Rebound Pruritus and Urticaria After Discontinuation of Chronic Antihistamine Use—A Scoping Review

ABSTRACT

Background

Rebound pruritus and urticaria have been increasingly reported following discontinuation of chronic antihistamines, particularly with cetirizine and levocetirizine, prompting the United States Food and Drug Administration to issue a recent safety warning for these two medications. Currently, there are significant gaps regarding the risk factors, course and optimal management of rebound pruritus and urticaria after discontinuation of chronic antihistamine use, and if this represents a class‐specific adverse effect. This review aimed to map the literature related to rebound pruritus and urticaria after discontinuation of chronic antihistamine use.

Methods

A scoping review was conducted across four major literature databases (PubMed, Embase, Web of Science and Cochrane database) and grey literature (GreySource, OpenGrey, Google Scholar) from inception to December 2025. Articles describing rebound pruritus following discontinuation of chronic antihistamine use in paediatric or adult populations were included. Antihistamines evaluated included all first‐ and second‐generation histamine‐1 antagonists. Non‐English articles were excluded. A narrative synthesis was conducted to summarise the reported risk factors, clinical course and potential management strategies for rebound pruritus following antihistamine discontinuation.

Results

Of the 17,346 records retrieved, two retrospective studies, one case series and one case report were included in the review. The studies were conducted in the United States (n = 2), the Netherlands (n = 1) and Singapore (n = 1). The main antihistamines implicated in after discontinuation rebound pruritus were cetirizine (n = 327), levocetirizine (n = 39) and, both cetirizine and levocetirizine (n = 2). Among these patients, 85 patients experienced concomitant urticaria after discontinuation of chronic antihistamines. No report was noted for other antihistamines. The patients' age ranged from 6 to 71 years, with a female predominance (76.1%). Antihistamine use ranged from months to years, with pruritus developing between 1 to 5 days after discontinuation. Among the common treatment strategies adopted, cetirizine or levocetirizine re‐initiation was the most effective (n = 136 of 137, 99.2%), while antihistamine tapering had the lowest rate of symptoms resolution (n = 11 of 33, 33.3%).

Conclusions

Rebound pruritus following discontinuation of chronic cetirizine or levocetirizine use represents a clinically relevant adverse effect that warrants careful monitoring and management. Future research is required to identify the optimal treatment strategy and if the discontinuation of other antihistamines could also lead to rebound pruritus.

Key Messages

• Rebound pruritus and urticaria may occur after stopping long‐term cetirizine or levocetirizine.

• Symptoms usually appear within 0.5–5 days after discontinuation, more frequently reported in female patients.

• Re‐starting antihistamines often relieves symptoms, highlighting clinician awareness when stopping long‐term therapy.

Rebound pruritus and urticaria have been reported after discontinuation of chronic cetirizine or levocetirizine use only. Symptoms typically occur within 0.5–5 days after stopping therapy and appear more frequently reported in female patients. Re‐initiation of antihistamines is the most commonly effective management strategy, highlighting the need for clinician awareness when discontinuing long‐term antihistamine therapy.

Abbreviations

FDA

Food and Drug Administration

PICO

Patient, intervention, comparator and outcomes

1. Introduction

Antihistamines, particularly histamine H1 receptor antagonists, are among the most commonly used medications for allergic conditions such as allergic rhinitis and urticaria [1]. Notably, an estimated 18–25 million people in the United States used over‐the‐counter antihistamines for allergies annually [2] while over 3.2 million prescriptions for oral antihistamines were procured annually in Australia [3]. These medications act by inhibiting histamine H1 G‐protein–coupled receptors, thereby providing symptomatic relief [4]. Over the past century, substantial research of H1 receptor antagonists has culminated in the development of two distinct sub‐classes of H1 antihistamines, namely first‐ and second‐ generation antihistamines [5]. Second‐generation antihistamines have greater selectivity for H1 receptors and reduced blood–brain‐barrier penetration, translating to fewer central nervous system‐related side effects such as sedation [6].

Chronic antihistamine use is common among patients with allergic conditions such as chronic urticaria and persistent allergic rhinitis, owing to their safety and efficacy [7, 8]. However, emerging evidence suggests potential adverse effects arising from the discontinuation of chronic antihistamine use [9, 10]. Initially, reports of pruritus and urticaria following the discontinuation of chronic cetirizine surfaced across medical forums and blogs [9, 10]. Subsequent analyses of pharmacovigilance databases in the United States and the Netherlands identified 146 and 12 cases respectively of patients experiencing similar adverse reactions after discontinuing cetirizine and levocetirizine [10, 11]. Notably, nearly all patients (98.1%) experienced severe pruritus with a second antihistamine discontinuation attempt [11]. More recently, the Food and Drug Administration (FDA) in the United States issued a warning for healthcare professionals regarding the risk of severe pruritus following discontinuation of cetirizine and levocetirizine [12].

The pathophysiology of rebound pruritus or urticaria in patients who undergo discontinuation of chronic antihistamines remains unclear. A postulated mechanism linked to downregulation of histamine H1 receptors has been suggested by Ekhart et al. and Konkel et al. [10, 13] Histamine H1 receptors belong to the family of G‐protein–coupled receptors that exist in equilibrium between active and inactive conformational states [14]. Through its inhibitory effects on inflammation responses and transcription factor protein complexes, antihistamines exert an indirect effect in downregulating gene expression of histamine H1 receptors [14]. Consequently, abrupt discontinuation following prolonged antihistamine use may increase the proportion of receptors available for histamine binding, potentially triggering pruritus [10].

Significant knowledge gaps currently exist regarding the pathophysiology, risk factors and clinical course of rebound pruritus and urticaria following chronic antihistamine use. Moreover, there is non‐consensus on the optimal management strategies or if this phenomenon is specific to levocetirizine and cetirizine. Therefore, this scoping review aims to address these research gaps by providing a map of the literature on the condition and its management.

2. Methods

2.1. Information Sources and Search Strategy

A scoping review was performed across four literature databases, namely: PubMed, Embase, Web of Science and Cochrane Library, as well as two grey literature databases: OpenGrey and GreySource. Additionally, the first 200 results from Google Scholar were screened to identify potentially relevant articles that may not yet have been indexed in traditional databases. No restriction was imposed on the commencement date of the literature search, while studies were included up till 29 December 2025. The search strategy encompassed terms related to rebound pruritus after discontinuation of chronic antihistamine use, which was adapted from another review [11] The details of the full search strategy are listed in File S1. The protocol for the study is registered on Open Science Framework.

2.2. Key Definitions in This Review

2.2.1. Chronic Antihistamine Use

There is no universal definition for the duration of chronic antihistamine use. For this review, chronic antihistamine use was defined as daily antihistamine use for four weeks or longer. The duration was adapted from the definition of atopic conditions that require prolonged antihistamine use and recommended time points for re‐assessment of continued antihistamine use. Specifically, the included conditions are persistent allergic rhinitis as per the Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines that require symptoms to last four or more weeks [7], and chronic urticaria was defined as persistent symptoms lasting six weeks or more [15] Clinical practice guidelines for urticaria also generally recommend for reassessment of treatment efficacy at two to four weeks [8] For the purposes of this review, chronic antihistamine use was defined as regular use for four weeks or more based on clinical management timelines commonly applied in allergic rhinitis and chronic urticaria. However, we acknowledge that definitions of chronic medication exposure vary in pharmacological research [7].

2.3. Eligibility Criteria and Selection Process

Full‐text articles in English language that evaluated rebound pruritus in patients who discontinue chronic antihistamine use were included. Eligible study designs included case reports, case series, cross‐sectional studies, cohort studies, case–control studies, randomised controlled trials, and other observational studies. Irrelevant systematic reviews and meta‐analyses were excluded. Using the PICO (patient, intervention, comparator and outcomes) framework, the target population of interest was both paediatric and adult populations. Intervention of interest was patients who discontinued chronic antihistamines. Both first‐ and second‐generation histamine‐1 receptor antagonists were included. Comparator groups included patients receiving standard of care or patients not on treatment. Outcomes of interest included the development of pruritus or urticaria after discontinuation of chronic antihistamine use.

References and abstracts that were identified were extracted to EndNote X9 software. Duplicated citations were removed. The screening of the titles, abstracts and full text of retrieved citations was performed by two independent reviewers (SJJB and PO) to identify relevant articles for inclusion in the review. All disagreements during the screening process were discussed and any unresolved disagreements were arbitrated by a third independent reviewer (NCT). In addition, hand‐searching of references within included studies was performed to identify other relevant studies.

2.4. Data Collection Process and Data Items

A standardised data collection form in Microsoft Excel was used for the data collection process. Information from studies was extracted independently by two reviewers. A pilot data extraction was performed for the first ten citations to ensure accuracy of data extraction. The information collected from studies included the study title, publication year, sample size, patient demographic, type of antihistamines, dosage used and duration of use. Additionally, details related to rebound pruritus after discontinuation of chronic antihistamine use, onset, severity and management of symptoms were collected.

2.5. Study Risk of Bias Assessment and Reporting Bias Assessment

As the study aims to provide a broad overview of existing literature, risk of bias analysis of the included studies was not conducted.

2.6. Effect Measures and Synthesis Methods

A narrative review was conducted for rebound pruritus after discontinuation of chronic antihistamine use. Details regarding the characteristics of included studies were pooled and reported using descriptive statistics. For studies with missing data, their corresponding authors will be contacted for clarification. Information that could not be obtained after two email reminders will be labelled as unavailable.

Due to the expected heterogeneity of included studies, meta‐analyses were not conducted. Based on the results from the identified literature, a workflow for monitoring and management of rebound pruritus or urticaria after discontinuation of chronic antihistamines was proposed. The workflow was designed by members of the project, in tandem with institution content experts, integrating recommendations from existing drug information leaflets.

3. Results

3.1. Characteristics of Included Studies

Of the 17,346 citations retrieved, four articles were included in this review, comprising two retrospective cohort studies [10, 11], one case series [13] and one case report [16] (Figure 1). The study characteristics are summarised in Table 1, with the full details of the included studies found in File S2. The studies were conducted in the United States (n = 2) [11, 13], the Netherlands (n = 1) [10] and Singapore (n = 1) [16].

FIGURE 1.

Flowchart for inclusion of articles.

TABLE 1.

Summary of study characteristics (n = 4).

Study details	Frequency (%)
Study design
Retrospective study	2 (50)
Case series	1 (25)
Case report	1 (25)
Country of study
United States	2 (50)
Netherlands	1 (25)
Singapore	1 (25)
Year of study
2015–2020	2 (50)
2021 and onwards	2 (50)
Sample size
1–10	1 (25)
11–100	1 (25)
101–200	1 (25)
201–300	1 (25)
Age group of population
Adult patients only	2 (50)
Both paediatric and adult patients	1 (25)
Not reported	1 (25)
Source of data
Medication adverse effects database	3 (75)
Patient reported	1 (25)

3.2. Summary of Patients With Rebound Pruritus After Discontinuation of Chronic Antihistamine Use

Table 2 describes the characteristics of the 386 patients who experienced rebound pruritus after discontinuation of chronic antihistamine use. The age range of patients spanned between 6 to 71 years old, where the majority of reported patients were female (76.1%). The majority of adverse reactions were reported by consumers (57.3%), and the most common co‐morbidity reported was hypothyroidism (n = 7, 1.9%).

TABLE 2.

Summary of cases of rebound pruritus or urticaria in patients who underwent discontinuation of antihistamines (n = 368).

Study details	Frequency (%) unless otherwise specified
Patient age (Range), years old	6–71
Gender (n = 159)
Male	38 (23.9)
Female	121 (76.1)
Reporting personnel
Consumers/patients	211 (57.3)
Combined (patients, consumers, and healthcare professional)	116 (31.5)
Manufacturer	28 (7.6)
Healthcare professional	10 (2.7)
Medical literature	3 (0.8)
Comorbidities of patients
Hypothyroidism	7 (1.9)
Anxiety	1 (0.3)
Dry skin	1 (0.3)
Depression	1 (0.3)
Anaemia	1 (0.3)
Hypertension	1 (0.3)
Hyperlipidemia	1 (0.3)
Not reported	263
Antihistamines implicated
Cetirizine	327 (88.9)
Levocetirizine	39 (10.6)
Cetirizine and levocetirizine	2 (0.5)
Indication for antihistamines
Seasonal or perennial allergies	323 (87.8)
Allergic rhinitis, or related symptoms	15 (4.1)
Asthma or allergic respiratory disease	13 (3.5)
Hypersensitivity	5 (1.4)
Food, drug, or dust mite allergy	5 (1.4)
Urticaria	2 (0.5)
Post nasal drip	2 (0.5)
Others	19 (5.2)
Not reported	2 (0.5)
Duration of antihistamine use prior to discontinuation (Range), months	0.3–276
Onset of pruritus following discontinuation of antihistamine, days
Cetirizine	0.5–5
Levocetirizine	1–5
Both levocetirizine and cetirizine	1
Overall	0.5–5
Location of pruritus
Widespread	110 (29.9)
Extremities	11 (3.0)
Extremities and head, neck or scalp	11 (3.0)
Extremities and trunk	5 (1.4)
Random sites	2 (0.5)
Not reported	229 (62.2)
Outcomes of serious adverse effects a
Disability	7
Hospitalisation	1
Neuropsychiatric events such suicide thoughts or self‐harm	2
Other outcomes e.g., impact on quality of life, sleep disturbances, patient distress, or physical management of pruritus such as bleeding b	135
Not reported	221
Number of patients with rebound urticaria
Yes	85 (23.1)
No	167 (45.4)
Not reported	116 (31.5)
Response to rechallenge (n = 160) c
Positive	156
Negative	0
Not reported	4
Naranjo's adverse drug probability scale score (n = 13) d
2	1
3	9
4	2
7	1

^a Each patient may be categorised into one or more outcomes. The adverse effects as per regulatory definitions encompass death, life‐threatening events, hospitalisation, disability and other serious important medical events.

^b Pooled results were reported as individual reactions were not segregated in the original study.

^c Positive rechallenge was resolution of pruritus after re‐initiation of antihistamine and recurrence of pruritus following subsequent tries at discontinuing the antihistamine.

^d Scoring for questionnaire for likelihood of an adverse drug reaction being caused by a drug: Definite (≥ 9), Probable [5, 6, 7, 8], Possible [1, 2, 3, 4], and Doubtful (≤ 0).

Cetirizine was the most frequently implicated antihistamine (n = 327, 88.9%), followed by levocetirizine (n = 39, 10.6%), and both cetirizine and levocetirizine (n = 2, 0.5%). No report was noted for other antihistamines. Antihistamines were most commonly prescribed for seasonal or perennial allergic conditions (87.8%) and allergic rhinitis (4.1%).

3.3. Characteristics of Rebound Pruritus After Discontinuation of Chronic Antihistamines

The duration of antihistamine use ranged between 0.3 to 276 months, with onset of pruritus occurring from 0.5 to 5 days following antihistamine discontinuation. Among cases that reported location of pruritus, the commonly affected sites included widespread (79.1%), extremities (7.9%) and both extremities and head, neck, or scalp (7.9%).

With regards to severity of adverse effects, a significant number of patients (n = 135) reported significant effects on patient outcomes such as quality of life and patient distress. Notably, one patient required hospitalisation, and two patients reported severe neuropsychiatric effects including thoughts of self‐harm or suicide, arising from rebound pruritus post discontinuation of therapy. This led to the continued use of antihistamine for nearly 20 years for one patient. Seven patient reported significant disability from the ensuing rebound pruritus.

3.4. Rebound Urticaria After Discontinuation of Chronic Antihistamines

Eighty‐five patients reported development of rebound urticaria after discontinuation of chronic antihistamines. Description of urticaria was provided in one case report, with onset of urticaria occurring two to three days after discontinuation of cetirizine, manifesting as non‐painful wheals over patient's forearm and trunk [16]. His symptoms resolved within days of cetirizine re‐initiation.

3.5. Pathophysiology of Rebound Pruritus or Urticaria After Discontinuation of Chronic Antihistamines

No study evaluated the pathophysiology of rebound pruritus or urticaria after discontinuation of chronic antihistamines.

3.6. Potential Factors Associated With Development of Rebound Pruritus or Urticaria After Discontinuation of Chronic Antihistamines

Only one study attempted to evaluate factors associated with the development of rebound pruritus or urticaria after discontinuation of chronic antihistamines [13]. Regular usage of cetirizine or levocetirizine for three months or greater was associated with this adverse reaction. Another study noted a female preponderance (75%) for the development of rebound pruritus or urticaria after discontinuation of chronic antihistamines [11]. However, these findings originate from observational studies and should be interpreted cautiously as hypothesis‐generating observations rather than established risk factors.

3.7. Management and Associated Outcomes for Rebound Pruritus After Discontinuation of Chronic Antihistamines

Table 3 summarises the management of rebound pruritus after discontinuation of chronic antihistamines. Re‐initiation of antihistamine was the most common strategy with a symptom resolution rate of 99.2%. Antihistamine tapering resulted in the resolution of symptoms in 33.3% of patients. While switching to an alternative antihistamine had the highest symptom resolution rate (1 of 1), it was limited by significant missing data with the outcome unreported in 30 of 31 cases. Other management strategies attempted with no or limited reports on efficacy included use of non‐steroidal and steroidal topicals, use of oral or parenteral steroids, and other measures such as cold compress use.

TABLE 3.

Summary of management and associated outcomes of rebound pruritus and urticaria across studies (n = 322).

Management	Frequency (%) unless otherwise specified	Resolution of rebound pruritus and urticaria, number of patients			Efficacy based on reported data a (%)
		Yes	No	Not reported
Re‐initiation of initial antihistamine	174	136	1	37	99.2
Tapering of antihistamine	42	11	22	9	33.3
Switch to alternative antihistamine	31	1	0	30	100
Abrupt discontinuation without restart or tapering	25	7 b	15	3	31.8
Other measures e.g., use of cool compress, low histamine diet, histamine‐2 blocker	17	0	0	17	Not available
Topical steroids	14	0	0	14	Not available
Oral or parenteral steroids	10	1	0	9	10
Non‐steroidal topical	9	0	0	9	Not available

^a Computed from responders/(responders + non responders) × 100%.

^b Includes patients with improvement or resolution of symptoms.

3.8. Proposed Monitoring and Management of Rebound Pruritus and Urticaria After Discontinuation of Chronic Antihistamines

Figure 2 depicts a proposed workflow for monitoring and management of rebound pruritus and urticaria after discontinuation of chronic antihistamines synthesised from the results of this review. Based on the reported number and efficacy of the management strategies, a tiered workflow was suggested to guide physicians with management of patients with this condition. The first line treatment recommendation would be antihistamine re‐initiation, congruent with recommendations from the manufacturer of cetirizine [17]. Noting the lack of antihistamine tapering regimes described by the identified articles, a duration of four weeks was suggested, drawing from antihistamine tapering guidelines in patients with chronic urticaria [18]. As there is currently no consensus on antihistamine tapering regimes, a gradual reduction in dose or frequency of antihistamine was considered reasonable [19].

FIGURE 2.

Proposed workflow for monitoring and management of rebound pruritus or urticaria after discontinuation of chronic antihistamine. ^#Sequence of recommended therapy synthesised based on reported rates of symptoms resolution and relative number of cases. ^Regimens that may be considered include every other day dosing, or reducing dose by half for 4 weeks before stopping.

4. Discussion

This is the first review which has summarised the course, risk factors and management of rebound pruritus or urticaria in patients who undergo discontinuation of chronic antihistamines. The findings of this review highlight an emerging but under‐recognised adverse drug phenomenon associated with chronic antihistamine use. Although antihistamines are generally considered safe and are widely available over the counter, the occurrence of rebound pruritus following discontinuation suggests that prolonged exposure may induce adaptive changes in histaminergic signalling pathways. Similar rebound phenomena have been described with other receptor‐modulating medications, such as proton pump inhibitors and topical corticosteroids, where receptor up‐regulation or altered receptor sensitivity contributes to symptom recurrence following treatment withdrawal.

In this review, female sex and the type of antihistamine used were identified as potential factors associated with this phenomenon. The female preponderance for rebound pruritus or urticaria observed may be linked to effects of sex‐linked hormones on immune responses [14]. Notably, oestrogens have been linked to greater immune humoral responses, auto‐immunity and allergic reactions which may be due to its effects on enhanced production of Th2 cytokines. Another potential cause could be the higher rates of allergic or atopic diseases in females [20].

Current literature has only implicated cetirizine and levocetirizine in rebound pruritus or urticaria with no reports noted for other antihistamines. One possible explanation may relate to differences in binding affinity of antihistamines to the H1 receptor [21]. Among antihistamines, levocetirizine and cetirizine have one of the highest affinities for histamine H1‐receptors [21, 22, 23]. Higher receptor affinity may lead to greater modulation of H1 receptor expression following prolonged exposure, through mechanisms such as inverse agonistic activity, hence increasing the risk of developing rebound pruritus or urticaria after discontinuation of therapy [24]. Overall, the precise mechanism underlying rebound pruritus following discontinuation remains unclear and the proposed explanation involving receptor modulation and compensatory histaminergic activity remains speculative, as none of the included studies directly evaluated the underlying pathophysiological mechanisms. Further mechanistic studies are needed to clarify this phenomenon. Another potential contributing factor for this finding could stem from the high use of cetirizine in the countries where the studies were conducted, with over 11 million prescriptions issued in 2023 in the United States [25].

In this review, a tiered workflow for monitoring and management of rebound pruritus after discontinuation of chronic antihistamines was proposed. The main strength of the workflow centers on using pooled data across four studies to generate management strategies based on rates of symptom resolution and the extent of available literature. Flexibility in shared decision making with the patient was also incorporated and accorded with safety nets, owing to the limited literature available.

Future research should focus on prospective observational studies to better characterise the incidence, risk factors, and clinical course of rebound pruritus following antihistamine discontinuation. In particular, studies comparing abrupt discontinuation with gradual tapering strategies may help determine optimal management approaches. Additionally, mechanistic studies evaluating histamine receptor expression or signalling following chronic antihistamine exposure may provide important insights into the biological basis of this phenomenon.

There were some limitations in our review. The currently available evidence is largely derived from case series and pharmacovigilance reports [10, 11, 13, 16]. As such, observed associations should be interpreted as preliminary signals rather than confirmed risk factors. The proposed clinical workflow was also intended as a pragmatic guide to support clinical awareness and inform future research rather than a formal management guideline. The second limitation was the inclusion of a small proportion of patients on antihistamines for under four weeks in the study by Konkel K et al. [13] Although the majority met the predefined criteria for chronic use, this variation may introduce heterogeneity in exposure definitions. Nonetheless, due to the study's relative importance to our review, it was included which may underestimate the true incidence of rebound pruritus or urticaria [13]. Thirdly, there were a significant proportion of missing data and inconsistencies in the reporting of rebound pruritus or urticaria in patients who discontinue antihistamines across the four studies. While attempts were made to contact the authors of the studies to mitigate the risk, these are likely driven by limitations from medication adverse effects databases as most cases were consumer or patient reported [26]. Databases such as the United States Of America Food and Drug Administration Adverse Event Reporting system that was used in two studies are also limited by incomplete or duplicated reports, potential under‐reporting due to voluntary reporting of adverse effects, inability to establish causality and compute incidence of adverse effects [26]. Lastly, most of the included studies and patients were from the United States, which may limit generalizability of the review findings to other countries due to differences in prescribing practices, patterns, formularies and drug availability.

5. Conclusion

Rebound pruritus after discontinuation of chronic cetirizine and levocetirizine use is a significant adverse effect that warrants careful monitoring and management. Potential factors associated with this condition include female sex and prolonged antihistamine use; however, these observations are derived from limited observational data and require confirmation in future studies. Current evidence supports cetirizine or levocetirizine re‐initiation in patients that experience this adverse effect, although other plausible strategies include tapering of antihistamines or switching to other antihistamines. Physicians should consider counselling patients who are initiating levocetirizine or cetirizine for chronic indications on this potential adverse effect. Future research is required to identify the optimal treatment strategy and if the discontinuation of other antihistamines could also lead to rebound pruritus.

Author Contributions

J.J.B.S. was the study's principal investigator and was responsible for the conception and design of the study. P.O. and N.C.T. were the co‐investigators. J.J.B.S., P.O., and N.C.T. were responsible for screening and the inclusion of relevant articles. J.J.B.S. and P.O. performed the data extraction from the included articles while all authors contributed to the interpretation of data. J.J.B.S. and P.O. prepared the initial draft of the manuscript. All authors revised the draft critically for important intellectual content and agreed to the final submission.

Funding

The publication cost is supported by SingHealth Polyclinics—Centre Grant 338 (CG21APR3006 (NMRC/CG3/001/2022‐SHP)).

Ethics Statement

The authors have nothing to report.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

File S1: cea70291‐sup‐0001‐FileS1.docx.

File S2: cea70291‐sup‐0002‐FileS2.xlsx.

Data Availability Statement

All data generated or analysed during this study are included in this published article.