Tobramycin (13 brand names, 5 dosage forms, 2 routes)
Available dosage forms: OINTMENT, SUSPENSION/DROPS, SOLUTION, POWDER, SOLUTION/DROPS.
Routes of administration: OPHTHALMIC, INHALATION.
Brand Names
- AKTOB
- BETHKIS
- KITABIS PAK
- LOTEPREDNOL ETABONATE AND TOBRAMYCIN
- TOBI
- TOBI PODHALER
- TOBRADEX
- TOBRADEX ST
- TOBRAMYCIN
- TOBRAMYCIN AND DEXAMETHASONE
- TOBRASONE
- TOBREX
- ZYLET
Boxed Warning
Patients treated with Tobramycin for injection, USP and other aminoglycosides should be under close clinical observation, because these drugs have an inherent potential for causing ototoxicity and nephrotoxicity. Neurotoxicity, manifested as both auditory and vestibular ototoxicity, can occur. The auditory changes are irreversible, are usually bilateral, and may be partial or total. Eighth-nerve impairment and nephrotoxicity may develop, primarily in patients having preexisting renal damage and in those with normal renal function to whom aminoglycosides are administered for longer periods or in higher doses than those recommended. Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching, and convulsions. The risk of aminoglycoside-induced hearing loss increases with the degree of exposure to either high peak or high trough serum concentrations. Patients who develop cochlear damage may not have symptoms during therapy to warn them of eighth-nerve toxicity, and partial or total irreversible bilateral deafness may continue to develop after the drug has been discontinued. Rarely, nephrotoxicity may not become apparent until the first few days after cessation of therapy. Aminoglycoside-induced nephrotoxicity usually is reversible. Renal and eighth-nerve function should be closely monitored in patients with known or suspected renal impairment and also in those whose renal function is initially normal but who develop signs of renal dysfunction during therapy. Peak and trough serum concentrations of aminoglycosides should be monitored periodically during therapy to assure adequate levels and to avoid potentially toxic levels. Prolonged serum concentrations above 12 mcg/mL should be avoided. Rising trough levels (above 2 mcg/mL) may indicate tissue accumulation. Such accumulation, excessive peak concentrations, advanced age, and cumulative dose may contribute to ototoxicity and nephrotoxicity (see PRECAUTIONS ). Urine should be examined for
Indications and Usage
Tobramycin is indicated for the treatment of serious bacterial infections caused by susceptible strains of the designated microorganisms in the diseases listed below: Septicemia in the neonate, child, and adult caused by P. aeruginosa, E. coli, and Klebsiella sp Lower respiratory tract infections caused by P. aeruginosa, Klebsiella sp, Enterobacter sp, Serratia sp, E. coli, and S. aureus (penicillinase and non-penicillinase-producing strains). Serious central-nervous-system infections (meningitis) caused by susceptible organisms. Intra-abdominal infections, including peritonitis, caused by E. coli, Klebsiella sp, and Enterobacter sp. Skin, bone, and skin structure infections caused by P. aeruginosa, Proteus sp, E. coli, Klebsiella sp, Enterobacter sp, and S. aureus Complicated and recurrent urinary tract infections caused by P. aeruginosa, Proteus sp, (indole-positive and indole-negative), E. coli, Klebsiella sp, Enterobacter sp, Serratia sp, S. aureus, Providencia sp, and Citrobacter sp. Aminoglycosides, including tobramycin sulphate, are not indicated in uncomplicated initial episodes of urinary tract infections unless the causative organisms are not susceptible to antibiotics having less potential toxicity. Tobramycin may be considered in serious staphylococcal infections when penicillin or other potentially less toxic drugs are contraindicated and when bacterial susceptibility testing and clinical judgment indicate its use. Bacterial cultures should be obtained prior to and during treatment to isolate and identify etiologic organisms and to test their susceptibility to tobramycin. If susceptibility tests show that the causative organisms are resistant to tobramycin, other appropriate therapy should be instituted. In patients in whom a serious life-threatening gram-negative infection is suspected, including those in whom concurrent therapy with a penicillin or cephalosporin and an aminoglycoside may be indicated, treatment with tobramycin sulphate may be initiate
Dosage and Administration
Tobramycin for injection, USP may be given intramuscularly or intravenously. Recommended dosages are the same for both routes. This insert is for a Pharmacy Bulk Package and is intended for preparing I.V. admixtures only. Dosage recommendations for intramuscular use are for informational purposes only. The patient’s pretreatment body weight should be obtained for calculation of correct dosage. It is desirable to measure both peak and trough serum concentrations (see WARNINGS box and PRECAUTIONS ). Administration for Patients with Normal Renal Function — Adults with Serious Infections: 3 mg/kg/day in 3 equal doses every 8 hours (see Table 3). Adults with Life-Threatening Infections: Up to 5 mg/kg/day may be administered in 3 or 4 equal doses (see Table 3). The dosage should be reduced to 3 mg/kg/day as soon as clinically indicated. To prevent increased toxicity due to excessive blood levels, dosage should not exceed 5 mg/kg/day unless serum levels are monitored (see WARNINGS box and PRECAUTIONS ). Table 3 DOSAGE SCHEDULE GUIDE FOR TOBRAMYCIN FOR INJECTION, USP IN ADULTS WITH NORMAL RENAL FUNCTION (Dosage at 8-Hour Intervals) For Patient Weighing Usual Dose for Serious Infections 1 mg/kg q8h (Total, 3 mg/kg/day) Maximum Dose for Life-Threatening Infections (Reduce as soon as possible) 1.66 mg/kg q8h (Total, 5 mg/kg/day) kg lb mg/dose* mL/dose* m g/dose mL/dose q8h q8h 120 264 120 mg 3 mL 200 mg 5 mL 115 253 115 mg 2.9 mL 191 mg 4.75 mL 110 242 110 mg 2.75 mL 183 mg 4.5 mL 105 231 105 mg 2.6 mL 175 mg 4.4 mL 100 220 100 mg 2.5 mL 166 mg 4.2 mL 95 209 95 mg 2.4 mL 158 mg 4 mL 90 198 90 mg 2.25 mL 150 mg 3.75 mL 85 187 85 mg 2.1 mL 141 mg 3.5 mL 80 176 80 mg 2 mL 133 mg 3.3 mL 75 165 75 mg 1.9 mL 125 mg 3.1 mL 70 154 70 mg 1.75 mL 116 mg 2.9 mL 65 143 65 mg 1.6 mL 108 mg 2.7 mL 60 132 60 mg 1.5 mL 100 mg 2.5 mL 55 121 55 mg 1.4 mL 91 mg 2.25 mL 50 110 50 mg 1.25 mL 83 mg 2.1 mL 45 99 45 mg 1.1 mL 75 mg 1.9 mL 40 88 40 mg 1 mL 66 mg 1.6 mL *Applicable to all product forms
Contraindications
A hypersensitivity to any aminoglycoside is a contraindication to the use of tobramycin. A history of hypersensitivity or serious toxic reactions to aminoglycosides may also contraindicate the use of any other aminoglycoside because of the known cross-sensitivity of patients to drugs in this class.
Adverse Reactions
Neurotoxicity — Adverse effects on both the vestibular and auditory branches of the eighth nerve have been noted, especially in patients receiving high doses or prolonged therapy, in those given previous courses of therapy with an ototoxin, and in cases of dehydration. Symptoms include dizziness, vertigo, tinnitus, roaring in the ears, and hearing loss. Hearing loss is usually irreversible and is manifested initially by diminution of high-tone acuity. Tobramycin and gentamicin sulfates closely parallel each other in regard to ototoxic potential. Nephrotoxicity — Renal function changes, as shown by rising BUN, NPN, and serum creatinine and by oliguria, cylindruria, and increased proteinuria, have been reported, especially in patients with a history of renal impairment who are treated for longer periods or with higher doses than those recommended. Adverse renal effects can occur in patients with initially normal renal function. Clinical studies and studies in experimental animals have been conducted to compare the nephrotoxic potential of tobramycin and gentamicin. In some of the clinical studies and in the animal studies, tobramycin caused nephrotoxicity significantly less frequently than gentamicin. In some other clinical studies, no significant difference in the incidence of nephrotoxicity between tobramycin and gentamicin was found. Other reported adverse reactions possibly related to tobramycin sulfate include anemia, granulocytopenia, and thrombocytopenia; and fever, rash, exfoliative dermatitis, itching, urticaria, nausea, vomiting, diarrhea, headache, lethargy, pain at the injection site, mental confusion, and disorientation. Laboratory abnormalities possibly related to tobramycin include increased serum transaminases (SGOT, SGPT); increased serum LDH and bilirubin; decreased serum calcium, magnesium, sodium, and potassium; and leukopenia, leukocytosis, and eosinophilia.
Overdosage
Signs and Symptoms —The severity of the signs and symptoms following a tobramycin overdose are dependent on the dose administered, the patient’s renal function, state of hydration, and age and whether or not other medications with similar toxicities are being administered concurrently. Toxicity may occur in patients treated more than 10 days, in adults given more than 5 mg/kg/day, children given more than 7.5 mg/kg/day, or patients with reduced renal function whose dose has not been appropriately adjusted. Nephrotoxicity following the parenteral administration of an aminoglycoside is most closely related to the area under the curve of the serum concentration versus time graph. Nephrotoxicity is more likely if trough blood concentrations fail to fall below 2 mcg/mL and is also proportional to the average blood concentration. Patients who are elderly, have abnormal renal function, are receiving other nephrotoxic drugs, or are volume depleted are at greater risk for developing acute tubular necrosis. Auditory and vestibular toxicities have been associated with aminoglycoside overdose. These toxicities occur in patients treated longer than 10 days, in patients with abnormal renal function, in dehydrated patients, or in patients receiving medications with additive auditory toxicities. These patients may not have signs or symptoms or may experience dizziness, tinnitus, vertigo, and a loss of high-tone acuity as ototoxicity progresses. Ototoxicity signs and symptoms may not begin to occur until long after the drug has been discontinued. Neuromuscular blockade or respiratory paralysis may occur following administration of many aminoglycosides. Neuromuscular blockade, respiratory failure, and prolonged respiratory paralysis may occur more commonly in patients with myasthenia gravis or Parkinson’s disease. Prolonged respiratory paralysis may also occur in patients receiving decamethonium, tubocurarine, or succinylcholine. If neuromuscular blockade occurs, it may be reversed b