Download Drug Class 5-HT3 Receptor Antagonists (Anti

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Drug Class
5-HT3 Receptor Antagonists (Anti- Emetics)
Drugs
Reviewed
Dolasetron
Granisetron
Ondansetron
Anzemet®
Kytril®
Zofran®, Zofran® ODT*
Executive Summary
Overview and Pharmacology
These agents exert their activities by the same mechanism, antagonism of the type serotonin (5-hydroxytryptamine
[5-HT3]) receptor. They are all highly selective with high affinities for this receptor.
The American Society of Clinical Oncology (ASCO) has developed evidence-based recommendations on the use of
the 5-HT3 receptor antagonists. These clinical practice guidelines conclude that at equivalent doses for acute,
delayed emesis (vomiting occurring > 24 hours after chemotherapy) and treatment of chemotherapy-induced emesis,
the 5-HT3 receptor antagonists have equivalent safety and efficacy and may be used interchangeably. For multiple
consecutive days of chemotherapy, the selected antiemetic should be administered for each day of the
chemotherapy. For radiation-induced emesis, a 5-HT3 receptor antagonist should be given with or without a
corticosteroid before each fraction and for at least 24 hours after.7
The American Society of Health System Pharmacists (ASHP) also published a guideline for the prevention of PONV.
It concluded that prophylactic antiemetic therapy for PONV is effective, but combinations of agents may be necessary
for high-risk patients. If PONV occurs in the immediate postoperative period, an antiemetic from a class different from
that of the prophylactic agents should be administered for the treatment of vomiting. For every 100 patients who vomit
postoperatively, 20-30 will stop vomiting who would not have done so had they received placebo instead of a 5-HT3
receptor antagonist. Study results that have been reported without clearly differentiating between efficacy for nausea
and efficacy for vomiting may give a false impression of the overall efficacy of 5-HT3 receptor antagonists. The
guideline also concluded that there was no difference in efficacy among ondansetron 1, 4, and 8 mg; dolasetron
mesylate 12.5, 25, 50, and 100 mg; and granisetron 0.1, 1, and 3 mg.8
The ASCO guidelines recommend that prevention of post-operative nausea and vomiting (PONV) should be reserved
for use in patients with high-risk factors such as obesity, preoperative anxiety, history of previous PONV or motion
sickness, delayed gastric emptying, abdominal, gynecological or otolaryngologic surgical procedures, or long duration
of surgery. The choice of agent should be based on patient-specific factors and cost.7
The American Society of Health System Pharmacists (ASHP) concludes the optimal approach to controlling delayed
emesis remains controversial. Control of acute nausea and vomiting is essential. It is one of the most important
predictors for the development of delayed nausea and vomiting and will have a major impact in its prevention.
Control of anticipatory nausea and vomiting is through effective pharmacologic prophylaxis for acute and delayed
emesis. There is no role for the 5-HT3 receptor antagonists in anticipatory nausea and vomiting. Round-the-clock
dosing of 5-HT3 receptor antagonists may be used in the management of breakthrough nausea and vomiting. The
optimal management of breakthrough nausea and vomiting has not been confirmed. Therefore, the choice of agent
should be based on adverse effects and cost. 8
Adverse Effects
All three 5-HT3 receptor antagonists share the same low side-effect pattern, with mild headache, transient
asymptomatic transaminase elevations, malaise, fatigue, constipation, and dizziness being among the most
commonly reported adverse events.
Special Populations
The safety and efficacy of these products in children has not been established.
Notice/Disclaimer: The clinical information contained herein is provided for the express purpose of aiding the Pharmacy and Therapeutics ("P&T") Committee members
in reviewing medications for inclusion in or exclusion from the Preferred Drug List. This information is not intended nor should it be used as a substitute for the expertise,
skill, and judgment of physicians, pharmacists, or other healthcare professionals. The absence of a warning for any given drug or drug combination should not be
construed to indicate that the drug or drug combination is safe, appropriate or effective for any given patient. This information is intended to supplement the knowledge
and additional resources available to the P&T Committee members and should not be considered the sole criteria used by the P&T Committee in deciding what
medications will be included or excluded from the Preferred Drug List.
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Drug Class
5-HT3 Receptor Antagonists (Anti- Emetics)
Use in Pregnancy
All of the 5-HT3 receptor antagonists are classified as pregnancy category B.
Efficacy
Few head-to-head comparative studies for the prevention of post-operative nausea and vomiting (PONV) exist with
the 5-HT3 receptor antagonists. However, studies of individual agents or in comparison to traditional antiemetics
show similar response rates for the prevention of PONV. Oral ondansetron and dolasetron have been shown to be
effective for the prevention of PONV when compared to placebo. Trials of parenteral granisetron have shown it to be
effective but an optimal dose is unclear. There are no published studies with oral granisetron in the prevention of
PONV due to general anesthesia or opioid-induced nausea and vomiting. Response rates were comparable to those
seen with droperidol and metoclopramide. There are no published studies supporting the use of granisetron for
treating PONV.
Several studies have supported the efficacy of dolasetron, granisetron or ondansetron in the prevention of
radiotherapy induced nausea and vomiting. When these agents are used, the drug should be given on each day of
radiotherapy with oral administration being the preferred route. The American Society of Clinical Oncology (ASCO)
Clinical Practice Guidelines concludes a 5-HT3 receptor antagonists should be given with or without a corticosteroid
before each fraction of total body irradiation and for at least 24 hours after. For intermediate risk (i.e., hemibody
irradiation) a 5-HT3 receptor antagonist or a dopamine receptor antagonist should be given before each fraction. For
low risk irradiation, antiemetic treatment should be given on an as-needed basis only.
Dolasetron, ondansetron, and granisetron are considered equally efficacious in preventing acute chemotherapyinduced nausea and vomiting from highly emetogenic chemotherapy. Both oral dolasetron and granisetron have
been proven to be highly effective in chemotherapy-induced emesis from high-dose cisplatin. Response rates have
equaled those obtained from the use of parenteral formulations. Similar response rates are seen with oral dolasetron,
granisetron, and ondansetron when used for prophylaxis of acute chemotherapy-induced emesis from moderately
emetogenic chemotherapy.
In summary, the 5-HT3 receptor antagonists are an essential part of the armamentarium in the prevention of postoperative nausea and vomiting and in the prevention of chemotherapy- and radiotherapy-induced nausea and
vomiting. Currently, the optimal approach to controlling delayed emesis remains controversial. Prevention of postoperative nausea and vomiting (PONV) should be reserved for use in patients with high-risk factors. Clinical studies
suggest clinical interchangeability for most patients; the availability of at least one agent without restrictions has been
recommended.
Notice/Disclaimer: The clinical information contained herein is provided for the express purpose of aiding the Pharmacy and Therapeutics ("P&T") Committee members
in reviewing medications for inclusion in or exclusion from the Preferred Drug List. This information is not intended nor should it be used as a substitute for the expertise,
skill, and judgment of physicians, pharmacists, or other healthcare professionals. The absence of a warning for any given drug or drug combination should not be
construed to indicate that the drug or drug combination is safe, appropriate or effective for any given patient. This information is intended to supplement the knowledge
and additional resources available to the P&T Committee members and should not be considered the sole criteria used by the P&T Committee in deciding what
medications will be included or excluded from the Preferred Drug List.
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Summary of Indications1-6
Dolasetron
Granisetron
Ondansetron
Indications
Anzemet®
Prevention of PONV+
Prevention of CINV‡ - highly emetogenic
Prevention of CINV‡ –moderately emetogenic
RINV§
Oral
√
√
Kytril®
Parenteral
√
√
√
Oral
√
√
√
Zofran®, Zofran® ODT*
Parenteral
√
√
√
Oral
√
√
√
Parenteral
√
√
√
+
Post-operative nausea and vomiting
Chemotherapy induced nausea and vomiting
Radiotherapy induced nausea and vomiting
‡
§
The 5-HT3 receptor antagonists are not indicated by the FDA to treat delayed chemotherapy-induced nausea and
vomiting, anticipatory nausea and vomiting from chemotherapy, or breakthrough vomiting from chemotherapy.
Available Products
Products
Date of FDA
Approval18
Generic
Available18
Dolasetron
Granisetron
Ondansetron
Anzemet®
Kytril®
Oral, Injection 1997
Oral tablets1995
Oral Solution 2001
Injection 1994
Zofran®, Zofran® ODT*
Oral 4 mg & 8 mg 1992; 24 mg 1999
Oral Solution 1997
ODT 1999
Injection 1991
No
(generic expected mid-2006)
No
No
Manufacturer1-6
Sanofi-Aventis
Roche
GlaxoSmithKline
Dosage Forms/
Route of
Administration 1-6
Tablets: 50 mg, 100 mg
Injection: 20 mg/ml (Available in 0.625
ml single-use ampules or vials; 5 ml
single-use vial & 25 ml multi-dose vial)
Tablets: 1 mg
Oral Solution: 2 mg/10 ml
Injection: 1 mg/1 ml as free base
[Available in 1 ml single-use and 4 ml multiuse vial; 0.1 mg/1ml (free base) in
preservative free single-use vials]
Prevention of PONV+
100 mg within 2 hours of surgery
Prevention of CINV‡ -moderately
emetogenic
100 mg 1 hour before
Prevention of CINV‡ - highly emetogenic
1 mg twice daily 1st dose hour or 2 mg daily
1 hour prior to treatment #
Prevention of CINV‡ -moderately
emetogenic
1 mg twice daily 1st dose hour or 2 mg daily
1 hour prior to treatment#
RINV§
2 mg within 1 hour of therapy
Tablets: 4 mg, 8 mg, 24 mg
ODT tablets: 4 mg, 8 mg
Oral Solution: 4 mg/ 5ml
Injection: 2 mg/ml (Available in 2 ml singledose and 20-ml multidose vials; 32 mg/50 ml in
5% dextrose)
Prevention of PONV+
16 mg dose 1 hour prior to treatment#
Prevention of CINV‡ - highly emetogenic
24 mg tablet single dose 30 min prior to start of
chemo
8 mg twice daily; first dose 1 hour prior to
treatment#
Prevention of CINV‡ -moderately emetogenic
8 mg 1-2 hours prior to treatment#
RINV§
8 mg 1-2 hours prior to treatment#
Dosing
Guidelines for
Healthy
Adults1-6
*Oral disintegrating tablet
+Postoperative nausea and vomiting (PONV)
‡Chemotherapy induced nausea and vomiting (CINV)
§Radiotherapy induced nausea and vomiting
#Given prior to chemotherapy or anesthesia
Notice/Disclaimer: The clinical information contained herein is provided for the express purpose of aiding the Pharmacy and Therapeutics ("P&T") Committee members in reviewing
medications for inclusion in or exclusion from the Preferred Drug List. This information is not intended nor should it be used as a substitute for the expertise, skill, and judgment of physicians,
pharmacists, or other healthcare professionals. The absence of a warning for any given drug or drug combination should not be construed to indicate that the drug or drug combination is
safe, appropriate or effective for any given patient. This information is intended to supplement the knowledge and additional resources available to the P&T Committee members and should
not be considered the sole criteria used by the P&T Committee in deciding what medications will be included or excluded from the Preferred Drug List.
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Pharmacology1-6
The 5-HT3 receptor antagonists are highly selective agents which competitively inhibit the binding of serotonin to 5-HT3
receptors. Their antiemetic effects result from peripheral blockage of 5-HT3 receptors on vagal nerve terminals and
central blockage in the area postrema and nucleus tractus solitarius. This equates with chemoreceptor trigger zone
(CTZ) blockade. The 5-HT3 receptor antagonists have essentially no affinity for alpha adrenergic, dopaminergic, or
histamine receptors. This characteristic eliminates the undesirable side effects of sedation, hypotension, and
extrapyramidal reactions that occur when using other nonselective antiemetic agents.
Pharmacokinetics1-6
Products
Bioavailability (%)
Protein binding (%)
Metabolism
Half-life (hours)
Excretion
†
Dolasetron
Granisetron
Ondansetron
Anzemet®
75
69-77
Hepatic-Cytochrome P450
7
Renal (50%)
Kytril®
60
60
Hepatic-Cytochrome P450
6.2
Renal (11% unchanged)
Zofran®, Zofran® ODT*
60
70-76
Hepatic-Cytochrome P450
3
Renal (5% unchanged)
Dolasetron undergoes rapid and near complete metabolism to the active metabolite hydrodolasetron in </= 10 minutes.
Contraindications1-6
All are contraindicated in patients with known hypersensitivity to the drug or to any of its components.
Drug Interactions1-6
Dolasetron, granisetron and ondansetron do not induce or inhibit the cytochrome P450 enzyme system. Inducers or
inhibitors of these P-450 enzymes may alter the clearance or half-life of the 5-HT3 receptor antagonists. There have
been no major drug-drug interaction studies to examine pharmacokinetic or pharmacodynamic interactions with other
drugs. However, 5-HT3 receptor antagonists have been safely administered with benzodiazepines, neuroleptics, and
anti-ulcer medications commonly prescribed with chemotherapy regimens.
Dolasetron should be administered with caution in patients receiving anti-arrhythmics, drugs that can prolong the QTc
interval, diuretics which can induce electrolyte disturbances and cumulative high dose anthracycline therapy.
Precautions/Warnings/Monitoring1-6
Hypersensitivity reactions may occur in patients who have exhibited hypersensitivity to other selective 5-HT3 receptor
antagonists.
Adverse Effects1-6
The adverse event profile for the 5-HT3 receptor antagonists are similar including headache, malaise or fatigue,
constipation, diarrhea, and dizziness.
Notice/Disclaimer: The clinical information contained herein is provided for the express purpose of aiding the Pharmacy and Therapeutics ("P&T") Committee members in reviewing
medications for inclusion in or exclusion from the Preferred Drug List. This information is not intended nor should it be used as a substitute for the expertise, skill, and judgment of physicians,
pharmacists, or other healthcare professionals. The absence of a warning for any given drug or drug combination should not be construed to indicate that the drug or drug combination is
safe, appropriate or effective for any given patient. This information is intended to supplement the knowledge and additional resources available to the P&T Committee members and should
not be considered the sole criteria used by the P&T Committee in deciding what medications will be included or excluded from the Preferred Drug List.
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Dosage and Administration1-6
Prevention of PONV+
Dolasetron
Granisetron
oral
parenteral
oral
100 mg within 2 hours of surgery
12.5 mg IV 15 minutes prior#
parenteral
Ondansetron
oral
16 mg dose 1 hour prior#
parenteral
4 mg IV dose #
Postoperative nausea and vomiting (PONV)
Chemotherapy induced nausea and vomiting (CINV)
#Given prior to chemotherapy or anesthesia
+
‡
Prevention of CINV‡ highly emetogenic
Prevention of CINV‡ moderately emetogenic
RadiotherapyInduced Nausea &
Vomiting
100 mg 1 hour before
1.8 mg/kg IV 30 minutes prior#
1 mg BID 1st dose or 2 mg
QD 1 hour prior#
10 mcg/kg within 30 minutes
prior#
24 mg tablet single dose 30 min
prior to start of chemo
8 mg BID first dose 1 hour prior#
Three 0.15 mg/kg doses
infused over 15 minutes 30 min
before and 4, 8 hours post first
dose OR 32 mg single dose
infused over 15 minutes 30
minutes prior#
1 mg BID 1st dose or 2 mg
QD 1 hour prior#
10 mcg/kg within 30 minutes
before#
8 mg 1-2 hours prior#
2 mg within 1 hour
of therapy
8 mg 1-2 hours prior#
BID= twice daily
QD= daily
Q8H=every 8 hours
Dosage and Administration for Special Populations1-6
No dosage adjustments are necessary for the elderly, pediatric, or renal failure patients for any of the three products.
Zofran sets a maximum daily dose of 8 mg for patients with severe hepatic impairment (Child-Pugh score of 10 or
greater). Neither Kytril nor Anzemet require a dosage adjustment for hepatically impaired patients.
Notice/Disclaimer: The clinical information contained herein is provided for the express purpose of aiding the Pharmacy and Therapeutics ("P&T") Committee members in reviewing
medications for inclusion in or exclusion from the Preferred Drug List. This information is not intended nor should it be used as a substitute for the expertise, skill, and judgment of physicians,
pharmacists, or other healthcare professionals. The absence of a warning for any given drug or drug combination should not be construed to indicate that the drug or drug combination is
safe, appropriate or effective for any given patient. This information is intended to supplement the knowledge and additional resources available to the P&T Committee members and should
not be considered the sole criteria used by the P&T Committee in deciding what medications will be included or excluded from the Preferred Drug List.
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Clinical Trials
Korttila K, Clergue F, Lesser R, et al. Intravenous Dolasetron and Ondansetron in Prevention of Postoperative Nausea and Vomiting:
A Multicenter, Double-blind, Placebo-controlled Study. Acta Anaesthesiologica Scandinavica 1997;41:914-22.
Drug
Regimens
Ondansetron
4 mg IV
versus
Dolasetron 25
mg oral
versus
Dolasetron 50
mg oral
versus
Placebo
N
N=
514
Study design,
demographics
Randomized
double-blind,
placebo controlled,
multi-centered
Population
studied:
Objective,
endpoints
Primary
Endpoint:
Response to
treatment and
nausea
incidence.
Adults
Doses given
15 minutes
prior to
induction of
anesthesia
Results/Comments
Dose and
Percentage of patients with
Number
Route
emesis or nausea
Complete Response (zero emetic episodes and no rescue medication)
ondansetron
4 mg IV
130
64%
dolasetron
25 mg oral
127
51%
dolasetron
50 mg oral
129
71%
placebo
128
49%
Total Response (complete response plus no nausea up to 6 hrs post-recovery)
ondansetron
4 mg IV
130
54%
dolasetron
25 mg oral
127
43%
dolasetron
50 mg oral
129
50%
placebo
128
36%
Nausea incidence
ondansetron
4 mg IV
130
38%
dolasetron
25 mg oral
127
43%
dolasetron
50 mg oral
129
29%
placebo
128
56%
Drug
Author’s Conclusion
No significant difference between ondansetron and dolasetron 25 mg or 50 mg.
Karamanlioglu B, Turan A, Memis D. Sut N. Comparison of oral dolasetron and ondansetron in the prophylaxis of postoperative
nausea and vomiting in children. European Journal of Anaesthesiology 2003;20:831-835.
Drug
Regimens
Dolasetron
1.8 mg/kg
oral
versus
Ondansetron
0.15 mg/kg
oral
versus
Placebo
N
N=150
Study design,
demographics
Randomized
double-blind,
placebo controlled,
multi-centered
Population
studied:
Children
Objective,
endpoints
Primary
Endpoint:
Evaluation of
nausea and
vomiting by
utilizing a
scale of 0-3
(0=no
nausea,
1=nausea;
2=retching;
3= vomiting)
Results/Comments
Postoperative
Dolasetron
period
N=50
0-1 hours
n
%
Score
0
42
84
1
4
8
2
2
4
3
2
4
Total PONV
8
16
1-24 hours
0
42
84
1
4*
8
2
2
4
3
2*
4
Total PONV
8
16
0-24 hours
0
34
68
1
8*
16
2
4
8
3
4*
8
Total PONV
16
32
*P<0.05 compared with placebo
Ondansetron
N=50
n
%
Placebo
N=50
n
%
40
5
2
3
10
80
10
4
6
20
35
8
2
5
15
70
16
4
10
30
36
8
1
5
14
72
16
2
10
28
26
12
2
10
24
52
24
4
20
48
26
13*
3
8*
24
52
26
6
16
48
11
20
4
15
39
22
40
8
30
78
Author’s Conclusion
There were no important differences between dolasetron and ondansetron, or
between ondansetron and placebo.
Notice/Disclaimer: The clinical information contained herein is provided for the express purpose of aiding the Pharmacy and Therapeutics ("P&T") Committee members in reviewing
medications for inclusion in or exclusion from the Preferred Drug List. This information is not intended nor should it be used as a substitute for the expertise, skill, and judgment of physicians,
pharmacists, or other healthcare professionals. The absence of a warning for any given drug or drug combination should not be construed to indicate that the drug or drug combination is
safe, appropriate or effective for any given patient. This information is intended to supplement the knowledge and additional resources available to the P&T Committee members and should
not be considered the sole criteria used by the P&T Committee in deciding what medications will be included or excluded from the Preferred Drug List.
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Martoni A, Angelelli B, Guaraldi M, Strocchi E, Pannuti F. An Open Randomized Cross-over Study on Granisetron Versus
Ondansetron in the Prevention of Acute Emesis Induced by Moderate Dose Cisplatin-containing Regimens. European Journal of
Cancer 1996;32A(1):82-85.
Drug
Regimens
Granisetron
(GRA) 3 mg
IV
versus
Ondansetron
(OND) 8 mg
IV + 8 mg
orally Q8H
for 3 doses
N
N= 124
Study design,
demographics
Randomized,
crossover
Objective,
endpoints
Primary
Endpoint:
Results/Comments
Primary Results
Emesis and
nausea control
First Cycle
Chemotherapy
Regimen:
cisplatin
Second Cycle
First & Second Cycle
n
No nausea
No vomiting
No nausea or vomiting
n
No nausea
No vomiting
No nausea or vomiting
n
No nausea
No vomiting
No nausea or vomiting
OND
58
60%
74%
59%
52
44%
61.5%.
40%
110
53%
58%
50%
GRA
66
64%
76%
62%
49
55%
65%
53%
115
60%
71%
58%
P*
0.70
0.83
0.69
0.25
0.73
0.20
0.27
0.61
0.21
*Person’s chi-square
Author’s Conclusion:
Cross-over analysis confirmed no difference between the two anti-emetic
treatments.
Gebbia V, Cannata G, Testa A, Curto G, Valenza R, Cipolla C, Latteri M, Gebbia N. Ondansetron versus Granisetron in the
Prevention of Chemotherapy-Induced Nausea and Vomiting. Cancer 1994;74:1945-52
Drug
Regimens
Ondansetron
(OND) 24 mg
IV
versus
Granisetron
(GRA) 3 mg
IV
N
N=182
Study design,
demographics
Randomized
prospective open
label trial
Objective,
endpoints
Emesis and
nausea control
Chemotherapy
Regimen:
Study 1:
Highly
emetogenic
chemotherapy
(cisplatin 70
2
mg/m or more
with cyclophosphamide,
epidoxorubicin
or vinca
alkaloids)
Study 2:
Moderately
emetogenic
chemotherapy
[CMF regimen
(cyclophospha
mide, methotrexate & 5fluorouracil)]
Results/Comments
Primary Results
Response
Study 1
n
Complete response (no vomit or retches)
Major response (1-2 emetic episodes)
Minor response (3-5 emetic episodes)
Failure (> 5 emetic episodes)
Study 1
n
Complete response (no vomit or retches)
Major response (1-2 emetic episodes)
Minor response (3-5 emetic episodes)
Failure (> 5 emetic episodes)
NS=not significant
OND
84
52%
29%
14%
5%
46
43%
22%.
26%
9%
GRA
82
49%
24%
12%
15%
46
35%
24%
15%
26%
P
NS
NS
NS
NS
NS
NS
NS
NS
Author’s Conclusion:
No statistically significant difference in any response category was seen between
the groups.
Notice/Disclaimer: The clinical information contained herein is provided for the express purpose of aiding the Pharmacy and Therapeutics ("P&T") Committee members in reviewing
medications for inclusion in or exclusion from the Preferred Drug List. This information is not intended nor should it be used as a substitute for the expertise, skill, and judgment of physicians,
pharmacists, or other healthcare professionals. The absence of a warning for any given drug or drug combination should not be construed to indicate that the drug or drug combination is
safe, appropriate or effective for any given patient. This information is intended to supplement the knowledge and additional resources available to the P&T Committee members and should
not be considered the sole criteria used by the P&T Committee in deciding what medications will be included or excluded from the Preferred Drug List.
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Perez EA, Hesketh P, et al. Comparison of Single-dose Oral Granisetron Versus Intravenous Ondansetron in the Prevention of
Nausea and Vomiting Induced by Moderately Emetogenic Chemotherapy: A Multicenter, Double-Blind, Randomized Parallel Study.
Journal of Clinical Oncology 1998;16:754-760.
Drug
Regimens
Granisetron
2 mg PO
versus
Ondansetron
32 mg IV
N
N=1085
Study design,
demographics
Randomized,
double-blind,
parallel-group
Objective,
endpoints
Emesis and
nausea control
Chemotherapy
Treatment
Cyclophospha
mide
Carboplatin
Results/Comments
Primary Results
Percent of Patients Who Achieved Total Control Over 24 and 48 hours by
Corticosteroid Use and Chemotherapy Type
Response 0-24 hours
OND
GRA
P
Use of dexamethasone/methylprednisolone
61.9%
59.8%
0.68
Nonuse of dexamethasone/methylprednisolone
48.5%
50.0%
Cyclophosphamide
55.3%
54.2%
NA
Carboplatin
74%
72.6%
Response 0-48 hours
Use of dexamethasone/methylprednisolone
48.3%
44.7%
0.384
Nonuse of dexamethasone/methylprednisolone
39.6%.
40%
Cyclophosphamide
41.5%
39.8%
NA
Carboplatin
63.9%
57.5%
Author’s Conclusion: No significant difference with emesis and nausea
Stewart A, McQuade B, Cronje JDE, et al. Ondansetron Compared with Granisetron in the Prophylaxis of Cyclophosphamideinduced Emesis in Outpatients: A Multicenter, Double-blind, Double-dummy, Randomized, parallel-group study. Oncology
1995;52:202-10.
Drug
Regimens
Granisetron
3 mg IV
versus
Ondansetron
8 mg IV + 8
mg PO BID
for 4 days
versus
Ondansetron
8 mg PO BID
for 4 days
N
N=488
Study design,
demographics
Randomized,
double-blind,
parallel-group
Objective,
endpoints
Results/Comments
Emesis control
Chemotherapy
Treatment
Cyclophospha
mide
Author’s Conclusion:
No significant differences in emesis control for day one. Significant difference on
day 2-5 with higher rescue and withdrawal with granisetron.
Notice/Disclaimer: The clinical information contained herein is provided for the express purpose of aiding the Pharmacy and Therapeutics ("P&T") Committee members in reviewing
medications for inclusion in or exclusion from the Preferred Drug List. This information is not intended nor should it be used as a substitute for the expertise, skill, and judgment of physicians,
pharmacists, or other healthcare professionals. The absence of a warning for any given drug or drug combination should not be construed to indicate that the drug or drug combination is
safe, appropriate or effective for any given patient. This information is intended to supplement the knowledge and additional resources available to the P&T Committee members and should
not be considered the sole criteria used by the P&T Committee in deciding what medications will be included or excluded from the Preferred Drug List.
PDL Drug Class Review
First Health Services Proprietary and Confidential
Unauthorized Reproduction and/or Distribution is Strictly Prohibited
Page 9
References
Anzemet® tablets product information. Sanofi-Aventis Pharmaceuticals. February 2005
Anzemet® injection product information. Sanofi-Aventis Pharmaceuticals. October 2003
Kytril® tablets and solution product information. Roche Pharmaceuticals. June 2001
Kytril® injection product information. Roche Pharmaceuticals. September 2004.
Zofran® and Zofran® ODT product information. GlaxoSmithKline. June 2005.
Zofran® injection product information. GlaxoSmithKline. June 2005.
American Society of Clinical Oncology. Recommendations for the Use of Antiemetics: Evidence-Based, Clinical
Practice Guidelines. Journal of Clinical Oncology 1999;17(9):2971-2994.
8. Golembiewski J, Chernin E, Chopra T. Prevention and Treatment of Postoperative Nausea and Vomiting. Am J
Health-Syst Pharm 2005;62(12):1247-1260.
9. Warr D, Bramwell V, Anderson D, Charette M, and the Systemic Treatment Disease Site Group. Use of 5-HT3
receptor antagonists in patient receiving moderately or highly emetogenic chemotherapy. Curr Oncol 2001;8:6982.
10. Korttila K, Clergue F, Lesser R, et al. Intravenous Dolasetron and Ondansetron in Prevention of Postoperative
Nausea and Vomiting: A Multicenter, Double-blind, Placebo-controlled Study. Acta Anaesthesiologica
Scandinavica 1997;41:914-22.
11. Karamanlioglu B, Turan A, Memis D. Sut N. Comparison of oral dolasetron and ondansetron in the prophylaxis of
postoperative nausea and vomiting in children. European Journal of Anaesthesiology 2003;20:831-835.
12. Martoni A, Angelelli B, Guaraldi M, Strocchi E, Pannuti F. An Open Randomized Cross-over Study on
Granisetron Versus Ondansetron in the Prevention of Acute Emesis Induced by Moderate Dose Cisplatincontaining Regimens. European Journal of Cancer 1996;32A(1):82-85.
13. Gebbia V, Cannata G, Testa A, Curto G, Valenza R, Cipolla C, Latteri M, Gebbia N. Ondansetron versus
Granisetron in the Prevention of Chemotherapy-Induced Nausea and Vomiting. Cancer 1994;74:1945-52
14. Perez EA, Hesketh P, et al. Comparison of Single-dose Oral Granisetron Versus Intravenous Ondansetron in the
Prevention of Nausea and Vomiting Induced by Moderately Emetogenic Chemotherapy: A Multicenter, DoubleBlind, Randomized Parallel Study. Journal of Clinical Oncology 1998;16:754-760.
15. Stewart A, McQuade B, Cronje JDE, et al. Ondansetron Compared with Granisetron in the Prophylaxis of
Cyclophosphamide-induced Emesis in Outpatients: A Multicenter, Double-blind, Double-dummy, Randomized,
parallel-group study. Oncology 1995;52:202-10.
16. VHA Pharmacy Benefits Management Strategic Healthcare Group and the Medical Advisory Panel, Drug Class
Review – 5-Hydroxytryptamine Receptor Antagonists. August 1999. http://www.pbm.va.gov/reviews/5ht3.pdf
Accessed 10/17/2005
17. Pharmacy Benefits Management Strategic Healthcare Group, Department of Veterans Affairs.
http://www.pbm.va.gov/PBM/menu.asp. Accessed 3/2006.
18. Drugs@FDA http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm accessed 3/2/2006.
1.
2.
3.
4.
5.
6.
7.
Notice/Disclaimer: The clinical information contained herein is provided for the express purpose of aiding the Pharmacy and Therapeutics ("P&T") Committee members in reviewing
medications for inclusion in or exclusion from the Preferred Drug List. This information is not intended nor should it be used as a substitute for the expertise, skill, and judgment of physicians,
pharmacists, or other healthcare professionals. The absence of a warning for any given drug or drug combination should not be construed to indicate that the drug or drug combination is
safe, appropriate or effective for any given patient. This information is intended to supplement the knowledge and additional resources available to the P&T Committee members and should
not be considered the sole criteria used by the P&T Committee in deciding what medications will be included or excluded from the Preferred Drug List.