World of Drug Information

World of Drug Information - Volume 9, Issue 1 - March 1998

In This Issue ...
 Current Clinical Issues 
 1998 Exhibit Schedule 
 Search Tips 
 Enhancement to Indexing Letters 
 Key References 
 FDA Approvals 
 Staff Profile 

Migraine Headaches and Intranasal Therapy

Reports of the number of migraine sufferers throughout the world vary. The Wall Street Journal reports the migraine drug market to be $1 billion (Langreth, 1997). A significant breakthrough in migraine treatment came in December 1992 when subcutaneous sumatriptan succinate, Imitrex®, was approved for marketing in the United States. In the study by the Subcutaneous Sumatriptan International Study Group, 86-92% of patients receiving subcutaneous sumatriptan experienced improvement in headache severity at 2 hours postdose vs. 37% of patients receiving placebo (p < 0.001) (Ferrari, 1991).

Most likely in response to people's dislike of needles, researchers developed an oral dosage form of sumatriptan succinate that was approved by the U.S. Food and Drug Administration in June 1995. While the oral dosage form may be more appealing than the subcutaneous route, nausea and vomiting sometimes limit its use. Slower absorption of the oral dose also leads to a delayed onset of action. Only 50% of patients taking 25 mg sumatriptan orally experienced pain relief at 2 hours postdose compared with 68% at 4 hours (Cutler, 1995). Consequently, intranasal preparations for treatment of migraine have been the next pharmaceutical venture in attempts to provide optimal therapy and attain more of the $1 billion migraine drug market. Sumatriptan nasal spray for treatment of migraine was FDA approved in August 1997. Dihydroergotamine nasal spray, Migranal®, was then approved in December 1997.

Through a multidisciplinary collaborative effort, members of the Canadian Headache Society developed guidelines for the diagnosis and management of migraine (Pryse-Phillips, 1997).

These guidelines were developed to improve the diagnosis and management of migraine, leading to reduced patient suffering, increased productivity and decreased economic burden. Therapy recommendations for the prophylaxis and treatment of mild to ultra severe migraine are provided. The level of supporting evidence is given for each therapy. The current place in therapy of the new intranasal therapies is yet to be determined. Along with relevant criteria such as cost, side effects and patient acceptance, the effectiveness of the intranasal preparations in treating acute migraine headaches will undoubtedly influence their future role in migraine treatment.

Search Strategy: Randomized controlled studies treating migraine headaches using intranasal preparations

There is more than one way to search for this information using the IDIS System/CD-ROM. The most precise way is to begin by clicking on the Thesaurus tab. When in the Thesaurus, type in Migraine and press <Enter> or click on Search. All the cross references in which Migraine appears are retrieved. Scrolling through the list, Migraine Headache is crossed to the valid disease term MIGRAINE 346. To copy and paste this term in the Disease field on the Main Search screen, begin by highlighting the complete term, MIGRAINE 346. With the term highlighted, click on Edit on the menu bar and select Copy. To return to the Main Search screen, click on the largest Binocular icon. This will return you to the previous screen (in the Thesaurus). At this point you may click on the Main Search tab near the bottom. This will return you to the Main Search screen. Position the cursor in the Disease field and then click on Edit and select Paste.

Valid search terms for randomized study and intranasal administration are available as descriptors in the IDIS database. You may select valid descriptor search terms utilizing the Look Up button at the end of the Descriptor field on the Main Search screen. Within the Look Up, the descriptors are arranged categorically beginning with Article Classification. Scrolling through the list, 135 STUDY RANDOMIZE ADULT is found under the heading Study. Select this term by clicking in the box next to it. The descriptor 126 ADM NOSE is found under the major heading Therapeutics, subcategory Administration. Select it by clicking in the box next to the term. Then, before clicking on OK, select And as the Connector (the default is Or). After OK, the chosen descriptors will appear in the Descriptor field. With the search terms entered in the fields, press <Enter> or click on Search. Index records for four articles are retrieved.

Clinical Information: Effectiveness of intranasal migraine preparations

Evaluating the efficacy and tolerability of intranasal sumatriptan for acute single migraine attack was the objective of two clinical studies (Ryan, 1997). Patients were men and women between the ages of 18 and 65 years who suffered from migraine headaches diagnosed using the International Headache Society criteria. Patients were randomized to treatment with sumatriptan nasal spray (10 mg or 20 mg) or placebo. Patients rated headache severity immediately before and 15, 30, 60, 90 and 120 minutes after dosing. Two hours after the first dose, "moderate or severe baseline pain was reduced to mild or none" in 62-63% of the 20-mg sumatriptan groups, 43-54% in the 10-mg groups and 29-35% in the placebo groups (p < 0.05, 10 mg or 20 mg vs. placebo). Complete headache relief at 2 hours postdose was experienced by 31-32% in the 20-mg groups, 20-23% in the 10-mg groups and 4-20% receiving placebo. Recurrent headache within the next 22 hours occurred in 32% of the 20-mg groups, 43-46% of the 10-mg groups and 34-55% of the placebo groups. The most frequent adverse event reported in the sumatriptan groups was unpleasant taste.

In another study, 81 subjects with International Headache Society-defined migraine were randomized to treatment with intranasal 4% lidocaine solution or placebo (Maizels, 1996). The objective of this study was to evaluate the effectiveness of intranasal lidocaine for the treatment of acute migraine headache with the primary outcome measure being at least 50% reduction of headache within 15 minutes of treatment. Headache severity was scored immediately after treatment and 2, 5, 10 and 15 minutes later. The authors reported a 50% decrease in mean pain intensity for the lidocaine group within 5 minutes (beginning average pain score 7.7 +/- 0.4 reduced to 4.4 +/- 0.7 on a scale of 0-10). Relapse of headache was reported as 42%, which was calculated from the number of patients who had pain relief from lidocaine and did not require rescue medication (10 relapse/24 responders). Side effects reported but not quantified included burning or numbness in the nose or around the eye, unpleasant taste and numbness in the throat with a sense of gagging.

Touchon (1996) compared sumatriptan and dihydroegotamine. Two hundred sixty-six patients with International Headache Society-defined migraine were randomized to treatment with either subcutaneous sumatriptan 6 mg or dihydroergotamine (DHE) 0.5 mg nasal spray once in each nostril. After the first treatment of migraine, patients were crossed over to the other study medication. Headache relief was maintained for 24 hours without deterioration in 54% of sumatriptan patients vs. 39% of dihydroergotamine patients (p < 0.001). Sumatriptan was also significantly more effective than dihydroergotamine from time 15 minutes onward (p < 0.001). Thirty-one percent of DHE patients had recurrence of headache, while only 17% of sumatriptan patients reported relapse. Malaise, fatigue, flushing, nausea and tingling were reported by sumatriptan users, whereas DHE patients experienced some nausea and nasal cavity/sinus problems.

In a study evaluating dihydroergotamine, 112 migraine patients were randomly assigned to intranasal dihydroergotamine 2 mg or placebo (Ziegler, 1994). Dihydroergotamine dose was 0.5 mg twice in each nostril 15 minutes apart. The mean change in headache intensity was calculated by subtracting the average pain intensity score at 4 hours from the average pain intensity score pretreatment. Headache intensity was measured on a scale of 1 = none, 2 = mild, 3 = moderate, 4 = severe and 5 = incapacitating. At 4 hours postdose, the mean change in headache intensity was 1.06 vs. placebo 0.01 (p < 0.001). The average pain relief score at 4 hours postdose was 2.95, based on a rating scale of 1 = none, 2 = little/none, 3 = some/moderate, 4 = a lot/good and 5 = complete. There was no mention of persons experiencing complete relief. Notably missing were data on the number of relapses. Twenty-nine percent of the DHE patients reported side effects. One patient experienced severe eyelid swelling shortly after DHE administration. Fourteen patients complained of nose or throat problems due to medication, and four complained of bitter/abnormal taste.

Besides the new nasal formulations, two new oral agents were recently approved. Zolmitriptan, Zomig®, was FDA approved in November 1997. Naratriptan, Amerge®, was approved in February 1998. Glaxo Wellcome Inc. also applied to the FDA for an Efficacy Supplemental New Drug Application to make a revision in the recommended adult dose for Imitrex® tablet. They received approval to make such changes on February 13, 1998. The new labeling states that there is now evidence that doses of 50 mg and 100 mg may provide greater effect than 25 mg. There is also evidence that 100-mg doses do not provide greater effect than 50-mg doses. The choice of dose should be on an individual basis as persons may vary in response to doses of Imitrex® tablets. The new maximum daily dose is listed as 200 mg (Glaxo Wellcome, 1998).

On January 14, 1998, the FDA approved Excedrin® Migraine (acetaminophen, aspirin, caffeine) for treatment of mild to moderate migraines. Experts do not expect persons taking prescription drugs to switch to this over-the-counter product, but they do expect it to be well received by the millions of migraine sufferers who do not have medical insurance or do not want to see a doctor (Ingersoll, 1998).

Whereas migraine sufferers once had few options for treatment, therapeutic options for migraine treatment are increasing. What share of the obviously very competitive migraine drug market and what role in migraine treatment guidelines intranasal preparations will eventually hold are yet to be seen. But for now, if nothing else, intranasal therapy offers at least one more treatment option for migraine sufferers.

Brad Gilchrist, R.Ph.

REFERENCES:

Cutler N, Mushet GR, Davis R et al. Oral sumatriptan for the acute treatment of migraine: Evaluation of three dosage strengths. Neurology. 1995;45(S7):S5-S9. (IDIS Article Number 352144)

Ferrari MD, Melamed E, Gawel MJ et al. Treatment of migraine attacks with sumatriptan. N Engl J Med. 1991;325:316-321. (IDIS Article Number 283296)

Imitrex® tablets package insert. Research Triangle Park, NC: Glaxo Wellcome Inc.; 1998 Feb.

Ingersoll B. FDA approves Extra-Strength Excedrin as over-the-counter migraine medicine. Wall St J (Midwest Ed). 1998;101(10):B12. (IDIS Article Number 397972)

Langreth R. Zeneca's migraine-headache drug gets marketing approval as rivalry grows. Wall St J (Midwest Ed). 1997;100(106):B2. (IDIS Article Number 395892)

Maizels M, Scott B, Cohen W et al. Intranasal lidocaine for treatment of migraine: A randomized, double-blind, controlled trial. JAMA. 1996;276:319-321. (IDIS Article Number 368694)

Prsye-Phillips WEM, Dodick DW, Edmeads JG et al. Guidelines for the diagnosis and management of migraine in clinical practice. Can Med Assoc J. 1997;156:1273-1287. (IDIS Article Number 384971)

Ryan R, Elkind A, Baker CC et al. Sumatriptan nasal spray for the acute treatment of migraine. Results of two clinical studies. Neurology. 1997;49:1225-1230. (IDIS Article Number 397206)

Touchon J, Bertin L, Pilgrim AJ et al. A comparison of subcutaneous sumatriptan and dihydroergotamine nasal spray in the acute treatment of migraine. Neurology. 1996;47:361-365. (IDIS Article Number 371392)

Ziegler D, Ford R, Kriegler J et al. Dihydroergotamine nasal spray for the acute treatment of migraine. Neurology. 1994;44:447-453. (IDIS Article Number 327300)


1998 Exhibit Schedule

Academy of Managed Care Pharmacy (AMCP)
Annual Meeting
April 30-May 2
New Orleans, Louisiana

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


SEARCH TIPS

IDIS-Windows® Search:
Raloxifene, Raloxifene and Estrogens, Raloxifene and Osteoporosis, Raloxifene and FDA Drug Approval

IDIS-Windows main search program opens with 14 searchable fields.

Choice of Drug Term

A search executed with a drug term entered in the Drug field retrieves all the records containing that term or its cross-referenced terms due to a seamless conversion to the valid drug term. For example, Evista® or raloxifene entered in the Drug field yields the same number of hits (20) (search executed against IDIS database from 1966 to February 1998). Terms in the Drug field with no specific Boolean connector are searched with Or.

A click on the Word button at the drug level opens a list of all single words used in the valid drug term vocabulary. Any term selected from the Word list can be searched as a single entity by automatic copy and paste. Terms from the list can be combined by using the Boolean operator And or Or, which is automatically transferred to the Drug field and searched.

Examples

Raloxifene. Click on the Word button, type ralox, click the left square box corresponding to raloxifene, and click <OK>. The main search template will appear with raloxifene automatically inserted in the Drug field. Scrolling down the word list and clicking in the corresponding square can also select the term and avoid some typing. Clicking on the Search button or pressing <Enter> brings the search result list (20 hits) with the full index record of the most recent citation. A click on the Image button allows you to view the article (starting with January 1998 articles).

Raloxifene and Estrogens. From the Main Search screen at the drug level, select raloxifene and estrogens from the Word list following the steps above. Then choose a connector (for example, And in this case) and click <OK>. Both selected terms and the selected boolean operator are now pasted in the Drug field and ready to be searched (seven hits).

A click on the Phrase button at the drug level opens an alphabetical list of all the valid drug definitions followed by their specific codes. Any term(s) selected from this list can be automatically pasted to the Drug field and searched. A term selected from the Phrase list can yield a more selective search than a term chosen from the Word list if the same term is used in more than one drug definition. For example, estrogens is used in the valid drug definitions estrogens and estrogens conjugated.

Examples

Raloxifene and Estrogens. A search done at the drug level with the terms estrogens and raloxifene selected from the Phrase list and connected with the Boolean operator And gives only six hits instead of seven hits (previous search).

Raloxifene and Estrogens Conjugated. A search done at the drug level with raloxifene and estrogens conjugated selected from the Phrase list and the connector And retrieves one hit.

The Thesaurus is another option for selecting a valid search term. The Thesaurus is a cross-reference of all valid drug (dr), disease (di) and descriptor (de) terms to their synonyms, trade names or similar concepts. A click on the Thesaurus button brings the Thesaurus screen. A valid term search can be done by using the Word list or by entering the terms in the Thesaurus field and clicking the Search button. The selected valid term(s) can be automatically exported to the chosen field and searched.

Choice of Disease Term

All steps used in a drug search can be used in the disease search.

Choice of Descriptor Term

Descriptors are used to further identify the contents of an article. A descriptor is seldom used as a sole query term, but constitutes a very powerful tool in narrowing a search.

A click on Phrase button brings a list of all valid IDIS descriptors terms available.

A click on Look Up button at the descriptor level opens a list of descriptors grouped by categories such as therapeutic, article classification, pharmaceutic and outcomes. In addition to the Thesaurus, the descriptor definitions file, available by clicking the Descriptors button from the main template, provides an excellent instrument in formulating effective search strategy.

A Thesaurus search shows that the concept drug approval is translated in IDIS by the descriptor Availability 109.

Combination of Terms From Different Fields

The 12 connector buttons on the main screen allow multiple combined field searching with the use of the logical operators And, Or and Not, the default being And.

Drug and Diseases: Raloxifene in the Treatment of Osteoporosis

Raloxifene and Osteoporosis. Select or copy and paste raloxifene from the drug Phrase list, and select or copy and paste osteoporosis from the disease Phrase list. Click the Search button or press <Enter> (11 citations).

Raloxifene or Osteoporosis; Raloxifene not Osteoporosis. A click on the connector button at the end of the Drug field uncovers the other choices. When the connector is changed to Or, 1,247 citations are found. A Not will retrieve nine citations.

Drug and Descriptors: FDA Approval of Raloxifene

Raloxifene was recently approved by the FDA for osteoporosis. Selecting the term raloxifene from the drug Phrase list and the term availability 109 from the descriptor Phrase list combined with the logical operator And pulls five citations related to the approval of this drug.

If you have any questions regarding how to search IDIS-Windows®, 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.

Some Searching Tips

IDIS Indexing of Letters-to-the-Editor--Enhancement

Beginning with the January 1998 update, letters-to-the-editor that comment on indexed articles in the database will be identified by including the article number in the title. The original article can be retrieved with the article number that appears in the title field of the letter. This will also allow the searcher to retrieve any letters for a particular article by entering the article number in the title field and then clicking on search. Any letters that have been indexed for that article will be retrieved.

For example, the title for the letter-to-the-editor identified as article number 398494 appears as follows:

ANTIBIOTIC PRESCRIBING AND RESPIRATORY TRACT INFECTIONS (REF MN 391325)

This indicates that the letter contains comments on IDIS Article 391325: Gonzales R, Steiner JF, Sande MA. Antibiotic prescribing for adults with colds, upper respiratory tract infections, and bronchitis by ambulatory care physicians. JAMA 1997;278:901-4.

To retrieve all letters in the database that contain comments on IDIS Article 391325, enter 391325 in the title field and click on search.

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

KEY REFERENCES

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 during October, November and December 1997. IDIS SYSTEM/CD-ROM was searched to retrieve key articles relevant to the new drugs and their approved uses.

Alatrovofloxacin Mesylate and Trofloxacin Mesylate

Ernst ME, Ernst EJ, Kelpser ME. Levofloxcin and trovafloxacin: the next generation of fluoroquinolones? Am J Health-Syst Pharm. 1997;54:2569-2584. (IDIS Article Number 395032). A comprehensive review of two of the newer fluroquinolones: trovafloxacin and levofloxacin.

Cutler NR, Vincent J, Jhee SS et al. Penetration of trovafloxacin into cerebrospinal fluid in humans following intravenous infusion of alatrofloxacin. Antimicrob Agts Chemother. 1997;41:1298- 1300. (IDIS Article Number 394213). A single-dose study of alatrofloxacin conducted to determine concentrations of trovafloxacin achieved in the cerebrospinal fluid relative to those in the serum of 12 healthy subjects after intravenous infusion of alatrofloxacin.

Andrews JM, Honeybourne D, Brenwald NP et al. Concentrations of trovafloxacin in bronchial mucosa, epithelial lining fluid, alveolar macrophages and serum after administration of single or multiple oral doses to patients undergoing fibre-optic bronchoscopy. J Antimicrob Chemother. 1997;39:797-802. (IDIS Article Number 389973). Investigators assessed the concentrations of trovafloxacin in bronchial mucosa, epithelial lining fluid, aleveolar macrophages and serum up to 24 hours after a single oral 200 mg dose of trovafloxacin in 18 patients and 6 hours after the last of four successive daily doses in nine patients.

Teng R, Dogolo LC, Willavize SA et al. Effect of Maalox and omeprazole on the bioavailability of trovafloxacin. J Antimicrob Chemother. 1997;39(Suppl B):93-97. (IDIS Article Number 387770). An open, placebo-controlled, randomized, fourway crossover study conducted in twelve healthy male volunteers that determined the effect of the concurrent administration of Maalox and omeprazole on the bioavailability of trovafloxacin.

Teng R, Dogolo LC, Willavize SA et al. Oral bioavailability of trovafloxacin with and without food in healthy volunteers. J Antimicrob Chemother. 1997;39(Suppl B):87-92. (IDIS Article Number 387769). In two randomized crossover studies, investigators determined the oral bioavailability of trovafloxacin in 12 healthy volunteers under fasted and fed conditions.

Vincent J, Teng R, Dogolo LC et al. Effect of trovafloxacin, a new fluoroquinolone antibiotic, on the steady-state pharmacokinetics of theophylline in healthy volunteers. J Antimicrob Chemother. 1997;39(Suppl B):81-86. (IDIS Article Number 387768). In a double-blind, placebo-controlled, parallel-group study, investigators assessed the effect of steady-state trovafloxacin concentrations on the steady-state pharmacokinetics of theophylline when theophylline doses were individualized to attain steady-state therapeutic concentrations in twelve healthy volunteers.

Hook EW, Pinson GB, Blalock CJ et al. Dose-ranging study of CP-99,219 (trovafloxacin) for treatment of uncomplicated gonorrhea. Antimicrob Agts Chemother. 1996;40:1720-1721. (IDIS Article Number 369813). In an open, randomized, non-comparative, dose-ranging study (50-200 mg), investigators assessed the effectiveness of trovafloxacin in treating 39 patients with uncomplicated gonorrhea.

Becaplermin, Platelet Derived Growth Factor

Mustoe TA, Cutler NR, Allman RM et al. A Phase II study to evaluate recombinant platelet-derived growth factor-BB in the treatment of stage 3 and 4 pressure ulcers. Arch Surg. 1994;129:213-219. (IDIS Article Number 325176). In a prospective, randomized, double-blind, placebo-controlled study, investigators assessed the efficacy of daily topical application of recombinant platelet-derived growth factor-BB in the treatment of deep pressure ulcers in 41 elderly patients.

Robson MC, Phillips LG, Thomason A et al. Platelet-derived growth factor BB for the treatment of chronic pressure ulcers. Lancet. 1992;339:23-25. (IDIS Article Number 290643). A randomized, phase I/II, double-blind, placebo-controlled study in which investigators assessed the effect of topically applied recombinant human BB homodimeric platelet-derived growth factor on the healing of chronic pressure ulcers in 20 patients for 28 days.

Cefdinir

Drehobl M, Bianchi P, Keyserling CH et al. Comparison of cefdinir and cefaclor in treatment of community-acquired pneumonia. Antimicrob Agts Chemother. 1997;41:1579-1582. (IDIS Article Number 389493). A multicenter, randomized, double-blind trial that compared the efficacy and safety of cefdinir (10 days of 300 mg twice daily) to cefaclor (10 days of 500 mg three times daily) in 690 patients with community-acquired pneumonia.

Gwaltney JM, Savolainen S, Rivas P et al. Comparative effectiveness and safety of cefdinir and amoxicillin-clavulanate in treatment of acute community-acquired bacterial sinusitis. Antimicrob Agts Chemother. 1997;41:1517-1520. (IDIS Article Number 389488). A report of two randomized, investigator-blind, multicenter trials that compared two dosage regimens of cefdinir (600 mg daily for 10 days and 300 mg twice daily for 10 days) to amoxicillin-clavulanate (500 mg three times daily for 10 days) for adult and adolescent acute community-acquired bacterial sinusitis in 1798 patients.

Tack KJ, Hedrick JA, Rothstein E et al. A study of 5-day cefdinir treatment for streptococcal pharyngitis in children. Arch Pediatr Adolesc Med. 1997;151:45-49. (IDIS Article Number 379950). Four hundred eight-two children were enrolled in an investigator-blind, randomized controlled trial conducted to compare the safety and efficacy of a 5-day regimen (7 mg/kg twice daily) of cefdinir with a conventional 10-day regimen of penicillin V for the treatment of streptococcal pharyngitis in children.

Sperling MJ, Puopolo A, Griffin TJ et al. Efficacy and safety of cefdinir in the treatment of patients with acute bronchitis. Clin Ther. 1996;18:626-634. (IDIS Article Number 373579). In this randomized, open-label, dose-comparative study, investigators enrolled 466 patients with acute bronchitis to assess the efficacy and safety of cefdinir.

Clopidrogrel Bisulfate

Gent M, Beaumont D, Blanchard J et al. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 1996;348:1329-1339. (IDIS Article Number 376382). A randomized, blinded, international study that assessed the relative efficacy of 75 mg clopidogrel once daily to 325 mg aspirin once daily for 1 to 3 years in reducing the risk of a composite outcome cluster of ischemic stroke, myocardial infarction or vascular death in 19,185 patients with atherosclerotic vascular disease and at risk for ischemic events.

Boneu B, Destelle G, Bachmann F et al. Platelet anti-aggregating activity and tolerance of clopidogrel in atherosclerotic patients. Thromb Haemost. 1996;76:939-943. (IDIS Article Number 379194). A multicenter, randomized, parallel-group study where clopidogrel was administered at increasing doses from 10 to 100 mg daily for 28 days to determine its pharmacological activity and tolerance in 150 patients with peripheral arterial disease or cardiac or cerebral manifestations of atherosclerosis.

Daclizumab

Vincenti F, Lantz M, Birnbaum J et al. A Phase I trial of humanized anti-interleukin 2 receptor antibody in renal transplantation. Transplantation. 1997;63:33-38. (IDIS Article Number 381037). A report of a Phase I study in which the safety, pharmacokinetics-dynamics, and immunosuppressive effect of a humanized anti-interleukin 2 monoclonal antibody was evaluated in 12 renal transplant recipients.

Eprosartan Mesylate

Tenero D, Martin D, Chapelsky M et al. Effect of hepatic disease on the pharmacokinetics and plasma protein binding of eprosartan. Pharmacotherapy. 1998;18:42-50. (IDIS Article Number 398631). A parallel-group study to evaluate the pharmacokinetics and plasma protein binding of a single oral dose of eprosartan 100 mg in 8 subjects with normal hepatic function and 8 patients with hepatic disease.

Fomepizole

Jobard E, Harry P, Turcant A et al. 4-methylpyrazole and hemodialysis in ethylene glycol poisoning. J Toxicol Clin Toxicol. 1996;34:373-377. (IDIS Article Number 372622). A report of two cases of ethylene glycol poisoning in which an infusion of fomepizole and hemodialysis were used to successfully treat the patients.

Faessel H, Houze P, Baud FJ et al. 4-methylpyrazole monitoring during haemodialysis of ethylene glycol intoxicated patients. Eur J Clin Pharmacol. 1995;49:211-213. (IDIS Article Number 357814). A report of two cases of ethylene glycol- intoxicated patients in which fomepizole plasma levels were closely monitored during IV administration of the drug during hemodialysis.

Baud FJ, Galliot M, Astier A et al. Treatment of ethylene glycol poisoning with intravenous 4-methylpyrazole. N Engl J Med. 1988;319:97-100. (IDIS Article Number 243317). A report of the clinical and toxicokinetic data of a case of acute ethylene glycol intoxication treated with intravenous fomepizole.

Grepafloxacin HCl

Topkis S, Swarz H, Breisch SA et al. Efficacy and safety of grepafloxacin 600 mg daily for 10 days in patients with community-acquired pneumonia. Clin Ther. 1997;19:975-988. (IDIS Article Number 397231). The efficacy and safety of grepafloxacin (600 mg daily for 10 days) was assessed in an open-label, noncomparative study of 273 patients with community acquired pneumonia.

Hook EW, McCormack WM, Martin D et al. Comparison of single-dose oral grepafloxacin with cefixime for treatment of uncomplicated gonorrhea in men. Antimicrob Agts Chemother. 1997;41:1843-1845. (IDIS Article Number 389709). In a randomized open study, investigators compared the safety and efficacy of single oral doses of grepafloxacin (400 mg) or cefixime (400 mg) in 351 male patients with uncomplicated gonorrhea.

Cook PJ, Andrews JM, Wise R et al. Concentrations of OPC-17116, a new fluoroquinolone antibacterial, in serum and lung compartments. J Antimicrob Chemother. 1995;35:317-326. (IDIS Article Number 343766). This study compared grepafloxacin concentrations in serum, bronchial mucosa, epithelial lining fluid and alveolar macrophages, in 24 patients undergoing diagnostic bronchoscopy who were receiving oral grepafloxacin 400 mg daily.

Oprelvekin, Recombinant Interleukin 11

Isaacs C, Robert NJ, Bailey FA et al. Randomized placebo-controlled study of recombinant human interleukin-11 to prevent chemotherapy-induced thrombocytopenia in patients with breast cancer receiving dose-intensive cyclophosphamide and doxorubicin. J Clin Oncol. 1997;15:3368-3377. (IDIS Article Number 396653). A randomized, blinded, placebo-controlled study of the efficacy and safety of subcutaneous recombinant human interleukin-11 to reduce the need for platelet transfusions in 77 women with advanced breast cancer who underwent dose-intensive chemotherapy.

Du X, Willliams DA. Interleukin-11: review of molecular, cell biology, and clinical use. Blood. 1997;89:3897-3908. (IDIS Article Number 387422). A comprehensive review of molecular, cell biology and the clinical use of interleukin-11.

Tepler I, Elias L, Smith JW et al. A randomized placebo-controlled trial of recombinant human interleukin-11 in cancer patients with severe thrombocytopenia due to chemotherapy. Blood. 1996;87:3607-3614. (IDIS Article Number 366230). In a multicenter, randomized, placebo-controlled trial investigators tested the ability of recombinant human interleukin-11 to prevent the need for platelet transfusions in 93 patients with cancer.

Raloxifene HCl

Delmas PD, Bjarnason NH, Mitlak BH et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med. 1997;337:1641-1647. (IDIS Article Number 397097). A report of the 24-month interim results of a long-term multicenter, placebo-controlled, double-blind study examining the effects of raloxifene on regional and total-body bone mineral density, bone turnover, serum lipid concentrations and endometrial thickness in 601 healthy postmenopausal women.

Heaney RP, Draper MW. Raloxifene and estrogen: comparative bone-remodeling kinetics. J Clin Endocrinol Metab. 1997;82:3425-3429. (IDIS Article Number 394863). A randomized, placebo-controlled study that compared the pattern of changes in human bone remodeling produced by long term therapy of raloxifene (60 mg/day) to that of hormone replacement therapy in 33 early postmenopausal women.

Repaglinide

Wolffenbuttel BHR, Nijst L, Sels JPJ et al. Effects of a new oral hypoglycaemic agent, repaglinide, on metabolic control in sulphonylurea-treated patients with NIDDM. Eur J Clin Pharmacol. 1993;45:113-116. (IDIS Article Number 321271). This open, randomized, controlled 12-week study compared the effects of repaglinide to glibenclamide twice daily in 44 patients with NIDDM, already treated with a sulfonylurea.

Rituximab

Maloney DG, Grillo-Lopez AJ, Bodkin DJ et al. IDEC-C2B8: results of a Phase I multiple-dose trial in patients with relapsed non-Hodgkin's lymphoma. J Clin Oncol. 1997;15:3266-3274. (IDIS Article Number 395156). In a Phase I study, investigators evaluated the safety, pharmacokinetics and biologic effect of multiple doses of rituximab in 20 patients with relapsed B-cell lymphoma. Maloney DG, Grillo-Lopez AJ, White CA et al. IDEC-C2B8 (rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma. Blood. 1997;90:2188-2195. (IDIS Article Number 393616). In a Phase II multicenter study, investigators monitored 37 patients with relapsed low-grade or follicular non-Hodgkin's lymphoma, who received four weekly infusions of 375 mg/m2 rituximab, for adverse events, antibody pharmacokinetics and clinical response.

Sibutramine

Luque CA, Rey JA, Fernandez A. Focus on Sibutramine: a new anorectic agent for the treatment of obesity. Formulary. 1997;32:1025-1039. (IDIS Article Number 396006). A comprehensive review of sibutramine as an anorectic agent.

Weintraub M, Rubio A, Golike A et al. Sibutramine in weight control: a dose-ranging, efficacy study. Clin Pharmacol Ther. 1991;50:330-337. (IDIS Article Number 289396). In a parallel-group, double-blind, placebo-controlled 12-week study, investigators evaluated the efficacy and safety of sibutramine, 5 and 20 mg, and placebo on weight loss in 60 obese patients.

Talc Aerosol

Yim APC, Chan ATC, Lee TW et al. Thoracoscopic talc insufflation versus talc slurry for symptomatic malignant pleural effusion. Ann Thorac Surg. 1996;62:1655-1658. (IDIS Article Number 377654). A prospective, randomized study in which investigators compared thoracoscopic talc insufflation to talc slurry in 57 patients with malignant pleural effusion.

Hartman DL, Gaither JM, Kesler KA et al. Comparison of insufflated talc under thoracoscopic guidance with standard tetracycline and bleomycin pleurodesis for control of malignant pleural effusions. J Thorac Cardiovasc Surg. 1993;105:743-748. (IDIS Article Number 313506). Investigators evaluated the insufflation of intrapleural talc under thoracoscopic guidance in 39 patients against documented controls that consisted of 85 patients who participated in a randomized study with tube thoracostomy drainage followed by either bleomycin or tetracycline sclerosis.

Zolmitriptan

Solomon GD, Cady RK, Klapper JA et al. Clinical efficacy and tolerability of 2.5 mg zolmitriptan for the acute treatment of migraine. Neurology. 1997;49:1219-1225. (IDIS Article Number 397205). A randomized, double-blind, placebo-controlled clinical trial in which investigators evaluated the efficacy of zolmitriptan 2.5 mg in 327 patients.

Rapoport AM, Ramadan NM, Adelman JU et al. Optimizing the dose of zolmitriptan (Zomig, 311C90) for the acute treatment of migraine. A multicenter, double-blind, placebo-controlled, dose-ranging study. Neurology. 1997;49:1210-1218. (IDIS Article Number 397204). Investigators in a randomized, double-blind, multicenter, placebo-controlled, dose range-finding study evaluated the efficacy of oral zolmitriptan 1, 2.5, 5, or 10 mg versus placebo for acute migraine in 1,144 patients.

Zamagi AS et al. 311C90: long-term efficacy and tolerability profile for the acute treatment of migraine. Neurology. 1997;48(Suppl 3):S25-S28. (IDIS Article Number 382026). Investigators in an open-label study assessed the tolerability and efficacy of repeated doses of 5 mg of zolmitriptan for acute treatment of multiple attacks for up to 1 year in 2,058 patients.

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
Alatrofloxacin Mesylate
(1S)**
Trovan I.V.
Pfizer
(Dec. 18)
ALATROFLOXACIN
8122027
(3 citations)
Broad spectrum antibacterial agent indicated for the treatment of infections caused by susceptible strains of microorganisms Infection, Bacterial NEC
041.
Becaplermin, Platelet Derived Growth Factor

Regranex
Ortho-McNeil
(Dec. 16)
GROWTH FACTOR, PLATELET-DERV
95000078
(13 citations)
Treatment of lower extremity diabetic neuropathic ulcers that extend into the subcutaneous tissue or beyond and have an adequate blood supply Ulcer, Skin, Chronic NEC
707.
Diabetes Mellitus
250.
Cefdinir
(1S)
Omnicef
Warner-Lambert
(Dec. 4)
CEFDINIR
8120666
(22 citations)
Treatment of community-acquired pneumonia, acute exacerbations of chronic bronchitis, acute bacterial otitis media, acute maximillary sinusitis, pharyngitis/tonsillitis and uncomplicated skin and skin structure infections Pneumonia, Bacterial NEC
482.
Bronchitis, Chronic NEC
491.
Sinusitis, Acute
461.
Clopidogrel Bisulfate
(1P)***
Plavix
Sanofi
(Nov. 17)
CLOPIDOGREL
20120645
(24 citations)
Reduction of atherosclerotic events (myocardial infarction, stroke, and vascular death) in patients with atherosclerosis documented by recent stroke, recent myocardial infarction or established peripheral arterial disease Infarction, Myocard, Acute
410.
Disease, Cerebrovascular NEC
436.
Atherosclerosis
440.
Daclizumab

Zenapax
Hoffmann-LaRoche
(Dec. 10)
DACLIZUMAB
82000444
(5 citations)
Prophylaxis of acute organ rejection in patients receiving renal transplants in combination with an immunosuppressive regimen Prophylaxis NEC
V07.
Complication, Organ Transpl
996.8
Transplant, Kidney
55.6
Eprosartan Mesylate
(1S)
Teveten
SmithKline Beecham
(Dec. 22)
EPROSARTAN
24080074
(5 citations)
For use in the management of essential hypertension Hypertension
401.
Fomepizole
(1S)
Antizol
Orphan Medical
(Dec. 4)
FOMEPIZOLE
44100006
(26 citations)
Antidote to ethylene glycol (antifreeze) poisoning in patients who have ingested, or are suspected of having ingested ethylene glycol Tx/Pois-Non Medicinal
989.
Grepafloxacin HCl
(1S)
Raxar
Glaxo Wellcome
(Nov. 6)
GREPAFLOXACIN
8122019
(21 citations)
Provides for the indications of acute bacterial exacerbations of chronic bronchitis, community-acquired pneumonia, uncomplicated gonorrhea, and nongonococcal urethritis and cervicitis Infection, Gonococcal, GU
098.0
Pneumonia, Bacterial NEC
482.
Urethritis, Nonsex Transit
597.
Oprelvekin, Recombinant Interleukin 11

Neumega
Genetics Institute
(Nov. 25)
INTERLEUKIN 11
14000409
(11 citations)
Prevention of severe thrombocytopenia and the reduction of the need for platelet transfusions following myelosuppressive chemotherapy in patients with nonmyeloid malignancies who are at high risk of severe thrombocytopenia Thrombocytopenia, Secondary
287.4
Prophylaxis NEC
V07.
Raloxifene HCl
(1P)
Evista
Lilly
(Dec. 9)
RALOXIFENE
68160408
(20 citations)
Prevention of osteoporosis in postmenopausal women Osteoporosis
733.0
Disorder, Menopause/Post NEC
627.
Repaglinide
(1P)
Prandin
Novo Nordisk
(Dec. 22)
REPAGLINIDE
68200402
(1 citation)
Adjunct to diet and exercise to lower blood glucose in patients with non-insulin dependent (Type II) diabetes mellitus whose hyperglycemia cannot be controlled satisfactorily with diet and exercise alone; for use in combination with metformin to lower blood glucose in patients whose hyperglycemia cannot be controlled by exercise, diet and either replaglinide or metformin alone Diabetes Mellitus
250.
Rituximab

Rituxan
Genentech
(Nov. 26)
RITUXIMAB
82000443
(7 citations)
Treatment of patients with relapsed or refractory low-grade or follicular, CD20 positive, B-cell non-Hodgkin's lymphoma Neop, Mgn-Lymph/Histio NEC
202.
Sibutramine
(1S)
Meridia
Knoll
(Nov. 22)
SIBUTRAMINE
28160461
(17 citations)
Management of obesity, including weight loss and maintenance of weight loss, and should be used in conjunction with a reduced calorie diet Obesity
278.0
Talc
(1P)
Sclerosol
Bryan
(Dec. 24)
TALC
96000008
(184 citations)
Malignant pleural effusions Neop, Sec-Pleura
197.2
Trovafloxacin Mesylate
(1S)
Trovan
Pfizer
(Dec. 18)
TROVAFLOXACIN
8122024
(55 citations)
Broad-spectrum antibacterial agent indicated for the treatment of infections caused by susceptible strains of microorganisms Infection, Bacterial NEC
041.
Zolmitriptan
(1S)
Zomig
Zeneca ZOLMITRIPTAN
92000257
(14 citations)
Treatment of migraine headache Migraine
346.

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


Staff Profile
The friendly and helpful voice greeting you when calling DDIS is most likely Liz Smothers. Liz has been a Secretary II with the University of Iowa since December 1986 and came to work in the main office at the Division of Drug Information Service in November 1997.

Her responsibilities in the division include making travel and exhibit arrangements, answering the phone and routing calls, scheduling meetings and performing word processing and database projects.

The most important aspects of Liz's life are her son, Nathan, who will graduate from high school in May, and her husband, Jerry. The three of them are very close and enjoy many activities together such as camping, swimming and riding their Harley Davidsons.


World of Drug Information is published quarterly
(March, June, September, December)
by the Division of Drug Information Service.
Editor: Donna Brus
Photographer: David Luck
Production Coordinator: Jane Heaton


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

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