Fexofenadine

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Continuing Education Activity

Fexofenadine is a metabolite of terfenadine and is a second-generation antihistamine. It is FDA approved to treat seasonal allergic rhinitis and chronic idiopathic urticaria. Fexofenadine is a medication used to manage and treat allergic rhinitis and chronic urticaria. Fexofenadine has approval for use in both children and adults. Children should be six months old or older, dependent upon the indication for use. This activity outlines the indications, action, and contraindications for fexofenadine as a valuable agent in treating allergic rhinitis and chronic urticaria. In addition, this activity will highlight the mechanism of action, adverse event profile, and other key factors (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, and relevant interactions) pertinent to members of the interprofessional team in the treatment of patients with seasonal allergic rhinitis and related conditions.

Objectives:

  • Identify the mechanism of action of fexofenadine.
  • Describe the adverse effects of fexofenadine.
  • Review the appropriate monitoring for the toxicity of fexofenadine.
  • Summarize interprofessional team strategies for improving care coordination and communication to advance fexofenadine and improve outcomes.

Indications

Fexofenadine is a metabolite of terfenadine and is a second-generation antihistamine. It is FDA approved to treat seasonal allergic rhinitis and chronic idiopathic urticaria. Fexofenadine has approval for use in both children and adults. Children should be six months old or older, dependent upon the indication for use.[1]

  • Seasonal allergic rhinitis is characterized by symptoms including nasal itching, sneezing, rhinorrhea, and nasal congestion, though antihistamines are less useful for nasal congestion symptoms. These symptoms can be triggered by seasonal or perennial allergens, including grass, pollens, dust, pet dander, mold, and others.[2] 
  • In a double-blind,placebo-controlled, randomized trial, compared with loratadine, fexofenadine had similar safety and efficacy. However, fexofenadine worked more effectively for eye symptoms and nasal congestion symptoms.[3]
  • As the name implies, chronic idiopathic urticaria is a chronic condition due to spontaneous mast cell degranulation.[2] Symptomatic triggers include water, sweat, sun, cold, or pressure and can consist of dermatographism and urticarial rash. ACE inhibitors and NSAIDs may also induce chronic urticaria.[4] Fexofenadine has also been used to treat cholinergic urticaria.[5]

Mechanism of Action

The mechanism of action of fexofenadine is to selectively antagonize H1 receptors on the surface of cells in different organ systems. It is a second-generation H1 receptor blocker. Fexofenadine also affects inflammatory mediators.[6][7] Compared to other first-generation antihistamines, fexofenadine crosses the blood-brain barrier to a minimal extent and thus does not cause drowsiness like other H1 blockers. Second-generation antihistamines such as fexofenadine have less affinity for cholinergic and alpha-adrenergic receptors and therefore display minimal anticholinergic effect.

In a study, second-generation antihistamines like desloratadine and loratadine demonstrated anticholinergic activity, but fexofenadine displayed no anticholinergic activity and high specificity for H1 receptors. Consequently, fexofenadine is one of the least sedating second-generation antihistamines.[8] Fexofenadine can also inhibit other mechanisms such as mast cell, basophilic histamine, and inflammatory cell release.[9] Prolonged use of fexofenadine does not cause tachyphylaxis.[10] Meta-analysis results revealed that the antihistamine effects of fexofenadine measured by the histamine-induced wheal and flare inhibition rate are significantly higher than placebo and are not different compared with the other second-generation antihistamines.[11]

Pharmacokinetics

Absorption: Fexofenadine is rapidly absorbed, attaining peak plasma concentrations one hour after oral administration at 1 hour for the oral suspension and 1.5 hours for the tablet. Maximum histamine inhibition is achieved approximately 1–2 h after administration. Fexofenadine is a long-acting antihistamine that allows for once-a-day administration.[12]

Distribution: Fexofenadine has approximately 60% to 70% plasma protein binding. Fexofenadine binds primarily with albumin and alpha-1 acid glycoprotein. Fexofenadine shows no receptor occupancy in the CNS at clinically relevant doses.[13]

Metabolism: Fexofenadine undergoes minimal hepatic metabolism. OATP2B1(Organic anion transporting polypeptides) and P-gp(permeability glycoprotein) play an essential role in the metabolism and transport of fexofenadine. P-gp is involved in intestinal secretion and systemic disposition of fexofenadine.[14]

Elimination: In healthy volunteers, the mean elimination half-life is approximately 14.4 hours after administering fexofenadine 60 mg twice daily. Fexofenadine is mainly excreted in feces via biliary excretion (80%). The half-life may be significantly prolonged in patients with renal disease.[15]

Administration

Fexofenadine comes in multiple different forms. It may be administered orally as a tablet, oral suspension (syrup), or orally disintegrating tablets. Fexofenadine may be used in adults and children, though the dose for children is lower than that of adults (up to 60 mg vs. 180 mg daily PO).

ODT tablets are branded and should be placed on the tongue, allowed to dissolve (with or without water) then swallowed. Patients should not chew and should take the medication before eating or drinking.

  • ODT tablets are typically used in pediatric patients, and dosing is 30 mg PO BID for ages 6 to 12 for seasonal allergic rhinitis and chronic urticaria.[16]

Adult Dosing

  • The dose for seasonal allergic rhinitis and chronic urticaria is 60 mg PO BID or 180 mg PO daily.
  • According to the American college of allergy, asthma & immunology (ACAAI) and American academy of allergy asthma & immunology (AAAAI) recommendations, a second-generation antihistamine such as fexofenadine is safe and effective. It is considered one of the first-line agents for treating chronic urticaria.[17]

Pediatrics Dosing (differs based on age and indication)

  • Seasonal Allergic Rhinitis 
    • Not approved for use in children less than two years of age
    • Children 2-12 years old: 30 mg PO BID
    • Children older than 12 years old: 60 mg PO BID or 180 mg PO daily
  • Chronic Urticaria
    • Not approved for use in infants less than six months old
    • Children 6 months to 2 years old: 15 mg PO BID
    • Children 2-12 years old: 30 mg PO BID
    • Children older than 12 years: 60 mg PO BID or 180 mg PO daily

Use in Specific Patient Population

Patients with Hepatic Impairment: The product manufacturer has not reported information on dose adjustment based on hepatic function.

Patients with Renal Impairment: (creatinine clearance less than 80 ml/min).

  • Adults should take 60 mg PO daily.
  • Dosing for pediatric patients with renal impairment varies by age as follows:
    • Children 6 months to 2 years old: 15 mg PO daily
    • Children 2-12 years old: 30 mg PO daily
    • Children older than 12 years: 60 mg PO daily
    • ESRD decreases nonrenal transporter function, as evident by a 63% decrease in clearance and a 2.8-fold increase in AUC for fexofenadine. Consequently, dose reduction is required in patients with ESRD.[18]

Pregnancy Considerations: Fexofenadine is not usually prescribed during pregnancy (former FDA pregnancy category C), and other antihistamines with more data could be used.[19] In a large nationwide cohort study, no association was evident between fexofenadine use during pregnancy and the risk of congenital malformations or stillbirth.[20] According to the ACOG (American college of obstetricians & gynecologists) and the ACAAI, a first-generation antihistamine such as chlorpheniramine is preferred. If the patient is intolerant to chlorpheniramine, loratadine, desloratadine, and cetirizine can be used after the first trimester.[21][22][23]

Breastfeeding Considerations: Fexofenadine might decrease milk production, especially if used with pseudoephedrine. While breastfeeding an infant, monitor for possible irritability and jitteriness.[24][25]

Adverse Effects

Reported side effects in a meta-analysis of other random, double-blind, placebo-controlled studies versus placebo are as follows[11]:

  • Headache
  • Epistaxis
  • Upper respiratory complaints include infection, sore throat, cough, and sinusitis.
  • Rash
  • Asthma
  • Infection
  • GI symptoms include abdominal pain, nausea, and diarrhea
  • Leukopenia
  • Back pain
  • Weakness
  • Sedation/drowsiness
  • Dry mouth[26]

The most frequently occurring side effects are drowsiness, fatigue, and dry mouth, which may occur in larger doses.[26]

Post-marketing surveillance has reported rare cases of Stevens-Johnson syndrome/Toxic Epidermal Necrolysis induced by fexofenadine.[27]

Drug-Drug and Drug-Food Interactions

  • It is essential to note that taking fexofenadine(regardless of the route of administration) with grapefruit, apple, or orange juice decreases bioavailability. This reduced bioavailability is because of the inhibition of the P-glycoprotein transporter (P-gp). Patients should be advised to separate the administration of fexofenadine and any of these juices by at least 4 hours.[28] 
  • Green tea can decrease the bioavailability of fexofenadine by inhibiting OATP1A2-mediated intestinal absorption of fexofenadine and reducing the efficacy of fexofenadine.[29]
  • Betahistine is an antagonist of histamine H3 receptors, a weak agonist of H1 receptors; consequently can decrease the therapeutic potential of fexofenadine.[30]
  • Pilolisant is a histamine-3 receptor antagonist and inverse agonist approved for narcolepsy. Concurrent use of antihistamines should be avoided.[31]
  • Concurrent administration of apalutamide with transporter substrates for P-glycoprotein (P-gp), i.e., fexofenadine, decreases the AUC of fexofenadine by 30%, which may result in loss of efficacy of fexofenadine.[32]

Contraindications

Hypersensitivity to fexofenadine or any of its components is the only true contraindication to this medication's use. There is little hepatic involvement in the clearance of this medication, so it is safe for patients with liver pathology. However, caution is necessary when treating patients with renal disease, and as noted above, renal dosing should be followed.[33]

There is no significant interaction between fexofenadine and concomitant use of alcohol or food. However, bioavailability decreases when used with grapefruit, apple, or orange juices.[34]

In animal models, fexofenadine has been shown to cause low birth weight and is currently a category C medication in pregnancy. Alternatives for symptom relief of allergic rhinitis include loratadine and cetirizine.[35]

Orally disintegrating tablets may contain phenylalanine as an excipient; caution is advised in patients with phenylketonuria.[36]

Monitoring

Monitoring fexofenadine involves monitoring for improvement or worsening of symptoms with use. Because of fexofenadine's close relationship with cardiotoxic terfenadine, patients with underlying cardiac conditions may need to be monitored with periodic EKG to watch for QT-prolongation and arrhythmias.[37]

A study out of Vietnam compared fexofenadine and levocetirizine for chronic urticaria. The study found that doses two times the recommended dosing showed improved urticarial symptoms without increasing adverse effects. The most common side effects noted were fatigue and drowsiness, which occurred at the same rates in patients taking the recommended dose rather than the higher dose. This same study mentions a European study in which dosing was quadrupled and had similar adverse effects.[38]

Monitor the quality of life using chronic urticaria quality of life questionnaire (CU-Q2oL) and the impact of fexofenadine therapy resulting in reduced urticaria symptoms by urticaria activity score (UAS7).[39]

Toxicity

As previously mentioned, fexofenadine is a metabolite of terfenadine, which proved to have cardiotoxic effects. Terfenadine blocked cardiac potassium channels, which, when taken in large doses or with other medications such as ketoconazole, caused prolonged QT intervals. Prolonged QT interval can lead to fatal arrhythmias. According to FDA guidelines, fexofenadine has replaced terfenadine in the United States because it does not block potassium channels. In multiple studies, it did not cause any arrhythmias or significantly prolonged QT intervals.[37]

Despite the findings of these studies, other case reports have found a relationship between fexofenadine and QT-interval elongation and ventricular arrhythmia though it is very rare. It is worth mentioning that using fexofenadine with hepatic CYP3A4 blockers (such as erythromycin and ketoconazole) can increase its concentration in the blood, and combined use with drugs such as rifampin and troglitazone will decrease the concentration. These effects are likely due to the interaction between these compounds and the P-glycoprotein transporter, removing fexofenadine from the blood.[40]

There is no antidote for fexofenadine. In case of overdose, treatment is mainly supportive. Contact the poison control center or medical toxicologist if multiple substance exposure is suspected.[41]

Enhancing Healthcare Team Outcomes

Fexofenadine is a commonly used medication for seasonal allergic rhinitis and chronic urticaria and is an overall safe and effective therapy when used correctly. While it is available to patients without a prescription, care is necessary when starting any new medication. Patients should discuss fexofenadine with their primary care providers and pharmacists to educate themselves on side effects, recommended dosing, and possible interactions with commonly ingested items such as fruit juices. Clinicians should ensure that renal and pediatric patients take the appropriate adjusted fexofenadine dosage. Immunologists should be consulted in refractory urticaria or allergic rhinitis. Nurses should verify the dose at each visit and reevaluate the patient periodically for the need for fexofenadine. Pharmacists should check drug interactions and perform medication reconciliation when counseling patients. In the overdose of fexofenadine, a critical care physician and medical toxicologist should be consulted.

The patient should be referred to a psychiatrist if the overdose is intentional. Collaboration and coordination between the interprofessional team of clinicians (MD, DO, NP, PA), specialists including immunologists, nursing staff, and pharmacists, would result in improved patient outcomes related to fexofenadine therapy. According to the European academy of allergy and clinical immunology, interprofessional and integrated care between clinicians, specialists, nurses, dietitians, psychologists, physician assistants, and pharmacists can enhance patient-centered care of allergic disorders in community care settings.[42] [Level 5]


Article Details

Article Author

Kari L. Craun

Article Editor:

Mark P. Schury

Updated:

12/5/2022 7:21:55 PM

References

[1]

Devillier P,Roche N,Faisy C, Clinical pharmacokinetics and pharmacodynamics of desloratadine, fexofenadine and levocetirizine : a comparative review. Clinical pharmacokinetics. 2008;     [PubMed PMID: 18336052]

[2]

Randall KL,Hawkins CA, Antihistamines and allergy. Australian prescriber. 2018 Apr;     [PubMed PMID: 29670310]

[3]

Van Cauwenberge P,Juniper EF, Comparison of the efficacy, safety and quality of life provided by fexofenadine hydrochloride 120 mg, loratadine 10 mg and placebo administered once daily for the treatment of seasonal allergic rhinitis. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2000 Jun;     [PubMed PMID: 10848909]

[4]

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, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology. 2022 May 13     [PubMed PMID: 35562767]

[5]

Iijima S,Kojo K,Takayama N,Hiragun M,Kan T,Hide M, Case of cholinergic urticaria accompanied by anaphylaxis. The Journal of dermatology. 2017 Nov     [PubMed PMID: 28665007]

[6]

Mahatme MS,Dakhale GN,Tadke K,Hiware SK,Dudhgaonkar SD,Wankhede S, Comparison of efficacy, safety, and cost-effectiveness of montelukast-levocetirizine and montelukast-fexofenadine in patients of allergic rhinitis: A randomized, double-blind clinical trial. Indian journal of pharmacology. 2016 Nov-Dec;     [PubMed PMID: 28066101]

[7]

Kawauchi H,Yanai K,Wang DY,Itahashi K,Okubo K, Antihistamines for Allergic Rhinitis Treatment from the Viewpoint of Nonsedative Properties. International journal of molecular sciences. 2019 Jan 8;     [PubMed PMID: 30626077]

[8]

Orzechowski RF,Currie DS,Valancius CA, Comparative anticholinergic activities of 10 histamine H1 receptor antagonists in two functional models. European journal of pharmacology. 2005 Jan 4     [PubMed PMID: 15627436]

[9]

Canonica GW,Blaiss M, Antihistaminic, anti-inflammatory, and antiallergic properties of the nonsedating second-generation antihistamine desloratadine: a review of the evidence. The World Allergy Organization journal. 2011 Feb     [PubMed PMID: 23268457]

[10]

Meltzer EO,Rosario NA,Van Bever H,Lucio L, Fexofenadine: review of safety, efficacy and unmet needs in children with allergic rhinitis. Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology. 2021 Nov 2;     [PubMed PMID: 34727966]

[11]

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 pharmacology & toxicology. 2019 Nov 29     [PubMed PMID: 31783781]

[12]

Simpson K,Jarvis B, Fexofenadine: a review of its use in the management of seasonal allergic rhinitis and chronic idiopathic urticaria. Drugs. 2000 Feb;     [PubMed PMID: 10730552]

[13]

Cole S,Bagal S,El-Kattan A,Fenner K,Hay T,Kempshall S,Lunn G,Varma M,Stupple P,Speed W, Full efficacy with no CNS side-effects: unachievable panacea or reality? DMPK considerations in design of drugs with limited brain penetration. Xenobiotica; the fate of foreign compounds in biological systems. 2012 Jan;     [PubMed PMID: 21970687]

[14]

Akamine Y,Miura M, An update on the clinical pharmacokinetics of fexofenadine enantiomers. Expert opinion on drug metabolism & toxicology. 2018 Apr     [PubMed PMID: 29635947]

[15]

Martinez JM,Khier S,Morita S,Rauch C,Fabre D, Population pharmacokinetic analysis of fexofenadine in Japanese pediatric patients. Journal of pharmacokinetics and pharmacodynamics. 2014 Apr     [PubMed PMID: 24633780]

[16]

Meltzer EO,Scheinmann P,Rosado Pinto JE,Bachert C,Hedlin G,Wahn U,Finn AF Jr,Ruuth E, Safety and efficacy of oral fexofenadine in children with seasonal allergic rhinitis--a pooled analysis of three studies. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 2004 Jun;     [PubMed PMID: 15209959]

[17]

Bernstein JA,Lang DM,Khan DA,Craig T,Dreyfus D,Hsieh F,Sheikh J,Weldon D,Zuraw B,Bernstein DI,Blessing-Moore J,Cox L,Nicklas RA,Oppenheimer J,Portnoy JM,Randolph CR,Schuller DE,Spector SL,Tilles SA,Wallace D, The diagnosis and management of acute and chronic urticaria: 2014 update. The Journal of allergy and clinical immunology. 2014 May     [PubMed PMID: 24766875]

[18]

Nolin TD,Frye RF,Le P,Sadr H,Naud J,Leblond FA,Pichette V,Himmelfarb J, ESRD impairs nonrenal clearance of fexofenadine but not midazolam. Journal of the American Society of Nephrology : JASN. 2009 Oct;     [PubMed PMID: 19696225]

[19]

Murase JE,Heller MM,Butler DC, Safety of dermatologic medications in pregnancy and lactation: Part I. Pregnancy. Journal of the American Academy of Dermatology. 2014 Mar     [PubMed PMID: 24528911]

[20]

Andersson NW,Torp-Pedersen C,Andersen JT, Association Between Fexofenadine Use During Pregnancy and Fetal Outcomes. JAMA pediatrics. 2020 Aug 1;     [PubMed PMID: 32478810]

[21]

Kar S,Krishnan A,Preetha K,Mohankar A, A review of antihistamines used during pregnancy. Journal of pharmacology & pharmacotherapeutics. 2012 Apr     [PubMed PMID: 22629082]

[22]

Powell RJ,Leech SC,Till S,Huber PA,Nasser SM,Clark AT,British Society for Allergy and Clinical Immunology., BSACI guideline for the management of chronic urticaria and angioedema. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2015 Mar     [PubMed PMID: 25711134]

[23]

Andersson NW,Poulsen HE,Andersen JT, Desloratadine Use During Pregnancy and Risk of Adverse Fetal Outcomes: A Nationwide Cohort Study. The journal of allergy and clinical immunology. In practice. 2020 May     [PubMed PMID: 32142963]

[24]

Fexofenadine Drugs and Lactation Database (LactMed). 2006     [PubMed PMID: 29999736]

[25]

Butler DC,Heller MM,Murase JE, Safety of dermatologic medications in pregnancy and lactation: Part II. Lactation. Journal of the American Academy of Dermatology. 2014 Mar     [PubMed PMID: 24528912]

[26]

Compalati E,Baena-Cagnani R,Penagos M,Badellino H,Braido F,Gómez RM,Canonica GW,Baena-Cagnani CE, Systematic review on the efficacy of fexofenadine in seasonal allergic rhinitis: a meta-analysis of randomized, double-blind, placebo-controlled clinical trials. International archives of allergy and immunology. 2011;     [PubMed PMID: 21969990]

[27]

Mancano MA, ISMP Adverse Drug Reactions: Propofol-Related Infusion Syndrome (PRIS){sup}1,2{/sup}; Ivermectin-Induced Stevens-Johnson Syndrome; Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis From Fexofenadine; Memantine-Related Drug Eruption. Hospital pharmacy. 2018 Jul     [PubMed PMID: 30038437]

[28]

Bailey DG, Fruit juice inhibition of uptake transport: a new type of food-drug interaction. British journal of clinical pharmacology. 2010 Nov     [PubMed PMID: 21039758]

[29]

Misaka S,Ono Y,Taudte RV,Hoier E,Ogata H,Ono T,König J,Watanabe H,Fromm MF,Shimomura K, Exposure of Fexofenadine, but Not Pseudoephedrine, Is Markedly Decreased by Green Tea Extract in Healthy Volunteers. Clinical pharmacology and therapeutics. 2022 Sep;     [PubMed PMID: 35678032]

[30]

Di Mizio G,Marcianò G,Palleria C,Muraca L,Rania V,Roberti R,Spaziano G,Piscopo A,Ciconte V,Di Nunno N,Esposito M,Viola P,Pisani D,De Sarro G,Raffi M,Piras A,Chiarella G,Gallelli L, Drug-Drug Interactions in Vestibular Diseases, Clinical Problems, and Medico-Legal Implications. International journal of environmental research and public health. 2021 Dec 8;     [PubMed PMID: 34948545]

[31]

Sarfraz N,Okuampa D,Hansen H,Alvarez M,Cornett EM,Kakazu J,Kaye AM,Kaye AD, pitolisant, a novel histamine-3 receptor competitive antagonist, and inverse agonist, in the treatment of excessive daytime sleepiness in adult patients with narcolepsy. Health psychology research. 2022     [PubMed PMID: 35774905]

[32]

Duran I,Carles J,Bulat I,Hellemans P,Mitselos A,Ward P,Jiao J,Armas D,Chien C, Pharmacokinetic Drug-Drug Interaction of Apalutamide, Part 1: Clinical Studies in Healthy Men and Patients with Castration-Resistant Prostate Cancer. Clinical pharmacokinetics. 2020 Sep     [PubMed PMID: 32338345]

[33]

Fexofenadine LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012     [PubMed PMID: 31643886]

[34]

Paśko P,Rodacki T,Domagała-Rodacka R,Palimonka K,Marcinkowska M,Owczarek D, Second generation H1 - antihistamines interaction with food and alcohol-A systematic review. Biomedicine     [PubMed PMID: 28622592]

[35]

Gonzalez-Estrada A,Geraci SA, Allergy Medications During Pregnancy. The American journal of the medical sciences. 2016 Sep     [PubMed PMID: 27650241]

[36]

van Wegberg AMJ,MacDonald A,Ahring K,Bélanger-Quintana A,Blau N,Bosch AM,Burlina A,Campistol J,Feillet F,Giżewska M,Huijbregts SC,Kearney S,Leuzzi V,Maillot F,Muntau AC,van Rijn M,Trefz F,Walter JH,van Spronsen FJ, The complete European guidelines on phenylketonuria: diagnosis and treatment. Orphanet journal of rare diseases. 2017 Oct 12;     [PubMed PMID: 29025426]

[37]

Pratt CM,Mason J,Russell T,Reynolds R,Ahlbrandt R, Cardiovascular safety of fexofenadine HCl. The American journal of cardiology. 1999 May 15     [PubMed PMID: 10335761]

[38]

Thi HT,Thi LP,Van TN,Minh PPT,Trong HN,Van TC,Huu SN,Minh TT,Huu ND,Van TH,Cam VT,Huyen ML,Hau KT,Thanh TN,Thi PH,Thuy LN,Gandolfi M,Satolli F,Feliciani C,Tirant M,Vojvodic A,Lotti T, The Efficacy of a Two-Fold Increase of H1-Antihistamine in the Treatment of Chronic Urticaria - the Vietnamese Experience. Open access Macedonian journal of medical sciences. 2019 Jan 30;     [PubMed PMID: 30745975]

[39]

Zuberbier T,Aberer W,Asero R,Bindslev-Jensen C,Brzoza Z,Canonica GW,Church MK,Ensina LF,Giménez-Arnau A,Godse K,Gonçalo M,Grattan C,Hebert J,Hide M,Kaplan A,Kapp A,Abdul Latiff AH,Mathelier-Fusade P,Metz M,Nast A,Saini SS,Sánchez-Borges M,Schmid-Grendelmeier P,Simons FE,Staubach P,Sussman G,Toubi E,Vena GA,Wedi B,Zhu XJ,Maurer M,European Academy of Allergy and Clinical Immunology.,Global Allergy and Asthma European Network.,European Dermatology Forum.,World Allergy Organization., The EAACI/GA(2) LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update. Allergy. 2014 Jul     [PubMed PMID: 24785199]

[40]

Paakkari I, Cardiotoxicity of new antihistamines and cisapride. Toxicology letters. 2002 Feb 28;     [PubMed PMID: 12052668]

[41]

Greenwald PW,Farmer BM,O'Neill M,Essner RA,Flomenbaum NE, Increasing frequency and fatality of poison control center reported exposures involving medication and multiple substances: data from reports of the American Association of Poison Control Centers 1984-2013. Clinical toxicology (Philadelphia, Pa.). 2016 Aug;     [PubMed PMID: 27214065]

[42]

Skypala IJ,de Jong NW,Angier E,Gardner J,Kull I,Ryan D,Venter C,Vlieg-Boerstra BJ,Grimshaw K, Promoting and achieving excellence in the delivery of Integrated Allergy Care: the European Academy of Allergy     [PubMed PMID: 30151118]