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
Rituxan Side Effects, and Drug Interactions - Rituximab
Rituxan Side Effects, and Drug Interactions - Rituximab
SIDE EFFECTS
Safety data are based on 315 patients treated in five single-agent
studies of RITUXAN™(Rituximab). This includes patients with bulky
disease (lesions >
10 cm), those who have received more than one course of RITUXAN,
and patients receiving 375 mg/m2
for eight doses.
Infusion-Related Events: An
infusion-related symptom
complex consisting of fever
and chills/rigors occurred in the majority of patients during the
first RITUXAN infusion. Other frequent infusion-related symptoms
included nausea, urticaria,
fatigue, headache,
pruritus, bronchospasm,
dyspnea, sensation
of tongue or throat
swelling (angioedema),
rhinitis, vomiting, hypotension,
flushing, and pain at disease
sites. These reactions generally occurred within 30 minutes to 2
hours of beginning the first infusion, and resolved with slowing
or interruption of the RITUXAN infusion and with supportive care
(IV saline, diphenhydramine,
and acetaminophen). The incidence
of infusion-related events decreased from 80% (7% Grade 3/4) during
the first infusion
to approximately 40% (5% to 10% Grade 3/4) with subsequent infusions.
Mild to moderate hypotension
requiring interruption of RITUXAN infusion
with or without the administration
of IV saline
occurred in 32 (10%) patients. Isolated occurrences of severe reactions
requiring epinephrine have been reported in patients receiving RITUXAN
for other indications. Angioedema was reported in 41 (13%) patients
and was serious in one patient. Bronchospasm occurred in 24 (8%)
patients; one-quarter of these patients were treated with bronchodilators.
A single report of bronchiolitis
obliterans was noted.
Immunologic Events: RITUXAN induced
B-cell depletion in
70 to 80% of patients and was associated with decreased serum
immunoglobulins in a minority of patients. The incidence
of infection does
not appear to be increased. During the treatment
period, 50 patients in the pivotal trial developed 68 infectious
events; six (9%) were Grade 3 in severity and none were Grade 4
events. Of the six serious infectious
events, none were associated with neutropenia. The serious bacterial
events included sepsis
due to Listeria (n=1), Staphylococcal bacteremia
(n=1) and polymicrobial
sepsis (n=1). In the post-treatment
period (30 days to 11
months following the last dose), bacterial infections included sepsis
(n=1); significant
viral infections included herpes
simplex infections (n=2) and herpes
zoster (n=3).
Retreatment Events: Twenty-one patients have received more
than one course of RITUXAN. The percentage of patients reporting
any adverse event upon retreatment was similar to the percentage
of patients reporting adverse events upon initial
exposure. The following adverse events were reported more frequently
in retreated subjects: asthenia,
throat irritation, flushing,
tachycardia, anorexia,
leukopenia, thrombocytopenia,
anemia, peripheral edema,
dizziness, depression,
respiratory symptoms,
night sweats, and pruritus.
Hematologic Events: During the treatment
period (up to 30 days
following last dose) severe thrombocytopenia
occurred in 1.3% of patients, severe neutropenia
occurred in 1.9% of patients, and severe anemia
occurred in 1.0% of patients. A single occurrence of transient
aplastic anemia (pure
red cell aplasia) and two
occurrences of hemolytic
anemia following RITUXAN
therapy were reported.
Cardiac Events: Four patients developed arrhythmias during
RITUXAN infusion. One of the four discontinued treatment
because of ventricular tachycardia, and supraventricular
tachycardias. The other three patients experienced trigeminy
(1) and irregular pulse
(2) and did not require discontinuation of therapy. Angina was reported
during infusion and
myocardial infarction
occurred four days post-infusion in one subject
with a prior history
of myocardial infarction.
Table 1.
Adverse Events greater than or equal to 5%
of Patients (N=315)
|
| |
Incidence
All Grades |
| N |
% |
| Any Adverse Event |
275 |
87 |
Body As A Whole |
|
Fever
|
154 |
49 |
|
Chills
|
102 |
32 |
|
Asthenia
|
49 |
16 |
|
Headache
|
43 |
14 |
|
Throat Irritation
|
19 |
6 |
|
Abdominal Pain
|
18 |
6 |
Cardiovascular System |
|
Hypotension
|
32 |
10 |
Digestive System |
|
Nausea
|
55 |
18 |
|
Vomiting
|
23 |
7 |
Hemic and Lymphatic System |
|
Leukopenia
|
33 |
11 |
|
Thrombocytopenia
|
25 |
8 |
|
Neutropenia
|
21 |
7 |
Metabolic and Nutritional System |
|
Angioedema
|
41 |
13 |
Musculo-Skeletal System |
|
Myalgia
|
21 |
7 |
Nervous System |
|
Dizziness
|
23 |
7 |
Respiratory System |
|
Rhinitis
|
25 |
8 |
|
Bronchospasm
|
24 |
8 |
Skin and Appendages |
|
Pruritus
|
32 |
10 |
|
Rash
|
31 |
10 |
|
Urticaria
|
24 |
8 |
Severe and life-threatening (Grade 3 and 4) events were reported
in 10% (32/315) of patients. The following Grade 3 and 4 adverse
events were reported: neutropenia
(1.9%), chills (1.6%), leukopenia
and thrombocytopenia (1.3% for each), hypotension,
anemia, bronchospasm,
and urticaria (1.0%
for each), headache,
abdominal pain,
arrhythmia (0.6%
for each), and asthenia, hypertension, nausea,
vomiting, coagulation
disorder, angioedema,
arthralgia, pain, rhinitis,
increased cough, dyspnea,
bronchiolitis
obliterans, hypoxia, asthma, pruritus,
and rash (one patient
each, 0.3%).
The following adverse events occurred in 1.0% but <5.0% of patients,
in order of decreasing
incidence: flushing, arthralgia,
diarrhea, anemia, cough
increase, hypertension,
lacrimation disorder,
pain, hyperglycemia, back
pain, peripheral
edema, paresthesia,
dyspepsia, chest
pain, anorexia, anxiety,
malaise, tachycardia,
agitation, insomnia,
sinusitis, conjunctivitis,
abdominal enlargement, postural
hypotension, LDH
increase, hypocalcemia, hypesthesia, respiratory
disorder, tumor pain,
pain at injection
site, bradycardia, hypertonia,
nervousness, bronchitis,
and taste perversion.
The proportion of patients reporting any adverse event was similar
in patients with bulky disease
and those with lesions <10 cm
in diameter. However, the incidence
of dizziness, neutropenia,
thrombocytopenia,
myalgia, anemia and chest
pain was higher in patients
with lesions >10 cm. The incidence of any Grade 3 and 4 event
was higher (31% vs. 13%) and the incidence of Grade 3 or 4 neutropenia,
anemia, hypotension,
and dyspnea was also
higher in patients with bulky disease
compared with patients with lesions <10 cm.
DRUG INTERACTIONS
Drug/Laboratory Interactions: There have been no
formal drug interaction studies performed with RITUXAN.
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