Geriatric Pharmacotherapy Update: New Medications, Recent Releases, and Coming Attractions

Fri, 9/5/08 - 4:54pm
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Author(s):

Peggy Soule Odegard, PharmD, BCPS, CDE, and Stephen M. Setter, PharmD, CDE, CGP, DVM

INTRODUCTION
Each year, many new medications or new uses for old medications are approved by the U.S. Food and Drug Administration (FDA). In 2004, 119 new medications and 147 new or expanded uses for already approved medications were approved for use in the United States.1 This article will focus on several of these new therapies submitted to the FDA for approval in 2004-2005, with an emphasis on agents potentially useful in conditions experienced by older adults. These agents include trospium (approved 5/28/04), eszopiclone (approved 12/15/04), inhaled insulin (approved 1/27/06), pramlintide (approved 3/16/05), exenatide (approved 4/28/05), and insulin detemir (approved 6/16/05). The mechanism of action (MOA), therapeutic application, side effects, and monitoring of these new drugs will be examined, with some discussion of how they compare to other therapies. Available data will be presented that support conclusive recommendations for use in older adults; however, cautious use is always recommended in this unique population.

URINARY INCONTINENCE
Several medications are available for the treatment of bladder dysfunction, including oxybutynin and tolterodine. Trospium was introduced to the market last year after approval by the FDA in May 2004. It is indicated for the treatment of overactive bladder (OAB), urinary incontinence, and neurogenic bladder. Trospium is an addition to the existing group of agents used for the treatment of urinary incontinence and shares a similar mechanism of action related to its antimuscarinic qualities. Specifically, the drug works as an antispasmodic and antimuscarinic, inhibiting peripheral muscarinic receptors, relaxing urogenital smooth muscle tone, and resulting in reduced urinary urgency and frequency.2 It is a quaternary ammonium compound, however, and so does not cross the blood-brain barrier or conjunctiva to the extent of other similar agents. Despite this, side effects are similar to other antimuscarinic (eg, anticholinergic) agents and include dry mouth (20.1%, N = 591 trospium vs 5.8%, N = 590 placebo) and constipation (9.6% vs 4.6% placebo).3 Theoretically, trospium may have reduced effect on the central nervous system and, therefore, a reduced risk of potential disease or drug interactions in those with dementia taking cholinergic medications. Precaution is recommended for those with urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma due to the potential for exacerbation of these conditions by anticholinergic agents. With the incidence of OAB increased in older age, data are available from clinical trials in older adults for trospium, with the mean age of study subjects in published trials of 63 years. Pharmacokinetic data on trospium are primarily based on information from healthy volunteers. Trospium has extremely limited oral absorption of less than 10%, and this is reduced significantly (80% decrease) by a fatty meal. The majority (60%) of the drug is eliminated by the kidney unchanged, dictating a need for dose reduction if creatinine clearance (CrCl) is less than 30 mL/min. Although 40% of the drug is metabolized by the liver, drug interactions are more a pharmacodynamic concern with other anticholinergic agents or drugs that increase acetylcholine, such as the acetylcholinesterase inhibitors (eg, donepezil).2 The dose of trospium recommended by the manufacturer is initiation at 20 mg orally twice daily, with titration down to 20 mg orally at bedtime in older adults who cannot tolerate the anticholinergic side effects. Given the potential difficulty in backing down from side effects, it seems prudent to initiate therapy at the lower 20 mg orally at bedtime in older adults, and titrating up to 20 mg orally twice daily if the medication is well tolerated and additional effects are desired.

References:

References
1. Center for Drug Evaluation and Research, 2004. Report to the Nation, Improving Public Health Through Human Drugs. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research. Available at: http://www.fda.gov/cder/reports/rtn/2004/ Rtn2004.pdf. Accessed January 26, 2006.

2. Rovner ES. Trospium chloride in the management of overactive bladder. Drugs 2004;64(21):2433-2446.

3. Available at Sanctura®, Full Prescribing Information, Odyssey Pharmaceuticals, Inc. Available at: http: //www.sanctura.com/professional/about_sanctura/safety.aspx, Accessed January 26, 2006.

4. Zinner N, Gittelman M, Harris R, et al; Trospium Study Group. Trospium chloride improves overactive bladder symptoms: A multicenter phase III trial. J Urol 2004;171 (6 Pt 1):2311-2315.

5. Halaska M, Ralph G, Wiedeman A, et al. Controlled, double-blind, multicentre clinical trail to investigate long-term tolerability and efficacy of trospium chloride in patients with detrusor instability. World J Urol 2003;20:392-399.

6. Junemann KP, Al-Shukri S. Efficacy and tolerability of trospium chloride and toleterodine in 234 patients with urge syndrome: A double-blind, placebo-controlled, multicentre, clinical trial. Neurourol Urodyn 2000;19(4):488-490.

7. Krystal AD, Walsh JK, Laska E, Caron J, et al. Sustained efficacy of eszopiclone over 6 months of nightly treatment: results of a randomized, double-blind, placebo-controlled study in adults with chronic insomnia. Sleep 2003;26(7):793-799.

8. Centers for Disease Control and Prevention. National diabetes fact sheet: general information and national estimates on diabetes in the United States, 2005. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention; 2005.

9. Himmelmann A, Jendle J, Mellen A, et al. The impact of smoking on inhaled insulin. Diabetes Care 2003;26:677-682.

10. Pfizer product information. NDA 21-868/EXUBERA US Package Insert. Pfizer Labs, Division of Pfizer, Inc., NY, NY 10017. Available at: http://www.fda. gov/cder/foi/label/2006/021868lbl.pdf. Accessed February 22, 2006.

11. Heinemann L, Traut T, Heise T. Time-action profile of inhaled insulin. Diabet Med 1997;14:63-72.

12. Skyler J for the Exubera™ Phase II Study Group. Sustained long-term efficacy and safety of inhaled insulin during 4 years continuous therapy. Diabetes 2004;53 (Suppl 2):A115.

13. Hollander PA, Blonde L, Rowe R, et al. Efficacy and safety of inhaled insulin (Exubera™) compared with subcutaneous insulin therapy in patients with type 2 diabetes: Results of a 6-month, randomized, comparative trial. Diabetes Care 2004;27(10):2356-2362.

14. Quattrin T, Belanger A, Bohanon NJV, Schwartz SL; Exubera™ Phase III Study Group. Efficacy and safety of inhaled insulin (Exubera™) compared with subcutaneous insulin therapy in patients with type 1 diabetes. Diabetes Care 2004;27(11):2622-2627.

15. Skyler JS, Weinstock RS, Raskin P, et al; Inhaled Insulin Phase III Type 1 Diabetes Study Group. Use of inhaled insulin in a basal/bolus insulin regimen in type 1 diabetic subjects: A 6-month, randomized, comparative trial. Diabetes Care 2005;28(7):1630-1635.

16. McQueen J. Pramlintide acetate. Am J Health Syst Pharm 2005;62:2363-2372.

17. Hollander P, Ratner R, Fineman M, et al. Addition of pramlintide to insulin therapy lowers HbA1c in conjunction with weight loss in patients with type 2 diabetes approaching glycaemic targets. Diabetes Obes Metab 2003;5:408-414.

18. Defronzo RA, Ratner RE, Han J, et al. Effects of exenatide (exendin-4) on glycemic control and weight over 30weeks in metformin-treated patients with type 2 diabetes. Diabetes Care 2005;28:1092-1100.

19. Buse JB, Henry RR, Han J, et al; Exenatide-113 Clinical Study Group. Effects of exenatide (exendin-4 on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care 2004;27:2628-2635.

20. Kendall DM, Riddle MC, Rosenstock J, et al. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care 2005;28:1083-1091.

21. Kurtzhals P, Havelund S, Honassen I, et al. Effect of fatty acids and selected drugs on the albumin binding of a long-acting, acylated insulin analogue. J Pharm Sci 1997;86:1365-1368.

22. Vague P, Selam JL, Skeie S, et al. Insulin detemir is associated with more predictable glycemic control and reduced risk of hypoglycemia than NPH insulin in patients with type 1 diabetes on a basal-bolus regimen with premeal insulin aspart. Diabetes Care 2003;26:590-596.

23. Home P, Bartley P, Russell-Jones D, et al; Study to Evaluate the Administration of Detemir Insulin Efficacy, Safety, and Suitability (STEADINESS) Study Group. Insulin detemir offers improved glycemic control compared with NPH insulin in people with type 1 diabetes. Diabetes Care 2004;27:1081-1087.