1) EMENDâ„¢ is a new NK1 receptor antagonist approved for preventing acute and delayed nausea and vomiting due to highly and moderately emetogenic chemotherapy. 2) It works by blocking the neurokinin-1 receptor pathway in the brain and should be used in combination with a 5-HT3 receptor antagonist and dexamethasone. 3) Clinical trials showed that combining EMENDâ„¢ with a 5-HT3 receptor antagonist and dexamethasone helped significantly more patients receiving cisplatin chemotherapy to remain vomit-free over 5 days compared to a regimen with just a 5-HT3 receptor antagonist and dexamethasone.

1. DRAFT COPY
Introducing EMEND™ (aprepitant)
The First Neurokinin-1 (NK1) Receptor Antagonist
For patients receiving highly emetogenic chemotherapy
and women receiving anthracycline and
cyclophosphamide-based chemotherapy
e
pl
m
sa
g
in
rit
iw
sk
w
ko
z
ac
K
al
st
ry
C
From the Start.
Combination therapy with EMEND ™
helps prevent CINV—from Cycle 1, Day 1.
DRug INTERAcTIoNS
INDIcATIoNS or back-up methods of contraception should be used during
treatment with EMEND™ and for 1 month following the last
Serious Drug Interactions
EMEND™ (aprepitant), in combination with a 5-HT3 antagonist
dose of EMEND™.
class of antiemetics and dexamethasone, is indicated for the: • EMEND™ should be used with caution in patients receiving
ADVERSE REAcTIoNS
concomitant medicinal products that are primarily metabolized
1. prevention of acute and delayed nausea and vomiting due to
through CYP3A4 and CYP2C9, including chemotherapy agents.
highly emetogenic cancer chemotherapy Clinical Trial Adverse Experiences
Inhibition of CYP3A4 by aprepitant could result The most common adverse experiences, regardless of causality,
2. prevention of nausea and vomiting in women due to treatment
in elevated plasma concentrations of these concomitant occurring in patients receiving highly emetogenic chemotherapy
with moderately emetogenic cancer chemotherapy consisting of
medicinal products. Induction of CYP2C9 by aprepitant could who were treated with aprepitant in clinical studies (cycle 1)
cyclophosphamide and anthracycline
result in decreased plasma were: asthenia/ fatigue (17.8%), nausea (12.7%), hiccups
concentrations of these concomitant medicinal products.
coNTRAINDIcATIoNS (10.8%), diarrhea (10.3%), constipation (10.3%), anorexia
(10.1%). The most common adverse experiences, regardless of
• The effect of EMEND™ on the pharmacokinetics of orally
EMEND™ is contraindicated in patients who are hypersensitive to
causality, occurring in patients receiving moderately emetogenic
any component of the formulation. EMEND™ should not be used administered CYP3A4 substrates is greater than the effect
chemotherapy who were treated with aprepitant in clinical studies
of EMEND™ on the pharmacokinetics of intravenously
concurrently with pimozide, terfenadine, astemizole, or cisapride.
(cycle 1) were: alopecia (24.0%), fatigue (21.9%), headache
administered CYP3A4 substrates.
Inhibition of cytochrome P450 isoenzyme 3A4 (CYP3A4) by
(16.4%), constipation (12.3%), neutropenia (8.9%).
aprepitant could result in elevated plasma concentrations of these • The efficacy of hormonal contraceptives during and for 28 days
drugs, potentially causing serious or life-threatening reactions. after administration of EMEND™ may be reduced. Alternative
Reference:
1. Data on file, Merck Frosst Canada Ltd.: EMEND™ — Product Monograph, 2007.
CINV = chemotherapy-induced nausea and vomiting
EMEND™ is a Trademark of Merck & Co., Inc. Used under license.

2. DRAFT COPY
5-HT3 receptor antagonists may not be enough
How Many of Your Patients
Treated With a 5-HT3 Receptor
Antagonist Still Experience
chemotherapy-induced Nausea
and Vomiting?
CINV Remains a Critical Problem
Observed Incidence of Nausea and Vomiting in Patients
Receiving Highly Emetogenic Chemotherapy (Cycle 1)
33%
Nausea
Acute
Day 1
12%
Vomiting
60%
Nausea
Delayed
Day 2–5
50%
Vomiting
0 10 20 30 40 50 60 70
% of patients with nausea or vomiting (N=67)
• Up to 60% of patients treated with antiemetics continued to
experience nausea and vomiting
Observed Incidence of Nausea and Vomiting in Patients
Receiving Moderately Emetogenic Chemotherapy (Cycle 1)
e
pl
m
sa
g
in
37%
rit
Nausea
iw
sk
Acute
w
ko
Day 1
z
ac
K
13%
al
Vomiting
st
ry
C
52%
Nausea
Delayed
Day 2–5
28%
Vomiting
0 10 20 30 40 50 60 70
% of patients with nausea or vomiting (N=231)
• Up to 52% of patients treated with antiemetics continued to
experience nausea and vomiting
Study Design and Results
In this multinational, prospective, observational study, physicians/nurses (N=13/11) estimated the frequency of acute (Day 1) and delayed (Days 2-5) nausea
and vomiting after first administration of highly or moderately emetogenic chemotherapy and antiemetic treatment. Chemotherapy-naive patients older than
18 years (N=298) received either single-agent or combination therapy: highly emetogenic chemotherapy, such as cisplatin >50 mg/m2 or cyclophosphamide
>1500 mg/m2, or moderately emetogenic chemotherapy, such as doxorubicin >20 mg/m2 or cyclophosphamide <1500 mg/m2. Patients recorded emetic
episodes, nausea assessments, and antiemetic medications taken daily in a 6-day diary, which was then evaluated and matched against the medical
predictions. Most patients (97%) received 5-HT3 antagonist; 78% also received a corticosteroid (mean 2.3 antiemetic agents per patient). The most common
duration of 5-HT3 antagonist and corticosteroid therapy was 3 days.
Reference:
Grunberg SM, Deuson RR, Mavros P et al. Incidence of chemotherapy-induced nausea and vomiting
after modern antiemetics. Cancer 2004;100:2261–2268.
CINV = chemotherapy-induced nausea and vomiting
EMEND™ is a Trademark of Merck & Co., Inc. Used under license.

3. DRAFT COPY
Chemotherapy-induced nausea and vomiting
2 Key Pathways can Trigger
Emetic Response1
central Pathway
Activated by substance P
Mediated by NK1 receptors in
the emetic center of the brain
Blocked by NK1 receptor
antagonist
— EMEND™
Peripheral Pathway
Activated by serotonin
e
Mediated by 5-HT3 receptors
pl
m
sa
g
in
in the gut
rit
iw
sk
w
ko
z
ac
K
al
Blocked by 5-HT3 receptor
st
ry
C
antagonists
— Zofran (ondansetron) ®
— Kytril (granisetron)
®
— Anzemet ® (dolasetron)
Adapted from Grunberg et al2 and Hesketh et al.1
EMEND + 5-HT3 Receptor Antagonist
™
Target Both Pathways
Reference:
1. Hesketh PJ, Van Belle S, Aapro M, et al. Differential involvement of neurotransmitters through the time
course of cisplatin-induced emesis as revealed by therapy with specific receptor antagonists.
Eur J Cancer. 2003;39:1074–1080.
2. Grunberg SM, Hesketh PJ. Control of chemotherapy-induced emesis. N Engl J Med. 1993;329:1790–1796.
EMEND™ is a Trademark of Merck & Co., Inc. Used under license.

4. DRAFT COPY
In many patients receiving cisplatin-based chemotherapy,
EMEND™ From the Start
Helped Significantly More Patients
to Remain Free of Vomiting over
5 Days
Time to First Emesis
Day 1
Control regimen Zofran® (32 mg IV), dexamethasone
20 mg PO, and placebo Day 1
EMENDTM regimen EMENDTM 125 mg PO,
Zofran® 32 mg IV, and dexamethasone 12 mg PO Day 1
100
90
Percentage of Patients With No Vomiting
EMENDTM regimen (n=260)
80
70 p<0.001
60
e
pl
Control regimen (n=260)
m
sa
g
in
rit
50
iw
sk
w
ko
Days 2–4
z
ac
Control regimen Dexamethasone 16 mg PO and
K
al
st
placebo Days 2–4
ry
40
C
Acute Delayed EMENDTM regimen EMENDTM 80 mg PO Days 2 and 3;
dexamethasone 8 mg PO Days 2–4
0–24 hours
Day 1 Day 2 Day 3 Day 4 Day 5
Dose 1 Dose 2 Dose 3
Days Since Initiation of Chemotherapy
Study Design and Results
In a multicenter, randomized, double-blind, placebo-controlled clinical study, combination therapy with EMENDTM was compared with a 5-HT3 receptor antagonist regimen
in 530 cisplatin-naive patients receiving a chemotherapy regimen that included cisplatin ≥70 mg/m2. Some patients also received additional chemotherapeutic agents.
The primary clinical end point was “complete response” (overall, Days 1–5), defined as no vomiting and no rescue medication for nausea or vomiting. The percentage of
patients achieving a complete response over 5 days were significantly improved with the EMEND™ regimen than the control regimen, respectively: overall phase 72.7%
vs 52.3%; acute phase 89.2% vs 78.1%; delayed phase 75.4% vs 55.8%, p<0.001). The most common drug-related adverse experiences reported in patients treated with
the aprepitant regimen and greater than control therapy were: hiccups, asthenia/fatigue and nausea occuring after day 5.
Therapy Regimen
*Combination therapy with EMENDTM=3 days EMENDTM (125 mg PO on Day 1 and 80 mg PO once daily on Days 2 and 3); plus 1 day ZOFRAN® (ondansetron) (32 mg IV
on Day 1); plus 4 days dexamethasone (12 mg PO on Day 1 and 8 mg PO once daily on Days 2–4).
**Control regimen=ZOFRAN® was administered at maximum dose of 32 mg IV on Day 1 and not followed by oral 5-HT3 therapy on Days 2-5.
Reference:
Hesketh PJ, Grunberg SM, Gralla RJ, et al; the Aprepitant Protocol 052 Study Group.
The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a
multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin-
the Aprepitant Protocol 052 Study Group. J Clin Oncol. 2003;21(22):4112-9.
EMEND™ is a Trademark of Merck & Co., Inc. Used under license.