL)

AKTob®, Tobrex®: 0.3% (5 mL)

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