TOBI SIDE EFFECTS

  • Generic Name: tobramycin
  • Brand Name: Tobi
Last updated on MDtodate: 10/12/2022

SIDE EFFECTS

TOBI was generally well tolerated during two clinical studies in 258 cystic fibrosis patients ranging in age from 6 to 48 years. Patients received TOBI in alternating periods of 28 days on and 28 days off drug in addition to their standard cystic fibrosis therapy for a total of 24 weeks.

Voice alteration and tinnitus were the only adverse experiences reported by significantly more TOBI-treated patients. Thirty-three patients (13%) treated with TOBI complained of voice alteration compared to 17 (7%) placebo patients. Voice alteration was more common in the on-drug periods.

Eight patients from the TOBI group (3%) reported tinnitus compared to no placebo patients. All episodes were transient, resolved without discontinuation of the TOBI treatment regimen, and were not associated with loss of hearing in audiograms. Tinnitus is one of the sentinel symptoms of cochlear toxicity, and patients with this symptom should be carefully monitored for high frequency hearing loss. The numbers of patients reporting vestibular adverse experiences such as dizziness were similar in the TOBI and placebo groups.

Nine (3%) patients in the TOBI group and nine (3%) patients in the placebo group had increases in serum creatinine of at least 50% over baseline. In all nine patients in the TOBI group, creatinine decreased at the next visit.

Table 1 lists the percent of patients with treatment-emergent adverse experiences (spontaneously reported and solicited) that occurred in > 5% of TOBI patients during the two Phase III studies.

Table 1: Percent of Patients With Treatment Emergent Adverse Experiences Occurring in > 5% of TOBI Patients

Adverse Event TOBI
(n=258) %
Placebo
(n=262) %
Cough Increased 46.1 47.3
Pharyngitis 38.0 39.3
Sputum Increased 37.6 39.7
Asthenia 35.7 39.3
Rhinitis 34.5 33.6
Dyspnea 33.7 38.5
Fever1 32.9 43.5
Lung Disorder 31.4 31.3
Headache 26.7 32.1
Chest Pain 26.0 29.8
Sputum Discoloration 21.3 19.8
Hemoptysis 19.4 23.7
Anorexia 18.6 27.9
Lung Function Decreased2 16.3 15.3
Asthma 15.9 20.2
Vomiting 14.0 22.1
Abdominal Pain 12.8 23.7
Voice Alteration 12.8 6.5
Nausea 11.2 16.0
Weight Loss 10.1 15.3
Pain 8.1 12.6
Sinusitis 8.1 9.2
Ear Pain 7.4 8.8
Back Pain 7.0 8.0
Epistaxis 7.0 6.5
Taste Perversion 6.6 6.9
Diarrhea 6.2 10.3
Malaise 6.2 5.3
Lower Respiratory Tract Infection 5.8 8.0
Dizziness 5.8 7.6
Hyperventilation 5.4 9.9
Rash 5.4 6.1
1Includes subjective complaints of fever.
2Includes reported decreases in pulmonary function tests or decreased lung volume on chest radiograph associated with intercurrent illness or study drug administration.

 

Adverse drug reactions ( < 5%) occurring more frequently with TOBI in the placebo-controlled studies and assessed as drug-related in ≥ 1% of patients:

Ear and Labyrinth Disorders

Tinnitus (3.1%, vs 0% for placebo)

Musculoskeletal and Connective Tissue Disorders

Myalgia (4.7%, vs 2.7% for placebo)

Infections and Infestations

Laryngitis (4.3%, vs 3.1% for placebo)

Adverse Drug Reactions Derived From Spontaneous Reports

The following adverse reactions have been identified during postapproval use of TOBI. 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.

Ear and Labyrinth Disorders

Hearing loss

Skin and Subcutaneous TissueDiisorders

Hypersensitivity, pruritus, urticaria, rash

Nervous System Disorders

Aphonia, dysgeusia

Respiratory, Thoracic, and Mediastinal Disorders

Bronchospasm, oropharyngeal pain

Metabolism and Nutrition Disorders

Decreased appetite

 

SRC: NLM .