Myocardial infarction and ischemic stroke with vasoconstrictors used as nasal decongestant for common cold: a French pharmacovigilance survey

Abstract

Oral (pseudoephedrine and phenylephrine) and intranasal (oxymetazoline, naphazoline, phenylephrine, ephedrine, and tuaminoheptane) vasoconstrictors with direct (alpha and/or beta-adrenergic agonist) and/or indirect (by increasing noradrenaline release from sympathetic nerves) sympathomimetic properties are widely used worldwide for nasal congestion during common cold [1]. In France, oral vasoconstrictors (associated with ibuprofen, paracetamol, and/ or H1 antihistaminics) are prescription-free drugs, whereas intranasal vasoconstrictors (with or without prednisolone or antiseptics) are prescription-only drugs. Regression of common cold is usually observed within 7 to 10 days with or without symptomatic drugs [2]. The 2016 Cochrane review assessing the efficacy of nasal decongestants (ND) in monotherapy was unable to conclude about the efficacy of single-dose. Multiple doses showed a small positive effect with no evidence of clinical relevance [3]. Several reports of ischemic adverse drug reactions (ADRs) associated with ND use have been reported to the French pharmacovigilance network. We thus reviewed all myocardial infarction (MI) and ischemic stroke (IS) reports associated with ND defined as “suspect” and registered in the French Pharmacovigilance Database (FPVD) from 1985 to the 1 June 2019 [4]. The FPVD recorded the main characteristics of patients (age, sex, and relevant comorbidities), the “suspected” drugs, and the ADR characteristics (seriousness and evolution). We defined a ND misuse if patients were under 15 years old, with uncontrolled hypertension, coronary insufficiency, previous history of stroke, convulsions, use for > 5 days, or simultaneous association of 2 vasoconstrictors. In FPVD, 21 “serious” MI with a ND “suspected” were reported, mainly in men (n = 16, 76.2%) with mean age 41.2 ± 14.4 years. More than 70 % (n = 15) had at least 1 cardiovascular risk factor (4 men > 50 years, 1 woman > 60 years, 4 familial histories of MI, 3 dyslipidemias, 3 tobacco smokers, 2 arterial hypertensions, 2 diabetes, 2 overweight patients). The most frequently “suspected” drugs were pseudoephed r ine (n = 14 , 66 .7%) fo l lowed by oxymetazoline (n = 4, 19.0%). Misuse was found in 13 reports (62.0%) including 10 uses for > 5 days and 2 coronary insufficiencies and 1 simultaneous association of 2 vasoconstrictors for > 5 days. Other drugs considered as “suspect”were found in 3 patients (2 estroprogestative contraceptions and 1 nonsteroidal anti-inflammatory drug NSAID). One patient died 2 h after taking pseudoephedrine. Fifty-two “serious” IS were registered, mainly in men (n = 30, 57.7%) with mean age 49.5 ± 18.0 years. Cardiovascular risk factors were found in 32 reports (61.5%) (10 men > 50 years, 9 women > 60 years, 10 arterial hypertensions, 8 dyslipidemias, 8 tobacco smokers, 5 migraines, 5 overweight patients, 1 diabetes, 1 atrial fibrillation). The most “suspected” drugs were * Margaux Lafaurie [email protected]