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AN UPDATE ON ANTIEPILEPTIC
AGENTS: FOCUS ON SECOND
GENERATION TREATMENT
OPTIONS

Jason Richey, Pharm.D. Candidate


Epilepsy is a neurological disorder characterized
by sudden recurring attacks of motor, sensory, or
psychic malfunction. This disorder affects approxi-
mately 2.3 million Americans.1 Even though recent
surgical advances in the treatment of epilepsy have
been made, the primary form of treatment is still
pharmacological.
Epilepsy has been viewed with a negative prog-
nosis throughout history. Hippocrates held the belief
that seizures beginning in adulthood lasted until
death.2 Gowers later said, "the spontaneous cessa-
tion of seizures is an event too rare to be anticipated
in any given case."3 These negative views of epi-
lepsy treatment were held for decades despite the
emergence of the anticonvulsants, phenytoin and
phenobarbital in the early 1900s. These medications
were the first approved for the treatment of epilepsy
by the FDA in 1939. The most recent FDA approval
for epilepsy was pregabalin in 2005, which has been
shown in combination with other antiepileptic drugs
to reduce the frequency of seizures.4
The cost of epilepsy has a large impact on both
the individual and society. The estimated annual
cost of epilepsy in the U.S. is $15.5 billion.5 The
individual's quality of life is affected from both a
physical and psychological standpoint. Kanner
showed that 20%-55% of patients with uncontrolled
epilepsy suffer from depression.6 Individuals with


this disorder must overcome limitations with inde-
pendence, problems with work and education, and
deal with the potential for social embarrassment.
This article will discuss some of the advantages to
choosing the newer second generation anticonvul-
sants when treating epilepsy.

TREATMENT OPTIONS: GENERAL OVERVIEW
Many of the recent advances in the pharmacol-
ogical treatment of epilepsy have been due to our
greater understanding of this disorder. The newer
second-generation agents offer more advantages in-
cluding improved safety and efficacy over first gen-
eration antiepileptic drugs (AEDs). Many of the
newer AEDs have more predictable pharmacokinet-
ics than the first generation AEDs. Most of the first
generation AEDs are metabolized hepatically and are
strong enzyme inducers of the cytochrome P450 sys-
tem phenytoinn, carbamazepine, phenobarbital, and
primidone). The second generation AEDs have less
hepatic metabolism and cytochrome P450 induction,
fewer drug interactions, and lower protein binding.8
However the newer AEDs are not more efficacious
than the older generation AEDs phenytoinn, valproic
acid and carbamazepine) when treating newly diag-
nosed partial or generalized seizures.9'10 While the
second generation AEDs exhibit similar efficacy



INSIDE THIS ISSUE:
AN UPDATE ON ANTIEPILEPTIC AGENTS: FOCUS ON
SECOND GENERATION TREATMENT OPTIONS

INDEX FOR VOLUME 23 (OCT. 2007-SEP. 2008)


mm


SPharmaNote


VOLUME 24, ISSUE 1 OCTOBER 2008
ti -


PharmaNote


Volume 24, Issue 1 October 2008








Table 1. Summary of First Generation Anticonvulsant Epileptic Drugs11-14

Typical
Proposed
Agent Mechanism of Indications PK Drug-Drug Serious Side Effects Target Cost
(year approved) Action (F,VD,T%) Interactions Dose
Action
(mg/day)

Rash, pseudolymphoma,
Modulates voltage- Partial, generalized 70-100% Rash, pseudolymphoa, 100mg
Phenytoin CYP enzyme in- Stevens-Johnson syn- 200-300,
S dependent sodium tonic-clonic, myo- 0.63L/kg YP enzyme in StevensJohnson syn 200300, (#100) =
(1939) ducer drome, lupus-like syn- bid, tid 2
channels clonic seizures 6-24 hrs $25.99
drome
Carbamazepine,
Phenobarbital Promotes GABA Partial, generalized 95% Lamotrigine, Cognition impaired, Ste- 50-200 64.8mg
responses, reduces tonic-clonic, myo- 0.55L/kg Oxcarbazepine, vens-Johnson syndrome, da, (#100) =
(1 ) glutamate effects clonic seizures 53-118 hrs Phenytoin, Tiaga- depression aly $12.99
bine, Valproate

Primidone Promotes GABA Partial, generalized 100% Cognition impaired, Ste- 250mg
Primidone CYP enzyme in- 500-750,
responses, reduces tonic-clonic, myo- 0.64-0.86L/kg ue vens-Johnson syndrome, d (#90)=
(1954) ducer tid
glutamate effects clonic seizures 5-18 hrs depression $69.99


Ethosuximide Modulates voltage- 93% Phenytoin, Val- Gastrointestinal events, 1000 250mg
Ethosuximide Absence and myo- 1000-
Sdependent T-type 0.70L/kg proate, Car- psychotic episodes, de- 0, (#30)=
(1960) clonic seizures 3600, bid
calcium channels 53 hrs bamazepine pression $42.99


Carbamazepe Blocks use- Partial, generalized 85% Lamotrigine, Rash, hyponatremia, 200mg
Carbamazepine 600-1200,
dependent sodium tonic-clonic, myo- 1.40L/kg Tiagabine, Val- Stevens-Johnson syn- bd, (#60) =
(1 ) channels clonic seizures 25-65 hrs proate drome $ 14.99


Partial, generalized Hyperammonemia, 600-1500, 250mg
V Increases GABA tonicclonic, absence 100% 250mg
Valproate ain cotonic-clonic, absence 0.92.25L/k CYP enzyme in- pancreatitis, bid slow (#30)
brain concentra- 0.92-1.25L/kg (#30)=
(1978) tions and myoclonic sei- 9-16 hrs hibitor, Phenytoin thrombocytopenia, release, $14.99
zures Aplastic anemia tid

F, bioavailability; VD, volume of distribution; T12, half-life; bid, twice a day; tid, three times a day; PK, pharmacokinetic


when treating newly diagnosed epilepsy, the newer SECOND GENERATION EPILEPSY TREATMENTS
treatment options have a favorable response rate in a The current second generation antiepileptic drugs
number of refractory epilepsy cases. The side effects include Felbamate, Gabapentin, Lamotrigine, Topi-
seen in first generation anticonvulsants are more se- ramate, Tiagabine, Zonisamide, Levetiracetam, Ox-
vere compared to most second generation AEDs. carbazepine and Pregabalin (see Table 2). For this
Many of the older AEDs require close monitoring of review five of the newer AEDs (Lamotrigine, Oxcar-
serum levels and have black-box warnings to warn bazepine, Topiramate, Pregabalin, and Tiagabine)
patients of these potentially life-threatening reac- were selected based on their spectrum of use and po-
tions. tential place in epilepsy treatment.


FIRST GENERATION EPILEPSY TREATMENTS CLINICAL TRIAL DATA
Before 1993, the management of epilepsy Stephen et al. performed a randomized, prospec-
was limited to six major AEDs. These were referred tive study to compare the efficacy and tolerability of
to as the older or traditional AEDs and consisted of sodium valproate (VPA) and lamotrigine (LTG)
Phenobarbital, Primidone, Phenytoin, Valproate, monotherapy.15 This study included 225 patients,
Carbamazepine and Ethosuximide. While all of the median age 35 years, who were followed for 12
older AED's were efficacious, their long-term safety months. Twelve month seizure-free rates were iden-
was questionable (see Table 1). Development of tical (47%) in the VPA and LTG treatment arms.
newer antiepileptic medications with few serious ad- But 23% VPA versus 13% LTG withdrew due to ad-
verse effects, minimal drug interactions, and broader verse events. Brodie et al. compared LTG to car-
spectrums of activity was needed, bamazepine (CBZ) for a 24 week period.16 They en-


PharmaNote 40 Volume 24, Issue 1 October 2008








Table 2. Summary of Second Generation Anticonvulsant Epileptic Drugs1-14

d Typical
Proposed
Agent ec sm of Id s PK Drug-Drug Serious Side Target Cost
Mechanism of Indications Cost
(Yr approved) Action (F,VD,T%) Interactions Effects Dose
(mg/daActiony)
(mg/day)


Fel e Excitatory NMDA and
Felbamate
inhibitory GABA
brain mechanisms


Indirect effects on
Gabapentin
S calcium channels and
(1994)
(994) increase GABA


SInhibition of voltage-
Lamotrigine
activated sodium
(1995) channels


Modulation of volt-
Topiramate age-dependent so-
(1995) dium channels and
GABA inhibition


.T e Blocks GABA reup-
Tia e take increasing GABA
(1996)ncentrations
concentrations


Zonisamide
(1999)



Levetiracetam
(1999)



Oxcarbazepine
(2000)


Pregabalin
(2005)


Blocks voltage-
sensitive sodium
channels



Unknown mecha-
nism


Blocks voltage-
sensitive sodium
channels


Indirect effects on
calcium channels and
increase GABA


Partial seizures and
Lennox-Gastaut
syndrome refrac-
tory to other AED

Adjunctive manage-
ment of partial
seizures

Partial, generalized
tonic-clonic, ab-
sence and myo-
clonic seizures


Adjunctive treat-
ment of partial
seizures



Adjunctive treat-
ment with partial
epilepsy


Adjunctive treat-
ment of partial
onset seizures

Adjunctive therapy
for the manage-
ment of partial
seizures, myoclonic
seizures

Partial seizures and
generalized tonic-
clonic seizures


Partial and secon-
dary generalized
tonic-clonic seizures


>90%
0.75L/kg
14-23 hrs

Dose de-
pendent
0.9L/kg
5-9 hrs

98%
1.2L/kg
15-35 hrs



81-95%
0.6-1L/kg
20-30 hrs



90-95%
1.4L/kg
5-8 hrs


40-60%
1.5L/kg
50-70 hrs


100%
0.5-0.7L/kg
6-8 hrs


95%
0.75L/kg
8-15 hrs


90%
0.56L/kg
5-7 hrs


Carbamazepine, Pheny-
toin, Valproic Acid and
Gabapentin



Cimetidine and Antacids


Carbamazepine, Pheny-
toin, Valproic Acid and
Phenobarbital


Carbamazepine, Pheno-
barbital, Phenytoin, Primi-
done, Valproic Acid and
Oral Contraceptives


Carbamazepine, Pheno-
barbital, Phenytoin, Primi-
done and Valproic Acid


Carbamazepine, Pheno-
barbital, Phenytoin, Primi-
done and Valproic Acid


Phenytoin


Phenytoin, Lamotrigine
and Oral Contraceptives



Oxycodone, Lorazepam
and Ethanol


Aplastic ane-
mia and he-
patic failure



None


Stevens-
Johnson syn-
drome



Kidney stones,
oligohidrosis,
glaucoma



Spike-wave
stupor



Kidney stones,
oligohidrosis,
rash


400mg
2400-3600 400mg
(#90) =
bid, tid
$205.79


600mg
900-2400, (#90)
bid, tid
$92.99



$89.99


14, mg
100-400,
(#60) =
bid (#60) =
$369.87



16mg
36-60, tid (#30) =
$225.39


50mg
300 daily (#100)=
$91.99


1000mg
1000-3000, l00mg
None (#60) =
bid
$428.88


600mg
Hyponatre- 800-1800, 60) 0
mia, rash bid, tid $25
$259.98


None


150mg
150-600, (#30
daily (73.49
$73.49


F, bioavailability; VD, volume of distribution; T12, half-life; bid, twice a day; tid, three times a day; PK, pharmacokinetic


rolled 150 elderly patients (>65 yrs) and found a
greater percentage of LTG patients remained seizure
free the last 16 weeks (LTG 39%, CBZ 21%, p =
0.027). The hazard ratio for withdrawal was 2.4
(95% CI 1.4-4.0) meaning that patients were more
than twice as likely to withdraw from the CBZ treat-
ment arm. Both of these trials showed similar effi-
cacy and better tolerability of lamotrigine compared
to first generation epilepsy treatments.
Schachter and colleagues conducted a double-
blind, randomized, placebo-controlled, monotherapy
trial for partial seizures comparing oxcarbazepine to


placebo.17 Oxcarbazepine 1,200mg was adminis-
tered twice daily in hospitalized patients with refrac-
tory partial seizures for ten days. The results showed
both the primary (time to meeting one of the exit cri-
teria) and secondary (percentage of patients who met
one of the exit criteria) efficacy variables were statis-
tically significantly better for the oxcarbazepine arm
(p= 0.0001). The total partial seizure frequency per
9 days was also significantly better for oxcar-
bazepine (p= 0.0001).
Bill and colleagues compared oxcarbazepine
(OXC) versus phenytoin (PHT) in a double-blind,


Phrm~oe oum 2, sse1 ctbe 20


PharmaNote


Volume 24, Issue 1 October 2008






randomized, parallel-group trial.18 The study used
287 patients randomized in a 1:1 ratio. No statisti-
cally significant difference was found in the efficacy
analysis between the two treatment arms. The OXC
arm had 3.5% of patients discontinue treatment early
for tolerability issues versus 11% in the PHT group.
This result showed a statistically significant differ-
ence in favor of OXC.
Privitera et al. completed a multinational, ran-
domized, double-blind trial comparing topiramate
(TPM), carbamazepine (CBZ), and valproate
(VPA).19 They randomized 613 newly diagnosed
epilepsy patients into two treatment arms. Treatment
was with the traditional antiepileptic drugs (CBZ or
VPA), TPM 100mg/day, or TPM 200mg/day. There
was no difference among the treatment groups with
regard to efficacy, but TPM 100mg/day was associ-
ated with the fewest discontinuations due to adverse
events.
Krakow and colleagues conducted an open-label,
observational prospective study assessing the effec-
tiveness of topiramate (TPM) as add-on therapy.20
The investigators enrolled 450 patients who had at
least one seizure in the previous 12 weeks. The vast
majority (95% of patients) were taking either CBZ or
VPA and were followed for 1 year. During the 12
month study, a median of 2.8 seizures per month
were recorded which was significantly reduced to 0.7
per month during the complete treatment phase (p=
0.0001). Nearly three-fourths of these patients
(72%) had greater than 50% seizure reduction and
only 5% ended treatment early because of adverse
effects.
Arroyo et al. performed an international, multi-
center, 12-week, double-blind, randomized study
comparing placebo, pregabalin (PGB) 150mg/day
and 600mg/day as add-on treatment for patients with
refractory partial seizures.21 This trial enrolled 287
patients and randomized them into three treatment
arms. The primary efficacy was the reduction of sei-
zures from baseline during the 12-week treatment.
PGB 150mg/day and 600mg/day were significantly
more effective than placebo in decreasing seizure
rates (p= 0.0007 and p<0.0001, respectively, vs. 0.9).
Additionally, PGB 150mg/day and 600mg/day was
efficacious and well tolerated when used as add-on
therapy in patients with partial seizures.
Another randomized, double-blind, placebo-
controlled study evaluating flexible-dose and fixed-
dose pregabalin treatment was recently published by


Elger, et al.22 This trial randomized 341 patients to
placebo, pregabalin 600mg/day BID fixed-dose arm
and a pregabalin flexible-dose arm (150 and 300mg/
day for 2 weeks each; 450 and 600mg/day for 4
weeks each, BID). Both PGB arms decreased sei-
zure frequency, by 35.4% in the flexible-dose arm
(p= 0.0091) and 49.3% in the fixed-dose arm (p=
0.0001), compared to 10.6% in the placebo arm (p=
0.0337). The authors concluded PGB to be highly
efficacious and well-tolerated in both the fixed and
flexible-dose arms compared to placebo.
Kalviainen et al. performed a multicenter, double
-blind, parallel-group, placebo-controlled trial com-
paring the efficacy and tolerability of tiagabine and
placebo in refractory partial seizures.23 Patients
(n=154) were randomized to either a tiagabine or
placebo treatment arm during the 12 week study.
There was a significant reduction in the median 4-
week seizure rate for all partial seizures and simple
partial seizures (p < 0.05). Tiagabine was generally
well-tolerated, with most adverse effects being mild
to moderate. This study showed tiagabine dosed
lower than what is normally accepted (10mg TID), is
well tolerated and has efficacy for treatment of re-
fractory partial seizures.
Dodrill et al. evaluated the differences between
tiagabine (TGB) carbamazepine (CBZ) and pheny-
toin (PHT) when used as add-on therapy in uncon-
trolled partial seizures.24 277 patients were divided
into two groups, one group currently receiving CBZ
and the other PHT. These groups each contained
two treatment arms, the CBZ baseline group received
either TGB or PHT add-on treatment and the PHT
baseline group received either CBZ or TGB treat-
ment. The results from the baseline CBZ group re-
vealed no differences in test scores between TGB
and PHT. The results from the baseline PHT group
showed patients in the TGB arm treatment had im-
proved verbal fluency as well as quicker responses
with motor speed tests compared to patients treated
with CBZ. But TGB patients in the baseline PHT
reported less positive mood and more financial con-
cerns than the CBZ treatment arm. Overall, treat-
ment with TGB showed very few differences when
compared to CBZ and PHT as add-on treatment in
uncontrolled partial seizures.

SUMMARY
Second generation AEDs may offer a favorable
choice in treating epileptic seizures but they have not


PharmaNote Volume 24, Issue 1 October 2008


PharmaNote


Volume 24, Issue 1 October 2008








Table 3. Overview of Clinical Trials Involving AED Treatments"1524

Patient
Trial Agent(s) Comparator(s) Design aateii Results
Characteristics


Stephen et al.
(2007)


Brodie et al.
(1999)


Schachter et al.
(1999)


Bill et al.
(1997)


Privitera et al.
(2003)


Krakow et al.
(2007)


Arroyo et al.
(2004)


Elger et al.
(2005)


Kalviainen et al.
(1998)


Dodrill et al.
(2000)


Lamotrigine




Lamotrigine


Oxcarbazepine




Oxcarbazepine



Topiramate


Carbamazepine w/ Topi-
ramate and Valproate w/
Topiramate


Pregabalin



Pregabalin



Tiagabine


Carbamazepine w/ Tiaga-
bine and Phenytoin w/
Tiagabine


Sodium Valproate




Carbamazepine


placebo




Phenytoin



Carbamazepine,
Valproate


Carbamazepine
and Valproate


placebo



placebo



placebo


Carbamazepine w/
Phenytoin and
Phenytoin w/ Car-
bamazepine


R, PS




M, R, DB


R, DB, PC


N = 226
Mean age 35yr
Age range 13-80

N = 150
Mean age 77yr
Age range >65

N = 102
Mean age 33yr
Age range 11-62


N = 287
Mean age 27yr Age range
R DB PG (OXC) 16-63
Age range (PHT) 15-91


M, R, DB



OL, O, P


M, R, DB



R, DB, PC



M, R, DB, PC


R, DB


N = 613
Mean age 29yr
Age range 6-64,>65

N = 450
Mean age 40yr
Age range 10-93

N= 287
Mean age 37yr
Age range 17-73

N= 341
Mean age 41yr
Age range 18-78

N = 154
Mean age 36yr
Age range 16-75


N = 277
Mean age 38yr
Age range >16


No difference in
efficacy, but Lamo-
trigine was better
tolerated (p= 0.046)

Seizure free last 16
weeks (LTG 39%, CBZ
21%, p= 0.027)

All variables studied
statistically favored
Oxcarbazepine
(p=0.0001)
No difference in
efficacy, but OXC
showed significant
better tolerability
Similar efficacy in all
arms, TPM 100mg/
day fewest adverse
events
72% had > 50% sei-
zure reduction, 5%
discontinued treat-
ment early
PGB was highly effi-
cacious and well-
tolerated v. placebo

PGB was highly effi-
cacious and well-
tolerated v. placebo

Significant seizure
reduction (p<0.05),
well-tolerated

Statistically no sig-
nificant differences
between treatment
arms


R = randomized; PS = prospective study; M = multicenter; DB = double-blind; PC = placebo-controlled; PG = parallel-group; OL = open-label; O = observational


replaced the first generation AEDs. The newer drugs
are as efficacious as the older ones with a trend to-
ward fewer side effects. The few head-to-head trials
between the older and newer AEDs makes the pref-
erential selection of any agent difficult. Although
the long term goal of seizure freedom remains a dif-
ficult task for many patients, a better understanding
of the disease will hopefully move treatment from
seizure suppression to prevention of epilepsy.


REFERENCES
1. Hauser WA, Annegers JF, Kurland LT. The prevalence of
epilepsy in Rochester, Minnesota, 1940-1980. Epilepsia.


1991;32:429-445.
2. Temkin O. The falling sickness: a history of epilepsy from
the Greeks to the beginnings of modern neurology, 2nd ed.
Baltimore: Johns Hopkins, 1971.
3. Gowers WR. Epilepsy and other chronic convulsive dis-
eases. London: Churchill, 1881.
4. Lozsadi D, Hemming K, Marson AG. Pregabalin add-on
for drug-resistant partial epilepsy. Cochrane Database of
Systematic Reviews 2008, Issue 1.
5. Epilepsy Foundation. Epilepsy facts and figures. 2005.
Available at: https://www.epilepsyfoundation.org
6. Kanner AM. Depression in epilepsy: Prevalence, clinical
semiology, pathogenic mechanisms, and treatment. Biol
Psychiatry 2003;54(3):388-98.
7. Gilliam F, Kuzniecky R, Faught E, et al. Patient validated


Phara~oe Vlum 24 Isse 1Octber200


PharmaNote


Volume 24, Issue 1 October 2008







content of epilepsy-specific quality of life measurement.
Epilepsy 1997:38(2):233-6.
8. LaRoche SM. A new look at the second generation antiepi-
leptic drugs: A decade of experience. The Neurologist
2007; 13(3):133-9.
9. Perucca E. Clinical pharmacology and therapeutic use of
the new antiepileptic drugs. Fundam Clin Pharmacol
2001;15(6):405-17.
10. Perucca E, Tomson T. Monotherapy trials with the new
antiepileptic drugs. Study designs, practical relevance and
ethical implications. Epilepsy Res 1999;33:247-62.
11. Elger C, Schmidt D. Modern management of epilepsy: A
practical approach. Epilepsy & Behavior 2008;12:501-39.
12. French J, Pedley T. Initial Management of epilepsy. N Engl
J Med 2008;359:166-76.
13. Parks JrB, Dostrow V, Noble S. Drug therapy for epilepsy.
American Family Physician 1994;50(3):639-49.
14. Epocrates Online. www.drugstore.com
15. Stephen L, Sills G, et al. Sodium valproate versus lamo-
trigine: a randomized comparison of efficacy, tolerability
and effects on circulating androgenic hormones in newly
diagnoses epilepsy. Epilepsy Research 2007;75:122-9.
16. Brodie M, Overstall P, Giorgi L, et al. Multicentre, double-
blind, randomized comparison between lamotrigine and
carbamazepine in elderly patients with newly diagnosed
epilepsy. Epilepsy Research 1999;37:81-7.
17. Schachter S. Vazquez B, Fisher R, et al. Oxcarbazepine:
double-blind, randomized, placebo-control, monotherapy
trial for partial seizures. Neurology 1999;52:732-42.
18. Bill P, Vigonius U, Pohlmann H, et al. A double-blinded
controlled clinical trial of oxcarbazepine versus phenytoin
in adults with previously untreated epilepsy. Epilepsy Re-
search 1997;27:195-204.
19. Privitera MD, Brodie MJ, Rattson RH, et al. Topiramate,
carbamazepine and valproate monotherapy: double-blinded
comparison in newly diagnosed epilepsy. Acta Neurol
Scand 2003;107:165-75.
20. Krakow K, Lengler U, Rettig K, et al. Topiramate in add-
on therapy: results from an open-label, observational study.
Seizure 2007;16:593-600.
21. Arroyo S, Anhut H, Kugler Ar, et al. Pregabalin add-on
treatment: a randomized double-blind placebo-controlled,
dose-response study in adults with partial seizures. Epilep-
sia 2004;45(1):20-7.
22. Elger CE, Brodie MJ, Anhunt H, et al. Pregabalin add-on
treatment in patients with partial seizures: a novel evalua-
tion of flexible-dose and fixed-dose treatment in a double-
blind placebo-controlled study. Epilepsia 2005;466
(12):1926-36.
23. Kalviainen R, Brodie MJ, Duncan J, et al. A double-blind
placebo-controlled trial of tiagabine given three-times daily
as add-on therapy for refractory partial seizures. Epilepsy
Research 1998;30:33-40.
24. Dodrill CB, Arnett JL, Deaton R, et al. Tiagabine versus
phenytoin and carbamazepine as add-on therapies: effects
on abilities, adjustment and mood. Epilepsy Research
2000;42:123-32.


Index for Volume 23 (Oct 2007 Sep 2008)


Topic


Alternative Medicine Update
Alzheimer's Disease

B-C-D
Bystolic
Ceftobiprole
DoribaxTM

E-F-G-H-I-J
Exforge
Genetics of Warfarin Therapy
Infectious Sinusitis

K-L-M-N
Maraviroc
Neupro
New Drug Approvals, 2007

O-P-Q-R
Onychomycosis & terbinafine
Pristiq
Resistant UTIs

S-T-U-V
Stress ulcer prophylaxis in the ICU
S) IIblcort '
Twlcmlllt'


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PharmaNote Volume 24, Issue 1 October 2008


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Services, UF Family Practice Medical
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Pharmacy Practice
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