Pseudoephedrine-Induced Risks of Posterior Reversible Encephalopathy Syndrome and Reversible Cerebral Vasoconstriction Syndrome

Abstract

Background Pseudoephedrine is a sympathomimetic drug used as a nasal/sinus decongestant in common cold remedies.

Objective The purpose of this review article is to discuss the pseudoephedrine-associated posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS), which have been reported to the Medicines and Healthcare products Regulatory Agency (MHRA) of United Kingdom and Pharmacovigilance Risk Assessment Committee (PRAC) and Committee for Medicinal Products for Human Use (CHMP) of European Medicines Agency (EMA).

Materials and Methods The aim is to review the literature pertinent to PRES and RCVS linked to the use of pseudoephedrine; the literature was searched in databases such as Medline/PubMed/PMC, Google Scholar, Science Direct, Ebsco, Scopus, Web of Science, Embase, and reference lists.

Results The review by MHRA of the United Kingdom and PRAC and CHMP of EMA, all available evidence, including postmarketing safety data, and a few case reports, have confirmed the rare risk of PRES and RCVS associated with the use of pseudoephedrine.

Conclusion Health care professionals should be aware of pseudoephedrine-associated PRES and RCVS. Patients with severe or uncontrolled hypertension or those with severe acute or chronic renal disease should avoid using products containing pseudoephedrine.

Keywords

pseudoephedrine - pharmacovigilance - adverse effects - posterior reversible encephalopathy syndrome - reversible cerebral vasoconstriction syndrome - pseudoephedrine-containing medicines

Authors' Contributions

N.M.P.M contributed to conceptualization and designing of the review and acquisition of data, and drafted the manuscript. R.B contributed to data analysis and interpretation of data, and reviewed the manuscript. A.S. assisted with data analysis and interpretation of data, and reviewed the manuscript. M.G. assisted with data analysis and interpretation of data, and reviewed the manuscript. M.H.J.H. assisted with data analysis and interpretation of data, and reviewed the manuscript.

Compliance with Ethical Principles

The manuscripts entitled “Enhanced risks of PRES and RCVS associated with the use of pseudoephedrine: a review” reporting data from the studies does not involving human or animal participants, since themanuscript is a review article. The study does not require approval from an appropriate institutional review board (IRB) or ethics committee.

Publikationsverlauf

Artikel online veröffentlicht:
30. August 2024

• References

• 1 European Medicines Agency. EMA confirms measures to minimize the risk of serious side effects with medicines containing pseudoephedrine. 2023 . Accessed February 21, 2024 at: https://www.ema.europa.eu/en/news/ema-confirms-measures-minimise-risk-serious-side-effects-medicines-containing-pseudoephedrine
• 2 European Medicines Agency. PRAC starts safety review of pseudoephedrine-containing medicines. 2023 . Accessed February 21, 2024 at: https://www.ema.europa.eu/en/documents/referral/pseudoephedrine-containing-medicines-article-31-referral-review-started_en.pdf
• 3 United Kingdom Medicines and Healthcare Products Regulatory Agency (MHRA). Vigilance, safety alerts and guidance. MHRA safety review of medicines containing pseudoephedrine. 2023 . Accessed February 21, 2024 at: https://www.gov.uk/government/news/mhra-safety-review-of-medicines-containing-pseudoephedrine
• 4 European Medicines Agency. PRAC recommends measures to minimize the risk of serious side effects with medicines containing pseudoephedrine. 2023 . Accessed February 21, 2024 at: https://www.ema.europa.eu/en/documents/referral/prac-recommends-measures-minimise-risk-serious-side-effects-medicines-containing-pseudoephedrine_en.pdf
• 5 De Sutter AI, Eriksson L, van Driel ML. Oral antihistamine-decongestant-analgesic combinations for the common cold. Cochrane Database Syst Rev 2022; 1 (01) CD004976
• 6 Petkovic S, Maletic I, Djuric S, Dragutinovic N, Milovanovic O. Evaluation of nasal decongestants by literature review. Serb J Exp Clin Res 2019; (e-pub ahead of print).
• 7 Munafò A, Frara S, Perico N. et al. In search of an ideal drug for safer treatment of obesity: The false promise of pseudoephedrine. Rev Endocr Metab Disord 2021; 22 (04) 1013-1025
• 8 Pandal P, Singh A, Sharma K. et al. Ephedrine and pseudoephedrine: a comprehensive review of their pharmacology and clinical applications. J Chem Health Risks 2024; 14 (01) 1447-1455
• 9 Li K, Yang Y, Guo D, Sun D, Li C. Clinical and MRI features of posterior reversible encephalopathy syndrome with atypical regions: a descriptive study with a large sample size. Front Neurol 2020; 11: 194
• 10 Anderson RC, Patel V, Sheikh-Bahaei N. et al. Posterior reversible encephalopathy syndrome (PRES): pathophysiology and neuro-imaging. Front Neurol 2020; 11: 463
• 11 Ribas MZ, Paticcié GF, de Medeiros SDP, de Oliveira Veras A, Noleto FM, Dos Santos JCC. Reversible cerebral vasoconstriction syndrome: literature review. Egypt J Neurol Psychiat Neurosurg 2023; 59 (01) 5
• 12 Chen SP, Wang SJ. Pathophysiology of reversible cerebral vasoconstriction syndrome. J Biomed Sci 2022; 29 (01) 72
• 13 Singhal AB. Reversible cerebral vasoconstriction syndrome: a review of pathogenesis, clinical presentation, and treatment. Int J Stroke 2023; 18 (10) 1151-1160
• 14 Ebbo M, Benarous L, Thomas G. et al. Posterior reversible encephalopathy syndrome induced by a cough and cold drug containing pseudoephedrine. Rev Med Interne 2010; 31 (06) 440-444
• 15 Zerbib Y, Gibert L, Bennis Y, Masmoudi K, Maizel J, Brault C. Posterior reversible encephalopathy syndrome after self-medication with an oral decongestant: a case report. Front Med (Lausanne) 2022; 9: 837324
• 16 Gunduz ZB. Posterior reversible encephalopathy syndrome occurred during the use of pseudoephedrine: a case report. Clin Neuropharmacol 2022; 45 (05) 145-147
• 17 United Kingdom Medicines and Healthcare Products Regulatory Agency (MHRA). Drug Safety Update. Pseudoephedrine: very rare risk of posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS). 2024 . Accessed February 21, 2024 at: https://www.gov.uk/drug-safety-update/pseudoephedrine-very-rare-risk-of-posterior-reversible-encephalopathy-syndrome-pres-and-reversible-cerebral-vasoconstriction-syndrome-rcvs
• 18 Farid H, Tatum JK, Wong C, Halbach VV, Hetts SW. Reversible cerebral vasoconstriction syndrome: treatment with combined intra-arterial verapamil infusion and intracranial angioplasty. AJNR Am J Neuroradiol 2011; 32 (10) E184-E187
• 19 Lee DH, Lee SC, Choi N, Lee SW, Lee TK. Reversible cerebral vasoconstriction syndrome induced by pseudoephedrine. J Neurocritical Care. 2016; 9 (01) 28-32
• 20 Jacoby N, Kaunzner U, Dinkin M, Safdieh J. Diagnosing RCVS without the CV: the evolution of reversible cerebral vasoconstriction syndrome. Neurohospitalist 2016; 6 (03) NP1-NP4
• 21 Pilato F, Distefano M, Calandrelli R. Posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome: clinical and radiological considerations. Front Neurol 2020; 11: 34
• 22 Jeanneret V, Jillella DV, Rangaraju S. et al. PRES and RCVS: two distinct entities or a spectrum of the same disease?. J Stroke Cerebrovasc Dis 2022; 31 (06) 106472
• 23 European Medicines Agency. Direct healthcare professional communication (DHPC): Pseudoephedrine—Risks of posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS). 2024 . Accessed February 21, 2024 at: https://www.ema.europa.eu/en/documents/dhpc/direct-healthcare-professional-communication-dhpc-pseudoephedrine-risks-posterior-reversible-encephalopathy-syndrome-pres-reversible-cerebral-vasoconstriction-syndrome-rcvs_en.pdf