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TREXIMET (SUMATRIPTAN
AND NAPROXEN): THE FIRST
COMBINATION TRIPTAN/
NSAID FOR ACUTE
MIGRAINE

Lisa Zeigler, Pharm.D. candidate

Headache is a common complaint in the
United States. Up to 20% of the adult population
suffers from primary headache.1 These numbers
may not reflect the true patient population because
many headache sufferers never seek diagnostic treat-
ment. "Primary headache" is a broad term which
encompasses migraine, cluster, tension, and miscel-
laneous headaches. Migraines are differentiated by
disability, nausea, and photophobia.2 Costs associ-
ated with alleviating migraine reach nearly 17 billion
3
dollars each year.3
Acute migraine treatment incorporates sev-
eral drug classes including NSAIDs, triptans, and
ergotamines. Current first line therapy is the use of
NSAIDs, including naproxen and effervescent aspi-
rin.4 Triptans and ergotamines are often used after
NSAID treatment has failed.
In April 2008, the Food and Drug Admini-
stration (FDA) approved the first triptan/NSAID
combination pill for the acute treatment of migraine:
sumatriptan/naproxen (Treximet). This article will
review the pathophysiology of migraine, pharmacol-
ogical properties, results of two clinical trials, and
adverse events of sumatriptan and naproxen.

PATHOPHYSIOLOGY OF MIGRAINE
The pathophysiology involved in migraines
have been widely debated. Migraine recurrence may


be an inherited or acquired defect in the trigemi-
nocervical CNS system. Inappropriate activation of
the trigeminocervical system may explain migraines
associated with aura and the menstrual cycle, while
both exogenous and endogenous triggers may result
in migraine in individuals with lowered activation
thresholds.5
The pathway of trigemino-cerebrovascular
involvement starts with the trigeminal nerve. The
first branch innervates intracranial vessels and the
meninges via sensory nerve fibers. The pathway ex-
tends through secondary neurons in the brainstem
through the trigeminal nucleus caudialis to the
trigeminocervical complex. From here, the cortical
areas are activated, leading to pain perception.1
Once the migraine threshold is reached, the
dorsal raphe releases both norepinephrine and sero-
6
tonin. Vasodilation occurs and vomiting centers
are activated. Vasodilation brought on by the release
of norepinephrine and serotonin is further enhanced
by trigeminal activation of cortical areas, which re-
lease neurokinin A, substance P, and calcitonin gene-
related peptide (CGRP).6
CGRP, a vasodilator, is thought to play an
integral role in migraine pathophysiology. The
trigeminal nerve ganglion contains many CGRP-
containing nerves. CGRP is released after vasocon-


INSIDE THIS ISSUE:
TREXIMET (SUMATRIPTAN AND NAPROXEN): THE
FIRST COMBINATION TRIPTAN/NSAID FOR ACUTE
MIGRAINE
AND
RESISTANT URINARY TRACT INFECTIONS
tl I F


mm


PharmaNote


VOLUME 23, ISSUE 1 1 AUGUST 2008
1-


Volume 23, Issue 11 August 2008


PharmaNote







striction in order to restore vascular tone. Addition-
ally, CGRP is elevated in acute migraine attack, and
decreased after treatment with a triptan.l'7
An inflammatory component may also play a
role in migraine pathophysiology. Prostaglandins
may make pain worse by attentuating the inflamma-
tory response.8

PHARMACOLOGY
The combination pill of sumatriptan and
naproxen contains sumatriptan succinate, a member
of the triptan class, and naproxen sodium, an NSAID.
The 5-HT1B/1D agonists, known as the
"triptans," help regulate CGRP levels. Their mecha-
nism of action is thought to be through 5-HTlB recep-
tor mediated vasoconstriction of cerebral vessels in
the smooth muscle layers of the meninges and cere-
bral arteries. A second mechanism of action may
occur through presynaptic trigeminal nerve receptors
to inhibit the release of GCRP, thus inhibiting vaso-
dilation mediated by the neuropeptide. All triptans
appear to have similar safety and efficacy profiles.4
Naproxen is an NSAID that works as an anal-
gesic and antipyretic in addition to having anti-
inflammatory properties. Naproxen inhibits both
COX-1 and COX-2 enzymes. Studies have shown


that NSAIDs may be as effective as the triptans in
aborting acute migraine.3

CLINICAL TRIALS
Brandes, et al. conducted two identical phase
3, randomized double-blind, parallel group, con-
trolled clinical studies comparing the effectiveness
and safety of sumatriptan and naproxen as a combi-
nation versus either agent alone or placebo in the
treatment of acute migraine attack.8 Inclusion and
exclusion criteria for the two trials were identical.
The only difference between the two studies were the
estimated enrollment numbers (estimated enrollment
for Study 1 was 1200 patients, estimated enrollment
for Study 2 was 1400 patients; actual enrollment for
Study 1 was 1461 patients, actual enrollment for
Study 2 was 1495 patients).8
The investigators used primary outcomes of
relief of headache 2 hours after dosing and absence
of photophobia, phonophobia, and nausea to evaluate
the efficacy of the combination treatment versus pla-
cebo. They employed sustained, pain-free response
as a primary outcome measure against each mono-
therapy. Secondary endpoints analyzed were sus-
tained pain relief after 24 hours and sustained relied
of photophobia, phonophobia, and nausea.8


Table 1: Clinical Trials Summary38o10


Treximet Sumatriptan Naproxen
85mg 500Treximetmg
85mg 500mg


p value
Placebo (vs. placebo)
(vs. placebo)


p value
(vs. sumatriptan)


Results from Landy, et al.


Return to Function
(median time)


Study 1

Study 2


7h llh

5h llh


9h 14h


Sustained Report of Study 1
Normal Function
(median time) Study 2


Results from Brandes, et al.8

Headache Relief Study 1
within 2 Hours (% of
patients) Study 2

24-hour Sustained Study 1
Pain Relief (% of
patients) Study 2


<.001

<.001

<.001

<.001


<.001

<.001

<.001

<.001


Not significant

<.002

Not Significant

.001


.009

.03

.009

<.001


Phrm~oe oum 2, sse11Auus 20


Volume 23, Issue 11 August 2008


PharmaNote







Against placebo, the combination pill was
more effective in relieving headache within the first
2 hours of use. In Study 1 of Brandes, et al., head-
ache relief was reported two hours after receiving
doses by 65% of sumatriptan/naproxen users, 55% of
sumatriptan users, 44% of naproxen users, and 28%
of placebo patients. In Study 2 of Brandes et. al, the
differences were 57%, 50%, 47%, and 29% respec-
tively. Differences between each treatment group
versus placebo were found to be significant (p<0.001
in both Study 1 and 2). A significant difference in
the number of patients that were pain free after 2
hours was also found between users of combination
therapy and sumatripan alone (Study 1: 65% vs.
55%, p=0.009; Study 2: 57% vs. 50%, p=0.03).8
Brandes, et al. also compared sumatriptan/
naproxen versus monotherapy and placebo in provid-
ing a sustained 24 hour pain free response. Com-
pared with placebo in both studies, sumatriptan/
naproxen was able to provide significant sustained
headache relief, pain free response, and relief from
nausea, photophobia and phonophobia (p<0.001 for
all comparisons). The combination pill was also
more effective in providing a pain free 24 hour pe-
riod following treatment compared with sumatriptan
alone (p=0.009 for Study 1, p<0.001 for Study 2).8
Landy, et al. utilized data collected on patient
questionnaires and diary cards from the above stud-
ies to compare ability to function and productivity.3
Landy and colleagues used ability to perform
work or usual activities as a marker for function.
They used a four point categorical scale that included
not impaired, mildly impaired, severely impaired,
and required bed rest. Diary cards were used to
measure pain, function and symptoms. Assessments
were completed every 30 minutes for the first 2
hours, and hourly until 24 hours after taking the dose
on the diary cards. At baseline, at least 40% of pa-
tients in both trials were found to be in either the
functional group that was severely impaired or re-
quired bed rest.3
They found that patients using sumatriptan
and naproxen in combination returned to work faster
compared to placebo, and were more satisfied with
the combination treatment than with other therapies.3
In Study 1 of Landy et. al, the median time to first
reported return to normal function was 4 hours with
sumatriptan and naproxen, compared with 4 hours in
the sumatriptan group, 7 hours in the naproxen
group, and 11 hours in placebo group (p<0.001 for


both naproxen and placebo groups). In Study 2 of
Landy et. al, return to function was significantly bet-
ter for combination sumatriptan/naproxen than ver-
sus either monotherapy or placebo. The median time
to first reported return to normal function was 3
hours in the sumatriptan/naproxen group. Both su-
matriptan and naproxen alone had a 5 hour median
return to normal function (p<0.002, p<0.001, respec-
tively), while the placebo arm had a median time of
11 hours (p<0.001).3
Landy, et al. also compared the median time
it took to obtain a sustained period of relief after dos-
ing. In both of the Landy et. al studies, use of suma-
triptan and naproxen in combination afforded an ear-
lier time to a sustained pain free period, but signifi-
cance versus sumatriptan alone was only shown in
study 2 (4 hours vs. 8 hours, p<0.001).3

WARNINGS AND ADVERSE EVENTS
Adverse events reported in clinical trials by
more than 2% of participants included nervous sys-
tem, gastrointestinal disorders, pain and other pres-
sure sensations (see table 2). Adverse events re-
ported by more than 1% of patients included flush-
ing, asthenia, palpitations, and muscle tightness.10
Sumatriptan is known to cause coronary va-
sospasms. Sumatriptan-containing therapies, includ-
ing sumatriptan and naproxen in combination, should
be avoided in patients with CAD. In patients with
risk factors for CAD, but have otherwise completed a
cardiovascular evaluation and are in need of suma-
triptan/naproxen therapy, the first dose should be ad-
ministered while the patient is in a physician's care
unless the patient has previously used sumatriptan.
Use of sumatriptan-containing products may lead to
an increased risk of myocardial ischemia and/or in-
farction. Sumatriptan and other 5-HT1A agonists can
be associated with serious cardiac events and fatali-
ties. NSAIDs, both selective and nonselective, have
been associated with an increased risk for cardiovas-
cular thrombotic events.
Patients taking sumatriptan have reported
cerebrovascular events including stroke, cerebral and
subarachnoid hemorrhaging. It is not clear whether
these events were primary and incorrectly perceived
as migraine, or what role sumatriptan had in these
events. Serotonin Syndrome may occur in patients
using 5-HT1A agonists, especially when combined
with selective serotonin reuptake inhibitors (SSRIs)


PharmaNote Volume 23, Issue 11 August 2008


Volume 23, Issue 11 August 2008


PharmaNote







Table 2: Warnings and Adverse Events Associated with Sumatriptan/Naproxen10


Adverse Event


Percent Reporting


(reported by > 2% ot patients) Sumatriptan/Naproxen Placebo
Dizziness 4 2
Somnolence 3 2
Nausea 3 <1
Chest Discomfort/Pain 3 1
Neck/Throat/Jaw Pain/Pressure/Tightness 3 1
Paresthesia 2 <1
Dyspepsia 2 1
Dry Mouth 2 <1
Occurred more frequently in sumatriptan/naproxen group than in any monotherapy or placebo groups.


or serotonin norepinephrine reuptake inhibitors
(SNRIs).
Both sumatriptan and naproxen can cause
significant increases in blood pressure. The combi-
nation of sumatriptan and naproxen is contraindi-
cated for patients with uncontrolled hypertension,
and should be used cautiously in patients with con-
trolled hypertension. Sumatriptan may cause in-
creases in blood pressure, which could lead to hyper-
tensive crisis, and peripheral vascular resistance.
Blood pressure monitoring should be performed dur-
ing sumatriptan/naproxen therapy.
Because sumatriptan/naproxen contains
naproxen sodium, warnings include those commonly
seen for NSAIDs. NSAIDs are associated with an
increased risk of congestive heart failure and edema.
Sumatriptan/naproxen contains naproxen as the so-
dium salt, and should be used cautiously in patients
restricting their sodium intake. Sumatriptan/
naproxen should be used cautiously in patients who
are retaining fluid or who have heart failure.
NSAIDs also carry a risk of GI bleed, perforation,
and ulceration.

DOSE
Treximet is only available in the fixed dose
of 119mg sumatriptan succinate, which is equivalent
to 85mg of sumatriptan, and 500mg of naproxen so-
dium.10 One tablet should be taken at the onset of
migraine, with not more than 2 tablets taken in a 24
hour time period.10 Treximet may be taken with or
without food, though food may delay time to maxi-
mum concentration by 0.6 h.10 Treximet is not rec-
ommended for really impaired patients (CrCl
<30mL/min) and hepatic impairment is a contraindi-


cation to therapy due to the fixed dosage of sumatrip-
tan.10 There are no warnings for use in the elderly.

COST


The average retail
Gainesville, FL for one
$212.89 (Range $199.98 -
tains 9 pills.


price of 3 pharmacies in
bottle of Treximet is
$233.70). One bottle con-


SUMMARY
Treximet is the first combination triptan/
NSAID product indicated for acute migraine relief.
It is composed of 119mg of sumatriptan succinate
(equivalent to 85mg sumatriptan) and 500 mg of
naproxen sodium. Treximet was approved by the
FDA in April of 2008. Clinical trials have shown
that it is more effective than placebo in relieving mi-
graine 2 hours after use, and is more effective in pro-
viding a 24 hour pain free period versus sumatriptan
alone, naproxen alone, or placebo.

REFERENCES
1. Link AS, Kuris A, Edvinsson L. Treatment of migraine
attacks based on the interaction with the trigemino-
cerebrovascular system. J Headache Pain 2008;9:5-12.
2. Mueller L. Diagnosis and management of migraine head-
ache. JAOA 2007 Suppl 6; 107(11).
3. Landy S, DeRossett SE, Rappaport A, et al. Two double-
blind, multicenter, randomized, placebo-controlled, single-
dose studies of sumatriptan/naproxen sodium in the acute
treatment of migraine: function, productivity and satisfac-
tion outcomes. MedGenMed 2007;9(2):53.
4. Mett A and Tfelt-Hansen P. Acute migraine therapy: recent
evidence from randomized comparative trials. Curr Opin
Neurol 2008;21(3):331-7.
5. Cutrer FM. Pathophysiology of Migraine. Semin Neurol
2006;26(2):171-9.


PharmaNote Volume 23, Issue 11 August 2008


Volume 23, Issue 11 August 2008


PharmaNote







6. Diamond S and Wenzel R. Practical approaches to mi-
graine management. CNS Drugs 2002;16(6):385-403.
7. Juhasz G, Zsombok T, Jakab B, et al. Sumatriptan causes
parallel decrease in plasma calcitonin gene-related peptitde
(CGRP) concentration and migraine headache during nitro-
glycerin induced migraine attack. Cephalalgia 2005;25
(3):179-83.
8. Brandes JL, Kudrow D, Stark SR, et al. Sumatriptan-
naproxen for acute treatment of migraine: a randomized
trial. JAMA 2007;297(13):1443-54.
9. Winner P, Cady RK, Ruoff GE, et al. Twelve-month toler-
ability and safety of sumatriptan-naproxen sodium for the
treatment of acute migraine. Mayo Clin Proc 2007;82(1):61
-8.
10. TREXIMET [Package Insert]. GlaxoSmithKline. 2008.


RESISTANT URINARY TRACT

INFECTIONS

Robyn Reilly, Pharm.D. candidate


The Infectious Disease Society of America
(IDSA) 1999 guidelines recommend that when
trimethoprim-sulfamethoxazole (TMP-SMX) resis-
tant E. coli exceeds 10-20% of the total isolates in a



Washington
.Montana N : .
Oregon


Idaho


South Dakota


community, empirical treatment of urinary tract in-
fections (UTIs) should utilize an alternative agent.1
Remaining options for empirical treatment include
fluoroquinolones (FQs), nitrofurantoin, and fosfomy-
cin. Beta-lactams are not as effective as the afore-
mentioned agents, because common uropathogens
have a high level of resistance.1 Of all of these
agents, the FQs are the most effective.l'2 In the past,
FQs were not first-line therapy due to higher cost,
worries that resistance might develop, and collateral
damage. Recent cost-analyses have shown that FQs
become cost-effective when local resistance to TMP-
SMX is 19-22%.3 Also, nation-wide, ciprofloxacin
resistance among E. coli has remained low, at less
than 3%.4
On a regional level, certain states in the
United States have TMP-SMX resistance that ex-
ceeds 20% (see Figure 1).4 It is in these states espe-
cially, but also in those with resistance > 10%, that
alternative empiric drug therapy should be consid-
ered. 1
Data from 2001 showed nation-wide average
resistance to TMP-SMX to be 16.1%.4 At the same
time, ciprofloxacin resistance was 2.5% and nitrofu-
rantoin resistance was 0.7%. 4 These resistance lev-
els have remained relatively consistent over time (see
Figure 2).


Maine


Wisconsin


Wyoming


Michigan


Nebraska


Illinois


Colorado


t. N.H.
New York a .

Pennsyluania New Jersey


D.C.


Missouri


New Mexico


South Carolina

sAi l m Georgia


Alaska


Hawaii


Figure 1: Prevalence of TMP-SMX Resistant E. coli Throughout the United States. Shaded states
have resistance >20%. Most states have resistance >10%, excluding PA, AL, and MO. Data is miss-
ing from AK, ME, MT, NV, NM, RI, and WY. Adapted from Karlowsky JA, et al, International Jour-
nal of Antimicrobial Agents, 2001.5


Phara~oe Vlum 23 Isse 1 Auust200


Volume 23, Issue 11 August 2008


PharmaNote







Trends in Resistant E. coli from 1995-2001


40

35

30

25

20
UJ
S15


1995


1996


1997


1998
Year


1999


2000


_C~C~- -


2001


Figure 2: National Percent of E. coli Isolates Resistant. Adapted from susceptibility data from the Surveillance Network Database-
USA, published in Karlowsky JA, et al, Antimicrobial Agents and Chemotherapy, 2002.4


Of the FQs available in the U.S., ciproflox-
acin, levofloxacin, gatifloxacin, and norfloxacin have
been the most commonly studied. With the develop-
ment of Cipro XR, all of these drugs can now be
given once a day, except norfloxacin, which requires
twice daily dosing.6 All FQs have similar efficacy in
the treatment of UTIs (see Table 1) and treatment
choice should depend on cost and ease of dosing.
For uncomplicated UTIs, longer-term regi-
mens are preferred over single-dose treatment (SDT),
due to increased bacterial eradication and decreased
recurrence (see Table 2).1
Other options for UTI treatment include ni-
trofurantoin and fosfomycin. A head-to-head trial of
521 patients evaluated nitrofurantoin 100 mg BID for
7 days versus fosfomycin as a single 3 g oral dose
and found no difference in overall clinical success
rate at 32 days (p = 0.16; CI -11.1 1.3).14 Several
other studies have found similar results, although one
study found a significantly increased incidence of
adverse events in the fosfomycin arm of the study
(fosfomycin 33%, nitrofurantoin 12%).15,16 These
side effects were mostly gastrointestinal or CNS.16
On the other hand, nitrofurantoin is contraindicated
in renal failure and also can cause significant pulmo-
nary and hepatic toxicity when given in high doses or


for long durations." Both can be used in pregnancy,
an advantage over the FQs which are pregnancy
category C.
In comparison to other classes of antibiotics,
a small meta-analysis found no difference in adverse
effects, eradication, or recurrence between single
dose fosfomycin and norfloxacin 400 mg BID for 5-
7 days, whereas nitrofurantoin is associated with
lower cure rates when compared to TMP-SMX or
ciprofloxacin.1,2,17 More studies need to be con-
ducted on both medications to determine their place
in the empiric treatment of UTI. Both will no doubt
be increasingly considered as TMP-SMX resistant E.
coli increases.
Unfortunately, no guidelines for the treatment
of UTI have been developed since the IDSA guide-
lines in 1999. For now, clinical trials and local resis-
tance data drive our empiric treatment of uncompli-
cated UTI.


PharmaNote Volume 23, Issue 11 August 2008


-*-Ampicillin
- Ciprofloxacin
-- Nitrofurantoin
-*-TMP-SMX


Volume 23, Issue 11 August 2008


PharmaNote







Table 1: Review of Fluoroquinolone Head-to-Head Trials
Eradication
Study Patient Diagnosis Study Drugs atn Statistical Analysis
Rates

Peterson J, et al., Complicated UTI Ciprofloxacin 86.7% Levofloxacin is non-inferior to cipro-
2008. (n=1093) or acute pye- 400 mg IV or 500 mg PO floxacin
lonephritis BID for 10 days

Levofloxacin 88.3% 95% CI (-8.8 to 4.1)
750 mg daily PO/IV for 5
days

8Naber KG, et al., Uncomplicated Ciprofloxacin 81.5% Both gatifloxacin dosing regimens
2004. (n=1095) UTI 250 mg BID for 3 days were equivalent to ciprofloxacin

Gatifloxacin 80.5% 95% CI (-5.86 to 8.67)
400 mg IV once

Gatifloxacin 82.9% 95% CI (-8.45 to 6.40)
200 mg daily for 3 days

9Arrendondo-Garcia, Uncomplicated Ciprofloxacin 91.8% Norfloxacin and TMP-SMX were
et al., 2004. (n=285) UTI 250 mg BID for 3 days non-inferior to ciprofloxacin

Norfloxacin 86.9% 95% CI (-2.1 to 14.2)
400 mg BID for 7 days

TMP-SMX 85.2% 95% CI (-0.9 to 16.6)
160/800 mg BID for 7 days

10Auquer F, et al., Uncomplicated Ciprofloxacin 91.2% Both ciprofloxacin and norfloxacin
2002. (n=325) UTI 500 mg single dose were equally efficacious

Norfloxacin 91.9% p= 0.016
400 mg BID for 3 days






Table 2: Fluoroquinolones: SDT versus Longer-term Treatment

Study Patient Diagnosis Study Drugs Outcome

Cure rate at 5 weeks:
1Arav-Boger R. 1994 Uncomplicated UTI Norfloxacin 63%
(n=113) 1200 mg SDT

Norfloxacin 83% (p = 0.03)
400 mg BID for 7 days

Cure rate at 4-6 weeks:
12Saignur R, Nicolle LE. 1992 Uncomplicated UTI Norfloxacin 78%
(n=182) 800 mg SDT

Norfloxacin 88% (p = 0.1, NS)
400 mg BID for 3 days




PharmaNote Volume 23, Issue 11 August 2008







Table 3: Fluoroquinolones: 3-day Treatment Duration versus Longer-Term Treatment

Study Patient Diagnosis Study Drugs Outcome* Adverse Effects

13Vogel T, et al., Uncomplicated UTI Ciprofloxacin Eradication 98%
2004 250 mg BID for 3 days Relapse 15% Drowsiness (p < 0.001),
(n=182) loss of appetite (p =
0.003), and abdominal
Ciprofloxacin Eradication 93% pain (p = 0.001) were
250 mg BID for 7 days Relapse 13 more common in the 7
day group.


* p = 0.16 for the comparison


REFERENCES:
1. Warren JW, et al. Guidelines for antimicrobial treatment of
uncomplicated acute bacterial cystitis and acute pye-
lonephritis in women. Clin Infect Dis. 1999;29:745-58.
2. Iravani A, et al. A trail comparing low-dose, short-course
ciprofloxacin and standard 7 day therapy with co-
trimoxazole or nitrofurantoin in the treatment of uncompli-
cated urinary tract infection. J Antimicrob Chemother
1999;43:SA 67-75.
3. Miller LG, et al. Treatment of uncomplicated urinary tract
infections in an era of increasing antimicrobial resistance.
Mayo Clin Proc. 2004;79(8):1048-1054.
4. Karlowsky JA, et al. Trends in antimicrobial resistance
among urinary tract infection isolates of Escherichia coli
from female outpatients in the United States. Antimicrob
Agents and Chemother 2002;46(8):2540-2545.
5. Karlowsky JA, et al. Prevalence of antimicrobial resis-
tance among urinary tract pathogens isolated from female
outpatients across the US in 1999. Int J Antimicrob
Agents. 2001;18:121-127.
6. Stamm WE. Scientific and clinical challenges in the man-
agement of urinary tract infections. The American Journal
of Medicine 2002;113(1A):1S-4S.
7. Peterson J, et al. A double-blind, randomized comparison
of levofloxacin 750 mg once-daily for five days with cipro-
floxacin 400/500 mg twice-daily for 10 days for the treat-
ment of complicated urinary tract infections and acute pye-
lonephritis. Urology 2008;71(1):17-22.
8. Naber KG, et al. Gatifloxacin 400 mg as a single shot or
200 mg once daily for 3 days is as effective as ciproflox-
acin 250 mg twice daily for the treatment of patients with
uncomplicated urinary tract infections. Int J Antimicrob
Agents 2004;23:596-605.
9. Arrendondo-Garcia JL, et al. Comparison of short-term
treatment regimen of ciprofloxacin versus long-term regi-
mens of trimethoprim/sulfamethoxazole or norfloxacin for
uncomplicated lower urinary tract infections: a random-
ized, multicentre, open-label, prospective study. J Antim-
icrob Chemother 2004;54:840-843.
10. Auquer F, et al. Single-dose ciprofloxacin versus 3 days of
norfloxacin in uncomplicated urinary tract infections in
women. Clin Microbiol Infect 2002;8:50-54.
11. Arav-Boger R, et al. Urinary tract infections with low and
high colony counts in young women. Spontaneous remis-


sion and single-dose vs multiple-day treatment. Arch In-
tern Med 1994;154(3):300-4.
12. Saginur R, Nicolle LE. Single-dose compared with 3-day
norfloxacin treatment of uncomplicated urinary tract infec-
tion in women. Arch Intern Med 1992;152(6):1233-7.
13. Vogel T, et al. Optimal duration of antibiotic therapy for
uncomplicated urinary tract infection in older women: a
double-blind randomized controlled trial. CMAJ 2004;170
(4):469-73.
14. Stein GE. Comparison of single-dose fosfomycin and a 7-
day course of nitrofurantoin in female patients with uncom-
plicated urinary tract infection. Clin Ther 1999;21(11):
1864-72.
15. Lobel B. Short term therapy for uncomplicated urinary
tract infection today. Clinical outcome upholds the theo-
ries. Int J Antimicrob Agents 2003;22:S85-S87.
16. Gupta K, et al. Isolation of fluoroquinolone-resistant rectal
Escherichia coli after treatment of acute uncomplicated
cystitis. J Antimicrob Chemother 2005;56(1):243-6.
17. Nicolle LE, et al. Urinary tract infection: traditional phar-
macologic therapies. The American Journal of Medicine
2002;113:Suppl 1A:35S-44S.
18. Guay DRP. Contemporary management of uncomplicated
urinary tract infections. Drugs 2008;68(9):1169-1205.



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


John G. Gums Editor
Pharm.D.

R. Whit Curry, M.D. Associate Editor

Steven M. Smith, Assistant Editor
Pharm.D.


m:m
PharmaNote Volume 23, Issue 11 August 2008


Volume 23, Issue 11 August 2008


PharmaNote




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