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CAS 153439-40-8
PharmaCompass
CAS 153439-40-8
Also known as: 153439-40-8, Fexofenadine hcl, Allegra, Telfast, 2-(4-(1-hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid hydrochloride, Fexofenidine hydrochloride
Molecular Formula
C32H40ClNO4
Molecular Weight
538.125  g/mol
InChI Key
RRJFVPUCXDGFJB-UHFFFAOYSA-N

1 2D Structure

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
2-[4-[1-hydroxy-4-[4-[hydroxy(diphenyl)methyl]piperidin-1-yl]butyl]phenyl]-2-methylpropanoic acid;hydrochloride
2.1.2 InChI
InChI=1S/C32H39NO4.ClH/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);1H
2.1.3 InChI Key
RRJFVPUCXDGFJB-UHFFFAOYSA-N
2.1.4 Canonical SMILES
CC(C)(C1=CC=C(C=C1)C(CCCN2CCC(CC2)C(C3=CC=CC=C3)(C4=CC=CC=C4)O)O)C(=O)O.Cl
2.2 Synonyms
2.2.1 Depositor-Supplied Synonyms

1. 153439-40-8

2. Fexofenadine Hcl

3. Allegra

4. Telfast

5. 2-(4-(1-hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic Acid Hydrochloride

6. Fexofenidine Hydrochloride

7. Mdl 16,455a

8. Fexofenadine (hydrochloride)

9. Terfenadine Carboxylate Hydrochloride

10. 138452-21-8

11. Mdl 16455 Hydrochloride

12. Mdl-16455a

13. Terfenidine Carboxylate Hydrochloride

14. Mfcd00865710

15. Allegra (tn)

16. Mdl-16455

17. C32h40clno4

18. Dsstox_cid_28642

19. Dsstox_rid_82912

20. Dsstox_gsid_48716

21. 2-(4-{1-hydroxy-4-[4-(hydroxydiphenylmethyl)piperidin-1-yl]butyl}phenyl)-2-methylpropanoic Acid Hydrochloride

22. Allegra Allergy

23. Allegra Hives

24. 2-[4-[1-hydroxy-4-[4-(hydroxy-diphenyl-methyl)-1-piperidyl]-butyl]phenyl]-2-methyl-propanoicacidhydrochloride

25. Smr000718798

26. Cas-153439-40-8

27. Ncgc00015453-05

28. Children's Allegra Hives

29. Children's Allegra Allergy

30. Altiva

31. Unii-2s068b75zu

32. Carboxyterfenadine Hydrochloride

33. Allegra Flash

34. Allegra Od

35. Ks-1057

36. Fexofenadine(hclform)

37. Fexofenadine Hydrochloride [usan:usp]

38. Mdl 16.455

39. Telfast Bd

40. Fexofenadinehydrochloride

41. Ac1l1y6v

42. Ac1q3e6w

43. C32h39no4.hcl

44. Schembl40914

45. Mls001306422

46. Mls001332493

47. Mls001332494

48. Fexofenadine(hcl Form)

49. Spectrum1504179

50. Chebi:5051

51. Chembl1200618

52. Dtxsid5048716

53. Ctk8b4006

54. Hy-b0801a

55. Molport-003-666-536

56. Rrjfvpucxdgfjb-uhfffaoysa-n

57. 2s068b75zu

58. Bb_sc-4132

59. Mdl 16455a

60. Pharmakon1600-01504179

61. Ks-000011xn

62. Tox21_113125

63. Anw-43654

64. Cf0042

65. Nsc758678

66. S3208

67. Akos015907422

68. Tox21_113125_1

69. Ab07499

70. Ccg-213275

71. Cs-4483

72. Nc00724

73. Nsc-758678

74. Rp17816

75. Rtr-006346

76. Alpha-(4-(1-carboxy-1-methylethyl)phenyl)-4-hydroxydiphenylmethyl-1-piperidinebutanol

77. Fexofenadine Hydrochloride (jp17/usan)

78. Ncgc00015453-02

79. Ncgc00015453-08

80. Ncgc00092389-01

81. Ncgc00095906-01

82. Ncgc00095906-02

83. (+-)-p-(1-hydroxy-4-(4-(hydroxydiphenylmethyl)piperidino)butyl)-alpha-methylhydratropic Acid Hydrochloride

84. Ac-24745

85. Ak-72915

86. Br-72915

87. Cpd000718798

88. He181612

89. Sam002700173

90. Fexofenadine Hydrochloride, >98% (hplc)

91. Ab0011964

92. Kb-222041

93. Ls-173025

94. Tr-006346

95. 4ch-009369

96. F0698

97. Ft-0631183

98. M-016455-o

99. Bim-0050472.0001

100. Carboxyterfenadine,terfenadinecarboxylate

101. D00671

102. J10191

103. S-5170

104. 452f218

105. J-505843

106. Z2210694607

107. Fexofenadine Hydrochloride, European Pharmacopoeia (ep) Reference Standard

108. 2-[4-(1-hydroxy-4-{4-[hydroxy(diphenyl)methyl]piperidin-1-yl}butyl)phenyl]-2-methylpropans

109. Fexofenadine Hcl, Pharmaceutical Secondary Standard; Certified Reference Material

110. Fexofenadine Hydrochloride, United States Pharmacopeia (usp) Reference Standard

111. 2-(4-(1-hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic Acid Hcl

112. 2-(4-(1-hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic Acid Hydr

113. 2-(4-(1-hydroxy-4-[4-(hydroxy-diphenyl-methyl)-piperidin-1-yl]-butyl)-phenyl)-2-methyl-propionic Acid Hydrochloride

114. 2-(4-{1-hydroxy-4-[4-(hydroxy-diphenyl-methyl)-piperidin-1-yl]-butyl}-phenyl)-2-methyl-propionic Acid; Hydrochloride

115. 2-[4-[1-hydroxy-4-[4-[hydroxy(diphenyl)methyl]piperidin-1-yl]butyl]phenyl]-2-methylpropanoic Acid Hydrochloride

116. 2-[4-[1-hydroxy-4-[4-[hydroxy(diphenyl)methyl]piperidin-1-yl]butyl]phenyl]-2-methylpropanoic Acid;hydrochloride

117. 4-[(4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-alpha,alpha-dimethylbenzeneacetic Acid Hydrochloride

118. 4-[1-hydroxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]butyl]-alpha,alpha-dimethyl-benzeneacetic Acid, Hydrochloride (1:1)

119. 4-[4-[4-(hydroxydiphenylmethyl)-1-pieridinyl]-1-hydroxybutyl]-alpha,alpha-dimethylbenzeneacetic Acid Hydrochloride

120. 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-alpha,alpha-dimethylbenzeneacetic Acid Hydrochloride

121. Benzeneacetic Acid, 4-(1-hydroxy-4-(4-(hydroxydiphenylmethyl)-1-piperidinyl)butyl)-alpha,alpha-dimethyl-, Hydrochloride

122. Benzeneacetic Acid, 4-(1-hydroxy-4-(4-(hydroxydiphenylmethyl)-1-piperidinyl)butyl)-alpha,alpha-dimethyl-, Hydrochloride, (+-)-

2.3 Create Date
2005-06-24
3 Chemical and Physical Properties
Molecular Weight 538.125 g/mol
Molecular Formula C32H40ClNO4
Hydrogen Bond Donor Count4
Hydrogen Bond Acceptor Count5
Rotatable Bond Count10
Exact Mass537.265 g/mol
Monoisotopic Mass537.265 g/mol
Topological Polar Surface Area81 A^2
Heavy Atom Count38
Formal Charge0
Complexity678
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count1
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count2
4 Drug and Medication Information
4.1 Drug Information
1 of 2  
Drug NameALLEGRA
Active IngredientFEXOFENADINE HYDROCHLORIDE
CompanySANOFI AVENTIS US (Application Number: N021963)

2 of 2  
Drug NameFEXOFENADINE HYDROCHLORIDE
Active IngredientFEXOFENADINE HYDROCHLORIDE
CompanyACTAVIS MID ATLANTIC (Application Number: A201311); BARR (Application Number: A076191); DR REDDYS LABS LTD (Application Number: A076502); MYLAN (Application Number: A077081); TEVA (Application Number: A076447)

4.2 Therapeutic Uses

Histamine H1 antagonists

National Library of Medicine's Medical Subject Headings online file (MeSH, 2006)


Antihistaminic

O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 718


Fexofenadine is indicated to relieve symptoms that are associated with seasonal allergic rhinitis, such as sneezing;rhinorrhea; itchy eyes, nose and throt; and red watery eyes. /Included in US product label/

Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 1470


Fexofenadine is indicated for the treatment of uncomplicated skin manifestations of chronic idiopathic urticaria. It significantly reduces pruritus and the number of wheals. /Included in US product label/

Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 1470


4.3 Drug Warning

In controlled clinical studies in patients 12 years of age and older with allergic rhinitis receiving oral fexofenadine hydrochloride dosages of 60 mg twice daily or placebo, drowsiness or fatigue occurred in 1.3% of patients, compared with 0.9% of those receiving placebo. In these studies in patients receiving fexofenadine hydrochloride dosages of 180 mg once daily (as conventional tablets) or placebo, headache was reported in 10.6 or 7.5% of patients, respectively. In controlled studies in children 6-11 years of age with seasonal allergic rhinitis receiving fexofenadine hydrochloride dosages of 30 mg twice daily or placebo, headache was reported in 7.2 or 6.6% of patients, respectively, while pain was reported in 2.4 or 0.4% of patients, respectively.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 33


Sleep disorder, insomnia, or paroniria has occurred in patients receiving fexofenadine hydrochloride.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 33


During controlled clinical studies, nausea and dyspepsia were reported in 1.6 and 1.3%, respectively, of patients receiving oral fexofenadine hydrochloride dosages of 60 mg twice daily versus 1.5 and 0.6%, respectively, of those receiving placebo.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 33


Clinical data from over 2000 patients indicate that fexofenadine hydrochloride lacks the cardiotoxic potential of its parent drug terfenadine. In 714 patients with seasonal allergic rhinitis, fexofenadine hydrochloride dosages of 60-240 mg twice daily were not associated with statistically significant mean increases in the QT interval corrected for rate (QTc) in controlled clinical studies. In addition, in 231 healthy individuals, fexofenadine hydrochloride dosages of 240 mg given once daily for 1 year also were not associated with statistically significant increases in the mean QTc. Even at dosages exceeding these (e.g., up to 400 mg twice daily for 6 days in 40 patients, up to 690 mg twice daily for about 1 month in 32 patients, up to 800 mg given in a single dose in 87 patients), statistically significant mean increases in the QTc or other ECG abnormalities have not been reported in healthy adults or patients with seasonal allergic rhinitis.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 33


Rash, urticaria, pruritus, and hypersensitivity reactions including angioedema, chest tightness, dyspnea, flushing, or anaphylaxis have been reported rarely in patients receiving fexofenadine hydrochloride.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 34


Viral infection (eg, cold, influenza) or dysmenorrhea was reported in 2.5 or 1.5% of patients 12 years of age and older receiving fexofenadine hydrochloride in dosages of 60 mg twice daily, respectively. In controlled clinical studies in adults and children 12 years of age and older receiving fexofenadine hydrochloride dosages of 180 mg once daily or placebo, upper respiratory tract infection was reported in 3.2 or 3.1% of patients, respectively, while back pain was reported in 2.8 or 1.4% of patients, respectively.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 34


In controlled studies in children 6-11 years of age with seasonal allergic rhinitis receiving fexofenadine hydrochloride 30 mg twice daily, upper respiratory tract infection, coughing, accidental injury, fever, and otitis media occurred in 4.3, 3.8, 2.9, 2.4, and 2.4% of children, respectively, while these adverse effects were reported in 1.7, 1.3, 1.3, 0.9, and 0%, respectively, in those receiving placebo.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 34


In controlled studies in adults and children 12 years and older with chronic idiopathic urticaria receiving fexofenadine hydrochloride dosages of 60 mg twice daily or placebo, both back pain and sinusitis were reported in 2.2 or 1.1% of patients, respectively.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 34


Fexofenadine is contraindicated in patients who are hypersensitive to the drug or any ingredient in its formulation.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 34


Safety and efficacy of fexofenadine hydrochloride have not been established in children younger than 6 years of age.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 34


It is not known if fexofenadine hydrochloride is distributed into breast milk ... Since there are no adequate and controlled studies to date on the use of fexofenadine during lactation in humans and because many drugs are excreted in human milk, the manufacturer states that fexofenadine alone or in fixed combination with pseudoephedrine hydrochloride should be used with caution in nursing women, and a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 34


FDA Pregnancy Risk Category: C /RISK CANNOT BE RULED OUT. Adequate, well controlled human studies are lacking, and animal studies have shown risk to the fetus or are lacking as well. There is a chance of fetal harm if the drug is given during pregnancy; but the potential benefits may outweigh the potential risk./

Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 1471


In clinical trials, dysmenorrhea occurred in 1.5% of patients receivingoral fexofenadine 60 mg twice daily, compared to 0.3% in patients receiving placebo.

Physicians Desk Reference 60th ed, Thomson PDR, Montvale, NJ 2006., p. 2859


To gain insight into possible mechanisms of and predisposing factors for torsades de pointes during terfenadine therapy, spontaneous reports in the US Food and Drug Administration's Spontaneous Reporting System database were examined. Based on the characteristics of the cases, in vitro cardiac electrophysiologic studies were conducted to test the hypothesis that terfenadine, and not its major metabolite, has actions similar to those of quinidine and is responsible for this form of cardiac toxicity. Spontaneous reports from the general medical community. As of April 1, 1992, 25 cases of torsades de pointes had been reported to the Food and Drug Administration's Spontaneous Reporting System. Predisposing factors in these cases indicated that the parent drug /(terfenadine)/, but not its metabolite /(fexofenadine)/, may have actions similar those of quinidine that are responsible for inducing arrhythmia. In vitro studies found that terfenadine is equipotent to quinidine as a blocker of the delayed rectifier potassium current in isolated feline myocytes. The metabolite, terfenadine carboxylate, did not inhibit this potassium current even at concentrations 30 times higher than the concentration of terfenadine producing a half-maximal effect. Since blockade of the potassium channel did not occur with the major metabolite of terfenadine, episodes of torsades de pointes are most likely the result of a quinidine-like action of the parent drug and of factors that impair the normally rapid metabolism of terfenadine. Dosage restriction and awareness of the clinical conditions and drug interactions capable of inhibiting the metabolism of terfenadine are essential for prevention of this serious reaction.

Woosley RL et al; JAMA 269 (12): 1532-6 (1993)


The effect of /fexofenadine/ on the corrected QT interval (QTc) was evaluated in dose-tolerance, safety, and drug-interaction studies with healthy volunteers, and in clinical studies in patients with seasonal allergic rhinitis (SAR). Twelve-lead electrocardiographic data were collected once before and after dosing or serially throughout these studies. Outliers were defined as QTc > 440 ms with a > or = 10 ms increase from baseline. The recommended fexofenadine HCl dose is 60 mg twice daily. Fexofenadine HCl doses up to 800 mg once daily or 690 mg twice daily for 28 days resulted in no dose-related increases in QTc. Longer term studies indicated no statistically significant QTc increases compared with placebo in patients receiving fexofenadine HCl 80 mg twice daily for 3 months, 60 mg twice daily for 6 months, or 240 mg once daily for 12 months. Interaction studies showed no significant increases in QTc when fexofenadine HCl 120 mg twice daily was administered in combination with erythromycin (500 mg 3 times daily) or ketoconazole (400 mg once daily) after dosing to steady state (6.5 days). Clinical trials in patients with SAR (n = 1,160) treated with 40, 60, 120, or 240 mg twice-daily fexofenadine HCl or placebo indicated no dose-related increases in QTc and no statistically significant increases in mean QTc compared with placebo. In controlled trials with approximately 6,000 persons, no case of fexofenadine-associated torsades de pointes was observed. The frequency and magnitude of QTc outliers were similar between fexofenadine HCl and placebo in all studies. Based on a large clinical database, /the authors/ conclude that fexofenadine HCl has no significant effect on QTc, even at doses > 10-fold higher than that is efficacious for SAR.

Pratt CM et al; Am J Cardiol 83 (10): 1451-4 (1999)


5 Pharmacology and Biochemistry
5.1 Pharmacology

Fexofenadine Hydrochloride is the hydrochloride salt form of fexofenadine, a carboxylated metabolic derivative of terfenadine and second generation, long-lasting selective histamine H1 receptor antagonist, with antihistaminic activity. Upon administration, fexofenadine competitively binds of peripheral H1-receptors in the gastrointestinal (GI) tract, blood vessels, and bronchial smooth muscle. This prevents binding of histamine to peripheral H1-receptors and prevents their activation. This prevents a histamine-mediated allergic reaction. Fexofenadine does not cross the blood-brain-barrier (BBB).


5.2 MeSH Pharmacological Classification

Histamine H1 Antagonists, Non-Sedating

A class of non-sedating drugs that bind to but do not activate histamine receptors (DRUG INVERSE AGONISM), thereby blocking the actions of histamine or histamine agonists. These antihistamines represent a heterogenous group of compounds with differing chemical structures, adverse effects, distribution, and metabolism. Compared to the early (first generation) antihistamines, these non-sedating antihistamines have greater receptor specificity, lower penetration of BLOOD-BRAIN BARRIER, and are less likely to cause drowsiness or psychomotor impairment.


Anti-Allergic Agents

Agents that are used to treat allergic reactions. Most of these drugs act by preventing the release of inflammatory mediators or inhibiting the actions of released mediators on their target cells. (From AMA Drug Evaluations Annual, 1994, p475)


5.3 Absorption, Distribution and Excretion

Fexofenadine hydrochloride is rapidly absorbed from the GI tract following oral administration. Following oral administration of two 60-mg fexofenadine hydrochloride capsules, peak plasma concentrations are achieved in about 2.6 hours. Following oral administration of a single 60-mg capsule or 60- or 180-mg conventional tablet in healthy individuals, mean peak plasma concentrations were 131, 142, and 494 ng/mL, respectively. In healthy men, peak plasma concentrations of 167 ng/mL were achieved within 1.42 hours following oral administration of 60-mg fexofenadine hydrochloride doses every 12 hours for 9 doses.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 35


Following oral administration of fexofenadine hydrochloride capsules in fasting children (mean age: 8-11.6 years) with a history of allergic rhinitis with or without mild asthma, peak plasma fexofenadine concentrations of about 178 or 286 ng/mL were attained in approximately 2.4 hours after a 30- or 60-mg dose, respectively.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 36


Following oral administration of a 60-mg dose of fexofenadine hydrochloride, the AUC was 56% greater in children 7-12 years of age with allergic rhinitis than in healthy adults. Plasma exposure in children receiving 30 mg of fexofenadine hydrochloride is similar to that of adults receiving 60 mg of the drug. Limited data indicate that peak plasma fexofenadine concentrations in adolescents (12-16 years of age) were similar to those in adults, while peak plasma concentrations in geriatric adults (65 years of age and older) were 99% greater than in healthy individuals younger than 65 years of age. AUC also was higher in geriatric adults (65-80 years of age) than in younger adults (19-45 years of age)...

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 36


Peak plasma concentrations of fexofenadine were 87 and 111% higher in patients with mild (creatinine clearance of 41-80 mL/minute) to severe (creatinine clearance of 11-40 mL/minute) renal impairment, respectively, compared with those observed in healthy adults. In patients undergoing dialysis (creatinine clearance of 10 mL/minute or less), peak plasma concentrations of fexofenadine were 82% higher than in healthy adults.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 36


Volume of distribution is 5.4 to 5.8 litrs/kilogram

Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 1470


Distribution of fexofenadine into human body tissues and fluids has not been fully elucidated. Following oral administration of fexofenadine hydrochloride in animals, the drug is distributed into the small and large intestines, stomach, pancreas, liver, and kidney. Fexofenadine distributes more extensively into plasma than into blood or saliva. The drug does not appear to cross the blood-brain barrier.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 36


It is not known if fexofenadine crosses the placenta or is distributed into breast milk.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 36


Fexofenadine is 60-70% bound to plasma proteins, principally albumin and alpha1-acid glycoprotein.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 36


Following oral administration of single 30- or 60-mg doses of fexofenadine hydrochloride as capsules in fasting children (mean age: 8-11.6 years), the apparent volume of distribution was about 5.4 or 5.8 L/kg, respectively.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 36


Limited data indicate that oral clearance of the drug is 33% lower in females than in males, although renal clearance of the drug appears to be similar in both genders. In addition, oral clearance in geriatric adults (65-80 years of age) was lower than in younger adults (19-45 years of age). Following oral administration of a 30- or 60-mg dose of fexofenadine hydrochloride capsules in fasting children (mean age: 8-11.6 years), clearance rates averaged about 14.4 or 18.4 mL/minute per kg, respectively.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 36


Fexofenadine is eliminated principally in feces; however, because the absolute bioavailability of fexofenadine hydrochloride has not been established, it remains to be established whether fecal component represents unabsorbed drug or it is the result of biliary excretion. The drug also is excreted in urine, and approximately 80 and 11-12% of the drug is excreted in feces and urine, respectively.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 36


Two randomized, double-blind, parallel-group, placebo-controlled dose-escalation studies were performed in healthy men to determine the maximum tolerated oral dose, pharmacokinetics, pharmacodynamics, and safety of fexofenadine hydrochloride. In the first study, 87 subjects (6 in the active drug group and 2 in the placebo group) received single oral doses of fexofenadine hydrochloride ranging from 10 to 800 mg or placebo. In the second study, 32 subjects (3 in the active drug group and 1 in the placebo group) received multiple fexofenadine hydrochloride doses ranging from 20 to 690 mg or placebo twice daily for 28 1/2 days. Serial plasma and urine samples were collected. Fexofenadine concentrations were determined by HPLC and fluorescence. Wheal and flare response to intradermal histamine was used to evaluate antihistaminic activity. Fexofenadine hydrochloride was rapidly absorbed, reaching peak concentrations in 0.83 to 1.33 hours. Single-dose mean concentration ranged from 46 to 6383 ng/mL, and steady-state maximum plasma concentration ranged from 58 to 4677 ng/mL. Mean area under the plasma concentration-time curve was approximately proportional to dose. Oral clearance, renal clearance, and cumulative percent of drug excreted in urine were similar after single and multiple doses and were generally constant over the dose range studied. Inhibition of skin wheal and flare was shown for single doses of 40 mg and higher and for all multiple doses. No fexofenadine dose-related trends or apparent differences from placebo were found for any safety parameter. Fexofenadine hydrochloride was well tolerated at oral doses up to 11 times the recommended therapeutic dose. In addition, fexofenadine hydrochloride showed significant antihistaminic activity and dose-proportional pharmacokinetics over a wide dosing range.

Russell T et al; Clin Pharmacol Ther 64 (6): 612-21 (1998)


5.4 Metabolism/Metabolites

About 5% of a single oral dose of fexofenadine is metabolized.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 36


Negligible amounts of fexofenadine (about 0.5-1.5% of a dose) are metabolized in the liver by the cytochrome P-450 microsomal enzyme system to an inactive metabolite, while about 3.5% of a fexofenadine dose is metabolized by a second metabolic pathway (unrelated to the cytochrome P-450 microsomal enzyme system) to the methyl ester derivative of fexofenadine. The methyl ester metabolite of fexofenadine is found only in feces, and it has been suggested that the intestinal flora probably are involved in this metabolism.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 36


5.5 Biological Half-Life

Following oral administration of 60 mg of fexofenadine hydrochloride twice daily in healthy individuals, the mean elimination half-life of the drug at steady state reportedly is about 14.4-14.6 hours; mean elimination half-life reportedly was similar in geriatric adults (65 years of age or older) who received a single 80-mg oral dose of fexofenadine hydrochloride.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 36


... Elimination half-life was about 18 hours in fasting children (mean age: 8-11.6 years) who received single oral 30- or 60-mg doses of fexofenadine hydrochloride as capsules.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 36


In patients with mild (creatinine clearance of 41-80 mL/minute) to severe (creatinine clearance of 11-40 mL/minute) renal impairment, mean elimination half-lives were 59 and 72% longer than those observed in healthy individuals, respectively.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 36


In patients undergoing dialysis (creatinine clearance of 10 mL/minute or less), elimination half-life was 31% longer than in healthy individuals.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 36


5.6 Mechanism of Action

Fexofenadine is a specific, selective, histamine H1-receptor antagonist. ... Fexofenadine has been shown to inhibit histamine release from peritoneal mast cells in rats. Unlike terfenadine, fexofenadine does not block the potassium channel involved in repolarization of cardiac cells (i.e., blockade of the delayed rectifier potassium current IK). As a result, fexofenadine lacks the cardiotoxic potential of terfenadine. Fexofenadine also does not possess appreciable anticholinergic, antidopaminergic, or alpha- or beta-adrenergic blocking effects at usual antihistaminic doses in pharmacologic studies.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 35


It has been suggested that the increased safety profile of fexofenadine compared with the parent drug results from the lack of fexofenadine-induced cardiotoxicity in addition to only minimal metabolism of fexofenadine in the liver by the cytochrome P-450 microsomal enzyme system. Evidence from animal models using fexofenadine have suggested that the apparent lack of cardiotoxic effects of the drug may have resulted at least in part from lack of blockade of the potassium channel involved in repolarization of cardiac cells (ie, blockade of the delayed rectifier potassium current IK). Prolongations in the QTc interval were not reported in dogs receiving oral fexofenadine hydrochloride dosages of 10 mg/kg daily for 5 days or in rabbits receiving an IV fexofenadine hydrochloride dose of 10 mg/kg (resulting in plasma fexofenadine concentrations 28 or 63 times the therapeutic plasma concentrations in humans, respectively, based on a dosage of 60 mg of fexofenadine hydrochloride given twice daily). In addition, no effect was observed on calcium-channel current, delayed potassium-channel current, or action potential duration in guinea pig myocytes, sodium current in rat neonatal myocytes, or on the delayed rectifier potassium channel cloned from human heart at fexofenadine concentrations up to 1.0 X10-5 M (approximately equivalent to 32 times the therapeutic plasma concentrations in humans, based on a dosage of 60 mg of fexofenadine hydrochloride given twice daily).

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 33


In vitro, terfenadine exhibits a similar affinity for histamine H1-receptors from brain and peripheral tissues; however, in vivo, unlike first generation antihistamines, terfenadine and fexofenadine do not readily cross the blood-brain barrier and therefore do not appear to interact appreciably with H1-receptors within the CNS at usual doses.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 35


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