DOI: http://dx.doi.org/10.18203/2349-3933.ijam20194226

Pregabalin and PR interval prolongation: any association?

Osama Shukir Muhammed Amin

Abstract


Background: Pregabalin is a well-tolerated medication that is commonly used in the treatment of chronic pain, epilepsy, fibromyalgia, and generalized anxiety disorders. A variety of pregabalin-related cardiac side effects have been described in the literature and first-degree AV block is a well-known consequence. We aimed to investigate whether pregabalin prolongs the PR interval or not.

Methods: This cross-sectional observational study was conducted at the Shorsh Military General Teaching Hospital, Iraq. A total of 80 patients, who had a multitude of cervical and lumbosacral radiculopathies were enrolled consecutively, from November 1, 2017, to January 31, 2019. Forty patients who were receiving pregabalin (the treatment group) were age-matched and gender-matched with another group of 40 patients who hadn’t been prescribed pregabalin (the control group). A single 12-lead ECG was done in all patients and the PR interval was calculated; a value of >0.20 second is considered a prolongation in the PR interval and defines first-degree AV block.

Results: Thirteen patients (32%; 7 males and 6 females) demonstrated a prolongation in the PR interval in the pregabalin arm while the PR interval was prolonged in 5 patients only in the control group (12%; 2 males and 3 females). There was no statistical difference between the maximum PR prolongation in both groups (p-value=0.13; 95% CI, -0.0121 to 0.0317).

Conclusions: This study hasn’t found a statistically significant prolongation in the PR interval among patients taking oral pregabalin monotherapy. Whether this observation is clinically significant or not, it needs further analytic studies to uncover its importance.


Keywords


Conduction defects, Heart block, Pregabalin, PR interval

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References


Calandre EP, Rico-Villademoros F, Slim M. Alpha2delta ligands, gabapentin, pregabalin and mirogabalin: a review of their clinical pharmacology and therapeutic use. Expert Rev Neurother. 2016;16(11):1263-77.

Schiavo A, Stagnaro FM, Salzano A, Marra AM, Bobbio E, Valente P, et al. Pregabalin-induced first degree atrioventricular block in a young patient treated for pain from extrapulmonary tuberculosis. Monaldi Archives for Chest Disease. 2017 Sep 28;87(3).

Şengüldür E. Pregabalin Intoxication-Induced Prolonged PR Interval on Electrocardiogram. Journal of Clinical and Experimental Investigations. 2018;9(2):100-2.

Sills GJ. The mechanisms of action of gabapentin and pregabalin. Curr Opin Pharmacol. 2006;6(1):108-13.

Stahl SM, Porreca F, Taylor CP, Cheung R, Thorpe AJ, Clair A. The diverse therapeutic actions of pregabalin: is a single mechanism responsible for several pharmacological activities?. Trends Pharmacol Sci. 2013;34(6):332-9.

Bockbrader HN, Wesche D, Miller R, Chapel S, Janiczek N, Burger P. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet. 2010;49(10):661-9.

Nada A, Gintant GA, Kleiman R, Gutstein DE, Gottfridsson C, Michelson EL, et al. The evaluation and management of drug effects on cardiac conduction (PR and QRS intervals) in clinical development. Am Heart J. 2013;165(4):489-500.

Mymin D, Mathewson FA, Tate RB, Manfreda J. The natural history of primary first-degree atrioventricular heart block. N Engl J Med. 1986;315:1183-7.

Cheng S, Keyes MJ, Larson MG, McCabe EL, Newton-Cheh C, Levy D, et al. Long-term outcomes in individuals with prolonged PR interval or first-degree atrioventricular block. JAMA 2009;301:2571-7.

Crisel RK, Farzaneh-Far R, Na B, Whooley MA. First-degree atrioventricular block is associated with heart failure and death in persons with stable coronary artery disease: data from the Heart and Soul Study. Eur Heart J. 2011;32:1875-80.

Aksakal E, Bakirci EM, Emet M, Uzkeser M. Complete atrioventricular block due to overdose of pregabalin. Am J Emerg Med. 2012;30(9):2101.

Scarano V, Casillo R, Bertogliatti S, Orlando V, Terracciano AM. Incomplete atrioventricular block in a patient on pregabalin therapy. Recenti progressi in medicina. 2013 Nov;104(11):574-6.

De Leon J, editor. A Practitioner's Guide to Prescribing Antiepileptics and Mood Stabilizers for Adults with Intellectual Disabilities. Springer Sci Bus Med; 2012 Mar 2.

Saldaña MT, Navarro A, Pérez C, Masramón X, Rejas J. Patient-reported-outcomes in subjects with painful lumbar or cervical radiculopathy treated with pregabalin: evidence from medical practice in primary care settings. Rheumatol Int. 2010;30(8):1005-15.

Lyrica [package insert on the Internet]. New York: Pfizer Inc; 2007 [updated 2019 May 1; cited 2019 Jun 10]. Available at: http://labeling.pfizer.com/ShowLabeling.aspx?id=561.

Food and Drug Administration. Drug Approval Package: Lyrica CR (pregabalin). Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209501Orig1s000TOC.cfm. Accessed on February 10, 2019.

Pregabalin. In: Joint Formulary Committee. British national formulary [Internet]. London: British Medical Association and Royal Pharmaceutical Society of Great Britain. Available at: https://bnf.nice.org.uk/drug/pregabalin.html. Updated 2019 Mar 21, cited 2019 August 2.