Tobramycin Sulfate APP Uses

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What is Tobramycin Sulfate APP?

Tobramycin Sulfate APP is an aminoglycoside (ah-meen-oh-GLY-ko-side) antibiotic. Tobramycin Sulfate APP fights infections that are caused by bacteria.

Tobramycin Sulfate APP inhalation is inhaled into the lungs using a nebulizer. Tobramycin Sulfate APP inhalation is used to treat lung infections in patients with cystic fibrosis.

Tobramycin Sulfate APP inhalation is for use in adults and children who are at least 6 years old.

Tobramycin Sulfate APP inhalation may also be used for purposes not listed in this medication guide.

Tobramycin Sulfate APP indications

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To reduce the development of drug-resistant bacteria and maintain the effectiveness of Tobramycin Sulfate APP injection and other antibacterial drugs, Tobramycin Sulfate APP 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.

Tobramycin Sulfate APP injection 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 pediatric patient 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 Sulfate APP, 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 Sulfate APP 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 Sulfate APP. If susceptibility tests show that the causative organisms are resistant to Tobramycin Sulfate APP, 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 Sulfate APP sulfate may be initiated before the results of susceptibility studies are obtained. The decision to continue therapy with Tobramycin Sulfate APP should be based on the results of susceptibility studies, the severity of the infection, and the important additional concepts discussed in the WARNINGS box above.

How should I use Tobramycin Sulfate APP?

Use Tobramycin Sulfate APP ointment as directed by your doctor. Check the label on the medicine for exact dosing instructions.

Ask your health care provider any questions you may have about how to use Tobramycin Sulfate APP ointment.

Uses of Tobramycin Sulfate APP in details

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Use: Labeled Indications

Cystic fibrosis: Management of cystic fibrosis in adults and pediatric patients ≥6 years of age with Pseudomonas aeruginosa.

Limitations of use: Safety and efficacy have not been demonstrated in patients with FEV <25% or >75% predicted (Tobramycin Sulfate APP; Tobramycin Sulfate APP), or in patients colonized with Burkholderia cepacia.

Off Label Uses

Non-cystic fibrosis bronchiectasis

According to a national consensus summary and international guidelines, aerosolized Tobramycin Sulfate APP should not be used for the treatment and prevention of non-cystic fibrosis bronchiectasis. Aerosolized antibiotics may be considered in patients who have experienced 3 or more exacerbations requiring antibiotic therapy per year; organism sensitivity should be considered when choosing an antibiotic. The risk of adverse events, cost of therapy, and patient status should be considered prior to initiating aerosolized Tobramycin Sulfate APP because the efficacy of aerosolized Tobramycin Sulfate APP in the treatment of non-cystic fibrosis bronchiectasis has not been well documented.

Tobramycin Sulfate APP description

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An aminoglycoside, broad-spectrum antibiotic produced by Streptomyces tenebrarius. It is effective against gram-negative bacteria, especially the pseudomonas species. It is a 10% component of the antibiotic complex, nebramycin, produced by the same species. [PubChem]

Tobramycin Sulfate APP dosage

Tobramycin Sulfate APP Dosage

Generic name: Tobramycin Sulfate APP 300mg in 5mL

Dosage form: inhalation solution

The information at Drugs.com is not a substitute for medical advice. Always consult your doctor or pharmacist.

Dosing Information

Administration of Tobramycin Sulfate APP Inhalation Solution

Each dose of Tobramycin Sulfate APP inhalation solution is administered by oral inhalation using only the co-packaged PARI LC PLUS Reusable Nebulizer (Model No. 022B81-T) included in the Tobramycin Sulfate APP, along with a DeVilbiss Pulmo-Aide air compressor (Model No. 5650D).

Tobramycin Sulfate APP inhalation solution is not for subcutaneous, intravenous or intrathecal administration.

Prior to administration, read the Patient Information/Instructions for Use for Tobramycin Sulfate APP for detailed information on how to use Tobramycin Sulfate APP and follow the manufacturer's instructions for use and care of the DeVilbiss Pulmo-Aide air compressor.

The entire Tobramycin Sulfate APP inhalation solution treatment should take approximately 15 minutes to complete. Continue treatment until all the Tobramycin Sulfate APP inhalation solution has been delivered, and there is no longer any mist being produced.

Tobramycin Sulfate APP inhalation solution should not be diluted or mixed with other drugs including dornase alfa (Pulmozyme®) in the nebulizer. Instruct patients on multiple therapies to take their medications prior to inhaling the Tobramycin Sulfate APP inhalation solution, or as directed by their physician.

Tobramycin Sulfate APP inhalation solution should not be used if it is cloudy, if there are particles in the solution, or if it has been stored at room temperature for more than 28 days.

More about Tobramycin Sulfate APP (Tobramycin Sulfate APP)

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Tobramycin Sulfate APP interactions

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What other drugs will affect Tobramycin Sulfate APP?

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No clinical drug interaction studies have been performed with Tobramycin Sulfate APP. In clinical studies, patients receiving Tobramycin Sulfate APP continued to take dornase alfa, bronchodilators, inhaled corticosteroids, and macrolides. No clinical signs of drug interactions with these medicines were identified.

Concurrent and/or sequential use of Tobramycin Sulfate APP with other drugs with neurotoxic, nephrotoxic, or ototoxic potential should be avoided.

Some diuretics can enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue. Tobramycin Sulfate APP should not be administered concomitantly with ethacrynic acid, furosemide, urea, or intravenous mannitol. The interaction between inhaled mannitol and Tobramycin Sulfate APP has not been evaluated.

Tobramycin Sulfate APP side effects

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What are the possible side effects of Tobramycin Sulfate APP?

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Tobramycin Sulfate APP has been evaluated for safety in 425 cystic fibrosis patients exposed to at least one dose of Tobramycin Sulfate APP, including 273 patients who were exposed across three cycles (6 months) of treatment. Each cycle consisted of 28 days on-treatment (with 112 mg administered twice-daily) and 28 days off-treatment. Patients with serum creatinine ≥2 mg/dL and blood urea nitrogen (BUN) ≥40 mg/dL were excluded from clinical studies. There were 218 males and 207 females in this population, and reflecting the cystic fibrosis population in the U.S., the vast majority of patients were Caucasian. There were 221 patients ≥20 years old, 121 patients ≥13 to <20 years old, and 83 patients ≥6 to <13 years old. There were 239 patients with screening FEV1 % predicted ≥50%, 156 patients with screening FEV1 % predicted <50%, and 30 patients with missing FEV1 % predicted.

The primary safety population reflects patients from Study 1, an open-label study comparing Tobramycin Sulfate APP with Tobramycin Sulfate APP (Tobramycin Sulfate APP inhalation solution, USP) over three cycles of 4 weeks on treatment followed by 4 weeks off treatment. Randomization, in a planned 3:2 ratio, resulted in 308 patients treated with Tobramycin Sulfate APP and 209 patients treated with Tobramycin Sulfate APP. For both the Tobramycin Sulfate APP and Tobramycin Sulfate APP groups, mean exposure to medication for each cycle was 28 to 29 days. The mean age for both arms was between 25 and 26 years old. The mean baseline FEV1 % predicted for both arms was 53%.

Table 1 displays adverse drug reactions reported by at least 2% of Tobramycin Sulfate APP patients in Study 1, inclusive of all cycles (on and off treatment). Adverse drug reactions are listed according to MedDRA system organ class and sorted within system organ class group in descending order of frequency.

Table 1: Adverse Reactions Reported in Study 1 (Occurring in ≥2% of Tobramycin Sulfate APP Patients)
1This includes adverse events of pulmonary or cystic fibrosis exacerbations
Primary System Organ Class

Preferred Term

Tobramycin Sulfate APP

N=308

%

Tobramycin Sulfate APP

N=209

%

Respiratory, thoracic, and mediastinal disorders
Cough 48.4 31.1
Lung disorder1 33.8 30.1
Productive cough 18.2 19.6
Dyspnea 15.6 12.4
Oropharyngeal pain 14.0 10.5
Dysphonia 13.6 3.8
Hemoptysis 13.0 12.4
Nasal congestion 8.1 7.2
Rales 7.1 6.2
Wheezing 6.8 6.2
Chest discomfort 6.5 2.9
Throat irritation 4.5 1.9
Gastrointestinal disorders
Nausea 7.5 9.6
Vomiting 6.2 5.7
Diarrhea 4.2 1.9
Dysgeusia 3.9 0.5
Infections and infestations
Upper respiratory tract infection 6.8 8.6
Investigations
Pulmonary function test decreased 6.8 8.1
Forced expiratory volume decreased 3.9 1.0
Blood glucose increased 2.9 0.5
Vascular disorders
Epistaxis 2.6 1.9
Nervous system disorders
Headache 11.4 12.0
General disorders and administration site conditions
Pyrexia 15.6 12.4
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain 4.5 4.8
Skin and subcutaneous tissue disorders
Rash 2.3 2.4

Adverse drug reactions that occurred in <2% of patients treated with Tobramycin Sulfate APP in Study 1 were: bronchospasm (Tobramycin Sulfate APP 1.6%, Tobramycin Sulfate APP 0.5%); deafness including deafness unilateral (reported as mild to moderate hearing loss or increased hearing loss) (Tobramycin Sulfate APP 1.0%, Tobramycin Sulfate APP 0.5%); and tinnitus (Tobramycin Sulfate APP 1.9%, Tobramycin Sulfate APP 2.4%).

Discontinuations in Study 1 were higher in the Tobramycin Sulfate APP arm compared to Tobramycin Sulfate APP (27% Tobramycin Sulfate APP versus 18% Tobramycin Sulfate APP). This was driven primarily by discontinuations due to adverse events (14% Tobramycin Sulfate APP versus 8% Tobramycin Sulfate APP). Higher rates of discontinuation were seen in subjects ≥20 years old and those with baseline FEV1 % predicted <50%.

Respiratory related hospitalizations occurred in 24% of the patients in the Tobramycin Sulfate APP arm and 22% of the patients in the Tobramycin Sulfate APP arm. There was an increased new usage of antipseudomonal medication in the Tobramycin Sulfate APP arm (65% Tobramycin Sulfate APP versus 55% Tobramycin Sulfate APP). This included oral antibiotics in 55% of Tobramycin Sulfate APP patients and 40% of Tobramycin Sulfate APP patients and intravenous antibiotics in 35% of Tobramycin Sulfate APP patients and 33% of Tobramycin Sulfate APP patients. Median time to first antipseudomonal usage was 89 days in the Tobramycin Sulfate APP arm and 112 days in the Tobramycin Sulfate APP arm.

The supportive safety population reflects patients from two studies: Study 2, a double-blind, placebo-controlled design for the first treatment cycle, followed by all patients receiving Tobramycin Sulfate APP (replaced placebo) for two additional cycles, and Study 3, a double-blind, placebo-controlled trial for one treatment cycle only. Placebo in these studies was inhaled powder without the active ingredient, Tobramycin Sulfate APP. The patient population for these studies was much younger than in Study 1 (mean age 13 years old).

Adverse drug reactions reported more frequently by Tobramycin Sulfate APP patients in the placebo-controlled cycle (Cycle 1) of Study 2, which included 46 Tobramycin Sulfate APP and 49 placebo patients, were:

Respiratory, thoracic, and mediastinal disorders

Pharyngolaryngeal pain (Tobramycin Sulfate APP 10.9%, placebo 0%); dysphonia (Tobramycin Sulfate APP 4.3%, placebo 0%)

Gastrointestinal disorders

Dysgeusia (Tobramycin Sulfate APP 6.5%, placebo 2.0%)

Adverse drug reactions reported more frequently by Tobramycin Sulfate APP patients in Study 3, which included 30 Tobramycin Sulfate APP and 32 placebo patients, were:

Respiratory, thoracic, and mediastinal disorders

Cough (Tobramycin Sulfate APP 10%, placebo 0%)

Ear and labyrinth disorders

Hypoacusis (Tobramycin Sulfate APP 10%, placebo 6.3%)

Audiometric Assessment

In Study 1, audiology testing was performed in a subset of approximately 25% of Tobramycin Sulfate APP (n=78) and Tobramycin Sulfate APP (n=45) patients. Using the criteria for either ear of ≥10 dB loss at two consecutive frequencies, ≥20 dB loss at any frequency, or loss of response at three consecutive frequencies where responses were previously obtained, five Tobramycin Sulfate APP patients and three Tobramycin Sulfate APP patients were judged to have ototoxicity, a ratio similar to the planned 3:2 randomization for this study.

Audiology testing was also performed in a subset of patients in both Study 2 (n=13 from the Tobramycin Sulfate APP group and n=9 from the placebo group) and Study 3 (n=14 from the Tobramycin Sulfate APP group and n=11 from the placebo group). In Study 2, no patients reported hearing complaints but two Tobramycin Sulfate APP patients met the criteria for ototoxicity. In Study 3, three Tobramycin Sulfate APP and two placebo patients had reports of ‘hypoacusis.’ One Tobramycin Sulfate APP and two placebo patients met the criteria for ototoxicity. In some patients, ototoxicity was transient or may have been related to a conductive defect.

Cough

Cough is a common symptom in cystic fibrosis, reported in 42% of the patients in Study 1 at baseline. Cough was the most frequently reported adverse event in Study 1 and was more common in the Tobramycin Sulfate APP arm (48% Tobramycin Sulfate APP versus 31 % Tobramycin Sulfate APP). There was a higher rate of cough adverse event reporting during the first week of active treatment with Tobramycin Sulfate APP (i.e., the first week of Cycle 1). The time to first cough event in the Tobramycin Sulfate APP and Tobramycin Sulfate APP groups were similar thereafter. In some patients, cough resulted in discontinuation of Tobramycin Sulfate APP treatment. Sixteen patients (5%) receiving treatment with Tobramycin Sulfate APP discontinued study treatment due to cough events compared with 2 (1%) in the Tobramycin Sulfate APP treatment group. Children and adolescents coughed more than adults when treated with Tobramycin Sulfate APP, yet the adults were more likely to discontinue: of the 16 patients on Tobramycin Sulfate APP in Study 1 who discontinued treatment due to cough events, 14 were ≥20 years of age, one patient was between the ages of 13 and <20, and one was between the ages of 6 and <13. The rates of bronchospasm (as measured by ≥20% decrease in FEV1 % predicted post-dose) were approximately 5% in both treatment groups, and none of these patients experienced concomitant cough.

In Study 2, cough was the most commonly reported adverse event during the first cycle of treatment (the double blind period of treatment) and occurred more frequently in placebo-treated patients (26.5%) than patients treated with Tobramycin Sulfate APP (13%). Similar percentages of patients in both treatment groups reported cough as a baseline symptom. In Study 3, cough events were reported by three patients in the Tobramycin Sulfate APP group (10%) and none in the placebo group (0%).

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of Tobramycin Sulfate APP. Because these reactions are 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.

Respiratory, thoracic, and mediastinal disorders

Aphonia, Sputum discolored

General disorders and administration site conditions

Malaise

Tobramycin Sulfate APP contraindications

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What is the most important information I should know about Tobramycin Sulfate APP?

A hypersensitivity to any aminoglycoside is a contraindication to the use of Tobramycin Sulfate APP. 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.

Active ingredient matches for Tobramycin Sulfate APP:

Tobramycin in United States.


List of Tobramycin Sulfate APP substitutes (brand and generic names)

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Unit description / dosage (Manufacturer)Price, USD
Tobran 40 mg Injection (Redson Pharmaceuticals)$ 0.53
TOBRANEG Injection / 80mg / 2ml units (Elder Pharmaceuticals Pvt Ltd)$ 0.72
TOBRANEG Injection / 20ml / 2ml units (Elder Pharmaceuticals Pvt Ltd)$ 0.34
TOBRANEG Injection / 60mg / 1.5ml units (Elder Pharmaceuticals Pvt Ltd)$ 0.60
Tobraneg 20mg/2mL VIAL / 1 (Elder Pharmaceuticals Pvt Ltd)$ 0.48
Tobraneg 60mg/1.5mL VIAL / 1 (Elder Pharmaceuticals Pvt Ltd)$ 0.66
Tobraneg 80mg/2mL VIAL / 1 (Elder Pharmaceuticals Pvt Ltd)$ 0.80
20 mg x 2 mL x 1's (Elder Pharmaceuticals Pvt Ltd)$ 0.48
60 mg x 1.5 mL x 1's (Elder Pharmaceuticals Pvt Ltd)$ 0.66
80 mg x 2 mL x 1's (Elder Pharmaceuticals Pvt Ltd)$ 0.80
Tobraneg 80 mg Injection (Elder Pharmaceuticals Pvt Ltd)$ 0.84
Tobraneg 20 mg Injection (Elder Pharmaceuticals Pvt Ltd)$ 0.28
Tobraneg 60 mg Injection (Elder Pharmaceuticals Pvt Ltd)$ 0.60
TOBRANEG 20MG INJECTION 1 vial / 2 ML injection each (Elder Pharmaceuticals Pvt Ltd)$ 0.49
TOBRANEG 20MG INJECTION 1 vial / 2 ML injection each (Elder Pharmaceuticals Pvt Ltd)$ 0.49
TOBRANEG 60MG INJECTION 1 vial / 1 ML injection each (Elder Pharmaceuticals Pvt Ltd)$ 0.69
TOBRANEG 80MG INJECTION 1 vial / 2 ML injection each (Elder Pharmaceuticals Pvt Ltd)$ 0.87
TOBRANEG inj 20 mg x 2 mL x 2ml (Elder Pharmaceuticals Pvt Ltd)$ 0.48
TOBRANEG inj 60 mg x 1.5 mL x 1.5ml (Elder Pharmaceuticals Pvt Ltd)$ 0.72
TOBRANEG inj 80 mg x 2 mL x 2ml (Elder Pharmaceuticals Pvt Ltd)$ 0.87
Tobraneg 20mg Injection (Elder Pharmaceuticals Pvt Ltd)$ 0.25
Tobraneg 60mg Injection (Elder Pharmaceuticals Pvt Ltd)$ 0.69
Tobraneg 80mg Injection (Elder Pharmaceuticals Pvt Ltd)$ 0.41
TOBRANEG 10MG INJECTION 1 vial / 2 ML injection each (Eli Lilly and Company India Pvt Ltd)$ 0.69
TOBRANEG 60MG INJECTION 1 vial / 1 ML injection each (Eli Lilly and Company India Pvt Ltd)$ 0.48
TOBRANEG 60MG INJECTION 1 vial / 2 ML injection each (Eli Lilly and Company India Pvt Ltd)$ 0.52
TOBRANEG 80MG INJECTION 1 vial / 2 ML injection each (Eli Lilly and Company India Pvt Ltd)$ 0.83
TOBRAPIC EYE DROP 1 packet / 10 ML eye drop each (PCI Pharmaceuticals)$ 0.12

References

  1. DailyMed. "TOBRAMYCIN SULFATE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
  2. PubChem. "tobramycin". https://pubchem.ncbi.nlm.nih.gov/com... (accessed September 17, 2018).
  3. DrugBank. "tobramycin". http://www.drugbank.ca/drugs/DB00684 (accessed September 17, 2018).

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