World of Drug Information - University of Iowa

World of Drug Information
Division of
Drug Information Service
In this Issue…
1
CURRENT
CLINICAL ISSUES
– SEARCH
STRATEGIES
5
NEW MOLECULAR
ENTITIES AND
BIOLOGICALS
Volume 21 Issue 3 September 2010
IDIS/Web Search Strategies for an
Integration of Pharmacogenetics into
Pharmacy Practice
Pharmacogenetics and pharmacogenomics is a fast growing field that has implications
for patients’care and health care professionals. The two terms are sometimes used
interchangeably although there are some differences in the definitions. Pharmacogenetics is
the study of inherited differences in drug response, whereas pharmacogenomics is the
“genome-wide analysis of genetic determinants of drug efficacy and toxicity”. 1 Genetic
testing is a step toward the practice of personalized medicine in the sense that it tailors a
medical treatment to the genetic characteristics of each patient. Better disease diagnosis and
early interventions, selective optimal therapy, enhancement of drug safety, and potential
About the Author:
health care cost saving are some of the benefits of personalized
medicine but the integration of pharmacogenetics into the
clinical setting is still a challenge. 2,3
The pharmacists working in the Division of Drug
Information Service at the University of Iowa have gathered
and indexed information for IDIS/Web from several types of
sources that are useful in answering questions related to
pharmacogenetics and pharmacogenomics. In 1995 IDIS added
a descriptor, “PHARMACOGENETICS 150”, to specifically
code articles pertaining to “the relationship between genetic
factors and the nature of responses to drugs.” Prior to 1995, the
concept was covered under a much broader descriptor
“MODIFICATION OF EFFECT 42”.
The IDIS database currently contains over 7,000 entries
indexed under the descriptor “PHARMACOGENETICS 150”.
The number of citations added to the database from 2005 to
2009 (3,309 hits) has almost doubled when compared to the
previous 5 years.
Representative examples on how you can best use
IDIS/Web to answer questions related to pharmacogenetics and
pharmacogenomics are presented below.
Searching IDIS for a pharmacogenetic
pharmacogenomic primer
If your goal is to locate example articles in which the
author used the term in the title, you may use truncation, e.g.
“pharmacog*” entered in the Title field on the search screen.
This allows retrieval of both pharmacogenetic
1
and
pharmacogenomic citations (568 hits).
Dr. ThaiBinh Ton-That, a
registered pharmacist, joined
the IDIS staff in 1984. She
earned a “Diplome National De
Pharmacien” from the “Faculte
Mixte de Medecine et de
Pharmacy” of Grenoble,
France and a Doctor of
Pharmacy degree from the
University of Southern
California. Her responsibilities
at IDIS include supervision of
indexing for the database,
indexing articles, providing
assistance to subscribers and
maintaining the disease
vocabulary.

Genetics is a rapidly evolving area, the most
recently published information can be
retrieved by restricting the “Year” field range
to 2010 (move the cursor down to Year field
and enter 2010 in “From” and “To” box).
The use of the descriptor “REVIEW” will
narrow the results further and restrict to
review articles (click Descriptor/Look Up
button to open the Descriptor list, scroll
down to “REVIEW”, select “REVIEW
ADULT”, “REVIEW PEDIATRIC”, and
“REVIEW GERIATRIC”, change the logic
operator to “OR” and hit “Submit” to paste
your selections in the Descriptor field of the
search screen). To finalize the search from
the search screen click the search button.
This search retrieves 12 articles that appear
relevant. Of particular interest are the 2
articles by Lee KC et al. and Gervasini G et
al. dealing with general pharmacogenomic concepts; the
applicability and impact of pharmacogenetic testing in a
clinical setting. 1,4
Searching IDIS for Genetic variants
and side effects
Tamoxifen use has been associated with
an increased risk of thromboembolism in patients
with hormone receptor-positive breast cancer and
women at high risk for the disease. Recently a
gene mutation has been identified as being a
significant risk factor in the incidence of this
serious complication. 5 An IDIS search
conducted with the term “tamoxifen” in the Drug
field and “PHARMACOGENETICS 150” in the
Descriptor field yields 155 hits relevant to
genetic variants in correlation with tamoxifen
effectiveness and side effects in general. An
additional descriptor is required in order to
restrict to drug-related thromboembolism side effect.
The use of IDIS Thesaurus identifies “SIDE EF
CARDIOVASCULAR 82” as the correct descriptor
search term for thromboembolism (for more information
about the correct use of the Thesaurus please refer to:
http://www.uiowa.edu/~idis/webtutorial/thesaur1.htm). By combining
the above search with “SIDE EF CARDIOVASCULAR
82” in the Descriptor field, 6 citations are found, with
two citations pertinent to the above news item. 5,6
2

Searching IDIS for Pharmacogenetics, Black Box Warning and FDA Label Revision
As new evidence of the implication of pharmacogenetics on drug safety and use emerges, more new drug
applications for US Food and Drug administration (FDA) review include pharmacogenomic data. 7,8 About 10% of
the FDA approved drugs contain pharmacogenomic information. 10 Genetic testing of patients is necessary before
initiating trastuzumab and dasatinib therapy. Testing is recommended but not required for patients receiving
irinotecan, azathioprine, carbamazepine,
valproic acid, warfarin, carbamazepine,
rasburicase and abacavir. 8-10
A reference table of valid genomic
biomarkers in the context of approved drug
labels is available at the FDA website. 11 The
FDA may initiate a label revision of approved
drugs to incorporate pharmacogenetic
information and genetic testing
recommendations. 9 For example: Label
Revision of Abacavir and Hypersensitivity.
A search conducted with the term
“abacavir” in the Drug field combined with
“SIDE EF IMMUNOLOGIC 90” in the
Descriptor field yields 97 hits. The same
search combined with “FDA BLACK BOX
WARNING 165” in the Descriptor field yields
3 citations. 11-13 The latest search combined
with “PHARMACOGENETICS 150” in the
Descriptor field yields 2 hits. 11,12 Please note
that as indicated in the article title, IDIS article
603279 is a revised version of a previous black
box warning (IDIS Article 555165). 13 Only the
revised version carries pharmacogenetic data in
the label. 12 Also notice that the output display format in the graphic included in this article was adjusted to
“Bibliography” to limit the information in the display. If you adjust the output display to “Full Results” you are able
to see the full abstract for the article which in the case of a boxed warning is the full text of that warning.
The original label of abacavir, a drug approved for HIV in 1998, carries a warning for fatal hypersensitivity
reaction in some patients receiving the drug. A 2008 revised black box warning now includes pharmacogenetic
information with recommendation for genetic testing before starting or re-starting abacavir therapy. Patients who
carry the HLA-B*5701 allele are at increased risk of experiencing a serious hypersensitivity reaction. Abacavir
product label recommends genetic testing prior to initiating treatment.
Whatever drug therapy information is needed in the clinical setting, many of the best resources can be found
in IDIS/Web. The searches presented here are a small sample of the pharmacogenetic information that can be
accessed quickly and accurately. In addition to these resources, the pharmacists at IDIS can be contacted by e-mail or
telephone to offer assistance in formulating a search.
3

References
1. Lee KC, Ma JD, Kuo GM. Pharmacogenomics:
bridging the gap between science and practice. J
Am Pharm Assoc. 2010;50(E1):E1-E17. (IDIS
Article Number 633284)
2. Anonymous. Personalized Medicine Coalition.
http://www.personalizedmedicinecoalition.org/a
bout/about-personalized-medicine/personalizedmedicine-101/promise
Accessed 09/23/2010
3. Ikediobi ON, Shin J, Nussbaum RL, Phillips KA,
et al. Addressing the challenges of the clinical
application of pharmacogenetic testing. Clin
Pharmacol Ther. 2009; 86 (1):28-31. (IDIS
Article Number 625597)
4. Gervasini G, Benitez J, Carrillo JA.
Pharmacogenetic testing and therapeutic drug
monitoring are complementary tools for optima;
individualization of drug therapy. Eur J Clin
Pharmacol. 2010;66(8):755-774. (IDIS Article
Number 641146)
5. Garber JE, Halabi S, Tolaney SM, Kaplan E, et
al. Factor V Leiden mutation and
thromboembolism risk in women receiving
adjuvant tamoxifen for breast cancer. J Natl
Cancer Inst. 2010; 102(13):942-949. (IDIS
Article Number 640790)
6. Cuzick J. Tamoxifen and the factor V Leiden
mutation. J Natl Cancer Inst. 2010;
102(13):918-919. (IDIS Article Number
640789)
7. Frueh FW, Amur S, Mummaneni P, Epstein RS,
et al. Pharmacogenomic biomarker information
in drug labels approved by the United States.
Pharmacotherapy. 2008;28 (8):992-998. (IDIS
Article Number 600114)
8. Haga SB, Thummel KE, Burke W. Adding
pharmacogenetics information to drug labels:
lessons learned. Pharmacogenet Genomics.
2006; 16 (12):847-854. (IDIS Article Number
567652)
9. Anonymous. Pharmacogenomics Knowledge
Base.
http://www.pharmgkb.org/clinical/index.jsp.
Accessed 09/09/2010
10. Anonymous. FDA US Food and Drug
Administration.
http://www.fda.gov/Drugs/ScienceResearch/Res
earchAreas/Pharmacogenetics/ucm083378.htm.
Accessed 9/9/2010.
11. Anonymous. Abacavir sulfate and lamivudine:
FDA black box warning. FDA Black Box
Warning. 2009. (IDIS Article Number 615539)
12. Anonymous. Revised (7/18/2008): Abacavir:
FDA black box warning [IDIS note: to view
outdated warning see article 555165]. FDA
Black Box Warning. 2008. (IDIS Article Number
603279)
13. Anonymous. Outdated: abacavir: FDA black box
warning [IDIS note: to view revised warning see
article 603279] . FDA Black Box Warning.
2004. (IDIS Article Number 555165)
4

New Molecular Entities
& Biologicals
FDA Approvals
June 2010–August 2010
An IDIS search retrieved articles relevant to the new drugs and their approved uses. These articles provide a
selection of key critical studies and reviews. Additional information on these newly approved drugs will be available
in the FDA Approval Package (an official United States Food and Drug Administration [FDA] document) that is
compiled for new drugs following approval. The FDA Approval Package includes reviews of the pivotal and
supportive clinical studies conducted during the approval process. These studies are often not published elsewhere.
FDA Approval Packages are selectively indexed and included as part of the IDIS database as they become available.
Use the descriptor 155 FDA APPROVAL PACKAGE in combination with the valid drug term to retrieve these
documents from the IDIS database.
For some newly approved drugs the FDA Approval Package may not yet be available. If the medication has
been reviewed by one of the FDA Advisory Committees, you may still access data from pivotal studies, even those
that have not been published in peer reviewed literature. These Committee reports are indexed in the IDIS database
using the descriptor “FDA ADVISORY COMMITTEE 164”. In addition to access to data from pivotal studies, these
reports provide critical commentary from the Advisory Committee members, and specific, important questions related
to the use and safety of the medication.
Generic Name
Trade Name
(FDA Review
Classification)
Alcaftadine
Lastacaft
(S)
Cabazitaxel
Jevtana Kit
(P)
Ulipristal acetate
Ella
(S)
Sponsor
(Approval Date)
Vistakon Pharms
LLC
(July 28, 2010)
Sanofi Aventis US
(June 17, 2010)
Laboratoire HRA
Pharma
(Aug. 13, 2010)
Valid IDIS Drug Term
Drug Number
(IDIS Citations)
(0 citations) No published
human studies have been
found for entry into the IDIS
database.
(0 citations) No published
human studies have been
found for entry into the IDIS
database.
ULIPRISTAL
68320008
FDA approved indication
(10 citations)
Total (15 citations)
Indication/Use
Dosage Form
Prevention of itching
associated with allergic
conjunctivitis.
Opthalmic Drops
Prostate cancer.
IV solution
Emergency Contraceptive.
Oral Tablet
Valid IDIS Disease Term
Modified ICD-9-CM
Number
Conjunctivitis, Acute
372.0
Neop, MGN-Prostate
185.
Contraceptive Management
V25.
Review Classification:
S=Standard Review, the drug appears to have therapeutic qualities similar to those of one or more already
marketed drugs.
AA=Accelerated Approval
FT=Fast Track
P=Priority Review, significant improvement compared to marketed products, in the treatment, diagnosis, or
prevention of a disease
BIOL=Biological
O=Orphan
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Selected Bibliography
Ulipristal acetate
Glasier AF, Cameron ST, Fine PM et al. Ulipristal acetate versus levonorgestrel for emergency contraception: a randomised
non-inferiority trial and meta-analysis. Lancet. 2010;375:555-562. (IDIS Article Number 633039)
A total of 1696 women were evaluable for efficacy in this randomized trial in which single oral doses of ulipristal 30 mg (n=844)
or levonorgestrel 1.5 mg (n=852) were given for emergency contraception within 72 hours after unprotected sexual intercourse.
Results were 15 pregnancies in the ulipristal group (1.8%, 95% CI 1.0-3.0) and 22 in the levonorgestrel group (2.6%, 1.7-3.9;
odds ratio [OR] 0.68, 95% CI 0.35-1.31). Headache was the most frequent adverse event in both groups. One serious adverse
event occurred in each group, dizziness in the ulipristal group and a molar pregnancy in the levonorgestrel group.
Creinin MD, Schlaff W, Archer DF et al. Progesterone receptor modulator for emergency contraception: a randomized controlled
trial. Obstet Gynecol.2006;108:1089-1097. (IDIS Article Number 564104)
This randomized, double-blind, controlled, non-inferiority trial of emergency contraception given within 72 hours of unprotected
intercourse included 775 women who received a single oral dose of CDB-2914 (ulipristal) 50 mg plus a placebo 12 hours later,
and 774 women who received two doses of levonorgestrel 0.75 mg given 12 hours apart. Seven pregnancies occurred in the
ulipristal group (0.9%, 95% CI 0.2-1.6) and 13 occurred in the levonorgestrel group (1.7%, 95% CI 0.8-2.6). Nausea was
reported more often by those given ulipristal than those given levonorgestrel, 29% to 24% respectively. Other adverse events,
such as headache, dizziness and fatigue, were similar in both groups.
Dr. Nicola Sarrazin is a 1984 graduate of the University of Iowa (B.A. in Anthropology and Asian
Studies) and a 1997 graduate of the University of Iowa College of Pharmacy (Pharm.D.). Since
that time she has been a pharmacist in the College of Pharmacy’s Division of Drug Information
Service. Nickie’s responsibilities include indexing articles for the IDIS database, overseeing the
Drug vocabulary and contributing articles for the World of Drug Information newsletter.
Division of Drug Information Service
The University of Iowa Research Park
2500 Crosspark Road, Room W145
Coralville, IA 52241-4710 USA
World of Drug Information is published quarterly
(March, June, September, December) by the Division
of Drug Information Service.
Editor-in-Chief…………………………... Dr. Kevin Moores
Assistant Editor………………………..... Mel Smith
Production/Design Coordinator..............Julie Tomash
Iowa Drug Information Service
Telephone: 319-335-4800
US Toll-Free: 800-525-IDIS
Fax: 319-335-4440
E-mail: IDIS@uiowa.edu
Web Site: http://www.uiowa.edu/~idis/
Iowa Drug Information Network
Telephone: 319-335-4800
US Toll-Free: 800-525-4347
Fax: 319-335-4440
E-mail: IDIN@uiowa.edu
Web Site: http://www.uiowa.edu/~idin/
The University of Iowa prohibits discrimination in employment, educational programs, and activities on the basis of race, national origin, color, creed, religion, sex, age,
disability, veteran status, sexual orientation, gender identity, or associational preference. The University also affirms its commitment to providing equal opportunities and
equal access to University facilities. For additional information contact the Office of Equal Opportunity and Diversity, (319) 335-0705 (voice) and (319) 335-0697 (text),
202 Jessup Hall, The University of Iowa, Iowa City, Iowa 52242-1316.
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