FDA Approves EMEND(R) (aprepitant), Merck's Antiemetic Therapy, for the Prevention of Postoperative Nausea and Vomiting; First New Class of Postoperative Nausea and Vomiting Therapy in More Than 10 Years.

WHITEHOUSE STATION, N.J. -- Merck & Co., Inc. announced today that the U.S. Food and Drug Administration (FDA) has approved EMEND(R) (aprepitant) for the prevention of postoperative nausea and vomiting (PONV), one of the most common side effects associated with surgical procedures. The recommended dose of EMEND for PONV is a single, oral 40 mg dose administered within three hours prior to the induction of anesthesia.

EMEND belongs to a class of medications called substance P/neurokinin 1 (NK-1) receptor antagonists and is believed to work through a novel mechanism, which primarily blocks nausea and vomiting signals to the brain. This novel mechanism is distinct from how current anti-vomiting therapies work, including 5-HT3 receptor antagonists (Zofran(R)). The 5-HT3 receptor antagonists primarily target nausea and vomiting signals in the gut. EMEND represents the first new class of therapy for the management of PONV in more than 10 years.

"Despite use of preventative medications, nearly a third of my patients suffer from postoperative nausea and vomiting. Most episodes of PONV occur after patients leave the postanesthesia care unit, even up to 48 hours after surgery," said Dr. Tong J. Gan, professor of anesthesiology, Department of Anesthesiology, Duke University Medical Center, Durham, NC. "The FDA approval of EMEND for PONV now provides physicians with a new option to help prevent post-operative nausea and vomiting."

The FDA approval for EMEND is based on two multicenter, randomized, double-blind, active comparator-controlled, parallel-group studies of 1,658 patients undergoing open abdominal surgery. Patients were randomized to receive EMEND 40 mg one to three hours before anesthesia or Zofran (ondansetron hydrochloride) 4 mg given intravenously immediately before anesthesia. A single 125 mg dose of EMEND was also studied; however, no additional clinical benefit was seen as compared to the 40 mg dose. Of the patients receiving EMEND 40 mg, 92 percent were women and eight percent were men, and the age of patients in the group ranged from 19-84 years with a mean age of 46 years.

EMEND 40 mg was superior to Zofran 4 mg IV in preventing vomiting through 24 hours following surgery

In study one, (N=573), EMEND 40 mg was superior to Zofran 4 mg IV for the prevention of vomiting (emesis) from 0 to 24 hours following surgery. Prevention of vomiting was defined as no emetic episodes and was one of two primary endpoints in the study. Of patients taking EMEND 40 mg, 84 percent of patients (246 out of 293) did not experience vomiting through 24 hours compared to 71 percent of patients taking Zofran 4 mg IV (200 out of 280, p<0.001).

Patients taking EMEND 40 mg achieved a complete response comparable to Zofran 4 mg IV

In a pre-specified non-inferiority analysis in study one, patients taking EMEND 40 mg had a complete response in the 0 to 24 hours following surgery comparable to Zofran 4 mg IV. Complete response was defined as no emetic episodes and no use of rescue therapy, and was the other primary endpoint in the study. In this analysis, 64 percent of patients (187 out of 293) taking EMEND 40 mg had a complete response compared to 55 percent of patients (154 out of 280) taking Zofran 4 mg IV. Complete response in the 24 hours following surgery was also evaluated based on a pre-specified superiority analysis in this study, which found that EMEND was not superior to Zofran on this endpoint.

Study two (N=494) did not satisfy its primary hypothesis that EMEND 40 mg is superior to Zofran 4 mg IV in the prevention of postoperative nausea and vomiting as measured by the proportion of patients with a complete response in the 24 hours following the end of surgery. In the second study, EMEND 40 mg demonstrated a clinically meaningful effect with respect to the secondary endpoint of "no vomiting" during the first 24 hours after surgery. EMEND 40 mg was associated with a 16 percent improvement over Zofran 4 mg IV in the prevention of vomiting.

EMEND 40 mg was superior to Zofran 4 mg IV in preventing vomiting through 48 hours following surgery

Also, in study one EMEND 40 mg was superior to Zofran 4 mg IV in the prevention of vomiting from 0 to 48 hours following surgery, a secondary endpoint. Of patients taking EMEND 40 mg, 82 percent of patients (238 out of 292) did not experience vomiting through 48 hours compared to 66 percent of patients taking Zofran 4 mg IV (185 out of 279, p<0.001). Stated differently, in this study almost twice as many patients taking Zofran 4 mg IV experienced vomiting (34 percent, or 94 out of 279 patients) as compared to patients taking EMEND 40 mg (18 percent, or 54 out of 292 patients) in the 48 hours following surgery.

EMEND was generally well tolerated

In these two well-controlled clinical studies, 564 patients received EMEND 40 mg orally and 538 patients received Zofran 4 mg IV. EMEND was generally well tolerated. Clinical adverse experiences were reported in approximately 60 percent of patients treated with EMEND compared to roughly 64 percent of people receiving Zofran. The most common adverse events reported with EMEND in the PONV studies vs. Zofran, respectively, were constipation (8.5 percent vs. 7.6 percent), nausea (8.5 percent vs. 8.6 percent), itching (7.6 percent vs. 8.4 percent), fever (5.9 percent vs. 10.6 percent), low blood pressure (5.7 percent vs. 4.6 percent), headache (5.0 percent vs. 6.5 percent) and slow heart rate (4.4 percent vs. 3.9 percent).

"Nausea and vomiting after surgery remains a significant problem, despite the number of different antiemetics on the market," said Robert McMahon, general manager, U.S. Human Health, Merck & Co., Inc. "EMEND offers a new and different approach to help reduce the incidence of nausea and vomiting."

Important information about EMEND

EMEND is only used to help prevent nausea and vomiting following surgery or, when used in combination with other antiemetics, it is used to help prevent nausea and vomiting caused by chemotherapy. It is not used to get rid of nausea and vomiting after they start.

Patients should tell their doctor about all of the medicines they are taking, if they are pregnant or plan to become pregnant, or if they have liver problems. Patients should not take EMEND with Orap(R) (pimozide), Seldane(R) (terfenadine), Hismanal(R) (astemizole), or Propulsid(R) (cisapride) as EMEND may cause serious or life-threatening problems if taken with these medicines. EMEND may also affect some medicines, causing them to work differently in your body. Chronic continuous use of EMEND for prevention of nausea and vomiting is not recommended because it has not been studied and because chronic continuous use of EMEND may cause some medicines to work differently in the body. Women who use birth control medicines during treatment with EMEND, and for up to one month after using EMEND, should also use a back-up method of contraception to avoid pregnancy.

About PONV

PONV is one of the most common side effects associated with surgical procedures. Studies show that nausea and vomiting may affect up to 30 percent of all patients undergoing surgery, and as many as 70 percent of high risk patients. One study shows that nearly 80 percent of PONV occurs within 48 hours after surgery. A study has also shown that patients find vomiting to be the most undesirable consequence of surgery, even ranking above surgical pain.

About Merck

Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit www.merck.com.

Merck Forward-Looking Statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the cautionary statements in Item 1 of Merck's Form 10-K for the year ended Dec. 31, 2005, and in its periodic reports on Form 10-Q and Form 8-K, which the Company incorporates by reference.

Prescribing information and patient product information for EMEND are attached.

EMEND is a registered trademark of Merck & Co., Inc. The brands listed are the registered trademarks of their respective owners and are not trademarks of Merck & Co., Inc.

9738706
EMEND(R)
(aprepitant)
CAPSULES

   DESCRIPTION

   EMEND* (aprepitant) is a substance P/neurokinin 1 (NK1) receptor
antagonist, chemically described as
5-(((2R,3S)-2-((1R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(4-flu
orophenyl)-4-morpholinyl)methyl)-1,2-dihydro-3H-1,2,4-triazol-3-one.
   Its empirical formula is C23H21F7N4O3, and its structural formula
is:

                           (GRAPHIC OMITTED)

   Aprepitant is a white to off-white crystalline solid, with a
molecular weight of 534.43. It is practically insoluble in water.
Aprepitant is sparingly soluble in ethanol and isopropyl acetate and
slightly soluble in acetonitrile.
   Each capsule of EMEND for oral administration contains either 40
mg, 80 mg, or 125 mg of aprepitant and the following inactive
ingredients: sucrose, microcrystalline cellulose, hydroxypropyl
cellulose and sodium lauryl sulfate. The capsule shell excipients are
gelatin, titanium dioxide, and may contain sodium lauryl sulfate and
silicon dioxide. The 40-mg capsule shell also contains yellow ferric
oxide, and the 125-mg capsule also contains red ferric oxide and
yellow ferric oxide.

   CLINICAL PHARMACOLOGY

   Mechanism of Action

   Aprepitant is a selective high-affinity antagonist of human
substance P/neurokinin 1 (NK1) receptors. Aprepitant has little or no
affinity for serotonin (5-HT3), dopamine, and corticosteroid
receptors, the targets of existing therapies for chemotherapy-induced
nausea and vomiting (CINV) and postoperative nausea and vomiting
(PONV).
   Aprepitant has been shown in animal models to inhibit emesis
induced by cytotoxic chemotherapeutic agents, such as cisplatin, via
central actions. Animal and human Positron Emission Tomography (PET)
studies with aprepitant have shown that it crosses the blood brain
barrier and occupies brain NK1 receptors. Animal and human studies
show that aprepitant augments the antiemetic activity of the
5-HT3-receptor antagonist ondansetron and the corticosteroid
dexamethasone and inhibits both the acute and delayed phases of
cisplatin-induced emesis.

   Pharmacokinetics

   Absorption

   Following oral administration of a single 40 mg dose of EMEND in
the fasted state, mean area under the plasma concentration-time curve
(AUC0-(Infinity)) was 7.8 mcg--hr/mL and mean peak plasma
concentration (Cmax) was 0.7 mcg/mL, occurring at approximately 3
hours postdose (Tmax). The absolute bioavailability at the 40-mg dose
has not been determined.
   Following oral administration of a single 125-mg dose of EMEND on
Day 1 and 80 mg once daily on Days 2 and 3, the AUC0-24hr was
approximately 19.6 mcg--hr/mL and 21.2 mcg--hr/mL on Day 1 and Day 3,
respectively. The Cmax of 1.6 mcg/mL and 1.4 mcg/mL were reached in
approximately 4 hours (Tmax) on Day 1 and Day 3, respectively. At the
dose range of 80-125 mg, the mean absolute oral bioavailability of
aprepitant is approximately 60 to 65%. Oral administration of the
capsule with a standard high-fat breakfast had no clinically
meaningful effect on the bioavailability of aprepitant.
   The pharmacokinetics of aprepitant are non-linear across the
clinical dose range. In healthy young adults, the increase in
AUC0-(Infinity) was 26% greater than dose proportional between 80-mg
and 125-mg single doses administered in the fed state.

   Distribution

   Aprepitant is greater than 95% bound to plasma proteins. The mean
apparent volume of distribution at steady state (Vdss) is
approximately 70 L in humans.
   Aprepitant crosses the placenta in rats and rabbits and crosses
the blood brain barrier in humans (see CLINICAL PHARMACOLOGY,
Mechanism of Action).

   Metabolism

   Aprepitant undergoes extensive metabolism. In vitro studies using
human liver microsomes indicate that aprepitant is metabolized
primarily by CYP3A4 with minor metabolism by CYP1A2 and CYP2C19.
Metabolism is largely via oxidation at the morpholine ring and its
side chains. No metabolism by CYP2D6, CYP2C9, or CYP2E1 was detected.
In healthy young adults, aprepitant accounts for approximately 24% of
the radioactivity in plasma over 72 hours following a single oral
300-mg dose of (14C)-aprepitant, indicating a substantial presence of
metabolites in the plasma. Seven metabolites of aprepitant, which are
only weakly active, have been identified in human plasma.

   Excretion

   Following administration of a single IV 100-mg dose of
(14C)-aprepitant prodrug to healthy subjects, 57% of the radioactivity
was recovered in urine and 45% in feces. A study was not conducted
with radiolabeled capsule formulation. The results after oral
administration may differ.
   Aprepitant is eliminated primarily by metabolism; aprepitant is
not renally excreted. The apparent plasma clearance of aprepitant
ranged from approximately 62 to 90 mL/min. The apparent terminal
half-life ranged from approximately 9 to 13 hours.

   Special Populations

   Gender

   Following oral administration of a single 125-mg dose of EMEND, no
difference in AUC0-24hr was observed between males and females. The
Cmax for aprepitant is 16% higher in females as compared with males.
The half-life of aprepitant is 25% lower in females as compared with
males and Tmax occurs at approximately the same time. These
differences are not considered clinically meaningful. No dosage
adjustment for EMEND is necessary based on gender.

   Geriatric

   Following oral administration of a single 125-mg dose of EMEND on
Day 1 and 80 mg once daily on Days 2 through 5, the AUC0-24hr of
aprepitant was 21% higher on Day 1 and 36% higher on Day 5 in elderly
((>=)65 years) relative to younger adults. The Cmax was 10% higher on
Day 1 and 24% higher on Day 5 in elderly relative to younger adults.
These differences are not considered clinically meaningful. No dosage
adjustment for EMEND is necessary in elderly patients.

   Pediatric

   The pharmacokinetics of EMEND have not been evaluated in patients
below 18 years of age.

   Race

   Following oral administration of a single 125-mg dose of EMEND,
the AUC0-24hr is approximately 25% and 29% higher in Hispanics as
compared with Whites and Blacks, respectively. The Cmax is 22% and 31%
higher in Hispanics as compared with Whites and Blacks, respectively.
These differences are not considered clinically meaningful. There was
no difference in AUC0-24hr or Cmax between Whites and Blacks. No
dosage adjustment for EMEND is necessary based on race.

   Hepatic Insufficiency

   EMEND was well tolerated in patients with mild to moderate hepatic
insufficiency. Following administration of a single 125-mg dose of
EMEND on Day 1 and 80 mg once daily on Days 2 and 3 to patients with
mild hepatic insufficiency (Child-Pugh score 5 to 6), the AUC0-24hr of
aprepitant was 11% lower on Day 1 and 36% lower on Day 3, as compared
with healthy subjects given the same regimen. In patients with
moderate hepatic insufficiency (Child-Pugh score 7 to 9), the
AUC0-24hr of aprepitant was 10% higher on Day 1 and 18% higher on Day
3, as compared with healthy subjects given the same regimen. These
differences in AUC0-24hr are not considered clinically meaningful;
therefore, no dosage adjustment for EMEND is necessary in patients
with mild to moderate hepatic insufficiency.
   There are no clinical or pharmacokinetic data in patients with
severe hepatic insufficiency (Child-Pugh score >9) (see PRECAUTIONS).

   Renal Insufficiency

   A single 240-mg dose of EMEND was administered to patients with
severe renal insufficiency (CrCl<30 mL/min) and to patients with end
stage renal disease (ESRD) requiring hemodialysis.
   In patients with severe renal insufficiency, the AUC0-(Infinity)
of total aprepitant (unbound and protein bound) decreased by 21% and
Cmax decreased by 32%, relative to healthy subjects. In patients with
ESRD undergoing hemodialysis, the AUC0-(Infinity) of total aprepitant
decreased by 42% and Cmax decreased by 32%. Due to modest decreases in
protein binding of aprepitant in patients with renal disease, the AUC
of pharmacologically active unbound drug was not significantly
affected in patients with renal insufficiency compared with healthy
subjects. Hemodialysis conducted 4 or 48 hours after dosing had no
significant effect on the pharmacokinetics of aprepitant; less than
0.2% of the dose was recovered in the dialysate.
   No dosage adjustment for EMEND is necessary for patients with
renal insufficiency or for patients with ESRD undergoing hemodialysis.

   Clinical Studies

   Prevention of Chemotherapy Induced Nausea and Vomiting

   Oral administration of EMEND in combination with ondansetron and
dexamethasone (aprepitant regimen) has been shown to prevent acute and
delayed nausea and vomiting associated with highly emetogenic
chemotherapy including high-dose cisplatin, and nausea and vomiting
associated with moderately emetogenic chemotherapy.

   Highly Emetogenic Chemotherapy

   In 2 multicenter, randomized, parallel, double-blind, controlled
clinical studies, the aprepitant regimen (see table below) was
compared with standard therapy in patients receiving a chemotherapy
regimen that included cisplatin >50 mg/m2 (mean cisplatin dose = 80.2
mg/m2). Of the 550 patients who were randomized to receive the
aprepitant regimen, 42% were women, 58% men, 59% White, 3% Asian, 5%

Black, 12% Hispanic American, and 21% Multi-Racial. The
aprepitant-treated patients in these clinical studies ranged from 14
to 84 years of age, with a mean age of 56 years. 170 patients were 65
years or older, with 29 patients being 75 years or older.
   Patients (N = 1105) were randomized to either the aprepitant
regimen (N = 550) or standard therapy (N = 555). The treatment
regimens are defined in the table below.

                              Treatment Regimens
                     Highly Emetogenic Chemotherapy Trials
----------------------------------------------------------------------
Treatment              Day 1                      Days 2 to 4
Regimen
----------------------------------------------------------------------
Aprepitant      Aprepitant 125 mg PO       Aprepitant 80 mg PO Daily
                Dexamethasone 12 mg PO     (Days 2 and 3 only)
                Ondansetron 32 mg IV       Dexamethasone 8 mg PO Daily
                                           (morning)

----------------------------------------------------------------------
Standard        Dexamethasone 20 mg PO     Dexamethasone 8 mg PO Daily
Therapy         Ondansetron 32 mg IV       (morning)
                                           Dexamethasone 8 mg PO Daily
                                           (evening)
----------------------------------------------------------------------
Aprepitant placebo and dexamethasone placebo were used to maintain
blinding.

   During these studies 95% of the patients in the aprepitant group
received a concomitant chemotherapeutic agent in addition to
protocol-mandated cisplatin. The most common chemotherapeutic agents
and the number of aprepitant patients exposed follows: etoposide
(106), fluorouracil (100), gemcitabine (89), vinorelbine (82),
paclitaxel (52), cyclophosphamide (50), doxorubicin (38), docetaxel
(11).
   The antiemetic activity of EMEND was evaluated during the acute
phase (0 to 24 hours post-cisplatin treatment), the delayed phase (25
to 120 hours post-cisplatin treatment) and overall (0 to 120 hours
post-cisplatin treatment) in Cycle 1. Efficacy was based on evaluation
of the following endpoints:

   Primary endpoint:

   --  complete response (defined as no emetic episodes and no use of
        rescue therapy)

   Other prespecified endpoints:

   --  complete protection (defined as no emetic episodes, no use of
       rescue therapy, and a maximum nausea visual analogue scale
       (VAS) score <25 mm on a 0 to 100 mm scale)

   --  no emesis (defined as no emetic episodes regardless of use of
       rescue therapy)

   --  no nausea (maximum VAS <5 mm on a 0 to 100 mm scale)

   --  no significant nausea (maximum VAS <25 mm on a 0 to 100 mm
       scale)

   A summary of the key study results from each individual study
analysis is shown in Table 1 and in Table 2.

                              Table 1
    Percent of Patients Receiving Highly Emetogenic Chemotherapy
    Responding by Treatment Group and Phase for Study 1 -- Cycle 1
-------------------------------------------------------------------
 ENDPOINTS                        Aprepitant  Standard    p-Value
                                    Regimen   Therapy
                                  (N = 260)+  (N =261)+
                                       %          %
-------------------------------------------------------------------
 PRIMARY ENDPOINT
-------------------------------------------------------------------
 Complete Response
-------------------------------------------------------------------
      Overall++                           73      52     <0.001
-------------------------------------------------------------------
 OTHER PRESPECIFIED ENDPOINTS
-------------------------------------------------------------------
 Complete Response
-------------------------------------------------------------------
      Acute phasess                       89      78     <0.001
Delayed phase||                           75      56     <0.001
-------------------------------------------------------------------
 Complete Protection
-------------------------------------------------------------------
      Overall                             63      49     0.001
Acute phase                               85      75      NS*
Delayed phase                             66      52     <0.001
-------------------------------------------------------------------
 No Emesis
-------------------------------------------------------------------
      Overall                             78      55     <0.001
Acute phase                               90      79     0.001
Delayed phase                             81      59     <0.001
-------------------------------------------------------------------
 No Nausea
-------------------------------------------------------------------
      Overall                             48      44      NS**
Delayed phase                             51      48      NS**
-------------------------------------------------------------------
 No Significant Nausea
-------------------------------------------------------------------
      Overall                             73      66      NS**
Delayed phase                             75      69      NS**
-------------------------------------------------------------------

+   N: Number of patients (older than 18 years of age) who received
    cisplatin, study drug, and had at least one post-treatment
    efficacy evaluation.

++  Overall: 0 to 120 hours post-cisplatin treatment.

ss  Acute phase: 0 to 24 hours post-cisplatin treatment.

|| Delayed phase: 25 to 120 hours post-cisplatin treatment.

*  Not statistically significant when adjusted for multiple
   comparisons.

** Not statistically significant.

   Visual analogue scale (VAS) score range: 0 mm = no nausea; 100 mm
   = nausea as bad as it could be.


                              Table 2
   Percent of Patients Receiving Highly Emetogenic Chemotherapy
                      Responding by Treatment
              Group and Phase for Study 2 -- Cycle 1
-------------------------------------------------------------------
 ENDPOINTS                        Aprepitant  Standard     p-Value
                                    Regimen   Therapy
                                  (N = 261)+  (N =263)+
                                       %         %
-------------------------------------------------------------------
 PRIMARY ENDPOINT
-------------------------------------------------------------------
 Complete Response
-------------------------------------------------------------------
      Overall++                           63      43     <0.001
-------------------------------------------------------------------
 OTHER PRESPECIFIED ENDPOINTS
-------------------------------------------------------------------
 Complete Response
-------------------------------------------------------------------
      Acute phasess                       83      68     <0.001
Delayed phase||                           68      47     <0.001
-------------------------------------------------------------------
 Complete Protection
-------------------------------------------------------------------
      Overall                             56      41     <0.001
Acute phase                               80      65     <0.001
Delayed phase                             61      44     <0.001
-------------------------------------------------------------------
 No Emesis
-------------------------------------------------------------------
      Overall                             66      44     <0.001
Acute phase                               84      69     <0.001
Delayed phase                             72      48     <0.001
-------------------------------------------------------------------
 No Nausea
-------------------------------------------------------------------
      Overall                             49      39      NS*
Delayed phase                             53      40      NS*
-------------------------------------------------------------------
 No Significant Nausea
-------------------------------------------------------------------
      Overall                             71      64      NS**
Delayed phase                             73      65      NS**
-------------------------------------------------------------------

+   N: Number of patients (older than 18 years of age) who received
    cisplatin, study drug, and had at least one post-treatment
    efficacy evaluation.

++  Overall: 0 to 120 hours post-cisplatin treatment.

ss  Acute phase: 0 to 24 hours post-cisplatin treatment.

||  Delayed phase: 25 to 120 hours post-cisplatin treatment.

*   Not statistically significant when adjusted for multiple
    comparisons.

**  Not statistically significant.

    Visual analogue scale (VAS) score range: 0 mm = no nausea; 100 mm
    = nausea as bad as it could be.

   In both studies, a statistically significantly higher proportion
of patients receiving the aprepitant regimen in Cycle 1 had a complete
response (primary endpoint), compared with patients receiving standard
therapy. A statistically significant difference in complete response
in favor of the aprepitant regimen was also observed when the acute
phase and the delayed phase were analyzed separately.
   In both studies, the estimated time to first emesis after
initiation of cisplatin treatment was longer with the aprepitant
regimen, and the incidence of first emesis was reduced in the
aprepitant regimen group compared with standard therapy group as
depicted in the Kaplan-Meier curves in Figure 1.

Figure 1: Percent of Patients Receiving Highly Emetogenic Chemotherapy
              Who Remain Emesis Free Over Time - Cycle 1

                           (GRAPHIC OMITTED)

   Patient-Reported Outcomes: The impact of nausea and vomiting on
patients' daily lives was assessed in Cycle 1 of both Phase III
studies using the Functional Living Index-Emesis (FLIE), a validated
nausea- and vomiting-specific patient-reported outcome measure.
Minimal or no impact of nausea and vomiting on patients' daily lives
is defined as a FLIE total score >108. In each of the 2 studies, a
higher proportion of patients receiving the aprepitant regimen
reported minimal or no impact of nausea and vomiting on daily life
(Study 1: 74% versus 64%; Study 2: 75% versus 64%).
   Multiple-Cycle Extension: In the same 2 clinical studies, patients
continued into the Multiple-Cycle extension for up to 5 additional
cycles of chemotherapy. The proportion of patients with no emesis and
no significant nausea by treatment group at each cycle is depicted in
Figure 2. Antiemetic effectiveness for the patients receiving the
aprepitant regimen is maintained throughout repeat cycles for those
patients continuing in each of the multiple cycles.

     Figure 2: Proportion of Patients Receiving Highly Emetogenic
         Chemotherapy With No Emesis and No Significant Nausea
                     by Treatment Group and Cycle

                           (GRAPHIC OMITTED)

   Moderately Emetogenic Chemotherapy

   In a multicenter, randomized, double-blind, parallel-group,
clinical study in breast cancer patients, the aprepitant regimen (see
table that follows) was compared with a standard of care therapy in
patients receiving a moderately emetogenic chemotherapy regimen that
included cyclophosphamide 750-1500 mg/m2; or cyclophosphamide 500-1500
mg/m2 and doxorubicin ((<=)60 mg/m2) or epirubicin ((<=)100 mg/m2).
   In this study, the most common combinations were cyclophosphamide
+ doxorubicin (60.6%); and cyclophosphamide + epirubicin +
fluorouracil (21.6%).
   Of the 438 patients who were randomized to receive the aprepitant
regimen, 99.5% were women. Of these, approximately 80% were White, 8%
Black, 8% Asian, 4% Hispanic, and <1% Other. The aprepitant-treated
patients in this clinical study ranged from 25 to 78 years of age,
with a mean age of 53 years; 70 patients were 65 years or older, with
12 patients being over 74 years.
   Patients (N = 866) were randomized to either the aprepitant
regimen (N = 438) or standard therapy (N = 428). The treatment
regimens are defined in the table that follows.


                               Treatment Regimens
                   Moderately Emetogenic Chemotherapy Trial
----------------------------------------------------------------------
Treatment              Day 1                       Days 2 to 3
Regimen
----------------------------------------------------------------------
Aprepitant      Aprepitant 125 mg PO+       Aprepitant 80 mg PO Daily
                Dexamethasone 12 mg PO++
                Ondansetron 8 mg PO x 2
                dosesss
----------------------------------------------------------------------

Standard        Dexamethasone 20 mg PO      Ondansetron 8 mg PO Daily
Therapy         Ondansetron 8 mg PO x 2     (every 12 hours)
                doses
----------------------------------------------------------------------
Aprepitant placebo and dexamethasone placebo were used to maintain
blinding.

+   1 hour prior to chemotherapy.
++  30 minutes prior to chemotherapy.
ss  30 to 60 minutes prior to chemotherapy and 8 hours after first
    ondansetron dose.

   The antiemetic activity of EMEND was evaluated based on the
following endpoints:

   Primary endpoint:

   Complete response (defined as no emetic episodes and no use of
rescue therapy) in the overall phase (0 to 120 hours
post-chemotherapy)

   Other prespecified endpoints:

   --  no emesis (defined as no emetic episodes regardless of use of
        rescue therapy)

   --  no nausea (maximum VAS <5 mm on a 0 to 100 mm scale)

   --  no significant nausea (maximum VAS <25 mm on a 0 to 100 mm
        scale)

   --  complete protection (defined as no emetic episodes, no use of
        rescue therapy, and a maximum nausea visual analogue scale
        (VAS) score <25 mm on a 0 to 100 mm scale)

   --  complete response during the acute and delayed phases.

   A summary of the key results from this study is shown in Table 3.


                                Table 3
   Percent of Patients Receiving Moderately Emetogenic Chemotherapy
          Responding by Treatment Group and Phase -- Cycle 1
-------------------------------------------------------------------
 ENDPOINTS                        Aprepitant  Standard    p-Value
                                    Regimen   Therapy
                                  (N = 433)+  (N =424)+
                                       %
-------------------------------------------------------------------
 PRIMARY ENDPOINT
-------------------------------------------------------------------
      Complete Response++                 51      42      0.015
-------------------------------------------------------------------
 OTHER PRESPECIFIED ENDPOINTS
-------------------------------------------------------------------
      No Emesis                           76      59       NS*
-------------------------------------------------------------------
      No Nausea                           33      33       NS
-------------------------------------------------------------------
      No Significant Nausea               61      56       NS
-------------------------------------------------------------------
      No Rescue Therapy                   59      56       NS
-------------------------------------------------------------------
      Complete Protection                 43      37       NS
-------------------------------------------------------------------

+   N: Number of patients included in the primary analysis of
    complete response.

++  Overall: 0 to 120 hours post-chemotherapy treatment.

*   NS when adjusted for prespecified multiple comparisons rule;
    unadjusted p-value <0.001.

   In this study, a statistically significantly (p=0.015) higher
proportion of patients receiving the aprepitant regimen (51%) in Cycle
1 had a complete response (primary endpoint) during the overall phase
compared with patients receiving standard therapy (42%). The
difference between treatment groups was primarily driven by the "No
Emesis Endpoint", a principal component of this composite primary
endpoint. In addition, a higher proportion of patients receiving the
aprepitant regimen in Cycle 1 had a complete response during the acute
(0-24 hours) and delayed (25-120 hours) phases compared with patients
receiving standard therapy; however, the treatment group differences
failed to reach statistical significance, after multiplicity
adjustments.
   Patient-Reported Outcomes: In a phase III study in patients
receiving moderately emetogenic chemotherapy, the impact of nausea and
vomiting on patients' daily lives was assessed in Cycle 1 using the
FLIE. A higher proportion of patients receiving the aprepitant regimen
reported minimal or no impact on daily life (64% versus 56%). This
difference between treatment groups was primarily driven by the "No
Vomiting Domain" of this composite endpoint.
   Multiple-Cycle Extension: Patients receiving moderately emetogenic
chemotherapy were permitted to continue into the Multiple-Cycle
extension of the study for up to 3 additional cycles of chemotherapy.
Antiemetic effect for patients receiving the aprepitant regimen is
maintained during all cycles.

   Prevention of Postoperative Nausea and Vomiting (PONV)

   In two multicenter, randomized, double-blind, active
comparator-controlled, parallel-group clinical studies (PONV Studies 1
and 2), aprepitant was compared with ondansetron for the prevention of
postoperative nausea and vomiting in 1658 patients undergoing open
abdominal surgery. Patients were randomized to receive 40 mg
aprepitant, 125 mg aprepitant, or 4 mg ondansetron. Aprepitant was
given orally with 50 mL of water 1 to 3 hours before anesthesia.
Ondansetron was given intravenously immediately before induction of
anesthesia. A comparison between the 125 mg dose and the 40 mg dose
did not demonstrate any additional clinical benefit. The remainder of
this section will focus on the results in the 40 mg aprepitant dose
recommended for PONV.
   Of the 564 patients who received 40 mg aprepitant, 92% were women
and 8% were men; of these, 58% were White, 13% Hispanic American, 7%
Multi-Racial, 14% Black, 6% Asian, and 2% Other. The age of patients
treated with 40 mg aprepitant ranged from 19 to 84 years, with a mean
age of 46.1 years. 46 patients were 65 years or older, with 13
patients being 75 years or older.
   The antiemetic activity of EMEND was evaluated during the 0 to 48
hour period following the end of surgery. The two pivotal studies were
of similar design; however, they differed in terms of study
hypothesis, efficacy analyses and geographic location. PONV Study 1
was a multinational study including the U.S., whereas, PONV Study 2
was conducted entirely in the U.S.

   Efficacy measures in PONV Study 1 included:

   --  no emesis (defined as no emetic episodes regardless of use of
       rescue therapy) in the 0 to 24 hours following the end of
       surgery (primary)

   --  complete response (defined as no emetic episodes and no use of
       rescue therapy) in the 0 to 24 hours following the end of
       surgery (primary)

   --  no emesis (defined as no emetic episodes regardless of use of
       rescue therapy) in the 0 to 48 hours following the end of
       surgery (secondary)

   --  time to first use of rescue medication in the 0 to 24 hours
       following the end of surgery (exploratory)

   --  time to first emesis in the 0 to 48 hours following the end of
       surgery (exploratory).

   A closed testing procedure was applied to control the type I error
for the primary endpoints.
   The results of the primary and secondary endpoints for 40 mg
aprepitant and 4 mg ondansetron are described in Table 4:

   Table 4

   PONV Study 1

   Response Rates for Select Efficacy Endpoints

   (Modified-Intention-to-Treat Population)


                                            Aprepitant
                                                Vs
                                           Ondansetron
   Treatment                n/m (%)     -----------------------------
                                        (DELTA)   Odds     Analysis
                                                 ratio+
------------------------ -------------- -----------------------------
Primary Endpoints
------------------------ -------------- -----------------------------
No Vomiting 0 to 24 hours (Superiority)
(no emetic episodes)
------------------------ -------------- -----------------------------
Aprepitant 40 mg         246/293 (84.0)  12.6%    2.1       P<0.001*
------------------------ -------------- -----------------------------
Ondansetron              200/280 (71.4)
------------------------ -------------- -----------------------------
Complete Response (Non-inferiority: If LB++ >0.65)
(no emesis and no rescue therapy, 0 to 24 hours)
------------------------ -------------- -----------------------------
Aprepitant 40 mg         187/293 (63.8)   8.8%    1.4       LB=1.02
------------------------ -------------- -----------------------------
Ondansetron              154/280 (55.0)
------------------------ -------------- -----------------------------
Complete Response (Superiority: If LB >1.0)
(no emesis and no rescue therapy, 0 to 24 hours)
------------------------ -------------- -----------------------------
Aprepitant 40 mg         187/293 (63.8)   8.8%    1.4       LB=1.02+
------------------------ -------------- -----------------------------
Ondansetron              154/280 (55.0)
------------------------ -------------- -----------------------------
Secondary Endpoint
------------------------ -------------- -----------------------------
No Vomiting 0 to 48 (Superiority)
(no emetic episodes)
------------------------ -------------- -----------------------------
Aprepitant 40 mg         238/292 (81.5)  15.2%    2.3       P<0.001*
------------------------ -------------- -----------------------------
Ondansetron              185/279 (66.3)
------------------------ -------------- -----------------------------

n/m =  Number of responders/number of patients in analysis.

(DELTA) Difference (%): Aprepitant 40 mg minus Ondansetron.

++  LB= lower bound of 1-sided 97.5% confidence interval for the odds
     ratio.

*  P-value of two-sided test <0.05.

+  Based on the prespecified fixed sequence multiplicity strategy,
   Aprepitant 40 mg was not superior to Ondansetron.

++ Estimated odds ratio for Aprepitant versus Ondansetron. A value of
   >1 favors Aprepitant over Ondansetron.


   The use of aprepitant did not affect the time to first use of
rescue medication when compared to ondansetron. However, compared to
the ondansetron group, use of aprepitant delayed the time to first
vomiting, as depicted in Figure 3.

                               Figure 3
              Percent of Patients Who Remain Emesis Free
             During the 48 Hours Following End of Surgery

                           (GRAPHIC OMITTED)


   Efficacy measures in PONV Study 2 included:

   --  complete response (defined as no emetic episodes and no use of
       rescue therapy) in the 0 to 24 hours following the end of
       surgery (primary)

   --  no emesis (defined as no emetic episodes regardless of use of
       rescue therapy) in the 0 to 24 hours following the end of
       surgery (secondary)

   --  no use of rescue therapy in the 0 to 24 hours following the
       end of surgery (secondary)

   --  no emesis (defined as no emetic episodes regardless of use of
       rescue therapy) in the 0 to 48 hours following the end of
       surgery (secondary)

   PONV Study 2 failed to satisfy its primary hypothesis that
aprepitant is superior to ondansetron in the prevention of PONV as
measured by the proportion of patients with complete response in the
24 hours following end of surgery.
   The study demonstrated that both dose levels of aprepitant had a
clinically meaningful effect with respect to the secondary endpoint
"no vomiting" during the first 24 hours after surgery and showed that
the use of 40 mg aprepitant was associated with a 16% improvement over
ondansetron for the no vomiting endpoint.

                                Table 5

                             PONV Study 2
               (Modified-Intention-to-Treat Population)

                                            Aprepitant
                                                Vs
                                           Ondansetron
 Treatment                  n/m (%)    ---------------------------
                                      (DELTA)  Odds     p-Value
                                               ratio+
---------------------- -------------  ----------------------------
Primary Endpoint
---------------------- -------------  ----------------------------
Complete Response
(no emesis and no rescue therapy, 0 to 24 hours)
---------------------- -------------  ----------------------------
Aprepitant 40 mg       111/248 (44.8)   2.5%    1.1      0.61
---------------------- -------------  ----------------------------
Ondansetron            104/246 (42.3)
---------------------- -------------  ----------------------------
Secondary Endpoints
---------------------- -------------  ----------------------------
No Vomiting
(no emetic episodes, 0 to 24 hours)
---------------------- -------------  ----------------------------
Aprepitant 40 mg       223/248 (89.9)  16.3%    3.2     <0.001*
---------------------- -------------  ----------------------------
Ondansetron            181/246 (73.6)
---------------------- -------------- ----------------------------
No Use of Rescue Medication
(for established emesis or nausea, 0 to 24 hours)
---------------------- -------------  ----------------------------
Aprepitant 40 mg       112/248 (45.2)  -0.7%   1.0       0.83
---------------------- -------------  ----------------------------
Ondansetron            113/246 (45.9)
---------------------- -------------  ----------------------------
No Vomiting 0 to 48 (Superiority)
(no emetic episodes, 0 to 48 hours)
---------------------- -------------  ----------------------------
Aprepitant 40 mg       209/247 (84.6)  17.7%   2.7       <0.001*
---------------------- -------------  ----------------------------
Ondansetron            164/245 (66.9)
---------------------- -------------  ----------------------------
n/m =  Number of responders/number of patients in analysis.

(DELTA)  Difference (%): Aprepitant 40 mg minus Ondansetron.

+   Estimated odds ratio: Aprepitant 40 mg versus Ondansetron.

*   Not statistically significant after pre-specified multiplicity
    adjustment.


   INDICATIONS AND USAGE

   EMEND, in combination with other antiemetic agents, is indicated
for the:

   --  prevention of acute and delayed nausea and vomiting associated
       with initial and repeat courses of highly emetogenic cancer
       chemotherapy including high-dose cisplatin

   --  prevention of nausea and vomiting associated with initial and
       repeat courses of moderately emetogenic cancer chemotherapy
       (see DOSAGE AND ADMINISTRATION).

   EMEND is indicated for the prevention of postoperative nausea and
vomiting (see DOSAGE AND ADMINISTRATION).

   CONTRAINDICATIONS

   EMEND is a weak-to-moderate (dose-dependent) CYP3A4 inhibitor.
EMEND should not be used concurrently with pimozide, terfenadine,
astemizole, or cisapride. Dose-dependent inhibition of cytochrome P450
isoenzyme 3A4 (CYP3A4) by aprepitant could result in elevated plasma
concentrations of these drugs, potentially causing serious or
life-threatening reactions (see PRECAUTIONS, Drug Interactions).
   EMEND is contraindicated in patients who are hypersensitive to any
component of the product.

   PRECAUTIONS

   General

   EMEND, a dose-dependent inhibitor of CYP3A4, should be used with
caution in patients receiving concomitant orally administered
medicinal products, including chemotherapy agents that are primarily
metabolized through CYP3A4. Moderate inhibition of CYP3A4 by
aprepitant, 125 mg/80 mg regimen, could result in elevated plasma
concentrations of these concomitant medicinal products.
   Weak inhibition of CYP3A4 by a single 40 mg dose of aprepitant is
not expected to alter the plasma concentrations of concomitant
medicinal products that are primarily metabolized through CYP3A4 to a
clinically significant degree.
   The effect of EMEND on the pharmacokinetics of orally administered
CYP3A4 substrates is greater than the effect of EMEND on the
pharmacokinetics of intravenously administered CYP3A4 substrates (see
PRECAUTIONS, Drug Interactions).
   Chemotherapy agents that are known to be metabolized by CYP3A4
include docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide,
imatinib, vinorelbine, vinblastine and vincristine. In clinical
studies, EMEND (125 mg/80 mg regimen) was administered commonly with
etoposide, vinorelbine, or paclitaxel. The doses of these agents were
not adjusted to account for potential drug interactions.
   In a separate pharmacokinetic study in patients receiving
docetaxel, which is also metabolized by CYP3A4, EMEND (125 mg/80 mg
regimen) did not influence the pharmacokinetics of docetaxel.
   Due to the small number of patients in clinical studies who
received the CYP3A4 substrates vinblastine, vincristine, or
ifosfamide, particular caution and careful monitoring are advised in
patients receiving these agents or other chemotherapy agents
metabolized primarily by CYP3A4 that were not studied (see
PRECAUTIONS, Drug Interactions).
   Chronic continuous use of EMEND for prevention of nausea and
vomiting is not recommended because it has not been studied and
because the drug interaction profile may change during chronic
continuous use.
   Coadministration of EMEND with warfarin may result in a clinically
significant decrease in International Normalized Ratio (INR) of
prothrombin time. In patients on chronic warfarin therapy, the INR
should be closely monitored in the 2-week period, particularly at 7 to
10 days, following initiation of the 3-day regimen of EMEND with each
chemotherapy cycle, or following administration of a single 40 mg dose
of EMEND for the prevention of postoperative nausea and vomiting (see
PRECAUTIONS, Drug Interactions).
   Upon coadministration with EMEND, the efficacy of hormonal
contraceptives during and for 28 days following the last dose of EMEND
may be reduced. Alternative or back-up methods of contraception should
be used during treatment with EMEND and for 1 month following the last
dose of EMEND (see PRECAUTIONS, Drug Interactions).
   There are no clinical or pharmacokinetic data in patients with
severe hepatic insufficiency (Child-Pugh score >9). Therefore, caution
should be exercised when EMEND is administered in these patients (see
CLINICAL PHARMACOLOGY, Special Populations, Hepatic Insufficiency and
DOSAGE AND ADMINISTRATION).

   Information for Patients

   Physicians should instruct their patients to read the patient
package insert before starting therapy with EMEND and to reread it
each time the prescription is renewed.
   Patients should be instructed to take EMEND only as prescribed.
For the prevention of chemotherapy induced nausea and vomiting,
patients should be advised to take their first dose (125 mg) of EMEND
1 hour prior to chemotherapy treatment. For the prevention of
postoperative nausea and vomiting, patients should receive their
medication (40 mg capsule of EMEND) within 3 hours prior to induction
of anesthesia.
   EMEND may interact with some drugs including chemotherapy;
therefore, patients should be advised to report to their doctor the
use of any other prescription, non-prescription medication or herbal
products.
   Patients on chronic warfarin therapy should be instructed to have
their clotting status closely monitored in the 2-week period,
particularly at 7 to 10 days, following initiation of the 3-day
regimen of EMEND 125 mg/80 mg with each chemotherapy cycle, or
following administration of a single 40 mg dose of EMEND for the
prevention of postoperative nausea and vomiting.
   Administration of EMEND may reduce the efficacy of hormonal
contraceptives. Patients should be advised to use alternative or
back-up methods of contraception during treatment with EMEND and for 1
month following the last dose of EMEND.

   Drug Interactions

   Aprepitant is a substrate, a weak-to-moderate (dose-dependent)
inhibitor, and an inducer of CYP3A4. Aprepitant is also an inducer of
CYP2C9.

   Effect of aprepitant on the pharmacokinetics of other agents

   Weak inhibition of CYP3A4 by a single 40 mg dose of aprepitant is
not expected to alter the plasma concentrations of concomitant
medicinal products that are primarily metabolized through CYP3A4 to a
clinically significant degree. However, higher aprepitant doses or
repeated dosing at any aprepitant dose may have a clinically
significant effect.
   As a moderate inhibitor of CYP3A4 at a dose of 125 mg/80 mg,
aprepitant can increase plasma concentrations of concomitantly
administered oral medicinal products that are metabolized through
CYP3A4 (see CONTRAINDICATIONS). For a given drug of CYP3A4 substrate,
aprepitant 125 mg/80 mg may increase its plasma concentrations to a
lesser extent when it is given intravenously rather than orally.
   Aprepitant has been shown to induce the metabolism of S(-)
warfarin and tolbutamide, which are metabolized through CYP2C9.
Coadministration of EMEND with these drugs or other drugs that are
known to be metabolized by CYP2C9, such as phenytoin, may result in
lower plasma concentrations of these drugs.
   EMEND is unlikely to interact with drugs that are substrates for
the P-glycoprotein transporter, as demonstrated by the lack of
interaction of EMEND with digoxin in a clinical drug interaction
study.
   5-HT3 antagonists: In clinical drug interaction studies,
aprepitant did not have clinically important effects on the
pharmacokinetics of ondansetron, granisetron, or hydrodolasetron (the
active metabolite of dolasetron).

   Corticosteroids:

   Dexamethasone: EMEND, when given as a regimen of 125 mg with
dexamethasone coadministered orally as 20 mg on Day 1, and EMEND when
given as 80 mg/day with dexamethasone coadministered orally as 8 mg on
Days 2 through 5, increased the AUC of dexamethasone, a CYP3A4
substrate, by 2.2-fold on Days 1 and 5. The oral dexamethasone doses
should be reduced by approximately 50% when coadministered with EMEND
(125 mg/80 mg regimen), to achieve exposures of dexamethasone similar
to those obtained when it is given without EMEND. The daily dose of
dexamethasone administered in clinical chemotherapy induced nausea and
vomiting studies with EMEND reflects an approximate 50% reduction of
the dose of dexamethasone (see DOSAGE AND ADMINISTRATION). A single
dose of EMEND (40 mg) when coadministered with a single oral dose of
dexamethasone 20 mg, increased the AUC of dexamethasone by 1.45-fold.
Therefore, no dose adjustment is recommended.
   Methylprednisolone: EMEND, when given as a regimen of 125 mg on
Day 1 and 80 mg/day on Days 2 and 3, increased the AUC of
methylprednisolone, a CYP3A4 substrate, by 1.34-fold on Day 1 and by
2.5-fold on Day 3, when methylprednisolone was coadministered
intravenously as 125 mg on Day 1 and orally as 40 mg on Days 2 and 3.
The IV methylprednisolone dose should be reduced by approximately 25%,
and the oral methylprednisolone dose should be reduced by
approximately 50% when coadministered with EMEND (125 mg/80 mg
regimen) to achieve exposures of methylprednisolone similar to those
obtained when it is given without EMEND. Although the concomitant
administration of methylprednisolone with the single 40 mg dose of
aprepitant has not been studied, a single 40 mg dose of EMEND produces
a weak inhibition of CYP3A4 (based on midazolam interaction study) and
it is not expected to alter the plasma concentrations of
methylprednisolone to a clinically significant degree. Therefore, no
dose adjustment is recommended.

   Chemotherapeutic agents: See PRECAUTIONS, General.

   Docetaxel: In a pharmacokinetic study, EMEND (125 mg/80 mg
regimen) did not influence the pharmacokinetics of docetaxel.
   Warfarin: A single 125-mg dose of EMEND was administered on Day 1
and 80 mg/day on Days 2 and 3 to healthy subjects who were stabilized
on chronic warfarin therapy. Although there was no effect of EMEND on
the plasma AUC of R(+) or S(-) warfarin determined on Day 3, there was
a 34% decrease in S(-) warfarin (a CYP2C9 substrate) trough
concentration accompanied by a 14% decrease in the prothrombin time
(reported as International Normalized Ratio or INR) 5 days after
completion of dosing with EMEND. In patients on chronic warfarin
therapy, the prothrombin time (INR) should be closely monitored in the
2-week period, particularly at 7 to 10 days, following initiation of
the 3-day regimen of EMEND with each chemotherapy cycle, or following
administration of a single 40 mg dose of EMEND for the prevention of
postoperative nausea and vomiting.
   Tolbutamide: EMEND, when given as 125 mg on Day 1 and 80 mg/day on
Days 2 and 3, decreased the AUC of tolbutamide (a CYP2C9 substrate) by
23% on Day 4, 28% on Day 8, and 15% on Day 15, when a single dose of
tolbutamide 500 mg was administered orally prior to the administration
of the 3-day regimen of EMEND and on Days 4, 8, and 15.
   Oral contraceptives: Aprepitant, when given once daily for 14 days
as a 100-mg capsule with an oral contraceptive containing 35 mcg of
ethinyl estradiol and 1 mg of norethindrone, decreased the AUC of
ethinyl estradiol by 43%, and decreased the AUC of norethindrone by
8%.
   In another study, a daily dose of an oral contraceptive containing
ethinyl estradiol and norethindrone was administered on Days 1 through
21, and EMEND was given as a 3-day regimen of 125 mg on Day 8 and 80
mg/day on Days 9 and 10 with ondansetron 32 mg IV on Day 8 and oral
dexamethasone given as 12 mg on Day 8 and 8 mg/day on Days 9, 10, and
11. In the study, the AUC of ethinyl estradiol decreased by 19% on Day
10 and there was as much as a 64% decrease in ethinyl estradiol trough
concentrations during Days 9 through 21. While there was no effect of
EMEND on the AUC of norethindrone on Day 10, there was as much as a
60% decrease in norethindrone trough concentrations during Days 9
through 21. The coadministration of EMEND may reduce the efficacy of
hormonal contraceptives during and for 28 days after administration of
the last dose of EMEND. Alternative or back-up methods of
contraception should be used during treatment with EMEND and for 1
month following the last dose of EMEND.
   While studies have not been done with the 40 mg single PONV dose,
the timing of EMEND administration relative to ovulation could cause
contraceptive failure. Thus, patients should be instructed to use
alternative or back-up methods of contraception during treatment with
EMEND and for 1 month following the last dose of EMEND.
   Midazolam: EMEND increased the AUC of midazolam, a sensitive
CYP3A4 substrate, by 2.3-fold on Day 1 and 3.3-fold on Day 5, when a
single oral dose of midazolam 2 mg was coadministered on Day 1 and Day
5 of a regimen of EMEND 125 mg on Day 1 and 80 mg/day on Days 2
through 5. The potential effects of increased plasma concentrations of
midazolam or other benzodiazepines metabolized via CYP3A4 (alprazolam,
triazolam) should be considered when coadministering these agents with
EMEND (125 mg/80 mg). A single dose of EMEND (40 mg) increased the AUC
of midazolam by 1.2-fold on Day 1, when a single oral dose of
midazolam 2 mg was coadministered on Day 1 with EMEND 40 mg; this
effect was not considered clinically important.
   In another study with intravenous administration of midazolam,
EMEND was given as 125 mg on Day 1 and 80 mg/day on Days 2 and 3, and
midazolam 2 mg IV was given prior to the administration of the 3-day
regimen of EMEND and on Days 4, 8, and 15. EMEND increased the AUC of
midazolam by 25% on Day 4 and decreased the AUC of midazolam by 19% on
Day 8 relative to the dosing of EMEND on Days 1 through 3. These
effects were not considered clinically important. The AUC of midazolam
on Day 15 was similar to that observed at baseline.
   An additional study was completed with intravenous administration
of midazolam and EMEND. Intravenous midazolam 2 mg was given 1 hour
after oral administration of a single dose of EMEND 125 mg. The plasma
AUC of midazolam was increased by 1.5-fold. Depending on clinical
situations (e.g., elderly patients) and degree of monitoring
available, dosage adjustment for intravenous midazolam may be
necessary when it is coadministered with EMEND for the chemotherapy
induced nausea and vomiting indication (125 mg Day 1 followed by 80 mg
on Days 2 and 3).

   Effect of other agents on the pharmacokinetics of aprepitant

   Aprepitant is a substrate for CYP3A4; therefore, coadministration
of EMEND with drugs that inhibit CYP3A4 activity may result in
increased plasma concentrations of aprepitant. Consequently,
concomitant administration of EMEND with strong CYP3A4 inhibitors
(e.g., ketoconazole, itraconazole, nefazodone, troleandomycin,
clarithromycin, ritonavir, nelfinavir) should be approached with
caution. Because moderate CYP3A4 inhibitors (e.g., diltiazem) result
in a 2-fold increase in plasma concentrations of aprepitant,
concomitant administration should also be approached with caution.
   Aprepitant is a substrate for CYP3A4; therefore, coadministration
of EMEND with drugs that strongly induce CYP3A4 activity (e.g.,
rifampin, carbamazepine, phenytoin) may result in reduced plasma
concentrations of aprepitant that may result in decreased efficacy of
EMEND.
   Ketoconazole: When a single 125-mg dose of EMEND was administered
on Day 5 of a 10-day regimen of 400 mg/day of ketoconazole, a strong
CYP3A4 inhibitor, the AUC of aprepitant increased approximately 5-fold
and the mean terminal half-life of aprepitant increased approximately
3-fold. Concomitant administration of EMEND with strong CYP3A4
inhibitors should be approached cautiously.
   Rifampin: When a single 375-mg dose of EMEND was administered on
Day 9 of a 14-day regimen of 600 mg/day of rifampin, a strong CYP3A4
inducer, the AUC of aprepitant decreased approximately 11-fold and the
mean terminal half-life decreased approximately 3-fold.
   Coadministration of EMEND with drugs that induce CYP3A4 activity
may result in reduced plasma concentrations and decreased efficacy of
EMEND.

   Additional interactions

   Diltiazem: In patients with mild to moderate hypertension,
administration of aprepitant once daily, as a tablet formulation
comparable to 230 mg of the capsule formulation, with diltiazem 120 mg
3 times daily for 5 days, resulted in a 2-fold increase of aprepitant
AUC and a simultaneous 1.7-fold increase of diltiazem AUC. These
pharmacokinetic effects did not result in clinically meaningful
changes in ECG, heart rate or blood pressure beyond those changes
induced by diltiazem alone.
   Paroxetine: Coadministration of once daily doses of aprepitant, as
a tablet formulation comparable to 85 mg or 170 mg of the capsule
formulation, with paroxetine 20 mg once daily, resulted in a decrease
in AUC by approximately 25% and Cmax by approximately 20% of both
aprepitant and paroxetine.

   Carcinogenesis, Mutagenesis, Impairment of Fertility

   Carcinogenicity studies were conducted in Sprague-Dawley rats and
in CD-1 mice for 2 years. In the rat carcinogenicity studies, animals
were treated with oral doses ranging from 0.05 to 1000 mg/kg twice
daily. The highest dose produced a systemic exposure to aprepitant
(plasma AUC0-24hr) of 0.7 to 1.6 times the human exposure (AUC0-24hr =
19.6 mcg--hr/mL) at the recommended dose of 125 mg/day. Treatment with
aprepitant at doses of 5 to 1000 mg/kg twice daily caused an increase
in the incidences of thyroid follicular cell adenomas and carcinomas
in male rats. In female rats, it produced hepatocellular adenomas at 5
to 1000 mg/kg twice daily and hepatocellular carcinomas and thyroid
follicular cell adenomas at 125 to 1000 mg/kg twice daily. In the
mouse carcinogenicity studies, the animals were treated with oral
doses ranging from 2.5 to 2000 mg/kg/day. The highest dose produced a
systemic exposure of about 2.8 to 3.6 times the human exposure at the
recommended dose. Treatment with aprepitant produced skin
fibrosarcomas at 125 and 500 mg/kg/day doses in male mice.
   Aprepitant was not genotoxic in the Ames test, the human
lymphoblastoid cell (TK6) mutagenesis test, the rat hepatocyte DNA
strand break test, the Chinese hamster ovary (CHO) cell chromosome
aberration test and the mouse micronucleus test.
   Aprepitant did not affect the fertility or general reproductive
performance of male or female rats at doses up to the maximum feasible
dose of 1000 mg/kg twice daily (providing exposure in male rats lower
than the exposure at the recommended human dose and exposure in female
rats at about 1.6 times the human exposure).
   Pregnancy. Teratogenic Effects: Category B. Teratology studies
have been performed in rats at oral doses up to 1000 mg/kg twice daily
(plasma AUC0-24hr of 31.3 mcg--hr/mL, about 1.6 times the human
exposure at the recommended dose) and in rabbits at oral doses up to
25 mg/kg/day (plasma AUC0-24hr of 26.9 mcg--hr/mL, about 1.4 times the
human exposure at the recommended dose) and have revealed no evidence
of impaired fertility or harm to the fetus due to aprepitant. There
are, however, no adequate and well-controlled studies in pregnant
women. Because animal reproduction studies are not always predictive
of human response, this drug should be used during pregnancy only if
clearly needed.

   Nursing Mothers

   Aprepitant is excreted in the milk of rats. It is not known
whether this drug is excreted in human milk. Because many drugs are
excreted in human milk and because of the potential for possible
serious adverse reactions in nursing infants from aprepitant and
because of the potential for tumorigenicity shown for aprepitant in
rodent carcinogenicity studies, a decision should be made whether to
discontinue nursing or to discontinue the drug, taking into account
the importance of the drug to the mother.

   Pediatric Use

   Safety and effectiveness of EMEND in pediatric patients have not
been established.

   Geriatric Use

   In 2 well-controlled chemotherapy-induced nausea and vomiting
clinical studies, of the total number of patients (N=544) treated with
EMEND, 31% were 65 and over, while 5% were 75 and over. In
well-controlled postoperative nausea and vomiting clinical studies, of
the total number of patients (N=1120) treated with EMEND, 7% were 65
and over, while 2% were 75 and over. No overall differences in safety
or effectiveness were observed between these subjects and younger
subjects. Greater sensitivity of some older individuals cannot be
ruled out. Dosage adjustment in the elderly is not necessary.

   ADVERSE REACTIONS

   The overall safety of aprepitant was evaluated in approximately
4400 individuals.

   Chemotherapy Induced Nausea and Vomiting

   Highly Emetogenic Chemotherapy

   In 2 well-controlled clinical trials in patients receiving highly
emetogenic cancer chemotherapy, 544 patients were treated with
aprepitant during Cycle 1 of chemotherapy and 413 of these patients
continued into the Multiple-Cycle extension for up to 6 cycles of
chemotherapy. EMEND was given in combination with ondansetron and
dexamethasone and was generally well tolerated. Most adverse
experiences reported in these clinical studies were described as mild
to moderate in intensity.
   In Cycle 1, clinical adverse experiences were reported in
approximately 69% of patients treated with the aprepitant regimen
compared with approximately 68% of patients treated with standard
therapy. Table 6 shows the percent of patients with clinical adverse
experiences reported at an incidence (>=)3%.

                             Table 6
Percent of Patients Receiving Highly Emetogenic Chemotherapy With
    Clinical Adverse Experiences (Incidence (>=)3%)  - Cycle 1

                              Aprepitant Regimen  Standard Therapy
                                  (N = 544)         (N = 550)
------------------------------------------------------------------
Body as a Whole/ Site
 Unspecified
 Abdominal Pain                             4.6              3.3
 Asthenia/Fatigue                          17.8             11.8
 Dehydration                                5.9              5.1
 Dizziness                                  6.6              4.4
 Fever                                      2.9              3.5
 Mucous Membrane Disorder                   2.6              3.1
------------------------------------------------------------------
Digestive System
 Constipation                              10.3             12.2
 Diarrhea                                  10.3              7.5
 Epigastric Discomfort                      4.0              3.1
 Gastritis                                  4.2              3.1
 Heartburn                                  5.3              4.9
 Nausea                                    12.7             11.8
 Vomiting                                   7.5              7.6
------------------------------------------------------------------
Eyes, Ears, Nose, and Throat
 Tinnitus                                   3.7              3.8
------------------------------------------------------------------
Hemic and Lymphatic System
 Neutropenia                                3.1              2.9
------------------------------------------------------------------
Metabolism and Nutrition
 Anorexia                                  10.1              9.5
------------------------------------------------------------------
Nervous System
 Headache                                   8.5              8.7
 Insomnia                                   2.9              3.1
------------------------------------------------------------------
Respiratory System
 Hiccups                                   10.8              5.6
------------------------------------------------------------------

   In addition, isolated cases of serious adverse experiences,
regardless of causality, of bradycardia, disorientation, and
perforating duodenal ulcer were reported in highly emetogenic CINV
clinical studies.

   Moderately Emetogenic Chemotherapy

   During Cycle 1 of a moderately emetogenic chemotherapy study, 438
patients were treated with the aprepitant regimen and 385 of these
patients continued into the Multiple-Cycle extension for up to 4
cycles of chemotherapy. In Cycle 1, clinical adverse experiences were
reported in approximately 73% of patients treated with the aprepitant
regimen compared with approximately 75% of patients treated with
standard therapy.
   The adverse experience profile in the moderately emetogenic
chemotherapy study was generally comparable to the highly emetogenic
chemotherapy studies. Table 7 shows the percent of patients with
clinical adverse experiences reported at an incidence (>=)3%.

                                Table 7

Percent of Patients Receiving Moderately Emetogenic Chemotherapy
 With Clinical Adverse Experiences (Incidence (>=)3%) -- Cycle 1
-----------------------------------------------------------------
                                   Aprepitant    Standard Therapy
                                      Regimen       (N = 428)
                                    (N = 438)
-----------------------------------------------------------------
Blood and Lymphatic System
 Disorders
Neutropenia                                  8.9             8.4
-----------------------------------------------------------------
Metabolism and Nutrition
 Disorders
Anorexia                                     4.3             5.8
-----------------------------------------------------------------
Psychiatric Disorders
Insomnia                                     4.1             5.6
-----------------------------------------------------------------
Nervous System Disorders
Dizziness                                    3.4             4.2
Headache                                    16.4            16.4
-----------------------------------------------------------------
Vascular Disorders
Hot Flush                                    3.0             1.4
-----------------------------------------------------------------
Respiratory, Thoracic and
 Mediastinal Disorders
Pharyngolaryngeal pain                       3.0             2.3
-----------------------------------------------------------------
Gastrointestinal Disorders
Constipation                                12.3            18.0
Diarrhea                                     5.5             6.3
Dyspepsia                                    8.4             4.9
Nausea                                       7.1             7.5
Stomatitis                                   5.3             4.4
-----------------------------------------------------------------
Skin and Subcutaneous Tissue
 Disorders
Alopecia                                    24.0            22.2
-----------------------------------------------------------------
General Disorders and General
 Administration Site Conditions
Asthenia                                     3.4             3.7
Fatigue                                     21.9            21.5
Mucosal inflammation                         2.5             3.5
-----------------------------------------------------------------


   Isolated cases of serious adverse experiences, regardless of
causality, of dehydration, enterocolitis, febrile neutropenia,
hypertension, hypoesthesia, neutropenic sepsis, pneumonia, and sinus
tachycardia were reported in the moderately emetogenic CINV clinical
study.

   Highly and Moderately Emetogenic Chemotherapy

   The following additional clinical adverse experiences (incidence
>0.5% and greater than standard therapy), regardless of causality,
were reported in patients treated with aprepitant regimen:
   Infections and infestations: candidiasis, herpes simplex, lower
respiratory infection, pharyngitis, septic shock, upper respiratory
infection, urinary tract infection.
   Neoplasms benign, malignant and unspecified (including cysts and
polyps): malignant neoplasm, non-small cell lung carcinoma.
   Blood and lymphatic system disorders: anemia, febrile neutropenia,
thrombocytopenia.
   Metabolism and nutrition disorders: appetite decreased, diabetes
mellitus, hypokalemia.

   Psychiatric disorders: anxiety disorder, confusion, depression.

   Nervous system: peripheral neuropathy, sensory neuropathy, taste
disturbance, tremor.

   Eye disorders: conjunctivitis.

   Cardiac disorders: myocardial infarction, palpitations,
tachycardia.

   Vascular disorders: deep venous thrombosis, flushing,
hypertension, hypotension.

   Respiratory, thoracic and mediastinal disorders: cough, dyspnea,
nasal secretion, pneumonitis, pulmonary embolism, respiratory
insufficiency, vocal disturbance.

   Gastrointestinal disorders: acid reflux, deglutition disorder, dry
mouth, dysgeusia, dysphagia, eructation, flatulence, obstipation,
salivation increased.

   Skin and subcutaneous tissue disorders: acne, diaphoresis, rash.

   Musculoskeletal and connective tissue disorders: arthralgia, back
pain, muscular weakness, musculoskeletal pain, myalgia.

   Renal and urinary disorders: dysuria, renal insufficiency.

   Reproductive system and breast disorders: pelvic pain.

   General disorders and administrative site conditions: edema,
malaise, rigors.

   Investigations: weight loss.

   Laboratory Adverse Experiences

   Table 8 shows the percent of patients with laboratory adverse
experiences reported at an incidence (>=)3% in patients receiving
highly emetogenic chemotherapy.


                                Table 8

            Percent of Patients Receiving Highly Emetogenic
           Chemotherapy With Laboratory Adverse Experiences
                     (Incidence (>=)3%) - Cycle 1

----------------------------------------------------
                           Aprepitant      Standard
                            Regimen        Therapy
                           (N = 544)      (N = 550)
----------------------------------------------------
ALT Increased                    6.0            4.3
AST Increased                    3.0            1.3
Blood Urea Nitrogen
 Increased                       4.7            3.5
Serum Creatinine
 Increased                       3.7            4.3
Proteinuria                      6.8            5.3
----------------------------------------------------


   The following additional laboratory adverse experiences (incidence
>0.5% and greater than standard therapy), regardless of causality,
were reported in patients treated with aprepitant regimen: alkaline
phosphatase increased, hyperglycemia, hyponatremia, leukocytes
increased, erythrocyturia, leukocyturia.
   The adverse experiences of increased AST and ALT were generally
mild and transient.
   The following laboratory adverse experiences were reported at an
incidence (>=)3% during Cycle 1 of the moderately emetogenic
chemotherapy study in patients treated with the aprepitant regimen or
standard therapy, respectively: decreased hemoglobin (2.3%, 4.7%) and
decreased white blood cell count (9.3%, 9.0%).
   The adverse experience profiles in the Multiple-Cycle extensions
for up to 6 cycles of chemotherapy were generally similar to that
observed in Cycle 1.
   Stevens-Johnson syndrome was reported as a serious adverse
experience in a patient receiving aprepitant with cancer chemotherapy
in another CINV study.

   Postoperative Nausea and Vomiting

   In well-controlled clinical studies in patients receiving general
anesthesia, 564 patients were administered 40 mg aprepitant orally and
538 patients were administered 4 mg ondansetron IV. EMEND was
generally well tolerated. Most adverse experiences reported in these
clinical studies were described as mild to moderate in intensity.
   Clinical adverse experiences were reported in approximately 60% of
patients treated with 40 mg aprepitant compared with approximately 64%
of patients treated with 4 mg ondansetron IV. Table 9 shows the
percent of patients with clinical adverse experiences reported at an
incidence (>=)3% of the combined studies.

                           Table 9

   Percent of Patients Receiving General Anesthesia With
       Clinical Adverse Experiences (Incidence (>=)3%)
-------------------------------------------------------------
                                 Aprepitant 40    Ondansetron
                                    mg (N=564)       (N=538)
-------------------------------------------------------------
Infections and Infestations
 Urinary Tract Infection                   2.3           3.2
-------------------------------------------------------------
Blood and Lymphatic System
 Disorders
 Anemia                                    3.0           4.3
-------------------------------------------------------------
Psychiatric Disorders
 Insomnia                                  2.1           3.3
-------------------------------------------------------------
Nervous System Disorders
 Headache                                  5.0           6.5
-------------------------------------------------------------
Cardiac Disorders
 Bradycardia                               4.4           3.9
-------------------------------------------------------------
Vascular Disorders
 Hypertension                              2.1           3.2
 Hypotension                               5.7           4.6
-------------------------------------------------------------
Gastrointestinal Disorders
 Constipation                              8.5           7.6
 Flatulence                                4.1           5.8
 Nausea                                    8.5           8.6
 Vomiting                                  2.5           3.9
-------------------------------------------------------------
Skin and Subcutaneous Tissue
 Disorders
 Pruritus                                  7.6           8.4
-------------------------------------------------------------
General Disorders and General
 Administration Site Conditions
 Pyrexia                                   5.9          10.6
-------------------------------------------------------------


   The following additional clinical adverse experiences (incidence
>0.5% and greater than ondansetron), regardless of causality, were
reported in patients treated with aprepitant:

   Infections and infestations: postoperative infection

   Metabolism and nutrition disorders: hypokalemia, hypovolemia.

   Nervous system disorders: dizziness, hypoesthesia, syncope.

   Vascular disorders: hematoma

   Respiratory, thoracic and mediastinal disorders: dyspnea, hypoxia,
respiratory depression.

   Gastrointestinal disorders: abdominal pain, abdominal pain upper,
dry mouth, dyspepsia.

   Skin and subcutaneous tissue disorders: urticaria

   General disorders and administrative site conditions: hypothermia,
pain.

   Investigations: blood pressure decreased

   Injury, poisoning and procedural complications: operative
hemorrhage, wound dehiscence.

   Other adverse experiences (incidence (<=)0.5%) reported in
patients treated with aprepitant 40 mg for postoperative nausea and
vomiting included:

   Nervous system disorders: dysarthria, sensory disturbance.

   Eye disorders: miosis, visual acuity reduced.

   Respiratory, thoracic and mediastinal disorders: wheezing

   Gastrointestinal disorders: bowel sounds abnormal, stomach
discomfort.

   There were no serious adverse drug-related experiences reported in
the postoperative nausea and vomiting clinical studies in patients
taking 40 mg aprepitant.

   Laboratory Adverse Experiences

   One laboratory adverse experience, hemoglobin decreased (40 mg
aprepitant 3.8%, ondansetron 4.2%), was reported at an incidence
(>=)3% in a patient receiving general anesthesia.
   The following additional laboratory adverse experiences (incidence
>0.5% and greater than ondansetron), regardless of causality, were
reported in patients treated with aprepitant 40 mg: blood albumin
decreased, blood bilirubin increased, blood glucose increased, blood
potassium decreased, glucose urine present.
   The adverse experience of ALT increased occurred with similar
incidence in patients treated with aprepitant 40 mg (1.1%) as in
patients treated with ondansetron 4 mg (1.0%).

   Other Studies

   Angioedema and urticaria were reported as serious adverse
experiences in a patient receiving aprepitant in a non-CINV/non-PONV
study.

   OVERDOSAGE

   No specific information is available on the treatment of
overdosage with EMEND. Single doses up to 600 mg of aprepitant were
generally well tolerated in healthy subjects. Aprepitant was generally
well tolerated when administered as 375 mg once daily for up to 42
days to patients in non-CINV studies. In 33 cancer patients,
administration of a single 375-mg dose of aprepitant on Day 1 and 250
mg once daily on Days 2 to 5 was generally well tolerated.
   Drowsiness and headache were reported in one patient who ingested
1440 mg of aprepitant.
   In the event of overdose, EMEND should be discontinued and general
supportive treatment and monitoring should be provided. Because of the
antiemetic activity of aprepitant, drug-induced emesis may not be
effective.

   Aprepitant cannot be removed by hemodialysis.

   DOSAGE AND ADMINISTRATION

   --  Prevention of Chemotherapy Induced Nausea and Vomiting

   EMEND is given for 3 days as part of a regimen that includes a
corticosteroid and a 5-HT3 antagonist. The recommended dose of EMEND
is 125 mg orally 1 hour prior to chemotherapy treatment (Day 1) and 80
mg once daily in the morning on Days 2 and 3.
   In clinical studies, the following regimen was used for the
prevention of nausea and vomiting associated with highly emetogenic
cancer chemotherapy:

                    Day 1          Day 2          Day 3         Day 4
----------------------------------------------------------------------
EMEND*              125 mg         80 mg          80 mg         none
----------------------------------------------------------------------
Dexamethasone**  12 mg orally   8 mg orally   8 mg orally  8 mg orally
----------------------------------------------------------------------
Ondansetron+       32 mg IV         none          none           none
----------------------------------------------------------------------

*   EMEND was administered orally 1 hour prior to chemotherapy
treatment on Day 1 and in the morning on Days 2 and 3.

**  Dexamethasone was administered 30 minutes prior to chemotherapy
    treatment on Day 1 and in the morning on Days 2 through 4. The
    dose of dexamethasone was chosen to account for drug interactions.

+   Ondansetron was administered 30 minutes prior to chemotherapy
    treatment on Day 1.

   In a clinical study, the following regimen was used for the
prevention of nausea and vomiting associated with moderately
emetogenic cancer chemotherapy:

                       Day 1          Day 2          Day 3
---------------------------------------------------------------
EMEND*                 125 mg         80 mg          80 mg
---------------------------------------------------------------
Dexamethasone**     12 mg orally       none          none
---------------------------------------------------------------
Ondansetron+      2 x 8 mg orally      none          none
---------------------------------------------------------------

*   EMEND was administered orally 1 hour prior to chemotherapy
    treatment on Day 1 and in the morning on Days 2 and 3.

**  Dexamethasone was administered 30 minutes prior to chemotherapy
    treatment on Day 1. The dose of dexamethasone was chosen to
    account for drug interactions.

+   Ondansetron 8-mg capsule was administered 30 to 60 minutes prior
    to chemotherapy treatment and one 8-mg capsule was administered 8
    hours after the first dose on Day 1.


   --  Prevention of Postoperative Nausea and Vomiting

   The recommended oral dosage of EMEND is 40 mg within 3 hours prior
to induction of anesthesia.

   General Information

   EMEND has not been studied for the treatment of established nausea
and vomiting.
   Chronic continuous administration is not recommended (see
PRECAUTIONS).
   See PRECAUTIONS, Drug Interactions for additional information on
dose adjustment for corticosteroids when coadministered with EMEND.
   Refer to the full prescribing information for coadministered
antiemetic agents.

   EMEND may be taken with or without food.

   No dosage adjustment is necessary for the elderly.

   No dosage adjustment is necessary for patients with renal
insufficiency or for patients with end stage renal disease undergoing
hemodialysis.
   No dosage adjustment is necessary for patients with mild to
moderate hepatic insufficiency (Child-Pugh score 5 to 9). There are no
clinical data in patients with severe hepatic insufficiency
(Child-Pugh score >9).

   HOW SUPPLIED

   No. 3854 -- 80 mg capsules: White, opaque, hard gelatin capsule
with "461" and "80 mg" printed radially in black ink on the body. They
are supplied as follows:

   NDC 0006-0461-30 bottles of 30 (with desiccant)

   NDC 0006-0461-06 unit-dose packages of 6.

   No. 3855 -- 125 mg capsules: Opaque, hard gelatin capsule with
white body and pink cap with "462" and "125 mg" printed radially in
black ink on the body. They are supplied as follows:

   NDC 0006-0462-30 bottles of 30 (with desiccant)

   NDC 0006-0462-06 unit-dose packages of 6.

   No. 3862 -- Unit-of-use tri-fold pack containing one 125 mg
capsule and two 80 mg capsules.

   NDC 0006-3862-03.

   No. 6741 - 40 mg capsules: Opaque, hard gelatin capsule with white
body and mustard yellow cap with "464" and "40 mg" printed radially in
black ink on the body. They are supplied as follows:

   NDC 0006-0464-10 unit-of-use package of 1.

   NDC 0006-0464-05 unit-dose packages of 5.

   Storage

   Bottles: Store at 20-25(degree)C (68-77(degree)F) (see USP
Controlled Room Temperature). The desiccant should remain in the
original bottle.
   Blisters: Store at 20-25(degree)C (68-77(degree)F) (see USP
Controlled Room Temperature).

   Rx only

   Issued June 2006

   * Registered trademark of MERCK & CO., Inc., Whitehouse Station,
New Jersey, 08889 USA

   COPYRIGHT (C) 2003,2005,2006 MERCK & CO., Inc.

   All rights reserved




                                                           9738804

                          Patient Information
                          EMEND(R) (EE mend)
                         (aprepitant) Capsules

    You should read this information before you take EMEND*. Also,
read the leaflet each time you refill your prescription, in case any
information has changed. This leaflet provides only a summary of
certain information about EMEND. Your doctor or pharmacist can give
you an additional leaflet that is written for health professionals
that contains more complete information. This leaflet does not take
the place of careful discussions with your doctor. You and your doctor
should discuss EMEND when you start taking your medicine.

    What is EMEND?

   EMEND is an antiemetic medicine for use in adult patients. An
antiemetic is a medicine used to prevent nausea and vomiting.

   --  EMEND is used to prevent nausea and vomiting caused by
       chemotherapy treatment. When used for this purpose, EMEND is
       always used WITH OTHER MEDICINES.

   --  EMEND is used to prevent nausea and vomiting caused by
       surgery.

   --  EMEND is not used to treat nausea and vomiting that you
       already have.

   Who should not take EMEND?

   Do not take EMEND if you:

   --  are taking any of the following medicines**:

   --  ORAP(R) (pimozide)

   --  SELDANE(R) (terfenadine)

   --  HISMANAL(R) (astemizole)

   --  PROPULSID(R) (cisapride)

   Taking EMEND with these medicines could cause serious or
life-threatening problems.

   --  are allergic to any of the ingredients in EMEND. The active
       ingredient is aprepitant. See the end of this leaflet for a
       list of all the ingredients in EMEND.

   What should I tell my doctor before and during treatment with
EMEND?

   Tell your doctor:

   --  if you are pregnant or plan to become pregnant. It is not
       known if EMEND can harm your unborn baby.

   --  if you are breast-feeding. It is not known if EMEND passes
       into your milk and if it can harm your baby.

   --  if you have liver problems.

   --  about all your medical problems.

   --  about all the medicines that you are taking or plan to take,
       prescription and nonprescription medicines, vitamins, and
       herbal supplements. EMEND may cause serious life-threatening
       reactions if used with certain medicines (see the section Who
       should not take EMEND?). Some medicines can affect EMEND.
       EMEND may also affect some medicines, including chemotherapy,
       causing them to work differently in your body.

   Your doctor may check to make sure your other medicines are
working, after you have taken EMEND. Patients who take COUMADIN(R)
(warfarin) may need to have blood tests after taking EMEND to check
their blood clotting.
   Women who use birth control medicines during treatment with EMEND
and for up to 1 month after using EMEND should also use a back-up
method of contraception to avoid pregnancy.

   How should I take EMEND?

   --  Take EMEND exactly as prescribed.

   --  EMEND is a capsule that you swallow with a drink.

   If you are a cancer patient, the recommended dose of EMEND is:

   --  one 125-mg capsule (white/pink) by mouth 1 hour before you
       start your chemotherapy treatment;

   AND

   --  one 80-mg capsule (white) each morning for the 2 days
       following your chemotherapy treatment.

   If you are a surgical patient, your doctor will give you a 40-mg
capsule of EMEND before surgery.

   --  EMEND may be taken with or without food. Follow your doctor's
       instructions about eating before surgery.

   --  Do not start taking EMEND if you already have nausea and
       vomiting. Ask your doctor what to do.

   --  If you take too much EMEND, call your doctor, local emergency
       room or poison control center right away.

   What are the possible side effects of EMEND?

   In patients taking the 125 mg/80 mg regimen of EMEND to prevent
nausea and vomiting caused by chemotherapy, the most common side
effects are:

   --  tiredness

   --  nausea

   --  hiccups

   --  constipation

   --  diarrhea

   --  loss of appetite

   --  headache

   --  hair loss

   In patients taking a single 40 mg dose of EMEND to prevent nausea
and vomiting caused by surgery, the most common side effects are:

   --  constipation

   --  nausea

   --  itch

   --  fever

   --  low blood pressure

   --  headache

   These are not all of the possible side effects of EMEND. For
further information ask your doctor or pharmacist. Talk to your doctor
about any side effect that bothers you.

   General information about the use of EMEND

   Medicines are sometimes prescribed for conditions that are not
mentioned in patient information leaflets. Do not use EMEND for a
condition for which it was not prescribed. Do not give EMEND to other
people, even if they have the same symptoms you have. It may harm
them. Keep EMEND and all medicines out of the reach of children.
   This leaflet summarizes the most important information about
EMEND. If you would like to know more information, talk with your
doctor. You can ask your doctor or pharmacist for information about
EMEND that is written for health professionals.

   What are the ingredients in EMEND?

   Active ingredient: aprepitant

   Inactive ingredients: sucrose, microcrystalline cellulose,
hydroxypropyl cellulose and sodium lauryl sulfate. The capsule shell
excipients are gelatin, titanium dioxide, and may contain sodium
lauryl sulfate and silicon dioxide. The 125-mg capsule shell also
contains red ferric oxide and yellow ferric oxide. The 40-mg capsule
shell also contains yellow ferric oxide.

   Issued June 2006

   MERCK & CO., Inc.

   Whitehouse Station, NJ 08889, USA

   *Registered trademark of MERCK & CO., Inc.

   COPYRIGHT (C) 2003,2005,2006 MERCK & CO., Inc.

   All rights reserved.

   **The brands listed are the registered trademarks of their
respective owners and are not trademarks of Merck & Co., Inc.