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
Pulmozyme Side Effects, and Drug Interactions - Dornase alfa
Pulmozyme Side Effects, and Drug Interactions - Dornase alfa
SIDE EFFECTS
Patients have been exposed to Pulmozyme for up to 12 months
in clinical trials.
In a randomized, placebo-controlled clinical trial in patients
with FVC 40% of predicted, over 600 patients received Pulmozyme once
or twice daily for six months; most adverse events were not more common on Pulmozyme
than on placebo and probably reflected the sequelae of the underlying lung disease.
In most cases events that were increased were mild, transient in nature, and
did not require alterations in dosing. Few patients experienced adverse events
resulting in permanent discontinuation from Pulmozyme, and the discontinuation
rate was similar for placebo (2%) and Pulmozyme (3%). Events that were more
frequent (greater than 3%) in Pulmozyme treated patients than in placebo-treated
patients are listed in Table 2.
In a randomized, placebo-controlled trial of patients with
advanced disease (FVC <40% of predicted) the safety profile for most adverse
events was similar to that reported for the trial in patients with mild to moderate
disease. For this study, adverse events that were reported with a higher frequency
(greater than 3%) in the Pulmozyme treated patients, are also listed in Table
2.
|
Table 2 Adverse Events Increased 3% or
More in Pulmozyme Treated Patients Over Placebo in CF Clinical Trials
|
|
|
Trial in Mild to Moderate CF Patients (FVC ³40%
of predicted) treated for 24 weeks
|
Trial in Advanced CF Patients (FVC <40% of predicted)
treated for 12 weeks
|
|
Adverse Event
|
Placebo
|
Pulmozyme
|
Pulmozyme
|
Placebo
|
Pulmozyme
|
|
(of any severity
|
|
QD
|
BID
|
|
QD
|
|
or seriousness)
|
n=325
|
n=322
|
n=321
|
n=159
|
n=161
|
|
Voice alteration
|
7%
|
12%
|
16%
|
6%
|
18%
|
|
Pharyngitis
|
33%
|
36%
|
40%
|
28%
|
32%
|
|
Rash
|
7%
|
10%
|
12%
|
1%
|
3%
|
|
Laryngitis
|
1%
|
3%
|
4%
|
1%
|
3%
|
|
Chest Pain
|
16%
|
18%
|
21%
|
23%
|
25%
|
|
Conjunctivitis
|
2%
|
4%
|
5%
|
0%
|
1%
|
|
Rhinitis
|
|
|
|
24%
|
30%
|
|
FVC decrease of ³10% of predicted°
|
|
|
|
17%
|
22%
|
|
Fever
|
Differences were less than 3% for these adverse events
in the Trial in mild to moderate CF patients
|
28%
|
32%
|
|
Dyspepsia
|
|
0%
|
3%
|
|
Dyspnea (when reported as serious)
|
Difference was less than 3% for this adverse event in
the Trial in mild to moderate CF patients
|
12%†
|
17%†
|
|
°Single measurement only, does not reflect overall FVC
changes.
|
|
†Total reports of dyspnea (regardless of severity
or seriousness) had a difference of less than 3% for the Trial in advanced
CF patients.
|
|
Events Observed at Similar Rates in Pulmozyme®
(dornase alfa) Inhalation Solution and Placebo Treated Patients
with FVC ³40% of Predicted
|
|
Body as a Whole
|
Abdominal pain, Asthenia, Fever, Flu syndrome, Malaise,
Sepsis
|
|
Digestive System
|
Intestinal Obstruction, Gall Bladder disease, Liver disease,
Pancreatic disease
|
|
Metabolic Nutritional System
|
Diabetes Mellitus, Hypoxia, Weight Loss
|
|
Respiratory System
|
Apnea, Bronchiectasis, Bronchitis, Change in Sputum,
Cough Increase, Dyspnea, Hemoptysis, Lung Function Decrease, Nasal Polyps,
Pneumonia, Pneumothorax, Rhinitis, Sinusitis, Sputum Increase, Wheeze
|
Mortality rates observed in controlled trials were similar
for the placebo and Pulmozyme treated patients. Causes of death were consistent
with progression of cystic fibrosis and included apnea, cardiac arrest, cardiopulmonary
arrest, cor pulmonale, heart failure, massive hemoptysis, pneumonia, pneumothorax,
and respiratory failure.
The safety of Pulmozyme, 2.5 mg by inhalation, was studied
with 2 weeks of daily administration in 98 patients with cystic fibrosis (65
aged 3 months to <5 years, 33 aged 5 to 10 years). The PARI BABY™
reusable nebulizer (which uses a facemask instead of a mouthpiece) was
utilized in patients unable to demonstrate the ability to inhale or exhale orally
throughout the entire treatment period (54/65, 83% of the younger and 2/33,
6% of the older patients). The number of patients reporting cough was higher
in the younger age group as compared to the older age group (29/65, 45% compared
to 10/33, 30%) as was the number reporting moderate to severe cough (24/65,
37% as compared to 6/33, 18%). Other events tended to be of mild to moderate
severity. The number of patients reporting rhinitis was higher in the younger
age group as compared to the older age group (23/65, 35% compared to 9/33, 27%)
as was the number reporting rash (4/65, 6% as compared to 0/33). The nature
of adverse events was similar to that seen in the larger trials of Pulmozyme®
(dornase alfa) Inhalation Solution.
Allergic Reactions
There have been no reports of anaphylaxis attributed to the
administration of Pulmozyme to date. Urticaria, mild to moderate, and mild skin
rash have been observed and have been transient. Within all of the studies,
a small percentage (average of 2–4%) of patients treated with Pulmozyme developed
serum antibodies to Pulmozyme. None of these patients developed anaphylaxis,
and the clinical significance of serum antibodies to Pulmozyme is unknown.
DRUG INTERACTIONS
Clinical trials have indicated that Pulmozyme can be effectively
and safely used in conjunction with standard cystic fibrosis therapies including
oral, inhaled and/or parenteral antibiotics, bronchodilators, enzyme supplements,
vitamins, oral or inhaled corticosteroids, and analgesics. No formal drug interaction
studies have been performed.
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