Tobramycin Inhalation Solution (TOBI) is an effective medication for controlling Pseudomonas aeruginosa infections in patients with cystic fibrosis; however, it may also cause a range of adverse reactions.

I. Side Effects of TOBI

1. Common Side Effects (Incidence >5%)

(1) According to two Phase III clinical studies, adverse reactions with an incidence exceeding 5% include: increased cough, pharyngitis, increased sputum production, dyspnea, hemoptysis, decreased pulmonary function, voice alteration, dysgeusia, and rash.

(2) Among these, voice alteration and tinnitus were two adverse reactions significantly more frequent in the TOBI group than in the placebo group.

2. Severe Side Effects Requiring Vigilance

(1) Ototoxicity: Transient tinnitus was reported in TOBI-treated patients in clinical studies, and cases of hearing loss have been reported during post-marketing surveillance. Vestibular toxicity may manifest as vertigo, ataxia, or dizziness.

(2) Nephrotoxicity: Although not observed in clinical studies, aminoglycosides as a class are associated with renal injury.

(3) Bronchospasm: Wheezing, chest tightness, cough and other symptoms may occur after inhalation.

(4) Exacerbation of neuromuscular disorders: May aggravate muscle weakness in patients with myasthenia gravis, Parkinson’s disease, and other related conditions.

3. Other Adverse Reactions Identified in Post-Marketing Surveillance

Including hearing loss, hypersensitivity reactions (pruritus, urticaria, rash), aphonia, taste disturbance, oropharyngeal pain, anorexia, etc.

II. Methods to Alleviate Side Effects

1. Management of Bronchospasm

(1) If wheezing, shortness of breath or chest tightness occurs after inhalation, inform a doctor immediately.

(2) The physician will prescribe bronchodilators or other symptomatic treatments based on the severity.

(3) It is recommended to remain seated or upright during administration, breathe normally, and avoid breath-holding.

2. Monitoring and Management of Ototoxicity

(1) If tinnitus, hearing loss, vertigo or balance disorders develop during treatment, seek medical attention promptly for hearing assessment and serum drug concentration monitoring.

(2) For patients with mitochondrial DNA variants (e.g., m.1555A>G), ototoxicity may occur even with normal serum drug concentrations, and alternative therapy should be considered.

(3) Once ototoxicity is confirmed, the physician may recommend discontinuation of treatment.

3. Prevention of Nephrotoxicity

(1) Renal function should be monitored before and during treatment, especially in patients with pre-existing renal disease or those receiving concomitant nephrotoxic medications.

(2) Maintain adequate fluid intake and avoid concurrent use of other aminoglycosides or potent diuretics (e.g., furosemide, ethacrynic acid).

(3) Evaluate the need for treatment discontinuation if serum creatinine is significantly elevated.

4. Voice Alteration and Pharyngeal Discomfort

(1) Voice alteration usually occurs during treatment and resolves after discontinuation.

(2) Rinsing the mouth with clean water after each inhalation may help reduce pharyngeal irritation and taste abnormalities.

5. General Recommendations

(1) Airway clearance techniques may be used when cough or sputum production increases.

(2) If symptoms persist or worsen, contact a physician to assess whether they result from worsening infection or adverse drug reactions.

(3) Seek immediate medical attention for any suspected hypersensitivity reactions (rash, pruritus, worsening dyspnea).

III. Storage Conditions for TOBI

1. Refrigerated Storage (Preferred)

(1) TOBI ampoules should be stored in a refrigerator at a constant temperature of 2°C–8°C (36°F–46°F).

(2) Unopened foil pouches may be placed directly in the refrigerator. Store protected from light, avoiding direct strong light exposure.

2. Room-Temperature Storage (Temporary or Under Limited Conditions)

(1) If refrigeration is unavailable or after removal from the refrigerator, TOBI foil pouches (opened or unopened) may be stored at room temperature not exceeding 25°C (77°F) for a maximum of 28 days.

(2) The product must not be used beyond 28 days.

3. Pre-Use Inspection

(1) Inspect the solution for clarity before each use.

(2) The normal solution is pale yellow; prolonged non-refrigerated storage may cause darkening of color, but this color change does not affect quality as long as storage requirements are met.

(3) Do not use if the solution is cloudy or contains particulate matter.

4. Expiry Date Management

(1) Under refrigerated storage, follow the expiry date printed on the ampoule.

(2) For room-temperature storage, the 28-day limit applies; whichever comes first shall prevail. Expired medication must not be used.

5. Other Precautions

(1) TOBI contains no preservatives; single-dose ampoules should be used immediately after opening, and any remaining solution must not be stored.

(2) Unused ampoules should remain in their original foil pouches to protect from moisture and light.