Dosing and uses of TOBI, Bethkis (tobramycin inhaled)
Adult dosage forms and strengths
solution for nebulization
- 300mg/4mL ampule (Bethkis)
- 300mg/5mL ampule (TOBI, Kitabis Pak)
- NOTE: Kitabis Pak includes tobramycin solution and nebulizer (PARI LC PLUS reusable nebulizer and DeVilbiss Pulmo-Aide compressor)
powder for inhalation
- 28mg/capsule
Pseudomonas aeruginosa Infection
Indicated for management Pseudomonas aeruginosa in patients with cystic fibrosis
Nebulizer: 300 mg inhaled orally via nebulizer BId
Powder for inhalation: 4 capsules (28 mg/capsule) inhaled PO BId
Nebulizer or powder for inhalation: Use in repeated cycles of 28 days on drug, followed by 28 days off drug, then resume therapy with the next 28 day on/28 day off cycle
Dosing Considerations
Safety and efficacy not established in the following patients
- Age <6 years
- FEV1 <25% or >80% predicted
- Colonized with Burkholderia cepacia
Administration
For oral inhalation only
Bethkis: Administer using a hand-held PARI LC Plus reusable nebulizer with a APRI Vios Air compressor over ~15 minutes
TOBI: Administer using a hand-held PARI LC Plus reusable nebulizer with a DeVilbiss Pulmo-Aide compressor over ~15 minutes
Kitabis: Administer using PARI LC PLUS reusable nebulizer and DeVilbiss Pulmo-Aide compressor over ~15 minutes
TOBI Podhaler: For use with Podhaler device for oral inhalation; do not swallow capsules
Doses should be taken as close to 12 hr apart as possible; and, not less than 6 hr apart
Do not dilute or mix with dornase alfa in nebulizer; patients taking multiple therapies should take other nebulized therapies first, followed by tobramycin inhaled
Storage
- Store ampules refrigerated (2-8°C [36-46°F])
- Avoid exposure to intense light
- May store the ampules foil pouches (opened or unopened) at room temperature (up to 25°C [77°F]) for up to 28 days
- Unrefrigerated solution may slightly darken beyond its normally light yellow color; however the quality/potency of the solution is maintained for up to 28 days
Bronchiectasis (Orphan)
TOBI: Orphan designation for treatment of bronchiectasis patients infected with Pseudomonas aeruginosa
Orphan sponsor
- Novartis Pharmaceuticals Corp; Drug Regulatory Affairs; One Health Plaza; East Hanover, NJ 07936-1080
Pediatric dosage forms and strengths
solution for nebulization
- 300mg/4mL ampule (Bethkis)
- 300mg/5mL ampule (TOBI, Kitabis Pak)
- NOTE: Kitabis Pak includes tobramycin solution and nebulizer (PARI LC PLUS reusable nebulizer and DeVilbiss Pulmo-Aide compressor)
powder for inhalation
- 28mg/capsule
Pseudomonas aeruginosa Infection
Indicated for management Pseudomonas aeruginosa in patients with cystic fibrosis
<6 years: Safety and efficacy not established
≥6 years
- Nebulizer: 300 mg inhaled orally via nebulizer BID
- Powder for inhalation: 4 capsules (28 mg/capsule) inhaled PO BID
- Nebulizer or powder for inhalation: Use in repeated cycles of 28 days on drug, followed by 28 days off drug, then resume therapy with the next 28 day on/28 day off cycle
Dosing Considerations
Safety and efficacy not established in the following patients
- Age <6 years
- FEV1 <25% or >80% predicted
- Colonized with Burkholderia cepacia
Administration
For oral inhalation only
Bethkis: Administer using a hand-held PARI LC Plus reusable nebulizer with a APRI Vios Air compressor over ~15 minutes
TOBI: Administer using a hand-held PARI LC Plus reusable nebulizer with a DeVilbiss Pulmo-Aide compressor over ~15 minutes
Kitabis: Administer using PARI LC PLUS reusable nebulizer and DeVilbiss Pulmo-Aide compressor over ~15 minutes
TOBI Podhaler: For use with Podhaler device for oral inhalation; do not swallow capsules
Doses should be taken as close to 12 hr apart as possible; and, not less than 6 hr apart
For patients taking several different inhaled medications and/or performing chest physiotherapy, it is recommended that TOBI Podhaler is taken last
Storage
- Store ampules refrigerated (2-8°C [36-46°F])
- Avoid exposure to intense light
- May store the ampules foil pouches (opened or unopened) at room temperature (up to 25°C [77°F]) for up to 28 days
- Unrefrigerated solution may slightly darken beyond its normally light yellow color; however the quality/potency of the solution is maintained for up to 28 days
TOBI, Bethkis (tobramycin inhaled) adverse (side) effects
>10%
Voice alteration (12.8%)
1-10%
Myalgia (4.7%)
Laryngitis (4.3%)
Tinnitus (3%)
Epistaxis (3%)
Postmarketing Reports
General disorders: Malaise
Ear and labyrinth disorders: Hearing loss
Skin and subcutaneous tissue disorders: Hypersensitivity, pruritus, urticaria, rash
Nervous system disorders: Aphonia, dysgeusia
Respiratory, thoracic, and mediastinal disorders: Bronchospasm, oropharyngeal pain, sputum discolored
Decreased appetite
Warnings
Contraindications
Hypersensitivity
Cautions
Known or suspected renal, auditory, vestibular, or neuromuscular dysfunction
Carefully monitor if on concomitant parenteral aminoglycosides
Tinnitus occurred in clinical trials of inhaled tobramycin; however, ototoxicity did not occur (postmarketing experience reported hearing loss, see Adverse effects)
Nephrotoxicity not observed in clinical trials, but has been associated with aminoglycosides as a class
May exacerbate muscular disorders (eg, myasthenia gravis, Parkinson disease); aminoglycosides aggravate muscle weakness because of a curare-like effect
Bronchospasm can occur
Pregnancy and lactation
Pregnancy category: d
Lactation: Unknown whether inhaled tobramycin will reach sufficient concentration to be distributed in breast milk; because of the potential for ototoxicity and nephrotoxicity in infants, a decision should be made whether to terminate breastfeeding or discontinue inhaled tobramycin
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of TOBI, Bethkis (tobramycin inhaled)
Mechanism of action
Aminoglycoside that acts by disrupting protein synthesis, leading to altered cell membrane permeability, progressive disruption of the cell envelope, and eventual cell death
In vitro activity against wide range of gram-negative organisms including Pseudomonas aeruginosa
Absorption
Sputum Concentration (10 min post dose): 1154 mcg/g (range: 39-8085 mcg/g)
Serum Concentration (1 hr post dose): 0.95 mcg/mL (single dose); 1.05 mcg/mL (after 20 weeks of therapy)
Elimination
Half-life: 2 hr (IV)
Excretion: Unabsorbed drug eliminated primarily in expectorated sputum
