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Purpose: The effects of first-generation antihistamines in preventing postoperative emergence agitation or delirium are unclear. Determining the postoperative effects of first-generation antihistamines may provide important insights into the management of patient safety. Therefore, we performed a systematic review of randomized controlled trials (RCTs) evaluating the efficacy and safety of postoperative first-generation antihistamines., Methods: Patients who used first-generation antihistamines in the intensive care unit or operating room were included. Primary outcomes were assessed postoperative emergence agitation or delirium with binary and continuous variables. The secondary outcome was any adverse event., Results: Nine studies were included. The frequency of postoperative emergence agitation, measured using binary variables, tended to be lower in patients receiving chlorpheniramine or diphenhydramine than those receiving saline. However, evaluation using the Richmond Agitation-Sedation Scale as a continuous variable revealed that only chlorpheniramine was effective at lowering postoperative emergence agitation. Only one study assessed delirium but found no benefit of first-generation antihistamines. Adverse events for first-generation antihistamines did not differ from that of other drugs., Conclusion: Our results provide limited evidence that some first-generation antihistamines may prevent postoperative emergence agitation and are safe. To further verify this possibility, new RCTs with clear and universal assessment criteria for postoperative emergence agitation or delirium should be conducted., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: The objectives are to determine whether diphenhydramine coadministered with prochlorperazine versus prochlorperazine only is associated with a difference in the risk of migraine treatment failure, as measured by the need for additional therapy, hospitalization rates, and 72-hour return rates, and to compare extrapyramidal adverse effects between groups., Methods: Retrospective cohort of patients aged 7 to 18 years treated in the emergency department for migraines using prochlorperazine with or without diphenhydramine between 2013 and 2019. Patients were included if they had International Classification of Diseases, Ninth or Tenth Revision, codes for migraine or unspecified headache and were treated with prochlorperazine as part of their initial migraine therapy. Data collected included demographics, medications administered, pain scores, neuroimaging, disposition, return visits, and documentation of extrapyramidal adverse effects. Multivariable logistic regression was used to estimate the association between diphenhydramine coadministration and each of the outcomes., Results: A total of 1683 patients were included. Overall, 13% required additional therapy with a 16.7% admission rate and a 72-hour return rate of 5.3%. There was no association between initial treatment with diphenhydramine and the odds of additional therapy (adjusted odds ratio [aOR], 0.74 [95% confidence interval {CI}, 0.53-1.03]), admission rates (aOR, 1.22 [95% CI, 0.89-1.67]), or return visit rates (aOR, 0.91 [95% CI, 0.55-1.51]). Extrapyramidal adverse effects occurred in 2.4% of patients in the prochlorperazine group and 0% in the prochlorperazine with diphenhydramine group., Conclusions: There was no association between diphenhydramine coadministration and the need for additional therapy, 72-hour return visit rates or admission rates. Extrapyramidal effects did not occur in patients treated with diphenhydramine., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: Given the underlying properties of cannabinoids, we aimed to assess associations between cannabinoid use and sedation requirements for esophagogastroduodenoscopy (EGD) and colonoscopy. Methods: A prospective cohort study was conducted at three endoscopy units. Adult outpatients undergoing EGD or colonoscopy with endoscopist-directed conscious sedation (EDCS) were given questionnaires on cannabinoid use and relevant parameters. Outcomes included intraprocedural midazolam, fentanyl, and diphenhydramine use, procedural tolerability, and adverse events. Multivariable logistic regression was performed to yield adjusted odds ratios (AORs) of outcomes. Results: A total of 419 patients were included. Baseline cannabinoid use was associated with high midazolam use, defined as ≥5 mg, during EGD (AOR 2.89, 95% confidence interval, CI: 1.19-7.50), but not during colonoscopy (AOR 0.89, 95% CI 0.41-1.91). Baseline cannabinoid use was associated with the administration of any diphenhydramine during EGD (AOR 3.04, 95% CI: 1.29-7.30) with a similar nonsignificant trend for colonoscopy (AOR 2.36, 95% CI: 0.81-7.04). Baseline cannabinoid use was associated with increased odds of requiring high total sedation, defined as any of midazolam ≥5 mg, fentanyl ≥100 mcg, or any diphenhydramine during EGD (AOR 3.72, 95% CI: 1.35-11.68). Cannabinoid use was not independently associated with fentanyl use, intraprocedural awareness, discomfort, or adverse events. Conclusions: Baseline cannabinoid use was associated with higher sedation use during endoscopy with EDCS, particularly with midazolam and diphenhydramine. Given increasingly widespread cannabinoid use, endoscopists should be equipped with optimal sedation strategies for this population. As part of the informed consent process, cannabis users should be counseled that they may require higher sedation doses to achieve the same effect.

Objective: Evaluation of the efficacy and safety of Levroso Long (fixed dose combination (hereinafter referred to as «FDC») diphenhydramine and melatonin, 25 mg + 3 mg and FDC diphenhydramine and melatonin 50 mg + 3 mg, respectively, capsules with modified release, NovaMedica Innotech LLC) in comparison with diphenhydramine medicines 50 mg (Diphenhydramine tablets, DALHIMFARM OJSC, Russia) and 3 mg melatonin (Melaxen tablets, Unipharm Inc., USA) in patients with insomnia., Materials and Methods: Material and methods. A multicenter open randomized comparative clinical trial was conducted in parallel groups. The study included 312 patients with an insomnia diagnosis verified in accordance with the DSM-IV criteria (ICD code F51.0-10) and an insomnia severity index (ICI) >8 points. The patients were randomized into 4 groups and took the following medications for 10 days: patients of group 1 - Levroso Long (25 mg diphenhydramine and 3 mg melatonin), group 2 - Levroso Long combination drug (50 mg diphenhydramine and 3 mg melatonin), Group 3 -Diphenhydramine 50 mg, 4 th - Melaxen 3 mg. A comparative assessment was performed on the 7 th and 10 th days of therapy according to the primary endpoint - ICI, and secondary endpoints - the results of the assessment based on the Leeds Sleep Assessment Questionnaire, the Pittsburgh Sleep Quality Questionnaire, the Scale of the overall clinical impression of improvement and the analysis of the profile of adverse events (NA)., Results: The FDC of diphenhydramine 25 mg + melatonin 3 mg was more effective than diphenhydramine 50 mg, and FDC diphenhydramine 50 mg + melatonin 3 mg was more effective than diphenhydramine 50 mg or melatonin 3 mg on both primary and secondary endpoints. In a safety assessment, the highest incidence of adverse events (48.7%) in the diphenhydramine 50 mg group was significantly lower in groups 1 (29.5%), 2 (12.8%) and 4 (1.3%). All reported adverse events in the FDC groups were mild or moderate in severity., Conclusion: The study showed that Levroso Long in two dosages surpassed monotherapy with 50 mg of Diphenhydramine (50 mg) or Melaxen (3 mg) in patients with insomnia in terms of efficacy parameters. The benefit/risk ratio of the studied drug is favorable compared to monotherapy.

Cetirizine, a second-generation antihistamine, and diphenhydramine, a first-generation antihistamine, are among the most widely used anti-allergic drugs. In addition to longer duration of action and less incidence of sedative side effects, recent clinical studies also indicate a higher potency of cetirizine than diphenhydramine in the treatment or prevention of allergic disorders. In the present study, using the differential-interference contrast (DIC) microscopy, we examined the effects of cetirizine and diphenhydramine (1 μM to 1 mM) on the degranulation from rat peritoneal mast cells. Using fluorescence imaging of a water-soluble dye, lucifer yellow, we also examined their effects on the deformation of the plasma membrane. At relatively higher concentrations (100 μM, 1 mM), both cetirizine and diphenhydramine significantly reduced the numbers of degranulating mast cells. Of note, at 1 mM, cetirizine more markedly reduced the number than diphenhydramine, almost entirely suppressing the degranulation of mast cells. Additionally, 1 mM cetirizine and levocetirizine, another second-generation antihistamine, almost totally inhibited the process of exocytosis in mast cells and washed out the trapping of the lucifer yellow on the cell surface, while diphenhydramine and chlorpheniramine, another first-generation antihistamine, did not. This study provided in vitro evidence for the first time that cetirizine more potently inhibited the process of exocytosis in mast cells than diphenhydramine, indicating its higher potency as a mast cell-stabilizer. Such mast cell-stabilizing property of cetirizine could be ascribed to its counteracting effect on the plasma membrane deformation in degranulating mast cells.

Many drugs carry some risk of QT interval prolongation, which can lead to life-threatening dysrhythmias including Torsades de Pointes (TdP). CredibleMeds.org identifies medications categorized as "Known Risk of TdP" but does not stratify risk in acute supratherapeutic ingestions. We sought to determine the proportion of cases exhibiting QTc prolongation and life-threatening dysrhythmias including ventricular tachycardia (VT)/ventricular fibrillation (VF), TdP, and asystole in patients exposed to these substances. Retrospective chart review of cases reported to our Regional Poison Center from 2014 to 2019 of exposures to one or more of the "Known Risk" substances was performed. Demographics, therapies, clinical effects, and medical outcome for each case were analyzed. There were 1125 exposures, of which 760 had a documented QTc interval. QTc ≥ 500 ms was reported in 138 (18.2%) of the 760 cases. The most common "Known Risk" substances were citalopram, escitalopram and cocaine. Although not in the "Known Risk" category, mirtazapine, amitriptyline, diphenhydramine, and trazodone had a statistically significant association with QTc > 500 ms. Life-threatening dysrhythmias occurred in 13 cases, with VT/VF in 6 of the 760 (0.8%) cases, and one case of TdP. Flecainide (OR 11.1, 95% CI 2.2-55.8) and methadone (OR 7.1, 95% CI 2.1-23.4) were associated with increased risk of all life-threatening dysrhythmias. Exposures to medications on the Credible Meds list of "Known Risk of TdP" QTc prolongation is common, but life-threatening dysrhythmias are rare. Mirtazapine, amitriptyline, diphenhydramine, and trazodone were associated with prolonged QTc. Flecainide and methadone had the highest associated risk of life-threatening dysrhythmias., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To estimate the incidence of potential in-hospital adverse reactions  with the use of alert drugs in a general hospital in southern Brazil. Method: Cross-sectional study, carried out in a hospital in southern Brazil. The  electronic medical records (TASY®) of patients hospitalized between January  and August 2020, who were prescribed one of the drugs earmarked for  tracking adverse drug reactions, were evaluated: the drugs included  flumazenil, fexofenadine hydrochloride, naloxone, promethazine, diphenhydramine and loperamide., Results: A total of 13,476 medical records were reviewed and 204 (1.5%)  were included in the study in which tracker use was indicated in the management of adverse drug reactions. In this study a total of 18 different signs or symptoms were found in medical records, with  pruritus/hyperemia/urticaria being the most reported symptoms (n = 76).  Among the drug classes that caused most adverse drug reactions, opioids were  the most mentioned (n = 44). It should be noted that in 49 medical  records the information on which drug caused the adverse events was not  reported. Regarding the cause of hospitalization of patients who used  creening drugs, cancer was the most frequent (n = 37)., Conclusions: This study indicates that the use of trackers can be a tool to  estimate the occurrence of adverse drug reactions and to establish adverse  events related to the use of medications, which should be reported to the  pharmacovigilance service, with a view to patient safety., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

Purpose: Cetirizine is a less sedative alternative to diphenhydramine for the prevention of infusion-related reactions (IRR) to paclitaxel. However, its use remains controversial. In this study, we assessed feasibility for a future definitive non-inferiority trial comparing cetirizine to diphenhydramine as premedication to prevent paclitaxel-related IRR., Methods: This was a single-center randomized prospective feasibility study. Participants were paclitaxel-naive cancer patients scheduled to start paclitaxel chemotherapy. They were randomly assigned to receive either intravenous diphenhydramine 50 mg + oral placebo (control) or intravenous placebo + oral cetirizine 10 mg (intervention) for their first two paclitaxel treatments. The percentage of eligible patients completing a first paclitaxel treatment and the recruitment rate were assessed (feasibility outcomes). Drowsiness was measured at baseline and at selected time points using the Stanford Sleepiness Scale (SSS) (safety outcome). IRR events were also documented (efficacy outcome)., Results: Among 37 eligible patients, 27 were recruited and randomized (control 13; intervention 14) and 25 completed the study. The recruitment rate was 4.8 participants/month, meeting the primary feasibility target. Drowsiness was the main adverse effect associated with the premedication. The increase in drowsiness compared to baseline (ΔSSS) was greater in the diphenhydramine group compared to the cetirizine group (median ΔSSS 2 (IQR 3.25) vs median ΔSSS 0 (IQR 1), p < 0.01) when measured one hour after the premedication administration. One participant had an IRR and no unexpected serious adverse event occurred., Conclusion: The trial methods were feasible in terms of recruitment, retention, and safety. Cetirizine was significantly less sedating than diphenhydramine. IRR were infrequent and a larger trial is warranted to confirm non-inferiority for IRR prevention., Trial Registration: ClinicalTrials.gov, NCT04237090 (22.01.2020)., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Since 1955, the only available H 1 antihistamines for intravenous administration have been first-generation formulations and, of those, only intravenously administered (IV) diphenhydramine is still approved in the USA. Orally administered cetirizine hydrochloride, a second-generation H 1 antihistamine, has been safely used over-the-counter for many years. In 2019, IV cetirizine was approved for the treatment of acute urticaria. In light of this approval, this narrative review discusses the changing landscape of IV antihistamines for the treatment of histamine-mediated conditions. Specifically, IV antihistamines will be discussed as a treatment option for acute urticaria and angioedema, as premedication to prevent infusion reactions related to anticancer agents and other biologics, and as an adjunct treatment for anaphylaxis and other allergic reactions. Before the development of IV cetirizine, randomized controlled trials of IV antihistamines for these indications were lacking. Three randomized controlled trials have been conducted with IV cetirizine versus IV diphenhydramine in the ambulatory care setting. A phase 3 trial of IV cetirizine 10 mg versus IV diphenhydramine 50 mg was conducted in 262 adults who presented to the urgent care/emergency department with acute urticaria requiring antihistamines. For the primary efficacy endpoint, defined as change from baseline in a 2-h patient-rated pruritus score, non-inferiority of IV cetirizine to IV diphenhydramine was demonstrated (score - 1.6 vs - 1.5, respectively; 95% CI - 0.1, 0.3). Compared with IV diphenhydramine, IV cetirizine demonstrated fewer adverse effects including less sedation, a significantly shorter length of stay in the treatment center, and fewer returns to the treatment center at 24 and 48 h. Similar findings were demonstrated in another phase 2 acute urticaria trial and in a phase 2 trial assessing IV cetirizine for pretreatment for infusion reactions in the oncology/immunology setting. IV cetirizine is associated with similar patient outcomes, fewer adverse effects, and increased treatment center efficiency than IV diphenhydramine., (© 2021. The Author(s).)

Objective: We conducted a randomized trial among emergency department patients with migraine to determine the relative impact on migraine-associated symptoms of hydromorphone, an opioid, versus prochlorperazine, an antidopaminergic antiemetic., Methods: This was a post hoc analysis of data from a double-blind study registered at http://clinicaltrials.gov (NCT02389829). Patients who met International Classification of Headache Disorders, 3rd edition criteria for migraine without aura or for probable migraine without aura were eligible for participation. Participants received either hydromorphone 1 mg IV or prochlorperazine 10 mg IV plus diphenhydramine 25 mg IV and could receive a second dose of the same medication 1 h later if needed. The outcomes were sustained relief of nausea, photophobia, and phonophobia., Results: A total of 127 patients were enrolled, of whom 63 received prochlorperazine and 64 received hydromorphone. Of 49 patients in the prochlorperazine arm who reported nausea at baseline, 34 (69.4%) reported complete resolution without relapse versus 15/49 (30.6%) in the hydromorphone arm (absolute risk reduction [ARR] = 38.8%, 95% CI: 20.5%-57.0%, p < 0.001). Of 55 patients in the prochlorperazine arm who reported photophobia at baseline, 23 (41.8%) reported complete resolution without relapse versus 13/62 (20.9%) patients treated with hydromorphone (ARR = 20.8%, 95% CI: 4.3%-37.3%, p = 0.014). Of 56 patients in the prochlorperazine arm who reported phonophobia at baseline, 25 (44.6%) reported complete resolution without relapse versus 16/59 (27.1%) in the hydromorphone arm (ARR = 17.5%, 95% CI: 0.3%-34.8%, p = 0.049). For adverse events, three patients in the prochlorperazine arm reported anxiety or restlessness, and nine patients in the hydromorphone arm reported dizziness or weakness., Conclusions: Prochlorperazine plus diphenhydramine is more efficacious than hydromorphone for the treatment of migraine-associated symptoms., (© 2021 American Headache Society.)

Introduction: Initial research following regulatory changes addressing the pediatric safety of cough and cold medications (CCMs) demonstrated decreases in adverse events (AEs). Using a national multi-source surveillance system, we studied subsequent CCM-related AE case rate trends and associated health-care facility (HCF) evaluation in children., Methods: Data were collected from 2009 to 2016. Case eligibility included: age <12 years; exposure to an over-the-counter product containing ≥1 CCM pharmaceutical ingredient; ≥1 significant AE that occurred in the United States., Results: About 4756 (72.6%) cases were determined at least potentially related to an index ingredient. Accidental unsupervised ingestions (AUIs; 3134; 65.9%) were the most common case type. Nearly half of AE cases involved children 2 to <4 years old (2,159; 45.4%). The AE case rate did not change significantly over time ( p  = 0.22). The proportion of AE cases resulting in HCF admission increased from 32.4% (207) in 2009 to 43.4% (238) in 2016 ( p  < 0.01). Exposures to diphenhydramine (1,305; 67.3%) and/or dextromethorphan (591; 30.5%) were involved in the majority of HCF admissions., Conclusions: The proportion of AE cases resulting in HCF admission increased from 2009 to 2016. Efforts to prevent AUIs such as packaging innovation and engineering controls, particularly for diphenhydramine and dextromethorphan-containing products, should be pursued.

Background: Diphenhydramine is commonly used in patients with kidney disease and end-stage kidney disease (ESKD) for sleep, allergic reactions, itching, and dialysis treatment related complications, and misuse associated with diphenhydramine is also reported. Diphenhydramine's pharmacokinetics property is reviewed and discussed., Areas of Uncertainty: Diphenhydramine is highly bound to albumin. The safety profile and dosing information of diphenhydramine use in ESKD population is lacking. The purpose of this study is to provide an overview of diphenhydramine pharmacokinetic properties and evaluate diphenhydramine use in ESKD population., Data Sources: A literature search was conducted during Spring 2019 using PubMed, CINAHL, Cochrane, Ovid, and Google Scholar. Search terms used include "diphenhydramine abuse," "diphenhydramine dialysis," and "diphenhydramine kidney disease.", Results: There is lack of studies available for diphenhydramine, kidney disease, and dialysis. There were case reports of diphenhydramine abuse and toxicity due to overdose. Diphenhydramine is highly bound to protein that limits its ability to dialyze, and therefore, it may predispose to side effects. Information on diphenhydramine used in the dialysis population is scarce, and dosing toxicity is unknown., Conclusions: The data available for use of diphenhydramine in ESKD and dialysis are limited. Clinicians should use caution with the use of diphenhydramine in this population., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Neuroleptics are commonly prescribed drugs to treat acute conditions (e.g., migraines) in the emergency department, but can cause serious adverse effects. Using diphenhydramine to prevent these adverse effects is very common but remains controversial., Objective: We performed a systematic review to determine whether prophylactic administration of diphenhydramine reduces the incidence of neuroleptic adverse effects in patients with acute conditions., Methods: Medline, Embase, Cochrane, PsycInfo, and Web of Science were searched for randomized controlled trials evaluating any neuroleptic with diphenhydramine vs. the same neuroleptic with any inactive agent. Primary outcome was incidence of any extrapyramidal adverse effect. Secondary outcomes were akathisia, rescue medication, subjective restlessness, neuroleptic malignant syndrome, and sedation. Independent reviewers scanned identified citations, extracted data, and assessed risk of bias. Meta-analysis was performed using random effect models., Results: Of 1566 identified citations, nine studies (n = 1648 patients) met eligibility criteria. Four studies were specifically designed to compare the incidence of neuroleptic adverse effects with and without co-administration of diphenhydramine. Four studies were at high risk of bias. In primary analysis, diphenhydramine had no effect on the incidence of extrapyramidal symptoms (7 studies, n = 1393, risk ratio [RR] 0.75; 95% confidence interval [CI] 0.44-1.31) or akathisia (5 studies, n = 1094; RR 0.78; 95% CI 0.33-1.82) or any of the secondary outcomes. In subgroup analysis, diphenhydramine was associated with a significant decrease in extrapyramidal adverse effects compared with placebo (4 studies, n = 705; RR 0.61; 95% CI 0.41-0.90). Dosage analysis yielded no further information., Conclusions: When compared with placebo, diphenhydramine was associated with a significant reduction of extrapyramidal adverse effects. Overall quality of evidence is low. Further studies are warranted., (Copyright © 2020 Elsevier Inc. All rights reserved.)

OBJECTIVE: The purpose of this systematic review is to evaluate the available evidence for safety and efficacy of over-the-counter (OTC) sleep aids used for the treatment of insomnia in older people.
DATA SOURCES: PubMed, EBSCO, and International Pharmaceutical Abstracts.
STUDY SELECTION: Five studies were included that involved humans 65 years of age and older being evaluated on OTC sleep aids in the outpatient setting.
DATA EXTRACTION: Data extraction from each study included primary and secondary efficacy endpoints, such as differences in the mean total sleep time, sleep latency, sleep efficiency, and number of awakenings, along with safety endpoints, such as psychomotor ability, cognitive ability, and adverse effect profiles. Both subjective and objective measures of changes in sleep and adverse effects were included.
DATA SYNTHESIS: Diphenhydramine had a statistically significant increase in sedation and decrease in number of awakenings but was not shown to be any less or more safe than compared products. Despite lacking safety issues, valerian was found to have no effect on subjective or objective sleep outcomes. Overall, melatonin had the most evidence and was found to have a statistically significant positive impact on sleep measures without safety issues.
CONCLUSION: Diphenhydramine and melatonin appear to be efficacious in improving some sleep measures while causing minimal adverse effects. However, there are very few studies that examine the use of over-the-counter sleep aids in those 65 years of age and older with primary insomnia. Additional studies are needed in this population.

Background: To evaluate the effectiveness of diphenhydramine, an antihistamine with anti-muscarinic properties, for prevention of postoperative catheter-related bladder discomfort (CRBD)., Methods: Ninety-six ASA physical status I and II adult female patients (20-60 years) scheduled for elective gynecologic laparoscopic surgery were included. Patients were randomized into two groups of 48 patients each. All patients received a detailed preoperative explanation of the possible consequences of CRBD. The control group received normal saline 2 ml, whereas the diphenhydramine group received diphenhydramine 30 mg intravenously after induction of general anesthesia. Then, all patients were catheterized with a 14F Foley catheter and the balloon was inflated with 10 ml of distilled water. All patients who complained of CRBD in the postoperative room were appeased with nursing. Ketorolac 30 mg was used as the rescue drug on patients' request or when the patient was evaluated as having moderate or severe CRBD. Bladder discomfort and its severity were assessed at 1, 2 and 6 h postoperatively. The severity of CRBD was graded as none, mild, moderate and severe. Adverse effects of diphenhydramine such as sedation, dry mouth or GI upset were recorded., Results: The incidence of CRBD was lower in the diphenhydramine group compared with the control group at 2 h (34.8 vs. 58.7%, p = 0.02) and 6 h (23.9 vs. 56.5%, p < 0.01) postoperatively. Diphenhydramine treatment also reduced the severity of CRBD at 6 h postoperatively (p = 0.01). Moreover, the request for rescue for CRBD was lower in diphenhydramine group at 2 h (8.7 vs. 26.1%, p = 0.03). There were no significant differences in side effects, such as sedation, dry mouth or gastrointestinal upset between the two groups (p > 0.05)., Conclusion: Prophylactic diphenhydramine 30 mg at induction of general anesthesia reduced the incidence and severity of postoperative bladder discomfort without significant side effects in patients receiving gynecologic laparoscopic surgery.

Objective: Out of hospital medication-related adverse events (AEs) from cough and cold medications (CCMs) can have significant public health impact. The objective of this study was to characterize pediatric medication error AEs involving over-the-counter (OTC) CCMs to identify preventable factors., Methods: Multisource national data surveillance system study using an expert panel evaluating CCM AEs related to medication errors., Inclusion Criteria: age <12 years, and at least 1 significant AE from at least 1 index ingredient from a CCM OTC product., Results: From 2009 through 2016, 4756 cases were determined to have a significant AE related to an OTC CCM ingredient and 513 (10.8%) cases were due to a medication error. Nearly half of medication errors involved children 2 to <6 years old (n = 235; 45.8%). Many involved administration by a parent (n = 231; 45.0%) or alternative caregiver (n = 148; 28.8%). In nearly all cases (93.2%), the medication error involved the wrong dose of the medication. Health care facility evaluation occurred in 381 (74.3%) cases. Diphenhydramine and dextromethorphan were responsible for most medication errors and medication errors involving health care facility evaluation. There were no deaths from medication errors., Conclusion: In this multiyear surveillance study, medication errors most commonly occurred in children <6 years old who received the wrong volume of a liquid product. Diphenhydramine and dextromethorphan dosing errors were the most common cause of medication errors resulting from CCM use. Continued standardization of measuring devices, concentrations, and units of measure along with consumer education are needed to further decrease medication errors from CCMs., (Published by Elsevier Inc.)

A 62-year-old patient living in a rural community was referred to participate in a pharmacist-led home visit program because of concerns with the patient's increasing falls and medication complexity. The patient reported experiencing an increasing number of falls over the past few months, resulting in a recent hospitalization and mild head trauma. The patient's past medical history included diabetes mellitus type 2, hypertension, hyperlipidemia, gastroesophageal reflux disease, paroxysmal atrial fibrillation, unspecified back pain, and benign prostatic hyperplasia. During the comprehensive medication review, pharmacists determined the patient had inadvertently purchased an acetaminophen/ diphenhydramine combination medication, rather than his usual acetaminophen. According to the 2019 Beers criteria, use of acetaminophen/diphenhydramine for back pain without insomnia is not the best option and may contribute to falls. With an estimated four to eight tablets per day, the patient was taking 200-400 mg of diphenhydramine daily. Pharmacist recommendations included contacting the prescribing physician to obtain a prescription for acetaminophen. By asking the local pharmacy to dispense acetaminophen as a prescription, the risk of the patient inadvertently purchasing an inappropriate product is reduced. After removing the diphenhydramine from the patient's regimen, the falls ceased. This case demonstrates the effects of inappropriate diphenhydramine use in an especially vulnerable population. It also highlights the critical role that rural community pharmacists can play in improving their patients' health care.

Introduction: Diphenhydramine (DPH) exposures in children may be the result of accidental unsupervised ingestions, caregiver error, and intentional misuse of DPH-containing cough and cold medications (CCM). We sought to understand the nature of pediatric ingestions of DPH, particularly the toxicity and outcome of a single product, single ingredient DPH (DPH-only) exposures, in order to derive ingredient-specific information about the clinical effects and course of such cases. Methods: As part of a U.S. multi-year safety surveillance program to assess the safety of over-the-counter (OTC) medications used in cough and cold preparations in children <12 years of age, an expert panel reviewed cases involving symptomatic adverse events potentially related to oral exposures to these medications. After individual review, the cases were categorized by causal relationship of the reported ingredients to the adverse event, exposure intent (therapeutic, non-therapeutic, unknown intent), and dose (therapeutic, supratherapeutic, or unknown). Following panel review, any disagreement on classification was discussed until a consensus was reached. The data were then analyzed with respect to descriptive findings. Results: The panel reviewed 6618 eligible cases and determined 2802 were at least potentially related to oral exposure to DPH. Of these, 2028 were DPH-only cases (39.1% of all cases judged at least potentially related to a cough and cold medication). The majority (79.5%) of DPH-only cases occurred in children 2 to <4 years of age and involved accidental unsupervised ingestions (74.7%). Liquid pediatric formulations were the most common (51.7%) products reported followed by solid pediatric formulations (24.0%). The most common adverse events were tachycardia (53.4%), hallucinations (46.5%), somnolence (34.7%), agitation (33.9%), and mydriasis (26.3%). Seizures occurred in only 5.5% of cases. Five (0.2%) deaths were reported; in the death cases, the DPH dose was judged supratherapeutic in one and unknown in the other four. Child abuse was reported in four of the five death cases and three of the five deaths were homicides. Conclusions: Exposures to DPH-only products were the most common type of exposure detected in our study of adverse events associated with CCM in children. The majority of the DPH-only cases were the result of accidental unsupervised ingestions. Most adverse events were relatively mild self-limited anticholinergic effects and few deaths occurred. Deaths involving DPH were often associated with child abuse or homicide. Interventions targeting the prevention of accidental unsupervised are likely to be impactful in preventing morbidity associated with DPH-only exposure.

In this paper, we reflect on health intervention translations as matters of their implementation practices. Our case is methadone treatment, an intervention promoted globally for treating opioid dependence and preventing HIV among people who inject drugs. Tracing methadone's translations in high-security prisons in the Kyrgyz Republic, we notice the multiple methadones made possible, what these afford, and the onto-political effects they make. We work with the idea of the 'becoming-methadone-body' to trace the making-up of methadone treatment and its effects as an intra-action of human and nonhuman substances and bodies. Methadone's embodied effects flow beyond the mere psycho-activity of substances incorporating individual bodies, to material highs and lows incorporating the governing practices of prisoner society. The methadone-in-practice of prisoner society is altogether different to that imagined as being in translation as an intervention of HIV prevention and opioid treatment, and has material agency as a practice of societal governance. Heroin also emerges as an actor in these relations. Our analysis troubles practices of 'evidence-based' intervention and 'implementation science' in the health field, by arguing for a move towards 'evidence-making' intervention approaches. Noticing the onto-politics of health intervention translations invites speculation on how intervening might be done differently., (© 2019 Foundation for the Sociology of Health & Illness.)

BACKGROUND Diphenhydramine is a commonly available over-the-counter antihistamine; however, there are few documented cases of treatment when ingested in toxic quantities, where it can cause a sodium channel blockade leading to wide-complex tachycardia, seizures, and death. Conventional treatment includes sodium bicarbonate infusion, but few cases have documented the addition of lipid emulsion therapy. CASE REPORT A 24-year-old African American female ingested 18 g (360 pills of 50 mg) over-the-counter diphenhydramine. She presented comatose, with hemodynamic instability and hypotension, intubated with pupil dilation to 6 to 7 mm, and initial electrocardiography findings showing a type 1 AV block with a QT/QTc of 360/402 ms which progressed into sinus tachycardia with widened QRS intervals of 134 ms and prolonged QT/QTc intervals of up to 638/759 ms. Treatment using sodium bicarbonate and magnesium was initiated; however, the intraventricular conduction delay persisted. Infusion of 20% intravenous lipid emulsion was administered; following this, the patient developed narrow complex QRS with sinus rhythm and shortened the QT/QTc interval to 448/516 ms. She recovered quickly and was transferred to inpatient psychiatric unit for further evaluation, and discharged 1 month later. CONCLUSIONS Lipid emulsion therapy has been utilized in treatment of various medication overdoses, but there are few documented cases in the treatment of diphenhydramine overdose. With the amount of diphenhydramine ingested by the patient in this case report, the use of combined conventional and lipid emulsion therapy was utilized in the stabilization and management of the patient, and should be considered in scenarios where conventional treatments have not improved the clinical outcome.

Importance: Oral mucositis causes substantial morbidity during head and neck radiotherapy. In a randomized study, doxepin mouthwash was shown to reduce oral mucositis-related pain. A common mouthwash comprising diphenhydramine-lidocaine-antacid is also widely used., Objective: To evaluate the effect of doxepin mouthwash or diphenhydramine-lidocaine-antacid mouthwash for the treatment of oral mucositis-related pain., Design, Setting, and Participants: A phase 3 randomized trial was conducted from November 1, 2014, to May 16, 2016, at 30 US institutions and included 275 patients who underwent definitive head and neck radiotherapy, had an oral mucositis pain score of 4 points or greater (scale, 0-10), and were followed up for a maximum of 28 days., Interventions: Ninety-two patients were randomized to doxepin mouthwash (25 mg/5 mL water); 91 patients to diphenhydramine-lidocaine-antacid; and 92 patients to placebo., Main Outcome and Measures: The primary end point was total oral mucositis pain reduction (defined by the area under the curve and adjusted for baseline pain score) during the 4 hours after a single dose of doxepin mouthwash or diphenhydramine-lidocaine-antacid mouthwash compared with a single dose of placebo. The minimal clinically important difference was a 3.5-point change. The secondary end points included drowsiness, unpleasant taste, and stinging or burning. All scales ranged from 0 (best) to 10 (worst)., Results: Among the 275 patients randomized (median age, 61 years; 58 [21%] women), 227 (83%) completed treatment per protocol. Mucositis pain during the first 4 hours decreased by 11.6 points in the doxepin mouthwash group, by 11.7 points in the diphenhydramine-lidocaine-antacid mouthwash group, and by 8.7 points in the placebo group. The between-group difference was 2.9 points (95% CI, 0.2-6.0; P = .02) for doxepin mouthwash vs placebo and 3.0 points (95% CI, 0.1-5.9; P = .004) for diphenhydramine-lidocaine-antacid mouthwash vs placebo. More drowsiness was reported with doxepin mouthwash vs placebo (by 1.5 points [95% CI, 0-4.0]; P = .03), unpleasant taste (by 1.5 points [95% CI, 0-3.0]; P = .002), and stinging or burning (by 4.0 points [95% CI, 2.5-5.0]; P < .001). Maximum grade 3 adverse events for the doxepin mouthwash occurred in 3 patients (4%); diphenhydramine-lidocaine-antacid mouthwash, 3 (4%); and placebo, 2 (2%). Fatigue was reported by 5 patients (6%) in the doxepin mouthwash group and no patients in the diphenhydramine-lidocaine-antacid mouthwash group., Conclusions and Relevance: Among patients undergoing head and neck radiotherapy, the use of doxepin mouthwash or diphenhydramine-lidocaine-antacid mouthwash vs placebo significantly reduced oral mucositis pain during the first 4 hours after administration; however, the effect size was less than the minimal clinically important difference. Further research is needed to assess longer-term efficacy and safety for both mouthwashes., Trial Registration: ClinicalTrials.gov Identifier: NCT02229539.

Background and Aims: Chronic opioid use increases tolerance to sedatives. Diphenhydramine is recommended for difficult-to-sedate patients during endoscopic procedures. We hypothesized that the addition of diphenhydramine to midazolam and fentanyl would improve objective and subjective measures of procedural sedation., Methods: This randomized, double-blind, placebo-controlled trial included patients on chronic opioids undergoing colonoscopy. Patients were randomized to receive 50 mg of diphenhydramine intravenously (n = 61) or placebo (n = 58), in addition to fentanyl and midazolam. Baseline characteristics, amount of fentanyl and midazolam, procedure times, and adverse events were recorded. Quality of sedation was assessed by the physician and nurse. Patients rated pain and amnesia on a 10-point scale., Results: There was no difference in amounts of fentanyl (125.4 ± 56.2 μg vs 126.9 ± 53.5 μg, P = .88) and midazolam (4.9 ± 2.1 mg vs 5 ± 1.9 mg, P = .79) used. The mean sedation scores from the physician (6.2 ± 1.1 vs 5.3 ± 1.2, P =.0002) and nurses (5.6 ± 1.5 vs 5.1 ± 1.4, P =.04) were statistically significant in favor of the diphenhydramine arm. Patient scores for pain (2.05 ± 2.17 vs 3.09 ± 3.95, P =.047) and amnesia (7.8 ± 3.4 vs 6.5 ± 3.8, P =.047) favored the group that received diphenhydramine. Qualitative assessment showed no significant difference between the groups. There was no difference in induction time (P = .86), procedure duration (P = .98), or recovery time (P = .16). Hypotensive episodes were more common in the placebo group (P = .027)., Conclusions: In patients on chronic opioid therapy, administration of diphenhydramine does not allow for lower doses of procedural sedatives but improves quality of sedation without increasing the number of adverse events. (Clinical trial registration number: NCT T01967433.)., (Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine the effectiveness of prophylactic anticholinergic medications in reducing extrapyramidal symptoms in patients taking acute antiemetics with a dopamine D2 receptor antagonist effect., Methods: Systematic searches of all published studies through March 2017 were identified from PubMed, Cochrane library, Embase, Web of Science and Scopus. Only randomised controlled trials of patients receiving dopamine D2 antagonist antiemetic therapy for acute migraine in which an anticholinergic or placebo was compared were included. Pooled ORs were calculated for incidence of extrapyramidal symptoms and sedation., Results: Four placebo-controlled randomised controlled trials consisting of 737 patients met the inclusion criteria for our meta-analysis. The effect of diphenhydramine differed depending on the method of administration of the antiemetic. When the antiemetic was delivered as a 2 min antiemetic bolus, the odds of extrapyramidal symptoms were significantly reduced in the diphenhydramine group compared with placebo (OR 0.42; 95% CI 0.22 to 0.81; P=0.01). However, when the antiemetic was given as a 15 min infusion, there was no significant difference in extrapyramidal symptoms with or without diphenhydramine (OR 1.06; 95% CI 0.58 to 1.91; P=0.85). The lowest incidence of extrapyramidal symptoms was observed in patients receiving a 15 min antiemetic infusion without diphenhydramine prophylaxis (9.8%). In two trials including 351 patients that dichotomously reported sedation scales, diphenhydramine had significantly higher rates of sedation (31.6%vs19.2%, OR 2.01, 95% CI 1.21 to 3.33; P=0.007)., Conclusion: Prophylactic diphenhydramine reduces extrapyramidal symptoms in patients receiving bolus antiemetic therapy with a dopamine D2 antagonist effect, but not when it is given as an infusion. Because of significantly greater sedation with diphenhydramine, the most effective strategy is to administer the D2 antagonist antiemetic as a 15 min infusion without prophylaxis., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Cough causes concern for parents and is a major cause of outpatient visits. Cough can impact quality of life, cause anxiety, and affect sleep in children and their parents. Honey has been used to alleviate cough symptoms. This is an update of reviews previously published in 2014, 2012, and 2010., Objectives: To evaluate the effectiveness of honey for acute cough in children in ambulatory settings., Search Methods: We searched CENTRAL (2018, Issue 2), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (2014 to 8 February 2018), Embase (2014 to 8 February 2018), CINAHL (2014 to 8 February 2018), EBSCO (2014 to 8 February 2018), Web of Science (2014 to 8 February 2018), and LILACS (2014 to 8 February 2018). We also searched ClinicalTrials.gov and the World Health Organization International Clinical Trial Registry Platform (WHO ICTRP) on 12 February 2018. The 2014 review included searches of AMED and CAB Abstracts, but these were not searched for this update due to lack of institutional access., Selection Criteria: Randomised controlled trials comparing honey alone, or in combination with antibiotics, versus no treatment, placebo, honey-based cough syrup, or other over-the-counter cough medications for children aged 12 months to 18 years for acute cough in ambulatory settings., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane., Main Results: We included six randomised controlled trials involving 899 children; we added three studies (331 children) in this update.We assessed two studies as at high risk of performance and detection bias; three studies as at unclear risk of attrition bias; and three studies as at unclear risk of other bias.Studies compared honey with dextromethorphan, diphenhydramine, salbutamol, bromelin (an enzyme from the Bromeliaceae (pineapple) family), no treatment, and placebo. Five studies used 7-point Likert scales to measure symptomatic relief of cough; one used an unclear 5-point scale. In all studies, low score indicated better cough symptom relief.Using a 7-point Likert scale, honey probably reduces cough frequency better than no treatment or placebo (no treatment: mean difference (MD) -1.05, 95% confidence interval (CI) -1.48 to -0.62; I² = 0%; 2 studies; 154 children; moderate-certainty evidence; placebo: MD -1.62, 95% CI -3.02 to -0.22; I² = 0%; 2 studies; 402 children; moderate-certainty evidence). Honey may have a similar effect as dextromethorphan in reducing cough frequency (MD -0.07, 95% CI -1.07 to 0.94; I² = 87%; 2 studies; 149 children; low-certainty evidence). Honey may be better than diphenhydramine in reducing cough frequency (MD -0.57, 95% CI -0.90 to -0.24; 1 study; 80 children; low-certainty evidence).Giving honey for up to three days is probably more effective in relieving cough symptoms compared with placebo or salbutamol. Beyond three days honey probably had no advantage over salbutamol or placebo in reducing cough severity, bothersome cough, and impact of cough on sleep for parents and children (moderate-certainty evidence). With a 5-point cough scale, there was probably little or no difference between the effects of honey and bromelin mixed with honey in reducing cough frequency and severity.Adverse events included nervousness, insomnia, and hyperactivity, experienced by seven children (9.3%) treated with honey and two children (2.7%) treated with dextromethorphan (risk ratio (RR) 2.94, 95% Cl 0.74 to 11.71; I² = 0%; 2 studies; 149 children; low-certainty evidence). Three children (7.5%) in the diphenhydramine group experienced somnolence (RR 0.14, 95% Cl 0.01 to 2.68; 1 study; 80 children; low-certainty evidence). When honey was compared with placebo, 34 children (12%) in the honey group and 13 (11%) in the placebo group complained of gastrointestinal symptoms (RR 1.91, 95% CI 1.12 to 3.24; I² = 0%; 2 studies; 402 children; moderate-certainty evidence). Four children who received salbutamol had rashes compared to one child in the honey group (RR 0.19, 95% CI 0.02 to 1.63; 1 study; 100 children; moderate-certainty evidence). No adverse events were reported in the no-treatment group., Authors' Conclusions: Honey probably relieves cough symptoms to a greater extent than no treatment, diphenhydramine, and placebo, but may make little or no difference compared to dextromethorphan. Honey probably reduces cough duration better than placebo and salbutamol. There was no strong evidence for or against using honey. Most of the children received treatment for one night, which is a limitation to the results of this review. There was no difference in occurrence of adverse events between the honey and control arms.

During the preclinical research period of drug development, animal testing is widely used to help screen out a drug's dangerous side effects. However, it remains difficult to predict side effects within the central nervous system. Here, we introduce a machine learning-based in vitro system designed to detect seizure-inducing side effects before clinical trial. We recorded local field potentials from the CA1 alveus in acute mouse neocortico-hippocampal slices that were bath-perfused with each of 14 different drugs, and at 5 different concentrations of each drug. For each of these experimental conditions, we collected seizure-like neuronal activity and merged their waveforms as one graphic image, which was further converted into a feature vector using Caffe, an open framework for deep learning. In the space of the first two principal components, the support vector machine completely separated the vectors (i.e., doses of individual drugs) that induced seizure-like events, and identified diphenhydramine, enoxacin, strychnine and theophylline as "seizure-inducing" drugs, which have indeed been reported to induce seizures in clinical situations. Thus, this artificial intelligence-based classification may provide a new platform to pre-clinically detect seizure-inducing side effects of drugs.

Background: Diphenhydramine (DPH) is most commonly used via oral, topical, intramuscular (IM) and intravenous (IV) routes for the palliation of pruritus, treatment of extrapyramidal symptoms, management of parkinsonism and for allergic reactions. However, many hospice patients are unable to take oral medications and/or do not have IV access. Moreover, topical administration has a relatively slow rate of absorption. For this reason, in the hospice setting it is not uncommon for diphenhydramine to be administered via the subcutaneous (SC) route secondary to its ease of access, low infection rates and its low levels of discomfort. In contrast, outside the hospice setting, subcutaneous DPH has not been widely used, primarily because of a handful of case reports published in the 1990's that report skin necrosis following subcutaneous administration of DPH for local anesthesia. Since these early case reports, however, there has been very little in the way of research to examine this further. The aim of this study is to provide objective data concerning the safe use of subcutaneous diphenhydramine, as part of our efforts to improve upon safe practices in our organization., Methods: This is a retrospective review of records from 6 of our inpatient hospice units obtained from our pharmacy database for patients who received at least one subcutaneous injection of diphenhydramine between 2012-2015. Selected patients were then subsequently screened for post-administration skin necrosis, as recorded in our quality assurance database during the same time period., Results: A total of 648 diphenhydramine subcutaneous injections were administered in109 individual patients. None of the patients were reported to have an adverse cutaneous reaction., Conclusions: This retrospective review demonstrates that subcutaneous diphenhydramine injection is a safe alternative to oral and other parenteral routes, and may be particularly valuable in terminally ill patients, who are often unable to swallow and are without IV access.

Objective: To determine outcomes among patients with migraine in the emergency department (ED) who receive IV hydromorphone vs IV prochlorperazine + diphenhydramine., Methods: This study was conducted in 2 EDs in New York City. Patients who met international criteria for migraine were eligible for participation if they had not used an opioid within the previous month. Clinicians, participants, investigators, and research personnel were blinded to treatment. Patients were randomized in blocks of 4. Participants received hydromorphone 1 mg or prochlorperazine 10 mg + diphenhydramine 25 mg. Diphenhydramine was administered to prevent akathisia, a common side effect of IV prochlorperazine. The primary outcome was sustained headache relief, defined as achieving a headache level of mild or none within 2 hours of medication administration and maintaining that level for 48 hours without the requirement of rescue medication. A planned interim analysis was conducted once 48-hour data were available for 120 patients., Results: The trial was halted by the data monitoring committee after 127 patients had been enrolled. The primary outcome was achieved in the prochlorperazine arm by 37 of 62 (60%) participants and in the hydromorphone arm by 20 of 64 (31%) participants (difference 28%, 95% confidence interval 12-45, number needed to treat 4, 95% confidence interval 2-9)., Conclusions: IV hydromorphone is substantially less effective than IV prochlorperazine for the treatment of acute migraine in the ED and should not be used as first-line therapy., Clinicaltrialsgov Identifier: NCT02389829., Classification of Evidence: This study provides Class I evidence that for patients in the ED with migraine, IV prochlorperazine + diphenhydramine is superior to IV hydromorphone., (© 2017 American Academy of Neurology.)

Objective: Sleep disorders are common in individuals with Williams syndrome (WS), and sleep disturbance has a significant negative effect on attention, learning, and behavior. The use of sleep-inducing medicine in individuals with WS has not been widely investigated. The objective of this study was to evaluate the use and effectiveness of sleep medications among a large sample of individuals with WS by parent survey., Methods: A survey of the use and effectiveness of sleep medications was completed by 513 (of 2846) members of the Williams Syndrome Association. The online survey asked for the age at initiation, degree of effectiveness (helpful, somewhat helpful, and not helpful), and side effects., Results: One hundred thirty participants (25%) indicated that their family member with WS had taken medication to help with sleep. Melatonin was the most commonly reported medication taken for sleep, with 91% of parents reporting that it was "helpful" or "somewhat helpful" for their child with WS. Those who reported taking melatonin reported very few, if any, side effects., Conclusion: This parent-completed survey is a preliminary study showing the positive benefit of melatonin for individuals with WS who have disrupted sleep. The findings support the need for further study of the use of melatonin, in addition to behavioral sleep aids, given evidence that sleep disturbance negatively influences cognition and behavior.

OBJECTIVE To evaluate the effects of IV diphenhydramine hydrochloride administration on cardiorespiratory variables in anesthetized dogs undergoing mast cell tumor (MCT) excision. DESIGN Randomized, blinded clinical trial. ANIMALS 16 client-owned dogs with MCTs. PROCEDURES In a standardized isoflurane anesthesia session that included mechanical ventilation, dogs received diphenhydramine hydrochloride (1 mg/kg [0.45 mg/lb], IV; n = 8) or an equivalent volume of saline (0.9% NaCl) solution (IV; control treatment; 8) 10 minutes after induction. Cardiorespiratory variables were recorded throughout anesthesia and MCT excision, and blood samples for determination of plasma diphenhydramine and histamine concentrations were collected prior to premedication (baseline), throughout anesthesia, and 2 hours after extubation. RESULTS Cardiorespiratory values in both treatment groups were acceptable for anesthetized dogs. Mean ± SD diastolic arterial blood pressure was significantly lower in the diphenhydramine versus control group during tumor dissection (52 ± 10 mm Hg vs 62 ± 9 mm Hg) and surgical closure (51 ± 10 mm Hg vs 65 ± 9 mm Hg). Mean arterial blood pressure was significantly lower in the diphenhydramine versus control group during surgical closure (65 ± 12 mm Hg vs 78 ± 11 mm Hg), despite a higher cardiac index value. Plasma histamine concentrations were nonsignificantly higher than baseline during maximal manipulation of the tumor and surgical preparation in the diphenhydramine group and during surgical dissection in the control group. CONCLUSIONS AND CLINICAL RELEVANCE IV administration of diphenhydramine prior to MCT excision had no clear clinical cardiorespiratory benefits over placebo in isoflurane-anesthetized dogs.

Purpose: H1-antihistamines are commonly used in infants and children for the relief of histamine-mediated symptoms in a variety of conditions. Little is known about their safety profile in these patients. We performed a comparative analysis of the safety profiles of H1-antihistamines using data from the WHO database (VigiBase)., Methods: We selected adverse drug reaction (ADR) reports on H1-antihistamines in children (0-16 years) up to June 2014 from VigiBase. ADRs were codified according to MedDRA terminology. The reporting odds ratios (RORs) with 95% confidence for drug-reaction pairs were calculated., Results: The analysis was performed on 8918 reports related to antihistamines, corresponding to 19503 drug reaction pairs for 68 different drugs. Most of reports involved children aged 2 to 6 years (32%) and 6 to 12 years (34%). Most reported drugs were cetirizine (1608 reports, corresponding to 18%), loratadine (16%), and diphenhydramine (10%). ADRs were classified as serious in 23% of cases, and 400 cases had a fatal outcome. We found a significant associations for several drug-reaction pairs such as levocetirizine and epilepsy (ROR, 6.57; 95% confidence interval [CI], 1.51-28.53) and chlorphenamine and toxic epidermal necrolysis (ROR, 7.29; 95% CI, 2.39-22.2)., Conclusions: H1-antihistamines are among the most used drugs in pediatrics, also in an off-label manner. Our data highlights associations with serious and unexpected ADRs. Educative intervention to clinicians and parents are needed to help doctors to make proper choices on the drug treatment and for the early detection of ADRs to maximize the benefits and reduce the risk of ADRs in these patients., (Copyright © 2017 John Wiley & Sons, Ltd.)

Background The unintentional misuse of over-the-counter sleep aids among older adults is an important public health problem and a focus of Healthy People 2020. Accordingly, the 2015 Beers Criteria for Potentially Inappropriate Medication Use in Older Adults recommends that individuals 65 years or older avoid use of diphenhydramine and doxylamine; however, many over-the-counter sleep products contain these active ingredients. Objective To identify the proportion of older adults using an over-the-counter medication containing diphenhydramine or doxylamine, and compare their characteristics with older adults using an over-the-counter medication that does not contain these ingredients. Setting Study participants were recruited from the Community Registry of the Pittsburgh Claude D. Pepper Older Americans Independence Center. Method The study sample was taken from a larger survey of 1025 participants on sleep health and over-the-counter sleep medication use conducted from February to April 2015. A subset of 169 participants aged 65 and older reporting taking at least one over-the-counter product to improve sleep within the past 30 days (16.5%) were selected for our analysis on associations between participant characteristics and potentially inappropriate use of over-the-counter sleep medications. Main outcome measure The proportion and characteristics of older adults taking at least one over-the-counter medication containing diphenhydramine or doxylamine. Results Of the 223 over-the-counter sleep medications listed by participants, 115 (52%) contained diphenhydramine or doxylamine. Using the Beers Criteria, we found that more than half of participants (59%) had used a potentially inappropriate over-the-counter medication containing diphenhydramine or doxylamine to improve sleep within the past 30 days. Participants taking at least one diphenhydramine or doxylamine containing medication were less likely to be aware of any safety risks in taking over-the-counter sleep medications than participants not taking these products (38 vs 49%, p = 0.016). Conclusion A majority of older adults in a limited sample from the United States taking an over-the-counter medication to improve sleep are taking a product containing diphenhydramine or doxylamine, both of which are classified as potentially inappropriate for older adults. Awareness of the safety risks of over-the-counter medications and addressing conditions that impact sleep quality could be facilitated through consultation with pharmacists and other healthcare providers.

Background: Fetal tachycardia is attributable to a variety of etiologies, including an untreated maternal medical condition or an indicator of potential fetal compromise. Maternal medication administration may also affect the fetal heart rate., Case: A 28-year-old nulliparous patient at 41 weeks of gestation was treated for pruritus with intravenous diphenhydramine after epidural administration of fentanyl. Within 14 minutes, the fetal heart rate increased from a baseline of 155 beats per minute (bpm) to more than 200 bpm while maintaining moderate variability. This was accompanied by an increase in uterine contractions occurring every 1.5 minutes. The fetal tachycardia lasted 51 minutes; several hours later, a healthy neonate was delivered., Conclusion: Diphenhydramine may produce transient fetal tachycardia as well as increased maternal uterine activity.

Various biological factors have been implicated in convulsive seizures, involving side effects of drugs. For the preclinical safety assessment of drug development, it is difficult to predict seizure-inducing side effects. Here, we introduced a machine learning-based in vitro system designed to detect seizure-inducing side effects. We recorded local field potentials from the CA1 alveus in acute mouse neocortico-hippocampal slices, while 14 drugs were bath-perfused at 5 different concentrations each. For each experimental condition, we collected seizure-like neuronal activity and merged their waveforms as one graphic image, which was further converted into a feature vector using Caffe, an open framework for deep learning. In the space of the first two principal components, the support vector machine completely separated the vectors (i.e., doses of individual drugs) that induced seizure-like events and identified diphenhydramine, enoxacin, strychnine and theophylline as "seizure-inducing" drugs, which indeed were reported to induce seizures in clinical situations. Thus, this artificial intelligence-based classification may provide a new platform to detect the seizure-inducing side effects of preclinical drugs., (Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Objective: Antihistamines are often used for treating allergic rhinitis. However, many older antihistamines cause sedative side effects. The sedative effects of antihistamines on car-driving have been investigated. This has not been investigated for levocetirizine, a new-generation antihistamine, in Asian populations, and so we evaluated its sedative effects in healthy Japanese subjects., Methods: In this double-blind, placebo-controlled, four-way crossover study, healthy volunteers received single doses of levocetirizine 5 mg, fexofenadine 60 mg, diphenhydramine 50 mg, and placebo at intervals of at least 6 days. Simple brake reaction time and choice brake reaction time task (CBRT), a lateral tracking (LT) task, and a multiple task, a mixture of CBRT and LT task, were used to compare driving performance between the four drugs. Subjective sedation was also assessed., Results: The simple brake reaction time and CBRT, and the CBRT component of the multiple task, did not show any significant differences between the drugs. In contrast, the LT, both as a single parameter and as a component of the multiple task, showed significant differences between diphenhydramine and the newer-generation antihistamines in a manner that corresponds with subjective sedation., Conclusions: Levocetirizine and fexofenadine did not impair psychomotor performance in subjects performing simulated car-driving tasks, while diphenhydramine did impair psychomotor performance in the subjects. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

To evaluate the safety and efficacy of Linkus, Aminophylline with Diphenhydramine group and Acefyllin Piperazine with Diphenhydramine cough syrup on children having cough and sleep difficulty associated with cough. To determine the effects of Linkus polyherbal syrup (group A) and compared with other parallel allopathic groups (Group B and C) for cough on children and associated sleep quality and improvement. 360 children having cough inducted in 3 different groups randomly selected. Three parallel groups were the part of the study. The first study group was the herbal syrup Linkus, second group of children were taking a syrup of multinational pharmaceutical industry having Aminophylline plus Diphenhydramine however the third group received another famous brand having Acefyllin Piperazine with Diphenhydramine. Informed assent and informed consent have taken from the study subjects and their parents. Subjects with acute cough were included in the study however the subjects with chronic cough considered to be excluded. Every group of individual in the study was informed about the investigational drugs provided. Ethnic groups, frequency of cough and diseases illness (<0.05) were determine on every group on the investigational syrup. Cough impact on child and its sleep of three different syrups (every group) were assessed on day1 and day 14(p<0.001) via a likert scale. For the evaluation of pain assessment Wong baker face scale were used and level of significance in each group (p<0.001). Significant results were observed in the Linkus Group as compared to the other parallel groups including Aminophylline plus Diphenhydramine and Acefyllin Piperazine with Diphenhydramine on day 14 (p<0.001). Side effects on group B and group C (Aminophylline with Diphenhydramine and Acefyllin Piperazine with Diphenhydramine) were almost similar in number however Linkus syrup has minimum side effects on study duration. Polyherbal syrup Linkus shows better results in treatment of cough including side effects as compare to the other parallel groups B and C (Aminophylline with Diphenhydramine and Acefyllin Piperazine with Diphenhydramine). For nocturnal sleep Linkus providing better results in cough and associated problems. Pain were significantly reduce on day 14 with the herbal Linkus syrup group A (<0.001). Group B and C found less effective with more side effects as compared to Linkus syrup. Poly herbal Linkus syrup could substantially improve the clinical effect and relieves coughs and benefit lung functions and better sleep facilitation.

Objective: Next-day residual effects of a nighttime dose of gabapentin 250 mg were evaluated on simulated driving performance in healthy participants in a randomized, placebo-controlled, double-blind, multicenter, four-period crossover study that included diphenhydramine citrate 76 mg and triazolam 0.5 mg., Methods: At treatment visits, participants (n = 59) were dosed at ~23:30, went to bed immediately, and awakened 6.5 h postdose for evaluation. The primary endpoint was the standard deviation of lateral position for the 100-km driving scenario. Additional measures of driving, sleepiness, and cognition were included., Results: Study sensitivity was established with triazolam, which demonstrated significant next-day impairment on all driving endpoints, relative to placebo (p < 0.001). Gabapentin demonstrated noninferiority to placebo on standard deviation of lateral position and speed deviation but not for lane excursions. Diphenhydramine citrate demonstrated significant impairment relative to gabapentin and placebo on speed deviation (p < 0.05). Other comparisons were either nonsignificant or statistically ineligible per planned, sequential comparisons. Secondary endpoints for sleepiness and cognitive performance were supportive of these conclusions., Conclusions: Together, these data suggest that low-dose gabapentin had no appreciable next-day effects on simulated driving performance or cognitive functioning. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background and Aims: Acetaminophen (APAP) is the most common cause of acute liver failure (ALF) in the west. It is unknown if APAP overdose in combination with diphenhydramine or opioids confers a different clinical presentation or prognosis. Study objectives were to compare (1) baseline patient characteristics; (2) initial clinical presentation; and (3) clinical outcomes among patients with ALF due to APAP alone or in combination with diphenhydramine or opioids., Methods: We analyzed 666 cases of APAP-related liver failure using the Acute Liver Failure Study Group database from 1998 to 2012. The database contains detailed demographic, laboratory, and clinical outcome data, including hemodialysis, transplantation, and death and in-hospital complications such as arrhythmia and infection., Results: The final sample included 666 patients with APAP liver injury. A total 30.3% of patients were overdosed with APAP alone, 14.1% with APAP/diphenhydramine, and 56.6% with APAP/opioids. Patients taking APAP with opioids were older, had more comorbidities, and were more likely to have unintentional overdose (all P<0.0001). On presentation, 58% in the APAP/opioid group had advanced encephalopathy as compared with 43% with APAP alone (P=0.001) The APAP/diphenhydramine group presented with the highest serum aminotransferase levels, no differences in laboratory values were noted at 3 days postenrollment. No significant differences were observed in clinical outcomes among the groups., Conclusions: Most patients with APAP-induced ALF were taking APAP combination products. There were significant differences in patient characteristics and clinical presentation based on the type of product ingested, however, there were no differences noted in delayed hepatotoxicity or clinical outcomes.

Treatment of allergic diseases of eyelids and conjunctiva (conjunctivites and blepharoconjunctivites) often presents difficulties due to peculiarities of their pathogenesis - allergic and vascular reactions, disorder of lacrimal production, meibomian gland dysfunction, and possible bacterial contamination. It has been suggested to use Ocumethyl, which contains zinc sulfate (binding, drying, anti-inflammatory, and antiseptic effect), diphenhydamine hydrochloride (an Н1-antihistamine that decreases capillary permeability and helps resolve conjunctival and eyelid edema), naphazoline hydrochloride (a sympathomimetic notable for its strong, rapid, and long-lasting vasoconstrictive effect), and methylene blue (antiseptic effect, disintoxication, and antioxidant activity). A total of 80 patients with chronic allergic conjunctivitis, blepharoconjuntivitis, or giant papillary conjunctivitis associated with contact lens wearing were treated with Ocumethyl instillations (3 times daily for 15-30 days). A clinically significant effect was obtained in 77-91% of patients depending on the disease entity.

AGEP is a rare skin reaction that causes the formation of numerous aseptic pustules on an erythematous base. In most cases, it presents after exposure to drugs, more often antibiotics. Fever and leukocytosis are common. The history, clinical appearance, and histology of the pustules confirm the diagnosis of AGEP. Pustular psoriasis, SJM, and EM must be ruled out. The lesions heal spontaneously within 2 weeks after discontinuation of the offending agent, an occurrence that further supports the diagnosis. Immediate withdrawal of the causative agent and supportive therapy is the mainstay of treatment for AGEP.

Background and Objectives: Migraine headache is a common pediatric complaint among emergency department (ED) patients. There are limited trials on abortive therapies in the ED. The objective of this study was to apply a comparative effectiveness approach to investigate acute medication regimens for the prevention of ED revisits., Methods: Retrospective study using administrative data (Pediatric Health Information System) from 35 pediatric EDs (2009-2012). Children aged 7 to 18 years with a principal diagnosis of migraine headache were studied. The primary outcome was a revisit to the ED within 3 days for discharged patients. The primary analysis compared the treatment regimens and individual medications on the risk for revisit., Results: The study identified 32,124 children with migraine; 27,317 (85%) were discharged, and 5.5% had a return ED visit within 3 days. At the index visit, the most common medications included nonopioid analgesics (66%), dopamine antagonists (50%), diphenhydramine (33%), and ondansetron (21%). Triptans and opiate medications were administered infrequently (3% each). Children receiving metoclopramide had a 31% increased odds for an ED revisit within 3 days compared with prochlorperazine. Diphenhydramine with dopamine antagonists was associated with 27% increased odds of an ED revisit compared with dopamine antagonists alone. Children receiving ondansetron had similar revisit rates to those receiving dopamine antagonists., Conclusions: The majority of children with migraines are successfully discharged from the ED and only 1 in 18 required a revisit within 3 days. Prochlorperazine appears to be superior to metoclopramide in preventing a revisit, and diphenhydramine use is associated with increased rates of return., (Copyright © 2015 by the American Academy of Pediatrics.)