Tobramycin
Solution · Ophthalmic, Intravenous, Respiratory (inhalation)
Uses
Tobramycin for Injection, is an aminoglycoside antibacterial indicated for the treatment of serious bacterial infections caused by susceptible isolates of the designated bacteria in the diseases listed below ( 1.1 ): Septicemia in the pediatric patient and adults caused by P. aeruginosa , E. coli , and Klebsiella species (spp). Lower respiratory tract infections caused by P. aeruginosa, Klebsiella spp, Enterobacter spp, Serratia spp, E. coli, and S. aureus Serious central nervous system infections (meningitis) caused by susceptible organisms. Intra-abdominal infections, including peritonitis, caused by E. coli, Klebsiella spp., and Enterobacter spp. Skin, bone, and skin structure infections caused by P. aeruginosa, Proteus spp, E. coli, Klebsiella spp., Enterobacter spp., and S. aureus. Complicated urinary tract infections caused by P. aeruginosa , Proteus spp., (indole-positive and indole-negative), E. coli , Klebsiella spp., Enterobacter spp., Serratia spp., S. aureus , Providencia spp., and Citrobacter spp. To reduce the development of drug-resistant bacteria and maintain the effectiveness of Tobramycin for Injection and other antibacterial drugs, Tobramycin for Injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria ( 1.2 ). 1.1 Septicemia Tobramycin for Injection is indicated for the treatment of septicemia caused by susceptible isolates of P. aeruginosa, E. coli, and Klebsiella spp., in adult and pediatric patients. 1.2 Lower Respiratory Tract Infections Tobramycin for Injection is indicated for the treatment of lower respiratory tract infections caused by susceptible isolates of P. aeruginosa, Klebsiella spp., Enterobacter spp., Serratia spp., E. coli, and S. aureus in adult and pediatric patients. 1.3 Central Nervous System Infections (Meningitis) Tobramycin for Injection is indicated for the treatment of bacterial meningitis caused by susceptible bacteria in adult and pediatric patients. 1.4 Intra-abdominal Infections Tobramycin for Injection is indicated for the treatment of intra-abdominal infections, including peritonitis, caused by susceptible isolates of E. coli, Klebsiella spp., and Enterobacter spp. in adult and pediatric patients. 1.5 Skin and Skin Structure Infections Tobramycin for Injection is indicated for the treatment of skin and skin structure infections caused by susceptible isolates of P. aeruginosa, Proteus spp., E. coli, Klebsiella spp., Enterobacter spp., and S. aureus in adult and pediatric patients. 1.6 Bone Infections Tobramycin for Injection is indicated for the treatment of bone infections caused by susceptible isolates of P. aeruginosa, Proteus spp., E. coli, Klebsiella spp., Enterobacter spp., and S. aureus in adult and pediatric patients 1.7 Complicated and Recurrent Urinary Tract Infections Tobramycin for Injection is indicated for the treatment of complicated urinary tract infections caused by susceptible isolates of P. aeruginosa, Proteus spp., (indole-positive and indole-negative), E. coli, Klebsiella spp., Enterobacter spp., Serratia spp., S. aureus, Providencia spp., and Citrobacter spp. in adult and pediatric patients 1.8 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of Tobramycin for Injection and other antibacterial drugs, Tobramycin for Injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Dosage and administration
2 DOSAGE AND ADMINISTRATION PHARMACY BULK PACKAGE-Not for Direct Infusion: Dispense single doses to many patients in a pharmacy admixture program. Pharmacy bulk package vial must be reconstituted and diluted prior to intravenous administration ( 2.1 , 2.8 ) Recommended adult dosages are as follows: Serious Infections: Administer 3 mg/kg/day in 3 equal doses (i.e. 1 mg/kg every 8 hours) Life-threatening Infections: Administer up to 5 mg/kg in 3 or 4 equal doses See full prescribing information for the recommended dosage for pediatric patients ( 2.3 ), patients with cystic fibrosis ( 2.5 ), patients with renal impairment ( 2.6 ), and obese patients ( 2.7 ). 2.1 Important Preparation and Administration Instructions Pharmacy Bulk Package-Not for Direct Infusion Tobramycin for Injection Pharmacy Bulk Package is intended for dispensing of single doses to many patients in a hospital pharmacy admixture service. It should only be prepared in an aseptic work area, such as a laminar flow hood. Tobramycin for Injection Pharmacy Bulk Package vial must be reconstituted and diluted prior to intravenous administration [see Dosage and Administration ( 2.8 )] . After reconstitution, the closure may be penetrated only one time using a suitable sterile transfer device or dispensing set, which allows measured dispensing of the contents. Use of a syringe and needle is not recommended as it may cause leakage. After penetration, the entire contents of the bulk vial must be dispensed within 24 hours. Do not administer Tobramycin for Injection as a direct, undiluted intravenous injection. 2.2 Dosage for Adult Patients with Normal Renal Function Tobramycin for Injection may be given intramuscularly or intravenously. Recommended dosages are the same for both routes. The recommended dosage is as follows: Adult Patients Adults with Serious Infections 3 mg/kg/day administered in 3 equal doses of 1 mg/kg every 8 hours. Adults with Life-Threatening Infections Up to 5 mg/kg/day may be administered in 3 or 4 equal doses (see Table 1 ). The dosage should be reduced to 3 mg/kg/day as soon as clinically indicated. To prevent increased toxicity due to excessive serum concentrations, dosage should not exceed 5 mg/kg/day unless serum concentrations are monitored [see Boxed Warning , Warnings and Precautions ( 5.2 )]. Table 1 DOSAGE SCHEDULE GUIDE FOR ADULTS WITH NORMAL RENAL FUNCTION (Dosage at 8-Hour Intervals) For Patient Weighing Usual Dose for Serious Infections 1 mg/kg Every 8 hours (h) kg lb (Total, 3 mg/kg/day) mg/dose mL/dose* q8h 120 264 120 mg 3 mL 115 253 115 mg 2.9 mL 110 242 110 mg 2.75 mL 105 231 105 mg 2.6 mL 100 220 100 mg 2.5 mL 95 209 95 mg 2.4 mL 90 198 90 mg 2.25 mL 85 187 85 mg 2.1 mL 80 176 80 mg 2 mL 75 165 75 mg 1.9 mL 70 154 70 mg 1.75 mL 65 143 65 mg 1.6 mL 60 132 60 mg 1.5 mL 55 121 55 mg 1.4 mL 50 110 50 mg 1.25 mL 45 99 45 mg 1.1 mL 40 88 40 mg 1 mL *Applicable to all product forms except the Tobramycin Injection, USP, (Pediatric). For Patient Weighing Maximum Dose for Life- Threatening Infections (Reduce as soon as possible) 1.66 mg/kg Every 8 hours kg lb (Total, 5 mg/kg/day) mg/dose mL/dose* Every 8h 120 264 200 mg 5 mL 115 253 191 mg 4.75 mL 110 242 183 mg 4.5 mL 105 231 175 mg 4.4 mL 100 220 166 mg 4.2 mL 95 209 158 mg 4 mL 90 198 150 mg 3.75 mL 85 187 141 mg 3.5 mL 80 176 133 mg 3.3 mL 75 165 125 mg 3.1 mL 70 154 116 mg 2.9 mL 65 143 108 mg 2.7 mL 60 132 100 mg 2.5 mL 55 121 91 mg 2.25 mL 50 110 83 mg 2.1 mL 45 99 75 mg 1.9 mL 40 88 66 mg 1.6 mL 2.3 Dosage for Pediatric Patients Pediatric Patients (Greater than 1 Week of Age): 6 to 7.5 mg/kg/day administered in 3 or 4 equally divided doses (2 to 2.5 mg/kg every 8 hours or 1.5 to 1.9 mg/kg every 6 hours). Premature or Full-Term Neonates (1 Week of Age or Less): Up to 4 mg/kg/day may be administered in 2 equal doses every 12 hours. 2.4 Duration of Treatment for Adult and Pediatric Patients The usual duration of treatment for adult and pediatric patients is 7 to10 days. A longer course of therapy may be necessary in complicated infections. In such cases, monitoring of renal, auditory, and vestibular functions is advised, because neurotoxicity is more likely to occur when treatment is extended longer than 10 days. 2.5 Dosage in Patients with Cystic Fibrosis or Burns In patients with cystic fibrosis, altered pharmacokinetics may result in reduced serum concentrations of aminoglycosides. An initial dosing regimen of 10 mg/kg/day in 4 equally divided doses is suggested as a guide. The serum concentrations of tobramycin should be monitored during treatment due to wide inter-patient variability. Similarly, altered pharmacokinetics may result in reduced serum concentrations in patients with extensive burns. Monitoring tobramycin serum concentration in these patients is especially important as a basis for determination of appropriate dosage [see Dosage and Administration ( 2.9 )] . 2.6 Dosage for Patients with Renal Impairment Following a loading dose of 1 mg/kg, subsequent dosage in these patients must be adjusted, either with reduced doses administered at 8-hour intervals or with normal doses given at prolonged intervals. Both of these methods are suggested as guides and dose should be adjusted based on serum concentration. The dosage adjustment for patients with renal impairment are based on either the creatinine clearance level or the serum creatinine level of the patient because these values correlate with the half-life of tobramycin. The dosage schedule derived from either method should be used in conjunction with careful clinical and laboratory observations of the patient and serum tobramycin concentration monitoring and should be modified as necessary. Neither method should be used when dialysis is being performed.
Dosage forms and strengths
Tobramycin for Injection, USP is supplied as a sterile dry powder in a pharmacy bulk package vial containing tobramycin sulfate equivalent to 1.2 g of tobramycin. The contents of the vial should be diluted with 30 mL of Sterile Water for Injection, USP, to provide a solution containing 40 mg of tobramycin per mL. Tobramycin for Injection, USP is supplied as a dry powder in a bulk package vial. Reconstitute the contents of the vial with 30 mL of Sterile Water for Injection, USP, to provide a solution containing 40 mg of tobramycin per mL ( 3 ).
Contraindications
Tobramycin for Injection is contraindicated in patients with a history of hypersensitivity to tobramycin or any other aminoglycoside [see Warnings and Precautions ( 5.4 )] . A history of hypersensitivity or serious toxic reactions to any aminoglycoside ( 4 ).
Warnings and precautions
Nephrotoxicity and ototoxicity: See Boxed Warning ( 5.1 , 5.2 ) Allergic Reactions: anaphylaxis, exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, and Stevens-Johnson Syndrome have been reported in patients on Tobramycin for Injection therapy. If an allergic reaction occurs, discontinue the drug and institute appropriate therapy ( 5.4 ) Neuromuscular Blockade: Respiratory paralysis can occur at high doses or with concurrent use of neuromuscular blocking agents. If neuromuscular blockade occurs, consider administration of calcium salts but mechanical assistance may be necessary. ( 5.5 ) Clostridioides difficile -associated diarrhea (CDAD): Evaluate patients if diarrhea occurs. ( 5.6 ) 5.1 Nephrotoxicity Systemic exposure to Tobramycin for Injection and other aminoglycosides can cause nephrotoxicity, primarily manifested as acute tubular necrosis. Signs of nephrotoxicity include rising blood urea nitrogen (BUN) and creatinine (Cr), decreased urinary output, and sodium, potassium, bicarbonate, magnesium, phosphate and calcium urinary losses. Aminoglycoside-induced nephrotoxicity may occur during therapy but may not become apparent until the first few days after cessation of therapy and usually is reversible. The risk for nephrotoxicity increases with tobramycin accumulation (indicated by rising trough levels above 2 mcg/mL), excessive peak concentrations (above 12 mcg/mL), total cumulative dose, advanced age, volume depletion, concurrent or sequential use of other nephrotoxic drugs and in patients with diabetes. Monitor serum tobramycin concentrations in all patients and avoid peak levels above 12 mcg/mL and trough levels above 2 mcg/mL [see Dosage and Administration ( 2.9 )] . Monitor renal function, serum electrolytes, potassium, sodium, magnesium, calcium and phosphate, urine output and urinalysis during therapy in all patients. Reduce the dose or discontinue treatment if renal impairment occurs. 5.2 Ototoxicity Ototoxicity with use of Tobramycin for Injection Tobramycin for Injection can cause both auditory and vestibular eighth nerve damage. The auditory changes are irreversible, are usually bilateral, and may be partial or total. Symptoms of ototoxicity can include dizziness, vertigo, tinnitus, roaring in the ears and hearing loss. Ototoxicity symptoms may manifest during therapy or after tobramycin has been discontinued. The risk of ototoxicity increases with higher peak and trough serum tobramycin concentrations, in patients who receive high doses or prolonged or prior treatment with tobramycin or other aminoglycosides, in patients with renal impairment, patients receiving with other nephrotoxic or ototoxic drugs and in the extremes of age. To decrease the risk of ototoxicity, use as short a duration of therapy as clinically appropriate, adequately hydrate patients, limit the use of other ototoxic drugs, and closely monitor tobramycin concentrations during therapy [see Dosage and Administration ( 2.9 )] . Monitor patients for signs and symptoms of auditory or vestibular toxicity and consider serial audiograms in high-risk patients. Discontinue tobramycin in patients with evidence of auditory or vestibular toxicity. Risk of Ototoxicity Due to Mitochondrial DNA Variants Cases of ototoxicity with aminoglycosides have been observed in patients with certain variants in the mitochondrially encoded 12S rRNA gene (MT-RNR1) , particularly the m.1555A>G variant. Ototoxicity occurred in some patients even when their aminoglycoside serum levels were within the recommended range. Mitochondrial DNA variants are present in less than 1% of the general US population, and the proportion of the variant carriers who may develop ototoxicity as well as the severity of ototoxicity is unknown. In case of known maternal history of ototoxicity due to aminoglycoside use or a known mitochondrial DNA variant in the patient, consider alternative treatments other than aminoglycosides unless the increased risk of permanent hearing loss is outweighed by the severity of infection and lack of safe and effective alternative therapies. 5.3 Embryo-Fetal Toxicity Aminoglycosides, including Tobramycin for Injection, can cause fetal harm when administered to a pregnant woman. Aminoglycosides cross the placenta. Streptomycin, another aminoglycoside, has been associated with several reports of total, irreversible, bilateral congenital deafness in pediatric patients whose mothers received streptomycin during pregnancy. Apprise patients of potential hazard to the fetus if Tobramycin for Injection is used during pregnancy or if the patient becomes pregnant while taking Tobramycin for Injection [see Use in Specific Populations ( 8.1 )] . 5.4 Allergic Reactions Serious and fatal allergic reactions including anaphylaxis and dermatologic reactions including exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, and Stevens-Johnson Syndrome have been reported in patients on tobramycin therapy [see Contraindications ( 4 ) and Adverse Reactions ( 6 )]. If an allergic reaction occurs, discontinue Tobramycin for Injection and institute appropriate therapy. A history of hypersensitivity to other aminoglycosides is a contraindication to the use of Tobramycin for Injection, because cross-allergenicity among aminoglycosides has been demonstrated [see Contraindications ( 4 )] . 5.5 Neuromuscular Blockade and Other Neurologic Adverse Reactions Neuromuscular blockade with respiratory paralysis and respiratory failure may occur following administration of aminoglycosides. Neuromuscular blockade, respiratory failure, and prolonged respiratory paralysis may occur more commonly and be more severe in patients with myasthenia gravis or Parkinson's disease and in patients concomitantly receiving neuromuscular blocking agents such as succinylcholine.
Side effects
The following serious adverse reactions are described below and elsewhere in the labeling: Nephrotoxicity [see Boxed Warning and Warnings and Precautions ( 5.1 )] Ototoxicity [see Boxed Warning and Warnings and Precautions ( 5.2 )] Embryo-Fetal Toxicity [see Boxed Warning and Warnings and Precautions ( 5.3 )] Allergic Reactions [see Warnings and Precautions ( 5.4 )] Neuromuscular Blockade [see Warnings and Precautions ( 5.5 )] The following adverse reactions associated with the use of Tobramycin for Injection were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and Lymphatic System Disorders: anemia, granulocytopenia, leukopenia, leukocytosis, eosinophilia and thrombocytopenia Ear and Labyrinth Disorders: Tinnitus, hearing loss, vertigo Gastrointestinal Disorders: nausea, vomiting, diarrhea General Disorders and Administration Site Conditions: fever, lethargy, pain at the injection site Immune system disorders: Anaphylaxis, hypersensitivity reactions Laboratory Investigations: elevated blood urea nitrogen, elevated serum creatinine, hyponatremia, hypokalemia, hypomagnesemia, hypocalcemia, hypophosphatemia, urinary casts, increased serum transaminases (AST, ALT); increased serum LDH and bilirubin Nervous System Disorders: headache, numbness, paresthesia, muscle twitching, convulsions, mental confusion, and disorientation Skin and Subcutaneous Tissue Disorders: rash, itching, urticaria Most common adverse reactions are ototoxicity and nephrotoxicity. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Drug interactions
7.1 Drugs with Nephrotoxic or Ototoxic Potential Avoid concurrent and/or sequential use of Tobramycin for Injection with other drugs with nephrotoxic and/or ototoxic potential. 7.2 Diuretics Some diuretics can enhance aminoglycoside toxicity by altering concentrations in serum and tissue and causing dehydration. Monitor serum concentrations, renal function, serum electrolytes, sodium, magnesium, calcium and phosphate, urine output and urinalysis, and signs of auditory or vestibular toxicity in patients concomitantly administered diuretics. 7.3 Drugs with Neuromuscular Blockade or Neurotoxic Potential Prolonged respiratory paralysis may occur in patients concomitantly receiving neuromuscular blocking agents with Tobramycin for Injection [see Boxed Warning , Warnings and Precautions ( 5.5 )] . If neuromuscular blockade occurs, it may be reversed by the administration of calcium salts but mechanical assistance may be necessary. In addition, avoid concurrent and/or sequential use of Tobramycin for Injection with other neurotoxic drugs.
Use in specific populations
8.1 Pregnancy Risk Summary Aminoglycosides, including Tobramycin for Injection, can cause fetal harm when administered to a pregnant woman. Published literature reports that use of streptomycin, an aminoglycoside, can cause total, irreversible, bilateral congenital deafness when administered to a pregnant woman [see Warnings and Precautions ( 5.3 )]. In animal reproduction studies with subcutaneous administration of tobramycin in pregnant rats and rabbits during organogenesis, there were no adverse developmental outcomes at doses up to 3.2 times and 1.3 times the maximum recommended clinical dose based on body surface area; however, ototoxicity was not evaluated in the offspring from these studies (see Data ). Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20% respectively. Data Animal Data Subcutaneous administration of tobramycin at doses of up to 100 mg/kg/day (rat) or 20 mg/kg/day (rabbit) during organogenesis was not associated with adverse developmental outcomes. These doses are 3.2 and 1.3 times the maximum recommended clinical daily dose of 5 mg/kg based on body surface area. Doses of tobramycin ≥40 mg/kg/day were maternally toxic to rabbits and precluded the evaluation of adverse developmental outcomes. Ototoxicity was not evaluated in offspring during nonclinical reproductive toxicity studies with tobramycin. 8.2 Lactation Risk Summary Limited published data with Tobramycin for Injection in lactating women indicate that tobramycin is present in human milk. There are no data on the effects of Tobramycin for Injection on milk production. Tobramycin may cause alteration in the intestinal flora of the breastfeeding infant. Advise a woman to monitor the breastfed infant for loose or bloody stools and candidiasis (thrush, diaper rash). The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Tobramycin for Injection and any potential adverse effects on the breastfed infant from Tobramycin for Injection or from the underlying maternal condition. 8.4 Pediatric Use Use Tobramycin for Injection with caution in premature infants and neonates because of their renal immaturity and the resulting prolongation of serum half-life. For pediatric dosing information [see Dosage and Administration ( 2.3 )]. Similar to adults, monitor renal function and serum tobramycin concentrations in pediatric patients receiving Tobramycin for Injection. 8.5 Geriatric Use Elderly patients may be at a higher risk of developing nephrotoxicity and ototoxicity while receiving Tobramycin for Injection [see Warnings and Precautions ( 5.1 )]. Tobramycin is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function and serum tobramycin levels [see Dosage and Administration ( 2.6 ) and Warnings and Precautions ( 5.1 )]. 8.6 Patients with Renal Impairment The dosage schedule of Tobramycin for Injection should be adjusted according to the degree of renal impairment and serum concentration [see Dosage and Administration ( 2.6 )]. In patients undergoing hemodialysis, 25% to 70% of the administered dose may be removed, depending on the duration and type of dialysis.
Pregnancy
8.1 Pregnancy Risk Summary Aminoglycosides, including Tobramycin for Injection, can cause fetal harm when administered to a pregnant woman. Published literature reports that use of streptomycin, an aminoglycoside, can cause total, irreversible, bilateral congenital deafness when administered to a pregnant woman [see Warnings and Precautions ( 5.3 )]. In animal reproduction studies with subcutaneous administration of tobramycin in pregnant rats and rabbits during organogenesis, there were no adverse developmental outcomes at doses up to 3.2 times and 1.3 times the maximum recommended clinical dose based on body surface area; however, ototoxicity was not evaluated in the offspring from these studies (see Data ). Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20% respectively. Data Animal Data Subcutaneous administration of tobramycin at doses of up to 100 mg/kg/day (rat) or 20 mg/kg/day (rabbit) during organogenesis was not associated with adverse developmental outcomes. These doses are 3.2 and 1.3 times the maximum recommended clinical daily dose of 5 mg/kg based on body surface area. Doses of tobramycin ≥40 mg/kg/day were maternally toxic to rabbits and precluded the evaluation of adverse developmental outcomes. Ototoxicity was not evaluated in offspring during nonclinical reproductive toxicity studies with tobramycin.
Pediatric use
8.4 Pediatric Use Use Tobramycin for Injection with caution in premature infants and neonates because of their renal immaturity and the resulting prolongation of serum half-life. For pediatric dosing information [see Dosage and Administration ( 2.3 )]. Similar to adults, monitor renal function and serum tobramycin concentrations in pediatric patients receiving Tobramycin for Injection.
Geriatric use
8.5 Geriatric Use Elderly patients may be at a higher risk of developing nephrotoxicity and ototoxicity while receiving Tobramycin for Injection [see Warnings and Precautions ( 5.1 )]. Tobramycin is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function and serum tobramycin levels [see Dosage and Administration ( 2.6 ) and Warnings and Precautions ( 5.1 )].
Overdosage
10.1 Signs and Symptoms Acute overdosage with Tobramycin for Injection can result in more severe manifestations of the types of toxicities known to occur with recommended doses, e.g., renal damage, ototoxicity, neuromuscular blockade. 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, age and whether or not other medications with similar toxicities are being administered concurrently. [see Warnings and Precautions ( 5.1 , 5.2 , 5.5 )] for signs and symptoms related to neurotoxicity, nephrotoxicity and neuromuscular blockade; and Adverse Reactions ( 6 )]. If tobramycin were ingested, toxicity would be less likely because aminoglycosides are minimally absorbed from an intact gastrointestinal tract. 10.2 Treatment In all cases of suspected overdosage with Tobramycin for Injection, call your Regional Poison Control Center or the National Poison Control center at 1-800-222-1222 or www.poison.org to obtain the most up-to-date information about the treatment of overdose. This recommendation is made because, in general, information regarding the treatment of overdosage may change more rapidly than the package insert. Management of Tobramycin for Injection overdosage is symptomatic and supportive. Maintain airway, provide adequate hydration and monitor renal function, serum electrolytes, and tobramycin concentrations until the serum tobramycin level falls below 2 mcg/mL. Tobramycin is removed by hemodialysis.
Description
Tobramycin sulfate, a water-soluble aminoglycoside antibacterial, drug derived from the actinomycete Streptomyces tenebrarius. Tobramycin for Injection, USP is supplied as a sterile powder in a pharmacy bulk package vial for intravenous use. It is intended for reconstitution with 30 mL of Sterile Water for Injection, USP. Each vial contains tobramycin sulfate equivalent to 1.2 g of tobramycin. After reconstitution, the solution will contain 40 mg of tobramycin per mL. The product contains no preservative or sodium bisulfite. Tobramycin sulfate is O-3-amino-3-deoxy-α-D-glucopyranosyl-(1→4)-O-[2,6-diamino-2,3,6-trideoxy-α-D-ribo-hexopyranosyl-(1→6)]-2-deoxy-L-streptamine, sulfate (2:5)(salt) and has the molecular formula (C 18 H 37 N 5 O 9 ) 2
• 5H 2 SO 4 . The molecular weight is 1425.42 g/mol. The molecular weight of the free base is 467.51 g/mol. The structural formula of tobramycin, free base, is as follows: Figure 2: Tobramycin Structure Figure 2: Tobramycin Structure
Mechanism of action
12.1 Mechanism of Action Tobramycin sulfate is an aminoglycoside antibacterial drug [see Microbiology ( 12.4 )].
How supplied
16.1 How Supplied Tobramycin for Injection, USP is supplied as a sterile dry powder containing tobramycin sulfate equivalent to 1.2 g tobramycin in a 50 mL Pharmacy Bulk Package Vial packaged in trays of 6. Product Code Unit of Sale Strength Each NP300351 NDC 63323-303-55 Unit of 6 1.2 g in 50 mL NDC 63323-303-21 50 mL Pharmacy Bulk Package Vial Vial stoppers do not contain natural rubber latex. 16.2 Storage and Handling Prior to reconstitution, the vial should be stored at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature]. After reconstitution, the solution should be kept in a refrigerator and used within 96 hours. If kept at room temperature, the solution must be used within 24 hours [see Dosage and Administration ( 2.1 , 2.8 )] . 16.1 How Supplied Tobramycin for Injection, USP is supplied as a sterile dry powder containing tobramycin sulfate equivalent to 1.2 g tobramycin in a 50 mL Pharmacy Bulk Package Vial packaged in trays of 6. Product Code Unit of Sale Strength Each NP300351 NDC 63323-303-55 Unit of 6 1.2 g in 50 mL NDC 63323-303-21 50 mL Pharmacy Bulk Package Vial Vial stoppers do not contain natural rubber latex.
Storage
16.2 Storage and Handling Prior to reconstitution, the vial should be stored at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature]. After reconstitution, the solution should be kept in a refrigerator and used within 96 hours. If kept at room temperature, the solution must be used within 24 hours [see Dosage and Administration ( 2.1 , 2.8 )] .
Patient information
Serious Allergic Reactions Advise patients that serious allergic reactions could occur with Tobramycin for Injection. Advise patients to report fever, swelling, difficulty breathing, wheezing, decrease blood pressure or dizziness, or skin rash. If an allergic reaction occurs, discontinue the drug and institute appropriate therapy immediately. Impairment of Kidney Function Advise patients that Tobramycin for Injection may cause impairment in kidney function and that periodic blood draws are required to monitor kidney function and tobramycin drug levels. Hearing Loss and Impaired Balance Advise patients that Tobramycin for Injection may cause serious and irreversible hearing loss and impaired balance. Advise patients to report hearing loss, ringing or roaring in the ears, dizziness or imbalance. Antibacterial Resistance Counsel patients that antibacterial drugs, including Tobramycin for Injection should be used to treat bacterial infections only. They do not treat viral infections (e.g., the common cold). When Tobramycin for Injection is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be administered exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Tobramycin for Injection or other antibacterial drugs in the future. Diarrhea Counsel patients that diarrhea is a common problem caused by antibacterials, and it usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as 2 or more months after having taken their last dose of the antibacterial. If this occurs, patients should contact their physician as soon as possible. Embryofetal Toxicity Advise pregnant women that aminoglycosides, including Tobramycin for Injection, can cause irreversible congenital deafness when administered to a pregnant woman [see Warnings and Precautions ( 5.3 ) and Use in Specific Populations ( 8.1 )]. Lactation Advise a woman to monitor their breastfed infants for diarrhea and/or bloody stools [see Use in Specific Populations ( 8.2 )]. Novaplus is a registered trademark of Vizient, Inc. Manufactured by: Fresenius Kabi Lake Zurich, IL 60047 www.fresenius-kabi.com/us 451027D Novaplus Logo
Label text from the FDA structured product label by Fresenius Kabi USA, LLC (revised Feb 7, 2024). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Tobramycin in 39 products
- Tobramycin Sulfate in 17 products
Tobramycin NDC products (56)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 50090-4190 | Tobramycin 3 mg/mL Solution/ Drops | A-S Medication Solutions | ANDA |
| 50090-2127 | Tobramycin 3 mg/mL Solution | A-S Medication Solutions | ANDA |
| 80425-0341 | Tobramycin 3 mg/mL Solution | Advanced Rx Pharmacy of Tennessee, LLC | ANDA |
| 60687-731 | Tobramycin 300 mg/5mL Solution | American Health Packaging | ANDA |
| 65162-914 | Tobramycin 300 mg/5mL Solution | Amneal Pharmaceuticals LLC | ANDA |
| 67877-678 | Tobramycin 300 mg/5mL Solution | Ascend Laboratories, LLC | ANDA |
| 76420-092 | Tobramycin 3 mg/mL Solution/ Drops | Asclemed USA, Inc. | ANDA |
| 76420-791 | Tobramycin 3 mg/mL Solution | Asclemed USA, Inc. | ANDA |
| 59651-129 | Tobramycin 300 mg/5mL Solution | Aurobindo Pharma Limited | ANDA |
| 24208-290 | Tobramycin 3 mg/mL Solution | Bausch & Lomb Incorporated | ANDA |
| 36000-244 | Tobramycin Sulfate 40 mg/mL Injection | Baxter Healthcare Corporation | ANDA |
| 36000-242 | Tobramycin Sulfate 40 mg/mL Injection | Baxter Healthcare Corporation | ANDA |
| 62250-110 | Tobramycin 3 mg/mL Solution/ Drops | Belcher Pharmaceuticals, LLC | ANDA |
| 61919-642 | Tobramycin 3 mg/mL Solution/ Drops | DirectRX | ANDA |
| 55150-470 | Tobramycin Sulfate 1.2 g/30mL Injection, Powder, Lyophilized, For Solution | Eugia US LLC | ANDA |
| 72266-163 | Tobramycin Sulfate 1.2 g/30mL Injection, Powder, Lyophilized, For Solution | Fosun Pharma USA Inc | ANDA |
| 63323-305 | Tobramycin Sulfate 10 mg/mL Injection, Solution | Fresenius Kabi USA, LLC | ANDA |
| 63323-306 | Tobramycin Sulfate 40 mg/mL Injection, Solution | Fresenius Kabi USA, LLC | ANDA |
| 68083-374 | Tobramycin 3 mg/mL Solution/ Drops | Gland Pharma Limited | ANDA |
| 68083-312 | Tobramycin Sulfate 1.2 g/30mL Injection, Powder, Lyophilized, For Solution | Gland Pharma Limited | ANDA |
| 68083-254 | Tobramycin Sulfate 40 mg/mL Injection | Gland Pharma Limited | ANDA |
| 68083-253 | Tobramycin Sulfate 10 mg/mL Injection | Gland Pharma Limited | ANDA |
| 68083-241 | Tobramycin Sulfate 40 mg/mL Injection | Gland Pharma Limited | ANDA |
| 0409-3578 | Tobramycin Sulfate 40 mg/mL Injection, Solution | Hospira, Inc. | ANDA |
| 86211-110 | Tobramycin 3 mg/mL Solution/ Drops | JVET PHARMACEUTICALS LLC | ANDA |
| 70756-617 | Tobramycin 300 mg/4mL Solution | Lifestar Pharma LLC | ANDA |
| 70756-604 | Tobramycin 300 mg/5mL Solution | Lifestar Pharma LLC | ANDA |
| 68180-962 | Tobramycin 300 mg/5mL Solution | Lupin Pharmaceuticals, Inc. | ANDA |
| 42571-408 | Tobramycin 300 mg/5mL Inhalant | Micro Labs Limited | ANDA |
| 67457-473 | Tobramycin Sulfate 40 mg/mL Injection | Mylan Institutional LLC | ANDA |
| 67457-428 | Tobramycin Sulfate 40 mg/mL Injection | Mylan Institutional LLC | ANDA |
| 72603-160 | Tobramycin Sulfate 1.2 g/30mL Injection, Powder, Lyophilized, For Solution | Northstar Rx LLC | ANDA |
| 72603-430 | Tobramycin 300 mg/5mL Solution | NorthStar RxLLC | ANDA |
| 72603-630 | Tobramycin 300 mg/4mL Solution | NorthStar RxLLC | ANDA |
| 66267-936 | Tobramycin 3 mg/mL Solution | NuCare Pharmaceuticals,Inc. | ANDA |
| 68071-2272 | Tobramycin 3 mg/mL Solution/ Drops | NuCare Pharmaceuticals,Inc. | ANDA |
| 68788-4149 | Tobramycin 3 mg/mL Solution | Preferred Pharmaceuticals Inc. | ANDA |
| 68788-7252 | Tobramycin 3 mg/mL Solution/ Drops | Preferred Pharmaceuticals Inc. | ANDA |
| 63187-902 | Tobramycin 3 mg/mL Solution/ Drops | Proficient Rx LP | ANDA |
| 71205-101 | Tobramycin 3 mg/mL Solution/ Drops | Proficient Rx LP | ANDA |
| 63187-973 | Tobramycin 3 mg/mL Solution | Proficient Rx LP | ANDA |
| 63187-024 | Tobramycin 3 mg/mL Solution | Proficient Rx LP | ANDA |
| 70518-1370 | Tobramycin 3 mg/mL Solution/ Drops | REMEDYREPACK INC. | ANDA |
| 76204-029 | Tobramycin 300 mg/5mL Solution | Ritedose Pharmaceuticals, LLC | ANDA |
| 61314-643 | Tobramycin 3 mg/mL Solution | Sandoz Inc | ANDA |
| 70436-110 | Tobramycin 1200 mg/30mL Injection, Powder, For Solution | Slate Run Pharmaceuticals, LLC | ANDA |
| 70069-131 | Tobramycin 3 mg/mL Solution/ Drops | Somerset Therapeutics, LLC | ANDA |
| 85766-025 | Tobramycin 3 mg/mL Solution | Sportpharm LLC | ANDA |
| 85766-189 | Tobramycin 3 mg/mL Solution/ Drops | Sportpharm LLC | ANDA |
| 60760-583 | Tobramycin 3 mg/mL Solution/ Drops | St. Mary's Medical Park Pharmacy | ANDA |
| 47335-171 | Tobramycin 300 mg/5mL Solution | Sun Pharmaceutical Industries, Inc. | ANDA |
| 0093-4085 | Tobramycin 300 mg/5mL Solution | Teva Pharmaceuticals USA, Inc. | ANDA |
| 39822-0412 | Tobramycin Sulfate 1.2 g/30mL Injection, Powder, Lyophilized, For Solution | XGen Pharmaceuticals DJB, Inc. | ANDA |
| 70700-173 | Tobramycin Sulfate 1.2 g/30mL Injection, Powder, Lyophilized, For Solution | Xiromed LLC | ANDA |
| 63323-303 | Tobramycin Sulfate 1200 mg/30mL Injection, Powder, For Solution | Fresenius Kabi USA, LLC | NDA |
| 70644-899 | Tobramycin 300 mg/5mL Solution | Genericus, Inc. | NDA AUTHORIZED GENERIC |
Tobramycin recalls
- D-0385-2024 Mar 20, 2024 · Class II · Terminated
Failed Stability Specification: Water determination was found not complying with specification.
Frequently asked questions
What is Tobramycin used for?
Tobramycin for Injection, is an aminoglycoside antibacterial indicated for the treatment of serious bacterial infections caused by susceptible isolates of the designated bacteria in the diseases listed below ( 1.1 ): Septicemia in the pediatric patient and adults caused by P. aeruginosa , E. coli , and Klebsiella species (spp). Lower respiratory tract infections caused by P. aeruginosa,…
What are the side effects of Tobramycin?
The following serious adverse reactions are described below and elsewhere in the labeling: Nephrotoxicity [see Boxed Warning and Warnings and Precautions ( 5.1 )] Ototoxicity [see Boxed Warning and Warnings and Precautions ( 5.2 )] Embryo-Fetal Toxicity [see Boxed Warning and Warnings and Precautions ( 5.3 )] Allergic Reactions [see Warnings and Precautions ( 5.4 )] Neuromuscular Blockade [see… See the full label for the complete list.
Who makes Tobramycin?
Tobramycin is listed by 38 labelers in the FDA NDC directory, including A-S Medication Solutions, Advanced Rx Pharmacy of Tennessee, LLC, American Health Packaging, Amneal Pharmaceuticals LLC.
Has Tobramycin been recalled?
The FDA enforcement database lists 1 recall for Tobramycin, most recently D-0385-2024 (class ii): Failed Stability Specification: Water determination was found not complying with specification.