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Current Emergency and Hospital Medicine Reports

Erschienen in:

01.06.2019 | Pharmacology Care (J Fanikos, Section Editor)

Cardiovascular Safety of Gabapentinoids

verfasst von: Leo F. Buckley, Emad Alsarraf

Erschienen in: Current Emergency and Hospital Medicine Reports | Ausgabe 2/2019

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Abstract

Purpose of Review

The objective of this manuscript is to describe the cardiovascular effects of the gabapentinoids gabapentin and pregabalin.

Recent Findings

The most frequent adverse effects of gabapentin and pregabalin affect the central nervous system, such as somnolence and fatigue. Additionally, pregabalin, and a much lesser extent, gabapentin, may adversely affect the cardiovascular system. Pregabalin induces peripheral edema and may cause or exacerbate heart failure. Pregabalin use has been associated with QTc prolongation in patients taking other QTc–prolonging agents, although the relative contributions of pregabalin to QTc prolongation may be minimal. Pregabalin and gabapentin have been associated with a dose-related increased risk of atrial fibrillation. Most evidence for adverse cardiovascular effects of gabapentinoids derives from case reports and observational studies.

Summary

Clinicians should be aware of the potential for pregabalin and possibly gabapentin to contribute to cardiovascular dysfunction.

Ramsay RE. Clinical efficacy and safety of gabapentin. Neurology [Internet]. 1994 [cited 2019 Jan 27];44:S23–30; discussion S31–2. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8022537

Gee NS, Brown JP, Dissanayake VU, Offord J, Thurlow R, Woodruff GN. The novel anticonvulsant drug, gabapentin (Neurontin), binds to the alpha2delta subunit of a calcium channel. J Biol Chem [Internet]. 1996 [cited 2019 Jan 28];271:5768–76. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8621444

Walters AS, Ondo WG, Kushida CA, Becker PM, Ellenbogen AL, Canafax DM, Barrett RW, XP045 Study Group. gabapentin enacarbil in restless legs syndrome. Clin Neuropharmacol [Internet]. 2009 [cited 2019 Feb 28];32:311–320. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19667976

Harden RN, Freeman R, Rainka M, Zhang L, Bell C, Berges A, Chen C, Graff O, Harding K, Hunter S, Kavanagh S, Schwartzbach C, Warren S, McClung C. A Phase 2a, randomized, crossover trial of gabapentin enacarbil for the treatment of postherpetic neuralgia in gabapentin inadequate responders. Pain Med [Internet]. 2013 [cited 2019 Mar 1];14:1918–1932. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24102928

Ben-Menachem E. Pregabalin pharmacology and its relevance to clinical practice. Epilepsia [Internet]. 2004 [cited 2019 Jan 27];45:13–18. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15315511

Zaccara G, Gangemi P, Perucca P, Specchio L. The adverse event profile of pregabalin: a systematic review and meta-analysis of randomized controlled trials. Epilepsia [Internet]. 2011 [cited 2019 Jan 28];52:826–836. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21320112

Carbone S, Dixon DL, Buckley LF, Abbate A. Glucose-lowering therapies for cardiovascular risk reduction in Type 2 diabetes mellitus: state-of-the-art Review [Internet]. Mayo Clin. Proc. 2018 [cited 2019 Feb 28];93:1629–1647. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30392544

• Murphy N, Mockler M, Ryder M, Ledwidge M, McDonald K. Decompensation of chronic heart failure associated with pregabalin in patients with neuropathic pain. J Card Fail [Internet]. 2007 [cited 2018 Dec 15];13:227–229. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17448421. This was one of the first case reports that described worsening heart failure associated with pregabalin use.

De Smedt RHE, Jaarsma T, van den Broek SAJ, Haaijer-Ruskamp FM. Decompensation of chronic heart failure associated with pregabalin in a 73-year-old patient with postherpetic neuralgia: a case report. Br J Clin Pharmacol [Internet]. 2008 [cited 2018 Dec 15];66:327–328. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18507657

10.

Page RL, Cantu M, Lindenfeld J, Hergott LJ, Lowes BD. Possible heart failure exacerbation associated with pregabalin: case discussion and literature review. J Cardiovasc Med [Internet]. 2008 [cited 2018 Dec 15];9:922–925. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18695430

11.

Erdoğan G, Ceyhan D, Güleç S. Possible heart failure associated with pregabalin use: case report. Agri [Internet]. 2011 [cited 2018 Dec 15];23:80–3. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21644108

12.

Matsuki Y, Morikawa M, Nishimoto T, Yasuda Y, Shigemi K. Heart failure assocated with pregabalin. Pain Physician [Internet]. [cited 2018 Dec 15];15:E536–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22828703

13.

Fong T, Lee AJ. Pregabalin-associated heart failure decompensation in a patient with a history of stage I heart failure. Ann Pharmacother [Internet]. 2014 [cited 2019 Jan 28];48:1077–1081. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24769529

14.

Guzelkucuk U, Duman I, Yılmaz B, Tan AK. Reversible post-pregabalin peripheral edema in a spinal cord injury patient. Spinal Cord [Internet]. 2012 [cited 2018 Dec 15];50:472–473. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21747401

15.

Gallagher R, Apostle N. Peripheral edema with pregabalin. Can Med Assoc J [Internet]. 2013 [cited 2018 Dec 15];185:E506–E506. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23128284

16.

Alp R, Citil M, Uzun M, Alp S, Topcu B, Uzlu E, Erdogan HM. Effects of therapeutic doses of Pregabalin on QTc interval in conscious rabbits. Eur Rev Med Pharmacol Sci [Internet]. [cited 2018 Dec 15];12:223–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18727453

17.

•• Chen D, Lal R, Zomorodi K, Atluri H, Ho J, Luo W, Tovera J, Bonzo D, Cundy K. Evaluation of gabapentin enacarbil on cardiac repolarization: a randomized, double-blind, placebo- and active-controlled, crossover thorough QT/QTc study in healthy adults. Clin Ther [Internet]. 2012 [cited 2019 Feb 28];34:351–362.e3. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22325733. This study demonstrates a lack of effect on QTc interval for the enacarbil formulation of gabapentin.

18.

Rasimas JJ, Burkhart KK. Cardiac conduction disturbances after an overdose of nefazodone and gabapentin. Am J Emerg Med [Internet]. 2006 [cited 2018 Dec 15];24:886–888. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17098120

19.

Hill CM, Mostafa P, Stuart AG, Thomas DW, Walker R V. ECG variations in patients pre- and post-local anaesthesia and analgesia. Br Dent J [Internet]. 2009 [cited 2018 Dec 15];207:E23–E23. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19893562

20.

Schiavo A, Stagnaro FM, Salzano A, Marra AM, Bobbio E, Valente P, Grassi S, Miniero M, Arcopinto M, Matarazzo M, Napoli R, Cittadini A. Pregabalin-induced first degree atrioventricular block in a young patient treated for pain from extrapulmonary tuberculosis. Monaldi Arch Chest Dis [Internet] 2017 [cited 2019 Jan 28];87:838. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29424197, 87

21.

Aksakal E, Bakirci EM, Emet M, Uzkeser M. Complete atrioventricular block due to overdose of pregabalin. Am J Emerg Med [Internet]. 2012 [cited 2019 Jan 29];30:2101.e1–4. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0735675712000897

22.

• Ortiz de Landaluce L, Carbonell P, Asensio C, Escoda N, López P, Laporte JR Gapentin and pregabalin and risk of atrial fibrillation in the elderly: a population-based cohort study in an electronic prescription database. Drug Saf [Internet]. 2018 [cited 2019 Feb 28];41:1325–1331. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29956217. This article reports a significant association of gabapentin and pregabalin to risk of atrial fibrillation. While further research should validate this association and elucidate its mechanism, clinicians should remain cognizant of the potential for these agents to contribute to the development of atrial fibrillation in older adults.

23.

Diaper A, Rich AS, Wilson SJ, Craig K, Dourish CT, Dawson GR, Nutt DJ, Bailey JE. Changes in cardiovascular function after venlafaxine but not pregabalin in healthy volunteers: a double-blind, placebo-controlled study of orthostatic challenge, blood pressure and heart rate. Hum Psychopharmacol Clin Exp [Internet]. 2013 [cited 2019 Jan 29];28:562–575. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23955418

24.

White AT, Light KC, Bateman L, Hughen RW, Vanhaitsma TA, Light AR. Effect of pregabalin on cardiovascular responses to exercise and postexercise pain and fatigue in fibromyalgia: a randomized, double-blind, crossover pilot study. Pain Res Treat [Internet]. 2015 [cited 2019 Jan 28];2015:1–10. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27026828

25.

Spiller HA, Dunaway MD, Cutino L. Massive gabapentin and presumptive quetiapine overdose. Vet Hum Toxicol [Internet]. 2002 [cited 2018 Dec 15];44:243–4. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12136976

26.

Singewald N, Pfitscher A, Philippu A. Effects of gamma-vinyl GABA (vigabatrin) on blood pressure and body weight of hypertensive and normotensive rats. Naunyn Schmiedebergs Arch Pharmacol [Internet] 1992 [cited 2018 Dec 15];345:181–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/1570022

27.

Behuliak M, Bencze M, Polgárová K, Kuneš J, Vaněčková I, Zicha J. Hemodynamic response to gabapentin in conscious spontaneously hypertensive rats. Hypertension [Internet]. 2018 [cited 2019 Jan 28];72:676–685. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30354755

Titel: Cardiovascular Safety of Gabapentinoids
verfasst von: Leo F. Buckley
Emad Alsarraf
Publikationsdatum: 01.06.2019
Verlag: Springer US
Erschienen in: Current Emergency and Hospital Medicine Reports / Ausgabe 2/2019
Elektronische ISSN: 2167-4884
DOI: https://doi.org/10.1007/s40138-019-00182-5

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Cardiovascular Safety of Gabapentinoids