World of Drug Information

World of Drug Information - Volume 10, Issue 1 - March 1999

In This Issue ...
 Current Clinical Issues 
 Transnational Alliance 
 Search Tips 
 Perspective From an IDIS Subscriber
 IDIS Welcomes Jordan Cohen 
 Year 2000 Compliance 
 Key References 
 FDA Approvals 
 1999 Exhibit Schedule 
 Staff Profile 

CURRENT CLINICAL ISSUES

Using IDIS to Find Best Evidence

Evidence-based medicine is a major topic of interest and discussion for health care professionals and students. Evidence-based medicine has been defined as "the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. The practice of evidence based medicine means integrating individual clinical expertise with the best available external clinical evidence from systematic search." (Sackett, 1996) After formulating the clinical question which best describes the information needed to help a particular patient, a search strategy must be designed for the fast and efficient retrieval of the necessary information. The IDIS database is an extremely useful tool for seeking best evidence information, primarily because it was designed especially to help health care practitioners find answers to their clinical questions.

Quality and methodological filters are an integral part of searching for the best evidence and are used to maximize both sensitivity and specificity in a search of the literature. Sensitivity refers to the degree to which all possible relevant articles are retrieved, and specificity is the degree to which irrelevant articles are not retrieved. Filtering for articles of high quality includes the use of such search terms as randomized, meta-analysis, systematic review, control or placebo. The nature of the clinical question for which an answer is sought determines what terms are most appropriate. ‘Methodological filters’ is the term used by D. Sackett, MD, and his colleagues to describe special MEDLINE search terms (Sackett, 1997). The filter concept can also be applied to IDIS and incorporates search strategies that are constructed to best find as much relevant information as possible, and to omit irrelevant information, that is, to be sensitive and specific.

Several databases might be used to conduct a search for best evidence literature, each having its own advantages and disadvantages. MEDLINE is the largest source, being a multi-purpose database. Over 4000 journals containing biomedical literature are indexed in MEDLINE and related databases (Hunt, 1997). This literature includes in-vitro and animal studies. While it is an impressive quantity of information, there are some drawbacks. Searching through such a large source can be cumbersome as well as time consuming, and there is a lapse of time before a published article appears in the database. Also, searching for information about a specific drug is sometimes difficult if that drug can only be searched by class or as a text word.

IDIS is a smaller and more specialized database in which searching for best evidence can be fast and efficient. Over 200 pharmaceutical and medical journals are indexed in the database. Journals indexed in IDIS are peer reviewed and contain primary literature. Criteria for indexing articles from these journals include human studies and drug related therapy. Generally, articles appear in the database within three months after receipt of the journal; even less for some priority journals. A new drug’s name is added to the database as soon as human studies of that drug are indexed.

The best way to demonstrate how to use quality and methodological filters in IDIS is to set up a case scenario, define the clinical question and conduct the search.

Scenario: A family practice physician, suspecting a 77-year-old patient to be depressed, contacts the patient’s pharmacist wanting to know what medication would be preferred for this patient. The patient is otherwise healthy.

Clinical question: "Which medications provide optimal safety and efficacy in the treatment of depression in the elderly?"

The key search terms from the question above are "depression " and "elderly." Since the IDIS database is restricted to drug therapy, the search strategy does not need to include the search term "therapy" or "treatment." The best evidence available from the primary literature will include randomized controlled trials, clinical practice guidelines, systematic reviews and meta-analyses. Key to conducting an efficient search for such evidence is to make use of the Thesaurus and Look Up buttons in IDIS to ensure that valid terms are used. Since the Drug, Disease, and Global fields of the Main Search screen will cross-reference any terms entered, it may be tempting to omit using the Thesaurus, but using the valid terms is the best method of retrieving the most useful information.

RANDOMIZED STUDIES

Depression and the elderly will be the basis of the search. Using the Thesaurus, the valid disease term for unspecified depression is DISORDER, DEPRESSIVE NEC 311. Enter the valid disease term (or just 311.) in the Disease field by copying and pasting from the Thesaurus. Enclose the complete term in quotation marks. The Descriptor field is used to restrict the search to elderly or geriatric patients. Each article type in the IDIS database is classified as ADULT, GERIATRIC or PEDIATRIC e.g. STUDY RANDOMIZE GERIATRIC 137. The article classification descriptors are found using the Look-Up button to the right of the Descriptor field on the Main Search screen or in the Thesaurus.

Note that the earliest randomized trial retrieved using this search strategy is from 1993. This is because the descriptor STUDY RANDOMIZE GERIATRIC 137 was added in January 1994 (this information is found in the Descriptor Tab searching the descriptor name or number). In this case scenario, information before 1993 is of less interest. For future reference, prior to 1993 randomized studies in geriatric patients were tagged with the descriptors STRUCT, SINGLE/CONTROL 71 or STRUCT, COMP/CONTROL 72 and STUDY GERIATRIC 5.

PRACTICE GUIDELINES

Clinical practice guidelines, treatment algorithms or consensus statements are found in the IDIS database by using the descriptor PRACTICE GUIDELINES 156. Practice guidelines generally appear in the form of reports or reviews. The descriptors REPORT GERIATRIC 92 and REVIEW GERIATRIC 23 limit the search to geriatric patients. The descriptor field follows Boolean logic so be sure to enclose the article type descriptors within parentheses. Alternatively, type only "geriatric" to limit to all geriatric publication types.

Using either strategy, two very promising records are retrieved: IDIS Article Number 416621, ASHP therapeutic position statement on the recognition and treatment of depression in older adults and IDIS Article Number 392714, Diagnosis and treatment of depression in late life: consensus statement update.

SYSTEMATIC REVIEWS

Within the IDIS database, systematic reviews are indexed with a REVIEW descriptor. It is possible to limit the search to systematic reviews by textword searching. Most systematic reviews are defined, as such, within the article abstract or title. To search the Title and Abstract field simultaneously, use the Global field as it will search all fields. Truncate system* and review* to retrieve all possible variations of these terms e.g. systematic, systemically, review, reviewed, reviewing and reviews. Enclose the search terms in " " to force adjacency.

A thorough search of systematic reviews would include searching "methodological", "quantitative" and "overview" as these terms are sometimes used when referring to systematic reviews.

META-ANALYSES

Descriptor META-ANALYSIS 145 tags all meta-analysis articles and it is generally combined with a REVIEW descriptor. The meta-analysis descriptor is useful in that it eliminates textword searching all the various forms of the word meta-analysis that may appear in the literature (e.g. metaanalysis, metaanalyses, meta analyses etc.).

The next step in this scenario would be the careful appraisal of all the information gathered. This is necessary in order to select the best evidence that can be applied to a patient(s) situation. The practitioner, using his or her own clinical expertise and knowledge, must decide on the validity and clinical applicability of the information retrieved and then apply these results to the clinical situation. The final step in practicing evidence-based medicine is then the evaluation of the actions or recommendations implemented.

Using quality and methodological filters, the IDIS database allows practitioners to retrieve the best evidence available quickly and efficiently, expediting the process from posing a clinical question to implementation of a clinical recommendation and its evaluation. Whether practicing, teaching or learning to use evidence-based medicine the IDIS database is a useful tool.

References

Hunt DL and McKibbon KA. Locating and appraising systematic reviews. Ann Intern Med 1997;126(7):532-538.

Sackett DL, Richardson WS, Rosenberg W, Haynes RB. 2: Searching for the best evidence. Evidence-based Medicine:How to Practice and Teach EBM. New York:Churchill Livingstone, 1997, 60.

Sackett DL, Rosenberg WMC, Gray JAM, Haynes RB and Richardson WS. Evidence based medicine: What it is and what it isn’t: It’s about integrating individual clinical expertise and the best external evidence. BMJ 1996;312 (7023):71-72.

Brad Gilchrist, R.Ph.
Nicola Sarrazin, R.Ph., Pharm.D.

University of Iowa, Universities of South Australia Form Transnational Alliance

The UI College of Pharmacy is linking up with the Universities of South Australia as part of a new Transnational Alliance that will provide educational and research opportunities for both institutions.

Dean Gilbert Banker traveled to Australia in November and visited with officials from the Universities of South Australia. Banker was the first UI representative to visit Australia under the auspices of the Transnational Alliance.

The Transnational Alliance between the UI and the Universities of South Australia, has been under development for four years by Dr. Geoffrey McLennan, internal medicine, and Christine McLennan, with the support of both campuses.

"The whole alliance acts as an umbrella," said Christine McLennan. "We facilitate getting people together. The alliance is a sharing of resources, personnel interaction, and exploration of opportunities. The result is a cooperative project that can benefit both sides."

The first joint project between the two universities is the development of an international drug information network. A proposal for the project was developed in the fall of 1997 with Dean Banker; Hazel Seaba, director of the Division of Drug Information Service and clinical professor at the College; Dr. Kevin Moores, director of the Iowa Drug Information Network, clinical assistant professor; and Dr. Andy Gilbert from the Pharmacy Practice Research Group at the School of Pharmacy and Medical Sciences at the Universities of South Australia. Dr. Shane Scott, clinical assistant professor in the UI Clinical and Administrative Pharmacy division, also helped facilitate communication between the two institutions.

Seaba said the idea is to take the model of the successful Iowa Drug Information Network and apply it to South Australia.

"Through the Iowa Drug Information Network, we’re providing advanced, customized pharmaceutical support to community practitioners," Seaba said. "This model has applications anywhere community pharmacists are implementing patient-focused practices."

Seaba said IDIS will try out the model at the Universities of South Australia and see how it works there.

"Once we have the background, we will have data to support a grant proposal to test the model in other countries," Seaba said. "This bi-national network of drug information services would grow and become international."

Plans include meetings between South Australia and UI faculty to put together drug information training materials; a multi-media training presentation that can be used in both South Australia and the UI; using technology such as the World Wide Web to access drug information databases; and having a drug information specialist within the South Australia system to provide additional local support for pharmacists in the area.

Seaba said the Universities of South Australia is a particularly good place to try out the model because of the similarities between Australia and the United States.

"They have the same language, use a lot of the same drugs, and the health care systems have similarities," Seaba said. "If we’re successful in Australia where there are just a few variables, it would lend support that we can succeed internationally in more complex environments with more variables."

Both institutions have pledged funds to this project, which is scheduled to be initiated during the spring semester of this year.

"This particular project between the two colleges of pharmacy is the first formal project developed jointly by the parties under the Transnational Alliance concept," Banker said. "We’ll probably be doing a lot more between the colleges with faculty, and collaborating in the research arena. The colleges will also be working together to finalize a student exchange agreement. I have every expectation that the Transnational Alliance will be a success and a benefit to both sides."

While the pharmacy departments are currently the most active participants, the Transnational Alliance includes other UI colleges such as medicine, engineering, business, nursing and dentistry, as well as the UI Hospitals and Clinics.

"This thing is driving change into the next millennium," said Dr. McLennan. "This is the way people and institutions will have to conduct themselves in order to survive in an increasingly changing world — otherwise, we’ll be irrelevant."

Anyone interested in supporting the Transnational Alliance or getting more information about it can contact Dr. McLennan at geoffrey-mclennan@uiowa.edu. There is also a web site, at http://everest.radiology.uiowa.edu/nlm/app/mc/alliance.html.

This article was contributed by the
UI Office of Health Science Relations.

Donna Brus, Editor

SEARCH TIPS

Streamline Your Search

You enter the necessary information into the Main Search screen and click on the "Search" button. To your surprise, you have retrieved a vast number of articles, many that do not match what you intended. How can you increase the specificity of your search and avoid retrieval of irrelevant articles? There are many ways, of course, but two of the most important involve the use of the Drug and Disease fields in the Main Search screen. Making good use of the Phrase buttons on the Main Search screen or the Thesaurus can save a lot of time that would be spent sifting through irrelevant articles. Utilize the power of the search software to find the most useful articles for you.

Either drug or disease names or their assigned controlled vocabulary numbers can be entered in the Drug and Disease fields. If the name of a drug or a disease is entered, it is automatically cross-referenced and will likely pull up articles on other topics. Also, remember that if you want two or more words to be searched together, for instance a drug term that has more than one word in its name (i.e. immune globulin), the words should be enclosed within quotation marks. Otherwise, each word will be searched separately as well as together.

Use the Thesaurus to find the controlled vocabulary terms for drugs and diseases, then, either Copy and Paste, or type them into the Main Search screen fields. If you use the entire term, name and number, it must be enclosed within quotation marks, or you can use the controlled vocabulary number without the name (and without the quotation marks). The Phrase buttons are most useful if you already know the term you need. In that case just scroll down to the term needed and click on the box next to it, then on OK and go back to the Main Search Screen.

Nicola Sarrazin, R.Ph., Pharm.D.


In search of inquisitive minds ...
Are you ever pondering how to execute the perfect search on a specific topic? We'll be happy to give you a solution. E-mail us at: Search Tips <idis@uiowa.edu>


Perspective from an IDIS Subscriber

Rash 10 Days After Starting Allopurinol – What to Do?

Re: 52 YOWF who presented with a maculopapular rash ten days after beginning allopurinol 300 mg QD. What is the appropriate course of action?

History of Present Illness: Patient presented to orthopedic specialist with complaints of bilateral hip pain and "all over body aches". Physician completed a series of blood tests: ANA (negative), Rheumatoid factor (negative), ESR wnl, Uric acid slightly elevated (9.0 mg/dL). Allopurinol therapy of 300 mg po QD begun for hyperuricemia. Ten days after starting therapy, a non-pruritic, maculopapular rash developed on the patient’s arms and legs.

LITERATURE:

Singer and Wallace report a severe allopurinol hypersensitivity syndrome, which presents initially as a maculopapular rash in most patients. The allopurinol hypersensitivity syndrome (AHS) is a well documented and life threatening condition associated with the accumulation of the metabolite, oxypurinol. Fourteen patient charts were reviewed. Out of the fourteen charts reviewed, eight patients met inclusion criteria of exposure to allopurinol as well as at least two of the following major criteria: worsening renal function, acute hepatocellular injury, or rash. Fever, eosinophilia, leukocytosis and lack of exposure to another drug that could produce the same clinical picture were considered to be minor criteria. If patients had both a major and minor criteria they were included in the evaluation. Three of the eight patients died from organ failure. Two of those patients were being treated for asymptomatic hyperuricemia. Common presenting signs and symptoms of AHS included fever, erythema multiforme, deteriorating renal function and abnormal liver function (Singer, 1986). However, cases affecting the heart, liver, kidneys, lungs, colon, testes, breasts, pancreas, prostate, spleen, skin and adrenal glands have been described (Arellano, 1993).

In addition to these eight patients, 72 other patients with AHS were studied. Duration of allopurinol therapy ranged from two to eight weeks. There was a 26% mortality rate in these patients. Some form of dermatitis was present in 89% of these patients, and approximately 60% had fever, hepatic cellular injury and worsened renal function.

Arellano and Sacristan reported on clinical findings in AHS in 1993. Inclusion criteria were similar to those used in Singer’s study. Many of the patients had chronic illnesses. AHS developed on average, one to two weeks after initiation of allopurinol therapy. Of 101 cases, 76 were being treated for asymptomatic hyperuricemia. A fever was present in 95.1% of the patients, 93.1% presented with a rash (53.5% maculopapular, 20.8% exfoliative dermatitis, 8.9% erythema multiforme, 25.7% TEN, 1 patient was described as just having a rash). Death occurred in 27% of the patients. Renal function worsened in 45.5% of the patients. Sixty-one patients were also on diuretics. The concomitant use of thiazide diuretics with allopurinol has been reported to be a risk factor for the development of AHS (Arellano, 1993).

Hande et al. indicated that patients with renal insufficiency receiving thiazide diuretic therapy were more likely to develop AHS. Six cases of AHS were discussed. Two of the six (33%) patients died from complications of this syndrome. All patients presented with some form of a rash and were on allopurinol 100-300 mg QD (Hande, 1984).

The mechanism by which AHS occurs is not known (Hande, 1984, Arellano, 1993). Existing data indicates that there may be three mechanisms involved in the development of this syndrome: immunologic factors, genetic predisposition, and accumulation of the drug’s metabolite (Arellano, 1993).

Hande hypothesizes that the clinical picture is consistent with a diffuse vasculitis. It is possible that it is caused by an immune hypersensitivity type III reaction. Depositions of immune complexes in the skin and glomerular basement membrane have been reported (Hande, 1984).

However, the more likely picture is the accumulation of oxypurinol, a metabolite of allopurinol (Hande, 1984, Arellano, 1993, McInnes, 1981). The primary mechanism of clearance of this metabolite is via the kidneys. Elevated serum concentrations of oxypurinol appear to correlate with the development of AHS. Oxypurinol is an inhibitor of purine nucleoside phosphorylase, which results in defective cell mediated immunity. Subsequent suppression of T-cells may lead to this hypersensitivity reaction (Martindale, 1996). In addition to these proposed mechanisms, it has also been noted by Ingeborg et al. that the conversion of allopurinol to oxypurinol by xanthine oxidase is associated with the generation of superoxide radicals (Ingeborg, 1996). Thus, these superoxides could also lead to the development of AHS.

Currently there is no treatment for this syndrome. Early detection of the signs and symptoms associated with AHS may decrease the morbidity and mortality associated with allopurinol use. In patients with normal renal function, probenecid may be used to increase the excretion of oxypurinol. Patients with severe renal insufficiency may benefit from hemodialysis (Hande, 1984, Elasy, 1995). A four-hour standard hemodialysis will reduce serum oxypurinol concentrations by 39% (Hande, 1984). Supportive therapy with corticosteroids is still controversial (Arellano, 1993, Elasy, 1995).

Upon development of signs and symptoms, the drug should be withdrawn immediately (Martindale, 1996).

COMMENTS:

The clinical presentation of this patient is consistent with data illustrating allopurinol hypersensitivity syndrome. The patient should be evaluated for other

signs and symptoms of AHS, including fever, renal and liver failure and eosinophilia. Based on the previous literature, the drug should be stopped immediately, and the physician should see the patient as soon as possible for further evaluation.

This syndrome occurs infrequently but is life threatening. Therefore, the presence of a rash associated with allopurinol should be considered serious. It is important to determine if the drug is truly indicated in this patient. Asymptomatic hyperuricemia has not been shown to be associated with increased morbidity or mortality associated with renal failure (Singer, 1986).

Oxypurinol has a half life of ~20 hours in patients with normal renal clearance (Hande, 1984). Assuming our patient has normal renal function, the metabolite should be cleared within a few days of discontinuing allopurinol therapy. Doses of allopurinol must be adjusted in patients with renal insufficiency to avoid the accumulation of the metabolite associated with this syndrome.

 

FOLLOW-UP:

Three days after discontinuing allopurinol, the rash was subsiding, and there were no signs or symptoms of hepatic damage. We were unable to evaluate renal function at that time.

References:

Arellano A, Sacristan A. Allopurinol hypersensitivity syndrome: A review. Ann Pharmacotherapy, 1993;27:337-343. (IDIS article number 312705)

Elasy T, et al. Alerts, notices, and case reports: Allopurinol hypersensitivity syndrome revisited, West J Med, 1995;162(4):360-361. (IDIS article number 345842)

Hande K et al. Severe allopurinol toxicity: Description and guidelines for prevention in patients with renal insufficiency. Am J Med, 1984;76:47-56. (IDIS article number 180407)

Ingeborg W, et al. Uric acid lowering effect of oxypurinol sodium in hyperuricemic patients-therapeutic equivalence to allopurinol. J Rheumatol, 1996;23(3):498-501. (IDIS article number 364846)

Martindale’s The Extra Pharmacopeia, 31st ed. Antigout agents: allopurinol. London: The Royal Pharmaceutical Society of Great Britain; 1996.

McInnes GT, et al. Acute adverse reactions attributed to allopurinol in hospitalized patients. Ann Rheum Dis, 1981;40:245-249. (IDIS article number 165199)

Singer J, Wallace S. The allopurinol hypersensitivity syndrome. Arthritis Rhuem, 1986;29(1):82-87. (IDIS article number 212499)


This article was prepared by Lara Hunt, Pharm.D. candidate.

Dave Mace, Drug Information Specialist, reviewed the article. Mace graduated from the University of Iowa College of Pharmacy in 1967. Since 1982 he has served as the Director of the Drug Information Center at BPVAMC, 10,000 Bay Pines Blvd., Bay Pines, FL 33744. His responsibilities include serving as a preceptor for drug information and Pharm.D. clerkship programs and responding to complex drug information requests from clinical staff.


EDITOR'S NOTE: From time to time, we publish articles contributed by IDIS subscribers. An article from Dave Mace, B.S.Pharm., is included in this issue. Dave Mace is from an institution that is a long-standing IDIS subscriber, utilizing the database on a regular basis. His consult illustrates when the use of the IDIS database contributed directly to patient care outcomes. The responsibility for errors is the author's alone and does not necessarily represent hospital views and recommendations. We hope you find the information interesting and useful and welcome comments. If you are interested in sharing your experiences using the IDIS database, please contact donna-brus@uiowa.edu.

IDIS Welcomes Dean Jordan Cohen

"I have been very much aware of the quality and impact that IDIS has had on drug information within Iowa, and at the national and international levels. Given the rapidly expanding need for timely, electronic data to assist practitioners and patients with decisions about drug therapy and outcomes, I am looking forward to working with the Service to identify new opportunities to increase the impact and scope of these programs." Dean Jordan Cohen

On March 1, 1999, Jordan Cohen will become the eighth Dean of the University of Iowa College of Pharmacy. He comes to the UI from the University of Kentucky, where he had been dean for 11 years. Previously, he was professor and coordinator of pharmaceutics at the University of Southern California School of Pharmacy. He received his Ph.D. in physical pharmacy and analytical chemistry in 1969 at the University of Wisconsin, Madison. He is currently president of the American Association of Colleges of Pharmacy and chair of the board of trustees of the United States Pharmacopeial Convention. Dean Cohen was interviewed by Anne Duggan and Susan Green of the UI Office of Health Science Relations on December 4, 1998.


Q: What brings you to Iowa?

A: The UI offers some incredible opportunities and I’m honored to have the opportunity to come here. I see the potential to make an impact on health care delivery, by helping pharmacists take on major new responsibilities in assuring optimal use of drugs, and on the future of drug development research. Everything is in place here at Iowa, especially since our College is a part of an exceptionally strong academic health center. After 11 years as dean at Kentucky, and being very pleased with our progress and success, I am excited about the College of Pharmacy and the UI in terms of becoming even more recognized as national leaders in pharmacy education and the pharmaceutical sciences. In addition, the strong partnership with pharmacists and the Iowa Pharmacy Association represents a special opportunity. Iowa is already clearly regarded as a leader in helping to transition pharmacy practice, and I look forward to helping continue to develop and validate this pharmaceutical care model.

The leadership team here is exceptional and positioned to allow pharmacy to become a major contributor to the University’s success. The College’s new building, recently adopted curriculum, and enhanced working relationship with UI Hospitals and Clinics also adds to the excitement.

Q: What do you see as the pharmacist’s role today?

A: In recent times the pharmacist has become visible as a crucial professional in the system of dispensing drug products to patients, but is less well recognized or paid for providing patient care services which enhance drug therapy. There is a critical need to standardize expectations for that type of care in all settings, with particular emphasis on community pharmacy. I think we have to recognize that a system of technical personnel, combined with the use of technology and pharmacist oversight, ultimately would be a cheaper, better way to distribute the drug products. The real role of the community pharmacist is in helping people make better use of their medications. And that’s really my working definition of pharmaceutical care.

The challenge will be to identify the educational needs for a different type of technical person to provide (and oversee) drug distribution systems in the future. This will require collaboration with pharmacy practice and boards of pharmacy to identify the roles, functions and models that need to be developed.

Q: Do you see it as an associated medical sciences type of training?

A: Yes, in effect. It may range from on-the-job training to two years at a community or technical college. The key question today is what will be the manpower needs for pharmacists capable of delivering pharmaceutical care, and how do we respond to today’s shortage of pharmacists to fill the rapidly growing number of prescriptions in community practice?

Q: Early on, the fear was that community pharmacists would resist the additional training necessary for pharmaceutical care. At least in Iowa that doesn’t seem to turning out to be a problem.

A: I think we’re well past that in Iowa compared to many other places. Iowa was one of the early programs to develop and make available a non-traditional degree program and design meaningful continuing education programs to help practicing pharmacists develop a new skill set. The Iowa Pharmacy Association and the two colleges of pharmacy here (UI and Drake) also became national leaders in working with practitioners to move to a pharmaceutical care practice mode. While continuing to work hard in this arena we must continue to create more practice opportunities that lead to reimbursement for these types of patient-oriented services.

Q: Have you met any Iowa alumni yet?

A: I’ve had an opportunity to meet several alumni at national meetings this winter. I also very recently met with 3-4 key alumni on a trip to Arizona with Alsatia Mellecker, the College’s development officer, and I have had a chance to get to know several key alumni leaders who I had been aware of at the national level. The development of strong alumni relationships is a very high priority for me in the next couple of years.

Q: Welcome to Iowa.

Thanks. This appears to be a terrific community and we are looking forward to the move in early March. I am originally from Wisconsin, though I must say that it’s been a long time since I had to live with a real winter. I spent 20 years in Los Angeles and then 11 years in Lexington, so I’m not only moving from climate to climate but to successively smaller communities. We are excited and looking forward to some new challenges and opportunities.

This article was contributed by the UI Office of Health Science Relations.


IDIS System/CD-ROM is Year 2000 compliant. The publication year is the only date field in the database and is currently in four-digit format. There is no code in the retrieval software which is affected by the system date. Please contact us if you need additional information.


KEY REFERENCES

NEW DRUG SELECTED BIBLIOGRAPHY

This new drug selected bibliography provides a selection of key clinical studies of new drugs approved by the FDA during November and December 1998 and January 1999. IDIS SYSTEM/CD-ROM was searched to retrieve key articles relevant to the new drugs and their approved uses.

Anti-thymocyte Globulin, Rabbit

Gaber AO, First MR, Tesi RJ et al. Results of the double-blind, randomized, multicenter, phase III clinical trial of Thymoglobulin versus Atgam in the treatment of acute graft rejection episodes after renal transplantation. Transplantation 1998;66:29-37. (IDIS Article Number 410978). Investigators compared 7-14 days therapy of Thymoglobulin (1.5 mg/kg/day) with Atgam (15 mg/kg/day) for the treatment of acute rejection after renal transplantation in 163 patients enrolled in the multicenter, double-blind, randomized trial. (A pivotal study on which FDA approval was based.)

Guttmann RD and Fleming C. Sequential biological immunosupression. Induction therapy with rabbit antithymocyte globulin. Clin Transplant 1997;11:185-192. (IDIS Article Number 389077). A report of 108 consecutive renal transplant patients treated during a four-year period with a protocol of quadruple sequential immunosuppression that included rabbit antithymocyte globulin. (This report was reviewed as part of a new drug application submission to regulatory authorities at the Bureau of Biologicals, Health Protection Branch of the Department of Health and Welfare, Government of Canada.)

Bell L, Girardin, C, Sharma A et al. Lymphocyte subsets during and after rabbit anti-thymocyte globulin induction in pediatric renal transplantation: Sustained T cell depletion. Transplant Proc 1997;29:6S-9S. (IDIS Article Number 397160). This paper describes the investigators’ experience with dosing, therapeutic monitoring and transplant outcome using rabbit anti-thymocyte globulin in 20 pediatric renal allograft recipients.

Celecoxib

Simon LS, Lanza FL, Lipsky PE et al. Preliminary study of the safety and efficacy of SC-58635, a novel cyclooxygenase 2 inhibitor. Arthritis Rheum 1998;41:1591-1602. (IDIS Article Number 411265). A report of four phase II trials conducted to investigate the efficacy and safety of SC-58635 (celecoxib); a randomized two-week osteoarthritis efficacy trial in 293 patients, a randomized four-week rheumatoid arthritis efficacy trial in 330 patients, a one-week endoscopic study of GI mucosal effects, and a one-week study of effects on platelet function.

Cilostazol

Dawson DL, Cutler BS, Meissner MH et al. Cilostazol has beneficial effects in treatment of intermittent claudication. Circulation 1998;98:678-686. (IDIS Article Number 412599). Investigators conducted a multicenter, randomized, placebo-controlled, 12-week clinical trial to evaluate the efficacy of cilostazol (100 mg PO BID) for treatment of stable, moderately, severe intermittent claudication in 81 patients 40 years of age or older.

Etanercept

Moreland LW, Baumgartner SW, Schiff MH et al. Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. N Engl J Med 1997;337:141-7). (IDIS Article Number 388682). Investigators conducted a multicenter, randomized, double-blind, placebo-controlled, three-month trial to evaluate the safety and efficacy of etanercept in 180 patients with active, refractory rheumatoid arthritis.

Weinblatt ME, Kremer JM, Bankhurst AD et al. A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med 1999;340:253-9. (IDIS Article Number 417654). A randomized, double-blind 24-week study was conducted by investigators to determine whether etanercept (25 mg subcutaneously twice weekly) combined with methotrexate would provide additional benefit to patients who still had active rheumatoid arthritis despite long-term methotrexate treatment.

Lyme Disease Vaccine (Recombinant OspA)

Steere AC, Sikand VK, Meurice F et al. Vaccination against Lyme disease with recombinant Borrelia burgdorferi outer-surface lipoprotein A with adjuvant. N Engl J Med 1998;339:209-15. (IDIS Article Number 408403). A multicenter, double-blind, randomized two-year trial was conducted to determine the efficacy, safety, and immunogenicity of Lyme disease vaccine in 10,936 subjects who lived in areas in which Lyme disease is endemic. (The pivotal study on which FDA approval was based.)

Sigal LH, Zahradnik JM, Lavin P et al. A vaccine consisting of recombinant Borrelia burgdorferi outer surface protein A to prevent Lyme Disease. N Engl J Med 1998;339:216-22. (IDIS Article Number 408404). A multicenter double-blind two-year trial in which investigators assessed the efficacy of recombinant OspA without adjuvant in 10,305 subjects 18 years of age or older in areas where Lyme disease was endemic.

Modafinil

Mitler MM, Guilleminault C, Harsh JR et al. Randomized trial of modafinil for the treatment of pathological somnolence in narcolepsy. Ann Neurol 1998;43:88-97. (IDIS Article Number 399820). The wake-promoting and safety properties of modafinil (200 mg to 400 mg once daily) were assessed in a multicenter randomized, double-blind, placebo controlled nine-week trial of 283 subjects with narcolepsy.

Broughton RJ, Fleming JA, George CF et al. Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of excessive daytime sleepiness in narcolepsy. Neurology 1997;49:444-451. (IDIS Article Number 390051). The short-term efficacy and safety of modafinil 200 mg or 400 mg in divided doses (morning and noon) was assessed in a six-week, three-period, randomized, crossover, placebo-controlled trial in 75 patients with narcolepsy.

Thyrotropin Alpha

Ladenson PW, Braverman LE, Mazzaferri EL et al. Comparison of administration of recombinant human thyrotropin with withdrawal of thyroid hormone for radioactive iodine scanning in patients with thyroid carcinoma. N Engl J Med 1997;337:888-896. (IDIS Article Number 391784). The study was designed to assess the efficacy and side effects of the administration of recombinant thyrotropin and compare it with withdrawal of thyroid hormone therapy for radioactive iodine scanning in 127 patients with previously treated thyroid carcinoma.

Meier CA, Braverman LE, Ebner SA et al. Diagnostic use of recombinant human thyrotropin in patients with thyroid carcinoma (Phase I/II study). J Clin Endocrinol Metab 1994;78:188-196. (IDIS Article Number 324878). Investigators report on the safety and preliminary efficacy of thyrotropin alpha used as a diagnostic tool with radioiodine in 19 patients with differentiated thyroid carcinoma.

Ruth Calloway, R.Ph., M.S.


FDA DRUG/BIOLOGIC APPROVALS

Generic Name

(FDA Therapeutic Classification)

Trade Name

Sponsor

(Approval Date)

Valid IDIS Drug Term

Drug Number

(IDIS Citations)*

Indication/Use

Valid IDIS Disease Term

Modified ICD-9-CM Number

Abacavir

Ziagen

Glaxo Wellcome Inc.

(Dec. 17)

ABACAVIR

8180817

(3 citations)

Treatment of HIV-1 infection in combination with other antiretroviral agents

INFECTION, HIV, ASYMPTOMATIC

V08.

Anti-thymocyte globulin, rabbit

Thymoglobulin

SangStat

(Dec. 30)

ANTI-THYMOCYTE GLOBULIN RABBIT

80040083

(79 citations)

Polyclonal antibody for use with concomitant immunosuppression for treatment of acute rejection of renal transplant

COMPLICATION, ORGAN TRANSPL

996.8

TRANSPLANT, KIDNEY

55.6

Celecoxib

(1P)**

Celebrex

GD Searle and Co.

(Dec. 31)

CELECOXIB

28080601

(8 citations)

For the signs and symptoms for osteoarthritis and rheumatoid arthritis

OSTEOARTHRITIS

715.

ARTHRITIS, RHEUMATOID

714.0

Cilostazol

(1S)***

Pletal

Otsuka America Pharmaceutical Inc.

(Jan. 15)

CILOSTAZOL

20120642

(13 citations)

For the reductions of symptoms of intermittent claudication

DISEASE, VASC, PERIPH NEC

443.

Etanercept

Enbrel

Immunex

(Nov. 2)

ETANERCEPT

14000041

(41 citations)

Reduction in signs and symptoms of moderately to severely active rheumatoid arthritis in patients who have an inadequate response to one or more disease-modifying anti-rheumatic drugs; & for use in combination with methotrexate in patients who do not respond adequately to methotrexate alone

ARTHRITIS, RHEUMATOID

714.0

Lyme Disease Vaccine (Recombinant OspA)

LYMErix

SmithKline Beecham Pharmaceuticals

(Dec. 21)

LYME VACCINE

80120088

(24 citations)

Vaccine for active immunization against Lyme disease in individuals 15 to 70 years of age

LYME DISEASE

088.81

Modafinil

(1S)

Provigil

Cephalon, Inc.

(Dec. 24)

MODAFINIL

28200060

(7 citations)

For the treatment of narcolepsy

CATAPLEXY AND NARCOLEPSY

347.

Thyrotropin alpha

(1P)

Thyrogen

Genzyme

(Nov. 30)

THYROTROPOIN ALFA

68280020

(12 citations)

Adjunctive diagnostic tool for serum thyroglobulin testing with or without radioiodine imaging in the follow-up of patients with well-differentiated thyroid cancers

NEOP, MGN-THYROID

193.

DIAG TEST- NEC

89.3


* Through January 1999 Update. Complete bibliographic citations will be provided upon request.
** (1P) New Molecular Entity given priority review by FDA
*** (1S) New Molecular Entity given a standard review by FDA

1999 EXHIBIT SCHEDULE

Academy of Managed Care Pharmacy Annual Meeting (AMCP)
Minneapolis, Minnesota
April 29-May 1

Iowa Pharmacists Association Annual Meeting
Cedar Rapids, Iowa
June 11-13

American Society of Health-System Pharmacists (ASHP)
Home, Hospice and Long-Term Care '99
Chicago, Illinois
July 31-August 2

Federation Internationale Pharmaceutique (FIP)
World Congress of Pharmacy and Pharmaceutical Sciences
Barcelona, Spain
September 5-10

American College Clinical Pharmacy (ACCP) Annual Meeting
Kansas City, Kansas
October 24-27

American Society of Health-System Pharmacists (ASHP)
Midyear Clinical Meeting
Orlando, Florida
December 5-9


STAFF PROFILE

Laura Kastens
Laura Kastens joined the IDIS staff as Division Secretary in September of 1998. She and her family moved from Columbia, Missouri to Iowa City in August 1998 when her husband assumed the job of Director, Hawkeye Marching Band, The University of Iowa.

Laura’s duties consist of general secretarial work and producing the quarterly newsletter. Outside of the office she enjoys spending time with her husband and two teenagers, reading, cooking and playing in her church’s handbell choir.

World of Drug Information is published quarterly (March, June, September, December) by the Division of Drug Information Service.

Editor: Donna Brus
Assistant Editor: Tracy Simenson
Production/Design: Laura Kastens
Photographer: David Luck


IDIS
Iowa Drug Information Service
Telephone: 319-335-4800
U.S. Toll-Free: 800-525-IDIS
Fax: 319-335-4440
E-mail: IDIS@uiowa.edu
Web Site: http://www.uiowa.edu/~idis
IDIN
Iowa Drug Information Network
Telephone: 319-335-4199
U.S. Toll-Free: 800-791-7055
Fax: 319-335-4440
E-mail: IDIN@uiowa.edu
Web Site: http://idin.idis.uiowa.edu

Division of Drug Information Service
The University of Iowa, 100 Oakdale Campus N330 OH
Iowa City, IA 52242-5000 USA


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