Version May 2024
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.
Missed dose: If <6 hours before next scheduled dose, skip the missed dose and resume usual dosing schedule.
Non–cystic fibrosis bronchiectasis (off-label use):
Acute exacerbation: Inhalation for nebulization: 80 mg twice daily in combination with systemic antimicrobial therapy. Note: Efficacy data for treatment are limited and inconclusive (Ref).
Chronic suppression: Inhalation for nebulization: 160 mg or 300 mg twice daily (Ref). Note: Reserve use for patients with ≥3 exacerbations requiring antibiotic therapy per year (Ref).
Pneumonia, hospital-acquired or ventilator-associated (adjunctive agent) (off-label use):
Inhalation for nebulization: 300 mg every 12 hours in combination with IV antimicrobial therapy. Note: Efficacy is uncertain (Ref); some experts reserve for patients with risk for multidrug-resistant pathogens (Ref).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling; however, does not undergo hepatic metabolism.
(For additional information see "Tobramycin (oral inhalation): Pediatric drug information")
Eradication of new or initial Pseudomonas aeruginosa airway culture in patients with cystic fibrosis: Limited data available: Infants ≥6 months, Children, and Adolescents: Inhalation: 300 mg every 12 hours for 28 days (Ref).
Pseudomonas aeruginosa colonization; chronic lung maintenance:
Patients with cystic fibrosis:
Bethkis, Kitabis Pak, Tobi: Children and Adolescents (limited data in children <6 years): Inhalation: 300 mg every 12 hours; administer in repeated cycles of 28 days on drug followed by 28 days off drug (Ref)
Tobi Podhaler: Children ≥6 years and Adolescents: Inhalation: 112 mg (4 x 28 mg capsules) every 12 hours; administer in repeated cycles of 28 days on drug followed by 28 days off drug (Ref).
Patients without cystic fibrosis: Limited data available:
Note: Doses are from initial studies of patients with cystic fibrosis (CF) using the IV product as inhalation (Ref). Some centers utilize this dose in patients without CF for treatment of pulmonary disease (eg, bronchiectasis, tracheitis) (Ref):
Children and Adolescents: Inhalation: 80 mg/dose 2 to 3 times daily.
There are no dosage adjustments provided in manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in manufacturer's labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>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%, postmarketing, and/or case reports: Aphonia, decreased appetite, hypersensitivity reaction, increased bronchial secretions, pneumonitis, pruritus, pulmonary congestion, urticaria
Hypersensitivity to tobramycin, other aminoglycosides, or any component of the formulation
Concerns related to adverse effects:
• Bronchospasm: Bronchospasm may occur; bronchospasm or wheezing should be treated appropriately if either arise.
• Nephrotoxicity: Nephrotoxicity was not observed during tobramycin inhalation clinical studies, but has been associated with aminoglycosides. Patients with known or suspected renal dysfunction or taking concomitant nephrotoxic drugs should be closely monitored (renal function tests and serum tobramycin concentrations) as clinically indicated. 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. Concomitant neuromuscular blocking agents may also increase risk for prolonged respiratory paralysis.
• Ototoxicity: 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). 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.
Special populations:
• Patients with genomic variants in MT-RNR1: Carriers of certain variants in the MT-RNR1 gene (eg, m.1555A>G) may be at increased risk for aminoglycoside-induced ototoxicity, including potentially significant hearing loss that may be irreversible, even when serum levels are within the normal range.
With use of Tobi Podhaler (oral capsule powder for inhalation), taste disturbance (dysgeusia) was reported more frequently in pediatric patients ≥6 years (7.4%) than adults (2.7%).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Inhalation:
Tobi Podhaler: 28 mg
Nebulization Solution, Inhalation:
Generic: 300 mg/5 mL (5 mL); 300 mg/4 mL (4 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); 300 mg/4 mL (4 mL)
May be product dependent
Capsules (Tobi Podhaler Inhalation)
28 mg (per each): $60.95
Nebulization (Bethkis Inhalation)
300 mg/4 mL (per mL): $33.14
Nebulization (Kitabis Pak Inhalation)
300 mg/5 mL (per mL): $19.29
Nebulization (Tobi Inhalation)
300 mg/5 mL (per mL): $35.30
Nebulization (Tobramycin Inhalation)
300 mg/4 mL (per mL): $31.15 - $31.48
300 mg/5 mL (per mL): $8.06 - $28.27
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Inhalation:
Tobi Podhaler: 28 mg
Nebulization Solution, Inhalation:
Tobi: 300 mg/5 mL (5 mL) [contains sodium chloride, sodium hydroxide, sulfuric acid]
Generic: 300 mg/5 mL (5 mL)
Inhalation:
Bethkis, Kitabis Pak, Tobi: To be orally 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.
Nebulization of injection formulation (off-label route): To prepare tobramycin injection solution for inhalation via nebulizer, further dilute 2 mL of tobramycin 40 mg/mL solution with 2 mL NS for an 80 mg dose (final volume: 4 mL) or 4 mL of tobramycin 40 mg/mL with 4 mL NS for a 160 mg dose (final volume: 8 mL) (Ref). Preservative-free injection formulations may be preferred to minimize adverse reactions (eg, bronchoconstriction, cough). Use with jet nebulizer; refer to nebulizer manufacturer's information for usage instructions and volume specifications (Ref).
Inhalation: Doses should be administered as close to prescribed schedule as possible; do not administer <6 hours apart. The Cystic Fibrosis Foundation recommends the following order for patients receiving multiple inhaled medications (as appropriate): Bronchodilator, hypertonic saline, dornase alfa, airway clearance, then inhaled tobramycin (Ref).
Bethkis, Kitabis Pak, Tobi: Use a PARI LC Plus reusable nebulizer and a PARI Vios air compressor (Bethkis) or a DeVilbiss Pulmo-Aide air compressor (Kitabis Pak, Tobi) for administration; patient should be sitting or standing upright and breathing normally through the mouthpiece of the nebulizer. Nebulizer treatment period is usually over 15 minutes. 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. Use the new Podhaler device provided with each weekly pack.
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 FEV1 <40% or >80% predicted (Bethkis) or FEV1 <25% or >80% predicted (TOBI Podhaler) or FEV1 <25% or >75% predicted (Kitabis Pak; TOBI), or in patients colonized with Burkholderia cepacia.
Non–cystic fibrosis bronchiectasis; Pneumonia, hospital-acquired or ventilator-associated
Tobramycin may be confused with Trobicin, vancomycin
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Loop Diuretics: May enhance the nephrotoxic effect of Tobramycin (Oral Inhalation). Loop Diuretics may enhance the ototoxic effect of Tobramycin (Oral Inhalation). Risk C: Monitor therapy
Mannitol (Systemic): May enhance the nephrotoxic effect of Tobramycin (Oral Inhalation). Risk X: Avoid combination
Aminoglycosides may cause fetal harm if administered to a pregnant woman. Systemic absorption of tobramycin following oral inhalation is expected to be low compared to intravenous administration; however, systemic exposure was associated with total irreversible bilateral congenital deafness in children whose mothers received another aminoglycoside during pregnancy.
Tobramycin inhalation may be used for the management of cystic fibrosis in pregnant patients with Pseudomonas aeruginosa (Edenborough 2008).
It is not known if tobramycin is present in breast milk following oral inhalation.
Tobramycin is present in breast milk following injection (Festini 2006; Uwaydah 1975). Systemic absorption following oral inhalation is expected to be low compared to IV administration.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Based on low serum concentrations and low absorption, breastfeeding is considered compatible in women using inhaled tobramycin for the management of cystic fibrosis (Edenborough 2008; Panchaud 2016). Infants should be monitored for loose or bloody stools and candidiasis.
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.
Inhalation: Serum concentrations are ~1 to 2 mcg/mL 1 hour following a dose in patients with normal renal function. Routine monitoring of serum concentrations is not required.
Interferes with bacterial protein synthesis by binding to 30S ribosomal subunit, 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
Half-life elimination:
Solution for inhalation: ~4.4 hours (Bethkis); ~3 hours (TOBI)
Powder for inhalation: ~3 hours (after a single 112 mg dose)
Time to peak, serum: Powder for inhalation: 60 minutes
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
