Fexofenadine

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Fexofenadine
Skeletal formula of fexofenadine
Ball-and-stick model of fexofenadine
Clinical data
Trade namesAllegra, others
AHFS/Drugs.comMonograph
MedlinePlusa697035
License data
Pregnancy
category
H1 receptor antagonist
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability30–41%[8]
Protein binding60–70%[9]
MetabolismHepatic (≤5% of dose)[9]
Elimination half-life14.4 hours
ExcretionFeces (~80%) and urine (~10%) as unchanged drug[9]
Identifiers
  • (±)-4-[1-Hydroxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-butyl]-α, α-dimethyl benzeneacetic acid
JSmol)
ChiralityRacemic mixture
  • O=C(O)C(c1ccc(cc1)C(O)CCCN2CCC(CC2)C(O)(c3ccccc3)c4ccccc4)(C)C
  • InChI=1S/C32H39NO4/c1-31(2,30(35)36)25-17-15-24(16-18-25) 29(34)14-9-21-33-22-19-28(20-23-33)32(37, 26-10-5-3-6-11-26)27-12-7-4-8-13-27/h3-8, 10-13,15-18,28-29,34,37H,9,14,19-23H2,1-2H3,(H,35,36) ☒N
  • Key:RWTNPBWLLIMQHL-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Fexofenadine, sold under the brand name Allegra among others,

urticaria.[11]

Therapeutically, fexofenadine is a selective peripheral H1 blocker. It is classified as a second-generation antihistamine because it is less able to pass the blood–brain barrier and cause sedation, compared to first-generation antihistamines.[12][13]

It was patented in 1979 and came into medical use in 1996.[14] It is on the World Health Organization's List of Essential Medicines.[15] Fexofenadine has been manufactured in generic form since 2011.[16] In 2021, it was the 262nd most commonly prescribed medication in the United States, with more than 1 million prescriptions.[17][18]

Medical uses

Fexofenadine is used for relief from physical symptoms associated with seasonal

urticaria.[12] It does not cure, but rather prevents the aggravation of allergic rhinitis and chronic idiopathic urticaria, and reduces the severity of the symptoms associated with those conditions, providing relief from repeated sneezing, runny nose, itchy eyes or skin, and general body fatigue. In a 2018 review, fexofenadine, along with levocetirizine, desloratadine, and cetirizine, was cited to be a safe drug to use for individuals with inherited long QT syndrome.[19]

Efficacy

For the treatment of allergic rhinitis, fexofenadine is similarly effective to cetirizine, but is associated with less drowsiness than cetirizine.[20] Fexofenadine was also shown to inhibit histamine-induced wheal and flare to a significantly greater degree than loratadine or desloratadine,[21] but was slightly less effective than levocetirizine.[22]

Fexofenadine at doses above 120 mg a day does not appear to provide additional efficacy in the treatment of allergic rhinitis.[23][24]

Side effects

The most common

fatigue for children ages 6 months to 5 years.[5]

Overdose

The safety profile of fexofenadine is quite favorable, as no

cardiovascular or sedative effects have been shown to occur even when taking 10 times the recommended dose.[25] Research on humans ranges from a single 800-mg dose, to a twice-daily, 690-mg dose for a month, with no clinically significant adverse effects, when compared to a placebo. No deaths occurred in testing on mice, at 5000 mg/kg body weight, which is 110 times the maximum recommended dose for an adult human.[5] If overdose were to occur, supportive measures are recommended. Theoretically, an overdose could present as dizziness, dry mouth, and/or drowsiness, consistent with an exaggeration of the usual side effects. Hemodialysis does not appear to be an effective means of removing fexofenadine from the blood.[5]

Pharmacology

Pharmacodynamics

Fexofenadine is a

H1 receptor antagonist. Blockage prevents the activation of the H1 receptors by histamine, preventing the symptoms associated with allergies from occurring. Fexofenadine does not readily cross the blood–brain barrier, so is less likely to cause drowsiness in comparison to other antihistamines that readily cross that barrier (i.e., first-generation antihistamines such as diphenhydramine). In general, fexofenadine takes about an hour to take effect, though this may be affected by the choice of dosage form and the presence of certain foods.[5][26]

Fexofenadine also exhibits no

beta-adrenergic receptor-blocking effects.[5]

Pharmacokinetics

  • Absorption: After oral application, maximum plasma concentrations are reached after 2–3 hours. Fexofenadine should not be taken with a high-fat meal, as mean concentrations of fexofenadine in the bloodstream are seen to be reduced from 20 to 60% depending on form of medication (tablet, ODT, or suspension).[5]
  • Distribution: Fexofenadine is 60–70% bound to plasma proteins, mostly albumin.[5]
  • Metabolism: Fexofenadine is a substrate of CYP3A4, but only about 5% is metabolized by the liver, indicating that hepatic metabolism is relatively minor in clearance from the body.[5]
  • Elimination: Most of the substance is eliminated unchanged via the feces (80%) and urine (11–12%).[5]

Interactions

Taking erythromycin or ketoconazole while taking fexofenadine does increase the plasma levels of fexofenadine, but this increase does not influence the QT interval. The reason for this effect is likely due to transport-related effects, specifically involving p-glycoprotein (p-gp).[5] Both erythromycin and ketoconazole are inhibitors of p-gp, a transporter protein involved in preventing the intestinal absorption of fexofenadine. When p-gp is inhibited, fexofenadine may be better absorbed by the body, increasing its plasma concentration by more than intended.[citation needed]

Fexofenadine is not to be taken with apple, orange, or grapefruit juice because they could decrease absorption of the drug. Therefore, it should be taken with water.[5] Grapefruit juice can significantly reduce the plasma concentration of fexofenadine.[27]

aluminum or magnesium should not be taken within 15 minutes of fexofenadine, as they reduce its absorption by almost 50%.[5] This is not thought to be due to a change in pH (in fact, absorption can actually increase under increasingly alkaline pH), but rather due to the formation of metal complexes with charged/polar moieties on fexofenadine. As suggested by Shehnaza et al (2014), various sites of the molecule are thought to be responsible for this interaction, including the piperidine nitrogen, the carboxylic acid (-COOH) group, and both hydroxyl (-OH) groups.[28]

History

The older antihistaminic agent

blockbuster drug status with global sales of US$1.87B in 2004 (with $1.49B coming from the United States). AMRI received royalty payments from Aventis that enabled the growth of AMRI.[citation needed
]

In January 2011, the FDA approved over-the-counter sales of fexofenadine in the United States, and Sanofi Aventis' version became available in March 2011.[30] In December 2020, the MHRA reclassified fexofenadine from prescription only to allow general sales in the United Kingdom.[31]

Society and culture

Brand names

Fexofenadine is marketed under many brand names worldwide.[10]

As of January 2017, it is marketed as a combination drug with pseudoephedrine under brand names including: Alerfedine D, Allegra-D, Allergyna-D, Allevia, Altiva-D, Dellegra, Fexo Plus, Fexofed, Fixal Plus, Ridrinal D, Rinolast D, Telfast D, and Treathay.[10]

As of January 2017, it is marketed as a combination drug with montelukast under brand names including Fexokast, Histakind-M, Monten-FX, Montolife-FX, Montair-FX and Novamont-FX.[10]

References

  1. ^ "Fexofenadine Use During Pregnancy". Drugs.com. 1 April 2019. Retrieved 26 July 2020.
  2. ^ "Telfast 30mg Film-coated Tablets - Summary of Product Characteristics (SmPC)". (emc). 25 October 2019. Retrieved 20 June 2021.
  3. ^ "Almerg 180 mg Film-Coated Tablets - Summary of Product Characteristics (SmPC)". (emc). Retrieved 20 June 2021.
  4. ^ "Fexofenadine Hydrochloride 120 mg Film-Coated Tablets - Summary of Product Characteristics (SmPC)". (emc). 22 March 2021. Archived from the original on 24 June 2021. Retrieved 20 June 2021.
  5. ^ a b c d e f g h i j k l m "Allegra (fexofenadine hydrochloride) tablet, orally disintegrating for oral use Allegra (fexofenadine hydrochloride) tablet, film coated for oral use Allegra (fexofenadine hydrochloride) suspension for oral useInitial U.S. Approval: 1996". DailyMed. 15 December 2008. Retrieved 13 February 2022.
  6. ^ "Allegra Allergy- fexofenadine hydrochloride tablet, coated". DailyMed. Retrieved 12 February 2022.
  7. ^ "ALLEGRA (fexofenadine hydrochloride) Product Monograph" (PDF). Sanofi Consumer Health Inc. 7 November 2019.
  8. PMID 20307657
    .
  9. ^
    S2CID 19048690
    .
  10. ^ a b c d "Fexofenadine - international brand names". Drugs.com. Retrieved 18 January 2017.
  11. PMID 19539095
    .
  12. ^
    PMID 21969990
    .
  13. PMID 14651723
    .
  14. ISBN 9783527607495
    .
  15. hdl:10665/345533
    . WHO/MHP/HPS/EML/2021.02.
  16. ^ "Dr. Reddy's announces the launch of Over-the-Counter Fexofenadine HCl and Pseudoephedrine HCl extended release tablets". Dr. Reddy's Laboratories Ltd. 30 August 2011. Archived from the original on 12 October 2016. Retrieved 27 May 2016.
  17. ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  18. ^ "Fexofenadine - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
  19. PMID 30059791
    .
  20. PMID 14582814
    .
  21. PMID 17345837
    .
  22. PMID 11868924
    .
  23. PMID 10389553
    .
  24. PMID 10550734
    .
  25. PMID 10748947
    .
  26. PMID 9330784
    .
  27. S2CID 17532347
    .
  28. doi:10.1016/j.arabjc.2013.01.011
    .
  29. ISBN 978-0-471-24510-0
    .
  30. ^ "Allegra FAQs". Sanofi-Aventis. Archived from the original on 20 May 2011. Retrieved 5 July 2011.
  31. ^ "PAR: Reclassification of Allevia 120mg tablets from Prescription Only Medicine (POM) to General Sales List (GSL)". MHRA. 22 December 2020.
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