THE IMPACT OF PHARMACOGENETICS ON ADVERSE DRUG REACTIONS TO PREDICT THE EFFICACY OF TRAMADOL MONOTHERAPY FOR THE TREATMENT OF POST HERPETIC NEURALGIA PATIENTS
Keywords:
Adverse drug reactions, Tramadol, CYP2D6, Post herpetic neuralgiaAbstract
Objective: To evaluate the potential role of tramadol treatment with respect to CYP2D6 polymorphism in reducing the incidence of adverse drug reactions.
Methods: The study comprised 246 patients of PHN receiving tramadol treatment. Adverse drug events during the time of the study were recorded by the physician. All samples were analyzed for CYP2D6 (*2, *4 and *10) polymorphism using PCR-RFLP method.
Results: The CYP2D6 polymorphism did not find significantly among onset at age, genders and weight in non-responders and responders. The CYP2D6*4 polymorphism was significantly associated with somnolence (p=0.009), dizziness (p=0.007), local site reactions (p=0.015), headache (p=0. 039), and nausea and vomiting (p=0. 017). The dizziness (p=0. 029) and headache (p=0. 004) were found associated with CYP2D6*2 both the groups. No associations were observed between adverse events compared with CYP2D6*2 and CYP2D6*10 polymorphisms (p>0.05).
Conclusion: CYP2D6*4 polymorphism may be as important drug toxicity marker predictors of experiencing adverse drug reactions as PHN patients undergoing tramadol treatment.
Â
Downloads
References
Meyer UA. Pharmacogenetics and adverse drug reactions. Lancet 2000;356:1667–71.
Schmitz G, Aslanidis C, Lackner KJ. Pharmacogenomics: implications for laboratory medicine. Clin Chim Acta 2001;308:43–53.
Beniczky S, Tajti J, TÃmea Varga E, Vécsei L. Evidence-based pharmacological treatment of neuropathic pain syndromes. J Neural Transm 2005;112:735–49.
Watson CP, Vernich L, Chipman M, Reed K. Nortriptyline versus amitriptyline in postherpetic neuralgia: a randomized trial. Neurol 1998;51:1166-71.
Rowbotham M, Harden N, Stacey B, Bernstein P, Magnus-Miller L. Gabapentin for treatment of postherpetic neuralgia. JAMA 1998;289:1837-42.
Boureau F, Legallicer P, Kabir-Ahmadi M. Tramadol in post-herpetic neuralgia: a randomized, double-blind, placebo-controlled trial. Pain 2003;104:323–31.
Saxena AK, Nasare NV, Jain S, Dhakate G, Ahmed RS, Bhattacharya SN, Mediratta PK, et al. A Randomized, Prospective study of efficacy and safety of oral tramadol in the management of post herpetic neuralgia in patients from north india. Pain Pract 2013;13:264-75.
Nasare NV, Deshmukh PS, Banerjee BD, Mediratta PK, Ahmed RS, Saxena AK, et al. CYP2D6*4 polymorphism in tramadol treatment and its clinical impact in patients of post herpetic neuralgia. Pers Med 2012;9:371-85.
Nasare NV, Banerjee BD, Deshmukh SP, Mediratta PK, Saxena AK, Ahmed RS, et al. CYP2D6*2 polymorphism as a predictor of failed outpatient tramadol therapy in postherpetic neuralgia patients. Am J Ther 2013 in press.
Desmond D, MacLachlan M. Psychological issues in prosthetic and orthotic practice: a 25 year review of psychology in Prosthetics and Orthotics International. Prosthet Orthot Int 2002;26:182-8.
Galer BS, Jensen MP, Ma T, Davies PS, Rowbotham MC. The lidocaine patch 5% effectively treats all neuropathic pain qualities: results of a randomized, double-blind, vehicle-controlled, 3-week efficacy study with use of the neuropathic pain scale. Clin J Pain 2002;18:297-301.
Cossmann M, Kohnen C, Langford R, McCartney C. Tolérance et séecurité d’emploi du tramadol. Résultats des études internationales et données de la pharmacovigilance. Drugs 1997;53:50–62.
Lehmann KA, Kratzenberg U, Schroeder-Bark B, Horrichs-Haermeyer G. Postoperative patient-controlled analgesia with tramadol: analgesic efficacy and minimus effective concentration. J Clin Pain 1990;6:212-20.
Follin SL, Charland SL. Actute pain management: operative or medical procedures and trauma. Ann Pharm 1997;31:1068-76.
Gan HG, Rusli I, Wan A, Wan Z. Impact of CYP2D6 Genetic polymorphism on tramadol pharmacokinetics and pharmacodynamics. Mol Diog Ther 2007;11:171-81.
Stamer U, Stuber F, Muders T, Musshoff F. Respiratory depression with tramadol in a patient with renal impairment and CYP2D6 gene duplication. Anesth Analg 2008;107:926–9.
Stamer UM, Musshoff F, Kobilay M, Madea B, Hoeft A, Stuber F. Concentrations of tramadol and O-desmethyltramadol enantiomers in different CYP2D6 genotypes. Clin Pharm Ther 2007;82:41-7.
Ingelman–Sundberg M. Genetic polymorphism of Cytochrome P4502D6 (CYP2D6): Clinical consequences, evolutionary aspects and functional diversity. Pharmaco J 2005;5:6-13.
Zanger UM, Fischer J, Raimundo S, Stüven T, Evert BO, Schwab M. Eichelbaum M. Comprehensive analysis of the genetic factors determining expression and function of hepatic CYP2D6. Pharmaco 2001;11:573–85.
Nageswararao D, Manjula G, Sailaja K, Raghunadharao S, Andvishnupriya R. Association of CYP2D6*4 polymorphism with acute leukemia. J Cell Tissue Res 2010;10:2201–5.
Kirchheiner J, Keulen JT, Bauer S, Roots I, Brockmöller J. Effects of the CYP2D6 gene duplication on the pharmacokinetics and pharmacodynamics of tramadol. J Clin Psychopharmacol 2008;28:78–83.
Cossmann M, Wilsmann KM. Effect and side–effects of tramadol. Ther 1987;37:3475–85.
Chalker J, Leuwer M, Lunde PKM, Mc Innes G, Schaffner A, Thelle D, et al. Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions. volume 14. 14th edition. Edited by Jeffrey K. Aronson, MNG. Dukes Pharmacol S FFPM 2000;6:1912.
Nolan L, O’Malley K. Prescribing for the elderly: part 1. Sensitivity of the elderly to adverse drug reactions. J Am Geriatr Soc 1988;36:142–9.
Montamat SC, Cusack B. Overcoming problems with polypharmacy and drug misuse in the elderly. Clin Geriatr Med 1992;8:143–58.
Stewart RB, Cooper JW. Polypharmacy in the aged. Practical solutions. Drugs Aging 1994;4:449–61.
Hurwitz N. Predisposing factors in adverse reactions to drugs. BMJ 1969;1:536–9.
Fattinger K1, Roos M, Vergères P, Holenstein C, Kind B, Masche U, et al. Epidemiology of drug exposure and adverse drug reactions in two swiss departments of internal medicine. Br J Clin Pharmacol 2000;49:158-67.
Martin RM, Biswas PN, Freemantle SN, Pearce GL, Mann RD. Age and sex distribution of suspected adverse drug reactions to newly marketed drugs in general practice in England: analysis of 48 cohort studies. Br J Clin Pharmacol 1998;46:505–11.
Zopf Y, Rabe C, Neubert A, Gabmann KG, Rascher W, Hahn EG, et al. Women encounter ADRs more often than do men. Eur J Clin Pharmacol 2008;64:999–1004.
Anderson GD. Sex and racial differences in pharmacological response: where is the evidence? Pharmacogenetics, pharmacokinetics, and pharmacodynamics. J Womens Health (Larchmt) 2005;14:19–29.
Anderson GD. Gender differences in pharmacological response. Int Rev Neurobiol 2008;83:1–10.
Soldin OP, Mattison DR. Sex differences in pharmacokinetics and pharmacodynamics. Clin Pharmacokinet 2009;48:143–57.
Schwartz JB. The current state of knowledge on age, sex, and their interactions on clinical pharmacology. Clin Pharmacol Ther 2007;82:87–96.
Kim AM, Tingen CM, Woodruff TK. Sex bias in trials and treatment must end. Nat 2010;465:688–9.
Rochon PA, Clark JP, Binns MA, Patel V, Gurwitz JH. Reporting of gender-related information in clinical trials of drug therapy for myocardial infarction. CMAJ 1998;159:321–7.
Harris DJ, Douglas PS. Enrollment of women in cardiovascular clinical trials funded by the National Heart, Lung, and Blood Institute. N Engl J Med 2000;343:475–80.
Kim ES, Carrigan TP, Menon V. Enrollment of women in the National Heart, Lung, and Blood Institute-funded cardiovascular randomized controlled trials fails to meet current federal mandates for inclusion. J Am Coll Cardiol 2008;52:672–3.
Ruiz CMT, Angeles PM. European Medicines Agency policies for clinical trials leave women unprotected. J Epidemiol Comm Health 2006;60:911–3.
Uhl K, Parekh A, Kweder S. Females in clinical studies: where are we going? Clin Pharmacol Ther 2007;81:600–2.
Scandlyn MJ, Stuart EC, Rosengren RJ. Sex-specific differences in CYP450 isoforms in humans. Expert Opin Drug Metab Toxicol 2008;4:413–24.
Veehof LJ, Stewart RE, Meyboom-de Jong B, Haaijer-Ruskamp FM. Adverse drug reactions and polypharmacy in the elderly in general practice. Eur J Clin Pharmacol 1999;55:533-6.
Leppert W. Progress in pharmacological pain treatment with opioid analgesics (Polish). Wspó³cz Onkol 2009;13:66–73.
Kirchheiner J, Keulen J-T HA, Bauer S, Roots I, Brockmöller J. Effects of the CYP2D6 gene duplication on the pharmacokinetics and pharmacodynamics of tramadol. J Clin Psychopharmacol 2008;28:78–83.
Linder MW, Valdes R. Pharmacogenetics in the practice of laboratory medicine. Mol Diagn 1999;4:365-86.
The LK, Ismail R, Yusoff R, Hussein A, Isa MN, Rahman, AR. Heterogeneity of the CYP2D6 gene among Malays in Malaysia. J Clin Pharm Ther 2001;26:205-11.
Rau T, Wohlleben G, Wuttke H, Thuerauf N, Lunkenheimer J, Lanczik M, et al. CYP2D6 genotype: Impact on adverse effects and non response during treatment with antidepressants: a pilot study. J Clin Pharmacol Ther 2004;75:386-93.
Hamelin BA, Dorson PG, Pabis D, Still D, Bouchard RH, Pourcher E, et al. CYP2D6 mutations and therapeutic outcome in schizophrenic patients. Pharmacotherapy 1999;19:1057–63.
Panagiotidis G, Arthur HW, Lindh JD, Dahl ML, Sjöqvist F. Depot haloperidol treatment in outpatients with schizophrenia on monotherapy: impact of CYP2D6 polymorphism on pharmacokinetics and treatment outcome. Ther Drug Monit 2007;27:417–22.
Blonk MI, van der Velde N, van den Bemt PM, van Schaik RH, van der Cammen TJ. CYP2D6*4, CYP3A5*3 and ABCB1 3435T polymorphisms and drug-related falls in elderly people. Pharm World Sci 2010;2:26-9.
McCleane G. Topical application of doxepin hydrochloride can reduce the symptoms of complex regional pain syndrome. A case report Injury. Int J Care Injured 2002;33:88-9.
Capsaicin Study Group. Effect of treatment with capsaicin on daily activities of patients with painful diabetic neuropathy. Diabetes Care 1992;15:159-65.
McCleane GJ. Topical doxepin hydrochloride reduces neuropathic pain: a randomized, double-blind placebo controlled study. The Pain Clin 2000;12:47-50.
Khaliq W, Alam S, Puri N. Topical lidocaine for the treatment of post herpetic neuralgia. Cochrane Database Syst Rev 2007;18:46-8.
Bernstein JE, Korman NJ, Bickers DR, Dahl MV, Millikan LE. Topical capsaicin treatment of chronic postherpetic neuralgia. J Am Acad Dermatol 1989;21:265-70.
Watson CP, Babul N. Efficacy of oxycodone in neuropathic pain: a randomized trial in postherpetic neuralgia. Neurol 1998;50:1837–41.
Watson CP, Moulin D, Watt-Wilson J, Gordon A, Eisenhoffer J. Controlled-release oxycodone relieves neuropathic pain: a randomized controlled trial in painful diabetic neuropathy. Pain 2003;105:71-8.
Ellison N, Loprinzi CL, Kugler J, Hatfield AK, Miser A, Sloan JA, et al. Phase III placebo-controlled trial of capsaicin cream in the management of surgical neuropathic pain in cancer patients. J Clin Oncol 1997;15:2974-80.
Indu: Capsaicin-Doxepin topical cream, oral, pregabalin and continuous epidural imfusion versus oral pregabalin and continuous epidural infusion for post herpetic neuralgia patients-A prospective, randomized, double-blind, placebo-controlled trial. MDThesis (Anesthesiology), Faculty of Medical Sciences, University of Delhi; 2010.