A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Tobi Side Effects, and Drug Interactions - Tobramycin
Tobi Side Effects, and Drug Interactions - Tobramycin
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)
% |
(n=262)
Placebo
% |
|
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 |
|
Fever 1
|
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 decreased 2
|
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 Resp. 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.
|
DRUG INTERACTIONS
In clinical studies of TOBI, patients taking TOBI concomitantly with dornase
alfa (PULMOZYME®, Genentech), (beta)-agonists, inhaled corticosteroids, other
anti-pseudomonal antibiotics, or parenteral aminoglycosides demonstrated adverse
experience profiles similar to the study population as a whole.
Concurrent and/or sequential use of TOBI with other drugs with neurotoxic or
ototoxic potential should be avoided. Some diuretics can enhance aminoglycoside
toxicity by altering antibiotic concentrations in serum and tissue. TOBI should
not be administered concomitantly with ethacrynic acid, furosemide, urea, or
mannitol.
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