Comparing the Risk of Infusion-Related Reactions and Tolerability in Patients Given Cetirizine or Diphenhydramine Prior to Ocrelizumab Infusion (PRECEPT).

Background: Ocrelizumab is an effective medication for multiple sclerosis. However, infusion-related reactions (IRRs) are a concern for patients and may lead to discontinuation of ocrelizumab. To minimize IRRs, pre-medications are administered. However, from our experience, these medications, especially diphenhydramine, can cause marked drowsiness. The primary objective of this study was to evaluate whether cetirizine is non-inferior to diphenhydramine in limiting the proportion and severity of reactions from ocrelizumab infusions. Methods: Twenty participants were serially randomized in a 1:1 ratio to receive 10 mg of cetirizine or 25 mg of diphenhydramine orally prior to their first three ocrelizumab infusions. Results: The rate of IRRs in this study was similar across both treatment groups with no increase in the risk of severity, and no grade 3 IRRs. Further, patients receiving cetirizine experienced a reduction in fatigue. While there was not a significant difference in global satisfaction, this score increased over time in the cetirizine arm while it remained unchanged in the diphenhydramine arm. Conclusions: Overall, our results suggest that cetirizine does not increase the risk of infusion-related reactions compared to diphenhydramine.

Transfer of cetirizine/levocetirizine into human breast milk and estimation of drug exposure to infants through breastfeeding: A human lactation study from the ConcePTION project.

Data on drug transfer into human breast milk are sparse. This study aimed to quantify concentrations of cetirizine and levocetirizine in breast milk and to estimate drug exposure to infants. Breastfeeding women at least 8 weeks postpartum and using cetirizine or its pure (R)-enantiomer levocetirizine were eligible to participate. Breast milk samples were collected at six predefined times during a dose interval (0, 2, 4, 8, 12 and 24 h after drug intake) at steady state. Infant drug exposure was estimated by calculating the absolute infant dose (AID) and the weight-adjusted relative infant dose (RID). In total, 32 women were eligible for final inclusion, 31 women using cetirizine and one woman using levocetirizine. Means of the individual maximum and average cetirizine milk concentrations were 41.0 and 16.8 µg/L, respectively. Maximum concentrations occurred on average 2.4 h after intake, and the mean half-life in milk was 7.0 h. Estimated AID and RID for cetirizine in a day were 2.5 µg/kg and 1.9%, respectively. The corresponding values for levocetirizine were 1.1 µg/kg and 1.9%. No severe adverse events were reported. Our findings demonstrate that the transfer of cetirizine and levocetirizine into breast milk is low and compatible with breastfeeding.

Comparative study on the efficacy and safety of bepotastine besilate versus levocetirizine in chronic spontaneous urticaria: A randomised, open-label, parallel study.

Background Urticaria is a common skin disease which often causes impairment in the quality of life. The ideal drug for chronic urticaria would have antihistaminic and anti-inflammatory actions. Bepotastine besilate is a recently approved novel anti-allergic agent with multiple mechanisms of action; levocetirizine is a potent and selective second-generation H1 receptor antagonist used in the treatment of urticaria. Aim To compare the efficacy and safety of bepotastine besilate versus levocetirizine in patients with chronic spontaneous urticaria. Methods The study design is a randomised, open-label, parallel-group, prospective interventional study. The study subjects were randomly assigned to either of the two groups a and b, each group had 50 patients with chronic urticaria. Statistical analyses were performed using (SPSS, version 18) for all the variables. Chi-square test was used for comparison between categorical variables. An unpaired student's t-test was done for quantitative variables. Results There was a significant decrease in mean urticaria activity score (P < 0.001), chronic urticaria quality of life (P < 0.001) and clinical global improvement (P < 0.001) in both the treatment groups but this improvement was higher in the bepotastine than in the levocetirizine group. There was no significant difference in the mean of absolute eosinophil count, C-reactive protein, aspartate transaminase, alanine transaminase from baseline to 4th week between the two study groups. Visual analogue scale showed statistically significant improvement from baseline to 4th week (P < 0.001) of follow-up but this increase was higher in levocetirizine group (0.64-4.24) than in bepotastine group (0.56-2.56) Limitations Blinding was not done. To assess the efficacy and safety of bepotastine, a larger study can be planned. Conclusion This study found that bepotastine is superior to levocetirizine and showed a statistically significant reduction in mean urticaria activity score 7, improved quality of life and clinical global improvement in patients with urticaria.

Topical cetirizine for treating androgenetic alopecia: A systematic review.

BACKGROUND: Cetirizine, a widely used agent for allergic disorders, has recently been topically used for treating androgenetic alopecia (AGA). We aimed to summarize the current evidence regarding the effectiveness and safety of topical cetirizine for treating AGA. METHODS: We searched Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. We included both randomized controlled trials (RCTs) and non-randomized clinical trials. FINDINGS: We initially identified 102 records, of which, we included two RCTs and one non-randomized clinical trial, which were of moderate-to-high risk of bias. All included trials used 1% topical cetirizine as the intervention with various regimens. Topical cetirizine was likely to be more effective than a placebo for treating AGA. In comparison with topical minoxidil, topical cetirizine appears to be less effective for improving total and vellus hair density, but it might have a longer-lasting effect. Further, cetirizine might be as effective as minoxidil in improving hair diameter. CONCLUSION: One percent topical cetirizine may serve as a choice for treating AGA, especially for patients with a negative response to topical minoxidil. In order to fully understand the role of topical cetirizine for AGA, additional well-designed RCTs are needed.

A randomized double-blind feasibility study comparing cetirizine and diphenhydramine in the prevention of paclitaxel-associated infusion-related reactions: the PREMED-F1 study.

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).

The Role of Cetirizine in the Changing Landscape of IV Antihistamines: A Narrative Review.

Since 1955, the only available H1 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 H1 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.

Antiallergic activities of shallot (Allium ascalonicum L.) and its therapeutic effects in allergic rhinitis.

BACKGROUND: Onion has antiallergic activity but lack of evidence for shallot. OBJECTIVE: To determine whether shallot owns similar antiallergic activity to onion and its therapeutic effects in allergic rhinitis when added to standard treatment. METHODS: In-vitro ß-hexosaminidase inhibitory activities of shallot was compared with onion on RBL-2H3 cells. In clinical study, a randomized, double-blind, placebo-controlled trial was performed. Sixteen AR patients were randomized equally into the controls who received cetirizine 10 mg once daily and placebo capsules for 4 weeks, and the treatment who received 3g of oral shallot per day (equivalent to 1 ½ bulbs) and cetirizine. Visual analog scores of overall symptoms (VAS), total nasal and ocular symptom scores (TNSS and TOSS), nasal airway resistance (NAR), and adverse events were assessed. RESULTS: Shallot extract at 200 µg/mL had an average ß-hexosaminidase inhibition rate of 97% while onion extract had 73%. HPLC chromatograms (λ = 290nm) of both plants showed nearly identical patterns of quercetin compounds, such as quercetin 3,4'-diglucoside, quercetin 4'-glucoside, and quercetin. After 4-week of treatment, 62.5% of patients in shallot group and 37.5% of patients in control group showed improvement of post-treatment VAS. TNSS were significantly reduced in both groups, however no difference between groups (P = 0.18). TOSS were significantly improved only in the shallot group (P = 0.01). Adverse events from shallot were not different from placebo. CONCLUSIONS: Shallot had antiallergic activity and similar quercetin compounds to onion. The shallot oral supplement and cetirizine was shown to improve the overall AR symptoms more than cetirizine alone.

Newer-generation antihistamines and the risk of adverse events in children: A systematic review.

BACKGROUND: H1-antihistamines (AHs) are widely used for the treatment of allergic diseases, being one of the most commonly prescribed classes of medications in pediatrics. Newer-generation AHs are associated with fewer adverse effects compared with first-generation AHs. However, their relative harms in the pediatric population still need scrutiny. METHODS: We performed a systematic review of randomized controlled trials (RCTs), which included comparisons of safety parameters between an orally administered newer-generation AH and another AH (first- or second-generation), montelukast, or placebo in children aged ≤12 years. We searched MEDLINE and CENTRAL, independently extracted data on study population, interventions, adverse events (AEs), and treatment discontinuations, and assessed the methodologic quality of the included RCTs using the Cochrane's risk of bias tool. RESULTS: Forty-five RCTs published between 1989 and 2017 met eligibility criteria. The majority of RCTs included school-aged children with allergic rhinitis and had a follow-up period of up to a month. Four RCTs reported serious AEs in patients receiving a newer-generation AH, but only two patients experienced a possibly drug-related serious AE. The occurrence of AEs, drug-related AEs, and treatment discontinuations due to AEs varied between RCTs. Most AEs reported were of mild intensity. Indirect evidence indicates that cetirizine is more sedating than the other newer-generation AHs. CONCLUSION: Our findings confirm that newer-generation AHs have a favorable safety and tolerability profile. However, we could not draw firm conclusions regarding the comparative safety profile of the newer-generation AHs due to the paucity of head-to-head RCTs, variation in definitions and reporting of AEs, and short follow-up duration.

Cetirizine-induced psychosis in a young adult with erythema multiforme.

We describe a case of a young man, taking no other routine medications, presenting with erythema multiforme and cetirizine-induced psychosis with re-challenge evidence. On retrospective elicitation of history, it was found that he had been involved in a motor vehicle collision 4 months prior and was a daily cannabis user; there were no objective abnormalities by MRI and neurological evaluations. Although rare, cetirizine-induced psychosis is an important adverse drug reaction that warrants the attention of healthcare practitioners.

Therapeutic implications of topical cetirizine 1% in treatment of male androgenetic alopecia: A case-controlled study.

BACKGROUND: Androgenetic alopecia (AGA) is the most common form of alopecia in men. Cetirizine, a second-generation H1 blocker, is known for its anti-inflammatory properties and its ability to decrease prostaglandin D2 (PGD2) production. AIM: To evaluate the efficacy and tolerability of topical cetirizine in male patients with AGA. METHODS: Two groups of 30 patients each (healthy males aged between 22 and 55 years) with different grades of AGA classified according to the Hamilton-Norwood classification were recruited for this study. Group A subjects applied 1 mL of 1% topical cetirizine daily, while group B subjects served as controls and were instructed to apply 1 mL of a placebo solution for 6 months. RESULTS: Dermoscopic assessment revealed significantly higher hair regrowth among the cetirizine-treated group (P < .001). The patients' satisfaction was significantly higher among the cetirizine-treated group (P < .001). CONCLUSION: The current study highlights a potential role cetirizine might have in treating AGA. It should be noted that studies are lacking in this regard and more randomized and controlled trials are warranted in order to confirm or refute such early findings.

A case report of sleep terrors exacerbated by cetirizine.

NONE: Sleep terrors are a type of sleep disorder that is classified as parasomnias and is more common in children than in adults. Cetirizine is a histamine H1 antagonist that is US Food and Drug Administration approved for the treatment of allergic rhinitis and urticaria and has common adverse effects of drowsiness and headaches. We present a case of an adult man with a history of chronic sleep terror disorder and allergic rhinitis who developed worsening of his sleep terrors after initiation of cetirizine that subsequently resolved after discontinuing cetirizine and starting paroxetine.

Levocetirizine Oral Disintegrating Tablet: A Randomized Open-Label Crossover Bioequivalence Study in Healthy Japanese Volunteers.

Levocetirizine is classified as a second-generation antihistamine. Levocetirizine is available for the treatment of allergic disorders such as allergic rhinitis and chronic idiopathic urticaria. This was a single-center, single-dose, open-label, randomized, 2-way crossover study in healthy Japanese male subjects consisting of 2 parts. Part 1 compared the bioavailability of levocetirizine oral disintegrating tablet (ODT) and levocetirizine immediate-release tablet (IRT) taken with water in the fasted state in 24 subjects; all subjects completed this part of the trial. In part 2, the bioavailability of levocetirizine ODT without water was compared with that of levocetirizine IRT with water in the fasted state in 48 subjects; 47 subjects completed this part of the trial. Bioequivalence was demonstrated between levocetirizine IRT 5 mg and ODT 5 mg. The safety profiles were generally similar between levocetirizine ODT and levocetirizine IRT, with no serious adverse events, deaths, or adverse events leading to withdrawal reported during the study.

The Effect Of Food On The Pharmacokinetic Properties And Bioequivalence Of Two Formulations Of Levocetirizine Dihydrochloride In Healthy Chinese Volunteers.

PURPOSE: The aim of this study is to assess the bioequivalence of a new generic formulation and the branded formulation of levocetirizine dihydrochloride in healthy Chinese volunteers under fasting and fed conditions, and food-intake effect on the pharmacokinetic properties is also evaluated. PATIENTS AND METHODS: Volunteers were randomly allocated into two groups to receive a single oral dose of generic formulation and branded formulation under fasting or fed conditions, respectively. Blood samples were collected at designated time points. Plasma concentrations of levocetirizine were determined by UFLC-MS/MS. Safety evaluations were carried out through the study. The main pharmacokinetic parameters of the two formulations of levocetirizine were calculated using non-compartmental analysis incorporated in WinNonlin® 7.0 software. RESULTS: Forty-nine volunteers were enrolled; 46 completed the studies. Under fasting and fed conditions, the 90% confidence intervals for the geometric mean of generic/branded ratios were in the range of 94.75-107.24% and 99.98-114.69% for the maximum observed concentration, and 97.13-102.50% and 98.36-103.98% for the area under the concentration-time curve. As a result of food intake before administration, the reduced rate and extent of absorption of levocetirizine were observed. Both formulations were generally well tolerated, with no serious adverse reactions reported. CONCLUSION: The two formulations demonstrated essentially identical pharmacokinetic profiles and were all well within the FDA/CFDA bioequivalence standards. Meanwhile, food intake can delay the absorption rate and reduced the bioavailability of levocetirizine in healthy Chinese volunteers.

Efficacy of Isotretinoin and Antihistamine versus Isotretinoin Alone in the Treatment of Moderate to Severe Acne: A Randomised Control Trial.

Background Acne vulgaris has considerable impact on physical and psychological health. Isotretinoin is considered most effective drug available for acne therapy but with limited acceptance because of its adverse effects. Antihistamine inhibits inflammatory mediators, Propionibacterium acne induced itching, reduction of squalene and sebum in sebocyte, reduces anxiety and further lessens hormonal derangement and inhibits mast cell induced fibrosis and scars. Clinical relevance is lacking in the use of antihistamine in the treatment of acne and its potential efficacy needs to be clarified. Objective To evaluate the efficacy and safety of combining isotretinoin and antihistamine compare to isotretinoin alone in patients with moderate to severe acne at week 12. Method One hundred patients with moderate to severe acne were included in this randomised, controlled comparative study. Fifty patients were treated with isotretinoin and 50 patients were treated with additional antihistamine, levocetirizine and assessment was done at baseline, 4, 8 and 12 weeks of treatment. Result At week 12, compared to isotretinoin only group, combination of isotretinoin and levocetirizine group showed more statistically significant decrease in score of global acne grading system (51.0 vs. 38.5%) and acne lesion counts (non-inflammatory lesion: 63.2 vs. 44.5%; inflammatory lesions: 75.9 vs. 62.7%; total lesions: 66.07 vs. 48.7%; all p< 0.05). Flaring up of acne occurred less frequently and adverse effects were more tolerable in levocetirizine group. Conclusion Use of antihistamine with isotretinoin provides synergic effect while minimizing the side effect of isotretinoin and greater clearance of the lesion and scars.

Efficacy of Desloratadine and Levocetirizine in Patients with Cedar Pollen-Induced Allergic Rhinitis: A Randomized, Double-Blind Study.

BACKGROUND: No comparative study of antihistamines that differ in structural system has been conducted in allergic rhinitis. OBJECTIVE: This was a randomized, double-blind, crossover comparative study to verify the efficacy of antihistamines that differ in structural system. METHODS: A total of 50 patients with moderate or more severe Japanese cedar pollen-induced allergic rhinitis were randomized to receive either placebo, desloratadine 5 mg (a tricyclic), or levocetirizine 5 mg (a piperazine). One dose of the study drug was orally administered at 9 pm on the day before a pollen exposure test, which was performed for 3 h (9 a.m. to 12 p.m.) to assess symptoms in an environmental challenge chamber (ECC). Nasal and ocular symptoms were compared at an airborne pollen level of 8,000 grains/m3. The primary endpoint was mean total nasal symptom score (TNSS) from 120 to 180 min in the ECC. Subjects with a difference of ≥1 in TNSS between 2 drugs were extracted to the relevant drug-responsive group. RESULTS: The difference in TNSS from placebo was -2.42 (p < 0.0001) with levocetirizine and -1.66 (p < 0.01) with desloratadine, showing that both drugs were significantly more effective than placebo in controlling symptoms, but with no statistically significant difference between the 2 drugs. There were 12 subjects in the desloratadine-responsive group and 24 subjects in the levocetirizine-responsive group, with no contributor to response was detected. CONCLUSION: Levocetirizine tended to control nasal symptoms more effectively than desloratadine. However, the response to each antihistamine varied among individuals and the predictors to the response are unknown. CLINICAL TRIAL REGISTRATION NUMBER: UMIN ID: UMIN000029653.