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Fexofenadine (trade names Allegra, Fexidine, Telfast, Fastofen, Tilfur, Vifas, Telfexo, Allerfexo) is an antihistamine pharmaceutical drug used in the treatment of allergy symptoms, such as hay fever, nasal congestion, and urticaria.^[3]

Fexofenadine is sometimes called a third-generation antihistamine because it is less able to pass the blood-brain barrier and cause sedation, compared to first-generation antihistamines.^[4]

Medical uses

Fexofenadine is used for relief from physical symptoms associated with seasonal allergic rhinitis and for treatment of chronic urticaria.^[4] It does not cure but rather prevents the aggravation of rhinitis and urticaria and reduces the severity of the symptoms associated with those conditions, providing relief from repeated sneezing, runny nose, itchy eyes and general body fatigue.

Dosage

Fexofenadine has been demonstrated to be safe and effective for children ages 2–5 years old and 6–11 years old in treatment of seasonal allergic rhinitis.^[5]^[6]

Renal Impairment: Due to decreased renal elimination in patients with creatinine clearance of less than 80mL/min, it is recommended that patients with renal impairment are started on a lower dose.^[7]

Hepatic Impairment: Perhaps because only a small percentage of fexofenadine is metabolized in the liver, altered levels of drug are not seen in patients with hepatic impairment and therefore doses do not need to be adjusted in this population.^[7]

Side effects

The most common side effects demonstrated in adults were headache, back pain, miosis or pinpoint pupils, drowsiness, and menstrual cramps. There have also been reports of anxiety and insomnia. The most common side effects demonstrated during clinical trials were cough, upper respiratory tract infection, fever, and otitis media for children ages 6 to 11 and fatigue for children ages 6 months to 5 years.^[7]

Additionally, the half-life of fexofenadine is shorter than cetirizine, so it often must be taken twice daily.^[8] However, there is also evidence that cetirizine causes more sleepiness than fexofenadine.^[9]

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.^[10] 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 one-hundred and ten times (110x) the maximum recommended dose for an adult human.^[7] If overdose were to occur, likely seen as dizziness, dry mouth, and/or drowsiness, supportive measures are recommended. It does not appear that hemodialysis is an effective mode to remove fexofenadine from the blood.^[7]

Mechanism of action

Fexofenadine is a selectively peripheral H1-blocker. 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 and is therefore unlikely to cause drowsiness. It also exhibits no anticholinergic, antidopaminergic, alpha1-adrenergic, or beta-adrenergic-receptor-blocking effects.^[7]

Pharmacokinetics

Absorption: After oral application, maximum plasma concentrations are reached after two to three hours. Fexofenadine should not be taken with a high fat meal, as mean concentrations of fexofenadine in the bloodstream is seen to be reduced from 20-60% depending on form of medication (tablet, ODT, or suspension).^[7]

Distribution: Fexofenadine is 60-70% bound to plasma proteins, mostly albumin.^[7]

Metabolism: Only a 5% is metabolized in the liver.^[7]

Elimination: Most of the substance is eliminated unchanged via the feces (80%) and urine (11–12%).^[7]

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.^[7]

Fexofenadine is not to be taken with apple, orange, or grapefruit juice because it could decrease absorption of the drug and should therefore be taken with water.^[7] Grapefruit juice can significantly reduce the plasma concentration of fexofenadine.^[11]

Antacids containing aluminium or magnesium should not be taken within 15 minutes of fexofenadine as they reduce the absorption of fexofenadine by almost 50%.^[7]

Special populations

Fexofenadine is a pregnancy category C and should be used if the benefits outweigh the risks.^[12]

No studies have been done to evaluate the presence of fexofenadine in breast milk. Therefore, nursing women are urged to take caution while using fexofenadine.^[7]

No sufficient studies have been done in patients over age 65. Therefore, it is advised that elderly patients use caution when using fexofenadine, particularly when there is concern for renal impairment.^[7]

History

The older antihistaminic agent terfenadine was found to metabolize into the related carboxylic acid, fexofenadine. Fexofenadine was found to retain all of the biological activity of its parent while giving fewer adverse reactions in patients, so terfenadine was replaced in the market by its metabolite.^[13] Fexofenadine was originally synthesized in 1993 by Massachusetts-based biotechnology company Sepracor, which then sold the development rights to Hoechst Marion Roussel (now part of Sanofi-Aventis), and was later approved by the Food and Drug Administration (FDA) in 1996. Albany Molecular Research Inc. (AMRI) holds the patents to the intermediates and production of fexofenadine HCl along with Roussel. Since that time, it has achieved blockbuster drug status with global sales of $1.87B USD in 2004 (with $1.49B USD coming from the United States). AMRI received royalty payments from Aventis that enabled the growth of AMRI.

On January 25, 2011, the FDA approved over-the-counter sales of fexofenadine in the United States, and Sanofi-Aventis' version became available on March 4, 2011.^[14]

References

^ Lappin G, Shishikura Y, Jochemsen R, Weaver RJ, Gesson C, Houston B, Oosterhuis B, Bjerrum OJ, Rowland M, Garner C (May 2010). "Pharmacokinetics of fexofenadine: evaluation of a microdose and assessment of absolute oral bioavailability". Eur J Pharm Sci 40 (2): 125–31. doi:10.1016/j.ejps.2010.03.009. PMID 20307657.
^ ^a ^b ^c Smith, SM; Gums, JG (July 2009). "Fexofenadine: biochemical, pharmacokinetic and pharmacodynamic properties and its unique role in allergic disorders.". Expert Opinion on Drug Metabolism & Toxicology 5 (7): 813–22. doi:10.1517/17425250903044967. PMID 19545214.
^ Bachert, C (May 2009). "A review of the efficacy of desloratadine, fexofenadine, and levocetirizine in the treatment of nasal congestion in patients with allergic rhinitis". Clin Ther 31 (5): 921–44. doi:10.1016/j.clinthera.2009.05.017. PMID 19539095. Retrieved 18 April 2014.
^ ^a ^b Compalati, E; Baena-Cagnani, R; Penagos, M; Badellino, H; Braido, F; Gómez, RM; Canonica, GW; Baena-Cagnani, CE (2011). "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 156 (1): 1–15. doi:10.1159/000321896. PMID 21969990.
^ Segall, N; Grubbe RE; Levy AL; Maloney MJ; Nayak AS; Kittner B; Quesada JT. (Jul–Aug 2008). "Pharmacokinetics, Safety and Tolerability of an Oral Suspension of Fexofenadine for Children with Allergic Rhinitis". Allergy Asthma Proc. 29 (4): 380–5. doi:10.2500/aap.2008.29.3136. PMID 18702885. Retrieved 17 April 2014.
^ Phan, H; Moeller, Nahata (2009). "Treatment of Allergic Rhinitis in Infants and Children: Efficacy and Safety of Second-Generation Antihistamines and the Leukotriene Receptor Antagonist Montelukast". Drugs 69 (18): 2541–76. doi:10.2165/9884960-000000000-00000. PMID 19943707. Retrieved 17 April 2014.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o Allegra (fexofenadine hydrochloride) tablets, ODT, and oral suspension package insert. Sanofi-Aventis; 2007.
^ Church, Martin; Church, Diana (2013). "Pharmacology of antihistamines". Indian Journal of Dermatology 58 (3): 219–224. doi:10.1097/WOX.0b013e3181f385d9. PMC 3666185. PMID 23282332. Retrieved 18 April 2014.
^ Tashiro, M; Sakurada Y; Iwabuchi K; Mochizuki H; Kato M; Aoki M; Funaki Y; Itoh M; Iwata R; Wong DF; Yanai K (Aug 2004). "Central effects of fexofenadine and cetirizine: measurement of psychomotor performance, subjective sleepiness, and brain histamine H1-receptor occupancy using 11C-doxepin positron emission tomography.". J Clin Pharmacol 44 (8): 890–900. doi:10.1177/0091270004267590. PMID 15286093. Retrieved 18 April 2014.
^ Philpot, EE (Jan–Feb 2000). "Safety of second generation antihistamines". Allergy Asthma Proc 21 (1): 15–20. doi:10.2500/108854100778249033. PMID 10748947. |accessdate= requires |url= (help)
^ Shirasaka, Y; Mori T; Murata Y; Nakanishi T; Tamai I (Feb 19, 2014). "Substrate- and Dose-Dependent Drug Interactions with Grapefruit Juice Caused by Multiple Binding Sites on OATP2B1". Pharm Res 31: 2035–2043. doi:10.1007/s11095-014-1305-7. PMID 24549825.
^ Mazzotta, P; Loebstein R; Koren G (Apr 1999). "Treating allergic rhinitis in pregnancy. Safety considerations.". Drug Saf. 20 (4): 361–75. doi:10.2165/00002018-199920040-00005. PMID 10230583. Retrieved 18 April 2014.
^ Daniel Lednicer (1999). The Organic Chemistry of Drug Synthesis 6. New York: Wiley Interscience. pp. 38–40. ISBN 0-471-24510-0.
^ "Allegra | FAQs". Sanofi-Aventis. Retrieved 5 July 2011.

External links

Fexofenadine (UK patient information leaflet)
Allegra (Fexofenadine Hydrochloride) label and research information
"fexofenadine" at medicinenet.com
Official website for Allegra brand Fexofenadine

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 慢性蕁麻疹：標準的なマネージメントおよび患者教育 chronic urticaria standard management and patient education
2. アレルギー性鼻炎および結膜炎に対する補完代替療法 complementary and alternative therapies for allergic rhinitis and conjunctivitis
3. アレルギー性鼻炎の薬物療法 pharmacotherapy of allergic rhinitis
4. 寒冷蕁麻疹 cold urticaria
5. アトピー性皮膚炎（湿疹）の治療 treatment of atopic dermatitis eczema

English Journal

Geneva cocktail for cytochrome P450 and P-glycoprotein activity assessment using dried blood spot.

Bosilkovska M1, Samer CF2, Déglon J3, Rebsamen M4, Staub C3, Dayer P2, Walder B5, Desmeules JA2, Daali Y2.Author information 1Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland.21] Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland [2] Swiss Center for Applied Human Toxicology, Geneva, Switzerland.3Unit of Toxicology, University Center of Legal Medicine, Geneva, Switzerland.4Department of Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland.5Division of Anesthesiology, Geneva University Hospitals, Geneva, Switzerland.AbstractThe capillary dried blood spot (DBS) sampling method suitability was assessed for simultaneous cytochromes P450 (CYP) and P-glycoprotein (P-gp) phenotyping using a cocktail approach.Ten volunteers received an oral cocktail capsule containing low dose probes bupropion (CYP2B6), flurbiprofen (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), midazolam (CYP3A) and fexofenadine (P-gp) with coffee/Coke (CYP1A2) on four occasions. They received the cocktail alone (session 1), with CYP inhibitors fluvoxamine and voriconazole (session 2) and quinidine (session 3). In session 4, subjects received the cocktail after a 7-day pre-treatment with inducer rifampicin. Probes/metabolites concentrations were determined in DBS and plasma using a single LC-MS/MS method.The drugs pharmacokinetic profiles were comparable in DBS and plasma. Important modulation of CYP and P-gp activities was observed in presence of inhibitors and inducer. Minimally invasive 1-point and 3-point (at 2, 3 and 6h) DBS sampling methods were found to reliably reflect CYPs and P-gp activities at each session.Clinical Pharmacology & Therapeutics (2014); Accepted article preview online 10 April 2014 doi:10.1038/clpt.2014.83.
Clinical pharmacology and therapeutics.Clin Pharmacol Ther.2014 Apr 10. doi: 10.1038/clpt.2014.83. [Epub ahead of print]
The capillary dried blood spot (DBS) sampling method suitability was assessed for simultaneous cytochromes P450 (CYP) and P-glycoprotein (P-gp) phenotyping using a cocktail approach.Ten volunteers received an oral cocktail capsule containing low dose probes bupropion (CYP2B6), flurbiprofen (CYP2C9),
PMID 24722393

Hypoxia/reoxygenation stress signals an increase in organic anion transporting polypeptide 1a4 (Oatp1a4) at the blood-brain barrier: relevance to CNS drug delivery.

Thompson BJ1, Sanchez-Covarrubias L2, Slosky LM2, Zhang Y2, Laracuente ML2, Ronaldson PT3.Author information 1Department of Physiology, University of Arizona College of Medicine, Tucson, Arizona, USA.2Department of Pharmacology, University of Arizona College of Medicine, Tucson, Arizona, USA.31] Department of Physiology, University of Arizona College of Medicine, Tucson, Arizona, USA [2] Department of Pharmacology, University of Arizona College of Medicine, Tucson, Arizona, USA.AbstractCerebral hypoxia and subsequent reoxygenation stress (H/R) is a component of several diseases. One approach that may enable neural tissue rescue after H/R is central nervous system (CNS) delivery of drugs with brain protective effects such as 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (i.e., statins). Our present in vivo data show that atorvastatin, a commonly prescribed statin, attenuates poly (ADP-ribose) polymerase (PARP) cleavage in the brain after H/R, suggesting neuroprotective efficacy. However, atorvastatin use as a CNS therapeutic is limited by poor blood-brain barrier (BBB) penetration. Therefore, we examined regulation and functional expression of the known statin transporter organic anion transporting polypeptide 1a4 (Oatp1a4) at the BBB under H/R conditions. In rat brain microvessels, H/R (6% O2, 60 minutes followed by 21% O2, 10 minutes) increased Oatp1a4 expression. Brain uptake of taurocholate (i.e., Oap1a4 probe substrate) and atorvastatin were reduced by Oatp inhibitors (i.e., estrone-3-sulfate and fexofenadine), suggesting involvement of Oatp1a4 in brain drug delivery. Pharmacological inhibition of transforming growth factor-β (TGF-β)/activin receptor-like kinase 5 (ALK5) signaling with the selective inhibitor SB431542 increased Oatp1a4 functional expression, suggesting a role for TGF-β/ALK5 signaling in Oatp1a4 regulation. Taken together, our novel data show that targeting an endogenous BBB drug uptake transporter (i.e., Oatp1a4) may be a viable approach for optimizing CNS drug delivery for treatment of diseases with an H/R component.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.J Cereb Blood Flow Metab.2014 Apr;34(4):699-707. doi: 10.1038/jcbfm.2014.4. Epub 2014 Jan 29.
Cerebral hypoxia and subsequent reoxygenation stress (H/R) is a component of several diseases. One approach that may enable neural tissue rescue after H/R is central nervous system (CNS) delivery of drugs with brain protective effects such as 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor
PMID 24473481

Population pharmacokinetic analysis of fexofenadine in Japanese pediatric patients.

Martinez JM1, Khier S, Morita S, Rauch C, Fabre D.Author information 1Disposition, Safety and Animal Research, Drug Disposition, Modeling and Simulations Entity, Sanofi-aventis Recherche & Développement, 371, rue du Professeur Joseph Blayac, 34184, Montpellier Cedex 04, France, jean-marie.martinez@sanofi.com.AbstractA population pharmacokinetic analysis was conducted to characterize the pharmacokinetics of fexofenadine in Japanese pediatric patients (6 months through 16 years) with perennial allergic rhinitis or atopic dermatitis. The dataset was composed of 515 patients (including 109 adults), for a total of 1,080 concentration-time points. The analysis was performed with NONMEM using the SAEM method. Several structural models and residual error models were evaluated. The relationship between the individual estimates and the potential covariates was then investigated: demographic and pathophysiologic characteristics were tested as potential model covariates (forward selection method). The qualification of the model was performed using visual predictive check and bootstrap. A two-compartment disposition model with first-order absorption best fitted the data. The inter-individual variability was modeled through an exponential error model for all parameters (except for ka for which no inter-individual term could be estimated), while a proportional error model was used to model the residual variability. The final model included two covariates on elimination clearance and one on the intercompartmental clearance. CL/F was related to BSA and patient's age (expressed in months) Q/F was also related to BSA. Once the model was correctly qualified, exposure parameters such as Cmax and AUCτ were computed and compared between each age sub-group and between Japanese and Caucasians patients. These comparisons did not reveal any major difference (less than 50 %) between subgroups.
Journal of pharmacokinetics and pharmacodynamics.J Pharmacokinet Pharmacodyn.2014 Apr;41(2):187-95. doi: 10.1007/s10928-014-9356-2. Epub 2014 Mar 16.
A population pharmacokinetic analysis was conducted to characterize the pharmacokinetics of fexofenadine in Japanese pediatric patients (6 months through 16 years) with perennial allergic rhinitis or atopic dermatitis. The dataset was composed of 515 patients (including 109 adults), for a total of
PMID 24633780

Japanese Journal

季節性アレルギー性鼻炎に対するフェキソフェナジン塩酸塩と塩酸プソイドエフェドリン配合剤の有効性及び安全性の検討 : 第？/？相,ランダム化,二重盲検,並行群間比較試験

大久保公裕
アレルギー・免疫 19(11), 1770-1782, 2012-11
NAID 40019464573

治療蕁麻疹・湿疹皮膚炎群(湿疹・皮膚炎・皮膚痒症・アトピー性皮膚炎)に伴う痒患者における塩酸フェキソフェナジンの効果と安全性(眠気)についての検討

伊藤宏太郎,今福信一,山口和記 [他]
西日本皮膚科 = The Nishinihon journal of dermatology : 日本皮膚科学会西部支部機関誌 74(5), 548-552, 2012-10
NAID 40019476261

Related Pictures

★リンクテーブル★

リンク元	「フェキソフェナジン」「Allegra」
拡張検索	「fexofenadine hydrochloride」

「フェキソフェナジン」

Fexofenadine
Systematic (IUPAC) name
	(±)-4-[1 hydroxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-butyl]-α, α-dimethyl benzeneacetic acid
Clinical data
Trade names	Allegra, Axodin
AHFS/Drugs.com	monograph
MedlinePlus	a697035
Licence data	US FDA:link
Pregnancy; category	AU: B2; US: C (Risk not ruled out);
Legal status	AU: Unscheduled; CA: OTC; UK: Prescription-only (POM); US: OTC;
Routes of; administration	Oral
Pharmacokinetic data
Bioavailability	30-41%
Protein binding	60-70%
Metabolism	Hepatic (≤5% of dose)
Biological half-life	14.4 hours
Excretion	Feces (~80%) and urine (~10%) as unchanged drug
Identifiers
CAS Registry Number	83799-24-0
ATC code	R06AX26
PubChem	CID: 3348
IUPHAR/BPS	4819
DrugBank	DB00950
ChemSpider	3231
UNII	E6582LOH6V
KEGG	D07958
ChEBI	CHEBI:5050
ChEMBL	CHEMBL914
Chemical data
Formula	C32H39NO4
Molecular mass	501.68 g/mol
	SMILES O=C(O)C(c1ccc(cc1)C(O)CCCN2CCC(CC2)C(O)(c3ccccc3)c4ccccc4)(C)C ;
	InChI 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) ; Key:RWTNPBWLLIMQHL-UHFFFAOYSA-N ;
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