, Volume 77, Issue 2, pp 175–186 | Cite as

Sedative Effects of Levocetirizine: A Systematic Review and Meta-Analysis of Randomized Controlled Studies

  • Kornkiat SnidvongsEmail author
  • Kachorn Seresirikachorn
  • Likhit Khattiyawittayakun
  • Wirach Chitsuthipakorn
Systematic Review



As a substrate of P-glycoprotein, levocetirizine should not cause sedative effects. However, while cetirizine, a mixture of levocetirizine and dextrocetirizine, can slightly penetrate the blood brain barrier, the sedative effects of levocetirizine are still under study.


The aim of this study was to investigate the sedative effects of levocetirizine.


An electronic literature search was performed using Medline and EMBASE from January 01, 2001 through August 6, 2015. Randomized controlled trials (RCTs) comparing levocetirizine with other antihistamines or placebo for patients with allergy and healthy subjects were selected. Primary outcome was risk ratio between levocetirizine and comparators. Secondary outcome was change in psychomotor speed. Data were pooled for meta-analysis using a fixed-effect model.


Forty-eight studies of 18,014 patients met the inclusion criteria. When compared to placebo, levocetirizine produced modest sedative effects (RR: 1.67; 95% CI 1.17, 2.38). However, when compared to other second-generation antihistamines, sedative effects of levocetirizine did not differ (RR: 1.23; 95% CI 0.96, 1.58). In subgroup analysis, there was no difference between the sedative effects of levocetirizine and fexofenadine (RR: 1.7; 95% CI 0.59, 4.88), desloratadine (RR: 1.58; 95% CI 0.9, 2.77), loratadine (RR: 1.56; 95% CI 0.28, 8.56), bilastine (RR: 1.17; 95% CI 0.48, 2.84), olopatadine (RR: 1.09; 95% CI 0.81, 1.47), azelastine (RR: 0.19; 95% CI 0.01, 3.68) and rupatadine (RR: 1.47; 95% CI 0.14, 15.72). When compared to first-generation antihistamines, levocetirizine had less sedative effects and less change of reaction time (mean difference: −250.76 s; 95% CI −338.53, −162.98).


Levocetirizine has modest sedative effects with a risk ratio of 1.67 when compared with placebo. The sedative effects observed for levocetirizine are not different from other second-generation antihistamines.


Risk Ratio Allergic Rhinitis Epworth Sleepiness Scale Cetirizine Loratadine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Authors contributions

Kornkiat Snidvongs: conception, development of protocol, study selection, data extraction, assessment of risk of bias, data analysis and interpretation, manuscript preparation. Kachorn Seresirikachorn: search strategy, study selection. Likhit Khattiyawittayakun: data extraction, assessment of risk of bias. Wirach Chitsuthipakorn: conception, development of protocol, critical review, final approval.

Compliance with Ethical Standards

Funding sources for the study

This was an unfunded study.

Authors’ financial disclosures

Kornkiat Snidvongs received honoraria for speaking at symposia for Merck Sharp & Dohme, GlaxoSmithKline, Takeda, Sanofi Aventis.

Kachorn Seresirikachorn, Likhit Khattiyawittayakun, and Wirach Chitsuthipakorn have no conflict of interest.

Supplementary material

40265_2016_682_MOESM1_ESM.eps (28 kb)
Fig. 1 Risk of bias graph: each risk of bias item presented as percentages across all included studies (EPS 28 kb)
40265_2016_682_MOESM2_ESM.eps (27 kb)
Fig. 2 Risk of bias summary: each risk of bias item for each included study (EPS 27 kb)
40265_2016_682_MOESM3_ESM.eps (93 kb)
Fig. 3 Funnel plot; risk of drowsiness: levocetirizine vs. other second-generation antihistaminesSE standard error, RR risk ratio (EPS 93 kb)
40265_2016_682_MOESM4_ESM.eps (529 kb)
Fig. 4 Funnel plot; risk of drowsiness: levocetirizine vs. placebo SE standard error, RR risk ratio (EPS 529 kb)


  1. 1.
    Bachert C. A review of the efficacy of desloratadine, fexofenadine, and levocetirizine in the treatment of nasal congestion in patients with allergic rhinitis. Clin Ther. 2009;31(5):921–44.CrossRefPubMedGoogle Scholar
  2. 2.
    Popov TA. Challenges in the management of chronic urticaria. World Allergy Organ J. 2011;4(3 Suppl):S28–31.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Gonzalez MA, Estes KS. Pharmacokinetic overview of oral second-generation H1 antihistamines. Int J Clin Pharmacol Ther. 1998;36(5):292–300.PubMedGoogle Scholar
  4. 4.
    De Sutter AI, Saraswat A, van Driel ML. Antihistamines for the common cold. Cochrane Database Syst Rev. 2015;(11):CD009345. doi: 10.1002/14651858.CD009345.pub2.
  5. 5.
    Yanai K, Rogala B, Chugh K, Paraskakis E, Pampura AN, Boev R. Safety considerations in the management of allergic diseases: focus on antihistamines. Curr Med Res Opin. 2012;28(4):623–42. doi: 10.1185/03007995.2012.672405.CrossRefPubMedGoogle Scholar
  6. 6.
    Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. The Cochrane Collaboration; 2011.
  7. 7.
    Review Manager (RevMan) [Computer program]. Version 5.1.6 ed. Copenhagen: The Nordic Cochrane Centre. The Cochrane Collaboration; 2011.Google Scholar
  8. 8.
    Anuradha P, Maiti R, Jyothirmai J, Mujeebuddin O, Anuradha M. Loratadine versus levocetirizine in chronic idiopathic urticaria: a comparative study of efficacy and safety. Indian J Pharmacol. 2010;42(1):12–6. doi: 10.4103/0253-7613.62399.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Bachert C, Bousquet J, Canonica GW, Durham SR, Klimek L, Mullol J, et al. Levocetirizine improves quality of life and reduces costs in long-term management of persistent allergic rhinitis. J Allergy Clin Immunol. 2004;114(4):838–44. doi: 10.1016/j.jaci.2004.05.070.CrossRefPubMedGoogle Scholar
  10. 10.
    Ciprandi G, Cirillo I, Vizzaccaro A, Tosca MA. Levocetirizine improves nasal obstruction and modulates cytokine pattern in patients with seasonal allergic rhinitis: a pilot study. Clin Exp Allergy. 2004;34(6):958–64. doi: 10.1111/j.1365-2222.2004.01960.x.CrossRefPubMedGoogle Scholar
  11. 11.
    Day JH, Briscoe MP, Rafeiro E, Ratz JD. Comparative clinical efficacy, onset and duration of action of levocetirizine and desloratadine for symptoms of seasonal allergic rhinitis in subjects evaluated in the environmental exposure unit (EEU). Int J Clin Pract. 2004;58(2):109–18.CrossRefPubMedGoogle Scholar
  12. 12.
    Devalia JL, De Vos C, Hanotte F, Baltes E. A randomized, double-blind, cross-over comparison among cetirizine, levocetirizine, and ucb 28557 on histamine-induced cutaneous responses in healthy adult volunteers. Allergy. 2001;56(1):50–7.CrossRefPubMedGoogle Scholar
  13. 13.
    Gandon JM, Allain H. Lack of effect of single and repeated doses of levocetirizine, a new antihistamine drug, on cognitive and psychomotor functions in healthy volunteers. Br J Clin Pharmacol. 2003;54:51–8.CrossRefGoogle Scholar
  14. 14.
    Grant JA, Riethuisen JM, Moulaert B, DeVos C. A double-blind, randomized, single-dose, cross-over comparison of levocetirizine with ebastine, fexofenadine, loratadine, mizolastine, and placebo: suppression of histamine-induced wheal-and-flare response during 24 hours in healthy male subjects. Ann Allergy Asthma Immunol. 2002;88(2):190–7. doi: 10.1016/S1081-1206(10)61995-3.CrossRefPubMedGoogle Scholar
  15. 15.
    Hindmarch I, Johnson S, Meadows R, Kirkpatrick T, Shamsi Z. The acute and sub-chronic effects of levocetirizine, cetirizine, loratadine, promethazine and placebo on cognitive function, psychomotor performance, and weal and flare. Curr Med Res Opin. 2001;17(4):241–55. doi: 10.1185/0300799019117011.CrossRefPubMedGoogle Scholar
  16. 16.
    Passalacqua G, Guerra L, Compalati E, Massacane P, Rogkakou A, Zanella C, et al. Comparison of the effects in the nose and skin of a single dose of desloratadine and levocetirizine over 24 hours. Int Arch Allergy Immunol. 2004;135(2):143–7. doi: 10.1159/000080657.CrossRefPubMedGoogle Scholar
  17. 17.
    Potter PC, Study G. Levocetirizine is effective for symptom relief including nasal congestion in adolescent and adult (PAR) sensitized to house dust mites. Allergy. 2003;58(9):893–9.CrossRefGoogle Scholar
  18. 18.
    Purohit A, Melac M, Pauli G, Frossard N. Twenty-four-hour activity and consistency of activity of levocetirizine and desloratadine in the skin. Br J Clin Pharmacol. 2003;56(4):388–94.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Stubner P, Zieglmayer R, Horak F. A direct comparison of the efficacy of antihistamines in SAR and PAR: randomised, placebo-controlled studies with levocetirizine and loratadine using an environmental exposure unit—the Vienna challenge chamber (VCC). Curr Med Res Opin. 2004;20(6):891–902. doi: 10.1185/030079904125003700.CrossRefPubMedGoogle Scholar
  20. 20.
    Verster JC, de Weert AM, Bijtjes SI, Aarab M, van Oosterwijck AW, Eijken EJ, et al. Driving ability after acute and sub-chronic administration of levocetirizine and diphenhydramine: a randomized, double-blind, placebo-controlled trial. Psychopharmacology. 2003;169(1):84–90. doi: 10.1007/s00213-003-1462-6.CrossRefPubMedGoogle Scholar
  21. 21.
    Wang DY, Hanotte F, De Vos C, Clement P. Effect of cetirizine, levocetirizine, and dextrocetirizine on histamine-induced nasal response in healthy adult volunteers. Allergy. 2001;56(4):339–43.CrossRefPubMedGoogle Scholar
  22. 22.
    Ciprandi G, Cirillo IG, Vizzaccaro A, Tosca MA. Levocetirizine improves nasal symptoms and airflow in patients with persistent allergic rhinitis: a pilot study. Eur Ann Allergy Clin Immunol. 2005;37(1):25–9.PubMedGoogle Scholar
  23. 23.
    de Blic J, Wahn U, Billard E, Alt R, Pujazon MC. Levocetirizine in children: evidenced efficacy and safety in a 6-week randomized seasonal allergic rhinitis trial. Pediatr Allergy Immunol. 2005;16(3):267–75. doi: 10.1111/j.1399-3038.2005.00216.x.CrossRefPubMedGoogle Scholar
  24. 24.
    Horak F, Zieglmayer PU, Zieglmayer R, Kavina A, Lemell P. Levocetirizine has a longer duration of action on improving total nasal symptoms score than fexofenadine after single administration. Br J Clin Pharmacol. 2005;60(1):24–31. doi: 10.1111/j.1365-2125.2005.02377.x.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Potter PC, Paediatric Levocetirizine Study G. Efficacy and safety of levocetirizine on symptoms and health-related quality of life of children with perennial allergic rhinitis: a double-blind, placebo-controlled randomized clinical trial. Ann Allergy Asthma Immunol. 2005;95(2):175–80. doi: 10.1016/S1081-1206(10)61208-2.CrossRefPubMedGoogle Scholar
  26. 26.
    Barnes ML, Ward JH, Fardon TC, Lipworth BJ. Effects of levocetirizine as add-on therapy to fluticasone in seasonal allergic rhinitis. Clin Exp Allergy. 2006;36(5):676–84. doi: 10.1111/j.1365-2222.2006.02478.x.CrossRefPubMedGoogle Scholar
  27. 27.
    Kapp A, Pichler WJ. Levocetirizine is an effective treatment in patients suffering from chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled, parallel, multicenter study. Int J Dermatol. 2006;45(4):469–74. doi: 10.1111/j.1365-4632.2005.02609.x.CrossRefPubMedGoogle Scholar
  28. 28.
    Nettis E, Colanardi MC, Barra L, Ferrannini A, Vacca A, Tursi A. Levocetirizine in the treatment of chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled study. Br J Dermatol. 2006;154(3):533–8. doi: 10.1111/j.1365-2133.2005.07049.x.CrossRefPubMedGoogle Scholar
  29. 29.
    Pasquali M, Baiardini I, Rogkakou A, Riccio AM, Gamalero C, Descalzi D, et al. Levocetirizine in persistent allergic rhinitis and asthma: effects on symptoms, quality of life and inflammatory parameters. Clin Exp Allergy. 2006;36(9):1161–7. doi: 10.1111/j.1365-2222.2006.02548.x.CrossRefPubMedGoogle Scholar
  30. 30.
    Lee CF, Sun HL, Lu KH, Ku MS, Lue KH. The comparison of cetirizine, levocetirizine and placebo for the treatment of childhood perennial allergic rhinitis. Pediatr Allergy Immunol. 2009;20(5):493–9. doi: 10.1111/j.1399-3038.2008.00816.x.CrossRefPubMedGoogle Scholar
  31. 31.
    Patel P, Patel D. Efficacy comparison of levocetirizine vs montelukast in ragweed sensitized patients. Ann Allergy Asthma Immunol. 2008;101(3):287–94. doi: 10.1016/S1081-1206(10)60494-2.CrossRefPubMedGoogle Scholar
  32. 32.
    Simons FE, Early Prevention of Asthma in Atopic Children Study G. Safety of levocetirizine treatment in young atopic children: an 18-month study. Pediatr Allergy Immunol. 2007;18(6):535–42. doi: 10.1111/j.1399-3038.2007.00558.x.CrossRefPubMedGoogle Scholar
  33. 33.
    Mansfield LE, Hampel F, Haeusler JM, Georges G. Study of levocetirizine in seasonal allergic rhinitis. Curr Med Res Opin. 2010;26(6):1269–75. doi: 10.1185/03007991003745233.CrossRefPubMedGoogle Scholar
  34. 34.
    Segall N, Gawchik S, Georges G, Haeusler JM. Efficacy and safety of levocetirizine in improving symptoms and health-related quality of life in US adults with seasonal allergic rhinitis: a randomized, placebo-controlled study. Ann Allergy Asthma Immunol. 2010;104(3):259–67. doi: 10.1016/j.anai.2009.12.003.CrossRefPubMedGoogle Scholar
  35. 35.
    Zuberbier T, Oanta A, Bogacka E, Medina I, Wesel F, Uhl P, et al. Comparison of the efficacy and safety of bilastine 20 mg vs levocetirizine 5 mg for the treatment of chronic idiopathic urticaria: a multi-centre, double-blind, randomized, placebo-controlled study. Allergy. 2010;65(4):516–28. doi: 10.1111/j.1398-9995.2009.02217.x.CrossRefPubMedGoogle Scholar
  36. 36.
    Hampel F, Ratner P, Haeusler JM. Safety and tolerability of levocetirizine dihydrochloride in infants and children with allergic rhinitis or chronic urticaria. Allergy Asthma Proc. 2010;31(4):290–5. doi: 10.2500/aap.2010.31.3349.CrossRefPubMedGoogle Scholar
  37. 37.
    Hong JB, Lee HC, Hu FC, Chu CY. A randomized, double-blind, active-controlled, parallel-group pilot study to compare the efficacy and sedative effects of desloratadine 5 mg with levocetirizine 5 mg in the treatment of chronic idiopathic urticaria. J Am Acad Dermatol. 2010;63(5):e100–2. doi: 10.1016/j.jaad.2010.03.007.CrossRefPubMedGoogle Scholar
  38. 38.
    Maiti R, Rahman J, Jaida J, Allala U, Palani A. Rupatadine and levocetirizine for seasonal allergic rhinitis: a comparative study of efficacy and safety. Arch Otolaryngol Head Neck Surg. 2010;136(8):796–800. doi: 10.1001/archoto.2010.128.CrossRefPubMedGoogle Scholar
  39. 39.
    Bautista AP, Eisenlohr CP, Lanz MJ. Nasal nitric oxide and nasal eosinophils decrease with levocetirizine in subjects with perennial allergic rhinitis. Am J Rhinol Allergy. 2011;25(6):383–7. doi: 10.2500/ajra.2011.25.3668.CrossRefPubMedGoogle Scholar
  40. 40.
    Marcucci F, Sensi LG, Abate P, Allocca G, Ugolini E, Di Cara G, et al. Anti-inflammatory activity and clinical efficacy of a 3-month levocetirizine therapy in mite-allergic children. Inflamm Allergy Drug Targets. 2011;10(1):32–8.CrossRefPubMedGoogle Scholar
  41. 41.
    Tzanetos DB, Fahrenholz JM, Scott T, Buchholz K. Comparison of the sedating effects of levocetirizine and cetirizine: a randomized, double-blind, placebo-controlled trial. Ann Allergy Asthma Immunol. 2011;107(6):517–22. doi: 10.1016/j.anai.2011.08.012.CrossRefPubMedGoogle Scholar
  42. 42.
    Guilemany JM, Garcia-Pinero A, Alobid I, Centellas S, Marino FS, Valero A, et al. The loss of smell in persistent allergic rhinitis is improved by levocetirizine due to reduction of nasal inflammation but not nasal congestion (the CIRANO study). Int Arch Allergy Immunol. 2012;158(2):184–90. doi: 10.1159/000331329.CrossRefPubMedGoogle Scholar
  43. 43.
    Jantarat C, Keskanokwong T. Pharmacokinetic and bioequivalence evaluation of two formulations of levocetirizine 5 mg in healthy Thai volunteers. Thai J Pharm Sci. 2013;37:1–11.Google Scholar
  44. 44.
    Schoepke N, Church MK, Maurer M. The inhibition by levocetirizine and fexofenadine of the histamine-induced wheal and flare response in healthy Caucasian and Japanese volunteers. Acta Derm Venereol. 2013;93(3):286–93. doi: 10.2340/00015555-1490.CrossRefPubMedGoogle Scholar
  45. 45.
    Yonekura S, Okamoto Y, Yamamoto H, Sakurai T, Linuma T, Sakurai D, et al. Randomized double-blind study of prophylactic treatment with an antihistamine for seasonal allergic rhinitis. Int Arch Allergy Immunol. 2013;162:71–8.CrossRefPubMedGoogle Scholar
  46. 46.
    Mahajan S, Gupta V, Gupta A, Matreja PS, Singh A, Khanna P, et al. Efficacy and safety of azelastine and levocetirizine in allergic rhinitis. J Pak Med Stud. 2013;3(3):143–7.Google Scholar
  47. 47.
    Munoz-Cano R, Valero A, Izquierdo I, Sanchez-Lopez J, Domenech A, Bartra J, et al. Evaluation of nasal symptoms induced by platelet activating factor, after nasal challenge in both healthy and allergic rhinitis subjects pretreated with rupatadine, levocetirizine or placebo in a cross-over study design. Allergy Asthma Clin Immunol. 2013;9(1):43. doi: 10.1186/1710-1492-9-43.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Sil A, Tripathi SK, Chaudhuri A, Das NK, Hazra A, Bagchi C, et al. Olopatadine versus levocetirizine in chronic urticaria: an observer-blind, randomized, controlled trial of effectiveness and safety. J Dermatol Treat. 2013;24(6):466–72. doi: 10.3109/09546634.2012.750414.CrossRefGoogle Scholar
  49. 49.
    Takeo T, Kasugai C, Tanaka R, Ando T, Ogawa A, Akita Y, et al. Evaluation of the antihistamine effects of olopatadine and levocetirizine during a 24-h period: a double-blind, randomized, cross-over, placebo-controlled comparison in skin responses induced by histamine iontophoresis. J Dermatol. 2013;40(12):987–92. doi: 10.1111/1346-8138.12326.CrossRefPubMedGoogle Scholar
  50. 50.
    Hiraoka K, Tashiro M, Grobosch T, Maurer M, Oda K, Toyohara J, et al. Brain histamine H1 receptor occupancy measured by PET after oral administration of levocetirizine, a non-sedating antihistamine. Expert Opin Drug Saf. 2015;14(2):199–206. doi: 10.1517/14740338.2015.989831.CrossRefPubMedGoogle Scholar
  51. 51.
    Johnson M, Kwatra G, Badyal D, Thomas E. Levocetirizine and rupatadine in chronic idiopathic urticaria. Int J Dermatol. 2015;54:1199–204.CrossRefPubMedGoogle Scholar
  52. 52.
    Snidvongs K, Rotjanasiriphong C, Phannaso C, Chusakul S, Aeumjaturapat S. Fexofenadine and levocetirizine have equivalent effectiveness for persistent allergic rhinitis. Asian Biomed. 2015;93:1–9.Google Scholar
  53. 53.
    Potter PC, Kapp A, Maurer M, Guillet G, Jian AM, Hauptmann P, et al. Comparison of the efficacy of levocetirizine 5 mg and desloratadine 5 mg in chronic idiopathic urticaria patients. Allergy. 2009;64(4):596–604. doi: 10.1111/j.1398-9995.2008.01893.x.CrossRefPubMedGoogle Scholar
  54. 54.
    Ozdemir PG, Karadag AS, Selvi Y, Boysan M, Bilgili SG, Aydin A, et al. Assessment of the effects of antihistamine drugs on mood, sleep quality, sleepiness, and dream anxiety. Int J Psychiatry Clin Pract. 2014;18(3):161–8. doi: 10.3109/13651501.2014.907919.CrossRefPubMedGoogle Scholar
  55. 55.
    Vacchiano C, Moore J, Rice GM, Crawley G. Fexofenadine effects on cognitive performance in aviators at ground level and simulated altitude. Aviat Space Environ Med. 2008;79(8):754–60.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  1. 1.Department of Otolaryngology, Faculty of MedicineChulalongkorn UniversityBangkokThailand
  2. 2.Department of OtolaryngologySawan Pracharak HospitalNakhon SawanThailand

Personalised recommendations