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Aims: Antihistamines are routinely taken to control allergic reactions or sedation to induce sleep. There are, however, growing concerns regarding sedating antihistamine misuse. This research aims to evaluate deaths related to antihistamines in England occurring during 2000-2019., Methods: Cases reported to the National Programme on Substance Abuse Deaths from England occurring in 2000-2019 with antihistamine detections at postmortem were extracted for analysis., Results: In total, 1666 antihistamine postmortem detections were identified from 1537 cases. Sedating antihistamines available for purchase under pharmacist supervision but without need for a prescription (pharmacy-only medications) were present in a significant majority of cases (85.2%, P < .01). Despite an increasing trend for antihistamine-related deaths over time, the proportion of deaths where an antihistamine was implicated declined over the same period. Specific concerns with regards to the misuse of these pharmacy-only sedating antihistamines are raised with regards to the significant proportion of cases that were concluded as suicide (20.9%, P < .01), and the high prevalence of their use in combination with other central nervous system depressants (94.8% of cases)., Conclusion: This is the first report in over 40 years regarding antihistamine-related mortality from England. The rising trend in sedating antihistamine-related deaths may be contributed to by their increasing availability and the perceived negligible dangers associated with antihistamines, both from the general public and learned professionals. Awareness of the dangerous sedative properties that some antihistamines possess is, however, heightened in individuals deliberately seeking these effects. Urgent review of sedating antihistamines currently assigned under the pharmacy-only classification is needed to achieve antihistamine harm reduction., (© 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Desloratadine is a non-sedating, long-acting histamine H(1) receptor antagonist indicated for the symptomatic relief of allergic rhinitis (AR) and chronic idiopathic urticaria in patients aged>12 years., Objective: To monitor the safety of desloratadine as prescribed in England, using the observational cohort technique of prescription event monitoring (PEM)., Methods: Exposure data were derived from dispensed prescriptions written by primary care physicians (general practitioners [GPs]) for desloratadine (March-May 2001); patient demographics, indication, pattern of use and outcome (event) data were obtained via simple questionnaires returned by GPs. Incidence density observation rates (IDobs) were calculated to compare the difference in event rates between months 1 and 2 (m1/m2) and were compared for the whole cohort and by groups defined by indication and pattern of use., Results: The cohort comprised 11 828 patients (median age 37 years [interquartile range 22, 54]; 59.9% were female). The most frequent indication was AR (n=8001; 67.6%). After 2 months, 36.8% (n=2464) of patients were still taking desloratadine. 'Condition improved' was the most common event and reason for stopping. Headache/migraine was uncommon but associated with starting treatment (IDobs(m1/m2) ratio 3.99 [95% CI 1.70, 10.83]). Cardiovascular events occurred rarely or very rarely, as did central and peripheral nervous system events. No serious adverse drug reactions (ADRs) were reported. Events related to effectiveness were more frequent in month 1 than month 2 for all patient subgroups., Conclusions: This postmarketing surveillance study shows that desloratadine is well tolerated when used in general practice in England. No previously unrecognized ADRs were detected. This study highlights how modifications to PEM are contributing to the evaluation of drug utilization factors in relation to risks.

Background and Objectives: Desloratadine and levocetirizine are histamine H(1) receptor antagonists (antihistamines) that were launched in the UK in 2001. Our objective was to compare the frequency with which drowsiness and sedation were reported for desloratadine and levocetirizine within the first 30 days of observation, as monitored using the observational cohort technique of prescription-event monitoring (PEM)., Methods: Exposure data were derived from dispensed prescriptions written by primary care physicians and outcome data were derived from questionnaires that were posted to prescribers at least 6 months after the date of the first prescription for each patient. The odds ratio (OR) was calculated using unconditional logistic regression modelling. The effect of age, sex, reported prescribing indication (allergic rhinitis with asthma/wheezing, allergic rhinitis without asthma/wheezing, 'other'), pattern of use and reported previous antihistamine use on the OR was examined. A time-to-event analysis was performed., Results: The cohorts comprised >24,000 patients in total. Cohort demographics were similar (both cohorts: median age 37 years; 60% women); the most frequently reported prescribing indication for both drugs was allergic rhinitis without asthma/wheezing (54%). The incidence of first reports of drowsiness/sedation for levocetirizine or desloratadine was low (46 [0.37%] and 9 [0.08%], respectively) and statistically different (p < 0.0001). These events tended to occur earlier for desloratadine than levocetirizine (50% at 7 or 14 days of observation, respectively; p = 0.6487), but the cumulative time to event differed, with more events observed for levocetirizine than expected (p < 0.0001; 46 vs 28.09). The final estimates of risk were the sex-adjusted ORs for each prescribing indication category: allergic rhinitis with asthma/wheezing (3.51; 95% CI 0.71, 17.43; n = 3357), allergic rhinitis without asthma/wheezing (6.75; 95% CI 2.37, 19.22; n = 12,627) and 'other' (3.11; 95% CI 0.86, 11.31; n = 6725)., Discussion: Although the reporting rates of drowsiness and sedation are low for both drugs, patients prescribed levocetirizine are more likely to experience drowsiness and sedation in the first month of observation (after starting treatment) than patients prescribed desloratadine. For patients with allergic rhinitis without asthma/wheezing, the sex-adjusted odds of drowsiness/sedation were over six times greater in patients using levocetirizine than desloratadine in the first month of observation, with the OR being statistically significant. For the other two indication categories, allergic rhinitis with asthma/wheezing and 'other', the OR was not statistically significant., Conclusions: Although the risk of drowsiness/sedation is low, conditions such as allergic rhinitis are common, which makes any impact on patient cognitive function important. Doctors should be aware of this when prescribing these products to patients where daytime sedation is undesirable. However, essential components of the comparative benefit-risk evaluation of these two products include assessment of efficacy and patient preference (neither of which forms part of this study).

Background: Fexofenadine is the active metabolite of the non-sedating anti-histamine terfenadine. Pre-licensing clinical trials in over 6000 patients suggested it was effective and well tolerated., Objective: To assess the tolerability and safety of fexofenadine immediately after its availability on the UK market in March 1997., Methods: Post-marketing non-interventional observational cohort study using the methodology of prescription-event monitoring. Exposure data derived from dispensed prescription details supplied in confidence by the Prescription Pricing Authority. Outcome data derived from questionnaires returned by general practitioners (GPs) in England between March and August 1997., Results: Of the 35,817 questionnaires sent, 18,238 (50.9%) were returned, of which 16,638 contained useful data. These included 40% male (mean age 36+/-19 years) and 59% female (mean age 39+/-19 years). Most common indications were allergic rhinitis (55%), not specified (28%), urticaria, pruritus or rash (10%) and other indications (7%). There were 40 reports of adverse drug reactions in 27 patients. Less than 2% of patients stopped the drug because of side effects. Events reported after exposure to fexofenadine were uncommon and already reported in clinical trials. There were eight reports of possible cardiac side effects (palpitations, three; chest pain, three; arrhythmia, one; and chest tightness, one). None was felt to be serious. There were no drug interactions reported. None of the 30 deaths was related to fexofenadine. None of the three adverse outcomes from the 47 pregnancies reported was related to fexofenadine., Conclusion: Within the limitations for an observational cohort study, fexofenadine was found to be well tolerated and safe in 16,638 users in general practice in England.

Of 817 patients in a general-practice survey of adverse reactions to drugs, 41% were thought to have "certainly" or "probably" had a reaction to the drug prescribed. Adverse effects on the gastrointestinal and central nervous systems were the most frequently reported, and 90% of reactions had occurred by the fourth day of treatment. More patients given drugs acting on the central nervous system and antihistamines reported reactions than those in other categories. A higher incidence of adverse drug effects is shown in this general-practice survey than in other, mainly hospital-based, surveys. Further intensive surveillance for adverse effects of drugs is recommended to provide additional information on the burden of drug-induced disease in the community.