Tobi (Tobramycin Inhalation) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

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

¹ Includes subjective complaints of fever.

² Includes reported decreases in pulmonary function tests or decreased lung volume on chest radiograph associated with intercurrent illness or study drug administration.

REPORTS OF SUSPECTED TOBI SIDE EFFECTS / ADVERSE REACTIONS

Possible Tobi side effects / adverse reactions in 68 year old female

Reported by a physician from United States on 2011-10-02

Patient: 68 year old female

Reactions: Adrenal Disorder

Adverse event resulted in: hospitalization

Suspect drug(s):
Tobi

Other drugs received by patient: Prednisone

Possible Tobi side effects / adverse reactions in 27 year old male

Reported by a individual with unspecified qualification from United States on 2011-10-04

Patient: 27 year old male weighing 70.3 kg (154.6 pounds)

Reactions: Ankle Fracture

Adverse event resulted in: hospitalization

Suspect drug(s):
Tobi

Possible Tobi side effects / adverse reactions in 21 year old female

Reported by a individual with unspecified qualification from United States on 2011-10-04

Patient: 21 year old female

Reactions: Upper Respiratory Tract Infection, Lung Infection

Adverse event resulted in: hospitalization

Suspect drug(s):
Tobi

Other drugs received by patient: Pulmozyme