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Tobramycin (Oral Inhalation)

Pronunciation

Pronunciation

(toe bra MYE sin)

Index Terms

  • Tobramycin Sulfate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Inhalation:

Tobi Podhaler: 28 mg

Nebulization Solution, Inhalation:

Tobramycin Pak: 300 mg/5 mL (5 mL [DSC]) [contains sodium chloride, sodium hydroxide, sulfuric acid]

Generic: 300 mg/5 mL (5 mL)

Nebulization Solution, Inhalation [preservative free]:

Bethkis: 300 mg/4 mL (4 mL)

Kitabis Pak: 300 mg/5 mL (5 mL)

Tobi: 300 mg/5 mL (5 mL)

Generic: 300 mg/5 mL (5 mL)

Brand Names: U.S.

  • Bethkis
  • Kitabis Pak
  • Tobi
  • Tobi Podhaler
  • Tobramycin Pak [DSC]

Pharmacologic Category

  • Antibiotic, Aminoglycoside

Pharmacology

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

Absorption

Inhalation: Peak serum concentrations:

Solution for inhalation: ~1 mcg/mL following a 300 mg dose

Powder for inhalation: ~1 mcg/mL (range: 0.49 to 1.55 mcg/mL) following a 112 mg dose

Distribution

Powder for inhalation: Vd (central compartment) for a typical cystic fibrosis patient: 85.1 L

Time to Peak

Serum: Powder for inhalation: 60 minutes

Half-Life Elimination

Solution for inhalation: 4.4 hours

Powder for inhalation: ~3 hours (after a single 112 mg dose)

Use: Labeled Indications

Management of cystic fibrosis patients with Pseudomonas aeruginosa.

Contraindications

Hypersensitivity to tobramycin, other aminoglycosides, or any component of the formulation

Dosing: Adult

Cystic fibrosis: Inhalation:

Bethkis, Kitabis Pak, Tobi: 300 mg every 12 hours (do not administer doses <6 hours apart); administer in repeated cycles of 28 days on drug followed by 28 days off drug.

Tobi Podhaler: 112 mg (4 x 28 mg capsules) every 12 hours (do not administer doses <6 hours apart); administer in repeated cycles of 28 days on drug followed by 28 days off drug.

Non-cystic fibrosis bronchiectasis (off-label use): Note: Use may be considered in patients who have ≥3 exacerbations requiring antibiotic therapy per year; generally given in addition to oral or IV antimicrobials. Inhalation for nebulization:

Acute exacerbation: 80 mg twice daily; Note: Dose prepared from preservative-free tobramycin injection solution (Le 2010)

Suppression: 160 mg or 300 mg twice daily. Note: 160 mg dose prepared from preservative-free tobramycin injection solution (Pasteur 2010)

Dosing: Pediatric

Cystic fibrosis: Children ≥6 years and Adolescents: Inhalation: Refer to adult dosing.

Non-cystic fibrosis bronchiectasis (off-label use): Children and Adolescents: Refer to adult dosing.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment

No dosage adjustment necessary; does not undergo hepatic metabolism.

Administration

Inhalation:

Bethkis, Kitabis Pak, Tobi: To be inhaled over ~15 minutes using a handheld reusable nebulizer (PARI-LC PLUS) with a PARI Vios air compressor (Bethkis) or a DeVilbiss Pulmo-Aide air compressor (Kitabis Pak, Tobi). If multiple different nebulizer treatments are required, administer bronchodilator first, followed by chest physiotherapy, any other nebulized medications, and then tobramycin last. Do not mix with other nebulizer medications.

Tobi Podhaler: Capsules should be administered by oral inhalation via Podhaler device following manufacturer recommendations for use and handling. Capsules should be removed from the blister packaging immediately prior to use and should not be swallowed. Patients requiring bronchodilator therapy should administer the bronchodilator 15 to 90 minutes prior to Tobi Podhaler. The sequence of chest physiotherapy and additional inhaled therapies is at the discretion of the healthcare provider; however, Tobi Podhaler should always be administered last. The Canadian labeling recommends that patients requiring bronchodilator therapy should administer the bronchodilator 15 to 90 minutes prior to administering Tobi Podhaler.

Storage

Powder, for inhalation (Tobi Podhaler): Store in original package at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture.

Solution, for inhalation (Bethkis, Kitabis Pak, Tobi): Store under refrigeration at 2°C to 8°C (36°F to 46°F). May be stored in foil pouch (opened or unopened) at room temperature of 25°C (77°F) for up to 28 days. Protect from light. The colorless to pale yellow solution may darken over time if not stored under refrigeration; however, the color change does not affect product quality. Do not use if solution has been stored at room temperature for >28 days.

Drug Interactions

Loop Diuretics: May enhance the nephrotoxic effect of Tobramycin (Oral Inhalation). Loop Diuretics may enhance the ototoxic effect of Tobramycin (Oral Inhalation). Monitor therapy

Mannitol (Systemic): May enhance the nephrotoxic effect of Tobramycin (Oral Inhalation). Avoid combination

Adverse Reactions

>10%:

Central nervous system: Voice disorder (4% to 14%), headache (11% to 12%)

Respiratory: Cough (powder: 10% to 48%, solution: 31%), rhinitis (solution: 11% to 35%), pulmonary disease (30% to 34%; includes pulmonary or cystic fibrosis exacerbations), reduced forced expiratory volume (solution: 1% to 31%, powder: 4%), discoloration of sputum (21%), productive cough (18% to 20%), rales (solution: 6% to 19%, powder: 7%), dyspnea (12% to 16%), decreased lung function (7% to 16%), oropharyngeal pain (11% to 14%), hemoptysis (12% to 13%), pharyngolaryngeal pain (powder: 11%, solution: 3%)

Miscellaneous: Fever (12% to 16%)

1% to 10%:

Cardiovascular: Chest discomfort (3% to 7%)

Central nervous system: Malaise (6%)

Dermatologic: Skin rash (2%)

Endocrine: Increased serum glucose (powder: 3%, solution: <1%)

Gastrointestinal: Nausea (8% to 10%), dysgeusia (powder: 4% to 7%, solution: <1%), vomiting (6%), diarrhea (2% to 4%)

Hematologic & oncologic: Increased erythrocyte sedimentation rate (solution: 8%), eosinophilia (solution: 2%), increased serum immunoglobulins (solution: 2%)

Neuromuscular & skeletal: Musculoskeletal chest pain (<1% to 5%), myalgia (solution: ≤5%)

Otic: Hypoacusis (powder: 10%), tinnitus (2% to 3%), deafness (≤1%; including unilateral deafness, reported as mild to moderate hearing loss or increased hearing loss)

Respiratory: Upper respiratory tract infection (7% to 9%), nasal congestion (7% to 8%), wheezing (5% to 7%), throat irritation (2% to 5%), bronchospasm (≤1% to 5%), laryngitis (solution: ≤5%) bronchitis (solution: 3%), epistaxis (2% to 3%), tonsillitis (solution: 2%)

<1% (Limited to important or life-threatening): Aphonia, decreased appetite, hypersensitivity reaction, increased bronchial secretions, pneumonitis, pruritus, pulmonary congestion

Warnings/Precautions

Concerns related to adverse effects:

• Bronchospasm: Bronchospasm may occur; bronchospasm or wheezing should be treated appropriately if either arise. Safety and efficacy have not been demonstrated in patients with FEV1 <40% or >80% predicted (Bethkis, TOBI) or FEV1 <25% or >80% predicted (TOBI Podhaler) or FEV1 <25% or >75% predicted (Kitabis Pak), in patients colonized with Burkholderia cepacia, or in patients <6 years of age.

• Nephrotoxicity: Nephrotoxicity was not observed during tobramycin inhalation clinical studies, but has been associated with aminoglycosides. If nephrotoxicity occurs, discontinue therapy until serum concentrations fall below 2 mcg/mL.

• Neuromuscular disorders: Use with caution in patients with neuromuscular disorders, including myasthenia gravis and Parkinson disease; neuromuscular blockade, respiratory failure, and prolonged respiratory paralysis may occur due to aminoglycoside-related curare-like effect on neuromuscular function.

• Neurotoxicity: Ototoxicity, as measured by complaints of hearing loss or tinnitus, has been reported. Tinnitus may be a sentinel symptom of ototoxicity, and therefore, the onset of this symptom warrants further investigation. Ototoxicity, manifested as both auditory and vestibular toxicity, has been reported with parenteral aminoglycosides. Vestibular toxicity may be manifested by vertigo, ataxia, or dizziness. Patients with known or suspected auditory or vestibular dysfunction should be closely monitored (audiometric evaluations and serum tobramycin concentrations). Consider monitoring serum tobramycin concentrations if neurotoxicity is suspected or with concurrent use of parenteral aminoglycosides. If neurotoxicity occurs, discontinue therapy until serum concentrations fall below 2 mcg/mL. Baseline audiogram should be considered for patients at increased risk of auditory dysfunction. Use with caution in patients with preexisting vertigo, tinnitus, or hearing loss

Monitoring Parameters

The utility of monitoring serum concentrations in patients with renal impairment should be per health care provider discretion; serum concentrations achieved following inhalation are significantly less than those achieved following parenteral therapy in patients with normal renal function. Monitor serum tobramycin concentrations in patients with known or history of auditory dysfunction, renal dysfunction, and/or concomitant use of nephrotoxic drugs. One hour after inhalation, serum concentrations of 1 to 2 mcg/mL have been observed.

Pregnancy Risk Factor

D

Pregnancy Considerations

Aminoglycosides may cause fetal harm if administered to a pregnant woman. Tobramycin crosses the placenta when given by injection. There are several reports of total irreversible bilateral congenital deafness in children whose mothers received another aminoglycoside (streptomycin) during pregnancy. Although serious side effects to the fetus/infant have not been reported following maternal use of all aminoglycosides, a potential for harm exists.

Tobramycin inhalation may be used for the management of cystic fibrosis in pregnant patients with Pseudomonas aeruginosa (Edenborough 2008).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, mouth pain, throat pain, pharyngitis, change in taste, change in voice, rhinorrhea, nausea, or vomiting. Have patient report immediately to prescriber signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), change in balance, dizziness, passing out, muscle weakness, tinnitus, angina, hearing impairment, hearing loss, persistent cough, coughing up blood, difficulty breathing, or wheezing (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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