Effect of Paracetamol on Blood Pressure: A Systematic Review

Authors

  • Saoussen Miladi Rheumatology department, Mongi Slim Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
  • Leila Rouached Rheumatology department, Charles Nicolle Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
  • Selma Bouden Rheumatology department, Charles Nicolle Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
  • Hiba Boussaa Rheumatology department, Mongi Slim Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
  • Yasmine Makhlouf Rheumatology department, Mongi Slim Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
  • Aicha Ben Tekaya Rheumatology department, Charles Nicolle Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
  • Siwar Ben Dhia Rheumatology department, Charles Nicolle Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
  • Ines Mahmoud Rheumatology department, Charles Nicolle Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
  • Raoudha Tekaya Rheumatology department, Charles Nicolle Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
  • Olfa Saidane Rheumatology department, Charles Nicolle Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
  • Kawther Ben Abdelghani Rheumatology department, Mongi Slim Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
  • Alia Fazaa Rheumatology department, Mongi Slim Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
  • Leila Abdelmoula Rheumatology department, Charles Nicolle Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
  • Ahmed Laatar Rheumatology department, Mongi Slim Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia

DOI:

https://doi.org/10.62438/tunismed.v103i9.6243

Keywords:

acetaminophen, hypertension, review, cardiovascular events, side effects

Abstract

Background: Paracetamol is widely used as a first-line analgesic for chronic pain, primarily due to its presumed safety profile. Unlike non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol has been for long time considered free of significant cardiovascular effects, particularly on blood pressure (BP). However, emerging evidence suggests that long terme paracetamol use may be associated with elevated BP, challenging its status as a risk-free alternative to NSAIDs.

This systematic review aimed to investigate the association between paracetamol intake and changes in BP by screening existing clinical and epidemiological data to clarify its potential hypertensive effects.

Methods: A comprehensive search of Medline, Cochrane Library, and Embase databases was conducted. Eligible studies included randomized clinical trials, interventional and longitudinal observational studi involving adults receiving standard doses of oral paracetamol. Exclusion criteria were studies on  pregnant women, patients with preeclampsia/eclampsia, and those using supratherapeutic doses. The primary outcome was variation in systolic and diastolic BP.

Results: A total of 10 studies was included comprinzing observational studies (n = 4) and randomized controlled trials (n = 6). Two observational studies reported a significant association between regular paracetamol use and an increased risk of hypertension particularly with high-dose (> 3 g/day) or prolonged use (> 30 days). The remaining two studies found no significant association, though one noted a trend toward elevated BP in older adults

Four RCTs demonstrated a small but consistent increase in systolic blood pressure (SBP), ranging from +0.2 to +4.0 mmHg. The effect appeared dose-dependent, with higher doses (> 2 g/day) linked to greater BP elevation.

Conclusion: Paracetamol may cause slight elevations in BP, with potential clinical implications in high- risk patients. Caution is warranted, and further prospective studies using ambulatory BP monitoring are needed to clarify this relationship.

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References

Sheen CL, Dillon JF, Bateman DN, Simpson KJ, Macdonald TM. Paracetamol

toxicity: epidemiology, prevention and costs to the health-care system. QJM Mon J

Assoc Physicians 2002;95:609–19. https://doi.org/10.1093/qjmed/95.9.609.

Sussman NL, Remien CH. The Headache of Acetaminophen Overdose: Getting the

NAC. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc

;15:563–4. https://doi.org/10.1016/j.cgh.2016.12.011.

Chidiac AS, Buckley NA, Noghrehchi F, Cairns R. Paracetamol (acetaminophen)

overdose and hepatotoxicity: mechanism, treatment, prevention measures, and

estimates of burden of disease. Expert Opin Drug Metab Toxicol 2023;19:297–317.

https://doi.org/10.1080/17425255.2023.2223959.

Graham GG, Scott KF, Day RO. Tolerability of paracetamol. Drug Saf 2005;28:227–

https://doi.org/10.2165/00002018-200528030-00004.

Blot WJ, Fischer T, Nielsen GL, Friis S, Mumma M, Lipworth L, et al. Outcome of

upper gastro-intestinal bleeding and use of ibuprofen versus paracetamol. Pharm World

Sci PWS 2004;26:319–23. https://doi.org/10.1007/s11096-004-9008-5.

Rumack BH. Acetaminophen hepatotoxicity: the first 35 years. J Toxicol Clin Toxicol

;40:3–20. https://doi.org/10.1081/clt-120002882.

Snowden S, Nelson R. The effects of nonsteroidal anti-inflammatory drugs on blood

pressure in hypertensive patients. Cardiol Rev 2011;19:184–91.

https://doi.org/10.1097/CRD.0b013e31821ddcf4.

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The

PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ

;372:n71. https://doi.org/10.1136/bmj.n71.

Miladi S, Rouached L, Bouden S, Boussaa H et al. Effect of paracetamol on blood

pressure: A systematic review protocol. La Tunisie Médicale.2025;103(5):557-559.

doi:10.62438/tunismed.v103i5.5525.

Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y, Chipponi J. Methodological

index for non-randomized studies (MINORS): development and validation of a new

instrument. ANZ J Surg. 2003;73(9):712-6. doi:10.1046/j.1445-2197.2003.02748.x.

Curhan GC, Willett WC, Rosner B, Stampfer MJ. Frequency of analgesic use and

risk of hypertension in younger women. Arch Intern Med 2002;162:2204–8.

https://doi.org/10.1001/archinte.162.19.2204.

Kurth T, Hennekens CH, Stürmer T, Sesso HD, Glynn RJ, Buring JE, et al.

Analgesic use and risk of subsequent hypertension in apparently healthy men. Arch

Intern Med 2005;165:1903–9. https://doi.org/10.1001/archinte.165.16.1903.

Forman JP, Rimm EB, Curhan GC. Frequency of analgesic use and risk of

hypertension among men. Arch Intern Med 2007;167:394–9.

https://doi.org/10.1001/archinte.167.4.394.

Dawson J, Fulton R, McInnes GT, Morton R, et al. Acetaminophen use and change in

blood pressure in a hypertensive population. J Hypertens. 2013;31(7):1485–90.

. Chalmers JP, West MJ, Wing LM, Bune AJ, Graham JR. Effects of indomethacin,

sulindac, naproxen, aspirin, and paracetamol in treated hypertensive patients. Clin Exp

Hypertens A. 1984;6(6):1077–93.

. Radack KL, Deck CC, Bloomfield SS. Ibuprofen interferes with the efficacy of

antihypertensive drugs. A randomized, double-blind, placebo-controlled trial of

ibuprofen compared with acetaminophen. Ann Intern Med. 1987;107(5):628–35.

. Pavlicevic I, Kuzmanic M, Rumboldt M, Rumboldt Z. Interaction between

antihypertensives and NSAIDs in primary care: a controlled trial. Can J Clin

Pharmacol. 2008;15(2):372–82.

. Sudano I, Flammer AJ, Roas S, Enseleit F, Noll G, Ruschitzka F. Nonsteroidal

antiinflammatory drugs, acetaminophen, and hypertension. Curr Hypertens Rep.

;14(4):304–9.

. Gualtierotti R, Zoppi A, Mugellini A, Derosa G, et al. Effect of naproxen and

acetaminophen on blood pressure lowering by ramipril, valsartan and aliskiren in

hypertensive patients. Expert Opin Pharmacother. 2013;14(13):1875–84.

MacIntyre IM, Turtle EJ, Farrah TE, Graham C, et al. Regular acetaminophen use and

blood pressure in people with hypertension: the PATH-BP trial. Circulation.

;145(6):416–23.

Hypertension in adults: diagnosis and management | Guidance | NICE 2011.

https://www.nice.org.uk/guidance/CG127 (accessed July 1, 2025).

Gupta R, Behnoush AH, Egeler D, Aronow WS. Effect of acetaminophen on blood

pressure: a systematic review and meta-analysis of randomized controlled trials. Eur J

Prev Cardiol 2022;29:e326–30. https://doi.org/10.1093/eurjpc/zwac112.

Turtle EJ, Dear JW, Webb DJ. A systematic review of the effect of paracetamol on

blood pressure in hypertensive and non-hypertensive subjects. Br J Clin Pharmacol

;75:1396–405. https://doi.org/10.1111/bcp.12032.

Douglas L, Akil M. Sodium in soluble paracetamol may be linked to raised blood

pressure. BMJ 2006;332:1133. https://doi.org/10.1136/bmj.332.7550.1133.

Rao S, Nazarzadeh M, Canoy D, Li Y, Huang J, Mamouei M, et al. Sodium-based

paracetamol: impact on blood pressure, cardiovascular events, and all-cause mortality.

Eur Heart J 2023;44:4448–57. https://doi.org/10.1093/eurheartj/ehad535.

Benitez-Camps M, Morros Padrós R, Pera-Pujadas H, Dalfó Baqué A, Bayó Llibre

J, Rebagliato Nadal O, et al. Effect of effervescent paracetamol on blood pressure: a

crossover randomized clinical trial. J Hypertens 2018;36:1656–62.

https://doi.org/10.1097/HJH.0000000000001733.

Roberts E, Delgado Nunes V, Buckner S, Latchem S, Constanti M, Miller P, et al.

Paracetamol: not as safe as we thought? A systematic literature review of observational

studies. Ann Rheum Dis 2016;75:552–9. https://doi.org/10.1136/annrheumdis-2014-

Kaur J, Nakafero G, Abhishek A, Mallen C, Doherty M, Zhang W. Incidence of

Side Effects Associated With Acetaminophen in People Aged 65 Years or More: A

Prospective Cohort Study Using Data From the Clinical Practice Research Datalink.

Arthritis Care Res 2025;77:666–75. https://doi.org/10.1002/acr.25471.

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Published

2025-11-09