Title: PharmaNote
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Permanent Link: http://ufdc.ufl.edu/UF00087345/00026
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Title: PharmaNote
Series Title: PharmaNote
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Creator: University of Florida College of Pharmacy
Publisher: College of Pharmacy, University of Florida
Publication Date: January 2005
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Anna Varughese, Pharm.D. Candidate

The World Health Organization recognizes
depression as one of the most debilitating diseases.
It affects almost 340 million people worldwide, in-
cluding 18 million Americans. The majority of pa-
tients with major depression (MD) have other co-
morbid conditions such as anxiety or substance
abuse disorders. The Diagnostic and Statistical
Manual of Mental Disorders (DSM-IV) defines de-
pressive symptoms as both physical and emo-
tional.2 Depression is thought to be mediated by the
neurotransmitters serotonin (5HT) and/or norepi-
nephrine (NE). They exert actions centrally within
the raphe nucleus and locus ceruleus which project
to the cerebral cortex and the limbic system in the
forebrain. Deficiency of 5HT and NE neurotrans-
mission is considered to be the substrate for symp-
toms associated with depression; consequently,
pharmacologic agents that inhibit reuptake of one
or both of these transmitters are expected to im-
prove symptoms of depression.6
Duloxetine (Cymbalta, Eli Lilly), a dual
reuptake inhibitor of 5HT and NE, was approved in
August 2004 for the treatment of depression and
September 2004 for the management of pain asso-
ciated with neuropathy. This review will evaluate

the current evidence of duloxetine's efficacy and
safety for the treatment of depression

Mechanism of action
Duloxetine inhibits the reuptake of both
5HT and NE, but its affinity for 5HT receptors is
greater. Duloxetine inhibits the reuptake of NE at
doses greater than or equal to 60 mg/day; compared
to venlafaxine, it is a more balanced inhibitor of
5HT and NE. Duloxetine does not exert significant
activity at dopaminergic, histaminergic, muscarinic,
alpha, opioid, 5HT1A, 5HT1B, 5HT1D, 5HT2A, or
5HT2c receptors.2 The metabolites of duloxetine are
pharmacologically inert. Although both duloxetine
and tricyclic antidepressants (TCA) are dual inhibi-
tors of NE and 5HT, duloxetine may be better toler-
ated than TCA's since it is devoid of cholinergic,
muscarinic, and adrenergic activity.1

Duloxetine is administered orally with a
recommended starting dose of 20 mg twice daily. It
adheres to a one compartment model with first or-
der kinetics. The volume of distribution (Vd) is
1943 liters, and the half-life is 12.5 hours.3 The
drug reaches steady state after 3 days.8 Compared
to SSRIs, duloxetine has a shorter onset of action


1 1 F4 I

PharmaNote Volume 20, Issue 4, January 2005




Volume 20, Issue 4, January 2005

Table 1. Mean changes (standard error) after the end of therapy in depression
Studies N HAMD 17HAMD 10 subfactor HAMA (total) Results
P<0.01 for HAMD 17 vs.
Placebo 115 -6.1 -0.5 -2.0 P<.1 for HAD 17vs.
Duloxetine 60 mg/dc 121 -10.9 -0.9 -3.0 placebo p<0.0 for HA
10 and A/S vs. placebo

Placebo' 136 -8.3 -0.6 -2.3 p< 0.05 for HAMD17 vs.
duloxetine 60 mg 123 -10.5 -0.8 -2.6 placebo
to ,Primary Endpoint: HAMD
Placebo 89 -5.0 -0.4 -1.4 -4.3 Primary Endpoint: HA
Duloxetine 40 mg/d 86 -7.4 -0.8 -2.1 -5.5 17
Duloxetine 80 mg/d 91 -8.6 -1.0 -2.9 -6.6placebo
Paroxetine 20 mg/d 87 -6.2 -0.8 -2.1 -5.2 < 0.001 vs. placebo
p= 0.150 vs. paroxetine

N = number of patients with at least 1 post baseline observation

because of its effects on both 5HT and NE.1Du-
loxetine is highly protein bound (>90%), and is
metabolized to several inactive metabolites in the
liver via CYP1A2 and CYP2D6.4 Bioavailability of
duloxetine is decreased by 66% in smokers due to
the induction of CYP1A2. However, no formal
dose alterations are recommended in this popula-
tion. Duloxetine is not recommended in patients
with hepatic impairment or moderate to severe re-
nal disease. Population pharmacokinetic studies do
not support a need for dosage adjustment in pa-
tients with mild renal disease. Duloxetine can be
administered without regard to meals. Safe and ef-
fective use of duloxetine in the elderly and in chil-
dren has not been established.8

Clinical trials
Several studies have investigated the effi-
cacy of duloxetine on depressed mood and physical
symptoms associated with depression. Two ran-
domized, double-blind, placebo-controlled trials
have been conducted.2 (Table 1) In both studies, pa-
tients taking duloxetine reported a significantly
greater reduction in painful symptoms associated
with MD (e.g., back pain, shoulder pain) within 2
weeks of therapy compared to placebo. The reduc-
tion in the Hamilton depression scores and the So-
matic Symptom Inventory scores from baseline to
end of follow up were higher in the duloxetine
group versus the placebo group (p<0.02, p<0.05,
respectively), indicating improvement. The authors
concluded that duloxetine showed significant im-
provement in Hamilton depression and pain scores

compared to placebo.2
A randomized, multicenter, double bind
trial compared the efficacy of duloxetine 20 mg
twice a day, 40 mg twice a day, placebo, and par-
oxetine 20 mg once daily in patients with MD dur-
ing 8 weeks of treatment.10 The efficacy measures
included HAMD 17 (17-item Hamilton Depression
rating scale), HAMA (Hamilton depression total
score), anxiety/somatization subfactor (A/S) and
HAMD 10 (10-item Hamilton depression rating
scale). The primary efficacy analysis used a mixed
effects model repeated measures method of analy-
sis. The patients were classified into lower and
higher strata depending on their baseline severity of
anxiety. Paroxetine 20 mg showed significant im-
provement in HAMD 10 and the A/S subfactor
when compared to placebo but there was no differ-
ence in the HAMD total score between paroxetine
and placebo. Duloxetine 40 mg/day showed signifi-
cantly greater improvement vs. placebo in HAMD
item 10 but there was no difference in the A/S sub-
factor or HAMA total score. Duloxetine 80 mg was
significantly better than placebo in all three meas-
ures. When compared to paroxetine, duloxetine 40
mg showed significant improvement in the A/S
subfactor only. Duloxetine 80 mg showed signifi-
cantly greater improvement than duloxetine 40 mg/
day on the A/S subfactor.10 These results suggest
that duloxetine is more effective than placebo for
the treatment of MD, including physical symptoms.
The effects of duloxetine are dose-dependent. At
the highest dose, duloxetine improved some meas-
ures to a greater extent than paroxetine.

PharmaNote Volume 20, Issue 4, January 2005


Volume 20, Issue 4, January 2005

Table 2: Adverse reactions* (%) of among patients treated with duloxetine or placebo9
Duloxetine 20 mg/day Duloxetine 40 mg/day Duloxetine 80 mg/day Placebo
Adverse reaction N = 138 N = 137 N = 140 N = 138
Headache 7 10 8 9
Nauseat 9 9 13 2
Constipation 4 4 6 1
Diarrhea 5 4- 4 3
Fatigue 1 8 10 3
Dizziness 2 6 7 2
Insomniat 2 7 7 1
Dry mouth 4 5 7 1
Sinusitis 4 4 4 6
Upper respiratory 2 2 1 5
Nasopharyngitis 8 4 6 4
*All occurred in >5% of subjects in any treatment arm. tP < .05, for overall treatment effect (Pearson's X2 test).

Adverse effects
Table 2 depicts adverse effects reported in a
placebo-controlled, dose-ranging study of patients
with urinary incontinence.9 Nausea, insomnia, and
fatigue were more likely to occur with duloxetine
than placebo, and are dose dependent.

Dosing and administration
Duloxetine may be administered orally
without regard to meals. The dosing criteria for du-
loxetine varies based on its indication. For depres-
sion, an initial dose of 40-60 mg/day given as a sin-
gle or divided dose by mouth is effective in adults.
Doses greater than 60 mg/day may not provide ad-
ditional benefit.8 The safe and effective use of du-
loxetine is not established in adolescents and chil-
dren. The maximum dose of duloxetine in adults is
120 mg/day, although no advantage over lower
doses has been identified. Duloxetine should not be
used in patients with hepatic impairment, ESRD or
severe renal impairment.8

Drug interactions
Duloxetine should not be used concurrently
with monoamine oxidase inhibitors, drugs with
MAOI activity like furazolidone, linezolid and pro-
carbazine due to the high risk for serotonin syn-
drome. Also, centrally-acting medications such as
TCAs, SSRIs, St. John's wort, Hypericum perfo-

tum, amphetamine and dextroamphetamine, buspi-
rone, cocaine, dexfenfluramine, fenfluramine, lith-
ium, phentermine, sibutramine, nefazodone and tra-
zodone should not be used concurrently with du-
loxetine. A drug-free interval of 5 days is recom-
mended following the cessation of duloxetine and
the intitiation of an MAOI and an interval of 14
days is recommended after the cessation of an
MAOI and intitiation of duloxetine.8 Duloxetine,
when used concurrently with tramadol, may de-
crease the analgesic effect of tramadol by inhibiting
the formation of tramadol's active metabolite. Dis-
orientation, delusions, and hallucinations have been
reported in patients treated with zolpidem and du-
loxetine concurrently.

The average retail cost of Cymbalta for
one month of therapy based on retail cost at 3 local
pharmacies is $97.30 at 20 mg/d; $111.21 at 30 mg/
d; and $111.21 for 60 mg/d.

Depression is a major health problem af-
fecting millions of people. Duloxetine inhibits the
reuptake of NE and 5HT, both of which are be-
lieved to play an important role in depression. It is
also effective in stress urinary incontinence and for
the management of pain associated with neuropa-
thy. Duloxetine has a quick onset of action, which

PharmaNote Volume 20, Issue 4, January 2005


Volume 20, Issue 4, January 2005

offers a unique advantage compared to SSRIs. Its
side effect profile appears to be favorable compared
to TCAs and similar to other antidepressants. It is
not clear whether duloxetine has the same effect as
other antidepressants on suicidality, but caution
should be used in patients at risk for this complica-

1. Tran, Pierre V. MD, Bymaster, Frank P. et al. Dual Mono-
amine for Improved Treatment of Major Depressive Disor-
der. Journal of Clinical Psychopharmacology 2003;23:78-
2. Dunner DL, Goldstein DJ, et al. Duloxetine in treatment of
anxiety symptoms associated with depression. Depression
And Anxiety 2003;18:53-61.
3. Sharma A, Goldberg MJ, et al. Pharmacokinetics and
safety of duloxetine, a dual serotonin and norepinephrine
reuptake inhibitor. Journal of Clinical Pharmacology 2000;
4. Skinner MH, Kuan H, et al. Duloxetine is both an inhibitor
of cytochrome P4502D6 in healthy volunteers. Clinical
Pharmacology and Therapeutics 2003;73:170-7.
5. Detke MJ, Lu Y, et al. Duloxetine 60 mg once daily dos-
ing versus placebo in the acute treatment of major depres-
sion. Journal of Psychiatric Research 2002;36:383-390.
6. Goldstein DJ, Lu Y, et al. Effects Of duloxetine on painful
physical symptoms associated with depression. Psy-
chomatics 2004;45:17-28.
7. Bymaster FP, Beedle EE, et al. Duloxetine, a dual inhibi-
tor of serotonin and norepinephrine reuptake. Bioorganic
& Medical Chemistry Letters 2003;13:4477-4480.
8. Clinical Pharmacology Online. Available at http://cpip.
9. Norton PA, Zinner NR, Yalcin I, et al. Duloxetine versus
placebo in the treatment of stress urinary incontinence.
American Journal of Obstetric Gynecology 2002;187:40-
10. Goldstein DJ, Lu Y, et al. Duloxetine in the treatment of
depression- a double blind placebo controlled comparison
with paroxetine. Journal of Clinical Psychopharmacology


Anne Rafidi, Pharm.D. Candidate

PharmaNote Volume 20, Issue 4, January 2005

Diarrhea is the most common medical prob-
lem among people traveling within and to develop-
ing countries. Mortality due to typical traveler's di-
arrhea is uncommon; however, the morbidity of un-
treated traveler's diarrhea is significant with at least
1% of sufferers requiring hospitalization, 20% con-
fined to bed and nearly 40% changing their itiner-
ary.1 Classic traveler's diarrhea is usually defined as
the passage of three or more unformed stools in a
24-hour period plus at least one symptom of enteric
disease such as abdominal pain or cramps, nausea,
vomiting, fever, or tenesmus. Traveler's diarrhea is
a self-limited disease but may last longer than one
week in 10% of patients and up to one month or
more in 2%. The most common cause of traveler's
diarrhea is contaminated food and water in which
80% of cases are caused by bacterial enteropatho-
At present, options for the prevention of
traveler's diarrhea include education and chemo-
prophylaxis with either bismuth subsalicylate
(BSS)-containing compounds or antibiotics, usually
sulfonamides or fluoroquinolones. Antibiotics pre-
vent approximately 80% of cases as long as they
have reliable activity against enteropathogens in
the destined regions.1 Antibacterial therapy is gen-
erally recommended after the passage of the third
stool in a 24 hour period; for diarrhea associated
with moderate-to-severe abdominal pain or cramps,
fever, or dysentery; and for symptoms that recur
when drugs are discontinued.2 The major benefits
of antibiotics are a significant reduction in the total
duration of diarrhea from 60-100 hours to approxi-
mately 30 hours and earlier relief of the accompa-
nying gastrointestinal symptoms.2 Currently, the
drug of choice for the treatment of traveler's diar-
rhea is a fluoroquinolone. Trimethoprim and sul-
famethoxazole (TMP/SMX) was once the drug of
choice, but due to increasing resistance it is no
longer recommended as empiric therapy. The use of
a non-absorbable antibiotic, such as rifaximin
(XifaxanTM, Salix Pharmaceuticals), is an attractive
choice for the treatment and prophylaxis of trav-
eler's diarrhea due to the potential of fewer adverse
effects, safety in children, pregnant women, and
possibly less impact on antibiotic resistance. The U.
S. Food and Drug Administration (FDA) granted
marketing approval for rifaximin in May 2004 for


Volume 20, Issue 4, January 2005

Table 1. Rifaximin studies in patients with traveler's diarrhea 45

Study Design (N) Regimens Results

Randomized, double-blind (254) Median time to last unformed
Median time to last unformed
R. Steffen et a14 placebo-controlled study con- Rifaximin 600 mg/day x 3d stool: rifaximin 32.5 hours; pla-
ducted in Mexico, Guatemala, and versus placebo cebo 60 hours. P-value0.001
cebo 60 hours. P-value=0.001

Randomized, double-blind, dou- Rifaximin 400 mg BID x3d Median time to last unformed
HL Dupont et al5 ble-dummy (187) conducted in versus ciprofloxacin 500 mg BID stool: rifaximin 25.7 hours; cipro-
Mexico and Jamaica x3d floxacin 25 hours. P-value=0.006

the treatment of patients (> 12 years of age) with
traveler's diarrhea caused by noninvasive strains of
Escherichia coli. This article will examine the
safety, efficacy, and tolerability of rifaximin.

Pharmacology and Pharmacokinetics
Rifaximin, a derivative of rifamycin, is a
semi-synthetic, non-systemic antibiotic. Rifaximin
acts by binding to the beta-subunit of bacterial
DNA-dependent RNA polymerase resulting in in-
hibition of bacterial RNA synthesis.3 Rifaximin is
not suitable for treating systemic bacterial infec-
tions because less than 0.4% of the drug is ab-
sorbed after oral administration. Absorption is not
affected by food. Rifaximin's mean peak plasma
concentration (Cmax) is minimal and is reached ap-
proximately 1.25 hours after oral administration.
Animal studies demonstrate that 80% to 90% of
orally administered rifaximin is concentrated in the
gut. Rifaximin induces cytochrome P450 3A4
(CYP 3A4). Despite limited oral bioavailability, its
effects on P450 in the gut wall may produce clini-
cally relevant drug interactions. Rifaximin is ex-
creted primarily in the feces. Because of the limited
systemic absorption, no specific dosing adjust-
ments are recommended for patients with hepatic
insufficiency. The pharmacokinetics of rifaximin in
patients with impaired renal function have not been

Drug-Drug Interactions
In an in vitro hepatocyte induction model,
rifaximin was shown to induce cytochrome
CYP3A4, an isoenzyme which rifampin is also
known to induce. Two clinical drug-drug interac-
tion studies were conducted using midazolam and
an oral contraceptive containing ethinyl estradiol
and norgestimate to assess the effect of rifaximin

ha rma Note 0

on the pharmacokinetics of these drugs.
The midazolam study was an open-label,
randomized, crossover, drug-interaction trial de-
signed to assess the effect of rifaximin 200 mg ad-
ministered orally (PO) every 8 hours (Q8H) for 3
days and Q8H for 7 days on the pharmacokinetics
of a single dose of either midazolam 2 mg intrave-
nously or midazolam 6 mg PO. No significant dif-
ference was observed.3 Rifaximin did not have
clinically significant effects on midazolam.
An open-label, crossover study in 28
healthy female subjects examined whether rifaxi-
min 200 mg PO administered Q8H for 3 days al-
tered the pharmacokinetics of a single dose of an
oral contraceptive containing 0.07 mg ethinyl estra-
diol and 0.50 mg norgestimate.3 The pharmacoki-
netics of single doses of ethinyl estradiol and
norgestimate were not altered by rifaximin.

Rifaximin has a relatively broad antimicro-
bial spectrum that includes aerobic and anaerobic
gram-positive and gram-negative bacteria.3 Rifaxi-
min is effective against E. coli (enterotoxigenic and
enteroaggregative strains). In in vitro studies, E.
coli was capable of developing microbiological re-
sistance to rifaximin. Organisms with high rifaxi-
min minimum inhibitory concentration (MIC) val-
ues also have elevated MIC values against ri-
fampin. Cross-resistance between rifaximin and
other classes of antimicrobials has not been studied.
The emergence of resistance to rifaximin under-
scores the importance of surveillance in preserving
the drugs activity.

Clinical Trials
The efficacy of rifaximin was demonstrated
in a limited number of controlled clinical trials in-

Volume 20, Issue 4, January 2005



Table 2. Adverse events occurring in 2 2% of patients receiving rifaximin 600 mg/day, in placebo-controlled studies

Number (%) of Patients
Adverse Effect
Rifaximin 600 mg/day _(N = 320) Placebo (N = 228)
Flatulence 36 (11.3%) 45 (19.7%)
Headache 31(9.7%) 21(9.2%)
Abdominal Pain 23 (7.2%) 23 (10.1%)
Rectal Tenesmus 23 (7.2%) 20 (8.8%)
Defecation Urgency 19 (5.9%) 21 (9.2%)
Nausea 17 (5.3%) 19 (8.3%)
Constipation 12 (3.8%) 8 (3.5%)
Pyrexia 10 (3.1%) 10 (4.4%)
Vomiting NOS 7 (2.2%) 4 (1.8%)

volving several hundred patients with traveler's di-
arrhea caused by noninvasive strains of E. coli
(Table 1). Clinical efficacy in these studies was pri-
marily based upon the time to return to normal,
formed stools and resolution of symptoms. Study
results show that the duration of diarrhea is signifi-
cantly shorter in patients treated with rifaximin
compared to placebo, and significantly more pa-
tients receiving rifaximin demonstrate a clinical
cure.4 Rifaximin appears to be similar in efficacy to
ciprofloxacin for the treatment of traveler's diar-
rhea.5 One advantage is that rifaximin is nonadsorb-
able and, thus, may have a lesser impact on antim-
icrobial resistance among non-targeted pathogens
(i.e., minimal collateral damage). The two pub-
lished clinical trials summarized in Table 1 were
conducted in traveler's diarrhea caused predomi-
nantly by E. coli.
A separate study, conducted in 72 US adults
traveling to Mexico evaluated four separate out-
comes: the most effective dose of rifaximin for the
treatment of traveler's diarrhea; the effectiveness of
rifaximin for eradication of causative bacterial en-
teropathogens; the relative safety and tolerability of
rifaximin; and the efficacy of rifaximin versus
TMP/SMX (which is effective in Mexico).6 Results
from that study suggest that 5 days of rifaximin
treatment is as effective as therapy with
trimethoprim/sulfamethoxazole (TMP/SMX) How-
ever due to the decreased efficacy of TMP/SMX
worldwide, these results may no longer be applica-


ble in all areas.

Dosage and Administration
Rifaximin can be administered orally with
or without food. For traveler's diarrhea, the recom-
mended dose is one 200 mg tablet taken three times
a day for 3 days. No specific information is avail-
able on the treatment of overdosage with rifaximin.
In clinical studies, at doses higher than the recom-
mended dose (>600 mg/day), adverse effects were
similar to the recommended dose (200 mg three
times a day). In the case of overdose, discontinue
rifaximin, treat symptomatically, and institute sup-
portive measures as necessary. Rifaximin is indi-
cated for the treatment of patients (> 12 years of
age) with traveler's diarrhea caused by noninvasive
strains of E. coli. Rifaximin should not be used in
patients with diarrhea complicated by fever or
blood in the stool or diarrhea due to pathogens
other than E. coli.

Warnings and Precautions
Rifaximin is not effective in patients with
diarrhea complicated by fever and/or blood in the
stool or diarrhea due to pathogens other than E.
coli. Rifaximin is not effective in cases of traveler's
diarrhea due to Campylobacter jejuni. The effec-
tiveness of rifaximin in traveler's diarrhea caused
by li/ge/ll/i spp. and Salmonella spp. has not been
proven. Rifaximin should be discontinued if diar-
rhea symptoms worsen or persist more than 24-48

Volume 20, Issue 4, January 2005



Table 3. Cost Comparison of Treatment for Traveler's Diarrhea7

Drug Dosage US Cost1
Azithromycin 1000 mg once or $31.24
500 mg once/d x 3d $46.86
Ciprofloxacin (generic) 500 mg bid x 3d $30.42
Ciprofloxacin (brand) 500 mg bid x 3d $33.60
Ciprofloxacin XR/XL (brand) 1000 mg once/d x 3d $28.17

Levofloxacin 500 mg once/d x 3d $31.50

Rifaximin 200 mg tid x 3d $32.76

Cost based on the most recent data (July 31, 2004) from retail pharmacies nationwide available from NDCHealth, a healthcare information services company.

hours after treatment is started; alternative antibi-
otic therapy should be considered. Pseudomembra-
nous colitis has been reported with nearly all anti-
bacterial agents and may range in severity from
mild to life-threatening. It is important to consider
this diagnosis in patients who present with diarrhea
subsequent to the administration of antibacterial
agents. The safety and effectiveness of rifaximin
has not been established in pediatric patients less
than 12 years of age. It is not known whether rifaxi-
min is excreted in human milk. Rifaximin is terato-
genic in rats at doses of 150 to 300 mg/kg and in
rabbits at doses of 62.5 to 100 mg/kg. There are no
adequate, well controlled studies in pregnant
women. Rifaximin should only be used during
pregnancy if the potential benefit outweighs the
risk to the fetus. Rifaximin is contraindicated in pa-
tients with a hypersensitivity to rifaximin or any of
the rifamycin antimicrobial agents, including ri-

Adverse Reactions
The safety of rifaximin 200 mg taken three
times a day (TID) was evaluated in 320 patients in
two placebo-controlled clinical trials with 95% of
patients receiving at least three days of treatment
with rifaximin. All adverse events that occurred at a
frequency > 2% in the two placebo-controlled trials
combined are depicted in Table 2.
The most common adverse effects of rifaximin is
flatulence, headache, abdominal pain, and rectal te-
nesmus. The following events have been reported
from postmarketing experience: hypersensitivity
reactions, including allergic dermatitis, rash, an-
gioneurotic edema, urticaria, and pruritus.

A comparison of the cost of antibacterial
agents frequently used to treat traveler's diarrhea
appears in Table 3.

Rifaximin should be considered as a non-
systemic treatment option for patients with trav-
eler's diarrhea caused by noninvasive strains of E.
coli. This drug has not been studied in cases of
traveler's diarrhea caused by ./ngel//l spp and Sal-
monella spp. and has been shown to be not ineffec-
tive in cases due to C. jejuni. Rifaximin has phar-
macologic and safety advantages over the existing
drugs for traveler's diarrhea. Rifaximin may have a
favorable safety profile compared to systemically
absorbed options. Rifaximin is a good alternative
for patients allergic to sulfonamides or in areas
where resistance to TMP/SMX is prevalent. Resis-
tance has been reported to the quinolones due to
widespread use and selective pressure. Thus, rifaxi-
min represents a viable alternative to the fluoroqui-
nolones for the treatment of traveler's diarrhea.

1. Ericsson CD. Traveler's Diarrhea. International Journal of
Antimicrobial Agents 2003; 21: 116-124.
2. DuPont HL, Ericsson CD. Prevention and Treatment of
Traveler's Diarrhea. N Engl J Med 1993;328:1821-7.
3. Salix Pharmaceuticals, Inc. XifaxanTM (rifaximin)
[package insert]. Raleigh, NC: (05/2004) reviewed
4. Steffen R, Sack DA, Riopel L, et al. Therapy of traveler's
diarrhea with rifaximin on various continents. Am J Gas-
troenterol 2003;98:1073-78.
5. Dupont HL, Jiang ZD, and Ericsson CD, et al. Rifaximin
versus ciprofloxacin for the treatment of traveler's diar-
rhea: a randomized, double-blind clinical trial. Clin Infect

Phamaot Vlue 0,Isue4,Jauay 00


Volume 20, Issue 4, January 2005

Dis 2001;33:1807-15.
6. Dupont HL, Ericsson CD, et al. Rifaximin: a nonabsorbed
antimicrobial in the therapy of traveler's diarrhea. Diges-
tion 1998;59:708-14.
7. The Medical Letter on Drugs and Therapeutics. 46 (1191):
September 13, 2004. Accessed online at www.
8. Farr BM. Rifamycins. In: Mandell GL, Bennett JE, Dolin
R, eds. Principles and practice of infectious diseases, 5t
ed. Philadelphia: Churchill Livingstone, 2000;348-361.

4 4

Labeling Changes

* The antidepressants citalopram, fluoxetine,
fluvoxamine, mirtazapine, nefazodone,
paroxetine, sertraline, and venlafaxine each now
carries a warning regarding the potential for
suicidal ideation and suicide attempts during

The following adverse effects have been reported
with ezetimibe (Zetia) and are now included in
the labeling under adverse events: cholelithiasis,
cholecystitis, pancreatitis, nausea, angioedema,
and rash. Also, the label was modified to reflect
an interaction with cyclosporine that significantly
increases systemic exposure to ezetemibe.

New Drug Approvals

Acamprosate (Campral) is approved for use as
maintenance therapy in recovering alcoholics
who are presently abstinent to increase the
likelihood of persistent abstinence. The
recommended dose is 666 mg three-times daily It
is available as a delayed-release tablet that
contains 333 mg. The dose should be decreased in
patients with renal insufficiency.

The PharmaNote is Published by:
The Department of Pharmacy
Services, UF Family Practice Medical
Group, Departments of Community
Health and Family Medicine and
Pharmacy Practice
University of Florida

John G. Gums Editor

R. Whit Curry, M.D. Associate Editor

Benjamin J. Epstein Assistant Editor

Phamaot Voum 2, Isu 4 Jauay 00

New Dosage Forms

* Gatifloxacin (Tequin) is now available in an
oral suspension that is fruit-flavored. It is
supplied in 1-, 2-, 3-, and 4-g unit-of-use bottles.
After constitution with water, the suspension
contains 200 mg of drug per 5 mL.

* Omeprazole (Zegerid) is available in 20 and 40
mg as an immediate-release powder for oral
suspension. The oral powder is approved for the
treatment of heartburn and other symptoms
related to gastroesophageal reflux, short-term
treatment and maintenance of healing erosive
esophagitis, and treatment of duodenal ulcers.

* Carbidopa and levodopa orally disintegrating
tablets (ParcopaTM) are indicated for the treatment
of Parkinson's disease. The immediate-release
formulation can be taken without water and is
designed to facilitate dosing in this population.
The recommended dose is the same as for
conventional carbidopa/levodopa tablets. Parcopa
is available in tablets containing phenylalanine,
citrus or mint flavoring, 10 or 25 mg of
carbidopa, and 100 or 250 mg of levodopa.

* Digoxin elixir is a lime flavored liquid, with 10%
alcohol, indicated for the treatment of mild to
moderate heart failure and the control of a resting
ventricular response rate in patients with chronic
atrial fibrillation.



Volume 20, Issue 4, January 2005

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