World of Drug Information

World of Drug Information - Volume 9, Issue 2 - June 1998

In This Issue ...
 Current Clinical Issues 
 Subscription Confirmation Reminder 
 Search Tips 
 Year 2000 Compliance 
 Perspective From an IDIS Subscriber
 Key References 
 FDA Approvals 
 1998 Exhibit Schedule 
 Staff Profile 

Parkinson's Disease:
New Therapeutic Alternatives

In the last year several new drugs have been added to the armamentarium for treatment of Parkinson's disease. Three of the new medications are dopamine agonists--pramipexole (Mirapex®) and ropinirole (Requip®), which are approved for use in the USA, and cabergoline (Cabsar®, Dostinex®), which is available in Europe. The other two new drugs are catechol-O-methyltransferase (COMT) inhibitors--tolcapone (Tasmar®), FDA approved in January 1998, and entacapone (Comtan®), which is now in the FDA approval process.

Parkinson's disease is the second most common adult-onset neurodegenerative disease, affecting about 1-2% of people over 65 years of age. The classic signs of Parkinson's disease are tremor, rigidity, akinesia and bradykinesia, all of which are caused by the loss of dopaminergic neurons in the substantia nigra and a reduction in striatal dopamine. By the time these symptoms occur, 70-80% of those dopaminergic neurons have already been lost.

Approaches to treatment of Parkinson's disease differ according to the age of the patient and comorbidities, but there are generally two goals of therapy: (1) treatment of symptoms in the short-term and (2) long-term treatment to maintain functional status (Watts, 1997). The mainstay of therapy has been use of levodopa (the precursor to dopamine), along with carbidopa to limit decarboxylation of levodopa in the periphery. This therapy has been effective but is limited by adverse effects, especially after long-term use. Within five years of starting levodopa therapy, most patients develop dyskinesias or motor fluctuations. They may also develop fluctuations in response, referred to as the "on-off" phenomenon or the "wearing-off" phenomenon. The recent introduction of new therapeutic agents for Parkinson's disease should help to alleviate some of these problems by allowing lower doses of levodopa to be given over the long-term.

SEARCH STRATEGIES

There are many ways to conduct a search in IDIS, depending on how broad or specific you would like the search to be. To find the disease code number for Parkinson's disease, click on the Thesaurus tab at the bottom of the Main Search screen. Type parkinson's (or you can truncate the word using the "*", e.g., park*) in the search field and use the <ENTER> key or click on Search. From the list that appears, you will find that 332. is the code number for Parkinson's disease. On the Main Search screen, if the search is done using the term parkinson's in the Disease field, there are 2550 hits, if using the term park*, 2895 hits, and if using 332., 2312 hits. When using the 332., remember that the decimal point is required, or an error message will appear when the search is executed.

The exact role the new Parkinson's disease drugs will play is not yet clear; however, clinical consensus guidelines are available which include information about these newer therapies. To search IDIS for Parkinson's disease treatment guidelines, use Descriptor 156 Practice Guideline. Type the disease state of interest (in this case parkinson's or 332.) in the Disease field of the Main Search screen, then enter guideline or the number 156 into the Descriptor field and click on Search. This will retrieve several guideline articles for Parkinson's disease, including a recently published algorithm of treatment which appeared in Neurology (Olanow, 1998).

Search aids for identifying appropriate descriptors include the Thesaurus and Descriptor tabs and the Phrase and Look Up buttons. If using the Thesaurus to find this descriptor number, type practice de or guideline de into the Thesaurus search field and click on Search. The term can also be truncated by using "*" after a part of the word. The definition for this (or any) descriptor can be found by typing the number or the descriptor name into the search field of the Descriptors screen.

Another area of interest for any new drug is the mechanism of action. This is especially true of the COMT inhibitors. Articles containing mechanisms of action can be retrieved by using descriptor 41 MECHANISM OF ACTION in the Descriptor field of the Main Search screen along with the drug of interest in the Drug field.

A list of valid descriptors can be found by clicking on the Look Up button located to the right of the Descriptor field on the Main Search screen. To select one or more descriptors from the list, click on the box to the left of each desired descriptor, click on And for the Connector (at the bottom of the screen), then click on OK. This will place the selected descriptors into the appropriate field on the Main Search screen. Your search can be made specific by using several descriptors, or you may want to search broadly at first, then narrow the field by adding more descriptors.

CLINICAL INFORMATION

Dopamine agonists

In addition to allowing lower doses of levodopa to be given and thereby limiting its side effects, it has been suggested that dopamine agonists may be neuroprotective. The metabolism of dopamine in the brain via auto-oxidation or monoamine oxidase-B may produce toxic free radicals and hydrogen peroxide. Normally, these products are neutralized by enzyme systems which include glutathione/glutathione peroxidase; however, this enzyme is reduced in Parkinson's patients (Evidente, 1997). Dopamine agonists, unlike levodopa, are not converted to dopamine and thus potentially toxic metabolites are not produced.

Cabergoline is a long-acting D2 specific dopamine agonist with a 63- to 69-hour elimination half-life that makes possible once-daily dosing. This drug has been found to be helpful in reducing motor fluctuations caused by levodopa. In one randomized, double-blind, placebo-controlled study with a total of 188 patients, the patients treated with cabergoline (oral dose = 0.5 to 5 mg/d) and levodopa had significantly improved scores for Activities of Daily Living (p = 0.032) and Motor Examination (p = 0.031) compared to levodopa and placebo. Levodopa daily dosage was decreased by 18% for the cabergoline patients compared to 3% in the placebo group (p < 0.001) (Hutton, 1996). Cabergoline is approved by the FDA only for treatment of hyperprolactinemic disorders, but it is available in Europe for treatment of Parkinson's disease.

Pramipexole acts largely as a D3 dopamine receptor agonist, but also has activity at the D2 and D4 receptors. Ropinirole is very selective as a D2 receptor agonist. Because these two drugs are not ergot derived, they have fewer CNS side effects. However, they do have the usual side effects associated with dopamine agonists, such as nausea, postural hypotension and psychiatric disturbances (Olanow, 1998). Both pramipexole and ropinirole were approved by the FDA in 1997 for treatment of Parkinson's disease.

The Parkinson Study Group conducted a randomized, double-blind, placebo-controlled study in 264 patients to investigate the safety and efficacy of pramipexole as monotherapy in early Parkinson's disease. The 10-week study showed that pramipexole-treated patients, using doses ranging from 1.5 to 6 mg/d, improved their total Unified Parkinson's Disease Rating Scale (UPDRS) by 20% compared with the placebo group. Scores showed mean improvement of 5.9-7.0 units compared with 0.9 units in the placebo group (p < 0.005) (Parkinson Study Group, 1997a).

Ropinirole has also been studied as monotherapy in treatment of early Parkinson's disease. One such study was a 6-month randomized, double-blind, placebo-controlled investigation using ropinirole doses of 1.5 mg-8 mg tid. Again using change in the UPDRS as the efficacy endpoint, the ropinirole-treated patients improved significantly, +24% compared with -3% in the placebo group (p < 0.001) (Adler, 1997).

COMT Inhibitors

Catechol-O-methyltransferase metabolizes levodopa in the periphery so that even when given with carbidopa, only 5-10% of the oral dose of levodopa reaches the brain. Two new drugs, entacapone and tolcapone, inhibit COMT and enable more of the levodopa dose to effectively reach the brain. Entacapone works only in the periphery, but tolcapone crosses the blood-brain barrier and can also work in the CNS (Evidente, 1997).

In another study by the Parkinson Study Group, 205 patients were randomized to receive either 200 mg/d of entacapone or matching placebo, in addition to levodopa. With change in percentage of "on" time as the primary measure of efficacy, the overall increase for entacapone-treated patients was 5 percentage points (range = 1.7-8.3, p = 0.003), or about 1 hour per day (Parkinson Study Group, 1997b).

Kurth et al. studied tolcapone in a double-blind, placebo-controlled trial of 151 patients in which levodopa/carbidopa-treated patients were randomized to the addition of tolcapone at doses of 50 mg, 200 mg or 400 mg tid or placebo. Change in the "off" time was among the primary measures of efficacy. Compared with placebo, tolcapone reduced the "off" time an average of 40% (p = <0.01) and increased the "on" time by approximately 25% at all dosages, though this increase did not reach statistical significance at the 0.05 level (Kurth, 1997). Tolcapone was FDA approved in January of 1998 as adjuvant therapy with levodopa/carbidopa for treatment of Parkinson's disease.

This array of new anti-Parkinson's medications offers relief from disease symptoms and medication side effects to patients in both early and late stages of the disease. If the metabolism of dopamine in the brain does create toxic free radicals, as many believe, perhaps the most important result of using these new medications will be the lower levodopa doses required over the long term. As these new drugs are used by the patient population, a clearer picture will develop as to their optimal role in therapy.

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

REFERENCES

Adler CH, Sethi KD, Hauser RA et al. Ropinirole for the treatment of early Parkinson's disease. Neurology 1997;49(2):393-399. (IDIS Article Number 390050)

Evidente VGH, Adler CH. Pharmacologic options for managing Parkinson's disease. Formulary 1997;32(6):594-610. (IDIS Article Number 388784)

Hutton JT, Koller WC, Ahlskog JE et al. Multicenter, placebo-controlled trial of cabergoline taken once daily in the treatment of Parkinson's disease. Neurology 1996;46(4):1062-1065. (IDIS Article Number 366788)

Kurth MC, Adler CH, St. Hilaire M et al. Tolcapone improves motor function and reduces levodopa requirement in patients with Parkinson's disease experiencing motor fluctuations: a multicenter, double-blind, randomized, placebo-controlled trial. Neurology 1997;48(1):81-87. (IDIS Article Number 379257)

Olanow CW, Koller CK. An algorithm (decision tree) for the management of Parkinson's disease: treatment guidelines. Neurology 1998;50(S3):S1-S57. (IDIS Article Number 403377)

Parkinson Study Group. Safety and efficacy of pramipexole in early Parkinson disease. JAMA 1997a;278(2):125-130. (IDIS Article Number 388331)

Parkinson Study Group. Entacapone improves motor fluctuation in levodopa-treated Parkinson's disease patients. Annals of Neurology 1997b;42(5):747-755. (IDIS Article Number 397305)

Watts RL. The role of dopamine agonists in early Parkinson's disease. Neurology 1997;49(S1):S34-S48. (IDIS Article Number 390124)

1998 Subscription Confirmation Reminder

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IDIS-Windows® Search

The March 1998 Search Tips focused on how to search IDIS-Windows®. As a continuation, this article discusses how to display, select and print articles, how to save a search strategy and how to export a search result.

How search results are displayed. Once a search is executed, the total number of records found is posted in the lower right corner of the screen. The search results are displayed in a split screen format. The lower screen, the Result List screen, shows the title and article number of all records matching the search criteria. In order to keep the search result in a list format, long titles are limited to a maximum of 80 characters.

The number and title of the most recent article meeting the search criteria are highlighted and listed first. The upper screen, the Display screen, gives the descriptive details of the highlighted record from the Result List screen. Article number, sequence number, title, author, journal source, drug, disease, descriptor and abstract along with the highlighted search term(s) provide a powerful tool in selecting articles for on-screen viewing. A click in the box on the left side of the article number selects the citation and brings the corresponding index record onto the Display screen for viewing, printing or exporting.

Viewing the article image. A click on the highlighted Image button brings the article to the screen for viewing. Only articles from 1998 updates are currently available for on-screen viewing. The Hand button, the arrows on the vertical side bar, or clicking on the side bar all have a scroll function and allow easy navigation within a page. The Plus and Minus magnifying glass buttons offer "zoom in, zoom out" functions for better article viewing. Two left and right arrows at the left lower corner allow paging through the document. A click on the Text button returns to the previous search result screen.

Printing search results. A click on the Printer button from the Tools bar opens the Print screen with various options. The font and printer types can be changed. Four choices are available for the selection of the record to print: a record range, selected records, all records found and the current record. The fields within an index record may be individually selected (the four arrow buttons), providing a variety of print formats. Choosing Fields from the print option box will print only the index record. The full text articles can be printed by selecting Images. The two print choices are not mutually exclusive. The default for the print program is the current index record with all fields selected.

Using the History feature. Search criteria from the Main Search screen are automat-ically saved during a search session. A click on the History button available in all IDIS search screens brings a list of all searches executed within a session with the most recent search criteria listed first. A search statement can be loaded again to review the results by highlighting it and clicking on the Load button. A search criterion from History can be combined with new search terms(s) by clicking on the Binocular button and entering additional criteria on the search template. Previous search statements listed on the History screen can be selected (by clicking) and combined by using one of the Boolean connectors And or Or and clicking on Load. The search history is erased after each session.

Saving your search strategies. Search strategies can be saved from one session to the next. A click on File opens a menu with various options such as save current search criteria, load previously saved searches, export or print search results. Save and Load are very efficient techniques for current awareness searches. Once reloaded, the search strategy can be edited to make the current awareness search specific for a given article number range.

Exporting a file. The results of a search can be exported into a file and saved. A click on File from the Result List screen opens the Export option with various choices such as document selection or field selection. A click on the "---" button allows you to assign the path and name of the output file.

If you have any questions regarding our software, please contact us via telephone (U.S. toll-free 1-800-525-IDIS), Fax, E-mail or regular mail, and an IDIS pharmacist will gladly assist you.

ThaiBinh TonThat, R.Ph., Pharm.D.

IDIS SYSTEM/CD-ROM and Year 2000 Compliance

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.

Perspective From an IDIS Subscriber:
Preparing a Drug Information Response

Editor's Note: From time to time, we will publish articles contributed by IDIS subscribers. If you are interested in sharing your experiences using the IDIS database, please send us an e-mail message at donna-brus@uiowa.edu.

Memo to: Donna Brus

I would like to share with your readers a few examples of when the use of IDIS contributed directly to improved patient care outcomes. We use IDIS on a daily basis in our Drug Information Center, in addition to standard drug, pharmacotherapy and pharmacological reference texts, when preparing patient-specific responses to various questions involving drug therapy. Usually these written responses are provided within 48-72 hours of receiving the request, reviewing the medical record and interviewing the patient, if necessary. We will search IDIS before conducting other computerized database searches because of our ability to produce a copy of any of the pertinent literature found by the search. We also have found that many of the descriptors available with IDIS are not found in the other systems. We believe the indexing of drug-related information, by the IDIS staff, is more complete than indexing by Medline. Except for a few subspecialty areas in which the IDIS collection is weak, we conduct the majority of our drug therapy-related initial searches in IDIS. If our search in IDIS produces no results, to be considered reasonably complete, we also conduct a Medline search.

Examples included were written by me or by one of our Pharm.D. clerkship students and reviewed by me. The responsibility for any errors is mine and mine alone, and I would appreciate any comments from your readers. I hope you find the information interesting and useful.

Dave Mace, B.S.(Pharm.)

Treatment of Diabetic Diarrhea

Introduction

Diabetic diarrhea is one of several disorders of gastrointestinal motility associated with diabetes mellitus (Feldman, 1983). The cause of idiopathic diabetic diarrhea is not known. One popular suggested cause is autonomic neuropathy.

Experimental Data

Schmidt and associates (1981) and Chang and associates (1985, 1986) have published their data describing diarrhea in streptozocin-treated rats. Diarrhea was not found in insulin-treated or acutely diabetic rats. After 4-5 months all of the chronically diabetic rats developed intermittent or persistent watery diarrhea. When sympathetic denervation was produced in nondiabetic rats by treatment with 6-OH dopamine, a pattern of impaired fluid absorption developed that was the same as in the chronically diabetic rats. They concluded that impaired intestinal absorption of fluid and electrolytes slowly develops in rats made diabetic with streptozocin and that the impairment was due to a loss of the normally present noradrenergic innervation of enterocytes. Whether or not diarrhea in humans with long-term diabetes mellitus can be explained by the same pathophysiological mechanism remains to be proven.

Intestinal Electrolyte Transport and Diarrhea

Field and associates (1989a, 1989b) have recently published a two-part review of the subject in the September 21st and 28th, 1989, New England Journal of Medicine. In the 1970s, knowledge of adrenergic regulation of electrolyte transport in the intestine contributed to the understanding of diarrhea. Drs. Chang, Field and co-workers have identified an alpha-2 receptor on the enterocyte (Chang, 1986). Stimulation of specific postsynaptic alpha-2 receptors present in the small and large bowel enterocytes increases sodium and chloride absorption by the villus epithelium and inhibits bicarbonate and chloride secretion by the crypt epithelium. Since intestinal fluid secretion results from the active secretion of the two principal anions, chloride and bicarbonate, any drug that blocks their secretion represents a possible antidiarrheal drug.

Diabetic Diarrhea

In Feldman and Schiller's review (1983), 22% of diabetic outpatients had loose stools or increased frequency at least 2-3 days per year. Many of these patients also had intermittent episodes of constipation. Fecal incontinence was common in patients with diabetic diarrhea. Many patients may complain of diarrhea when they DO NOT have an increased stool volume. In their opinion, this distinction is important because low-volume diarrhea has a different cause than high-volume diarrhea. They discuss the differential diagnosis of increased stool weight in diabetic patients. They considered the cause of diabetic diarrhea to be unknown. But they noted that both truncal vagotomy and sympathectomy may cause diarrhea in humans. The fact that diabetic diarrhea sometimes responded to antibiotic therapy has been used to support the importance of bacterial overgrowth.

Classic Treatment

Diabetic diarrhea has often been described as incapacitating and refractory to conventional antidiarrheal therapy. A 2-week course of antibiotics (tetracycline 500-1000 mg/day) was given if steatorrhea was also present. Opiates, metoclopramide, anticholinergics and psyllium have all been used with moderate success according to Feldman and Schiller (1983).

Clonidine Therapy

Clinical data, although limited to a few case reports, support the use of clonidine in patients with chronic diabetic diarrhea. Clonidine has also been reported to be effective in the treatment of one patient who experienced diarrhea associated with lung cancer (McArthur, 1982).

After their success in the treatment of diarrhea in streptozocin-treated rats, Chang, Bergenstal and Field (1985) reported the empiric treatment of 3 diabetic patients with diarrhea. In each of them stool volume was substantially reduced by clonidine. The clonidine was given PO at a dose of 0.1 mg every 12 hours and increased to 0.5 or 0.6 mg every 12 hours over the next 72 hours. Clonidine did not worsen existing postural hypotension and did not induce it when it was not present. Symptoms of gastroparesis were not intensified. Diabetic control and renal function were unchanged. The onset of action of clonidine occurred within the first day of treatment. In each case the diarrhea recurred when the clonidine was withdrawn and remitted when the drug was reintroduced.

Not all patients with diabetic diarrhea have tolerated even modest doses of clonidine. Dharmsathaphorn (1986) found that in his patients, clonidine, in the dose normally required to have an antidiarrheal effect (0.3 mg/day or >), postural hypotension was a problem. He also reported light-headedness, drowsiness and depression, which caused him to discontinue clonidine in about 50% of the patients given the drug to control chronic diarrhea. Although many patients seem to tolerate the clonidine well, one of his patients could not tolerate even a very low dose.

Migliore and associates (1988) have reported the successful treatment of 1 patient with a 7-year history of water diarrhea (7-8 times daily) resistant to antibiotic therapy; the patient did not have incontinence. Clonidine 0.15 mg orally daily caused a decrease in stool frequency and volume; stool consistency increased and nocturnal diarrhea disappeared.

Topical Clonidine Therapy

In the 3 patients described by Fedorak above (1985), the frequency of bowel movements did not decrease, but they clustered into 1-2 periods during the day. It has been suggested that the clustering of the bowel movements observed with oral clonidine therapy might have coincided with trough serum levels. These troughs might be avoided with the topical administration of clonidine.

Sacerdote (1986) reported the use of topical clonidine in a 50-year-old female with diabetic diarrhea refractory to pectins and Lomotil. Prior to the use of the topical clonidine, she had 15-20 semisolid to liquid stools per day. On Clonidine TTS-1, the frequency of her stools decreased to 1 or 2 daily, and they were well formed. There was no dry mouth or hypotension and only minimal drowsiness. Discontinuation and rechallenge resulted in recurrence and subsequent control of the diarrhea syndrome.

In another report, Roof (1987) treated a 48-year-old female with the complaint of "severe, intermittent, voluminous stools", which resulted in severe volume depletion. She began with oral clonidine, but experienced limiting sedation at 0.2 mg per day, a dose which did not control the diarrhea. She was then treated with topical clonidine in gradually increasing doses (no description of time sequence) and eventually at a dose of 2 Clonidine TTS-3 patches (worn at the same time) per week she had marked resolution of her diarrhea. The only side effect was moderate local dermatitis in the area of the patches.

Report of Paradoxical Hypertension

Young and associates (1984) reported a paradoxical hypertensive response in a hypertensive diabetic patient given clonidine to control hypertension. The blood pressure increased from 160/100 to as high as 230/150 mm Hg when the clonidine dose was increased to 1.2 mg per day. Abrupt discontinuation of the clonidine resulted in a marked fall in blood pressure to pretreatment levels. They treated another hypertensive diabetic patient whose blood pressured increased to 200/120 mm Hg after treatment with clonidine. They suggest that clonidine may cause a paradoxical rise in blood pressure in the presence of autonomic denervation.

Summary

The use of clonidine as an antidiarrheal drug is supported by experimental data. Knowledge of its efficacy and incidence of adverse effects is based on a limited number of case reports. No controlled human data is available to my knowledge. Some patients tolerated doses in the upper range of usual antihypertensive doses (0.8-1.2 mg oral or 1-2 TTS-3 patches per week), but others could not tolerate even low doses without experiencing hypotension and other side effects.

The report of paradoxical hypertension by Young (1984) suggests that in some diabetic patients clonidine may increase rather than decrease blood pressure.

Follow-Up

The patient, a 50-year-old female with a long history of refractory diarrhea and a 20-year history of NIDDM, was essentially housebound due to voluminous diarrhea episodes. A 3-day therapeutic trial of clonidine PO 0.1 mg BID titrated up to 0.3 mg BID was completed. Both the number of daily diarrhea episodes and the volume of each episode were significantly reduced. She was converted to the weekly clonidine patch with further improvement. At discharge, she indicated that if the improvement in her diarrhea syndrome could be maintained over the long term, she would feel secure enough to resume some of her prior social activities. To the best of my knowledge, the improvement was sustained.

References

Chang EB, Bergenstal RM, Field M. Diarrhea in streptocozin-treated rats. Loss of adrenergic regulation of intestinal fluid and electrolyte transport. J Clin Invest 1985;75:1666-1670.

Chang EB, Fedorak RN, Field M. Experimental diabetic diarrhea in rats. Intestinal mucosal denervation hypersensitivity and treatment. Gastroenterology 1986;91:564-569.

Dharmsathaphorn K. Alpha2-adrenergic agonists: a newer class of antidiarrheal drug. Gastroenterology 1986;91:769-770.

Fedorak R, Field M, Change EB. Treatment of diabetic diarrhea with clonidine. Ann Intern Med 1985;102:197-199. (IDIS Article Number 195777)

Feldman M, Schiller LR. Disorders of gastrointestinal motility associated with diabetes mellitus. Ann Intern Med 1983;98:378-384. (IDIS Article Number 167195)

Field M, Rao MC, Chang EB. Intestinal electrolyte transport and diarrheal disease. Part I. N Engl J Med 1989;321:800-806.

Field M, Rao MC, Chang EB. Intestinal electrolyte transport and diarrheal disease. Part II. N Engl J Med 1989;321:879-883. (IDIS Article Number 295045)

McArthur KE, Anderson DS et al. Clonidine and lidamidine to inhibit watery diarrhea in a patient with lung cancer. Ann Intern Med 1982;96:323-325. (IDIS Article Number 146181)

Migliore A, Barone C, Manna R et al. Diabetic diarrhea and clonidine. Ann Intern Med 1988;109:170-171. (IDIS Article Number 244171)

Roof LW. Treatment of diabetic diarrhea with clonidine. Am J Med 1987;83:603-604. (IDIS Article Number 234179)

Sacerdote A. Topical clonidine for diabetic diarrhea. Ann Intern Med 1986;105:139. (IDIS Article Number 217857)

Schmidt RE, Nelson JS, Johnson EM. Experimental diabetic autonomic neuropathy. Am J Pathol 1981;103:210-225.

Young E, Levey BA, Shapiro AP. Paradoxical hypertension from clonidine. Ann Intern Med 1984;101:282-283. (IDIS Article Number 188481)

Dave Mace, B.S.(Pharm.), Drug Information Specialist, 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.

New Drug Selected Bibliography

This new drug selected bibliography provides a selection of key clinical studies and reviews of new drugs approved by the FDA since the first of the year. IDIS SYSTEM/CD-ROM was searched to retrieve key articles relevant to the new drugs and their approved uses.

Basiliximab

Nashan B, Moore R, Amlot P et al. Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. Lancet 1997;350:1193-1198. (IDIS Article Number 394766). A multicenter, randomized, controlled trial of 380 kidney transplant patients in which investigators assessed the ability of basiliximab to prevent acute rejection episodes in renal allograft recipients, and to monitor the drug's safety and tolerability.

Kovarik J, Wolf P, Cisterne JM et al. Disposition of basiliximab, an interleukin-2 receptor monoclonal antibody, in recipients of mismatched cadaver renal allografts. Transplantation 1997;64:1701-1705. (IDIS Article Number 401592). Investigators characterized the pharmacokinetics of basiliximab in a multicenter, open-label, prospective, dose-escalation study to identify a single-dose regimen providing interleukin-2 receptor-saturating serum concentrations in the first posttransplant month for 32 renal allograft recipients.

Fibrin Sealant

Rousou J, Levitsky S, Gonzalez-Lavin L et al. Randomized clinical trial of fibrin sealant in patients undergoing resternotomy or reoperation after cardiac operations: a multicenter study. J Thorac Cardiovasc Surg 1989;97:194-203. (IDIS Article Number 258294). A multicenter, randomized, controlled trial was conducted to test the efficacy and safety of fibrin sealant as a topical hemostatic agent in 333 patients undergoing either reoperative cardiac surgery or emergency resternotomy.

Atkinson JB, Gomperts ED, Kang R et al. Prospective, randomized evaluation of the efficacy of fibrin sealant as a topical hemostatic agent at the cannulation site in neonates undergoing extracorporeal membrane oxygenation. Am J Surg 1997;173:479-484. (IDIS Article Number 389443). Investigators conducted a multicenter, prospective, randomized, controlled study to evaluate the use of a fibrin sealant as a topical hemostatic agent in 149 neonates at particular risk for surgical bleeding who were undergoing extracorporeal membrane oxygenation.

Lepirudin (HBW 023)

Schiele F, Lindgaerde F, Eriksson H et al. Subcutaneous recombinant hirudin (HBW 023) versus intravenous sodium heparin in treatment of established acute deep vein thrombosis of the legs: a multicentre prospective dose-ranging randomized trial. Thromb Haemost 1997;77:834-838. (IDIS Article Number 387221). One hundred fifty-five patients were enrolled in a multicenter, prospective, randomized, dose-ranging study to compare the safety and efficacy of subcutaneous lepirudin [recombinant hirudin (HBW 023)] against intravenous sodium heparin in acute lower limb deep venous thrombosis.

Loteprednol Etabonate

Dell SJ, Shulman DG, Lowry GM et al. A controlled evaluation of the efficacy and safety of loteprednol etabonate in the prophylactic treatment of seasonal allergic conjunctivitis. Am J Ophthalmol 1997;123:791-797. (IDIS Article Number 387183). In a randomized, double-blind, placebo-controlled, 6-week study, investigators evaluated the efficacy and safety of loteprednol etabonate as prophylactic treatment for ocular signs and symptoms of seasonal allergic conjunctivitis in 293 adults with a history of seasonal allergic conjunctivitis.

Friedlaender MH, Howes J et al. A double-masked, placebo-controlled evaluation of the efficacy and safety of loteprednol etabonate in the treatment of giant papillary conjunctivitis. Am J Ophthalmol 1997;123:455-464. (IDIS Article Number 383467). Investigators conducted a 6-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the safety and effectiveness of loteprednol etabonate in reducing ocular signs and symptoms accompanying contact lens-associated giant papillary conjunctivitis in 223 adults with this condition.

Montelukast

Knorr B, Matz J, Bernstein JA et al. Montelukast for chronic asthma in 6- to 14-year-old children: a randomized, double-blind trial. JAMA 1998;279:1181-1186. (IDIS Article Number 402889). Investigators conducted an 8-week, multicenter, randomized, double-blind study to determine the clinical effect of 5 mg montelukast once daily at bedtime in 336 children with asthma.

Naratriptan

Mathew NT, Asgharnejad M, Peykamian M et al. Naratriptan is effective and well tolerated in the acute treatment of migraine. Results of a double-blind, placebo-controlled, crossover study. Neurology 1997;49:1485-1490. (IDIS Article number 398099). Seven hundred forty patients were enrolled in a multicenter, double-blind, placebo-controlled, four-way crossover study to evaluate the efficacy and tolerability of naratriptan tablets (2.5 mg, 1 mg, and 0.25 mg) in the acute treatment of migraine.

Risedronate

Patel S, Pearson D, Bhallah A et al. Changes in bone mineral density in patients with Paget's disease treated with risedronate. Ann Rheum Dis 1997;56:405-409. (IDIS Article Number 391884). Changes in bone mineral density were studied in 20 patients with Paget's disease who were treated with oral risedronate 30 mg daily for 3 months.

Tolcapone

Waters CH, Kurth M, Bailey P et al. Tolcapone in stable Parkinson's disease: efficacy and safety of long-term treatment . Neurology 1997;49:665-671. (IDIS Article Number 395274). In a multicenter, randomized, double-blind, parallel-group, placebo-controlled trial, investigators studied the long-term efficacy and tolerability of tolcapone (100 or 200 mg three times daily for 6 months) in 298 patients with Parkinson's disease.

Rajput AH, Martin W, Saint-Hilaire MH et al. Tolcapone improves motor function in Parkinsonian patients with the 'wearing-off' phenomenon: a double-blind, placebo-controlled, multicenter trial. Neurology 1997;49:1066-1071. (IDIS Article Number 393988). In a multicenter, randomized, double-blind, parallel-group, placebo-controlled trial, investigators assessed the effect of 3 months' add-on treatment of tolcapone (100 or 200 mg three times daily) on the "wearing-off" phenomenon in 202 Parkinsonian patients receiving levodopa.

Kurth MC, Adler CH, St Hilaire M et al. Tolcapone improves motor function and reduces levodopa requirement in patients with Parkinson's disease experiencing motor fluctuations: a multicenter, double-blind, randomized, placebo-controlled trial. Neurology 1997;48:81-87. (IDIS Article Number 379257). In a 6-week, multicenter, randomized, double-blind, placebo-controlled study, investigators used 10-hour evaluations to compare the efficacy and safety of three doses of tolcapone (50, 200, and 400 mg tid) with placebo in 151 patients with Parkinson's disease experiencing motor fluctuations from levodopa/carbidopa.

Gottwald MD, Bainbridge JL, Dowling GA et al. New pharmacotherapy for Parkinson's disease. Ann Pharmacother 1997;31:1205-1217. (IDIS Article Number 392974). A comprehensive review of the new pharmacotherapy, including tolcapone, for Parkinson's disease.Ruth Calloway, R.Ph., M.S.

FDA Drug/Biological 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
Basiliximab

Simulect
Norvatis
(May 12)
BASILIXIMAB
82000445
(3 citations)
Prophylaxis of acute organ rejection in patients receiving renal transplantation when used as part of an immunosuppression regimen that includes cyclosporine and corticosteroids Complication, Organ Transpl
996.8
Prophylaxis NEC
V07.
Transplant, Kidney
55.6
Capecitabine
(1P)**
Xeloda
Hoffmann-LaRoche
(Apr. 30)
CAPECITABINE
10080418
(1 citation)
Treatment of advanced breast cancer Neop, Mgn-Female Breast
174.
Fibrin Sealant

Tisseel VH Kit
Osterreichisches Institut Fur Haemoderivate Ges.m.
(May 1)
FIBRINOGEN
16000002
THROMBIN
20121606
(61 citations)
Adjunct to hemostasis in surgeries involving cardiopulmonary bypass and treatment of splenic injuries due to blunt or penetrating trauma to the abdomen, when control of bleeding by conventional surgical techniques, including suture, ligature and cautery, is ineffective or impractical; also indicated as an adjunct for the closure of colostomies Hemorrhage, Postoperative
998.1
Hemorrhage NEC
459.0
Lepirudin
(1P)
Refludan
Hoechst Marion Roussel
(Mar. 6)
HIRUDIN
20120425
(120 citations)
For anticoagulation in patients with heparin-induced thrombocyptopenia (HIT) and thromboembolic disease in order to prevent further thromboembolic complications Thombocytopenia, Secondary
287.4
Embolism/Thrombosis, VN NEC
453.
Prophylaxis NEC
V07.
Loteprednol Etabonate
(1S)***
Lotemax
Bausch & Lomb
(Mar. 9)
LOTEPREDNOL
52080002
(2 citations)
For the treatment of steroid responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea and anterior segment of the eye Conjunctivitis, Acute
372.0
Montelukast
(1S)
Singulair
Merck
(Feb. 20)
MONTELUKAST
86000039
(19 citations)
Prophylaxis and chronic treatment of asthma in patients age 6 to 14 years of age Asthma NEC
493.
Prophylaxis NEC
V07.
Naratriptan HCl
(1S)
Amerge
Glaxo Wellcome
(Feb. 10)
NARATRIPTAN
28081291
(4 citations)
For the acute treatment of migraine headache Migraine
346.
Risedronate
(1S)
Actonel
Hoechst Marion Roussel/Procter & Gamble
(Mar. 27)
RISEDRONATE
92000229
(19 citations)
Treatments of Paget's disease of the bone (osteitis deformans) Osteitis Deformans
731.0
Sildenafil Citrate
(1P)
Viagra
Pfizer
(Mar. 27)
SILDENAFIL
44100042
(7 citations)
Treatment of erectile dysfunction Impotence, Organic
607.84
Tolcapone
(1S)
Tasmar
Hoffmann-LaRoche
(Jan. 29)
TOLCAPONE
44100071
(13 citations)
As an adjunct to levodopa and carbidopa for the treatment of the signs and symptoms of idiopathic Parkinson's disease Parkinson's Disease
332.
Tolterodine Tartrate
(1S)
Detrol
Pharmacia & Upjohn
(Mar. 25)
TOLTERODINE
86000047
(1 citation)
Treatment of patients with an overactive bladder with symptoms of urinary frequency, urgency or urge incontinence Polyuria & Urinary Frequency
788.4
Incontinence, Urine
788.3

*Through May 1998 update. Complete bibliographic citations will be provided upon request.
**(1P) New Molecular Entity given a priority review by FDA.
***(1S) New Molecular Entity given standard review by FDA.


1998 Exhibit Schedule

American Society of Health-System Pharmacists (ASHP)
Home Care 1998
August 22-24
Chicago, Illinois

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

August 31-September 4
The Hague, The Netherlands

American College of Clinical Pharmacy (ACCP)
Annual Meeting
November 8-11
Cincinnati, Ohio

American Society of Health-System Pharmacists (ASHP)
Midyear Clinical Meeting (MCM)
December 6-10
Las Vegas, Nevada


Staff Profile

Tim Kardon

Hired under the Goodwill Supported Employment Threshold Program, Tim Kardon joined the IDIS staff in November of 1997. Tim was born in La Crosse, Wisconsin, and lived there until he was 10 years old. He and his family then moved to Iowa City, and Tim has lived here since that time.

Tim's responsibilities in the division include database production support activities including double data entry, proofing and fill in tasks. In his leisure time, he enjoys playing basketball and various video games.



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