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Fexofenadine

Editor: Mark P. Schury Updated: 2/8/2024 10:35:24 PM

Indications

Fexofenadine, a second-generation antihistamine, is a metabolite of terfenadine. The US Food and Drug Administration (FDA) approved fexofenadine to treat seasonal allergic rhinitis and chronic idiopathic urticaria. Fexofenadine is approved for use in both children and adults. Depending on the specific indications, children may be eligible for treatment starting at 6 months or older.[1]

FDA-Approved Indications

Seasonal allergic rhinitis: Seasonal allergic rhinitis is characterized by nasal itching, sneezing, rhinorrhea, and nasal congestion. However, antihistamines are typically less effective in relieving nasal congestion. Triggers for seasonal or perennial allergic rhinitis may include grass, pollens, dust, pet dander, and mold.[2] In a double-blind, placebo-controlled, randomized trial, fexofenadine demonstrated comparable safety and efficacy to loratadine. Notably, fexofenadine was found to be effective in alleviating ocular and nasal congestion symptoms.[3] According to the American Academy of Allergy, Asthma, & Immunology (AAAAI), clinicians may consider supplementing treatment with pseudoephedrine if allergic rhinitis and nasal congestion persist despite oral antihistamine use. The fixed-dose combination of fexofenadine and pseudoephedrine has proven to be beneficial.[4]

Chronic idiopathic urticaria: Chronic idiopathic urticaria is caused by spontaneous mast cell degranulation.[2] Symptomatic triggers include water, sweat, sun, cold, or pressure, including dermatographism and urticarial rash. In addition, angiotensin-converting enzyme (ACE) inhibitors and nonsteroidal anti-inflammatory drugs (NSAIDs) may induce chronic urticaria.[5] Fexofenadine is also effective in treating cholinergic urticaria.[6] According to AAAAI and the American College of Allergy, Asthma & Immunology (ACAAI), second-generation antihistamines, such as fexofenadine, are considered safe and effective for managing cholinergic urticaria.[7] 

Off-Label Uses

Eczema (add-on treatment): A systematic review evaluated the effectiveness of oral H1 antihistamines as supplementary therapy alongside topical treatments for eczema. Despite varying evidence regarding their effectiveness, the review indicated that fexofenadine might relieve pruritus. However, challenges arose from limitations in the quality of evidence due to suboptimal study designs and imprecise outcomes, hindering the ability to reach definitive conclusions.[8]

Mechanism of Action

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Mechanism of Action

The mechanism of action of fexofenadine is to selectively antagonize H1 receptors on cell surfaces across various organ systems, thereby affecting inflammatory mediators.[9][10] Compared to other first-generation antihistamines, fexofenadine crosses the blood-brain barrier minimally and does not cause drowsiness. As a second-generation antihistamine, fexofenadine exhibits reduced affinity for cholinergic and α-adrenergic receptors, which results in minimal anticholinergic effects.

In a study, second-generation antihistamines such as desloratadine and loratadine showed anticholinergic activity, whereas fexofenadine exhibited no anticholinergic effects and displayed high specificity for H1 receptors. As a result, fexofenadine is recognized as one of the least sedating second-generation antihistamines.[11] Fexofenadine can also inhibit other mechanisms such as mast cell, basophilic histamine, and inflammatory cell release.[12] Prolonged use of fexofenadine does not cause tachyphylaxis.[13] Meta-analysis findings indicate that the antihistamine effects of fexofenadine, as measured by the histamine-induced wheal and flare inhibition rate, are significantly superior to placebo and comparable to other second-generation antihistamines.[14]

Pharmacokinetics

Absorption: Fexofenadine demonstrates rapid absorption, reaching peak plasma concentrations within 1 hour after oral administration for the suspension and 1.5 hours for the tablet. Maximum histamine inhibition occurs approximately 1 to 2 hours post-administration. As a long-acting antihistamine, fexofenadine is recommended for daily use.[15]

Distribution: Fexofenadine exhibits approximately 60% to 70% plasma protein binding. The drug predominantly binds to albumin and alpha-1 acid glycoprotein. Notably, fexofenadine does not occupy receptors in the central nervous system.[16]

Metabolism: Fexofenadine undergoes minimal hepatic metabolism. The metabolism and transportation of fexofenadine in the body rely significantly on organic anion transporting polypeptides (OATP2B1) and permeability glycoprotein (P-gp). Notably, P-gp facilitates both intestinal secretion and systemic disposition of fexofenadine.[17]

Elimination: In healthy volunteers, the mean elimination half-life of fexofenadine is approximately 14.4 hours when administered at a dosage of 60 mg twice daily. Fexofenadine is primarily excreted in feces via biliary excretion, accounting for 80% of elimination. However, the half-life of fexofenadine may be significantly prolonged in patients with renal disease.[18]

Administration

Available Dosage Forms and Strengths

Fexofenadine is available in various formulations for oral administration, including tablets, oral suspension (syrup), and orally disintegrating tablets (ODTs). In addition, a combination product that contains both fexofenadine and pseudoephedrine is available.[19]

Adult Dosage

Although fexofenadine is suitable for both adults and children, the dosage for children is lower than that for adults (up to 60 mg versus 180 mg PO daily). ODT tablets are branded and should be administered by placing the tablet on the tongue, allowing it to dissolve with or without water, and swallowing without chewing. Notably, it is recommended that patients should take the medication before having any food or drinks. ODT tablets are commonly prescribed for pediatric patients, with a dosage of 30 mg PO BID for children aged 6 to 12 for managing seasonal allergic rhinitis and chronic urticaria.[20] 

A fixed-dose combination containing 60 mg of fexofenadine and 120 mg of pseudoephedrine, formulated for treating seasonal allergic rhinitis with nasal congestion, is administered to patients every 12 hours. Another fixed-dose combination containing 180 mg of fexofenadine and 240 mg of pseudoephedrine is administered daily. The seasonal allergic rhinitis and chronic urticaria dosage is 60 or 180 mg PO daily.[7]

Specific Patient Populations

Hepatic impairment: The manufacturer of the product has not provided recommendations for dosage adjustment based on hepatic function.

Renal impairment: The recommendations for individuals with a creatinine clearance below 80 mL/min are provided below.

  • Adults: Adults should take 60 mg of fexofenadine PO daily.
  • Pediatric patients: Dosing for pediatric patients with renal impairment varies by age, as mentioned below.
    • Children aged 6 to 24 months: 15 mg PO daily.
    • Children aged 2 to 12: 30 mg PO daily.
    • Children aged 12 or older: 60 mg PO daily.
  • End-stage renal disease (ESRD) decreases nonrenal transporter function, resulting in a 63% decrease in clearance and a 2.8-fold increase in area under the curve (AUC) for fexofenadine. Therefore, dose reduction is necessary in patients with ESRD.[21]

Pregnancy considerations: Fexofenadine (formerly categorized as an FDA pregnancy category C drug) is typically avoided during pregnancy, with other antihistamines supported by more extensive data being preferred.[22] However, a large nationwide cohort study found no apparent association between fexofenadine use during pregnancy and the risk of congenital malformations or stillbirth.[23] According to the American College of Obstetricians and Gynecologists (ACOG) and the ACAAI guidelines, a first-generation antihistamine, such as chlorpheniramine, is preferred during pregnancy. If a patient is intolerant to chlorpheniramine, alternatives such as loratadine, desloratadine, and cetirizine are considered safe to use during pregnancy after the first trimester.[24][25][26]

Breastfeeding considerations: Fexofenadine, combined with pseudoephedrine, may reduce milk production. While breastfeeding, monitoring the infant for signs of irritability and jitteriness is important.[27][28]

Pediatrics patients: Fexofenadine dosages vary depending on age and the specific condition of the patient being treated.

  • Seasonal allergic rhinitis: The specific dosages for this condition are mentioned below.
    • Children aged <2: Not approved for use
    • Children aged 2 to 12: 30 mg PO BID
    • Children aged 12 or older: 60 mg PO BID or 180 mg PO daily
  • Chronic urticaria: The specific dosages for this condition are mentioned below.
    • Infants aged <6 months: Not approved for use
    • Children aged 6 to 24 months: 15 mg PO BID
    • Children aged 2 to 12: 30 mg PO BID
    • Children aged 12 or older: 60 or 180 mg PO daily

Older patients: Fexofenadine is frequently prescribed as an antihistamine for managing allergic rhinitis in older individuals due to its favorable safety profile, which is attributed to its limited penetration of the blood-brain barrier. Furthermore, second-generation antihistamines are associated with fewer anticholinergic adverse effects compared to first-generation antihistamines.[29]

Adverse Effects

The most common dose-dependent adverse drug reactions associated with fexofenadine include drowsiness, fatigue, and dry mouth.[30] In addition, post-marketing surveillance has reported rare occurrences of Stevens-Johnson syndrome or toxic epidermal necrolysis induced by fexofenadine.[31]

Adverse effects reported in a meta-analysis of randomized controlled trials include [14] headache, epistaxis, sinusitis, rash, abdominal pain, diarrhea, leukopenia, back pain, weakness, sedation or drowsiness, and dry mouth.[30]

Drug-Drug and Drug-Food Interactions

  • Fexofenadine, regardless of the route of administration, exhibits decreased bioavailability when taken with grapefruit, apple, or orange juice. This reduced bioavailability occurs due to the inhibition of the P-gp transporter. Patients should be advised to administer fexofenadine and any of these juices at least 4 hours apart.[32] 
  • Green tea has been found to reduce the bioavailability of fexofenadine by inhibiting the OATP1A2-mediated intestinal absorption of fexofenadine, thereby decreasing its efficacy.[33]
  • Betahistine, acting as an antagonist of histamine H3 receptors and a weak agonist of H1 receptors, can decrease the therapeutic potential of fexofenadine.[34]
  • Pilolisant is a histamine-3 receptor antagonist and inverse agonist approved for narcolepsy. However, concurrent use of antihistamines is not recommended.[35]
  • Apalutamide decreases the AUC of fexofenadine by 30% when administered concurrently with transporter substrates for P-gp, such as fexofenadine, which may result in a loss of efficacy for fexofenadine.[36]
  • Case reports have shown instances where fexofenadine yielded false-positive results for tramadol in urine drug screenings designed for substance use disorders. Therefore, caution is advised when interpreting positive tramadol results in urine tests for individuals taking fexofenadine. Further research is required to gain a comprehensive understanding of this interaction.[37]

Contraindications

Box Warnings

Hypersensitivity to fexofenadine or any of its components is the sole true contraindication to its use. Although hepatic involvement in the clearance of this medication is minimal, it is safe for patients with liver pathology. However, caution is necessary when treating patients with renal disease, and as mentioned above, adherence to renal dosing guidelines is essential in these cases.[38] 

Warning and Precautions

No significant interaction is evidenced between fexofenadine and concomitant alcohol or food consumption. However, fexofenadine's bioavailability decreases when consumed with grapefruit, apple, or orange juices.[39] In animal studies, fexofenadine has been associated with low birth weight and is categorized as an FDA category C drug during pregnancy. Alternative options for relieving allergic rhinitis symptoms include loratadine and cetirizine.[40] ODTs of fexofenadine may contain phenylalanine as an excipient, necessitating caution in patients with phenylketonuria.[41]

Monitoring

Monitoring fexofenadine involves evaluating for any improvement or worsening of symptoms with use. Due to its historical association with cardiotoxicity in terfenadine, patients with underlying cardiac conditions may require periodic electrocardiogram (ECG) monitoring to detect any potential QT prolongation or arrhythmias.[42]

A study comparing fexofenadine and levocetirizine for chronic urticaria revealed that dosage twice the recommended dose demonstrated improved urticarial symptoms without increasing adverse effects. The most frequently reported adverse effects were fatigue and drowsiness, occurring at similar rates in patients taking the recommended dose compared to those taking the higher dose. In addition, the study referenced a European study where the dosage was quadrupled, resulting in similar adverse effects.[43] 

The Rhinitis Control Assessment Test is a valuable tool for clinicians to assess the effectiveness of treatments in managing allergic rhinitis.[4] In addition, monitoring the quality of life can be achieved through the use of the Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL), while the impact of fexofenadine therapy on reducing urticaria symptoms can be evaluated using the Urticaria Activity Score (UAS7).[44]

Toxicity

Signs and Symptoms of Overdose

Fexofenadine, a metabolite of terfenadine, is associated with cardiotoxic effects. Terfenadine, when taken in high doses or with certain medications like ketoconazole, blocks cardiac potassium channels, resulting in prolonged QT intervals, which can lead to fatal arrhythmias. Following FDA guidelines, fexofenadine has replaced terfenadine in the United States due to its lack of potassium channel blockade. Multiple studies have confirmed that fexofenadine does not induce arrhythmias or significantly prolong QT intervals.[42] 

Despite the findings of these studies, some case reports have suggested a potential association between fexofenadine and QT-interval elongation and ventricular arrhythmia. Concurrent use of fexofenadine with hepatic CYP3A4 blockers, such as erythromycin and ketoconazole, may elevate blood concentration levels. In contrast, combined use with drugs such as rifampin and troglitazone can decrease concentration levels. These effects are likely attributed to interactions between these compounds and the P-gp transporter, which facilitates the removal of fexofenadine from the bloodstream.[45]

Management of Overdose

No specific antidote exists for fexofenadine overdose. Therefore, treatment in the event of an overdose primarily involves supportive measures. If an overdose is suspected, it is recommended to contact the poison control center or consult with a medical toxicologist, particularly if exposure to multiple substances is suspected.[46]

Enhancing Healthcare Team Outcomes

Fexofenadine is a commonly prescribed medication for seasonal allergic rhinitis and chronic urticaria. In addition, it is important to exercise caution when initiating any new medication without a prescription. Patients should engage in discussions with their primary care clinicians and pharmacists regarding fexofenadine to understand potential adverse effects, recommended dosing, and potential interactions with commonly consumed items such as fruit juices. Clinicians should also ensure that patients receive the appropriate adjusted dosage of fexofenadine. Immunologists should be consulted for cases of refractory urticaria or allergic rhinitis. Nurses should verify the dosage of fexofenadine at each visit and periodically reassess patients' conditions. Pharmacists should conduct thorough checks for drug interactions and perform medication reconciliation while counseling patients. In the event of fexofenadine overdose, critical care clinicians and medical toxicologists should be consulted.

If the overdose is determined to be intentional, the patient should be promptly referred to a psychiatrist for further evaluation and management. Collaborative efforts and coordination among the interprofessional healthcare team, comprising clinicians, specialists such as immunologists, nurses, and pharmacists, are critical in improving patient outcomes related to fexofenadine therapy. As advocated by the European Academy of Allergy and Clinical Immunology, integrated care involving clinicians, specialists, nurses, dietitians, psychologists, and pharmacists can significantly enhance patient-centered care for allergic disorders in community settings.[47]

References


[1]

Devillier P, Roche N, Faisy C. Clinical pharmacokinetics and pharmacodynamics of desloratadine, fexofenadine and levocetirizine : a comparative review. Clinical pharmacokinetics. 2008:47(4):217-30     [PubMed PMID: 18336052]

Level 2 (mid-level) evidence

[2]

Randall KL, Hawkins CA. Antihistamines and allergy. Australian prescriber. 2018 Apr:41(2):41-45. doi: 10.18773/austprescr.2018.013. Epub 2018 Apr 3     [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:30(6):891-9     [PubMed PMID: 10848909]

Level 1 (high-level) evidence

[4]

Dykewicz MS, Wallace DV, Amrol DJ, Baroody FM, Bernstein JA, Craig TJ, Dinakar C, Ellis AK, Finegold I, Golden DBK, Greenhawt MJ, Hagan JB, Horner CC, Khan DA, Lang DM, Larenas-Linnemann DES, Lieberman JA, Meltzer EO, Oppenheimer JJ, Rank MA, Shaker MS, Shaw JL, Steven GC, Stukus DR, Wang J, Chief Editor(s):, Dykewicz MS, Wallace DV, Joint Task Force on Practice Parameters:, Dinakar C, Ellis AK, Golden DBK, Greenhawt MJ, Horner CC, Khan DA, Lang DM, Lieberman JA, Oppenheimer JJ, Rank MA, Shaker MS, Stukus DR, Wang J, Workgroup Contributors:, Dykewicz MS, Wallace DV, Amrol DJ, Baroody FM, Bernstein JA, Craig TJ, Finegold I, Hagan JB, Larenas-Linnemann DES, Meltzer EO, Shaw JL, Steven GC. Rhinitis 2020: A practice parameter update. The Journal of allergy and clinical immunology. 2020 Oct:146(4):721-767. doi: 10.1016/j.jaci.2020.07.007. Epub 2020 Jul 22     [PubMed PMID: 32707227]


[5]

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 13:18(1):41. doi: 10.1186/s13223-022-00677-z. Epub 2022 May 13     [PubMed PMID: 35562767]


[6]

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:44(11):1291-1294. doi: 10.1111/1346-8138.13951. Epub 2017 Jun 30     [PubMed PMID: 28665007]

Level 3 (low-level) evidence

[7]

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:133(5):1270-7. doi: 10.1016/j.jaci.2014.02.036. Epub     [PubMed PMID: 24766875]


[8]

Matterne U, Böhmer MM, Weisshaar E, Jupiter A, Carter B, Apfelbacher CJ. Oral H1 antihistamines as 'add-on' therapy to topical treatment for eczema. The Cochrane database of systematic reviews. 2019 Jan 22:1(1):CD012167. doi: 10.1002/14651858.CD012167.pub2. Epub 2019 Jan 22     [PubMed PMID: 30666626]

Level 1 (high-level) evidence

[9]

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:48(6):649-653. doi: 10.4103/0253-7613.194854. Epub     [PubMed PMID: 28066101]

Level 1 (high-level) evidence

[10]

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 8:20(1):. doi: 10.3390/ijms20010213. Epub 2019 Jan 8     [PubMed PMID: 30626077]


[11]

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 4:506(3):257-64     [PubMed PMID: 15627436]

Level 3 (low-level) evidence

[12]

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:4(2):47-53. doi: 10.1097/WOX.0b013e3182093e19. Epub 2011 Feb 23     [PubMed PMID: 23268457]


[13]

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 2:17(1):113. doi: 10.1186/s13223-021-00614-6. Epub 2021 Nov 2     [PubMed PMID: 34727966]


[14]

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 29:20(1):72. doi: 10.1186/s40360-019-0363-1. Epub 2019 Nov 29     [PubMed PMID: 31783781]

Level 1 (high-level) evidence

[15]

Simpson K, Jarvis B. Fexofenadine: a review of its use in the management of seasonal allergic rhinitis and chronic idiopathic urticaria. Drugs. 2000 Feb:59(2):301-21     [PubMed PMID: 10730552]


[16]

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:42(1):11-27. doi: 10.3109/00498254.2011.617847. Epub 2011 Oct 4     [PubMed PMID: 21970687]


[17]

Akamine Y, Miura M. An update on the clinical pharmacokinetics of fexofenadine enantiomers. Expert opinion on drug metabolism & toxicology. 2018 Apr:14(4):429-434. doi: 10.1080/17425255.2018.1459565. Epub 2018 Apr 11     [PubMed PMID: 29635947]

Level 3 (low-level) evidence

[18]

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:41(2):187-95. doi: 10.1007/s10928-014-9356-2. Epub 2014 Mar 16     [PubMed PMID: 24633780]


[19]

Mansfield LE. Once-daily immediate-release fexofenadine and sustained-release pseudoephedrine combination: a new treatment option for allergic rhinitis. Expert opinion on pharmacotherapy. 2006 May:7(7):941-51     [PubMed PMID: 16634716]

Level 3 (low-level) evidence

[20]

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:15(3):253-60     [PubMed PMID: 15209959]

Level 1 (high-level) evidence

[21]

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:20(10):2269-76. doi: 10.1681/ASN.2009010082. Epub 2009 Aug 20     [PubMed PMID: 19696225]

Level 3 (low-level) evidence

[22]

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:70(3):401.e1-14; quiz 415. doi: 10.1016/j.jaad.2013.09.010. Epub     [PubMed PMID: 24528911]


[23]

Andersson NW, Torp-Pedersen C, Andersen JT. Association Between Fexofenadine Use During Pregnancy and Fetal Outcomes. JAMA pediatrics. 2020 Aug 1:174(8):e201316. doi: 10.1001/jamapediatrics.2020.1316. Epub 2020 Aug 3     [PubMed PMID: 32478810]


[24]

Kar S, Krishnan A, Preetha K, Mohankar A. A review of antihistamines used during pregnancy. Journal of pharmacology & pharmacotherapeutics. 2012 Apr:3(2):105-8. doi: 10.4103/0976-500X.95503. Epub     [PubMed PMID: 22629082]


[25]

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:45(3):547-65. doi: 10.1111/cea.12494. Epub     [PubMed PMID: 25711134]


[26]

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:8(5):1598-1605. doi: 10.1016/j.jaip.2020.02.017. Epub 2020 Mar 3     [PubMed PMID: 32142963]


[27]

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


[28]

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:70(3):417.e1-10; quiz 427. doi: 10.1016/j.jaad.2013.09.009. Epub     [PubMed PMID: 24528912]


[29]

Bozek A. Pharmacological Management of Allergic Rhinitis in the Elderly. Drugs & aging. 2017 Jan:34(1):21-28. doi: 10.1007/s40266-016-0425-7. Epub     [PubMed PMID: 27913982]


[30]

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. 2011:156(1):1-15     [PubMed PMID: 21969990]

Level 1 (high-level) evidence

[31]

Mancano MA. ISMP Adverse Drug Reactions: Propofol-Related Infusion Syndrome (PRIS)(1,2); Ivermectin-Induced Stevens-Johnson Syndrome; Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis From Fexofenadine; Memantine-Related Drug Eruption. Hospital pharmacy. 2018 Jul:53(4):220-222. doi: 10.1177/0018578718776857. Epub 2018 Jun 6     [PubMed PMID: 30038437]


[32]

Bailey DG. Fruit juice inhibition of uptake transport: a new type of food-drug interaction. British journal of clinical pharmacology. 2010 Nov:70(5):645-55. doi: 10.1111/j.1365-2125.2010.03722.x. Epub     [PubMed PMID: 21039758]


[33]

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:112(3):627-634. doi: 10.1002/cpt.2682. Epub 2022 Jun 29     [PubMed PMID: 35678032]


[34]

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 8:18(24):. doi: 10.3390/ijerph182412936. Epub 2021 Dec 8     [PubMed PMID: 34948545]


[35]

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. 2022:10(3):34222. doi: 10.52965/001c.34222. Epub 2022 May 30     [PubMed PMID: 35774905]


[36]

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:59(9):1135-1148. doi: 10.1007/s40262-020-00882-2. Epub     [PubMed PMID: 32338345]


[37]

Yousuf SM, Alater AM, Alabdulla M, Osman M. False Positive Tramadol Urine Testing in Patients Taking Fexofenadine: A Tale of Two Consecutive Cases. Case reports in psychiatry. 2023:2023():4370648. doi: 10.1155/2023/4370648. Epub 2023 Jan 5     [PubMed PMID: 36643013]

Level 3 (low-level) evidence

[38]

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


[39]

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 & pharmacotherapy = Biomedecine & pharmacotherapie. 2017 Sep:93():27-39. doi: 10.1016/j.biopha.2017.06.008. Epub 2017 Jun 13     [PubMed PMID: 28622592]

Level 1 (high-level) evidence

[40]

Gonzalez-Estrada A, Geraci SA. Allergy Medications During Pregnancy. The American journal of the medical sciences. 2016 Sep:352(3):326-31. doi: 10.1016/j.amjms.2016.05.030. Epub 2016 Jun 3     [PubMed PMID: 27650241]


[41]

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 12:12(1):162. doi: 10.1186/s13023-017-0685-2. Epub 2017 Oct 12     [PubMed PMID: 29025426]


[42]

Pratt CM, Mason J, Russell T, Reynolds R, Ahlbrandt R. Cardiovascular safety of fexofenadine HCl. The American journal of cardiology. 1999 May 15:83(10):1451-4     [PubMed PMID: 10335761]


[43]

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 30:7(2):259-263. doi: 10.3889/oamjms.2019.069. Epub 2019 Jan 28     [PubMed PMID: 30745975]


[44]

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:69(7):868-87. doi: 10.1111/all.12313. Epub 2014 Apr 30     [PubMed PMID: 24785199]


[45]

Paakkari I. Cardiotoxicity of new antihistamines and cisapride. Toxicology letters. 2002 Feb 28:127(1-3):279-84     [PubMed PMID: 12052668]

Level 3 (low-level) evidence

[46]

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:54(7):590-6. doi: 10.1080/15563650.2016.1183777. Epub 2016 May 23     [PubMed PMID: 27214065]


[47]

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 & Clinical Immunology competencies for allied health professionals working in allergy. Clinical and translational allergy. 2018:8():31. doi: 10.1186/s13601-018-0218-7. Epub 2018 Aug 21     [PubMed PMID: 30151118]