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
Kytril Side Effects, and Drug Interactions - Granisetron
Kytril Side Effects, and Drug Interactions - Granisetron
SIDE EFFECTS
Injection
TABLE 10 gives the comparative frequencies of the five most commonly
reported adverse events ( ≥3%) in patients receiving granisetron
HCl injection, in single-day chemotherapy
trials. These patients received chemotherapy, primarily cisplatin,
and intravenous
fluids during the 24-hour period
following granisetron HCl injection
administration. Events were generally recorded over seven days post-granisetron
HCl injection administration.
In the absence of a placebo
group, there is uncertainty as to how many of these events should
be attributed to granisetron HCl, except for headache,
which was clearly more frequent than in comparison groups.
TABLE 10 - Principal Adverse Events in Clinical
Trials--Single-Day Chemotherapy
| Number of Patients with Event |
|
Kytril Injection |
Comparator1 |
| |
40 mcg/kg |
|
| |
(n=1,268) |
(n=422) |
|
Headache
|
14% |
6% |
|
Asthenia
|
5% |
6% |
|
Somnolence
|
4% |
15% |
|
Diarrhea
|
4% |
6% |
|
Constipation
|
3% |
3% |
|
1 Metoclopramide/dexamethasone and phenothiazines/
dexamethasone.
|
In over 3,000 patients receiving granisetron HCl injection
(2 to 160 mcg/kg) in single-day and multiple-day clinical
trials with emetogenic cancer therapies, adverse events, other than
those in TABLE 10, were observed; attribution of many of these events
to granisetron HCl is uncertain:
Hepatic: In comparative
trials, mainly with cisplatin
regimens, elevations of AST
and ALT (>2 times the
upper limit of normal)
following administration of granisetron HCl injection
occurred in 2.8% and 3.3% of patients, respectively. These frequencies
were not significantly different from those seen with comparators
(AST: 2.1%; ALT: 2.4%).
Cardiovascular: Hypertension (2%); hypotension,
arrhythmias such as sinus
bradycardia, atrial
fibrillation, varying
degrees of A-V block, ventricular
ectopy including non-sustained
tachycardia, and
ECG abnormalities have been
observed rarely.
Central Nervous System: Agitation, anxiety,
CNS stimulation
and insomnia were seen in less than 2% of patients. Extrapyramidal
syndrome occurred rarely and only in the presence of other drugs
associated with this syndrome.
Hypersensitivity: Rare cases of anaphylactoid reactions,
other allergic reactions and skin
rashes have been reported.
Other: Taste disorder
(2%), fever (3%). In
multiple-day comparative studies, fever
occurred more frequently with granisetron HCl injection (8.6%) than
with comparative drugs (3.4%, P<0.014), which usually
included dexamethasone.
Tablets
Over 2,600 patients have received oral
granisetron HCl in clinical
trials with emetogenic cancer
therapies consisting primarily of cyclophosphamide or cisplatin
regimens.
In patients receiving oral
granisetron HCl 1 mg b.i.d.
for 1, 7 or 14 days, the following table ( TABLE 11) lists adverse
experiences reported in more than 5% of the patients with comparator
and placebo incidences.
TABLE 11 - Principal Adverse Events in Clinical
Trials
| |
Oral Kytril1 |
Comparator2 |
Placebo |
| 1 mg b.i.d. |
|
|
| (n=978) |
(n=599) |
(n=185) |
|
Headache3
|
21% |
13% |
12% |
|
Constipation
|
18% |
16% |
9% |
|
Asthenia
|
14% |
10% |
4% |
|
Diarrhea
|
8% |
10% |
4% |
|
Abdominal pain
|
6% |
6% |
3% |
|
1 Adverse events were recorded for 7 days when
oral Kytril was given
on a single day and for up to 28 days when oral
Kytril was administered for 7 or 14 days.
2 Metoclopramide/dexamethasone; phenothiazines/dexamethasone;
dexamethasone alone; prochlorperazine.
3 Usually mild to moderate in severity.
|
Gastrointestinal: In
single-day dosing studies in which adverse events were collected
for 7 days, nausea (15%)
and vomiting (9%) were
recorded as adverse events after the 24-hour efficacy
assessment period.
Hepatic: In comparative
trials, elevation
of AST and ALT
(>2 times the upper limit
of normal) following the administration
of oral granisetron HCl
occurred in 5% and 6% of patients, respectively. These frequencies
were not significantly different from those seen with comparators
(AST: 2%; ALT: 9%).
Cardiovascular: Hypertension (1%); hypotension,
angina pectoris, atrial
fibrillation and
syncope have been observed
rarely.
Central Nervous System: Dizziness (3%), insomnia
(3%), anxiety (2%), somnolence
(1%). One case compatible
with but not diagnostic
of extrapyramidal symptoms has been reported in a patient
treated with oral granisetron
HCl.
Hypersensitivity: Rare cases of hypersensitivity
reactions, sometimes severe (e.g., anaphylaxis,
shortness of breath, hypotension,
urticaria) have been reported.
Other: Fever (5%). Events often associated with chemotherapy
also have been reported: leukopenia
(11%), decreased appetite
(5%), anemia (4%), alopecia
(3%), thrombocytopenia
(3%).
Over 5,000 patients have received injectable
granisetron HCl in clinical trials.
TABLE 12 gives the comparative frequencies of the five commonly
reported adverse events ( ≥3%) in patients receiving granisetron
HCl injection, 40 mcg/kg, in single-day chemotherapy
trials. These patients received chemotherapy, primarily cisplatin,
and intravenous
fluids during the 24- hour period following granisetron HCl injection
administration.
TABLE 12 - Principal Adverse Events in Clinical
Trials--Single-Day Chemotherapy
| Number of Patients with Event |
|
Kytril Injection1 |
Comparator2 |
| |
40 mcg/kg |
|
| |
(n=1,268) |
(n=422) |
|
Headache
|
14% |
6% |
|
Asthenia
|
5% |
6% |
|
Somnolence
|
4% |
15% |
|
Diarrhea
|
4% |
6% |
|
Constipation
|
3% |
3% |
|
1 Adverse events were generally
recorded over 7 days post-Kytril Injection administration.
|
|
2 Metoclopramide/ dexamethasone
and phenothiazines/ dexamethasone.
|
In the absence of a
placebo group, there
is uncertainty as to how many of these events should be attributed
to granisetron HCl, except for headache, which was clearly more
frequent than in comparison groups.
DRUG INTERACTIONS
Granisetron does not induce or inhibit the cytochrome
P-450 drug- metabolizing enzyme system. There have been no
definitive drug-drug
interaction studies to examine pharmacokinetic or pharmacodynamic
interaction with other drugs but, in humans, granisetron HCl injection
has been safely administered with drugs representing benzodiazepines,
neuroleptics and anti-ulcer medications commonly prescribed with
antiemetic treatments.
Granisetron HCl injection also does not appear to interact with
emetogenic cancer chemotherapies.
Because granisetron is metabolized by hepatic
cytochrome P-450
drug-metabolizing enzymes, inducers or inhibitors of these enzymes
may change the clearance and, hence, the half-life
of granisetron.
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