World of Drug Information

World of Drug Information - Volume 8, Issue 2 - June 1997

In This Issue ...
 Current Clinical Issues  
 Search Tip 
 FDA Approvals 
 Key References 
 Exhibit Schedule 
 Staff Profile 

CURRENT CLINICAL ISSUES

AIDS Drugs in Pregnancy

The AIDS Clinical Trials Group (ACTG) Protocol 076 showed that the maternal-infant transmission of Human Immunodeficiency Virus Type 1 was reduced significantly when pregnant women with HIV infection took zidovudine (Connor EM, et al, 1994). In the time since that study was published, new aids drugs with different mechanisms of action have reached the market. In non-pregnant HIV patients, combination therapy is the new standard of treatment. What new information is available regarding the treatment of pregnant women with HIV infection?

Search Strategy: Pregnancy and HIV Infection

One strategy to search this and other topics, though not specific or refined, is to enter keywords in the Global field of the Field Search template (the default search template). Search terms entered into the Global field are automatically cross referenced. Looking through the records retrieved from these searches will help you identify the pertinent valid drug, disease and descriptor terms used to index this topic area. These searches alone may provide the desired information. If not, the next step is to search the Thesaurus with keywords to accurately define the valid search terms, e.g. AIDS, HIV infection and Pregnancy. Entering Preg*and HIV (not case sensitive) in the Global field locates 213 index records. The index records for the most recently added articles appear first. Scrolling through the titles, two recent reviews are chosen.

Clinical Information: Zidovudine Still Main Treatment in Pregnancy

Very few studies have been done in pregnant women with antiretrovirals other than zidovudine. Comparing the 1994 Agency for Health Care Policy and Research and 1996 International AIDS Society-USA treatment guidelines for HIV infection, the recommended therapy for pregnant women has not changed substantially. Zidovudine during the antepartum and intrapartum in all pregnant women, not restricted to CD4 counts <500 cells/mm3 , is the current standard therapy (Doran, 1997). One of the concerns of using zidovudine in all pregnant women is the decreased efficacy of other treatment regimens in patients who have been on zidovudine compared to zidovudine-naive patients (Minkoff, 1997). Besides zidovudine, however, no other agents have been studied or proven effective in the prevention of mother-to-child transmission of HIV. For this reason, even if one of the new combination therapies is chosen to treat the mother, zidovudine should still be part of the therapy (Minkoff, 1997). In cases where zidovudine resistance is shown, there may still be reason to continue using zidovudine. Although the predominant strain in the mother may not be susceptible, some "escape mutants" which are susceptible could be transmitted from the mother to the child (Minkoff, 1997).

Search Strategy: Studies in Pregnant Women with AIDS/HIV Infection

Using the Thesaurus reduces false hits...

To reduce the number of false hits, and to take full advantage of the IDIS pharmacists' expert indexing, we highly recommend using the Thesaurus to identify valid search/indexing terms. This will ensure specific search results. The Thesaurus is accessed by pressing <F3> and selecting Thesaurus. Drug (DR), Disease (DI) and Descriptors (DE), the key indexing vocabularies of the IDIS database, are combined in one Thesaurus. To limit a search of the Thesaurus to only Drug, Disease , or Descriptor, enter DR, DI or DE along with the keyword(s). Entering AIDS alone in the Thesaurus field returns forty-eight different drug and disease cross-reference and valid terms. Typing AIDS DI, limits the search to disease terms and only thirteen different entries are found. Note that the first disease term that appears, AIDS (Acquired Immune Deficiency Syndrome) is cross referenced to SYN-ACQ IMMUNE DEFICIENCY 042., the valid disease term for AIDS. Either the name (SYN-ACQ IMMUNE DEFICIENCY) or the code number (042.) may be used when searching.

Asymptomatic HIV infection and AIDS are classified by the ICD-9 as two distinct disease states. Typing HIV in the Thesaurus field will locate V08. ASYMPTOMATIC, INFECTION, HIV. This disease term is used when an article is discussing persons infected with HIV but exhibiting no symptoms of AIDS. The term SEROPOSITIVITY, HIV 795.8, which also appears, is an outdated term. It predates V08. ASYMPTOMATIC, INFECTION, HIV which was added in 1995. For a comprehensive search, both terms need to be searched.

Indexing Notes is accessed by pressing <F3>...

More complete definitions and internal indexing guidelines for the AIDS disease terms appear in the Indexing Notes which is accessed by pressing <F3> and then selecting Indexing Notes. Indexing Notes is also searchable by keyword(s).

The last keywords to verify in the Thesaurus are Pregnancy and Study. Entering Preg* or Pregnancy retrieves all the various pregnancy disease terms. Scrolling through the terms PREGNANCY NEC V22. is the most appropriate term. Again, the Indexing Notes contain specific information concerning the use of the pregnancy disease terms. Entering study in the Thesaurus pulls all of the various study design descriptors e.g. randomized, cohort, case controlled. Note that all the valid descriptor names for the various study types contain the word "study" as well as an age range (e.g. STUDY RANDOMIZE PEDIATRIC). Entering only STUDY in the descriptor field will pull all study types for all ages. The valid search terms identified are: PREGNANCY V22., SYN-ACQ IMMUNE DEFICIENCY 042., ASYMPTOMATIC, INFECTION, HIV V08. and 795.8 HIV, SEROPOSITIVITY, and STUDY.

Using the Field Search template, execute three separate searches. In the Disease field enter V22. and 042. and in the descriptor field enter study. This combination locates 4 index records. You may print these results by Pressing <F6> Output and proceeding through the menu choices.

After printing press <Esc> to go back to edit the original search, delete 042. and replace it with V08. Press <Enter> to execute the search. Six additional records are found. Print results and <Esc> as before to edit the search once more, delete V08., replace it with 795.8 and press <Enter>. Five records are retrieved, two overlap with the first search and three are new, for a total of 13 unique articles.

Clinical Information: Zidovudine Effective Prevention of Perinatal HIV Infection

An observational cohort study of 321 women in New York City, retrospectively confirmed the effectiveness of antenatal zidovudine in preventing vertical transmission of HIV-1 (Matheson, 1995). They identified that the efficacy of zidovudine in preventing transmission was not related to CD4+ lymphocyte level. They concluded from this that women with severe CD4+ depression, who represent the highest risk of passing on the virus, may also benefit from zidovudine therapy. A follow-up-study to the Pediatric AIDS Clinical Trials Group Protocol 076 Study looked at the relationship between maternal viral load and HIV-1 transmission (Sperling, 1996). Again, they found that zidovudine was effective in reducing transmission rate regardless of the mother's HIV-1 RNA level (which measures viral load) or CD4+ count at the beginning of the study. Dickover, 1996, noted that maternal HIV-1 RNA levels were predictive of perinatal transmission and that zidovudine reduced maternal HIV-1 RNA levels.

The usefulness of zidovudine monotherapy in pregnant women is documented by these and other studies. As more trials of combination therapy in non-pregnant patients are concluded, trials and case reports of combination therapy in pregnancy may soon follow. It is interesting to note that some of the newer AIDS drugs, saquinavir and ritonavir, have at least initially been classified as category B drugs by the FDA use-in-pregnancy rating, whereas zidovudine is a category C (Minkoff, 1997). Until new studies take place however, the standard treatment for pregnant women infected with HIV for prevention of perinatal HIV virus transmission is: oral administration of 100 mg zidovudine five times daily during the antepartum period; during labor intravenous administration of zidovudine in a 1-hour loading dose of 2 mg/kg of body weight, followed by a continuous infusion of 1 mg/kg per hour until delivery; and oral administration of zidovudine to the newborn (ZDV syrup at 2 mg/kg of body weight per dose every 6 hours) for the first 6 weeks of life, beginning 8 to 12 hours after birth (Anon, 1994).

Brad Gilchrist, R.Ph.

REFERENCES:

Anonymous, Recommendations of the U.S. Public Health Service Task Force on the use of Zidovudine to Reduce Perinatal Transmission of Human Immunodeficiency Virus. MMWR. 1994;43:1-20. (IDIS Article Number 335532)

Connor EM, Sperling RS, Gelber R., et al. Reduction of Maternal-Infant Transmission of Human Immunodeficiency Virus Type I with Zidovudine Treatment. N Engl J Med. 1994; 331:1173-1180. (IDIS Article Number 337544)

Dickover RE, Garratty EM, Herman SA., et al. Identification of Levels of Maternal HIV-1 RNA Associated With Risk of Perinatal Transmission. JAMA. 1996;275:599-605. (IDIS Article Number 361114)

Doran CM. New Approaches to Using Antiretroviral Therapy for The Management of HIV Infection. Annals of Pharmacotherapy. 1997;31:228-236. (IDIS Article Number 379909)

Matheson PB, Abrams EJ, Thomas PA. Efficacy of Antenatal Zidovudine in Reducing Perinatal Transmission of Human Imunodeficiency Virus Type I. The Journal of Infectious Diseases. 1995;172:353-358. (IDIS Article Number 353316)

Minkoff H, Augenbraun M. Antiretroviral Therapy for Pregnant Women. Am J Obstet Gynecol. 1997;176:478-489. (IDIS Article Number 382721)

Sperling RS, Shapiro DE, Coombs RW., et al. Maternal Viral Load, Zidovudine Treatment, and the Risk of Transmission of Human Immunodeficiency Virus Type 1 from Mother to Infant. N Engl J Med. 1996;335:1621-1629. (IDIS Article Number 376556)


SEARCH TIP

Searching for Information on Drugs With the Same Therapeutic Classification

Each valid drug term in the IDIS database is assigned its own unique code number. The beginning numbers of the code identify the therapeutic class to which the drug term has been assigned. For example, FLUOXETINE (a selective serotonin reuptake inhibitor or SSRI) has been assigned the code number 28160701. Effective with the June, 1997, update, all drugs classified as SSRIs begin with the number 281607. SSRIs are classified as a subcategory under psychotherapeutic agents. Psychotherapeutic agents begin with the number 2816. These drugs belong to a larger class of drugs identified as central nervous system agents that begin with the number 28.

28        CENTRAL NERVOUS SYSTEM AGENTS
2816      PSYCHOTHERAPEUTIC AGENTS
281607    ANTIDEPRESSANTS-SSRIS

Since drugs assigned to a specific therapeutic class begin with the same code numbers, you can search the entire therapeutic class at one time by using the truncated drug code for that class. Use the Thesaurus to identify the appropriate truncated drug code for a therapeutic class of drugs. The truncated drug code is listed below the entry for the therapeutic category and is preceded by the word Search.

The IDIS Thesaurus Entry will look like this:

       IDIS Thesaurus
(DR) ANTIDEPRESSANTS-SSRIS
Search 281607*

For example, if you are interested in the use of SSRIs in the treatment of obsessive compulsive disorder, select the truncated drug code 281607* and combine it with the disease term OBSESSIVE COMPULSIVE D/OR or the code number (300.3) the valid disease term for obsessive compulsive disorder. This search will retrieve all articles in the database that contain information on any SSRI and obsessive compulsive disorder.

Using the truncated drug code for a therapeutic class of drugs allows you to search all drug terms within a given class at one time, rather than searching each drug term individually. However, beware that search using the drug term ANTIDEPRESSANTS-SSRIS rather than the truncated drug code 281607* will retrieve only the articles indexed with the more general term. Articles only indexed with specific SSRI drug terms will not be retrieved in this search.

Note: The search process may be slower than normal when searching a therapeutic drug class that contains a large number of drug terms.

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

Anagrelide HCl (1P)**
Agrylin
Roberts Pharmaceutical Corp.
(Mar. 14)
ANAGRELIDE
20120412
(14 citations)
Treatment of patients with essential thrombocythemia to reduce the elevated platelet count and the risk of thrombosis and ameliorate associated symptoms Thrombocytopenia, Primary
287.3
Delavirdine (1P) Rescriptor
Pharmacia & Upjohn
(Apr. 4)
DELAVIRDINE
8180086
(13 citations)
Treatment of HIV-1 infection in combination with appropriate antiviral agents when therapy is warranted Syn-Acq Immune Deficiency
042.
Imiquimod (1S)***
Aldara
3M Pharmaceuticals Inc.
(Feb. 27)
IMIQUIMOD
14000019
(1 citation)
Treatment of external genital and perianal warts/condyloma acuminata in adults Wart, Viral
078.1

Nelfinavir Mesylate (1P)
Viracept

Agouron Pharmaceuticals Inc.
(Mar. 14)
NELFINAVIR
8180093
(16 citations)
Treatment of HIV infection when antiretroviral therapy is warranted Syn-Acq Immune Deficiency
042.

Samarium Sm 153 EDTMP (1S)
Quadramet

Cytogen
(Mar. 28)
SAMARIUM SM 153 LEXIDRONAM
78040155
(16 citations)
For relief of pain in patients with confirmed osteoblastic metastatic bone lesions that enhance on radionuclide bone scan Neop, Sec-Bone and Marrow
198.5
Pain NEC
782.2

Tamsulosin HCl (1S)
Flomax
Boehringer Ingelheim Pharmaceuticals Inc.
(Apr. 15)
TAMSULOSIN
12160411
(10 citations)
Treatment of the signs and symptoms of benign prostatic hyperplasia (BPH) Hyperplasia, Prostate
600.
Tiludronate Disodium (1S)
Skelid

Sanofi Winthrop Inc.
(Mar. 7)
TILUDRONATE
92000065
(19 citations)
Treatment of patients with Paget's disease of bone who have a level of serum alkaline phosphatase at least twice the upper limit of normal or who are at risk for future complications of their disease Osteitis Deformans
731.0

Troglitazone (1P)
Rezulin/Prelay
Parke-Davis/Sankyo USA
(Jan. 29)
TROGLITAZONE
68200401
(22 citations)
Treatment of Type II diabetes patients currently on insulin therapy whose hyperlycemia is inadequately controlled despite insulin therapy over 30 units per day given as multiple injections Diabetes Mellitus
250.

*Through May 1997 Update. Complete bibliographic citations will be provided upon request.
**(1P) New Molecular Entity given a priority review.
***(1S) New Molecular Entity given standard review by FDA.


KEY REFERENCES

NEW DRUG SELECTED BIBLIOGRAPHY

This bibliography provides a selection of key clinical studies and reviews of new drugs approved by the FDA during the first four months of 1997.

Anagrelide HCl

Chintagumpala MM, Kennedy LL, Steuber CP. Treatment of essential thrombocythemia with anagrelide. J Pediatr 1995;127:495-498. (IDIS Article Number 354213). A report of the successful use of anagrelide in three pediatric patients with thrombocythemia.

Silverstein MN, Petitt RM, Solberg LA, et al. Anagrelide, a therapy for thrombocythemic states: experience in 577 patients. Am J Med 1992;92:69-76. (IDIS Article Number 291184). A report evaluating safety and efficacy of anagrelide when used to decrease platelet counts in patients with thrombocythemic states.

Delavirdine

Gazzard BG, Moyle GJ, Weber J et al. British HIV association guidelines for antiretroviral treatment of HIV seropositive individuals. Lancet 1997;349:1086-1092. (IDIS Article Number 383573) . The British HIV Association consensus statement for antiretroviral treatment of HIV seropositive individuals.

Doran CM. New approaches to using antiretroviral therapy for the management of HIV infection. Ann Pharmacotherapy 1997;31:228-236. (IDIS Article Number 379909) A review of the changes in the 1994 to 1996 guidelines for the management of HIV infection with antiretroviral agents.

Morse GD, Fischl MA, Shelton MJ et al. Single-dose pharmacokinetics of delavirdine mesylate and didanosine in patients with human immunodeficiency virus infection. Antimicrob Agts Chemother 1997;41:169-174. (IDIS Article Number 378388). A three-way crossover single-dose study that evaluated the effect of didanosine on the absorption of delavirdine in twelve HIV-infected patients.

Davey RT, Chaitt DG, Reed GF et al. Randomized, controlled phase I/II trial of combination therapy with delavirdine (U-90152S) and conventional nucleosides in human immunodeficiency virus type 1-infected patients. Antimicrob Agts Chemother 1996;40:1657-1664. (IDIS Article Number 369810). A randomized controlled phase I/II study that evaluated the safety, toxicity, pharmacokinetics and antiretroviral activities of two-drug and three-drug combinations of delavirdine and conventional doses of nucleoside analogs compared with those of both delavirdine monotherapy and two-drug nucleoside analog therapy.

Spooner KM, Lane HC, Masur H. Guide to major clinical trials of antiretroviral therapy administered to patients infected with human immunodeficiency virus. Clin Infect Dis 1996;23:15-27. (IDIS Article Number 369501). An update from the National Institutes of Health on the results of clinical trials, meta-analyses, and observational studies of antiretroviral therapy administered to patients infected with human immunodeficiency virus type 1.

Nelfinavir Mesylate

Gazzard BG, Moyle GJ, Weber J et al. British HIV association guidelines for antiretroviral treatment of HIV seropositive individuals. Lancet 1997;349:1086-1092. (IDIS Article Number 383573). The British HIV Association consensus statement for antiretroviral treatment of HIV seropositive individuals.

Doran CM. New approaches to using antiretroviral therapy for the management of HIV infection. Ann Pharmacotherapy 1997;31:228-236. (IDIS Article Number 379909). A review of the changes in the 1994 to 1996 guidelines for the management of HIV infection with antiretroviral agents.

Deeks SG, Smith M, Holodniy M et al. HIV-1 protease inhibitors: a review for clinicians. JAMA 1997;277:145-153. (IDIS Article Number 378091). A systematic review of available data on the HIV-specific protease inhibitors saquinavir, ritonavir, indinavir, and nelvinavir through September 1996.

Samarium Sm 153 Lexidronam

Bayouth JE, Macey DJ, Kasi LP et al. Dosimetry and toxicity of samarium-153-EDTMP administered for bone pain due to skeletal metastases. J Nucl Med 1994;35:63-69. (IDIS Article Number 324718). A phase I/II clinical trial to evaluate the pharmacokinetics of repeated injections of samarium-153-EDTMP and to observe its biological response in 19 patients.

Collins C, Eary JF, Donaldson G et al. Samarium-153-EDTMP in bone metastases of hormone refractory prostate carcinoma: a phase I/II trial. J Nucl Med 1993;34:1839-1844. (IDIS Article Number 323516). A phase I/II trial to determine the maximally tolerated dose and of samarium-153-EDTMP and its effect on pain in 52 patients with hormone refractory prostate cancer with bony metastases.

Farhangi M, Holmes RA, Volkert W A et al. Samarium-153-EDTMP: pharmacokinetic, toxicity and pain response using an escalating dose schedule in treatment of metastatic bone cancer. J Nucl Med 1992;33:1451-1458. (IDIS Article Number 301097). A report of the radiopharmacokinetics, toxicity and therapeutic results of samarium-153-EDTMP using escalating doses, from 0.1 to 1.0 mCi/kg, in 22 patients with painful metastatic bone cancer.

Tamsulosin HCl

Eri LM and Tveter KJ. Alpha-blockade in the treatment of symptomatic benign prostatic hyperplasia. J Urol 1995;154:923-934. (IDIS Article Number 351642).A review of 29 original reports of placebo controlled clinical trials of alpha-blockers in the treatment of symptomatic benign prostatic hyperplasia.

Kawabe K, Ueno A, Takimoto Y et al. Use of an alpha1-blocker, YM617, in the treatment of benign prostatic hypertrophy. J Urol 1990;144: 908-912. (IDIS Article Number 275219). A multicenter randomized, double-blind, placebo controlled trial in which tamsulosin HCl was evaluated in 270 patients with benign prostatic hypertrophy.

Tiludronate Disodium

Roux C, Gennari C, Farrerons J et al. Comparative prospective, double-blind, multicenter study of the efficacy of tiludronate and etidronate in the treatment of Paget's disease of bone. Arthritis Rheum 1995;38:851-858. (IDIS Article Number 348782). A six month prospective, randomized, double-blind, multicenter clinical trial that compared the efficacy and safety of tiludronate and etidronate at the same dosage (400 mg/day) for the treatment of active Paget's disease in 234 patients.

Reginster JY, Colson F, Morlock G et al. Evaluation of the efficacy and safety of oral tiludronate in Paget's disease of bone: a double-blind, multiple-dosage, placebo-controlled study. Arthritis Rheum 1992;35:967-974. (IDIS Article Number 300141). A three month double-blind, randomized, placebo-controlled trial of oral tiludronate in 149 patients with Paget's disease of bone.

Troglitazone

Ghazzi MN, Perez JE, Antonucci TK et al. Cardiac and glycemic benefits of troglitazone treatment in NIDDM. Diabetes 1997;46:433-439. (IDIS Article Number 382996). A 48 week multicenter randomized study comparing the cardiac and glycemic benefit of troglitazone to glyburide in 154 NIDDM patients.

Iwamoto Y, Kosaka K, Kuzuya T et al. Effects of troglitazone: a new hypoglycemic agent in patients with NIDDM poorly controlled by diet therapy. Diabetes Care 1996;19:151-156. (IDIS Article Number 363062). A twelve week multicenter, randomized, double-blind placebo controlled study that evaluated troglitazone in 284 NIDDM patients.

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


EXHIBIT SCHEDULE

American Society of Health-System Pharmacists (ASHP)
Home Care `97

Reno, Nevada
August 16-18, 1997

Federation Internationale Pharmaceutique (FIP)
World Congress of Pharmacy and Pharmaceutical Sciences

Vancouver, Canada
August 31-September 5, 1997

American Society of Health-System Pharmacists (ASHP)
Midyear Clinical Meeting (MCM)

Atlanta, Georgia
December 7-11, 1997


STAFF PROFILE

Yaw Adu-Sarkodie, R.Ph., Pharm.D. Candidate, joined DDIS in September of 1996 as a staff pharmacist. Originally from Ghana, Yaw graduated from the University of Iowa in 1990. He then moved to Wisconsin where he did postgraduate internship rotations in a hospital, a long-term care facility and at an independent practice site. In January 1991 he accepted a staff position at Mercy Medical Center in Cedar Rapids. In charge of formulary management, he particularly enjoyed work on a formulary standardization project designed to facilitate patient care between Mercy Medical Center and St. Luke's Hospital in the Cedar Rapids area. In January 1994 he accepted an offer to work at Dahl Pharmacy in Wisconsin. While there, Yaw participated in "Pharmcare" (pharmaceutical care) training, obtained preceptor certification and managerial experience in the retail setting. There he had an opportunity to consult with group homes and L.T.C.F's. An active role in the conversion of several group homes into a unit-dose system was very rewarding to him. In July 1996, Yaw moved back to Iowa City to join his wife, a post-doctoral fellow at the Dental College and then one-year-old, daughter. He enjoys playing soccer, volleyball and bicycling. He also likes to watch a good game of basketball but he generally favors the Discovery Channel.


World of Drug Information is published quarterly
(March, June, September, December) by the Division of Drug Information Service
EDITOR: DONNA BRUS
PRODUCTION/DESIGN: JULIE TOMASH
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
Home Page: 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
Home Page: http://idin.idis.uiowa.edu

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

Return to IDIS Home Page