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
Zinecard Side Effects, and Drug Interactions - Dexrazoxane
Zinecard Side Effects, and Drug Interactions - Dexrazoxane
SIDE EFFECTS
ZINECARD at a dose of 500 mg/m 2 has been administered in combination
with FAC in randomized, placebo-controlled, double-blind studies to patients
with metastatic breast cancer. The dose of doxorubicin was 50 mg/m 2 in
each of the trials. Courses were repeated every three weeks, provided recovery
from toxicity had occurred. Table 2 below lists the incidence of adverse experiences
for patients receiving FAC with either ZINECARD or placebo in the breast cancer
studies. Adverse experiences occurring during courses 1 through 6 are displayed
for patients receiving ZINECARD or placebo with FAC beginning with their first
course of therapy (column 1 & 3, respectively). Adverse experiences occurring
at course 7 and beyond for patients who received placebo with FAC during the
first six courses and who then received either ZINECARD or placebo with FAC
are also displayed (column 2 & 4, respectively).
-
TABLE 2
|
|
PERCENTAGE (%) OF BREAST CANCER
PATIENTS WITH
ADVERSE EXPERIENCE |
|
|
FAC + ZINECARD
|
FAC + PLACEBO
|
|
ADVERSE
EXPERIENCE
|
Courses 1-6
N = 413
|
Courses >/= 7
N = 102
|
Courses 1-6
N = 458
|
Course >/= 7
N = 99
|
|
Alopecia
|
94 |
100 |
97 |
98 |
|
Nausea
|
77 |
51 |
84 |
60 |
|
Vomiting
|
59 |
42 |
72 |
49 |
|
Fatigue/Malaise
|
61 |
48 |
58 |
55 |
|
Anorexia
|
42 |
27 |
47 |
38 |
|
Stomatitis
|
34 |
26 |
41 |
28 |
|
Fever
|
34 |
22 |
29 |
18 |
|
Infection
|
23 |
19 |
18 |
21 |
|
Diarrhea
|
21 |
14 |
24 |
7 |
|
Pain on Injection
|
12 |
13 |
3 |
0 |
|
Sepsis
|
17 |
12 |
14 |
9 |
|
Neurotoxicit
|
17 |
10 |
13 |
5 |
|
Streaking/Erythema
|
5 |
4 |
4 |
2 |
|
Phlebitis
|
6 |
3 |
3 |
5 |
|
Esophagitis
|
6 |
3 |
7 |
4 |
|
Dysphagia
|
8 |
0 |
10 |
5 |
|
Hemorrhage
|
2 |
3 |
2 |
1 |
|
Extravasation
|
1 |
3 |
1 |
2 |
|
Urticaria
|
2 |
2 |
2 |
0 |
|
Recall Skin Reaction
|
1 |
1 |
2 |
0 |
The adverse experiences listed above are likely
attributable to the FAC regimen with the exception of pain on injection that
was observed mainly on the ZINECARD arm.
Myelosuppression
Patients receiving FAC with ZINECARD experienced more severe leucopenia, granulocytopenia
and thrombocytopenia at nadir than patients receiving FAC without ZINECARD,
but recovery counts were similar for the two groups of patients.
Hepatic and Renal
Some patients receiving FAC + ZINECARD or FAC + placebo experienced marked
abnormalities in hepatic or renal function tests, but the frequency and severity
of abnormalities in bilirubin, alkaline phosphatase, BUN, and creatinine were
similar for patients receiving FAC with or without ZINECARD.
DRUG INTERACTIONS
ZINECARD does not influence the pharmacokinetics of doxorubicin.
Carcinogenesis, Mutagenesis, Impairment of Fertility (see WARNINGS
section for information on human carcinogenicity) No long-term carcinogenicity
studies have been carried out with dexrazoxane in animals. Dexrazoxane was not
mutagenic in the Ames test but was found to be clastogenic to human lymphocytes
in vitro and to mouse bone marrow erythrocytes in vivo (micronucleus
test).
The possible adverse effects of ZINECARD on the fertility of humans and experimental
animals, male or female, have not been adequately studied. Testicular atrophy
was seen with dexrazoxane administration at doses as low as 30 mg/kg weekly
for 6 weeks in rats (1/3 the human dose on a mg/m 2 basis) and as
low as 20 mg/kg weekly for 13 weeks in dogs (approximately equal to the human
dose on a mg/m 2 basis).
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