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BMC Health Services Research
Published in: BMC Health Services Research 1/2015

Open Access 01-12-2015 | Research article

A retrospective, matched cohort study of potential drug-drug interaction prevalence and opioid utilization in a diabetic peripheral neuropathy population initiated on pregabalin or duloxetine

Authors: Jeffrey J Ellis, Alesia B Sadosky, Laura L Ten Eyck, Pallavi Mudumby, Joseph C Cappelleri, Lilian Ndehi, Brandon T Suehs, Bruce Parsons

Published in: BMC Health Services Research | Issue 1/2015

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Abstract

Background

Anticipating and controlling drug-drug interactions (DDIs) in older patients with painful diabetic peripheral neuropaty (pDPN) presents a significant challenge to providers. The purpose of this study was to examine the impact of newly initiated pregabalin or duloxetine treatment on Medicare Advantage Prescription Drug (MAPD) plan pDPN patients’ encounters with potential drug-drug interactions, the healthcare cost and utilization consequences of those interactions, and opioid utilization.

Methods

Study subjects required a pregabalin or duloxetine pharmacy claim between 07/01/2008-06/30/2012 (index event), ≥1 inpatient or ≥2 outpatient medical claims with pDPN diagnosis between 01/01/2008-12/31/2012, and ≥12 months pre- and ≥6 post-index enrollment. Propensity score matching was used to balance the pregabalin and duloxetine cohorts on pre-index demographics and comorbidities. Potential DDIs were defined by Micromedex 2.0 and identified by prescription claims. Six-month post-index healthcare utilization (HCU) and costs were calculated using pharmacy and medical claims.

Results

No significant differences in pre-index demographics or comorbidities were found between pregabalin subjects (n = 446) and duloxetine subjects (n = 446). Potential DDI prevalence was significantly greater (p < 0.0001) among duoxetine subjects (56.7%) than among pregabalin subjects (2.9%). There were no significant differences in HCU or costs between pregablin subjects with and without a potential DDI. By contrast, duloxetine subjects with a potential DDI had higher mean all-cause costs ($13,908 vs. $9,830; p = 0.001), more subjects with ≥1 inpatient visits (35.6% vs 25.4%; p = 0.02), and more subjects with ≥1 emergency room visits (32.8% vs. 20.7%; p = 0.005) in comparison to duloxetine subjects without a potential DDI. There was a trend toward a difference between pregabalin and duloxetine subjects in their respective pre-versus-post differences in milligrams (mg) of morphine equivalents/30 days used (60.2 mg and 176.9 mg, respectively; p = 0.058).

Conclusion

The significantly higher prevalence of potential DDIs and potential cost impact found in pDPN duloxetine users, relative to pregabalin users, underscore the importance of considering DDIs when selecting a treatment.
Literature
1.
Thomas PK. Classification, differential diagnosis, and staging of diabetic peripheral neuropathy. Diabetes. 1997;46:S54–7.PubMed
2.
Freeman R. Autonomic peripheral neuropathy. Lancet. 2005;365(9466):1259–70.PubMed
3.
Schmader KE. Epidemiology and impact on quality of life of postherpetic neuralgia and painful diabetic neuropathy. Clin J Pain. 2002;18(6):350–4.PubMed
4.
Boulton AJM, Malik RA, Arezzo JC, Sosenko JM. Diabetic somatic neuropathies. Diabetes Care. 2004;27(6):1458–86.PubMed
5.
Boulton AJ, Vinik AI, Arezzo JC, Bril V, Feldman EL, Freeman R, et al. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care. 2005;28(4):956–62.PubMed
6.
Barrett AM, Lucero MA, Le T, Robinson RL, Dworkin RH, Chappell AS. Epidemiology, public health burden, and treatment of diabetic peripheral neuropathic pain: a review. Pain Med. 2007;8 Suppl 2:S50–62.PubMed
7.
Fischer TZ, Waxman SG. Neuropathic pain in diabetes–evidence for a central mechanism. Nat Rev Neurol. 2010;6(8):462–6.PubMed
8.
Eaton SE, Harris ND, Rajbhandari SM, Greenwood P, Wilkinson ID, Ward JD, et al. Spinal-cord involvement in diabetic peripheral neuropathy. Lancet. 2001;358(9275):35–6.PubMed
9.
Hovaguimian A, Gibbons CH. Clinical approach to the treatment of painful diabetic neuropathy. Ther Adv Endocrinol Metab. 2011;2(1):27–38.PubMedPubMedCentral
10.
Vinik AI, Casellini CM. Guidelines in the management of diabetic nerve pain: clinical utility of pregabalin. Diabetes Metab Syndr Obes. 2013;6:57–78.PubMedPubMedCentral
11.
Tesfaye S. Advances in the management of diabetic peripheral neuropathy. Curr Opin Support Palliat Care. 2009;3(2):136–43.PubMed
12.
Gore M, Brandenburg NA, Hoffman DL, Tai K-S, Stacey B. Burden of illness in painful diabetic peripheral neuropathy: the patients' perspectives. J Pain. 2006;7(12):892–900.PubMed
13.
Lesser H, Sharma U, LaMoreaux L, Poole RM. Pregabalin relieves symptoms of painful diabetic neuropathy: a randomized controlled trial. Neurology. 2004;63(11):2104–10.PubMed
14.
Rosenstock J, Tuchman M, LaMoreaux L, Sharma U. Pregabalin for the treatment of painful diabetic peripheral neuropathy: a double-blind, placebo-controlled trial. Pain. 2004;110(3):628–38.PubMed
15.
Richter RW, Portenoy R, Sharma U, Lamoreaux L, Bockbrader H, Knapp LE. Relief of painful diabetic peripheral neuropathy with pregabalin: a randomized, placebo-controlled trial. J Pain. 2005;6(4):253–60.PubMed
16.
Goldstein DJ, Lu Y, Detke MJ, Lee TC, Iyengar S. Duloxetine vs. placebo in patients with painful diabetic neuropathy. Pain. 2005;116(1–2):109–18.PubMed
17.
Raskin J, Pritchett YL, Wang F, D’Souza DN, Waninger AL, Iyengar S, et al. A double-blind, randomized multicenter trial comparing duloxetine with placebo in the management of diabetic peripheral neuropathic pain. Pain Med. 2005;6(5):346–56.PubMed
18.
Wernicke JF, Pritchett YL, D’Souza DN, Waninger A, Tran P, Iyengar S, et al. A randomized controlled trial of duloxetine in diabetic peripheral neuropathic pain. Neurology. 2006;67(8):1411–20.PubMed
19.
Hoy SM. Tapentadol extended release: in adults with chronic pain. Drugs. 2012;72(3):375–93.PubMed
20.
Schwartz S, Etropolski M, Shapiro DY, Okamoto A, Lange R, Haeussler J, et al. Safety and efficacy of tapentadol ER in patients with painful diabetic peripheral neuropathy: results of a randomized-withdrawal, placebo-controlled trial. Curr Med Res Opin. 2011;27(1):151–62.PubMed
21.
Jensen TS, Backonja M-M, Hernández Jiménez S, Tesfaye S, Valensi P, Ziegler D. New perspectives on the management of diabetic peripheral neuropathic pain. Diabetes Vasc Dis Res. 2006;3(2):108–19.
22.
Zin CS, Nissen LM, O’Callaghan JP, Duffull SB, Smith MT, Moore BJ. A randomized, controlled trial of oxycodone versus placebo in patients with postherpetic neuralgia and painful diabetic neuropathy treated with pregabalin. J Pain. 2010;11(5):462–71.PubMed
23.
Gimbel JS, Richards P, Portenoy RK. Controlled-release oxycodone for pain in diabetic neuropathy: a randomized controlled trial. Neurology. 2003;60(6):927–34.PubMed
24.
Watson CPN, Moulin D, Watt-Watson J, Gordon A, Eisenhoffer J. Controlled-release oxycodone relieves neuropathic pain: a randomized controlled trial in painful diabetic neuropathy. Pain. 2003;105(1–2):71–8.PubMed
25.
Roy S, Loh HH. Effects of opioids on the immune system. Neurochem Res. 1996;21(11):1375–86.PubMed
26.
Lee C, Ludwig S, Duerksen DR. Low serum cortisol associated with opioid use: case report and review of the literature. Endocrinol. 2002;12:5–8.
27.
Daniell HW. Opioid endocrinopathy in women consuming prescribed sustained-action opioids for control of nonmalignant pain. J Pain. 2008;9(1):28–36.PubMed
28.
Pergolizzi J, Böger RH, Budd K, Dahan A, Erdine S, Hans G, et al. Opioids and the management of chronic severe pain in the elderly: consensus statement of an International Expert Panel with focus on the six clinically most often used World Health Organization Step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone). Pain Pract. 2008;8(4):287–313.PubMed
29.
Gore M, Zlateva G, Tai KS, Chandran AB, Leslie D. Retrospective evaluation of clinical characteristics, pharmacotherapy and healthcare resource use among patients prescribed pregabalin or duloxetine for diabetic peripheral neuropathy in usual care. Pain Pract. 2011;11(2):167–79.PubMed
30.
Gore M, Tai KS, Chandran A, Zlateva G, Leslie D. Clinical comorbidities, treatment patterns, and healthcare costs among patients with fibromyalgia newly prescribed pregabalin or duloxetine in usual care. J Med Econ. 2012;15(1):19–31.PubMed
31.
Gore M, Sadosky A, Tai K-S, Stacey B. A retrospective evaluation of the use of gabapentin and pregabalin in patients with postherpetic neuralgia in usual-care settings. Clin Ther. 2007;29:1655–70.PubMed
32.
Gore M, Tai K-S, Zlateva G, Chandran AB, Leslie D. Clinical characteristics, pharmacotherapy, and healthcare resource use among patients with diabetic neuropathy newly prescribed pregabalin or gabapentin. Pain Pract. 2011;11:1–12.
33.
Wu N, Chen SY, Hallett LA, Boulanger L, Fraser KA, Patel CK, et al. Opioid utilization and health-care costs among patients with diabetic peripheral neuropathic pain treated with duloxetine vs. other therapies. Pain Pract. 2011;11:48–56.PubMed
34.
Johnston SS, Udall M, Cappelleri JC, Johnson BH, Shrady G, Chu BC, et al. Cost comparison of drug-drug and drug-condition interactions in patients with painful diabetic peripheral neuropathy treated with pregabalin versus duloxetine. Am J Health Syst Pharm. 2013;70(24):2207–17.PubMed
35.
Dworkin RH, Panarites CJ, Armstrong EP, Malone DC, Pham SV. Healthcare utilization in people with postherpetic neuralgia and painful diabetic peripheral neuropathy. J Am Geriatr Soc. 2011;59(5):827–36.PubMed
36.
Burke JP, Sanchez RJ, Joshi AV, Cappelleri JC, Kulakodlu M, Halpern R. Health care costs in patients with painful diabetic peripheral neuropathy prescribed pregabalin or duloxetine. Pain Pract. 2012;12(3):209–18.PubMed
37.
Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol. 1992;45:613–9.PubMed
38.
Klabunde CN, Potosky AL, Legler JM, Warren JL. Development of a comorbidity index using physician claims data. J Clin Epidemiol. 2000;53:1258–67.PubMed
39.
Von Korff MV, Saunders K, Thomas Ray G, Boudreau D, Campbell C, Merrill J, et al. De facto long-term opioid therapy for non-cancer pain. Clin J Pain. 2008;24(6):521–7.PubMed
40.
Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika. 1983;70:41–55.
41.
D’Agostino Jr RB. Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med. 1998;17:2265–81.PubMed
42.
Rosner B. Fundamentals of Biostatistics. 7th ed. Boston, MA: Brooks/Cole Cengage Learning; 2010.
43.
Jones AM, Rice N, Bago d’Uva T, Balia S. Applied Health Economics. 2nd ed. New York, NY: Routledge; 2013.
44.
Lyrica® (pregabalin) package insert. New York, IN: Pfizer Inc.; 2013
45.
Cymbalta® (duloxetine) package insert. Indianapolis, IN: Eli Lilly and Company; 2012.
46.
Pergolizzi Jr JV, Labhsetwar SA, Puenpatom RA, Joo S, Ben-Joseph RH, Summers KH. Prevalence of exposure to potential CYP450 pharmacokinetic drug-drug interactions among patients with chronic low back pain taking opioids. Pain Pract. 2011;11(3):230–9.PubMed
47.
Pergolizzi Jr JV, Labhsetwar SA, Puenpatom RA, Joo S, Ben-Joseph R, Summers KH. Exposure to potential CYP450 pharmacokinetic drug-drug interactions among osteoarthritis patients: incremental risk of multiple prescriptions. Pain Pract. 2011;11(4):325–36.PubMed
48.
Mallet L, Spinewine A, Huang A. The challenge of managing drug interactions in elderly people. Lancet. 2007;370(9582):185–91.PubMed
49.
Hines LE, Murphy JE. Potentially harmful drug-drug interactions in the elderly: a review. Am J Geriatr Pharmacother. 2011;9(6):364–77.PubMed
50.
Summers KH, Puenpatom RA, Rajan N, Ben-Joseph R, Ohsfeldt R. Economic impact of potential drug–drug interactions in opioid analgesics. J Med Econ. 2011;14:390–6.PubMed
51.
Pergolizzi Jr JV, Labhsetwar SA, Puenpatom RA, Ben-Joseph R, Ohsfeldt R, Summers KH. Economic impact of potential CYP450 pharmacokinetic drug–drug interactions among chronic low back pain patients taking opioids. Pain Pract. 2012;12:45–56.PubMed
52.
Pergolizzi Jr JV, Labhsetwar SA, Puenpatom RA, Ben-Joseph R, Ohsfeldt R, Summers KH. Economic impact of potential drug–drug interactions among osteoarthritis patients taking opioids. Pain Pract. 2012;12:33–44.PubMed
Metadata
Title
A retrospective, matched cohort study of potential drug-drug interaction prevalence and opioid utilization in a diabetic peripheral neuropathy population initiated on pregabalin or duloxetine
Authors
Jeffrey J Ellis
Alesia B Sadosky
Laura L Ten Eyck
Pallavi Mudumby
Joseph C Cappelleri
Lilian Ndehi
Brandon T Suehs
Bruce Parsons
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Health Services Research / Issue 1/2015
Electronic ISSN: 1472-6963
DOI
https://doi.org/10.1186/s12913-015-0829-9

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