Question | |
Should any specific individual oral H1-antihistamines vs. other individual oral H1-antihistamines be used for the treatment of allergic rhinitis? | |
Population: | Patients with allergic rhinitis |
Intervention: | any specific individual oral H1-antihistamines |
Comparison: | other individual oral H1-antihistamines |
Main outcomes: | Nasal symptomsOcular symptomsQuality of lifeAdverse events (any)Serious adverse events |
Setting: | |
Perspective: | Clinical recommendation – Population perspective |
Background: | There are several second-generation OAH available with different chemical formulae, rendering it important not only to provide recommendations at a class level but also in relation to individual OAHs. |
Conflict of interests: | AWMF conflict of interest declaration and management policies were applied, the assessment performed by the AWMF with guidance and help from Juan Jose Yepes Nuñez. |
Assessment
ProblemIs the problem a priority? | ||
Judgement | Research evidence | Additional considerations |
Allergic rhinitis (AR) is a common condition affecting 18.1% of the population, and its symptoms can significantly reduce the quality of life and pose a high economic burden (mainly because of indirect costs related to lost school days and workdays). [Savoure] Studies of patients consulting general practitioners for AR reported that 18–48 % had symptoms that were not controlled by pharmacotherapy. [Bousquet, Bhattacharyya, Vandenplas] Despite the bothersome nature of symptoms, AR is often trivialized by the patient – only 45% seek medical advice or treatment for their condition, which results in under-treatment and poor control of symptoms. [Linneberg] Problems related to disease Economic burden A systematic review performed to estimate the financial burden of AR in European countries [Linneberg] suggests that the GP services bore the majority of the direct costs for AR. However, the majority of the overall cost burden correspond to indirect costs caused by high absenteeism and presenteeism. In the United States, annual costs for medications for rhinitis patients can be estimated at approximately $1.3 billion. In total, direct costs are estimated to be >$4.6 billion for rhinitis management, including treatment, allergy testing, clinical visits and hospital procedures. [Roland] Similar findings were found for Asia. An analysis of the indirect costs associated with insufficiently treated AR and urticaria patients revealed an annual burden of USD 105.4 billion. This translates to a cost ranging from USD 1,137 to USD 2,195 per patient due to absenteeism and presenteeism [Kulthanan] Clinical burden The median prevalence of allergic rhinitis was found to be 18.1%, based on a dataset that included 310 reported prevalences. The prevalence of AR ranged from as low as 1.0% to as high as 54.5%.
These statistics indicate that AR is a relatively common condition affecting a significant portion of the population, with variations in prevalence observed across different regions or studies. [Savouré] References:
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Desirable EffectsHow substantial are the desirable anticipated effects? | ||
Judgement | Research evidence | Additional considerations |
Nasal symptoms In a systematic review with network meta-analysis performed by our team [1], the improvement of nasal symptoms was assessed in patients under oral antihistamines (OAH). We considered the Total Nasal Symptom Score (TNSS) computed based on four symptoms. However, for most OAH, pivotal randomised trials (RCTs) are old and have computed the TNSS based on three symptoms. For patients with seasonal allergic rhinitis, it was possible to meta-analytically pool the TNSS results of 38 RCTs. With the exception of astemizole, fexofenadine, levocetirizine and terfenadine, all OAHs were associated with a significantly higher improvement in the TNSS when compared to placebo (of note, astemizole and terfenadine are no longer on the market due to safety concerns). Cetirizine, desloratadine, ebastine, mequitazine, loratadine, olopatadine and rupatadine were associated with a probability >75% of displaying a clinically meaningful improvement in TNSS levels compared to placebo. With the exception of medications assessed by one study only, the medications with highest probability of resulting in an at least moderate improvement in the TNSS were cetirizine (30.8%), ebastine (22.8%) and rupatadine (10.9%). Among drugs evaluated by more than one RCT, fexofenadine, levocetirizine and terfenadine were found to be less effective in improving the TNSS compared to other active drugs, including bilastine, cetirizine, desloratadine and ebastine. Except for the comparison between bilastine versus terfenadine, for all these comparisons there was an at least 50% probability of a clinically meaningful difference. Olopatadine and mequitazine were also associated with non-trivial probability of TNSS improvement compared to other active drugs. However, they were assessed by a single RCT each. Without considering the medications evaluated by a single RCT, cetirizine, ebastine and desloratadine were the medications displaying the highest probability of being the most effective improving the TNSS. For patients with perennial allergic rhinitis, it was possible to meta-analytically pool the four symptom TNSS results of 13 RCTs. All OAHs, apart from loratadine, were associated with a significantly higher improvement in the TNSS when compared to placebo. All drugs except desloratadine and loratadine were associated with a probability >75% of displaying a clinically meaningful improvement in TNSS levels compared to placebo. Rupatadine was the medication with highest probability of resulting in an at least moderate improvement in the TNSS (16.7%). There were no significant differences between individual OAHs, except for rupatadine, which was associated with a significantly higher improvement in the TNSS compared with loratadine (71% probability of a clinically meaningful improvement; 65% probability of that improvement being small). Rupatadine was the OAH displaying the highest probability of being the most effective in improving the TNSS, followed by ebastine. Ocular symptoms In a systematic review with network meta-analysis performed by our team [1], the improvement of ocular symptoms was assessed in patients under OAHs. For patients with seasonal allergic rhinitis, it was possible to meta-analytically pool the results of 12 RCTs which assessed the total ocular symptom score (TOSS) computed as the sum of 3 individual ocular symptoms. Except for fexofenadine, all OAHs were associated with a significantly higher improvement in the TOSS when compared to placebo. All drugs except fexofenadine were associated with a probability >75% of displaying a clinically meaningful improvement in TOSS levels compared to placebo. The medications with highest probability of resulting in an at least moderate improvement in the TOSS were desloratadine (28.5%), rupatadine (21.6%) and bilastine (11.9%). There were no significant differences in the comparisons between different OAHs, with the exception of fexofenadine, which was associated with a significantly lower improvement in the TOSS compared with bilastine, cetirizine, levocetirizine and loratadine. For all these comparisons there was an at least 50% probability of a clinically meaningful difference. Loratadine was the OAH displaying the highest probability (87%) of being the most effective in improving the TOSS, followed by desloratadine and cetirizine. For patients with perennial allergic rhinitis, no primary studies were identified allowing for the comparison between individual OAHs on their effect on TOSS (computed as the sum of three or four nasal symptom). Quality-of-life In a systematic review with network meta-analysis performed by our team [1], the improvement of quality-of-life was assessed in patients under OAH. For patients with seasonal allergic rhinitis, it was possible to meta-analytically pool the rhinocojunctivitis quality of life questionnaire (RQLQ) results of 24 RCTs. All OAHs, with the exception of chlorpheniramine, were associated with a significantly higher improvement in the RQLQ compared with placebo. Desloratadine, fexofenadine, loratadine, olopatadine and rupatadine were associated with a probability >75% of displaying a clinically meaningful improvement in RQLQ levels compared to placebo. With the exception of medications assessed by one study only (rupatadine and olopatadine), all other medications displayed a <10% probability of resulting in an at least moderate improvement in the RQLQ. Olopatadine and rupatadine displayed significantly better results in improving the RQLQ compared to other active drugs, but they were assessed by one RCT each. With the exception of medications assessed by one study only (rupatadine and olopatadine), the medication with highest probability of resulting in an at least moderate improvement in the RQLQ was desloratadine. For patients with perennial allergic rhinitis, it was possible to meta-analytically pool the RQLQ results of 6 RCTs. All assessed OAHs (cetirizine, desloratadine, levocetirizine and rupatadine) were associated with a significantly higher improvement in the RQLQ when compared to placebo. Levocetirizine and cetirizine were associated with a probability >75% of displaying a clinically meaningful improvement in RQLQ levels compared to placebo. The probability of resulting in an at least moderate improvement was of 32.3% in levocetirizine and 11.8% for cetirizine. There were no significant differences in the comparisons between different OAHs. Levocetirizine and desloratadine were the OAHs displaying the highest probability of being the most effective in improving the RQLQ (90% and 69%, respectively). The following table summarises the p-scores-based ranks for the individual OAH evaluated across more than one outcome. The p-score ranks interventions on the probability they display of being the most effective ones:  Reference: 1. Vieira RJ, Gil-Mata S, Ferreira A, Riera-Serra P, Bognanni A, Duarte VH, et al. Efficacy and safety of oral antihistamines for allergic rhinitis: Network meta-analysis. 2025 [link with the full results] | ||
Undesirable EffectsHow substantial are the undesirable anticipated effects? | ||
Judgement | Research evidence | Additional considerations |
Adverse events In a systematic review with network meta-analysis performed by our team [1], the frequency of patients developing at least one adverse event was assessed in patients under oral antihistamines (OAH). A total of 44 randomised controlled trials (RCTs) reported data on the number of patients with seasonal allergic rhinitis reporting at least one adverse event. No substantial differences were observed in the comparisons between different OAHs, except that bilastine and levocetirizine were associated with a significantly lower frequency of adverse events than rupatadine or terfenadine. For patients with perennial allergic rhinitis, it was possible to meta-analytically pool the results of 21 RCTs. There were no significant differences in the comparisons between different OAHs, except that bepotastine was associated with an increased risk of adverse events compared to most other individual OAH. Subgroup considerations: Children and adolescents A subgroup analysis of studies in children and adolescents was not performed due to insufficient number of primary studies assessing each individual medication. Serious adverse events In a systematic review with network meta-analysis performed by our team [1], the frequency of patients developing at least one serious adverse event was assessed in patients under OAH. However, the frequency of events was too scarce to perform network meta-analysis comparing individual medications. The (non-pooled) frequency of serious adverse events per individual OAH is displayed in the following table. The provided intervals are fully within the “trivial” category.  Pharmacovigilance In an additional analysis of pharmacovigilance data among patients taking either first-generation or second-generation oral antihistamines (OAH)—regardless of an allergic rhinitis diagnosis—we identified the drugs most strongly associated with disproportionately reported adverse drug reactions, based on their reporting odds ratio (ROR). Among the highest RORs, most were observed for first-generation OAH, particularly:
We also identified some second-generation OAH associated with high RORs, though generally lower than those of first-generation agents:
Input of the panel experts The panel experts highlighted – based on their clinical practice – that some OAH (even of the second generation) can have sedative effects. This is the case of cetirizine. On the other hand, fexofenadine does not have a sedative effect. This input is in accordance with the indications of the Federal Aviation Administration, which allows the use of fexofenadine or loratadine but discourages the use of cetirizine or levocetirizine due to their sedative effects [2]. Subgroup considerations: Children and adolescents A subgroup analysis of studies in children and adolescents was not performed due to insufficient number of primary studies assessing each individual medication. References: 1. Vieira RJ, Gil-Mata S, Ferreira A, Riera-Serra P, Bognanni A, Duarte VH, et al. Efficacy and safety of oral antihistamines for allergic rhinitis: Network meta-analysis. 2025 [link with the full results] 2. Federal Aviation Administration. What Over-the-Counter (OTC) medications can I take and still be safe to fly? Available at: https://www.faa.gov/sites/faa.gov/files/licenses_certificates/medical_certification/medications/OTCMedicationsforPilots.pdf (last accessed: June 2, 2025). | ||
Certainty of evidenceWhat is the overall certainty of the evidence of effects? | ||
Judgement | Research evidence | Additional considerations |
For each outcome, the distribution (number) of comparisons per certainty of evidence (CoE) is the following:  For TNSS and RQLQ SAR, most judgements of “very low” CoE are observed for comparisons involving medications that are only evaluated in a single clinical RCT (typically with low precision). When these are excluded, the following results are obtained:  Reference (where complete CoE assessments can be found): 1. Vieira RJ, Gil-Mata S, Ferreira A, Riera-Serra P, Bognanni A, Duarte VH, et al. Efficacy and safety of oral antihistamines for allergic rhinitis: Network meta-analysis. 2025 [link with the complete CoE assessments] | ||
ValuesIs there important uncertainty about or variability in how much people value the main outcomes? | ||
Judgement | Research evidence | Additional considerations |
Utility values Symptoms Regarding specific symptoms, in two studies, utilities (measured by VAS) were lower for severe nasal congestion and severe rhinorrhea compared to severe sneezing, severe throat itching, and severe itchy eyes (certainty of evidence: low). When utilities were elicited with the standard gamble technique, severe itchy eyes were rated by US patients as the least preferred AR symptom (certainty of evidence: low).  Studies of rating or ranking of outcomes Adults
 Children/caregivers sample Seven studies assessing children or their caregivers were included in the relative importance analysis. Most of these studies only assessed symptom-related attributes. Similarly to the adult population, a nasal symptom was frequently ranked as the most or second most important attribute (certainty of evidence: low). In particular, nasal congestion was identified as the most important attribute in five studies (certainty of evidence: low).  | ||
Balance of effectsDoes the balance between desirable and undesirable effects favor the intervention or the comparison? | ||
Judgement | Research evidence | Additional considerations |
Taking into account both benefits and harms of oral antihistamines (OAH), we can consider the following:
These considerations were based on the medications evaluated by more than one RCTs, and most differences between individual OAH were trivial. There are other medications which tended to display favourable results (e.g., olopatadine), but which were assessed only by one RCT with low precision. Plus, there were medications such as desloratadine, whose comparative favourable profile in terms of efficacy was not corroborated by the clinical expertise of the panel members. | Cetirizine, bilastine, desloratadine, ebastine and rupatadine were the specific individual antihistamines most frequently identified as having a higher efficacy. Fexofenadine was the specific individual antihistamine most frequently identified as having lower efficacy, despite displaying a lower sedative effect. Terfenadine was also identified as having an unfavourable balance of effects, but it has been out of the market due to safety issues. | |
Resources requiredHow large are the resource requirements (costs)?” | ||
Judgement | Research evidence | Additional considerations |
We have included one CDR pharmacoeconomic review report that provides data on the resource use of specific medications, including oral antihistamine – Cetirizine, and one analysis of Asian countries in terms of resource use [Kulthanan 2018] In relation to the reported costs of AR treatment in Canada, presented in submission dossier for Dymista, the average daily costs for oral antihistamines range from $0.4298 to $0.8595 for Cetirizine. In the analysis of resource use in Asian countries, the cost per daily dose of selected second-generation antihistamines ranged from USD 0.45 to 0.93 for bilastine, USD 0.19 to 0.79 for cetirizine, USD 0.62 to 0.75 for desloratadine, USD 0.22to 0.58 for ebastine, USD 0.10 to 1.51 for fexofenadine, USD 0.06to 1.29 for ketotifen, USD 0.42 to 0.57 for levocetirizine, USD0.04 to 1.29 for loratadine and USD 0.31 to 1.16 for rupatadine. All prices refer to innovators and/or locally produced drugs. [Kulthanan 2018]  Survey results We conducted a survey, having received responses from specialists from 41 countries (mostly in Europe, America and Asia). The yearly across-countries costs are displayed below:  The least expensive and most expensive individual OAH in each country are displayed in the following maps:   References: 1. CDR PHARMACOECONOMIC REVIEW REPORT FOR DYMISTA – https://www.cda-amc.ca/sites/default/files/cdr/pharmacoeconomic/SR0408_Dymista_PE_Report.pdf 2. Kulthanan K, Chusakul S, Recto MT, Gabriel MT, Aw DCW, Prepageran N, Wong A, Leong JL, Foong H, Quang VT, Zuberbier T. Economic Burden of the Inadequate Management of Allergic Rhinitis and Urticaria in Asian Countries Based on the GA²LEN Model. Allergy Asthma Immunol Res. 2018 Jul;10(4):370-378. doi: 10.4168/aair.2018.10.4.370. PMID: 29949833; PMCID: PMC6021592. | Among OAH identified in RCTs as having a better efficacy profile: cetirizine is frequently the least expensive OAH (8 countries); desloratadine is the least expensive OAH in 9 countries but the most expensive in 7 countries; bilastine, ebastine and rupatadine were never identified as the least expensive in any country but were identified as the most expensive in some countries. | |
Certainty of evidence of required resourcesWhat is the certainty of the evidence of resource requirements (costs)? | ||
Judgement | Research evidence | Additional considerations |
Given that oral antihistamines have been around for a long time, there is a reasonably high degree of certainty about the general costs. However, it should be noted that some available evidence comes from a survey of experts. | ||
Cost effectivenessDoes the cost-effectiveness of the intervention favor the intervention or the comparison? | ||
Judgement | Research evidence | Additional considerations |
Evidence from the literature We identified three pharmacoeconomic reports that provides data on the cost-effectiveness of specific oral antihistamine [Nash 2000, Kozma 1996 Goodman 2008]. In cost effectiveness within trial study, medication cost per treatment success (defined as either a significant or a moderate improvement in rhinitis symptoms at the end of the trial as reported by the study patients) was the lowest for fluticasone compared with loratadine and combination of loratadine/fluticasone: $48.42, $109.40, $109.20 respectively. In cost effectiveness within trial study performed by Kozma et al., the cost-efficacy ratio (1% symptom reduction) for intranasal fluticasone propionate 200 mg once daily were more favorable than the ratios for terfenadine 60 mg twice daily: $0.44 vs $0.86. In the study performed by Goodman, the incremental cost-effectiveness ratio for levocetirizine dominated desloratadine and fexofenadine (both branded or generic).  However, all these studies are more than 15 years ago. Evidence from direct patient data Considering the costs reported in the survey alongside differences in VAS EQ-5D assessed using MASK-air data (inverse probability weighting methods were used to account for confounding), we get the results summarised in the following table on the number of countries for which each medication within each comparison is cost-effective. (In each cell, the number between brackets corresponds to the number of countries where each medication of each comparison is cost-effective for a willingness-to-pay threshold of 50,000 USD per QALY gained):  References: 1. Goodman MJ, Jhaveri M, Saverno K, Meyer K, Nightengale B. Cost-effectiveness of second-generation antihistamines and montelukast in relieving allergic rhinitis nasal symptoms. Am Health Drug Benefits. 2008 Oct;1(8):26-34. PMID: 25126257; PMCID: PMC4106503. 2. Nash DB, Sullivan SD, Mackowiak J. Optimizing quality of care and cost effectiveness in treating allergic rhinitis in a managed care setting. Am J Manag Care. 2000 Jan;6(1 Suppl):S3-15; quiz S19-20. PMID: 11009751. 3.. Kozma CM, Schulz RM, Sclar DA, Kral KM, Mackowiak JI. A comparison of costs and efficacy of intranasal fluticasone propionate and terfenadine tablets for seasonal allergic rhinitis. Clin Ther. 1996 Mar-Apr;18(2):334-46; discussion 302. doi: 10.1016/s0149-2918(96)80014-2. PMID: 8733993 | Cost-effectiveness analysis depends on country-specific costs; in addition, estimates were made based on EQ-5D VAS data (rather than utility data) | |
EquityWhat would be the impact on health equity? | ||
Judgement | Research evidence | Additional considerations |
Availability We conducted a survey, having received responses from specialists from 41 countries (mostly in Europe, America and Asia). The percentage of countries in which each oral antihistamine is available for the treatment of allergic rhinitis ranged from 51% to 100%:  Other equity-related aspects  | ||
AcceptabilityIs the intervention acceptable to key interest-holders? | ||
Judgement | Research evidence | Additional considerations |
SATISFACTION 2 publications presenting data on patient satisfaction were identified. [Ferrer 2010, De Vos 2008]. One of these studies was performed in North America or Europe, and one was international. 1. Patient satisfaction The first study was a multinational survey that analyzed both satisfaction of patients and physicians who treat allergic disease in European countries. [De Vos 2008] Levocetirizine and cetirizine had similar mean patient satisfaction scores for treatment efficacy (figure 2), for impact on sleep (figure 3) and activities of daily living (ADL). Furthermore, the responses of the levocetirizine group for each of these parameters were generally significantly different from those of the other treatment groups, except for cetirizine. Overall, patients were highly satisfied with the efficacy of their treatments. Levocetirizine had the highest mean score (8,12), which was significantly different from the mean scores for the other treatment groups except cetirizine.   Regarding the global satisfaction of the patients, a total of 68.2% patients receiving levocetirizine were ‘very satisfied’ with their treatment compared with 57.2% for cetirizine, 48.7% for fexofenadine 180 mg/day, 45.8% for desloratadine, 41.7% forebastine 20 mg/day, 38.9% for loratadine, 38.2% for fexofenadine 120 mg/day, and 36.9% for ebastine 10 mg/day. [De Vos 2008] Another international observational survey [Ferrer 2010] that aims to investigate parent and physician satisfaction with the efficacy and tolerability of oral antihistamine treatment in children reveal similar results. Overall, the parents were satisfied with the efficacy of all antihistamine treatments, as indicated by a score of >6 out of 10 for each treatment and an overall mean (–SD) score of 8.24 (–1.82). A comparison among the antihistamines showed levocetirizine to score significantly higher than cetirizine, desloratadine and loratadine, but not significantly higher than fexofenadine (adjusted mean [95% CI] = -0.52[-1.34, 0.30]. Similarly, assessment of mean (–SD) satisfaction scores for tolerability (figure 3b) and global satisfaction (figure 3c) for the different antihistamines rendered the highest scores for levocetirizine and fexofenadine, both of which were also higher than the overall mean (SD) antihistamine tolerability and global satisfaction scores of 8.75 (–1.64) and 8.38 (–1.79), respectively   2. Practitioners satisfaction Practitioners’ global satisfaction with treatment was significantly higher in the levocetirizine group than in the other treatment groups compared with all other agents except cetirizine. The mean global satisfaction score was 8.43 (SD 1.45) [maximum of 10] with levocetirizine, 8.20 (SD 1.94) with cetirizine, 7.36 (SD 2.03) with desloratadine, 7.16 (SD 2.06) with fexofenadine 180 mg/day, 7.13 (SD 2.43) with loratadine, 7.00 (SD 2.03) with ebastine 20 mg/day, 6.99 (SD 2.24) with ebastine 10 mg/day and 6.80 (SD 2.47) with fexofenadine 120 mg/day. [De Vos 2008] In the Ferrer 2010 study , the physicians’ satisfaction scores for efficacy, tolerability and global satisfaction with the antihistamine treatment closely resembled the parents’ scored for these outcome measures. Levocetirizine and fexofenadine generally scored highest for efficacy, tolerability and global satisfaction, as well as for impact on the child’s ability to function at school, quality of school activities and quality of sleep.   WILLINGNESS TO CONTINUE 2 publications presenting data on patient safisfaction were identified. [Ferrer 2010, De Vos 2008]. One of these studies was performed in North America or Europe, and one was international. In the multinational survey, significantly more patients (94.9%) receiving levocetirizine were willing to continue treatment compared with those receiving the other agents (cetirizine 88.3%; desloratadine 75.9%; fexofenadine 180 mg/day 75.6%; ebastine20 mg/day 72.0%; ebastine 10 mg/day 71.2%;loratadine 69.9%; fexofenadine 120 mg/day 63.8%;p < 0.001 in all cases) [De Vos 2008] In the second multinational study, overall, 92.1% of parents and 92.6% of physicians were willing to use or recommend the same antihistamine treatment in the future, with assessment of individual antihistamines indicating even higher numbers for levocetirizine (97.2%of parents and 97.4% of physicians). [Ferrer 2010] Evidence from direct patient data: In the MASK-air dataset, the following information was available for days in which OAH were used and for which patients provided information on how satisfied they were with their treatments (higher values indicating higher satisfaction) [Sousa-Pinto et al. 2025]:  In multivariable mixed-effects models adjusted for the previous day CSMS (a proxy for the severity before taking medication) and for the ARIA score (an indicator of baseline severity), no relevant differences were observed when comparing satisfaction levels between individual oral antihistamines, except for the comparisons: Bilastine/Levocetirizine/Loratadine vs. Desloratadine (favouring Desloratadine).  In multivariable mixed-effects models adjusted for the previous day CSMS and for the ARIA score, fexofenadine was associated with higher chances of being used in co-medication than cetirizine, desloratadine and loratadine, while ebastine was associated with higher chances of being used in co-medication than loratadine.  Onset of action A rapid review of the literature on the onset of action of specific medications was carried out. The following results were found:  References: 1. De Vos C, Mitchev K, Pinelli ME, Derde MP, Boev R. Non-interventional study comparing treatment satisfaction in patients treated with antihistamines. Clin Drug Investig. 2008;28(4):221-30. doi: 10.2165/00044011-200828040-00003. PMID: 18345712. 2. Ferrer M, Morais-Almeida M, Guizova M, Khanferyan R. Evaluation of treatment satisfaction in children with allergic disease treated with an antihistamine: an international, non-interventional, retrospective study. Clin Drug Investig. 2010;30(1):15-34. doi: 10.2165/11530910-000000000-00000. PMID: 19995095 3. Sousa-Pinto B, Vieira RJ, Bognanni A, et al. Comparison of Allergic Rhinitis Treatments on Patient Satisfaction: A MASK-air and EAACI Methodological Committee Report. Allergy. 2025. doi.org/10.1111/all.70055 | ||
FeasibilityIs the intervention feasible to implement? | ||
Judgement | Research evidence | Additional considerations |
Barriers – safety and effectiveness-related We identified one study that provides data on barriers in taking OAH in France [1]. Physicians justified why they chose to stop the previous treatment. “Lack of efficacy” was the most cited reason (90.9% for ebastine; 88.0% for desloratadine), followed by “tolerance issue” (29.2% for mizolastine; 22.4% for levocetirizine; 21.9% for cetirizine). References: 1. Demoly P, Chiriac AM, Berge B, Rostin M. Reasons for prescribing second generation antihistamines to treat allergic rhinitis in real-life conditions and patient response. Allergy Asthma Clin Immunol. 2014 Jun 6;10(1):29. doi: 10.1186/1710-1492-10-29. PMID: 24944561; PMCID: PMC4062518 | ||
Planetary healthWhat would be the impact on planetary health? | ||
Judgement | Research evidence | Additional considerations |
There is currently no evidence on the specific impact of individual OAH on planetary health. Key considerations include the availability of locally produced medications, as well as medication effectiveness in reducing healthcare resource utilization. | ||
Summary of judgements
Judgement | |||||||
|---|---|---|---|---|---|---|---|
Problem | No | Probably no | Probably yes | Yes | Varies | Don’t know | |
Desirable Effects | Trivial | Small | Moderate | Large | Varies | Don’t know | |
Undesirable Effects | Trivial | Small | Moderate | Large | Varies | Don’t know | |
Certainty of evidence | Very low | Low | Moderate | High | No included studies | ||
Values | Important uncertainty or variability | Possibly important uncertainty or variability | Probably no important uncertainty or variability | No important uncertainty or variability | |||
Balance of effects | Favors the comparison | Probably favors the comparison | Does not favor either the intervention or the comparison | Probably favors the intervention | Favors the intervention | Varies | Don’t know |
Resources required | Large costs | Moderate costs | Negligible costs and savings | Moderate savings | Large savings | Varies | Don’t know |
Certainty of evidence of required resources | Very low | Low | Moderate | High | No included studies | ||
Cost effectiveness | Favors the comparison | Probably favors the comparison | Does not favor either the intervention or the comparison | Probably favors the intervention | Favors the intervention | Varies | No included studies |
Equity | Reduced | Probably reduced | Probably no impact | Probably increased | Increased | Varies | Don’t know |
Acceptability | No | Probably no | Probably yes | Yes | Varies | Don’t know | |
Feasibility | No | Probably no | Probably yes | Yes | Varies | Don’t know | |
Planetary health | Reduced | Probably reduced | Probably no impact | Probably increased | Increased | Varies | Don’t know |
Type of recommendation
Conclusions
Recommendation |
In adults with allergic rhinitis, the ARIA guideline panel suggests that the choice of specific oral antihistamines over others should be based on patients’ preferences on efficacy and safety and on availability and affordability (conditional recommendation based on mostly very low certainty of evidence). |
Justification |
There are cases of oral antihistamines (OAH) which display high efficacy but may be more sedative of some patients (and vice-versa), rendering it important to evaluate whether patients value more efficacy over safety or vice-versa. Some individual medications should be highlighted:
|
Subgroup considerations |
In pre-school and school children, no evidence was available to support a specific recommendation due to insufficient number of primary studies. In pregnant women, existing studies do not suggest a teratogenic effect of oral antihistamines and the FDA considers loratadine and cetirizine generally safe in pregnancy. |
Implementation considerations |
This recommendation concerns second-generation oral antihistamines. In low-middle income countries, specific individual medications may be preferred based on local availability and affordability. Other aspects may be considered when choosing an antihistamine: (i) rupatadine displays a briefer onset of action, while at the same time displaying high effectiveness, (ii) planetary health concerns may be taken into account, with consideration for locally preferred generics, (iii) in the patients with renal or hepatic impairment, bilastine and fexofenadine do not require dose adjustment. However, fexofenadine and bilastine blood levels may be reduced because of interactions with grapefruit and some other fruit juices, so they should be taken with water. Oral antihistamines with more sedative effect (e.g., cetirizine) may be preferentially taken in the evening. |
Monitoring and evaluation |
Research priorities |
Research priorities by domain of the certainty of evidence assessment:
Other research priorities
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