fexofenadine hydrochloride

• フェキソフェナジン fexofenadine、塩酸フェキソフェナジン

WordNet

1. a complex consisting of an organic base in association with hydrogen chloride

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/06/12 21:35:26」(JST)

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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)
Half-life	14.4 hours
Excretion	Feces (~80%) and urine (~10%) as unchanged drug
Identifiers
CAS Registry Number	83799-24-0 Y
ATC code	R06AX26
PubChem	CID: 3348
DrugBank	DB00950 Y
ChemSpider	3231 Y
UNII	E6582LOH6V Y
KEGG	D07958 Y
ChEBI	CHEBI:5050 Y
ChEMBL	CHEMBL914 Y
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)  N Key:RWTNPBWLLIMQHL-UHFFFAOYSA-N  Y
N (what is this?)  (verify)

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.

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.

Medical uses

Fexofenadine is used for relief from physical symptoms associated with seasonal allergic rhinitis and for treatment of chronic urticaria. 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.

• 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.

• 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.

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.

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

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. 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. 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.

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.

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).

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

Metabolism: Only a 5% is metabolized in the liver.

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

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.

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. Grapefruit juice can significantly reduce the plasma concentration of fexofenadine.

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

Special populations

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

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.

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.

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. 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.

See also

• Azacyclonol
• Terfenadine

References

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

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• 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. 肥満細胞活性化障害 mast cell activation disorders

English Journal

• Effects of verapamil on the pharmacokinetics and hepatobiliary disposition of fexofenadine in pigs.

• Sjögren E1, Hedeland M2, Bondesson U2, Lennernäs H3.
• European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.Eur J Pharm Sci.2014 Jun 16;57:214-23. doi: 10.1016/j.ejps.2013.09.014. Epub 2013 Sep 27.
• The pharmacokinetics (PK) of fexofenadine (FEX) in pigs were investigated with the focus on exploring the interplay between hepatic transport and metabolism when administered intravenously (iv) alone or with verapamil. The in vivo pig model enabled simultaneous sampling from plasma (pre-liver, post-
• PMID 24075962

• Effects of one-time apple juice ingestion on the pharmacokinetics of fexofenadine enantiomers.

• Akamine Y1, Miura M, Komori H, Saito S, Kusuhara H, Tamai I, Ieiri I, Uno T, Yasui-Furukori N.
• European journal of clinical pharmacology.Eur J Clin Pharmacol.2014 Jun 7. [Epub ahead of print]
• PURPOSE: We examined the effect of a single apple juice intake on the pharmacokinetics of fexofenadine enantiomers in healthy Japanese subjects.METHODS: In a randomized two phase, open-label crossover study, 14 subjects received 60 mg of racemic fexofenadine simultaneously with water or apple juice
• PMID 24903351

• H1-antihistamines exacerbate high fat diet-induced hepatic steatosis in wild-type but not in apolipoprotein E-knockout mice.

• Vimala Raveendran V1, Kassel KM1, Smith DD1, Luyendyk J2, Williams KJ2, Cherian R3, Reed GA1, Flynn CA1, Csanaky IL1, Lickteig AL1, Pratt-Hyatt MJ1, Klaassen CD1, Dileepan KN4.
• American journal of physiology. Gastrointestinal and liver physiology.Am J Physiol Gastrointest Liver Physiol.2014 May 22. pii: ajpgi.00027.2014. [Epub ahead of print]
• We examined the effects of two over-the-counter H1-antihistamines on the progression of fatty liver disease in male C57Bl/6 wild-type and ApoE-/- mice. Mice were fed a high-fat diet (HFD) for 3 months, together with administration of either cetirizine (4 mg/kg b.w.) or fexofenadine (40 mg/kg b.w.) i
• PMID 24852568

Japanese Journal

• 小児通年性アレルギー性鼻炎患者を対象としたフェキソフェナジン塩酸塩ドライシロップ剤の安全性及び有効性の検討 : 第Ⅲ相,多施設共同,非盲検,無対照試験

• 眞弓 光文,佐藤 俊明,高木 義治 [他]
• アレルギー・免疫 21(2), 306-319, 2014-02
• NAID 40019951660

• Oral Administration of Fexofenadine Hydrochloride can Attenuate Nasal Symptoms and Restore the Impaired Cognitive Function in School-Age Patients with Japanese Cedar Pollinosis

• 青井 典明,清水 保彦,森倉 一朗[他]
• Shimane journal of medical science 29(2), 79-86, 2013-02-01
• NAID 110009591609

• 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Ⅱ/Ⅲ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

Related Links

• Fexofenadine - Wikipedia, the free encyclopedia

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 ...

• Allegra (Fexofenadine Hcl) Drug Information: Description, User ...

Learn about the prescription medication Allegra (Fexofenadine Hcl), drug uses, dosage, side effects, drug interactions, warnings, reviews and patient labeling.

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★リンクテーブル★

リンク元	「フェキソフェナジン」「Allegra」
関連記事	「hydrochloride」「fexofenadine」

「フェキソフェナジン」

　　[★]

英

fexofenadine

化

塩酸フェキソフェナジン fexofenadine hydrochloride

商

アレグラ

関

テルフェナジン

• 抗ヒスタミン薬

• 第二世代ヒスタミン薬

• ピペリジン系

• テルフェナジンの活性代謝物。テルフェナジンのようにQT延長を起こさない。
• アレグラはアレロック、ジルテックより眠くならない。アレグラ、クラリチンは服用後の自動車運転について注意書きがないくらい覚醒に及ぼす影響が小さいらしい。

「Allegra」

　　[★]

アレグラ

関

fexofenadine、fexofenadine hydrochloride

「hydrochloride」

　　[★] 塩酸塩、ハイドロクロライド 　

「fexofenadine」

　　[★] フェキソフェナジン