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
Depocyt Side Effects, and Drug Interactions - Cytarabine
Depocyt Side Effects, and Drug Interactions - Cytarabine
SIDE EFFECTS
The toxicity database
consists of the observations made during an early uncontrolled study
and the controlled multi-arm study described above. In the early
study, patients received DepoCyt at doses ranging from 12.5 mg to
125 mg. In the randomized
multi-arm study DepoCyt was administered at a dose
of 50 mg every two weeks
and was compared to standard
intrathecal chemotherapy (cytarabine or methotrexate) in patients
with lymphoma, leukemia
and solid tumors; twenty-eight
lymphoma patients,
5 leukemia patients
and 59 solid tumor
patients received study drug.
Arachnoiditis is an expected and well-documented side
effect of both neoplastic
meningitis and of
intrathecal chemotherapy.
For clinical studies
of DepoCyt, chemical
arachnoiditis
was defined as the occurrence of any one of the symptoms of neck
rigidity, neck pain,
meningism, or any two of the symptoms of nausea,
vomiting, headache,
fever, back
pain, or CSF pleocytosis;
the grade assigned to
an episode of chemical
arachnoiditis was the highest severity grade
of its component symptoms.
Since most of the adverse events reported in the trials were transient
episodes associated with drug
exposure, the incidence
of these events is best expressed by drug cycle. A cycle
of treatment for all
treatment groups was
defined as the 14-day period
between DepoCyt doses. The duration
of reported symptoms was from 1 to 5 days. Although it was sometimes
difficult to distinguish between drug-related chemical
arachnoiditis, infectious
meningitis, or disease
progression, >90% of the chemical
arachnoiditis
cases reported occurred within 48 hours of the administration
of intrathecal drug,
indicating a drug etiology.
In the early study, chemical
arachnoiditis
was observed in 100% of cycles without dexamethasone
prophylaxis; with concurrent administration
of dexamethasone, chemical arachnoiditis
was observed in 33% of cycles. Patients receiving DepoCyt should
be treated concurrently with dexamethasone
to mitigate the symptoms of chemical
arachnoiditis
(see DOSAGE AND ADMINISTRATION).
Table 2 shows the rate
of all adverse events occurring in ³10
% of patients, as a rate
per cycle, in the lymphoma
randomized study.
Table 2
Comparison of Adverse Events Occurring in ³
10% of Patients, by Cycle
Patients with Lymphomatous Meningitis Receiving DepoCyt or
Cytarabine (ara-C) in the Randomized Study
|
|
Patients with Lymphomatous Meningitis
Receiving DepoCyt or Cytarabine (ara-C) in the Randomized
Study
|
|
All Adverse Events
%
|
Grade 3 or 4 Adverse Events
%
|
|
Number of Cycles
|
n = 74
|
n = 45
|
n = 74
|
n = 45
|
|
Body System/Adverse Event
|
DepoCyt
|
Ara-C
|
DepoCyt
|
Ara-C
|
|
Body as a Whole
|
53
|
60
|
18
|
22
|
|
Headache*
|
28
|
9
|
5
|
2
|
|
Asthenia
|
19
|
33
|
5
|
9
|
|
Fever*
|
11
|
24
|
4
|
0
|
|
Back Pain*
|
7
|
11
|
0
|
2
|
|
Pain
|
11
|
20
|
3
|
0
|
|
Nervous System
|
45
|
53
|
18
|
18
|
|
Confusion
|
14
|
7
|
4
|
2
|
|
Somnolence
|
12
|
11
|
4
|
2
|
|
Abnormal Gait
|
4
|
11
|
1
|
2
|
|
Digestive System
|
27
|
44
|
7
|
9
|
|
Nausea*
|
11
|
16
|
0
|
4
|
|
Vomiting*
|
12
|
18
|
3
|
2
|
|
Constipation
|
7
|
11
|
0
|
0
|
|
Metabolic and Nutritional Disorders
|
16
|
24
|
0
|
0
|
|
Peripheral Edema
|
7
|
11
|
0
|
0
|
|
Hematologic
|
19
|
22
|
11
|
13
|
|
Neutropenia
|
9
|
11
|
8
|
11
|
|
Thrombocytopenia
|
8
|
16
|
5
|
11
|
|
Anemia
|
1
|
13
|
1
|
4
|
|
Urogenital System
|
11
|
20
|
3
|
2
|
|
Urinary Incontinence
|
3
|
11
|
0
|
0
|
|
Special Senses
|
16
|
18
|
1
|
2
|
- *Components of Chemical Arachnoiditis.
DRUG INTERACTIONS
No formal drug interaction
studies of DepoCyt and other drugs were conducted. Concomitant administration
of DepoCyt with other antineoplastic
agents administered by the intrathecal
route has not been studied. With intrathecal cytarabine and other
cytotoxic agents administered
intrathecally, enhanced neurotoxicity has been associated with co-administration
of drugs.
Laboratory Test Interactions
Since DepoCyt particles are similar in size and appearance
to white blood cells, care must be taken in interpreting CSF
examinations following DepoCyt administration.
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