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ISBN: 978-1-56363-780-3
2908/SAUX e MOVIPREP
Hypokalemia . 10 (5.8)
Hyperphosphatemia 10 (5.8)
1
adverse reactions-were adverse events that
were possibly, probably, or definitely. related to the study
drug. In addition to the recording of spontaneous adverse
events, patients were also . specifically asked about the
occurrence of the following symptoms: shivering; anal
irritations, abdominal bloating or fullness, sleep loss,
nausea: vomiting, weakness, hunger sensation, abdomina}
cramps or pain, thirst sensation, and dizziness:
2
OSPS is Oral Sodium Phosphate Solution
Isolated .cases of )ll'ticaria, rhinorrhea, ,dermat,itis, and ana-
phylactic reaction have been wjth PEG-based prod-
ucts andmay represent allergic reactions.
Published literature contains isolated reports of serious ad-
verse events following the administration of PEG-based
products in patients over 60 years of age. These adverse
events inch1ded. upper gastroiptestinal bleeding from a
Mallory-Weiss tear, esophageal perfc;>ration, asystole, and
acute pulmonary. edema after aspirating. the. PEG-based
preparation.. . .
Postmarketing Experience . .
In addition to adverse events reported from Clinical trials,
the following adverse events have been identified during
post-approval use ofMoviPrep. Because they are reported
voluntarily from a population of unknown size, estimates of
frequency cannot be made. These events have been chosen
for inclusion due to either thek seriousness, frequency of
reporting or causal.connection-to MoviPrep, or a combina-
tion ofthe.se factors.
General: Hypersensitivity reactions including anaphylaxis
(some of which wer:e .severe, including shock), rash, urti-
caria, pruritus, lip, tongue and facial swelling, dyspnea,
chest tightness and thToat tightness. Fever, chills and dehy-
dration.
OVERDOSAGE
There have been no reported cases of overdose with
MoviPrep. Purposeful or gross accidental ingestion: of
more than. the recommended dose of MoviPrep might be
expected to lead to severe electrolyte disturbances,
ing hyponatremia and/or hypokalemia, as well as dehydra.:
tion and hypovolemia, with signs and symptoms of these
disturbances. The patient who has taken an overdose
shoUld be monitored carefully, and treated symptomatically
for complications until stable.
DOSAGE AND ADMINISTRATION
The MoviPrep dose for colon cleansing for adult patients is
2 liters (approximate1y 64 ounces) of MoviPrep solution
(With 1 additionalllter of clear fluids) taken orally prior to
the colonoscopy ii1 one of the following ways: .
11 Split-dose MoviPrep regimen: The evening before the
colonoscopy, take the first liter of MoviPrep solution over
onehour (one 8 ounce glass every 15 minutes) and then
drink. 0.5 liters (approximately 16 ounces) of clear fluid.
Then, on the morning of the colonoscopy, take the second
liter of solution overone'hour and then drink
0.5 liters of clear 'liqUid at least one hour prior to the start of
the colonoscopy; or
21 Evening-only MoviPrep regimen: Around 6
PM in the evening before the colonoscopy, take the first liter
of MoviPrep solution ove.r one hour (one 8 ounce glass ev-
ery 15 minutes) and then about 1.5 hours later take the sec-
ond liter ofMoviPrepsolution over one hour. In addition,
take 1 liter (approximately 32 ounces) of additional clear
liquid during the evening before the colonoscopy.
Preparation of' the MoviPrep solution: MoviPrep
solution is prepared by emptying the. contents of 1 pouch A
and 1 pouch B into a suitable glass container (or the con-
tainer provided) and adding to the container 1 liter of luke-
warm water. Mix the solution to ensure that the ingredients
are completely dissolved. If the patient. prefers, the
MoviPrep solution can be refrigerated prior to drinking.
The reconstituted solution should be used within 24 hours.
After consumption of the first liter of MoviPrep solution,
the above mixirig procedure should be repeated with the
second pouch A and pouch B to reconstitute the second liter
of the MoviPrep solution.
HOW SUPPLIED
MoviPrep is supplied in povydered form. MoviPrep is ad-
ministered as an oral solution after reconstitution.
MoviPrep is available in the following presentations:
Carton: The MoviPrep carton contains a disposable con-
tainer for reconstitution of MoviPrep and an inner carton
containing 4 pouches (2 of pouch A and 2 of pouch B). Pouch
A contains polyethylene glycol (PEG) 3350 100 grams,
sodium sulfate 7.5 grams, sodium chloride 2.69 grams, and
potassilli:n chloride 1.015 grams. Pouch B contains ascorbic
acid 4. 7 grams and sodium ascorbate 5.9 grams. 1 pouch A
For .the latest PDR product information, visit PDR
.net
and 1 pouch B should be dissolved together in 1liter ofluke-
warm water. When reconstituted. to 1liter volume with, wa-
ter, the solution contains 29.6 mmol/L, sodium
181.6 mmol/L (of which not more than 56.2 mmol is absorb-
able), sulfate 52.8 mmol/L, chloride 59.8 nimol!L, potassium
14.2 mmol/L, and ascorbate 29.8 mmol/L. -
NDC 65649-201-75
Rx only
STORAGE
Store carton/container at 25C (77F); excursions permitted
to 15-3ooc (59-86F). When reconstituted, store upright and
keep solution refrigerated. Use within 24
Manufactured by:
Norgine B.V.
Hogehilweg 7
1101 CAAmsterdam Zuidoost
Netherlands
For:
Salix Pharmaceuticals, Inc.
Morrisville, NC 27560
2006 Salix Pharmaceuticals Inc.
VENART 53-4/JUN 10
Product protected by US Patent Nos. pn,d
7,658,914. '
Shown in Product Identification Guide, page 318
OSMOPREP :ij
[AhZ-MO-prep]
(sodium phosphate monobasic:monohydrate
and sodium phosphate dibasic anhydrous)
Tablet
WARNINGS
There have been rare, but serious reports of
phosphate nephropatl).y in patients who received oral.
sodium phosphate products for colon cleansing prior to
colonoscopy. Some cases have resulted in
pairment of renal. .and so.me p!).tients required
long-term dialysis. While some cas_es have oc_curred in '
patients without identifiable risk fa.ctors, patients at in-
creased risk of acute phosphate nephropathy may
elude those with increased age, hypovolemia; increased
bowel transit time (such as bowel obstruction); active
colitis, or baseline kidney disease, and those using
medicines that affect renal perfusion or function (such
as diuretics, angiotensin converting -[ACE] in-,
hibitors, angiotensin receptor blockers [ARBs], and pos-
sibly noristeriodal anti-inflammatory drugs [NSAIDs]).
See WARNINGS. . . . . . ' . ..
It is important to use 'the dose and dosing regimen as
recommended (plniam split dose).
See DOSAGE and ADMINISTRATION.
' -
DESCRIPTION
OsmoPrep (sodium phosphate monobasic monohydrate,
USP, and sodium phosphate dibasic anhydrous, USP) is !).
purgative used to dean the colon prior to colonoscopy:
OsmoPrep is manufactured with a highly soluble' tablet
binder and does not contain mkrocrystalline
(MCC). OsmoPrep Tablets are oval, white td off" white com-
pressed tablets, de bossed with ''SLX" on one side of the
bisect and "102" on the other side of the bisect. Each
OsmoPrep tablet contains 1.102 grams of sodium phosphate
monobasic monohydrate, USP and 0.398 grams of sodiUm.
phosphate dibasic anhydrous, USP for a total of 1.5 grams
of sodium phosphate per tablet. Inert ingredients include
polyethylene glycol 8000, NF; and magnesium stearate, NF.
OsmoPrep is gluten-free.
The structural and molecular formulae and molecular
weights of the active ingredients are shown below: .
Sodium pli.ospnate monobasic monohydrate, USP
Molecular Formula: NaH
2
P0
4
H
2
.0
Molecular Weight: 137.99
0
II H20
A-OH
Na+o OH
Sodium phosphate dibasic anhydrous,. USP,
Molecular Formula: Na
2
HP0
4
Molecular Weight: 141.96
0
II
)\-o-Na+
HO O"Na+
OsmoPrep Tablets are for oral administra:tion ohly.
CLINICAL PHARMACOLOGY
OsmoPrep Tablets, a dosing regimen containing 48 grams of
sodium phosphate (32 tablets), induces diarrhea,' which ef-
fectively cleanses the entire colon. Each administrati h
a purgative effect for approximately 1 to 3 hours.
mary mode of action is thought to be through the
0
Pr.
1
-
effect of sodium, causing large amounts of water
drawn into the colon, promoting evacuation.
0
be
Pharmacokinetics
Pharmacokinetic studies with OsmoPrep have not been
ducted. However, the following pharmacokinetic study con.
conducted with Visicol tablets which contain the sarn Was
tive ingredients (sodium phosphate) as OsmoPrep. In
tion, Visicol is administered at a dose that is 25% gr:a:
than the OsmoPrep dose. er
An open-label pharmacokinetic of Visicol in health,
v_olunteers was perform.ed to the concentratio;.
time profile of serum morgamc phosphorus levels aft
Visicol_ administration. All subjects received the
Visicol dosing regimen (60 grams of sodium phosphate
a total liquid volume of 3.6 quarts) for colon cleansing A
gram dose (20 gi_ven as Q ev_ery 15 minutes
8 of clear hqmds) was giVen beginning at 6 PM
m the evenmg. The 30 . gram dose (20 tablets given as
3
tablets every 15 minutes with 8 ounces of clear liquids) wa
repeated the following morning beginning at 6 AM. s
'1\venty-three healthy subjects 57 years old; 57%
male and 43% female; and 65% H1sparnc, 30% Caucasian
and 4% African-American) participated in this pharmacoki:
netic study. The serum phosphorus level rose from a mean
( standard deviation) baseline of 4.0 ( 0.7) mg/dL to
7.7 ( 1.6 mg/dL), at a median of 3 hours after the admin-
istration of the first 30-gram dose of sodium phosphate
tablets (see Figure 1). The serum phosphorus level rose to a
mean of 8.4 ( 1.9) mg/dL, at a median of 4 hours after the
administration of the second 30-gram dose of sodium
phosphate tablets. The serum phosphorus level remained
above baseline for a median of 24 hours after the adminis-
tration of the initial dose of sodium phosphate tablets
(range 16 to 48 hours).
Figure 1. (standard deviation) serum phosphorus concentrations
12
:::J
10
.s
(.)
c
0
()

.!:
c.
(/)
0
.!:
0..
E
2
Q)
en
Time (h)
The upper (4.5 mg/dL) and lower (2.6 mg/dL) reference lim-
its for serum phosphate are represented by solid bars.
Special Populations
Renal Insufficiency: The effect of renal dysfunction on the
pharmacokinetics of OsmoPrep Tablets has not been stud-
ied. Since the inorganic form of phosphate in the circulating
plasma is excreted almost entirely by the kidneys, patients
with renal disease may have difficulty excreting a large
phosphate _load. Thus, OsmoPrep Tablets should be used
with caution in patients with impaired renal function (see
WARNINGS). .
Hepatic Insufficiency: OsmoPrep Tablets have not been in-
vestigated in patients with hepatic failure.
Geriatric: In a single pharmacokinetic study of sodium
phosphate tablets, which included 6 elderly volunteers,
plasma half-life increased two-fold in subjects > 70 years of
age compared to subjects < 50 years of age (3 subjects and 5
subjects, respectively).
Gender: No difference in. serum phosphate AUC values
were observed in the single pharmacokinetic study con
ducted with sodium phosphate tablets in 13 male and 10
female healthy volunteers.
CLINICAL STUDIES
The colon cleansing efficacy and safety of OsmoPrep.was
evaluated in 2 randomized, investigator-blinded, actively
controlled, multicenter, U.S. trials in patients scheduled to
have an elective colonoscopy. The trials consisted of a dose
ranging and a confirmatory phase 3 study. . f
In the phase 3 trial, patients were randomized mto
the following three sodium phosphate treatment gro.ups ..
Visicol containing 60 grams of sodium phosphate gwen ill
split doses (30 grams in the evening before the
and 30 grams on the next day) with at least 3.6
0
clear liquids; 2) OsmoPrep containing 60 grams of
phosphate given in split doses (30 grams in the everung .:h
fore the colonoscopy and 30 grams on the next day).'"?
2.5 quarts of clear liquids; and 3) OsmoPrep
48 grams of sodium phosphate (30 grams in the evelllng
IMPORTANT NOTICE: Updated drug information is sent bi-monthly via the PDR lfpdate Insert. For monthly email updates; register at PDR.net.
comPlimentary CME for PDR-Iisted products at PDR.net OSMOPREP SALIX/2909
fore the colonoscopy and 18 grams on the next day) with 2
be arts of clear liquids. Patients were instructed to eat a
ilu ht breakfast before noon on the day prior to the colonos-
gpy and then were told to drink only clear .liquids after
co on on the day prior to the colonoscopy.
;e primary efficacy endpoint was the overall colon cleans-
. g response rate in the 4-point Colonic Contents Scale. Re-
was defined as a rating of"excellent" or "good" on the
scale as determined by the blinded colonoscopist.
This phase 3 study was planned to assess the non-
inferiority of the two OsmoPrep groups compared to the
Visicol group.
The'efficacy analysis included 704 adult patients who had
an elective colonoscopy. Patients ranged in age from 21 to 89
ears old (mean age 56 years old) with 55% female and 45%
patients. Race was distributed as follows: 87% Cauca-
sian, 10% African American, and 3% other race. The
OsmoPrep 60 gram and 48 gram treatment groups demon-
strated non-inferiority compared to Visicol. See Table 1 for
the results.
[See table 1 at right]
Electrolyte
In the OsmoPrep clinical studies, expected serum electro-
lyte changes (including phosphate, calcium,, potassium, and
sodium. levels) have been observed in pa:tients taking
OsmoPrep. In the overwhelming majority of patients, elec-
trolyte abnormalities were not associated with any adverse
events.
Iii the OsmoPrep phase 3 study, 96%, 96%, and 93% of pa-
tients who took 60 grams ofVisicol, 60grams ofOsmoPrep,
and 48 grams of OsmoPrep, respectively, developed hyper-
phosphatemia (defined as phosphate level > 5.1 mgldL) on
thEfday of the colonoscopy. In this study, patients who took
60'grams pfVisicol; 60 grams of OsmoPrep, and 48 grams of
OsinoPrep had baseline mean phosphate levels of 3.5, 3.5,
a'nd 3.6 mg/dL and subsequently developed mean phosphate
levels of 7.6, 7.9, and 7.1 mg/dL; respectively, ori the day of
the colonoscopy. .
In the OsmoPrep phase 3 studY, 20%, 22%, arid 18% of pa-
tients who took 60 grams ofVisicol; 60 grams ofOsmoPrep,
arid 48 grams of OsmoPrep, . respectively, developed
hypokalemia (defined as a potassium level< 3.4 mEq!L).on
the day of the colonoscopy. In this study, patients who took
60 grams ofVisicol, 60 grams of OsmoPrep, arid 48 grams of
OsmoPrep all had baseline potassium levels of about
4.3 rnEq/1 and then developed a: me::m potassium level of
3,7 mEq/1 on the day of the colonoscopy.
fn the OsmoPrep phase 3 trial, several patients on all three
sodium phosphate regimens developed hypocalcemia and
hypernatremia that did not require treatment.
INDICATIONS AND USAGE
OsmoPrep Tablets are indicated for cleansing of the colon as
a for colonoscopy in adults 18 years. of age or
older.
CONTRAINDICATIONS
OsmoPrep Tablets are contraindicated in patients with
biopsy-proven acute phosphate nephropathy.
OsmoPrep Tablets are contraindicated. in patients with a
known allergy or hypersensitivity to sodium phosphate
salts or of its ingredients.
WARNINGS
Administration of sodium phosphate products prior to colon-
oscopy for colon cleansing has resulted in fatalities due to
significant fluid shifts, severe electrolyte abnormalities, and
C!\fdiac arrhythmias. These fatalities have been observed in
patients with renal insufficiency, in patients with bowel per-
foration, and in patients who misused or overdosed sodium
phosphate products. It is recommended that patients receiv-
mg OsmoPrep be advised to adequately hydrate before, dur-
ing, and after the use of OsmqPrep.
Considerable caution should be advised before OsmoPrep
Tablets are used in patients with the following illnesses: se-
vere renal insufficiency cleanmce less .than
30 mlJminute), congestive heart failure, ascites, unstable
angina, gastric retention, ileus, acute bowel obstruction,
P.seudo-obstruction of the bowel, severe chronic constipa-
tion, bowel perforation, acute colitis, toxic megacolon, gas-
tric bypass or stapling surgery, or hypomotility syndrome.
Consider performing baseline and labs
(phosphate, calcium, potassium, sodium, creatinine, and
BUN) in patients who may be at increased risk for serious
adverse events, including those with history. of renal insuf-
ficiency, history of - or at greater risk of - acute phosphate
nephropathy, known or suspected electrolyte disorders, sei-

arrhythmias, cardiomyopathy, prolonged QT; recent
story of a MI and those with known or suspected hyper-
Phosphatemia, hypocalcemia, hypokalemia, and hyperna-
tremia. Also if patients develop vomiting and/or signs of de-
hydratjon then- measure post-colonoscopy labs (phosphate,
calcium, potassium, sodium, creatinine, and BUN).
Table 1: Phase 3 Study - Overall Colon Content Cleansing Response Rates
1
Treatment Arm No. oftablets No. of tablets Excellent Good Fair Inadequate Overall
(grams of sodium taken at 6 PM on taken the next Response
phosphate) the day prior to day2 Rate
colonoscopy (Excellent
or Good)
OsmoPrep 20 12 76% 19% 3% 2% 95%
32 tabs
(48 g)
n=236
OsmoPrep 20 20 73% 24% 2% 1% 97%
40 tabs
(60 g)
n=233
Visicol '20 20 51% 43% 6% '0% 94%
40 tabs
(60 g)
n=235
1
Colon-cleansing efficacy was based on response rate to treatment. A patient was to be a responder if overall
colon cleansing was rated as "excellent" or "good" on a 4-point scale based on the amount of retained "colonic contents."
Excellent was defined as >90% of mucosa seen, mostly liquid stool, minimal suctioning needed for adequate visualization.
Good was defined as >90% of mucosa seen, mostly liquid .!ltool, significant suctioning needed for adequate visualization.
Fair was defined as >90% of mucosa seen, mixture of liquid and semisolid stool, could be suctioned and/or washed.
Inadequate was defined as <90% of mucosa seen, mixture of semisolid and solid stool which could not be suctioned or
washed. .
2
On the day of the colonoscopy,study medication was taken 3 to 5 hours before the start of the colonoscopy.
Renal Disease, Acute Phosphate Nephropathy, and Electro
lyte Disorders
There have been rare, but serious, reports of renal failure,
acute phosphate nephropathy, and nephrocalcinosis in pa-
tients who received oral sodium phosphate products (includ-
ing oral sodium phosphate solutions and tablets) for colon.
cleansing prior to colonoscopy. These cases often resulted in
permanent impairment of renal function and several pa-
tients required long-term dialysis. The time to onset is typ-
ically within days; however, in some cases, the diagnosis of
these events has been delayed up to several months after
the ingestion of these products. Patients at increased risk of
acute phosphate nephropathy may include patients with
the following: hypovolemia, baseline kidney disease, in-
creased age, and patients using medicines that affect renal
perfusion or function [such as diuretics, angiotensin con-
verting enzyme (ACE) inhibitors, angiotensin receptor
blockers, and possibly nonsteroidal anti-inflammatory
drugs (NSAIDs).
Use OsmoPrep with caution in patients with impaired renal
function, patients with a history of acute phosphate' neph-
ropathy, known or suspected electrolyte disturbances (such
as dehydration), or people taking concomitant medications
that may affect electrolyte levels (such as diuretics). Pa-
tients with electrolyte abnormalities such as hypernatre-
mia, hyperphosphatemia, hypokalemia, or hypocalcemia
should have their electrolytes corrected before treatment
with OsmoPrep Tablets.
Seizures
There have been rare reports of generalized tonic-clonic sei-
zures and/or loss of consciousness associated with use of
sodium phosphate products in patients with no prior history
of seizures. The seizure cases were associated with electro-
lyte abnormalities (e.g., hyponatremia, hypokalemia, hypo-
calcemia, and hypomagnesemia) and low serum osmolality.
The neurologic abnormalities resolved with correction of
fluid and electrolyte abnormalities. OsmoPrep should be
used with caution in patients with a history of seizures and
in patients at higher risk of seizure [patients using concom-
itant medications that lower the seizure threshold (such as
tricyclic antidepressants), patients withdrawing from alco-
hol or benzodiazepines; or patients with known or suspected
hyponatremia].
Cardiac Arrhythmias
There have been rare, but serious, reports of arrhythmias
associated with the use of sodium phosphate products.
OsmoPrep should be used with caution in patients with
higher risk of arrhythmias (patients with a history of car-
diomyopathy, patients with prolonged QT, patients with a
history of uncontrolled arrhythmias, and patients with are-
cent history of a myocardial infarction). Pre-dose and post-
colonoscopy ECGs should be considered in patients with
high risk of serious, cardiac arrhythmias.
PRECAUTIONS
General
Patients should be instructed to drink 8 ounces of clear liq-
uids with each 4-tablet dose of OsmoPrep Tablets. Patients
should take a total of 2 quarts of clear liquids with
OsmoPrep. Inadequate fluid intake, as with any effective
purgative, may lead to excessive fluid loss, hypovolemia,
and dehydration. Dehydration from purgation may be exac-
erbated by inadequate oral fluid intake, vomiting, and/or
use of diuretics.
Patients should be instructed not to administer additional
laxative or purgative agents, particularly additional sodium
phosphate-based or enema products.
Prolongation of the QT interval has been observed in some
patients' who were dosed with sodium phosphate colon
preparations. QT prolongation with sodium phosphate tab-
lets has been associated with electrolyte imbalances, such
as hypokalemia and hypocalcemia. OsmoPrep Tablets
should be used with. caution in patients who are taking
medications known to prolong the QT interval,' since serious
complications may occur. Pre-dose . and post-colonoscopy
EGGs should be considered in patients with known pro-
longed QT.
Administration of OsmoPrep Tablets may induce colonic
mucosal aphthous ulcerations, since this endoscopic finding
was observed with other sodium phosphate cathartic prepa-
rations. In the OsmoPrep clinical program, aphthous ulcers
were observed in 3% of patients who took the 48 gram
OsmoPrep dosing regimen. This colonoscopic finding shoUld
be coi:J.sidenid in patients with kno'Wn or suspected inflam-
matory bowel disease.
Becal1se published data suggest that sodium phosphate ab-'
sorption may be enhanced in patients experiencing an acute
exacerbation . of chronic bowel disease,
OsmoPrep Tablets should be use.d with caution in such
patients.
Drug Interactions ,
Medications administered in close proximity to OsmoPrep
Tablets may i:J.ot be absorbed from the gastrointestinal tract
due to the rapid intestinal peristalsis and watery diarrhea
mduced by the pUJ:'gative agent.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals have not been performed to
evaluate the carcinogenic potential of OsmoPrep. Studies to
evaluate the effect of OsmoPrep on fertility or its mutagenic
potential have not' been performed.
Pregnancy. Teratogenic Effects: Pregnancy Category C
Animal reproduction studies have not been conducted with
OsmoPrep. It is not known whether can cause
fetal harm when administered to a pregnant woman, or can
affect reproduction capacity. OsmoPrep Tablets should be
given to a pregnant woman only if clearly needed.
Pediatric Use
The safety and efficacy of OsmoPrep Tablets have not been
demonstrated in patients less than 18 years of age.
Geriatric Use
In controlled colon preparation .trials of OsmoPrep, !?28
(24%)of931patients were 65 years of age or older. In addi-
tion, 49 (5%) of the 931 patients were 75 years of age or
older. .
Of the 228 geriatJ:ic patients in the trials, 134 patients
(59%) received at least 48 grams of OsmoPrep. Of the 49
patients 75 years old or older in the trials, 27 (55%) patients
received at least 48 grams of OsmoPrep. No overall differ,
ences in safety or effectiveness were observed between ger-
iatric patients and younger patients. However, the mean
phosphate levels in geriatric patients were greater than the
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2910/SALIX OSMOPREP
phosphate levels in younger patients after OsmoPrep ad-
ministration. The mean colonoscopy-day phosphate levels in
patients 18-64, 65-74, and :2: 75 years old who received
48 grams of OsmoPrep in the phase 3 study were 7.0, 7,3,
and 8.0 mg/dL, respectively. In addition, in all three sodium
phosphate treatment groups, the mean phosphate levels in
patients 18-64, 65-74, and :2: 75 years old in the phase 3
study were 7.4, 7.9, and 8.0 mg/dL, respectively, after
sodium phosphate administration. Greater sensitivity Of
some older individuals cannot be ruled out; therefore,
OsmoPrep Tablets should be used with caution in geriatric
patients. .
Sodium phosphate is known to be substantially excreted by
the kidney, and the risk of adverse reactions with sodium
phosphate may be greater in patients with impaired renal
function. Since geriatric patients are more likely to have im-
paired renal function, consider performing baseline and
post-colonoscopy labs (phosphate, calcium, potassium, so-
dium, creatinine, and BUN) in .these. patients (see WARN-
INGS). It is recommended that patients . receiving
OsmoPrep be advised to adequately hydrate before, during,
and after the use of OsmoPrep.
ADVERSE REACTIONS
Abdominal bloating, abdominal pain, nausea, and vomiting
were the most common adverse events reported with the
use of OsmoPrep Tablets. Dizziness and headache were re-
ported less frequently. Since diarrhea was considered as a
. part of.the efficacy oLOsmoPrep, diarrhea was not defined
as an adverse event in the clinical studies. Table 2 shows .
the most common adverse events associated with the use of
48 grams of OsmoPrep, 60 grams of OsnioPrep, and
60 grams of Visicol in the colon preparation (n=931).
2: Adverse Events, of Any Se"erity
Occurring .in Great17r Than 3% of in the
OsmoPrep Trials
.,
OsmoPrep OsmoP,rep Visicol
32 tabs 40tabs 40Wbs
148g).

(60 g)
:
,N:272' N:265 I i\1:268.
.
Bloating 31% 39% :41%
.
Nausea 26% 37% 30%
Abdominal Pain 23% ' .. 24% 25%
Vomiting 4% 10% 9%
Postmarketh1g Experience . . .... . ,_ . .
In addition to adverse. ev,ents reported from clinical triilis,
the following 'events have been identified during
post-approval use ofOsmoPtep. Because they are reported
voluntarily from a populcition of u:nk:iwwn size, estimates of
frequency cannot be made: These events have been chosen
for inclusion due to either their seriousness, frequency of
reporting or causal connection to OsmoPrep,or a combina-
tion of these factors.
Generi& Hypersensitivity inclvding
laXis, rash, pruritus, urticaria, throat tightness, broncho-
spasm, dyspnea, pharyngeal edema, dysphagi,a, paz:esthesia
and swelling of the lipsand tongue, and facial
Cardiovascular: Arrhythmias
Nervous system: Seizures .
Renal: Renal impairment, increased blood urea nitrogen
(BUN), increased creatinine, acute renal faihire, acute
nephropathy, nephr,Jcalcinosis, arid rerial tubu-
lar necrosis.
DRUG ABUSE AND DEPENDENCE
Laxatives and purgatives (including OsmoPrep) have the
potential for abuse by bulimia nervosa patients who fre-
quently have binge eating and vomiting.
OVERDOSAGE
There have been no reported cases of overdpsage with
OsmoPrep Tablets. Purposeful or accidental of
more than the recommended dosage of OsmoPrep Tablets
might be expected to lead to severe electrolyte disturbances,
including. hypocalcemia,
mia, or hypokalemia, as well as dehydration and hypovole-
mia, with attendant sigus and symptoms of these
bartces.' Certain severe electrolyte disturbances resulting
from overdose may lead to cardiac arrhythmias, seizure, re-
nal failure, and death. The patient who has taken an over-
dosage should be monitored carefully, and treated symptom-
atically'for C?mplications until stable.
DOSAGE AND ADMINISTRA'l'ION
The recommended: dose of osmoPrep Tablets for colon
cleansing for adult patients is 32 tablets (48 grams of
sodium phosphate) taken orally with a total of 2 quarts of
clear liquids in-the following manlier:
The evening befoe the oolonoooopy pooedue: :: :he ::;;,
OsmoP.rep Tablets with 8 ounces of clear liquids .every 15 rhea. Cleaning your colon helps your doctor see theine t9.r. 1
minutes for a total of 20 tablets. ' your colon more clearly during the colonoscopy.
81
e of J
On the day of the colonoscopy procedure:. Starting 3-5 It is not known if OsmoPrep is safe and works in child I
hours before the procedure, take 4 OsmoPrep Tablets with under age 18. ren
8 ounces of clear liquids every 15 minutes for a total of 12 Who should not take OsmoPrep?
tablets. Do not take OsmoPrep if:
Patients should be advised of the importance of taking the
8
you have had a kidney biopsy that shows you have kidn
recommended fluid regimen: It is recommended that pa- problems because of too much phosphate ey
tients receiving OsmoPrep be advised to adequately hydrate you are allergic to sodium phosphate salts or any of th
during, and after the use of OsmoPrep. . . . i?' Osn:oPrep_. See end of this Medicati e
Pat1ents should not use OsmoPrep for colon cleansmg Gmde for a hst of mgred1ents m OsmoPrep. on
within seven days of previous administration. No additional What should I tell my doctor before taking OsmoPrep?
enema or laxative is required, and patients should be ad- Before taking OsmoPrep, tell your doctor about all of y
vised NOT to take additional agents, particularly those con- medical conditions, including if you have: our
taining sodium phosphate. any of the medical conditions listed in the section "Wh
HOW SUPPLIED is the most important information I should know abo
OsmoPrep Tablets are supplied in child-resistant bottles
containing 100 tablets. Each tablet contains 1.102 g sodium
phosphate monobasic monohydrate, USP and 0.398 g
sodium phosphate dibasic anhydrous, USP for a. total of
1.5 g of sodium phosphate per tablet.
Each bottle qontains. two silica desiccap.t which
f:\hould not be ingested.
NDC.65649-701-41 (100 tablet bottle)
Rx only. .
, Store at 25C ('Z7F);, excursions per:mitted to 15-30C
(See USP Controlled Room Temperature]. Discar9.
any unused portion.
Manufactured by:. , . . .
WellSpring Pharmaceutical Canada Corp.
Oakville, Ontario Canada L6H 1M5
for:
Salix Pharmaceuticals, Inc:
Morrisville, NC 27560
in Canada
VENART-30-4
Revised March 2009
Product protected by US Patent No. 5,616,346 and other
pending applications'. -
MEDicATION GUIDE
OsmoPrep (AhZ-MO-prep) (sodium phosphate monobasic
monohydrate, . USP and sodium phosphate dibasic
anhydrous, USP) Tablets
Read the Medication Guide that comes with OsmoPrep be-
fore you take it and each time you take it. This Medication
Guide does not take the place of .talking with your doctor
about your medical condition or your treatment. If you have
any questions about OsmoPrep, ask your doctor or pharma-
cist.
What is the most important information J. sho.uld know
about OsmoPrep?;.
OsmoPrep can.cause serious side effects, including:.
Serious kidney problems. Rare, but serious kidney prob-
lems can happen in people who take medicines made with
sodium phosphate, including OsmoPrep, to clean your colon
before colonoscopy. These kidney problems can sometimes
lead to kidney failure or the n.eed for dialysis for a long time.
These. problems often happen within a few days, but some-.
times may happen several months after taking OsmoPrep.
Conditions that can make you more at risk for having seri-
ous kidney problems with OsmoPrep include if you:
lose too much body fluid (dehydration)
have slow moving bowels
have bowels blocked with stool (constipation)
have severe stomach pain or bloating .
have any disease that causes bowel irritation (colitis)
have kidney disease
have heart failure
,,.take w'ater pills or non-steroidal anti-inflammatory drugs
. (NSAIDS) _
Your age may also affect your risk for having kidney prob-
lems with OsmoPrep.
Before you start taking OsmoPrep tell your doctor if you:
have kidney problems.
o take any medicines for blood pressure,'.heart disease, or
kidney disease.
Severe fluid Joss. People who take medicines that contain
sodium phosphate can have severe loss of body fluid,: with
severe changes in body salts in the blood, and abnorm,al
heart rhythms. These problems can lead to death.
Tell your doctor if you have any of these symptoms ofloss of
too much body fluid (dehydration) while taking OsmoPrep:
vomiting
dizziness
urinating less often than normal
headache
See "What are the possible side effects of for
more information about side effects.
What is OsmoPrep?
OsmoPrep is a prescription medicine used in adults 18
years and older, to clean .. your colon before a colonoscopy.
OsmoPrep?" u
irritation of the bowel (colitis). OsmoPrep can cause sym
toms of irritable bowel disease to flare-up. P
damage to your bowels
problems with abnormal heart beat
had a recent heart attack or have other heart problems
symptoms of too much body fluid loss (dehydration) in-
cluding vomiting, dizziness, urinating less often than nor-
mal, or headache
had stomach surgery
a history of seizures
o. if you drink alcohol
are on a low salt diet
are pregnant. It is not known if OsmoPrep will harm your
unborn baby.
Tell yo.ur.doctor about all including
prescnptwn and non-prescnptwn med1emes, VItamins, and
herbal supplements. Any medicine that.you take close to the
time .that you take OsmoPrep may not work as well. Espe-
cially tell your doctor if you take:
" water pills (diuretics)
medicines for blood pressure or heart problems
medicines for kidney damage
0
medicines for pain, such as aspirin or a non-steroidal anti-
inflammatory d:J:ug (NSAID)
.. a medicine for seizures
o a laxativ:e for constipation in the last 7 days. You should
not take another medicine that contains sodium
phosphate while you.take OsmoPrep.
Ask your doctor ifyou are not sure if your medicine is listed
above.
Know the medicines you take. Keep a list of your medicines
to show your doctor or pharmacist when you get a new
prescription.
How should I take OsmoPrep? .
Take OsmoPrep exactly as prescribed by your doctor.
" It is important for you to drink clear liquids before, dur;
ing, and after taking OsmoPrep. This may help prevent
kidney damage. Examples of clear liquids are water, fla-
vored water, lemonade (no pulp), ginger ale or apple juice.
Do not drink any liquids colored purple or red.
You must read, understand, and follow these instructions
to take OsmoPrep the right way:
On the evening before your colonoscopy, you will take a
total of 20 OsmoPrep tablets, as follows:
1. Take 4 OsmoPrep tablets \vith 8 ounces of clear liquids.
2. Wait 15 minutes.
3. Take 4 more OsmoPrep tablets with 8 ounces of clear liq
uids.
4. Repeat step's 2 and 3 above, three more times. Make sure
you wait 15 minutes after each time.
On the day of your colonoscopy, you will take a total of
12 OsmoPrep tablets, starting about 3 to 5 hours before
your colonoscopy, as follows:
1. Take 4 OsmoPrep tablets with 8 ounces of clear liquids .
2. Wait 15 minutes.
3. Take 4 more OsmoPrep tablets with 8 ounces of clear liq
uids.
4. Repeat steps 2 and 3 one more time. .
Tell your doctor if you have any of these symptoms while
taking OsmoPrep:
vomiting, dizziness, or if you urinate less often than no_rd
mal. These may be signs that you have lost too much f!Ul
while taking OsmoPrep.
trouble drinking clear fluids
severe stomach cramping, bloating, nausea, or headache.
If you take too much OsmoPrep, call your doctor or get
medical help right away.
What should I avoid while taking OsmoPrep? . h
o You shoUld not take other laxatives or enemas made Wit
sodium phosphate, while taking OsmoPrep. 't
You should not use OsmoPrep if you have already used
1
in the last 7 days.
What are the possible side effects of OsmoPrep?
OsmoPrep can cause serious side effects, including: ld
See "What is the most important information I shoU
know about OsmoPrep?"
IMPORTANT NOTICE: Update<! <!rug Information Is sent bi-monthly via the PDR Update Insert' For monthly email updates, register at PDR.n:........J
mentary CME for PDR-Iisted products at PDR.net
Seizures or fainting (black-outs). People who take a med-
:ciJle that contains sodium phosphate, such as OsmoPrep,
1
an have seizures or faint (become unconscious) even if
have not had seizures before. Tell your doctor right
'awaY if you have a seizure or faint while taking
osmoPrep
1
j\bnormal heart beat (arrhythmias: .
1
changes your blood levels of calcmm, phosphate, potas-
sium, sodium .
rfhe common side effects of OsmoPrep are:
1
bloatmg
1
stomach area (abdominal) pain
1
nausea
1 1
omitiilg
These are not all the possible side effects of OsmoPrep. For
more information, ask your doctor or pharmacist.
call your doctor for medical advice about side effects. You
may report side effects to FDA at 1-800-FDA-1088.
HoW do I store OsmoPrep? .
1
Store OsmoPrep at room temperature, between 59' F t6
86' F (15' C to 30' C). . . . . .
, Throw away any OsmoPrep that is not needed.
, Keep OsmoPrep and all medicines' out of the reach of
children. . . .
General information about OsmoPrep . . .
Medicines are sometimes prescribed for purposes other than
those listed in a Medication Guide; Do not US!.'l OsmoPrepfor
a condition for which it was not prescribed. Do not give
OsmoPrep to other people, even if they have the same s:Ymp-
toms that you have. It may harm them.
This Medication Guide summarizes the most in-
formation about OsmoPrep. Ifyouwould.like more informa-
tion ab.out OsmoPrep, talk with your doctor or pharmacist.
You can ask your doctor or pharmacist for information that
is written for healthcare professionals. For more informa-
tion, call1-866-669-7597 free) or go to www.Salix.com.
What are the ingredients in OsmoPrep?
Active ingredients: sodium phosphate monobasic
monohydrate and sodium phosphate dibasic anhydrous
Inactive ingredients: polyethylene glycol 8090 and magne-
sium stearate ' ' . . .
This Medication Guide has been approved by the U.S. Food
and Drug Administration.
Revised March 2009
SaliX Pharmaceuticals, Inc.
Morrisville, NC 27560, USA
This Medication Guide has been. approved by the Food
and Drug Administration. ' =
VENART-30-4
Revised March 2009 .
Shown in Product Identification page 318.
XIFAXAN
[zuhFAXin]
(rifaximinl
Tablets
OF PRESCRIBING. INFORMATION
These highlights do not include all the information
to use XIFAXAN,-safely. and effectively. See full prescribing
information for XIFAXAN.
XIFJU{AN (rifaximinl. Tablets
Initial. U.S. Approval: 2004 . '
TO reduce the development of drug-resistant bacteria.:and
maintain the effectiveness of XIFAXAN and other antibac-
terial drugs, XIFAXAN should be.tised only to treat or pre-
vent infections that are proven or strongly suspected to be
caused by bacteria. .. :
----R.ECENT MAJOR CHANGES-----.,
Indications and Usage,
Hepatic Encephalopathy (1.2) 03/2010
Dosage and Administration,
Hepatic Encephalopathy (2.2) 03/2010
'. . INDICATIONS :AND USAOE----'-..,----'-
XlFAXAN is a rifamycin antibacteriai indicated for:
The treatment of patients ("2::: 12 years of age) with trav-
elers' diarrhea (TD) caused by noninvasive of
Escherichia coli (1.1)
' Reduction in risk of overt hepatic encephalopathy (H;E)
recurrence in patients <::: 18 years of age (1.2)
of Use
TD: Do not use in patients with diarrhea complicated by
fever or blood in the stool or diarrhea due to pathogens
other than Escherichia coli (1.1)
-DOSAGEAND ADMINISTRATION-,--_ --
.Travelers' diarrhea: One 200 mg tablet taken orally
three times a day for 3 days, with or without food (2.1)
. .Hepatic encephalopathy: One 550 mg tablet taken orally
two times a day, with or without food (2.2)
-DOSAGEFORMSAND STRENGTHS-
200 mg and 550 mg tablets (3)

History of hypersensitivity to rifaximin, rifamycin antimi-
crobial agents, or any of the components of XIFAXAN ( 4.1)
---WARNINGS AND
Travelers' Diarrhea Not Caused by E. coli: XIFAXAN
was not effective iri diarrht:Ja complicated by fever and/or
blood in the stool or diarrhea due to pathogens other than
E. coli. If diarrhea symptoms get worse or.persist for more
than 24-48 hours, discontinue XIFAXAN .and consider al-
ternative antibiotics (5.1) . . . .
Clostridium difficile-Associated Diarrhea:. 'E'Valuate if
diarrhea occurs after therapy or does not improve or wors-
ens during therapy (5.2) . ,
Hepatic Impairment: Use with caution in patients with
severe (Child-Pugh C) hepatic impairment (5;4, 8.7)
-----.ADVERSE __ _
Most common adverse reactions in travelers' diarrhea
(<::: 5%): Flatulence, headache, abdominal pain, rectal te-
nesmus, defecation urgency and nausea (6.1)
Most common adverse reactions in HE (<::: 10%}: Periph-
eral edema, nausea, dizziness, fatigue, ascites, flatulence,
and headache (6.1)
To report suspected adverse reactions, contact Salix Phar-
maceuticals at 1866-669-7597 and .www.Salix.com or FDA
at 1-800-FDA-1088 or WW111f.lda.gov/medwatch
--.,--USE IN SPECIFIC POPULATIONS---
Pregnancy: Based on animal data, may cause fetal harm
(8.1)
.Nursing Mothers: Discontinue nursing or drug, .taking
into account the importance of the drug to the mother
(8.3)
See 17 for. PATIENT COUNSELING INFORMATION
Revised: Mar/2010
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
1.1 Travelers' Diarrhea
1.2 Hepatic Encephalopathy
2 DOSAGE AND ADMINISTRATION
2.1 Dosage for Travelers' Diarrhea
2.2 Dosage for Hepatic Encephalopathy
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
4.1 Hypersensitivity
5 WARNINGS AND PRECAUTIONS
5.1 Travelers' Diarrhea Not Caused by Escherichia
coli
5.2 Clostridium. difficile-ASsociated Diarrhea
5.3 Development of Drug Resistant Bacteria
5.4 Severe (Child-Pugh C) Hepatic Impairment'
6 ADVERSE REACTIONS
6.1 Clinical Studies Experience
6.2 Postmarketing Experience
7 DRUG INTERACTIONS
8 USE IN SPECIFIC POPULATIONS .
8.1 Pregnancy
8.3 Nursing Mothers.
8.4 Pediatric Use
. 8.5 . Geriatric Use
8.6 Renal Impairment
8. 7 Hepatic Impairment
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1. Mechanism of Action
12.3 Pharmacokinetics
12.4 Microbiology
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fer-
tility
13.2 Animal Toxicology and/or Pharmacology
14 CLINICAL STUDIES
14.1 Travelers' Diarrhea
14.2 Hepatic Encephalopathy
15 REFERENCES
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
17.1 Persistent Diarrhea
17.2 Clostridium difficile-Associated Diarrhea
17.3. Administration with Food .
17.4 Antibacterial Resistance
17.5 Severe Hepatic Inipafrment
* Sections or subsections omitted from the full prescribing
information are not listed
FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
To reduce .the development of drug-resistant bacteria and
maintain the effectiveness of XIFAXAN and other antibac"
terial drugs, XIFAXAN when used to treat infection should
be used only to treat or prevent infections that are proven or
strongly suspected to be caused by susceptible bacteria.
When culture and susceptibility information are available,
XIFAXAN SALIX/2911
they should be considered in selecting or modifYing antibac-
terial therapy. In the absence of such data, local epidemiol-
ogy and susceptibility patterns may contribute to the em-
piric selection of therapy.
1.1 .Travelers' Diarrhea . .
XIFAXAN 200 mg is indicated for the treatment of patients
(<::: 12 years of age) with travelers' diarrhea caused by non-
invasive strains of Escherichia 'coli [see Warnings and Pre-
cautions (5), Clinical Pharmacology (12.4) and Clinical
Studies (14.1)].
Limitations o Use
F s oul not be used in patients with diarrhea com
plica ted by fever or blood in the stoat or diarrhea Clue to
pathogens other than Escherichia coli.
1.2 Hepatic Encephalopathy
XIFAXAN 550 mg is indicated for reduction in risk of overt
hepatic encephalopathy (HE) recurrence in patients <::: 18
years of age.
In the trials ofXIFAXAN for HE, 91% of the patients were
using lactulose concomitantly. Differences in t:reatment
effect of those patients not using lactulose concomitantly
could not be assessed.
XIFAXAN has not been studied in patients with MELD
(Model for End-Stage Liver Disease) scores > 25, and only
8.6% of patients in the controlled trial-had MELD scores
over 19. There is increased systemic exposure in patients
with more severe hepatic dysfunction [see Warnings and
Precautions (5.4), Use in Specific Populations (8. 7), Clinical
Pharmacology (12.3)].
2 DOSAGE AND ADMINISTRATION
2.1 Dosage for Travelers' Diarrhea
The recommended dose of XIFAXAN is one 200 mg tablet
taken orally three times a day for 3 days. XIFAXAN can be
administered orally, with or without food [see Clinica'l Phar-
macology (12.3)]. .
2.2 Dosage for Hepatic Encephalopathy
The recommended dose of XIFAXAN is one 550 nig tablet
taken orally two times a day, with or without food [see Clin"
ical Pharmacology (12.3)].
3 DOSAGE FORMS AND STRENGTHS
XIFAXAN is a pink-colored biconvex tablet and is available
in the following strengths: '
" 200 mg - a rounq tablet debossed with "Sx" on one side.
o 550 mg - an oval tablet debossed with "rfx" on one side.
4 CONTRAINDICATIONS
4.1 Hypersensitivity
XIFAXAN is contraindicated in patients with a hypersensi-
tivity to rifaximin, any of the rifamycin antimicrobial
agents, or any of the components in XIFAXAN. Hypersensi-
tivity reactions have included exfoliative dermatitis, angio-
neurotic edema, and anaphylaxis [see Adverse Reactions
(6.2)].
5 WARNINGS AND PRECAUTIONS
5.1 Travelers' Diarrhea Not Caused by Escherichia coli
XIFAXAN W;=tS not found to be effective in patients with di-
arrhea complicated by fever and/or blood in the stool.or di-
arrhea due to pathogens other than Escherichiq, coli:
Discontinue XIFAXAN if diarrhea symptoms get worse or
persist more than 24-48 hours and alternative antibiotic
therapy should be considered. . , .
XIFAXAN is not effective in cases of travelers' diarrhea due
to Campylobacter jejuni. The effectiveness of XIFAXAN in
travelers' diarrhea caused by Shigella spp. and Salmonella.
spp. has not been proven. XIFAXAN should not be used in
patients where Campylobacter jejuni, Shigella spp., or Sal-
monella spp. may be suspected as causative. pathogens.
5.2 Clostridium difficile-Associated Diarrhea
. Clostridium difficile"associated diarrhea (CDAD).has. been
1
reported with use of nearly all antibacterial agents, includ-
ing XIFAXAN, and may range in severity from mild .diar-
rhea to fatal colitis. Treatment with antibacterial agents al-
ters the flora of the colon which' may lead to
overgrowth of C. difficile.
C. difficile produces toxills A and B which contribute to the
development 'of CDAD. Hypertoxin producing strains of C.
difficilr; cause increased morbidity ;=tnd mortality, as these
infections can be refractory to antimicrobial therapy arid
may require colectomy. CDAD must be considered in all pa-
tients who present with diarrhea following antibiotic use.
Carefui medical history is necessary since CDAD has been
reported to occur over two months after the administration
of antibacterial agents. . . .
If CDAD is suspected or confirmed, ongoing a:iJ.tibiotic use
not directed against C. difficile may need to be discontinued.
Appropriate fluid and electrolyte management, protein sup-
plementation, antibiotic treatment of C. difficile, and surgi-
cal evaluation should be instituted as clinically indicated.
5.3 Development of Drug Resistant Bacteria
Prescribing XIFAXAN for travelers' diarrhea in the absence
of a proven or strongly suspected bacterial infection or a
prophylactic indication is unlikely to provide benefit to the
patient and increases the risk of the development of drug-
resistant bacteria.
Visit PDR.netto register for Product Safety Alerts and to download mobi/ePDR free to U.S. prescribers