Fexofenadine Hydrochloride: Antihistamine for Allergic Diseases

Fexofenadine hydrochloride is an antihistamine that is taken to help treat allergy symptoms, such as a runny nose, itchy or watery eyes, sneezing, or an itchy nose or throat. Common side effects may include vomiting, headache, diarrhea, dizziness, and drowsiness. If you have trouble swallowing tablets, this drug comes in other forms, including tablets that dissolve in your mouth and a liquid.

Fexofenadine hydrochloride in the treatment of allergic disease

The allergic response in people with atopic disorders involves exposure of the immune system to the antigen, antigen presentation, mediator release with amplification signals, and production of antigen specific IgE, which binds to mast cells. Upon re-exposure to the allergen, bridging of the mast cell bound allergen specific IgE results in the release of preformed and newly synthesized bioactive and pro-inflammatory mediators, which results in the symptoms of allergic rhinitis and chronic idiopathic urticaria, and contributes to the symptoms of atopic dermatitis and allergic asthma. Antihistamines form the cornerstone of treatment for allergic disorders. Fexofenadine hydrochloride has been marketed in the US as a selective H1 antagonist since 2000. However, the drug appears to exhibit some anti-inflammatory activity. The US Food and Drug Administration (FDA) approved an oral suspension of fexofenadine on October 16, 2006. The approval is for twice-daily dosing, for the treatment of symptoms associated with seasonal allergic rhinitis, in patients 2 to 11 years of age, and for the treatment of symptoms of chronic idiopathic urticaria, in patients 6 months to 11 years of age. The studies cited in this text provide information based upon other oral formulations of fexofenadine. Information on fexofenadine hydrochloride oral suspension remains sparse. Information based upon efficacy studies financially supported only by the manufacturer is not included, unless stated in the text.[1]

Although high doses of fexofenadine do not appear to provide much toxicity, interaction with other drugs that use the P450 CYP3A4 degradation pathway, P-glycoprotein and the organic anion transporter peptides, prominent transporter proteins, may increase the risks of adverse events. The FDA approved fexofenadine hydrochloride for treatment of the symptoms of allergic rhinitis and chronic idiopathic urticaria. The drug appeared effective in the treatment of its indicated conditions. Subjects tolerated fexofenadine well. However, concern remains regarding fexofenadine’s interactions with other medications that use the P-glycoprotein and the organic anion transporter peptides, which may result in an increased risk of adverse events to those other medications. This concern comes from the pharmacokinetic data, which suggest that although only a small proportion of fexofenadine hydrochloride is metabolized, fexofenadine moves into and out of the blood and tissues by at least P-glycoprotein and organic anion transporter peptides, which transport a number of other medications. In addition to blocking H1 receptors, fexofenadine hydrochloride appears to diminish the production of LTC4, LTD4, and LTE4, PGE2, and PGF2α; inhibits cyclo-oxygenase 2; inhibits the generation of thromboxane (perhaps through cyclo-oxygenase 2); and limits iNOS generation of NO, as well as ICAM-1, ELAM-1, VCAM-1, RANTES, I-TAC, MDC, TARC, MMP-2, MMP-9, and tryptase, which may contribute to its benefit.

Urticaria management with fexofenadine hydrochloride

Urticaria and angioedema are frequent conditions among the general population requiring medical consultation, diagnostic testing, and implementation of preventive and pharmacological approaches to control the disabling symptoms suffered by the patient. Second-generation antihistamines are the first-line pharmacological approach to resolve urticaria’ symptoms. Fexofenadine hydrochloride (HCl) is one of the second-generation antihistamines available on the market and a valid option for the treatment of urticaria in adult and pediatric populations. The present article provides an updated review of the current knowledge on urticaria with a focus on the efficacy and safety of fexofenadine hydrochloride (HCl). A literature search was conducted on Embase and Medline. Eligible articles included information on urticaria prevalence, classification, pathogenesis, etiology, disease burden, impact on patient’s quality of life (QoL), diagnostic approach and practical management, and clinical studies on the safety and/or efficacy of fexofenadine HCl. The search was limited to articles published in English between 1999 and 2020 and a total of 180 publications were reviewed. Following the outbreak of the coronavirus disease 2019 (COVID-19) and the occurrence of urticaria manifestations in COVID-19 patients, available studies on this matter are also briefly discussed.[2]

As a second-generation, non-sedating antihistamine, fexofenadine hydrochloride has been widely used in allergic diseases and is available as an oral tablet, or liquid suspension for the control of urticaria symptoms. The approved dose for the treatment of chronic urticaria is oral tablet 180 mg once a day or 60 mg orally 2 times a day both in adults and children 12 years and older. In adults, second-generation antihistamines are not considered to be cardiotoxic (e.g. potassium channel blockade or QT interval prolongation). In healthy individuals, fexofenadine hydrochloride did not prolong QTc or decrease heart rate. Prolongation of QTc occurs through blockade of potassium channels in ventricular myocytes, leading to a delay in ventricular repolarization; fexofenadine HCl does not appear to block this channel. The burden of acute and chronic urticaria is high, in terms of patient quality of life and disability-adjusted life years. The aim of treatment for urticaria is that of full control of the associated wheals and angioedema, and second-generation anti-histamines such as fexofenadine hydrochloride have been shown to significantly reduce these symptoms whilst being well-tolerated. Recently, urticaria has been reported as a manifestation of COVID-19, however further analyses are needed to fully establish the link.

Antihistamine effects and safety of fexofenadine

The incidence of allergic diseases such as allergic rhinitis (AR), allergic asthma (AA), chronic idiopathic urticaria (CIU) and atopic dermatitis (AD) has continued to rise over the past several decades, affecting a large number of people worldwide. Symptoms such as itching, sneezing, rhinorrhea and rhinobyon caused by allergic diseases usually lower the quality of life. However, some of the second-generation antihistamines, such as terfenadine and astemizole, are rarely used because of their apparent cardiotoxicity. As a new generation antihistamine and an active metabolite of terfenadine - a highly selective H1 antagonist, fexofenadine hydrochloride has positive antihistamine effects. As the substrate of P-glycoprotein, fexofenadine that is difficult to pass the blood-brain barrier may have no sedative effect and other central nervous functions. To date, there is still a lack of collective evidence regarding the antihistamine effects and safety profiles of fexofenadine hydrochloride relative to other antihistamine drugs and placebo. As such, the aim of this study was to analyze the antihistamine effects and safety of fexofenadine in healthy subjects and patients with allergic diseases including AR, AA, CIU, and AD when compared with other antihistamines or placebo.[3]

Based on our review of the literature, this is the first meta-analysis to assess the antihistamine effects and sedative effects of fexofenadine.  Fexofenadine hydrochloride has a positive antihistamine effect, which is probably no worse than the second-generation antihistamines. Fexofenadine probably has a favorable safety profile, which is more likely better than that of the first-generation antihistamines. There is lack of data to support that fexofenadine has a better overall safety profile compared to the second-generation antihistamines, however, some presently available evidence on sedative effects and certain aspects of cognitive/psychomotor function favors fexofenadine. Therefore, fexofenadine may be worthy of recommendation for safety related workers. However, more multicenter, large sample, long-term follow-up and well-designed head-to-head trials are required to the further understanding of the efficacy and safety of fexofenadine hydrochloride.

References

[1]Axelrod D, Bielory L. Fexofenadine hydrochloride in the treatment of allergic disease: a review. J Asthma Allergy. 2008 Sep 19;1:19-29. doi: 10.2147/jaa.s3092. PMID: 21436982; PMCID: PMC3121339.

[2]Ansotegui IJ, Bernstein JA, Canonica GW, Gonzalez-Diaz SN, Martin BL, Morais-Almeida M, Murrieta-Aguttes M, Sanchez Borges M. Insights into urticaria in pediatric and adult populations and its management with fexofenadine hydrochloride. Allergy Asthma Clin Immunol. 2022 May 13;18(1):41. doi: 10.1186/s13223-022-00677-z. Erratum in: Allergy Asthma Clin Immunol. 2022 Jul 23;18(1):65. doi: 10.1186/s13223-022-00705-y. PMID: 35562767; PMCID: PMC9103601.

[3]Huang CZ, Jiang ZH, Wang J, Luo Y, Peng H. Antihistamine effects and safety of fexofenadine: a systematic review and Meta-analysis of randomized controlled trials. BMC Pharmacol Toxicol. 2019 Nov 29;20(1):72. doi: 10.1186/s40360-019-0363-1. PMID: 31783781; PMCID: PMC6884918.

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