Tobramycin

Tobramycin
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

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Overview

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Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

• Tobramycin is an antibacterial aminoglycoside indicated for the management of cystic fibrosis patients with Pseudomonas aeruginosa.

Dosing Information

• The recommended dosage for patients six years of age and older is to administer one single-use ampule (300 mg/4 mL) twice daily by oral inhalation in repeated cycles of 28 days on drug, followed by 28 days off drug. The doses should be taken as close to 12 hours apart as possible and not less than 6 hours apart.
• The 300 mg/4 mL dose of BETHKIS is the same for patients regardless of age or weight. BETHKIS has not been studied in patients less than six years old.

Administration

• BETHKIS is administered by oral inhalation. Do not use by any other route.
• BETHKIS is administered by inhalation using a hand‑held PARI LC PLUS Reusable Nebulizer with a PARI Vios Air compressor over an approximately 15 minute period and until sputtering from the output of the nebulizer has occurred for at least one minute.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Condition1

• Developed by:

• Class of Recommendation:

• Strength of Evidence:

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Tobramycin in adult patients.

Non–Guideline-Supported Use

Condition1

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Tobramycin in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Condition1

• Dosing Information

• Dosage

Condition2

There is limited information regarding FDA-Labeled Use of Tobramycin in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

Condition1

• Developed by:

• Class of Recommendation:

• Strength of Evidence:

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Tobramycin in pediatric patients.

Non–Guideline-Supported Use

Condition1

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Tobramycin in pediatric patients.

Contraindications

BETHKIS is contraindicated in patients with a known hypersensitivity to any aminoglycoside.

Warnings

Ototoxicity

• Caution should be exercised when prescribing BETHKIS to patients with known or suspected auditory or vestibular dysfunction.
• Findings related to ototoxicity as measured by audiometric evaluations and auditory adverse event reports were similar between BETHKIS and placebo in controlled clinical trials.
• Hearing loss was reported in two (1.1%) BETHKIS-treated patients and in one (0.9%) placebo-treated patient during clinical studies. Additionally, dizziness and vertigo, both of which may be manifestations of vestibular forms of ototoxicity, were observed in similar numbers of BETHKIS- and placebo-treated patients.
• Dizziness occurred in two (1.1%) BETHKIS-treated patients and one (0.9%) placebo-treated patient and vertigo occurred in two (1.1%) BETHKIS‑treated patients versus no placebo patients in clinical studies.
• None of the BETHKIS patients discontinued their therapy due to hearing loss, dizziness or vertigo.
• Tinnitus may be a sentinel symptom of ototoxicity. No reports of tinnitus occurred in patients during clinical studies with BETHKIS, but because it has been observed with inhaled tobramycin solutions, onset of this symptom warrants caution.
• Ototoxicity, manifested as both auditory and vestibular toxicity, has been reported with parenteral aminoglycosides. Vestibular toxicity may be manifested by vertigo, ataxia or dizziness.

Nephrotoxicity

• Caution should be exercised when prescribing BETHKIS to patients with known or suspected renal dysfunction.
• Nephrotoxicity was not seen during BETHKIS clinical studies but has been associated with aminoglycosides as a class. If nephrotoxicity occurs in a patient receiving BETHKIS, therapy should be discontinued until serum concentrations fall below 2 mcg/mL.
• Twenty-six (14%) BETHKIS patients and 15 (13%) placebo patients had increases in serum creatinine of at least 50% over baseline. Follow-up values were obtained for 17 of the 26 BETHKIS patients, all of which decreased to serum creatinine values that were within the upper limit of normal.
• Patients who experience an increase in serum creatinine during treatment with BETHKIS should have their renal function closely monitored.

Neuromuscular Disorders

• BETHKIS should be used cautiously in patients with muscular disorders, such as myasthenia gravis or Parkinson’s disease, since aminoglycosides may aggravate muscle weakness because of a potential curare-like effect on neuromuscular function.

Bronchospasm

• Bronchospasm can occur with inhalation of tobramycin. In clinical studies with BETHKIS, bronchospasm was observed in one (0.5%) BETHKIS-treated patient and in no placebo-treated patients.
• Wheezing occurred in ten (5%) BETHKIS-treated patients and four (4%) placebo-treated patients. Bronchospasm and wheezing should be treated as medically appropriate.

Laboratory Tests

Audiograms

• Clinical studies of inhaled tobramycin solutions did not identify hearing loss using audiometric tests which evaluated hearing up to 8000 Hz.
• Physicians should consider an audiogram for patients who show any evidence of auditory dysfunction, or who are at increased risk for auditory dysfunction.Tinnitus may be a sentinel symptom of ototoxicity, and therefore the onset of this symptom warrants caution.

Serum Concentrations

• In patients with normal renal function treated with BETHKIS, serum tobramycin concentrations range from approximately 0.06-1.89 mcg/mL one hour after dose administration and do not require routine monitoring.
• Serum concentrations of tobramycin in patients with renal dysfunction or patients treated with concomitant parenteral tobramycin should be monitored at the discretion of the treating physician.

Renal Function

• The clinical studies of BETHKIS did not reveal any imbalance in the percentage of patients who experienced at least a 50% rise in serum creatinine from baseline in either the BETHKIS group (n=26, 14%) or the placebo group (n=15, 13%).
• Laboratory tests of urine and renal function should be conducted at the discretion of the treating physician.

Use in Pregnancy

• Aminoglycosides can cause fetal harm when administered to a pregnant woman. * Aminoglycosides cross the placenta, and streptomycin has been associated with several reports of total irreversible, bilateral congenital deafness in pediatric patients exposed in utero. Patients who use BETHKIS during pregnancy, or become pregnant while taking BETHKIS should be apprised of the potential hazard to the fetus.

Adverse Reactions

Clinical Trials Experience

Clinical Trials Experience

• Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of drugs cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
• The data described below reflect exposure to BETHKIS in two placebo-controlled studies in 305 cystic fibrosis patients. Patients receiving BETHKIS ranged in age from 6 to 31 years.
• In Study 1, an eight week study, 29 patients received BETHKIS versus 30 patients who received placebo for a total of four weeks on drug and four weeks off drug.
• All patients were ≤ 30 years of age (mean age 12.6 years) and 46% were females. 52.5% of patients were 6 to 12 years of age while 30.5% of patients were 13-17 years old. Only 16.5% of patients were adults (> 17 years old).
• Eighty percent (80%) of patients were chronically colonized with Pseudomonas aeruginosa while 20.3% of patients were initially or intermittently colonized with Pseudomonas aeruginosa during the study.
• More patients in the placebo group discontinued/dropped out of Study 1 than in the BETHKIS group (23% [7/30] vs 3.4% [1/29], respectively). Five patients in the placebo group compared to none in the BETHKIS group discontinued/dropped out because of treatment-emergent adverse events (TEAEs) such as pulmonary exacerbations and respiratory disorders.
• In Study 2, a 24 week study, 161 patients received BETHKIS versus 85 patients who received placebo in alternating four week on-off cycles for three cycles.
• All patients were ≤ 46 years of age (mean age 14.8 years) and 45% were females. 41% of patients were 6-12 years old while 29% of patients were 13-17 years old. Only 30% were adults (>17 years).
• Eighty-seven percent (87%) of patients were chronically colonized with P. aeruginosa. Only 13% were either initially or intermittently colonized with P. aeruginosa during the study.
• More patients in the placebo group discontinued/dropped out of Study 2 than in the BETHKIS group (9.4% [8/85] vs 4.3% [7/161], respectively). Of these, 3 patients in the BETHKIS group (1.9%) compared to 2 patients in the placebo group (2.4%) withdrew due to a TEAE.
• The most common TEAEs causing patients to discontinue from the study drug are respiratory, thoracic, and mediastinal disorders.
• The most common adverse experiences reported were respiratory disorders, consistent with the underlying disease in the patient population being evaluated and these were similarly distributed between both BETHKIS- and placebo-treated patients.
• The following adverse reactions were more commonly reported in ≥ 2% of the BETHKIS-treated patients compared to the placebo-treated patients: decreased forced expiratory volume, rales, red blood cell sedimentation rate increased, and dysphonia (Table 1).

This image is provided by the National Library of Medicine.

This image is provided by the National Library of Medicine.

Postmarketing Experience

• In postmarketing experience, some patients receiving inhaled tobramycin have reported hearing loss. Some of these reports occurred in patients with previous or concomitant treatment with systemic aminoglycosides. Patients with hearing loss frequently reported tinnitus.
• 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.

Drug Interactions

• Drug

• Description

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

• Pregnancy Category

Pregnancy Category (AUS):

• Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Tobramycin in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Tobramycin during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Tobramycin with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Tobramycin with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Tobramycin with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Tobramycin with respect to specific gender populations.

Race

There is no FDA guidance on the use of Tobramycin with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Tobramycin in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Tobramycin in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Tobramycin in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Tobramycin in patients who are immunocompromised.

Administration and Monitoring

Administration

• Oral

• Intravenous

Monitoring

There is limited information regarding Monitoring of Tobramycin in the drug label.

• Description

IV Compatibility

There is limited information regarding IV Compatibility of Tobramycin in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

• Description

Management

• Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Tobramycin in the drug label.

Pharmacology

There is limited information regarding Tobramycin Pharmacology in the drug label.

Mechanism of Action

Structure

This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Tobramycin in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Tobramycin in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Tobramycin in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Tobramycin in the drug label.

How Supplied

Storage

There is limited information regarding Tobramycin Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Tobramycin in the drug label.

Precautions with Alcohol

• Alcohol-Tobramycin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

• ®

Look-Alike Drug Names

• A® — B®

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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