Download Drug Information Letter New Drug Evaluation Multaq (dronedarone) Tablets

CENTER FOR DRUG INFORMATION AND RESEARCH
School of Pharmacy – LECOM, Erie, PA
Drug Information Letter
Independent best evidence analyses and commentary
Date: August 2009
Volume 3
Issue 3
New Drug Evaluation
Multaq (dronedarone) Tablets
Editor’s Note: This review is based on the professional product label, or
package insert, for dronedarone using the framework developed by the LECOM
Center for Drug Information and Research for evaluating the therapeutic value of
newly marketed drugs.
ASSESSMENT OF MULTAQ (DRONEDARONE)
DECREASE HOSPITALIZATIONS FOR ATRIAL FIBRILLATION AND
INCREASED RISK OF DEATH
Dronedarone is a new molecule that is indicated for a select subset of patients
to reduce the risk of cardiovascular hospitalization in patients with paroxysmal or
persistent atrial fibrillation (AF) or atrial flutter (AFL), with a recent episode of
AF/AFL and associated cardiovascular risk factors who are in sinus rhythm or
who will be cardioverted.
Dronedarone carries a black box warning concerning deaths in patients with
severe heat failure requiring hospitalizations or referral to specialized heart
failure clinics for worsening symptoms. It is important to know which patient
populations have benefited or been harmed from dronedarone use in the
following trials; ATHENA1, EURIDIS2, ADONIS2, ERATO3, DAFNE4, and
ANDROMEDA5.
1
Hohnloser SH, Crijns HJ, van Eickels M, et al. Effect of dronedarone on cardiovascular events
in atrial fibrillation. N Engl J Med. 2009. 360(7):668-78.
2
Singh BN, Connolly SJ, Crijns HJ, et al. Dronedarone for maintenance of sinus rhythm in atrial
fibrillation or flutter. N Engl J Med. 2007. 357(10):987-99.
3
Davy JM, Herold M, Hoglund C, et al. Dronedarone for the control of ventricular rate in
permanent atrial fibrillation: the efficacy and safety of dronedarone for the control of ventricular
rate during atrial fibrillation (ERATO) study. AM Heart J. 2008. 156(3):527.e1-9.
4
Touboul P, Brugada J, Capucci A, et al. Dronedarone for prevention of atrial fibrillation: a doseranging study. Eur Heart J. 2003. 24(16):1481-7.
5
Kober L, Torp-Pedersen C, McMurray JJ, et al. Increased mortality after dronedarone therapy
for severe heart failure. N Engl J Med. 2008. 358(25):2678-87.
Dronedarone is required to be dispensed with a Medication Guide.
CAUTION
DO NOT SUBSTITUTE LEXICOMP OR OTHER COMMERCIAL THIRD-PARTY DRUG
INFORMATION SOURCES FOR FDA-APPROVED PROFESSIONAL PRODUCT
LABELS.
Food and Drug Administration (FDA) Approval6
Dronedarone, an antiarrhythmic benzofuran derivative, was approved by
the FDA on July 1, 2009, to reduce the risk of cardiovascular hospitalization in
patients with paroxysmal or persistent AF/AFL with a recent episode of AF/AFL,
and associated cardiovascular risk factors (i.e.,
age > 70, hypertension, diabetes, prior
cerebrovascular accident, left atrial diameter ≥
IN THIS ISSUE
50 mm or left ventricular ejection fraction <
• New Drug Evaluation 40%), who are in sinus rhythm or who will be
Multaq (dronedarone)
cardioverted.
•
The FDA has required dronedarone’s
professional product label to display a Black Box
Warning concerning heart failure. Black Box
Warnings are the strongest type of warnings that
the FDA can require. The following Black Box
Warning is verbatim from the package insert:
Drug Topics – Top 200
Drugs
WARNING: HEART FAILURE
Multaq is contraindicated in patients with NYHA Class IV heart failure, or NYHA
Class II-III heart failure with a recent decompensation requiring hospitalization or
referral to a specialized heat failure clinic.
In a placebo-controlled study in patients with severe heat failure requiring recent
hospitalization or referral to a specialized heart failure clinic for worsening
symptoms (the ANDROMEDA5 Study), patients given dronedarone had a greater
than two-fold increase in mortality. Such patients should not be given
dronedarone.
6
Multaq (dronedarone) Professional Product Label. At:
http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022425lbl.pdf. Accessed: July 28,
2009.
The above ANDROMEDA5 Study mentioned in the Black Box Warning
and the following studies ATHENA1, EURIDIS2, ADONIS2, ERATO3, and
DAFNE4 have been reviewed in the FDA’s product labeling for dronedarone. All
of these studies were placebo controlled.
Note that there is no regulatory requirement for new drugs to be
therapeutically superior to drugs already marketed before approval. In the
clinical trials submitted by manufacturers to support the new drug’s approval, the
new drug, in many cases, is compared only to a placebo.
Description of Dronedarone
Dronedarone has antiarrhythmic properties belonging to all four VaughanWilliams classes, but the true clinical effect to each of these is unknown. There
is a dose related effect increasing PR and QTc intervals. Unlike amiodarone,
another benzofuran derivative, dronedarone possesses no iodine molecules, but
does possess a potentially clinically relevant sulfonamide group (see below).
O
(CH2 )3CH3
(CH2)3 CH3
H3 CO 2SHN
O
N
(CH2)3 CH3
O
HCl
Multaq (dronedarone)
O
(CH2)3CH3
I
OCH2CH2 N(C2H5)2
O
I
HCl
7
Pacerone (amiodarone)
There is no indication in the professional product label of patients having
sulfonamide related allergic reactions but there could be a potential for cross
allergenicity with other sulfonamide medications based on dronedarone’s
chemical structure.
7
Figure adapted from: Pacerone (amiodarone) Professional Product Label. At:
http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=10301. Accessed: July 28, 2009.
Therapeutic Efficacy of Dronedarone
The Clinical Studies section of the professional product label lists four
placebo controlled studies.
Study 1 – ATHENA1
ATHENA was a randomized, double blind, multicenter, multinational study.
The study included AF/AFL patients who were ≥ 75 years of age, or ≥ 70 years
old with at least one cardiovascular risk factor. If patients were not in sinus
rhythm, they were expected to be electrically or chemically converted. Patients
were randomized to either dronedarone 400 mg twice daily (2301 patients) or
placebo (2327 patients) while patients were actively in AF/AFL or in sinus
rhythm. Patients were also on conventional therapy for cardiovascular diseases.
The primary endpoint of the study was time to first hospitalization for
cardiovascular reasons or death from any cause.
Table 1 – ATHENA Primary Endpoint Analysis
Placebo
Dronedarone
Absolute
Reduction
Number
Needed to
Treat (NNT)
(n = 2327)
(n = 2301)
913 (39.2%)
727 (31.6%)
7.6%
≈ 13
- Cardiovascular hospitalization
856 (36.8%)
669 (29.1%)
7.7%
≈ 13
- Death from any cause
57 (2.4%)
58 (2.5%)
-----
----
Primary Endpoint
Cardiovascular hospitalization or death from any cause
Primary Endpoint Components (as first event)
Table 1 reflects the primary endpoint analysis of the ATHENA Study.
Overall, 13 patients must be treated with dronedarone to prevent one
hospitalization for 22 months, but mortality was slightly higher in the dronedarone
group.
Study 2 and 3 – EURIDIS2 and ADONIS2
Patients in sinus rhythm with a prior history of AF/AFL were randomized to
dronedarone 400 mg twice daily (n = 828) or placebo (n = 409) for a total of 1237
patients in EURIDIS and ADONIS in an outpatient setting. Patients ranged in
age from 20 to 88 years of age, with the majority being Caucasian (97%).
Patients were also taking conventional therapies for cardiovascular diseases.
Patients were followed for 12 months. The primary endpoint was time to first
recurrence of AF/AFL. In the pooled analysis from both EURIDIS2 and ADONIS2
dronedarone lowered the recurrence of AF/AFL during the 12 month study
period. The absolute difference in recurrence rate was about 11% at 12 months.
This reflects a number needed to treat of around 9 patients for 12 months.
Study 4 – ANDROMEDA5
In ANDROMEDA patients were either randomized to dronedarone (n =
310) or placebo (n = 317) who were recently hospitalized with symptomatic heart
failure and severe left ventricular systolic dysfunction. The primary composite
end point was all-cause mortality or hospitalization for heart failure. The study
was terminated early because of excess mortality in the dronedarone group.
Twenty-five patients in the dronedarone group (8.1%) versus 12 patients in the
placebo group (3.8%) had died. This is more than double the amount of deaths
versus placebo. The main reason for death was worsening heart failure.
Contrasting ANDROMEDA5 and ATHENA1
The ANDROMEDA and ATHENA populations differed markedly. In
ANDROMEDA, the majority of patients had either NYHA Class II (40%) or III
(50%). In ATHENA, only 25% of patients had NYHA Class I or II heart failure,
and only 4% where in class III. All patients in ATHENA had AF/AFL but only
38% of the patients had AF/AFL in ANDROMEDA. It is important to note that
those patients in ATHENA who had a LVEF < 35% (n = 179) did not benefit from
dronedarone treatment. There was no difference in first cardiovascular
hospitalization or death from any cause in this population. Based on these trials
it is reasonable to recommend not giving dronedarone to any patient with heart
failure. Risks highly outweigh the benefits.
Safety of Dronedarone
Beyond the important safety data in ANDROMEDA5 which resulted in
the FDA to give dronedarone a Black Box Warning, and the unpublished safety
data of the DIONYSOS8 trial, five additional placebo controlled trials totaling
6285 patients where evaluated for safety, ATHENA1, EURIDIS2, ADONIS2,
ERATO3, and DAFNE4. Throughout the five trials, 3282 patients were treated
with dronedarone, and 2875 patients were given placebo. The average exposure
was 12 months. The most common adverse reactions included diarrhea,
nausea, abdominal pain, vomiting, and asthenia. Clinically important laboratory
data and ECG data not necessarily reported in the trials as adverse reactions is
reported below.
Table 2 – Laboratory data and ECG parameters
Serum creatinine increased ≥ 10% five days after treatment
initiation
QTc Bazett prolongation (> 450 ms in males and > 470 ms in
females)
Placebo
Dronedarone
(n = 2875)
(n = 3282)
21%
51%
(n = 2237)
(n = 2701)
19%
28%
The elevation in serum creatinine has a rapid onset, reaches a plateau after 7
days and is reversible after discontinuation. The change in serum creatinine is
the result of dronedarone’s inhibition of creatinine’s tubular secretion. If the QTc
Bazett interval is ≥ 500 ms, dronedarone should be discontinued.
Dronedarone is contraindicated in the following situations:
•
NYHA Class IV heart failure or NYHA Class II - III heart failure with a
recent decompensation requiring hospitalization or referral to a specialized
heart failure clinic.
•
Second- or third-degree atrioventricular (AV) block or sick sinus syndrome
(except when used in conjunction with a functioning pacemaker)
•
Bradycardia <50 bpm.
•
Concomitant use of strong CYP 3A inhibitors, such as ketoconazole,
itraconazole, voriconazole, cyclosporine, telithromycin, clarithromycin,
nefazodone and ritonavir.
•
Concomitant use of drugs or herbal products that prolong the QT interval
and might increase the risk of Torsade de Pointes, such as phenothiazine
anti-psychotics, tricyclic antidepressants, certain oral macrolide antibiotics,
and Class I and III antiarrhythmics.
•
QTc Bazett interval ≥500 ms or PR interval >280 ms.
•
Severe hepatic impairment.
•
Pregnancy (Category X): dronedarone is contraindicated in women who
are or may become pregnant.
•
Nursing Mothers.
Beyond avoiding CYP 3A inhibitors, dronedarone has additional clinically
important drug interactions. Patients should also avoid grapefruit juice, and
rifampin and other CYP 3A inducers. If a patient is also taking digoxin, the
digoxin dose should be halved. Various statin product labeling should also be
followed closely because dronedarone has CYP 3A and P-gP inhibitor qualities.
Dose adjustments to statins will need to be made depending on statin product.
Patients’ potassium levels should be within normal ranges prior to the initiation of
dronedarone. Concurrent therapy with potassium deleting diuretics may induce
hypokalemia or hypomagnesemia.
Conclusion
There has been one trial, ATHENA1, indicating that dronedarone has
decreased hospitalizations in patients with AF/AFL. To date dronedarone has
not been shown to decrease mortality, and has shown to increase mortality in
patients with heart failure (ANDROMEDA Study5). More patients in the
dronedarone group also died in the ATHENA Study1. The question is, should a
medication studied in such a select population showing a decrease in
hospitalizations, but no mortality benefit be prescribed?
Prescribing practices from medications such as Accutane (isotretinoin)
teach us that this medication may be misused and patients may be placed in
harms way. The large number of contraindications, drug interactions and
potential for death outweigh the drug’s potential benefit.
The FDA has instituted a Risk Evaluation and Mitigation Strategy (REMS)
for dronedarone. The goal of the REMS is to prevent improper prescribing and
inform patients about the risks of the drug. Elements of the REMS include a
Medication Guide required by regulation to be given to patients, and a
communication plan to inform healthcare professionals about the risks of the
drug. The communication plan includes an informational sheet, and print
advertisements in professional society journals. It is clear from the Black Box
Warning and the REMS that the FDA is warning physicians on prescribing this
medication and after this review it looks as if the risks highly outweigh the
benefits for dronedarone use.
Information Not Available in the Professional Product Label
DIONYSOS trial8 – Unpublished data of the safety and efficacy of dronedarone
versus amiodarone
1. DIONYSOS efficacy data
DIONYSOS is an unpublished multicenter, randomized, double-blind,
parallel-arm study to compare the safety and efficacy of dronedarone (400 mg
BID) versus amiodarone (600 mg daily for 28 days, then 200 mg daily thereafter)
to maintain sinus rhythm in patients with AF. It is important to note that there is
no mention of the DIONYSOS trial in the product labeling. To date the trial data
listed below has not been reviewed or commented on by the FDA. Results were
first released by Sanofi-Aventis as a press release on December 23, 2008.9
Then a further review of the trial and a more complete analysis appears in
Sanofi-Aventis’s Briefing Material for the March 18, 2009 Meeting of the
Cardiovascular and Renal Drugs Advisory Committee.8 A total of 504 patients
were randomized into the trial, 249 patients randomized to dronedarone and 255
patients to amiodarone. The primary composite endpoint was time to first AF
recurrence or premature study drug discontinuation for intolerance or lack of
efficacy. More patients randomized to dronedarone (75.1%) had a first
recurrence of AF or premature study drug discontinuation at 12 months than the
patients randomized to amiodarone (58.8%) (HR = 1.589, CI [1.275; 1.980] log-
8
Sanofi-Aventis. Multaq (Dronedarone) – Briefing Document – Advisory Committee Meeting of
the Cardiovascular and Renal Drugs Division of the US Food and Drug Administration. March 18,
2009. At
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Cardiova
scularandRenalDrugsAdvisoryCommittee/UCM134981.pdf. Accessed 8/10/09.
9
Sanofi-Aventis. DIONYSOS Study Results Showed the Respective Profiles of Dronedarone and
Amiodarone. Press Release. December 23, 2008. At http://en.sanofiaventis.com/binaries/20081223_dionysos_fe_en_en_tcm28-23624.pdf. Accessed 8/10/09.
rank p-value < 0.0001). The Kaplan-Meier curve below reflects the time to first
recurrence of AF or premature study drug discontinuation.
Table 3 - Components of the primary endpoint.
Number of patients with the combined primary endpoint
Atrial fibrillation recurrence
Documented atrial fibrillation after conversion
Unsuccessful electrical cardioversion
No spontaneous conversion and no electrical cardioversion on
day 10 to day 28
Premature study drug discontinuation
Lack of efficacy
Intolerance
Dronedarone
(n = 249)
184 (73.9%)
158 (63.5%)
91 (36.5%)
29 (11.6%)
38 (15.3%)
Amiodarone
(n = 255)
141 (55.3%)
107 (42.0%)
62 (24.3%)
16 (6.3%)
29 (11.4%)
26 (10.4%)
1 (0.4%)
25 (10.0%)
24 (13.3%)
0
34 (13.3%)
Efficacy Conclusion: It is clear that dronedarone is not as effective as
amiodarone in reducing AF recurrence.
2. DIONYSOS safety data
The main safety endpoint in DIONYSOS was the time to first occurrence
of thyroid, hepatic, pulmonary, neurological, skin, eye or gastrointestinal specific
events or premature study drug discontinuation following any adverse effect.
The main safety endpoint occurred in 39.3% of dronedarone treated patients and
44.5% of amiodarone treated patients after 12 months (HR = 0.80, 95% CI =
0.60; 1.07, log-rank p value = 0.13). The Kaplan-Meier curve below represents
time to first study drug intake to main safety endpoint.
The main safety endpoint was driven by lower thyroid, neurological, skin and
ocular effects in the dronedarone group. The main gastrointestinal adverse
effects were driven by a higher non-serious diarrheal occurrence in the
dronedarone group (9.2%) versus the amiodarone group (3.1%).
Table 4 - Analysis of time from first study drug intake to first specific event – All
randomized and treated patients (DIONYSOS)
Thyroid event
Dronedarone
(n = 249)
Amiodarone
(n = 255)
Absolute
Difference
3 (1.2%)
20 (7.8%)
6.6%
Neurological Event(sleep disorders and tremor)
3 (1.2%)
24 (9.4%)
8.2%
Skin Event (Photosensitivity reaction)
3 (1.2%)
5 (2.0%)
0.8%
Dronedarone
(n = 249)
Amiodarone
(n = 255)
Absolute
Difference
Overall incidence of treatment emergent adverse
effects (TEAEs)
60.6%
67.5%
6.9%
Incidence of serious TEAEs
13.7%
14.5%
0.8%
Serious TEAEs of Hepatobiliary Disorders
2 (0.8%)
2 (0.8%)
---
Incidence of AEs leading to premature study drug
discontinuation
12.9%
17.6%
4.7%
2 (0.8%)
5 (2.0%)
1.2%
Deaths (on study period)
4 (1.6%)
7 (2.7%)
1.1%
QTcB interval above 500 msec
10.9%
20.5%
9.6%
Low hemoglobin values
1.3%
4.7%
3.4%
Table 5 – Additional adverse events (DIONYSOS)
Deaths (on treatment period)
#
#
Last drug intake plus 10 days
It is important to note there were no cases of torsades de pointes, or
pulmonary events in either group. There were a higher proportion of patients
with bradycardia and conduction disorders in the amiodarone group compared to
dronedarone (number of patients not reported). In those patients taking oral
anticoagulation the risk of hemorrhage was decreased by 50% in the
dronedarone group compared to the amiodarone group (numbers of patients not
reported). Along with thyroid events, thyroid abnormalities were also higher in
the dronedarone group compared to the amiodarone group.
Safety Conclusion: Other than non-serious gastrointestinal adverse effects it
appears from the sponsor that dronedarone is safer than amiodarone in this 12
month analysis.
Overall DIONYSOS Conclusion
In an unpublished multicenter, randomized, double-blind, parallel-arm
study to compare the safety and efficacy of dronedarone versus amiodarone to
maintain sinus rhythm in patients with AF it appears that dronedarone is safer
than amiodarone, but not as effective. The only available statement from the
FDA, found in a FDA briefing document, was “…the effectiveness of dronedarone
in preventing atrial fibrillation is substantially less than that of amiodarone.”10
Amiodarone is not FDA approved for the treatment of AF, and has not been
proven safe or effective for the conversion or maintenance treatment of AF/AFL.
TOP 200 Drugs
In May, Drug Topics has published the top 200 branded and generic drugs
by retail dollars and total prescriptions in 2008. Each of the top 200 drug lists
can be found from the table below.
2008 Top 200 Drugs
10
Source
US Food and Drug Administration. Multaq (Dronedarone) – Briefing Document – Advisory
Committee Meeting of the Cardiovascular and Renal Drugs Division of the US Food and Drug
Administration. March 18, 2009. At
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Cardiova
scularandRenalDrugsAdvisoryCommittee/UCM176354.pdf. Accessed 8/10/09.
Branded drugs by total prescriptions
http://drugtopics.modernmedicine.com/dr
ugtopics/data/articlestandard//drugtopics/
222009/599845/article.pdf
Branded drugs by retail dollars
http://drugtopics.modernmedicine.com/dr
ugtopics/data/articlestandard//drugtopics/
192009/597083/article.pdf
Generic drugs by total prescriptions
http://drugtopics.modernmedicine.com/dr
ugtopics/data/articlestandard//drugtopics/
222009/599844/article.pdf
Generic drugs by retail dollars
http://drugtopics.modernmedicine.com/dr
ugtopics/data/articlestandard//drugtopics/
192009/597086/article.pdf
The top 200 drugs can be useful to give guidance on prescribing patterns
throughout the United States and provide an avenue to teach students. Below is
a table that can be converted into a poster for the “Top 100 Branded Drugs By
Total Prescriptions” with brand/generic names, chemical structure, indications
and usages, black box warnings, and total prescriptions. Feel free to use the
poster as an educational tool.
See attached PDF Table
The Drug Information Letter is a publication of the Center for Drug Information and Research,
LECOM School of Pharmacy, Erie, PA 16509
Editors:
Sana R. Sukkari, B.Sc.Pharm., M.Phil
LECOM School of Pharmacy
G. Elliott Cook, Pharm.D., BCPS
LECOM School of Pharmacy
Erin Brown, Pharm.D.
LECOM School of Pharmacy
Larry D. Sasich, Pharm.D., MPH, FASHP
LECOM School of Pharmacy
Steven Levy, MD, FACP
LECOM College of Medicine
Matt Madurski
Communications Assistant / Media Relations
LECOM College of Medicine
Ashok Philip, Ph.D.
LECOM School of Pharmacy
© Lake Erie College of Osteopathic Medicine. All material subject to this copyright may be
photocopied or digitally reproduced only for noncommercial educational and scientific uses.
Please contact the editor in writing for permission to reprint articles or portions of articles. Proper
credit and copyright must accompany all reprinted material.
Opinions expressed by individuals in this publication do not necessarily represent the official
position of the School of Pharmacy Lake Erie College of Osteopathic Medicine unless otherwise
noted.
2008 Top 100 Branded Drugs By Total Prescriptions
Ashok Philip, Ph.D., G. Elliott Cook, Pharm.D., BCPS
1
LIPITOR
(atorvastatin calcium)
2
NEXIUM
(esomeprazole magnesium)
3
LEXAPRO
(escitalopram oxalate)
4
SINGULAIR
(montelukast sodium)
5
PLAVIX
(clopidogrel bisulfate)
6
SYNTHROID
(levothyroxine sodium)
7
PREVACID
(lansoprazole)
8
9
ADVAIR DISKUS
(fluticasone propionate & salmeterol)
EFFEXOR XR
(venlafaxine hydrochloride)
10
HOOC
N
MOA
* Selective competitive inhibitor of HMGCoA reductase
ZETIA
(ezetimibe)
Rxs: 26,267,000
Rxs:25,787,000
Rxs: 25,148,000
Rxs: 23,113,000
Rxs: 18,632,000
Rxs: 16,910,000
Indications and Usage
* Treatment of GERD
* Risk reduction of NSAID- associated
Gastric Ulcer
* H. pylori eradication to reduce the risk of
Duodenal Ulcer Recurrence
* Pathological hypersecretory conditions
Including Zollinger-Ellison (Z-E) Syndrome
Indications and Usage
* Major Depressive Disorder
* Generalized Anxiety Disorder
Indications and Usage
* Prophylaxis and chronic treatment of
asthma
* Prevention of exercise-induced
bronchoconstriction
* Relief of symptoms of allergic rhinitis,
and perennial allergic rhinitis
Indications and Usage
* Reduction of atherothrombotic events:
Recent MI, Recent Stroke or Established
Peripheral Arterial Disease and Acute
Coronary Syndromes
Indications and Usage
* Hypothyroidism
* Pituitary TSH Suppression
Indications and Usage
* Short-Term Treatment of Active
Duodenal Ulcer (DU)
* H. pylori Eradication to Reduce Risk of
DU Recurrence
* Maintenance of Healed DU
* Short-Term Treatment of Active Benign
Gastric Ulcer(GU)
* Healing of NSAID-Associated GU
* Risk Reduction of NSAID-Associated
GU
* GERD
* Maintenance of Healing of Erosive
Esophagitis (EE)
* Pathological Hypersecretory Conditions
Including Z-E Syndrome
Indications and Usage
* Major Depressive Disorder
* Generalized Anxiety Disorder
* Social Anxiety Disorder
* Panic Disorder
MOA
* Proton pump inhibitor that suppresses
gastric acid secretion by inhibiting the
+ +
gastric H /K ATPase at the secretory
surface of gastric parietal cells
22
MOA
* Escitalopram (S-enantiomer of racemic
citalopram) inhibits CNS reuptake of
serotonin (5-HT)
BLACK BOX WARNING
* Increase risk of suicidal thinking and
suicidality in children, adolescents, and
young adults
TRICOR
(fenofibrate)
23
CELEBREX
(celecoxib)
MOA
* Inhibits physiologic actions of LTD4 at
CysLT1 receptor
MOA
* A synthetic T4 that binds to thyroid
receptor attached to DNA
MOA
* The active metabolite irreversibly inhibits
binding of ADP to its platelet P2Y12
BLACK BOX WARNING
receptor thereby inhibiting platelet
* Do not use for the treatment of obesity
aggregation
or for weight loss
24
NASONEX
(mometasone furoate monohydrate)
25
PREMARIN
(conjugated estrogens)
26
LANTUS
(insulin glargine)
27
VIAGRA
(sildenafil citrate)
Rxs: 17,820,000
Indications and Usage
* Maintenance Treatment of Asthma
* Maintenance Treatment of Chronic
Obstructive Pulmonary Disease
MOA
* Fluticasone propionate is a synthetic
trifluorinated corticosteroid with potent
anti-inflammatory activity
* Salmeterol is a selective, long-acting
beta2-adrenergic agonist
BLACK BOX WARNING
* Increase risk of asthma-related death
28
YAZ
(Drospirenone and ethinyl estradiol)
Rxs: 10,997,000
MOA
* Ezetimibe reduces blood cholesterol by
inhibiting absorption of cholesterol by
small intestine
Rxs: 10,259,000
Rxs: 10,463,000
Rxs: 10,759,000
Indications and Usage
* Osteoarthritis (OA)
* Rheumatoid Arthritis (RA)
* Juvenile Rheumatoid Arthritis (JRA)
* Ankylosing Spondylitis (AS)
* Acute Pain (AP)
* Primary Dysmenorrhea (PD)
* Familial Adenomatous Polyposis (FAP)
Indications and Usage
* Seasonal allergic and perennial allergic
rhinitis
* Prophylaxis of nasal symptoms of
seasonal allergic rhinitis
* Treatment of nasal polyps
MOA
* A corticosteroid demonstrating antiinflammatory properties
MOA
* An NSAID that selectively inhibits
cyclooxygenase-2 (COX-2)
Rxs: 10,442,000
Indications and Usage
* Treatment: Moderate to severe
vasomotor symptoms and vulvar and
vaginal atrophy due to menopause,
hypoestrogenism due to hypoganidism,
castration or primary ovarian failure,
breast cancer (palliation only), advanced
androgen-dependent carcinoma of
prostate (palliation only)
* Prevention of postmenopausal
osteoporosis
Indications and Usage
Rxs: 10,112,000
* Treatment of adult and pediatric patients
with type 1 diabetes mellitus or adult
Indications and Usage
patients with type 2 diabetes mellitus
* Treatment of erectile dysfunction (ED)
MOA
* Long-acting recombinant human insulin
analog
* Lowers blood glucose levels by
stimulating peripheral glucose uptake,
especially by skeletal muscle and fat, and
by inhibiting hepatic glucose production
* Inhibits lipolysis in adipocyte, inhibits
proteolysis, and enhances protein
synthesis
MOA
* Reduce elevated levels of gonadotropins
(LH and FSH) in postmenopausal women
BLACK BOX WARNING
* Cardiovascular risk
* Gastrointestinal risk
MOA
* Enhances effect of nitric oxide (NO) by
inhibiting phosphodiesterase type 5
(PDE5)
* NO activates guanylate cyclase,
resulting in increased cGMP levels
* cGMP causes smooth muscle relaxation
and increased blood flow into corpus
cavernosum
* PDE5 degrades cGMP
BLACK BOX WARNING
* Endometrial cancer
* Increased risk of MI, stroke, invasive
breast cancer, pulmonary emboli, and
DVT
* Increased risk of dementia
BENICAR HCT
(olmesartan medoxomil and
hydrochlorothiazide)
42
CYMBALTA
(duloxetine hydrochloride)
14
PROAIR HFA
(albuterol sulfate)
15
KLOR-CON
(potassium chloride)
S
LYRICA
(pregabalin)
O
N
Rxs: 13,929,000
N
N
HN
Rxs: 15,684,000
Indications and Usage
* Hypertension
* Heart Failure
* Post-Myocardial Infarction
30
ADDERALL XR
(Dextroamphetamine Sulfate,
Dextroamphetamine saccharate,
Amphetamine sulfate and
Amphetamine aspartate)
31
VALTREX
(valacyclovir hydrochloride)
CH3
Rxs: 14,422,000
Rxs: 15,125,000
Indications and Usage
* Hyperlipidemia and Mixed Dyslipidemia
* Hypertriglyceridemia
MOA
* Homozygous Familial
Rxs: 14,559,000
* Venlafaxine and its active metabolite, OHypercholesterolemia
desmethylvenlafaxine are potent inhibitors MOA
* Slowing of the Progression of
Indications and Usage
of neuronal serotonin and norepinephrine * Blocks vasoconstrictor and aldosterone- Atherosclerosis
* Primary Hyperlipidemia
reuptake and weak inhibitors of dopamine secreting effects of angiotensin II by
* Homozygous Familial
reuptake
selectively blocking binding of angiotensin MOA
Hypercholesterolemia (HoFH)
*
Selective
and
competitive
inhibitor
of
II to the AT1 receptor in tissues, such as
BLACK BOX WARNING
vascular smooth muscle and the adrenal HMG-CoA reductase
MOA
* Increase risk of suicidal thinking and
gland
* Ezetimibe reduces blood cholesterol by
suicidality in children, adolescents, and
inhibiting absorption of cholesterol by
young adults
BLACK BOX WARNING
small intestine
* Use in pregnancy can cause injury and
* Simvastatin (a prodrug) is hydrolyzed to
its active β-hydroxyacid form (simvastatin
even death to the developing fetus
acid) Simvastatin is a specific inhibitor of
HMG-CoA reductase
29
ARICEPT
(donepezil hydrochloride)
43
ORTHO TRI-CYCLEN LO
(norgestimate and ethinyl estradiol)
44
HYZAAR
(losartan potassium and
hydrochlorothiazide)
45
TRI-SPRINTEC
(norgestimate and ethinyl estradiol)
46
CIALIS
(tadalafil)
47
OXYCONTIN
(oxycodone hydrochloride)
Rxs: 9,962,000
Indications and Usage
* Management of neuropathic pain
associated with diabetic peripheral
neuropathy
* Management of postherpetic neuralgia
* Adjunctive therapy for adult patients with Rxs: 8,799,000
partial onset seizures
Indications and Usage
* Management of fibromyalgia
* Treatment of Attention Deficit
Hyperactivity Disorder (ADHD)
MOA
Indications and Usage
* Prevention of pregnancy (Oral
contraception)
* Treatment of symptoms of premenstrual * Binds with high affinity to alpha2-delta
dysphoric disorder (PMDD)
subunit of voltage-gated calcium channels
and inhibits release of excitatory
MOA
neurotransmitter
ethinyl estradiol:
* Act by suppression of gonadotropins
* Primarily act by inhibition of ovulation
* Changes in cervical mucus and
endometrium
drospirenone:
* Spiranolactone analog with
antimineralocorticoid activity
* Exhibits antiandrogenic activity
BLACK BOX WARNING
* Smoking increases the risk of serious
cardiovascular side effects
48
ACIPHEX
(rabeprazole sodium)
49
LUNESTA
(eszopiclone)
MOA
* Non-catecholamine sympathomimetic
amines with CNS stimulant activity
* Amphetamines block reuptake of
norepinephrine and dopamine into
presynaptic neuron and increase release
of these monoamines into extraneuronal
space
32
COZAAR
(losartan potassium)
Rxs: 8,521,000
Indications and Usage
* Herpes Zoster
* Genital Herpes
* Cold Sores (Herpes Labialis)
MOA
* Rapidly converted to acyclovir
* Competitive inhibition of viral DNA
polymerase
* Incorporation and termination of the
growing viral DNA chain
* Inactivation of viral DNA polymerase
Indications and Usage
* Major Depressive Disorder
* Generalized Anxiety Disorder
* Diabetic Peripheral Neuropathic Pain
* Fibromyalgia
MOA
* Potent inhibitor of neuronal serotonin
and norepinephrine reuptake
BLACK BOX WARNING
* Increase risk of suicidal thinking and
suicidality in children, adolescents, and
young adults
33
TOPAMAX
(topiramate)
LAMICTAL
(lamotrigine)
Rxs: 8,389,000
Indications and Usage
* Bronchospasm
* Exercise-Induced Bronchospasm
MOA
* A beta2-adrenergic agonist
* Activation of beta2-adrenergic receptors
leads to activation of adenylcyclase and to
an increase in intracellular concentration
of cAMP. This increase of cAMP is
associated with activation of protein
kinase A, which in turn inhibits
phosphorylation of myosin and lowers
intracellular ionic calcium concentrations,
resulting in muscle relaxation
34
CONCERTA
(Methylphenidate hydrochloride)
Indications and Usage
* Hypertension
* Hypertensive patients with left
ventricular hypertrophy
* Nephropathy in type 2 diabetic patients
MOA
* Blocks vasoconstrictor and aldosteronesecreting effects of angiotensin II by
selectively blocking binding of angiotensin
II to the AT1 receptor in tissues, such as
vascular smooth muscle and the adrenal
gland
Rxs: 7,888,000
Rxs: 7,863,000
Indications and Usage
* Monotherapy - Epilepsy
* Adjunctive Therapy - Epilepsy
* Migraine prophylaxis
Indications and Usage
* Attention Deficit Hyperactivity Disorder
(ADHD)
MOA
* Blocks voltage-dependent sodium
channels
* Augments activity of GABA at some
subtypes of GABA-A receptor
* Antagonizes AMPA/kainate subtype of
the glutamate receptor
* Inhibits carbonic anhydrase enzyme,
particularly isozymes II and IV
17
LEVAQUIN
(levofloxacin)
18
ACTOS
(pioglitazone hydrochloride)
Indications and Usage
* Hypokalemia with or without metabolic
acidosis
* Digitalis intoxication
* Hypokalemic periodic familial periodic
paralysis
* Prevention of Hypokalemia
MOA
+
* K the principal intracellular cation
participates in a number of essential
physiological processes that include
maintenance of intracellular tonicity,
transmission of nerve impulses,
contraction of cardiac, skeletal and
smooth muscle maintenance of normal
renal function
35
LEVOXYL
(levothyroxine sodium)
51
DETROL LA
(tolterodine tartrate)
52
CHANTIX
(varenicline tartrate)
MOA
* A racemic mixture comprised of the Dand L-isomers
* D-isomer is more pharmacologically
active than L-isomer
* Block reuptake of norepinephrine and
dopamine into presynaptic neuron and
increase release of these monoamines
into extraneuronal space
Rxs: 7,745,000
Indications and Usage
* Hypothyroidism
* Pituitary TSH Suppression
MOA
* A synthetic T4 that binds to thyroid
receptor attached to DNA
BLACK BOX WARNING
* Do not use for the treatment of obesity
or for weight loss
Rxs:12,898,000
Rxs:13,196,000
Indications and Usage
* Hypertension
Indications and Usage
* Nosocomial Pneumonia
* Community-Acquired Pneumonia
* Acute Bacterial Sinusitis
* Acute Bacterial Exacerbation of Chronic
Bronchitis
* Complicated & Uncomplicated Skin and
Skin Structure Infections
* Chronic Bacterial Prostatitis
* Complicated & Uncomplicated Urinary
Tract Infections
* Acute Pyelonephritis
* Inhalational Anthrax (Post-Exposure)
19
FLOMAX
(tamsulosin hydrochloride)
MOA
* Valsartan blocks vasoconstrictor and
aldosterone-secreting effects of
angiotensin II by selectively blocking the
binding of angiotensin II to the AT1
receptor in tissues, such as vascular
smooth muscle and the adrenal gland
* Hydrochlorothiazide affects renal
MOA
tubular mechanisms of electrolyte
* Inhibition of bacterial topoisomerase IV
reabsorption, directly increasing excretion and DNA gyrase
of Na and Cl in approximately equivalent
amounts
BLACK BOX WARNING
Increased risk of tendinitis and tendon
BLACK BOX WARNING
rupture
* Use in pregnancy can cause injury and
even death to the developing fetus
37
AMBIEN CR
36
ACTONEL
(zolpidem tartrate)
(risedronate sodium)
Rxs: 7,261,000
Indications and Usage
* Postmenopausal Osteoporosis
* Osteoporosis in Men
* Glucocorticoid-Induced Osteoporosis
* Paget's Disease
MOA
* Exhibits affinity for hydroxyapatite
crystals in bone and acts as an
antiresorptive agent
* At cellular level inhibits osteoclasts
Rxs:12,518,000
Rxs:11,576,000
Indications and Usage
* Adjunct to diet and exercise to improve
glycemic control in adults with type 2
diabetes mellitus
Indications and Usage
* Treatment of signs and symptoms of
benign prostatic hyperplasia (BPH)
MOA
* Potent agonist for peroxisome
proliferator-activated receptor-gamma
(PPARγ)
53
AVAPRO
(irbesartan)
54
PROVENTIL HFA
(albuterol sulfate)
55
ABILIFY
(aripiprazole)
56
YASMIN 28
(drospirenone and ethinyl estradiol)
MOA
* A selective alpha1A adrenoceptor
blocking agent in the human prostate.
Approximately 70% of the alpha1receptors in human prostate are of the
alpha1A subtype
BLACK BOX WARNING
* May cause or exacerbate congestive
heart failure
* Not recommended in patient with
symptomatic heart failure
20
SEROQUEL
(quetiapine fumarate)
38
SPIRIVA
(tiotropium bromide monohydrate)
39
BENICAR
(olmesartan medoxomil)
40
XALATAN
(latanoprost)
Rxs: 6,251,000
Indications and Usage
Rxs: 7,121,000
* Treatment of insomnia, characterized by
difficulties with sleep onset and/or sleep
Indications and Usage
maintenance
* Maintenance treatment of
bronchospasm associated with chronic
MOA
obstructive pulmonary disease (COPD),
* Binds the BZ1 receptor preferentially
including chronic bronchitis and
with a high affinity ratio of the
emphysema
alpha1/alpha5 subunits
MOA
* Long-acting, antimuscarinic agent
* In the airways inhibits M3-receptors at
the smooth muscle leading to
bronchodilation
BUDEPRION XL
(bupropion)
Indications and Usage
* Depressive episodes associated with
bipolar disorder
* acute manic episodes associated with
bipolar I disorder as either monotherapy
or adjunct therapy to lithium or divalproex
* Schizophrenia
MOA
* Atypical antipsychotic with D2 and 5HT2A antagonism
Also antagonizes H1, alpha 1 and alpha 2
receptors
Rxs: 7,214,000
57
Rxs:11,509,000
BLACK BOX WARNING
* Increased mortality in elderly patients
with dementia-related psychosis
* Increase risk of suicidal thinking and
suicidality in children, adolescents, and
young adults
BLACK BOX WARNING
* Drug dependence, use with caution in
patients with a history of drug dependence
or alcoholism
BLACK BOX WARNING
* Use in pregnancy can cause injury and
even death to the developing fetus
BLACK BOX WARNING
* High potential for abuse
* Misuse may cause sudden death and
serious cardiovascular adverse effects
50
16
DIOVAN HCT
(valsartan and hydrochlorothiazide)
KCl
Rxs: 13,549,000
Rxs: 9,845,000
Indications and Usage
* Treatment of Hypercholesterolemia
* Treatment of Hypertriglyceridemia
Indications and Usage
* Primary Hyperlipidemia – Monotherapy, MOA
combination w/ statins, combination w/
* Activates peroxisome proliferator
fenofibrate
activated receptor α (PPARα)
* Homozygous Familial
Fenofibric acid is the active metabolite of
hypercholesterolemia (HoFH)
fenofibrate
* Homozygous Sitosterolemia
Rxs: 11,046,000
41
13
O
OCH3
Rxs: 26,856,000
MOA
+ +
* Specific inhibition of H /K -ATPase
pump in gastric parietal cell
21
VYTORIN
(ezetimibe and simvastatin)
CH3
HN
Indications and Usage
* Prevention of cardiovascular disease
* Hypercholesterolemia
12
CH3
N
H3C
Rxs: 49,043,000
CRESTOR
(rosuvastatin calcium)
CH3
H
N
S
N
11
DIOVAN
(valsartan)
O
H3C
H3CO
58
NIASPAN
(niacin)
Rxs: 6,821,000
Indications and Usage
* Hypertension
Indications and Usage
* Reduction of elevated intraocular
pressure in patients with open-angle
glaucoma or ocular hypertension.
MOA
MOA
* Reduces intraocular pressure (IOP) by
* Blocks vasoconstrictor and aldosteroneincreasing the outflow of aqueous humor
secreting effects of angiotensin II by
selectively blocking binding of angiotensin
II to the AT1 receptor in tissues, such as
vascular smooth muscle and the adrenal
gland
BLACK BOX WARNING
* Use in pregnancy can cause injury and
even death to the developing fetus
59
COMBIVENT
(ipratropium bromide and albuterol
sulfate)
60
JANUVIA
(sitagliptin)
F
F
N
H
H3C
H3C
O
Rxs: 5,381,000
O
Rxs: 6,,214,000
Rxs: 6,235,000
Indications and Usage
* Mild, moderate and severe Alzheimer's
disease
Indications and Usage
* Hypertension
MOA
* Postulated to exert its therapeutic effect
MOA
by enhancing cholinergic function. This is
* Olemesartan:
accomplished by increasing the
Blocks vasoconstrictor and aldosterone- concentration of acetylcholine through
secreting effects of angiotensin II by
reversible inhibition of its hydrolysis by
selectively blocking binding of angiotensin acetylcholinesterase
II to the AT1 receptor in tissues, such as
vascular smooth muscle and the adrenal
gland
* Hydrochlorothiazide:
Affects renal tubular mechanisms of
electrolyte reabsorption, directly
increasing excretion of Na and Cl in
approximately equivalent amounts
BLACK BOX WARNING
* Use in pregnancy can cause injury and
even death to the developing fetus
61
BONIVA
(ibandronate sodium)
NH2 O
N
N
Rxs: 5,221,000
O
62
TRINESSA
(norgestimate and ethinyl estradiol)
Rxs: 5,780,000
Rxs: 6,069,000
Rxs: 6,,021,000
Indications and Usage
* Prevention of pregnancy (Oral
contraception)
MOA
ethinyl estradiol:
* Act by suppression of gonadotropins
* Primarily act by inhibition of ovulation
* Changes in cervical mucus and
endometrium
* norgestimate:
and 17-deacetyl norgestimate (major
serum metabolite) combine high
progestational activity with minimal
intrinsic androgenicity
BLACK BOX WARNING
* Does not protect against HIV infection
(AIDS) and other STDs
63
NUVARING
(etonogestrel and ethinyl estradiol)
Indications and Usage
* Hypertension
* Hypertensive patients with left
ventricular hypertrophy
Indications and Usage
* Prevention of pregnancy (Oral
contraception)
* Treatment of moderate acne vulgaris in
females
MOA
losaratan:
* Blocks vasoconstrictor and aldosteronesecreting effects of angiotensin II by
selectively blocking binding of angiotensin
II to the AT1 receptor in tissues
Hydrochlorothiazide:
* Affects renal tubular mechanisms of
electrolyte reabsorption, directly
increasing excretion of Na and Cl in
approximately equivalent amounts
MOA
ethinyl estradiol:
* Act by suppression of gonadotropins
* Primarily act by inhibition of ovulation
* Changes in cervical mucus and
endometrium
* norgestimate:
and 17-deacetyl norgestimate (major
serum metabolite) combine high
progestational activity with minimal
intrinsic androgenicity
BLACK BOX WARNING
* Use in pregnancy can cause injury and
even death to the developing fetus
BLACK BOX WARNING
* Smoking increases the risk of serious
cardiovascular side effects
64
65
RISPERDAL
(risperidone)
POLYMAGMA PLAIN
Rxs: 5,689,000
Rxs: 5,601,000
Rxs: 5,677,000
Indications and Usage
Indications and Usage
* Management of moderate to severe pain Rxs: 5,675,000
* Treatment of erectile dysfunction
when a continuous, around-the-clock
analgesic is needed for extended period Indications and Usage
* Healing of Erosive or Ulcerative GERD
MOA
of time
* Maintenance of healing of erosive of
* Inhibition of phosphodiesterase type 5
Ulcerative GERD
(PDE5) enhances erectile function by
MOA
* Treatment of Symptomatic GERD
increasing the amount of cGMP.
* Oxycodone is a pure opioid agonist
* Healing of Duodenal Ulcers
* cGMP causes smooth muscle relaxation whose principal therapeutic action is
* Helicobacter pylori eradication to reduce
and increased blood flow into corpus
analgesia
risk of Duodenal Ulcer recurrence
cavernosum
* Treatment of pathological
BLACK BOX WARNING
hypersecretory conditions, including Z-E
* Schedule II, with an abuse liability
syndrome
similar to morphine
* 80 and 160 mg for use in opioid-tolerant
MOA
patients only
* Not intended for use as a PRN analgesic * Proton pump inhibitor that suppresses
gastric acid secretion by inhibiting the
* Swallow whole, not to be broken,
+ +
gastric H /K -ATPase at the secretory
chewed or crushed
surface of gastric parietal cells
Rxs: 5,423,000
Rxs: 5,622,000
Indications and Usage
Indications and Usage
* Epilepsy:
* Treatment of overactive bladder with
Indications and Usage
Adjunctive Therapy: Partial seizures,
* Treatment of insomnia, decreased sleep Primary generalized tonic-clonic seizures, symptoms of urge urinary incontinence,
latency and improved sleep maintenance Generalized seizures of Lennox-Gastaut urgency, and frequency
syndrome
MOA
Monotherapy: Conversion to monotherapy MOA
* Tolterodine and its active metabolite 5* Nonbenzodiazepine hypnotic of the
in adults with partial seizures
hydroxymethyl are competitive muscarinic
cyclopyrrolone class
receptor antagonists
* Effect is believed to result from
MOA
interaction with GABA-receptor complexes * Inhibits voltage-sensitive sodium
at binding domains located closely to or
channels and thereby stabilizing neuronal
allosterically coupled to benzodiazepine membranes and consequently modulating
receptors
release of presynaptic excitatory amino
Rxs: 5,243,000
Indications and Usage
* Aid to smoking cessation treatment
MOA
* Binds with high affinity and selectivity at
α4β2 neuronal nicotinic acetylcholine
receptors
* The efficacy of CHANTIX in smoking
cessation is believed to be the result of its
agonistic effects at the nicotinic receptor,
while simultaneously preventing nicotine
binding to α4β2 receptors
acids (Glutamate and Aspartate)
BLACK BOX WARNING
* Serious skin rashes
Indications and Usage
* Bronchospasm
* Exercise-Induced Bronchospasm
Rxs: 5,330,000
MOA
* A beta2-adrenergic agonist
Indications and Usage
* Activation of beta2-adrenergic receptors
* Hypertension
leads to activation of adenylcyclase and to
* Nephropathy in Type 2 Diabetic Patients
an increase in intracellular concentration
of cAMP. This increase of cAMP is
MOA
associated with activation of protein
* Blocks vasoconstrictor and aldosteronekinase A, which in turn inhibits
secreting effects of angiotensin II by
phosphorylation of myosin and lowers
selectively blocking binding of angiotensin
intracellular ionic calcium concentrations,
II to the AT1 receptor in tissues, such as
resulting in muscle relaxation
vascular smooth muscle and the adrenal
gland
BLACK BOX WARNING
* Use in pregnancy can cause injury and
even death to the developing fetus
Indications and Usage
* Schizophrenia
* Bipolar Disorder
* Adjunctive Treatment of Major
Depressive Disorder
* As an injection for agitation Associated
with Schizophrenia or Bipolar Mania
MOA
* Mediated through a combination of
partial agonist activity at D2 and 5-HT1A
receptors and antagonist activity at 5HT2A receptors
F
N
Rxs: 5,083,000
Rxs: 5,146,000
Indications and Usage
* Major depressive disorder
Rxs: 5,157,000
Indications and Usage
* Prevention of pregnancy (Oral
contraception)
BLACK BOX WARNING
* Increased mortality in elderly patients
with dementia-related psychosis
* Increase risk of suicidal thinking and
suicidality in children, adolescents, and
young adults
MOA
ethinyl estradiol:
* Act by suppression of gonadotropins
* Primarily act by inhibition of ovulation
* Changes in cervical mucus and
endometrium
drospirenone:
* Spiranolactone analog with
antimineralocorticoid activity
* Exhibits antiandrogenic activity
75
76
MOA
* Weak inhibitor of neuronal uptake of
norepinephrine and dopamine
BLACK BOX WARNING
* Increase risk of suicidal thinking and
suicidality in children, adolescents, and
young adults
MOA
* Partial inhibition of release of free fatty
acids from adipose tissue
* Increases lipoprotein lipase activity,
which may increase the rate of
chylomicron triglyceride removal from
plasma
77
78
N
CF3
Indications and Usage
* Primary hyperlipidemia
* Mixed dyslipidemia
* Reduce risk of recurrent non-fatal
myocardial infarction
Rxs: 4,878,000
* Slow progression or promote regression
of atherosclerotic disease
Indications and Usage
* Severe hypertriglyceridemia
* COPD on a regular aerosol
bronchodilator who continue
to have
evidence of bronchospasm and who
require a second bronchodilator
Rxs: 4,868,000
Indications and Usage
* Monotherapy and Combination Therapy
to improve glycemic control in type 2
diabetes mellitus
MOA:
* DPP 4 inhibitor
* DPP 4 is the primary protease
responsible for degrading incretin
hormones (GLP-1 and GIP)
MOA:
* ipratropium bromide:
Anticholinerigic agent
* albuterol:
β2 adrenergic agonist
BLACK BOX WARNING
* Smoking increases the risk of serious
cardiovascular side effects
66
FLOVENT HFA
(fluticasone propionate)
67
IMITREX
(sumatriptan succinate)
68
EVISTA
(raloxifene hydrochloride)
69
AVELOX
(moxifloxacin hydrochloride)
70
DEPAKOTE ER
(divalproex sodium)
71
PROTONIX
(pantoprazole sodium)
72
AVALIDE
(irbesartan and hydrochlorothiazide)
73
LIDODERM
(Lidocaine)
74
ZYPREXA
(olanzapine)
NAMENDA
(memantine hydrochloride)
A hydrated silicate of aluminum and
magnesium
TUSSIONEX
(hydrocodone polistirex and
chlorpheniramine polistirex)
ARMOUR THYROID
(thyroid tablets)
HUMALOG
(insulin lispro)
79
VIGAMOX
(moxifloxacin hydrochloride)
80
TAMIFLU
(oseltamivir phosphate)
Rxs: 4,476,000
Indications and Usage
* Management of diarrhea
Rxs: 4,789,000
Indications and Usage
* Treatment and Prevention of
Postmenopausal Osteoporosis
MOA
* Exhibits affinity for hydroxyapatite
crystals in bone and acts as an
antiresorptive agent
* At cellular level inhibits osteoclasts
Rxs: 4,633,000
Rxs: 4,783,000
Rxs: 4,733,000
Indications and Usage
* Prevention of pregnancy (Oral
contraception)
* Treatment of moderate acne vulgaris in
females
Indications and Usage
* Prevention of pregnancy (Oral
contraception)
MOA
ethinyl estradiol:
* Act by suppression of gonadotropins
* Primarily act by inhibition of ovulation
* Changes in cervical mucus and
endometrium
norgestimate:
* norgestimate and 17-deacetyl
norgestimate (major serum metabolite)
combine high progestational activity with
minimal intrinsic androgenicity
Indications and Usage
* Schizophrenia
* Bipolar Mania
* Irritability Associated with Autistic
Disorder
MOA
* Works by adsorbing (binding) large
numbers of bacteria and toxins and
reducing the loss of water
MOA
* Mediated through a combination of
dopamine Type 2 (D2) and serotonin Type
2 (5HT2) receptor antagonism
MOA
* Combination hormonal contraceptives
act by suppression of gonadotropins
* Primary effect of this action is inhibition
of ovulation
BLACK BOX WARNING
* Other alterations include changes in the * Increased mortality in elderly patients
cervical mucus (which increase the
with dementia-related psychosis
difficulty of sperm entry into the uterus)
and the endometrium (which reduce the
likelihood of implantation)
Rxs: 4,313,000
Rxs: 4,400,000
Indications and Usage
* Treatment and rrevention of
Indications and Usage
* Acute treatment of migraine attacks with osteoporosis in postmenopausal women
* Reduction in risk of invasive breast
or without aura in adults
cancer in postmenopausal women with
osteoporosis
MOA
* Reduction in risk of invasive breast
* A selective agonist of vascular 5cancer in postmenopausal women at high
hydroxytryptamine 1 (5-HT1D & 5-HT1B)
risk of invasive breast cancer
receptor family
* Activation of these receptors causes
MOA
MOA
vasoconstriction (an action in humans
* Anti-inflammatory actions of
correlating with the relief of migraine and * A selective estrogen receptor modulator
(SERM)
corticosteroids contribute to their efficacy cluster headache)
* As an estrogen agonist in bone,
in asthma
decreases bone resorption and bone
turnover, increases bone mineral density
(BMD) and decreases fracture incidence
Rxs: 4,403,000
Indications and Usage
* Maintenance treatment of asthma as
prophylactic therapy in patients 4 years of
age and older
* Also indicated for patients requiring oral
corticosteroid therapy for asthma
BLACK BOX WARNING
* Increased risk of venous
thromboembolism and death from stroke
BLACK BOX WARNING
* Smoking increases the risk of serious
cardiovascular side effects
BLACK BOX WARNING
* Smoking increases the risk of serious
cardiovascular side effects
81
BUDEPRION SR
(bupropion)
82
SUBOXONE
(buprenorphine hydrochloride and
naloxone hydrochloride)
Rxs: 4,086,000
Indications and Usage
* Acute bacterial sinusitis
* Acute bacterial exacerbation of chronic
bronchitis
* Community acquired pneumonia
* Complicated and uncomplicated skin
and skin structure infections
* Complicated intra-abdominal infections
MOA
* Inhibits topoisomerase II (DNA gyrase)
and topoisomerase IV required for
bacterial DNA replication, transcription,
repair, and recombination
* C8-methoxy moiety contributes to
enhanced activity and lower selection of
resistant mutants of gram-positive
bacteria
* Bulky bicycloamine substituent at C-7
prevents active efflux
Rxs: 3,860,000
Rxs: 4,059,000
Indications and Usage
* Mania
* Epilepsy
* Migraine
Rxs: 4,023,000
Rxs: 4,044,000
Indications and Usage
MOA
* Short-term treatment of erosive
* Divalproex sodium dissociates to the
esophagitis associated with GERD
valproate ion in gastrointestinal tract
* Maintenance of healing of erosive
* Suggested activity in epilepsy is related esophagitis
to increased brain concentrations of
* Pathological hypersecretory conditions
gamma-aminobutyric acid (GABA)
including Z-E syndrome
BLACK BOX WARNING
* Hepatotoxicity
* Teratogenicity
* Pancreatitis
MOA
* Proton pump inhibitor that suppresses
gastric acid secretion by inhibiting the
+ +
gastric H /K ATPase at the secretory
surface of gastric parietal cells
Indications and Usage
* Hypertension
Indications and Usage
* Relief of pain associated with postherpetic neuralgia
MOA
* Lidocaine is an amide-type local
MOA
anesthetic agent and is suggested to
* Irbesartan:
Blocks vasoconstrictor and aldosterone- stabilize neuronal membranes by
inhibiting the ionic fluxes required for the
secreting effects of angiotensin II by
selectively blocking binding of angiotensin initiation and conduction of impulses
II to the AT1 receptor in tissues, such as
vascular smooth muscle and the adrenal
gland
* hydrochlorthiazide:
Affects renal tubular mechanisms of
electrolyte reabsorption, directly
increasing excretion of Na and Cl in
approximately equivalent amounts
BLACK BOX WARNING
* Use in pregnancy can cause injury and
even death to the developing fetus
LANOXIN
(digoxin)
84
LOESTRIN 24 Fe
(norethindrone acetate and ethinyl
estradiol)
85
AVODART
(dutasteride)
86
COUMADIN
(warfarin sodium)
87
WELLBUTRIN XL
(bupropion)
88
ENDOCET
(acetaminophen and oxycodone)
* Increased risk of tendinitis and tendon
rupture
89
SKELAXIN
(metaxalone)
90
NASACORT AQ
(triamcinolone acetonide)
91
KEPPRA
(levetiracetam)
Rxs: 3,806,000
Indications and Usage
* Schizophrenia
* Bipolar I Disorder (Manic or Mixed
Episodes)
* ZYPREXA IntraMuscular: Agitation
Associated with Schizophrenia and
Bipolar I Mania
* ZYPREXA and Fluoxetine in
Combination: Depressive Episodes
Associated with Bipolar I Disorder
* ZYPREXA and Fluoxetine in
Combination: Treatment Resistant
Depression
Indications and Usage
* Treatment of moderate to severe
dementia of the Alzheimer's type
Rxs: 3,722,000
Rxs: 3,738,000
Rxs: 3,789,000
MOA
* A low to moderate affinity uncompetitive Indications and Usage
(open-channel) NMDA receptor antagonist * Relief of cough and upper respiratory
which binds preferentially to the NMDA
symptoms associated with allergy or a
receptor-operated cation channels
cold in adults and children 6 years of age
and older
Indications and Usage
* Replacement or supplemental therapy in
patients with hypothyroidism of any
etiology, except transient hypothyroidism
during the recovery phase of subacute
thyroiditis
* In the treatment or prevention
of various types of euthyroid goiters
MOA
* As diagnostic agents in suppression
* A semisynthetic narcotic antitussive and tests to differentiate suspected mild
analgesic and is believed to act directly on hyperthyroidism or thyroid gland
the cough center
autonomy
* Chlorpheniramine is an H1 receptor
antagonist that also possesses
MOA
anticholinergic and sedative activity
* A natural T3 and T4 that binds to thyroid
receptor attached to DNA
MOA
* Efficacy in Schizophrenia is mediated
through a combination of dopamine and
serotonin type 2 (5HT2) antagonism
* MOA of in the treatment of acute manic
or mixed episodes associated with
Bipolar I Disorder is unknown
93
92
ALLEGRA-D 12 Hour
(fexofenadine HCl and pseudophedrine
HCl)
STRATTERA
(atomoxetine HCl)
94
LOVAZA
(omega-3-acid ethyl esters)
Indications and Usage
* Treatment of patients with diabetes
mellitus for the control of hyperglycemia
Rxs: 3,545,000
Indications and Usage
* Treatment of bacterial conjunctivitis
MOA
MOA
* Inhibits topoisomerase II (DNA gyrase)
* A rapid-acting agent
and topoisomerase IV required for
* Regulation of glucose metabolism
* In muscle and other tissues (except the bacterial DNA replication, transcription,
brain): Causes rapid transport of glucose repair, and recombination
& amino acids intracellularly, promotes
anabolism, and inhibits protein catabolism
* In the liver: Promotes uptake and
storage of glucose in form of glycogen,
inhibits gluconeogenesis, and promotes
conversion of excess glucose into fat
Rxs: 3,468,000
Indications and Usage
* Treatment of Influenza
* Prophylaxis of Influenza
MOA
* An ethyl ester prodrug requiring ester
hydrolysis for conversion to the active
form, oseltamivir carboxylate
* Oseltamivir carboxylate is an inhibitor of
influenza virus neuraminidase
BLACK BOX WARNING
* Do not use for the treatment of obesity
or for weight loss
BLACK BOX WARNING
* Increased mortality in elderly patients
with dementia-related psychosis
BLACK BOX WARNING
83
Rxs: 3,813,000
95
AVANDIA
(rosiglitazone)
96
OCELLA
(drospirenone and ethinyl estradiol)
97
VYVANSE
(lisdexamfetamine dimesylate)
98
TOPROL XL
(metoprolol succinate)
99
LEVITRA
(vardenafil)
100
ASTELIN
(azelastine HCl)
Rxs: 3,088,000
Indications and Usage
* Major depressive disorder
MOA
* Weak inhibitor of neuronal uptake of
norepinephrine and dopamine
BLACK BOX WARNING
* Increase risk of suicidal thinking and
suicidality in children, adolescents, and
young adults
Rxs: 3,439,000
Indications and Usage
* Treatment of opioid dependence
MOA
* buprenorphine:
Partial opioid agonist at μ and Κ receptors
* naloxone:
Non-specific opioid antagonist
Indications and Usage
* Mild to moderate heart failure
* Control of ventricular response rate in
patients with chronic atrial fibrillation
MOA
* Inhibits sodium-potassium ATPase, an
enzyme that regulates the quantity of
sodium and potassium inside cells
Rxs: 3,218,000
Rxs: 3,303,000
Rxs: 3,385,000
Rxs: 3,462,000
Rxs: 3,315,000
Rxs: 3,379,000
Indications and Usage
* Prevention of pregnancy (Oral
contraception)
MOA
* Act by suppression of gonadotropins
* Primarily act by inhibition of ovulation
* Changes in cervical mucus and
endometrium
BLACK BOX WARNING
* Smoking increases the risk of serious
cardiovascular side effects
Indications and Usage
* Monotherapy; Treatment of symptomatic
benign prostatic hyperplasia (BPH) in men
with an enlarged prostate
* Combination: With alpha-blocker
tamsulosin is indicated for treatment of
symptomatic BPH in men with an
enlarged prostate
Indications and Usage
* Prophylaxis and/or treatment of venous
thrombosis and its extension, and
pulmonary embolism
* Prophylaxis and/or treatment of
thromboembolic complications associated
with atrial fibrillation and/or cardiac valve
replacement
* To reduce risk of death, recurrent
myocardial infarction, and thromboembolic
events such as stroke or systemic
embolization after myocardial infarction
Indications and Usage
* Adjunct to rest, physical therapy, and
other measures for relief of discomforts
associated with acute, painful
musculoskeletal conditions
Rxs: 3,301,000
Rxs: 3,255,000
Indications and Usage
* Major depressive disorder
Indications and Usage
* Moderate to severe pain
MOA
* Weak inhibitor of neuronal uptake of
norepinephrine and dopamine
MOA
* oxycodone: A semisynthetic pure opioid MOA
agonist whose principal therapeutic action * May be due to general central nervous
system depression
is analgesia
* acetaminophen: A non-opiate, nonsalicylate analgesic and antipyretic
* Site and mechanism for analgesic effect
of acetaminophen has not been
determined
* Antipyretic effect of acetaminophen is
accomplished through inhibition of
endogenous pyrogen action on
hypothalamic heat-r egulating centers
BLACK BOX WARNING
MOA
* Increase risk of suicidal thinking and
* A competitive and non-selective inhibitor
suicidality in children, adolescents, and
of type 1 and type 2 5α-reductase
young adults
MOA
* Conversion of testosterone to
* Inhibit synthesis of vitamin K dependent
dihydrotestosterone (DHT) is inhibited
clotting factors (Factors II, VII, IX and X)
* DHT (androgen) primarily responsible for
and anticoagulant proteins C and S
initial development and subsequent
enlargement of prostate gland
BLACK BOX WARNING
Bleeding risk
Rxs: 3,126,000
Rxs: 3,195,000
Rxs: 3,206,000
Indications and Usage
* Treatment of nasal symptoms of
seasonal and perennial allergic rhinitis
MOA
* A corticosteroid demonstrating antiinflammatory properties
Indications and Usage
* Treatment of partial onset seizures
* Treatment of myoclonic seizures
* Treatment of primary generalized tonicclonic seizures
MOA
* Thought to interact with SV2A protein
which may contribute to antiepileptic
action
Rxs: 3,138,000
Rxs: 3,130,000
Indications and Usage
* Seasonal allergic rhinitis
Indications and Usage
* ADHD
MOA
* fexofenadine: Selective peripheral H1
receptor antagonist
* pseudophedrine: Mixed acting
sympathomimetic which exerts a nasal
decongestant action
MOA
* Thought to be related to selective
inhibition of pre-synaptic norepinephrine
transporter
BLACK BOX WARNING
* Suicidal ideation in children and
adolescents
Indications and Usage
* Adjunct to diet to reduce triglyceride
levels
Rxs: 3,103,000
Indications and Usage
* ADHD
Indications and Usage
* To improve glycemic control in adults
with type 2 diabetes
MOA
MOA
* Highly selective and potent agonist for
* Inhibition of acyl CoA: 1,2-diacylglycerol
the peroxisome proliferator-activated
acyl transferase, increased mitochondrial
receptor-gamma (PPARγ)
and peroxisomal β-oxidation in liver,
decreased lipogenesis in liver and
BLACK BOX WARNING
increased plasma lipoprotein lipase
* May cause or exacerbate congestive
activity
heart failure
* Not recommended in patient with
symptomatic heart failure
* Increase risk of MI
Rxs: 3,091,000
Indications and Usage
* Prevention of pregnancy (Oral
contraception)
MOA
ethinyl estradiol:
* Act by suppression of gonadotropins
* Primarily act by inhibition of ovulation
* Changes in cervical mucus and
endometrium
drospirenone:
* Spiranolactone analog with
antimineralocorticoid activity
* Exhibits antiandrogenic activity
BLACK BOX WARNING
*Smoking increases the risk of serious
cardiovascular side effects
References:
Drug Topics. 2008 Top 200 branded
drugs by total prescriptions. At:
http://drugtopics.modernmedicine.com
/drugtopics/data/articlestandard//drugt
opics/222009/599845/article.pdf.
Accessed: July, 21, 2009.
DailyMed. Professional Product Labels
accessed at:
http://dailymed.nlm.nih.gov/dailymed/a
bout.cfm.
MOA
* Prodrug of dextroamphetamine
* Amphetamines block reuptake of
norepinephrine and dopamine into
presynaptic neuron and increase release
of these monoamines into extraneuronal
space
BLACK BOX WARNING
* High potential for abuse
* Misuse may cause sudden death and
serious cardiovascular adverse effects
Rxs: 2,812,000
Rxs: 3,060,000
Indications and Usage
* Hypertension
* Angina pectoris
* Heart failure
MOA
*Selective β1-blocker
Rxs: 2,835,000
Indications and Usage
* ED
Indications and Usage
* Seasonal allergic rhinitis
* Vasomotor rhinitis
MOA
* H1 receptor antagonist
* Major metabolite desmethyl azelastine
also possess H1 receptor antagonism
MOA
* Inhibition of phosphodiesterase type 5
(PDE5) enhances erectile function by
increasing the amount of cGMP.
* cGMP causes smooth muscle relaxation
and increased blood flow into corpus
cavernosum