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Farya Zafar / Journal of Pharmacy Research 2012,5(3),1646-1649 Review Article Available online through ISSN: 0974-6943 http://jprsolutions.info A review of hydrochloride Farya Zafar* Department of Pharmaceutics, Faculty of Pharmacy, University of Karachi, Karachi, Pakistan. Received on:10-12-2011; Revised on: 15-01-2012; Accepted on:12-02-2012

ABSTRACT Fexofenadine is the hydrochloride salt of ’s active metabolite. In 2006, the FDA approved an oral suspension for the management of chronic idiopathic urticaria and seasonal allergic rhinitis in children. This review article summarizes the clinical pharmacology, therapeutic applications, drug-drug interactions, adverse events and food-drug interactions of fexofenadine that have been reported in pervious years.

Key words: Fexofenadine hydrochloride, chronic idiopathic urticaria, clinical pharmacology, therapeutic applications.

INTRODUCTION

More than 45 H1- are accessible worldwide, including the various symptoms such as sneezing, rhinorrhea, nasal pruritus and watery major class of drugs used in the management of allergic disorders [1-5]. eyes [15] associated with allergic rhinitis [16-18]. Authors reported that antihis-

Fexofenadine, is a H 1- having chemical name tamines (second generation) particularly, fexofenadine have anti-inflamma- (+)-4-[1-hydroxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-butyl]- [19, 15] tory response that may decrease nasal congestion . H1 receptor antago- a,a-dimethylbenzeneaceticacid hydrochloride. The empirical formula and nists usually have slight effect on this indication [20-22]. can be [23- the molecular weight is C32H39NO4.HCl and 538.13, respectively. combined with pseudoephedrine, to give complete symptomatic relief Fexofenadine hydrochloride is a racemate and exists as zwitterions in aque- 25]. ous media at physiological pH [6]. The major therapeutic applications of fexofenadine are as follows:

CLINICAL PHARMACOLOGY OF FEXOFENADINE Seasonal allergic rhinitis Mechanism of action Allergic rhinitis is described as inflammation due to an allergic reaction [26]. Fexofenadine is the active metabolite of terfenadine [7, 8]. Fexofenadine hy- Allergic rhinitis is a frequent disorder related with the incidence of morbid- [27] drochloride is an antihistamine having selective peripheral H1- receptor ity . Fexofenadine is particularly renowned for its effective against this antagonist activity. Both enantiomers of fexofenadine hydrochloride showed inflammatory process [28, 26], chronic urticaria [29] and perennial allergic rhini- equivalent antihistaminic response [6]. tis [30]. Fexofenadine may offer equal or superior efficacy in managing aller- gic disorders as compared with other existing second-generation histamine Pharmacokinetics receptor blocker [31-33]. Fexofenadine HCl 60 mg/pseudoephedrine HCl 120 Fexofenadine hydrochloride is absorbed rapidly achieving maximum con- mg is useful in the management of patients having moderate-to-severe sea- centration within 1 to 2 hours [9] after oral administration of a single dose of sonal allergic rhinitis with an excellent safety profile [34]. The effectiveness two 60 mg capsules to male healthy subjects the maximum plasma concen- of fexofenadine hydrochloride (180 mg) and (10 mg) in patients tration was achieved after 2.6 hrs post dose. After administration of a single having seasonal allergic rhinitis were determined. It was found that 60 mg capsule to healthy subjects, the mean maximum plasma concentra- fexofenadine hydrochloride (180 mg) once daily given for 2 weeks showed tion was 131ng/mL. After single oral administration of either the 60 and 180 clinically similar progress in symptoms and extensively less drowsiness in mg tablet to male subjects, maximum plasma concentrations were 142 and patients as compared with cetirizine (10 mg) [35, 36]. Also - 494 ng/mL, respectively. Fexofenadine hydrochloride is 60-70 % bound to montelukast and fexofenadine-pseudoephedrine have equivalent efficacy in [6] [37] plasma proteins, primarily albumin and a 1-acid glycoprotein . Fexofenadine managing the symptoms of nasal obstruction in seasonal allergic rhinitis . hydrochloride undergoes negligible metabolism [10, 11]. Approximately, 5 % Allergic rhinitis affected paediatric residents in a huge percentage. Due to of the total oral dose was metabolized [6]. Fexofenadine is unmetabolized by the availability of number of agents, it has become a test to select the most the liver [9]. Elimination half-life achieved from 13 to 16 hours [12], the mean suitable management for this population. Second-generation antihistamines elimination half life was 14.4 hrs after adminstration of 60 mg twice daily, in are considered relatively secure for use in paediatric population [38, 39]. Segall normal subjects [6]. Approximately, 90% of fexofenadine is found unchanged et al. in 2008 formulated an oral suspension of fexofenadine hydrochloride in the feces and the urine [13]. and evaluated the pharmacokinetic performance, safety and acceptability of oral suspension by administering Fexofenadine HCl (30 mg) as a 6-mg/ THERAPEUTIC APPLICATIONS OF FEXOFENADINE mL suspension (5 mL) to the patients. Plasma samples were collected up to The advantages of H receptor antagonists are well known [14]. The H 1 1 24 hrs. Mean Cmax of fexofenadine was 224 ng/mL and mean AUC was 898 receptor antagonists are the commonly prescribed class of drug for the ng . hour/mL [40]. Similarly, Ngamphaiboon et al. in 2005 suggested the safe management of allergic rhinitis [13]. Antihistamines give useful relief from use of a oral dose of fexofenadine HCl 30 mg (twice-daily) in children aged from 6-11 years having seasonal or perennial allergic rhinitis [41]. Pretreat- ment with fexofenadine could prevent the incidence of severe specific im- *Corresponding author. munotherapy-related systemic reactions facilitated by immunotherapy in Farya Zafar* patients having allergic rhinitis [42]. Department of Pharmaceutics, Faculty of Pharmacy, Chronic idiopathic urticaria University of Karachi, Chronic idiopathic urticaria can have an intense outcome on patient quality Karachi, 75270, Pakistan. of life. Any therapy used to manage chronic idiopathic urticaria without producing side effects is useful [43]. The causes of chronic idiopathic urti-

Journal of Pharmacy Research Vol.5 Issue 3.March 2012 1646-1649 Farya Zafar / Journal of Pharmacy Research 2012,5(3),1646-1649 caria include reactions to drugs, food, infections and thyroid disease etc. tance for residents receiving fexofenadine [61]. Drug-drug interactions would For this purpose the use of new low-sedating antihistamines such as be observed when terfenadine and were prescribed along with , fexofenadine and should be tried first [44] and antibiotics (macrolide) and/or the antifungal agents (itraconazole or fexofenadine, desloratadine and loratadine should be selected over cetirizine ketoconazole) which may result in severe adverse event including death. [43]. Fexofenadine is well-accepted for the management for chronic idio- Fexofenadine and loratadine are least likely nonsedating antihistamines to pathic urticaria [45-47]. It reduces itching, size, number and duration of wheals facilitate interaction with other drugs [62]. Fexofenadine does not undergo and flares [48]. biotransformation; also coadministration of fexofenadine with ketoconazole, erythromycin and azithromycin may elevate fexofenadine plasma concen- Paclitaxel-induced hypersensitive reactions trations [60]. Itraconazole and verapamil elevated the drug plasma concentra- Patients suffering from Paclitaxel showed intense hypersensitivity reac- tions by inhibiting P-glycoprotein activity [63-66]. The AUC0-8 for (S) - and tions such as blood pressure drop and impaired breathing. Fexofenadine (R) - fexofenadine were considerably elevated by 348 and 238% with prevents different hypersensitive reactions in these patients [49]. verapamil and 401 and 307% with itraconazole, respectively [67]. St. John’s wort and rifampin reduces the drug plasma concentrations of fexofendine Atopic alopecia areata [68, 69]. Inui et al. in 2009 assessed the response of fexofenadine in patients suffer- ing from alopecia areata, for this purpose they examined 121 patients ADVERSE EVENTS retrospectively with alopecia areata having alopecia in > 50% of the scalp. Immense overdoses of H1-antihistamines (second generation) particularly Results indicated that fexofenadine is useful in the management of atopic fexofenadine, cetirizine and loratadine have not been linked with respira- alopecia areata with contact immunotherapy [50]. tory depression, seizures, coma or fatality [70, 48]. In children aged between 2 to 5 years having allergic rhinitis, fexofenadine showed some frequent Histamine-induced wheal and flare adverse events which were fever, upper respiratory tract infection and Meltzer and Gillman in 2007 studied fexofenadine versus desloratadine in vomiting [71]. Kulthanan et al. in 2001 reported the toxicity of fexofenadine decreasing histamine-induced skin flares and wheals in patients. They car- in the patients having chronic idiopathic urticaria. From 108 objects only ried out randomized, two-center, crossover study. Results showed that 20 objects showed the occurrence of only one undesirable event which was fexofenadine decreases skin flares drastically than desloratadine [51]. drowsiness, headache, dizziness, elevation in weight and cough [72].

Pruritus associated with atopic dermatitis Possible adverse events in vulnerable patients Kawashima et al. in 2003 found that fexofenadine is helpful in producing The clinical pharmacology of H1-antihistamines (second generation) have relief from pruritus associated with atopic dermatitis. For this purpose been examined prospectively in elderly patients and in patients with im- they carried out placebo-controlled, double-blind, study in patients aged paired renal or hepatic function. If needed, precise instructions for decrease >or= 16 years with atopic dermatitis. Results showed that fexofenadine in dose or frequency should be provided. Considering teratogenicity, reduced the severity of pruritus, it improve both diurnal and nocturnal fexofenadine has been classified as FDA Pregnancy Category C. No CNS pruritus. The Xincidence of adverse events was low and similar across all undesirable events have been studied in nursing infants and in neonates. treatment groups [52]. Also long-term safety of fexofenadine has been verified in young children [48]. Seasonal allergic conjunctivitis FOOD-DRUG INTERACTION In patients having allergic conjunctivitis, H1-antihistamines relieve itching, edema, erythema and tearing [48]. Oral fexofenadine therapy with ophthalmic Authors reported that fruit juice may affect the pharmacokinetics of solution (nedocromil sodium 2%) reduces ocular indication of seasonal fexofenadine [29, 73]. Intake of grapefruit juice with fexofenadine decreases allergic rhinoconjunctivitis [53]. the bioavailability of drug [74], orange and apple juice decrease the oral bioavailability of fexofenadine by inhibiting the activity of organic anion Cedar pollinosis transporter polypeptides (OATPs) [75]. Miyabe et al. in 2003 studied the effectiveness of fexofenadine hydrochlo- ride in patients with cedar pollinosis. They concluded that patients admin- CONCLUSION istered with fexofenadine hydrochloride having cedar pollinosis are able to Fexofenadine is suitable for acute allergic reaction and it also provides a manage the worsening of their indications after the considerable pollen basis for future expansion of H1 antagonists with more efficient anti-inflam- scattering [54]. matory response [76].

Anaphylaxis ACKNOWLEDGEMENTS The author reported that no conflict of interest and no funding were col- No randomized controlled trials are reported for H1- antihistamine that gave acceptable support for their use in anaphylaxis. But they relieve hives lected on this work. and itch [55]. REFERENCES Other disorders 1. Keam SJ, Plosker GL. : a review of its use in the manage- H -antihistamines are used to manage different indications of upper respi- ment of allergic disorders. Drugs. 2007; 67: 457-74. 1 2. Church MK. Efficacy and tolerability of rupatadine at four times the ratory tract infections such as otitis, sinusitis, acute otitis media, nonspe- recommended dose against histamine- and platelet-activating fac- cific cough, nonallergic and nonspecific itching [48]. tor-induced flare responses and ex vivo platelet aggregation in healthy males. Br J Dermatol. 2010; 163:1330-2. DRUG-DRUG INTERACTIONS 3. Horak F, Zieglmayer P, Zieglmayer R, Lemell P. The effects of Drug–drug interactions are due to the variations in the activities of enzymes compared with cetirizine, fexofenadine, and placebo on [56, 59] allergen-induced nasal and ocular symptoms in patients exposed to and transporters . Drug interactions are not bound to metabolism but aeroallergen in the Vienna Challenge Chamber. Inflamm Res. 2010; the bioavailability of compound may be varied by coadministration of 59: 391-8. compounds that produce its impact on absorption through active transport 4. Hampel FC, Ratner PH, Van Bavel J, Amar NJ, Daftary P, Wheeler systems [60]. W, et al. Double-blind, placebo-controlled study of and fluticasone in a single nasal spray delivery device. Ann Allergy Carbamazepine considerably decreases fexofenadine concentrations in Asthma Immunol. 2010; 105: 168-73. 5. Bohets H, McGowan C, Mannens G, Schroeder N, Edwards-Swanson plasma. Therefore, Carbamazepine treatment is of moderate clinical impor- Journal of Pharmacy Research Vol.5 Issue 3.March 2012 1646-1649 Farya Zafar / Journal of Pharmacy Research 2012,5(3),1646-1649 K, Shapiro A. Clinical pharmacology of alcaftadine, a novel antihis- tamine for the prevention of allergic conjunctivitis. J Ocul Pharmacol Drugs. 2000; 59:301-21. Ther. 2011; 27:187-95. 30. Bunnag C, Jareoncharsri P, Tunsuriyawong P, Pumhirun P, 6. PDR. The Physicians’ Desk Reference. 2006. Thomason PDR NJ. Limprasertsiri S, Chochaipanichnon L, Supiyaphun P, Kongpatanakul 2857-2858. S. A non-comparative trial of the efficacy and safety of fexofenadine 7. Markham A, Wagstaff AJ. Fexofenadine. Drugs. 1998; 55: 269-76. for treatment of perennial allergic rhinitis. Asian Pac J Allergy 8. Garteiz DA, Hook RH, Walker BJ, Okerholm RA. Pharmacokinetics Immunol. 2000; 18(3):127-33. and biotransformation studies of terfenadine in man. Arzneim-Forsch 31. Smith SM, Gums JG. Fexofenadine: biochemical, pharmacokinetic Drug Res. 1982; 32: 1185-90. and pharmacodynamic properties and its unique role in allergic 9. Lippert C, Ling J, Brown P, Burmaster S, Eller M, Cheng L, et al. disorders. Expert Opin Drug Metab Toxicol. 2009; 5(7):813-22. Mass balance and pharmacokinetics of MDL 16,455A in healthy 32. Meltzer EO, Casale TB, Nathan RA, Thompson AK. Once-daily male volunteers. Pharm Res. 1995; 12:390. fexofenadine HCl improves quality of life and reduces work and 10. Chen C. Some pharmacokinetic aspects of the lipophilic terfenadine activity impairment in patients with seasonal allergic rhinitis. Ann and zwitterionic fexofenadine in humans. Drugs R. Dev. 2007; 8 Allergy Asthma Immunol. 1999; 83(4):311-7. (5), 301–314. 33. Howarth PH, Stern MA, Roi L, Reynolds R, Bousquet J. Double- 11. Cvetkovic M, Leake B, Fromm MF, et al. OATP and P-glycoprotein blind, placebo-controlled study comparing the efficacy and safety transporters mediate the cellular uptake and excretion of of fexofenadine hydrochloride (120 and 180 mg once daily) and fexofenadine. Drug Metab Dispos. 1999; 27:866-71 cetirizine in seasonal allergic rhinitis. J Allergy Clin Immunol. 1999; 12. Day JH, Briscoe MP, Welsh A, Smith J, Mason J. Onset of action, 104(5):927-33. efficacy and safety of a single dose of 60 mg and 120 mg fexofenadine 34. Berkowitz RB, McCafferty F, Lutz C, Bazelmans D, Godfrey P, HCl for ragweed (RW) allergy using controlled antigen exposure in Meeves S, Liao Y, Georges G. Fexofenadine HCl 60 mg/ pseudoephe- an environmental exposure unit (EEU). J Allergy Clin Immunol. drine HCl 120 mg has a 60-minute onset of action in the treatment 1996; 97:434. of seasonal allergic rhinitis symptoms, as assessed in an allergen 13. Sussman GL, Mason J, Compton D, Stewart J and Ricard N. The exposure unit. Allergy Asthma Proc. 2004; 25(5):335-43. efficacy and safety of fexofenadine HCl and pseudoephedrine, alone 35. Hampel F, Ratner P, Mansfield L, Meeves S, Liao Y, Georges G. and in combination, in seasonal allergic rhinitis. J Allergy Clin Fexofenadine hydrochloride, 180 mg, exhibits equivalent efficacy Immunol. 1999; 104 (1): 100-106. to cetirizine, 10 mg, with less drowsiness in patients with moderate- 14. Simons FER. H1 receptor antagonists: clinical pharmacology and to-severe seasonal allergic rhinitis. Ann Allergy Asthma Immunol. therapeutics. J Allergy Clin Immunol. 1989; 84: 845-66. 2003 ; 91(4):354-61. 15. Bernstein DI, Schoenwetter WF, Nathan RA, Storms W, Ahlbrandt 36. López García A, Paz Martínez D, Orea Solano M, Hernández R, Mason J. Efficacy and safety of fexofenadine hydrochloride for Valencia G, Ramírez García A, Ramírez Ojeda H, Sánchez Medal LF, treatment of seasonal allergic rhinitis. Ann Allergy Asthma Immunol. Soda Mehry A, Velarde Domínguez T, Betancourt Suárez MA, Méndez 1997; 79: 443-8. Vera JL. Efficacy and safety of fexofenadine and cetirizine in the 16. -Bousquet J, van Cauwenberge P, Khaltaev N, for the Aria Workshop treatment of allergic rhinitis. Rev Alerg Mex. 2001;48(6):168-72. Group and the World Health Organization. Allergic rhinitis and its 37. Moinuddin R, deTineo M, Maleckar B, Naclerio RM, Baroody FM. impact on asthma. J Allergy Clin Immunol. 2001;1 08(Suppl):S147– Comparison of the combinations of fexofenadine-pseudoephedrine S334. and loratadine-montelukast in the treatment of seasonal allergic 17. Price D, Bond C, Bouchard J, et al. International Primary Care rhinitis. Ann Allergy Asthma Immunol. 2004; 92(1):73-9. Respiratory Group (IPCRG) guidelines: Management of allergic rhini- 38. Phan H, Moeller ML, Nahata MC. Treatment of allergic rhinitis in tis. Prim Care Respir J. 2006; 15: 58–70. infants and children: efficacy and safety of second-generation anti- 18. Dykewicz MS, Fineman S, Skoner DP, et al. For the American and the leukotriene receptor antagonist montelukast. Academy of Allergy, Asthma, and Immunology. Diagnosis and man- Drugs. 2009; 69(18):2541-76. agement of rhinitis: Complete guidelines of the Joint Task Force on 39. Wahn U, Meltzer EO, Finn AF Jr, Kowalski ML, Decosta P, Hedlin Practice Parameters in Allergy, Asthma and Immunology. Ann Al- G, Scheinmann P, Bachert C, Rosado Pinto JE, Baena-Cagnani C, lergy Asthma Immunol. 1998; 81: 478–518. Potter P, Simons FE, Ruuth E. Fexofenadine is efficacious and safe 19. Bachert C. A Review of the Efficacy of Desloratadine, Fexofenadine, in children (aged 6-11 years) with seasonal allergic rhinitis. J Al- and in the Treatment of Nasal Congestion in Pa- lergy Clin Immunol. 2003; 111(4):763-9. tients with Allergic Rhinitis. Clinical Therapeutics. 2009; 31(5): 40. Segall N, Grubbe RE, Levy AL, Maloney MJ, Nayak AS, Kittner B, 921-944. Quesada JT. Pharmacokinetics, safety and tolerability of an oral 20. Howarth PH, Holgate ST. Comparative trial of two non- sedative suspension of fexofenadine for children with allergic rhinitis. Al- H1-antihistamines, terfenadine and astemizole, for hayfever. Tho- lergy Asthma Proc. 2008; 29(4):380-5. rax. 1984; 39: 668-72. 41. Ngamphaiboon J, Direkwattanachai C, Visitsunthorn N, 21. Kemp JP, Buckley CE, Gershwin ME, et al. Multi-centre, double- Vangveeravong M, Tiensuwan M. The efficacy and safety of 30 mg blind, placebo controlled trial of terfenadine in seasonal allergic fexofenadine HCl bid in pediatric patients with allergic rhinitis. rhinitis and conjunctivitis. Ann Allergy. 1985; 54: 502-9. Asian Pac J Allergy Immunol. 2005; 23(4):169-74. 22. Clissold SP, Sorkin EM, Goa KL. Loratadine: a preliminary review 42. Ohashi Y, Nakai Y, Murata K. Effect of pretreatment with of its pharmacodynamic properties and therapeutic efficacy. Drugs. fexofenadine on the safety of immunotherapy in patients with 1989; 37:42-57. allergic rhinitis. Ann Allergy Asthma Immunol. 2006; 96(4):600-5. 23. Storms WW, Bodman SF, Nathan RA, et al. SCH 434: a new antihis- 43. Monroe E. Review of H1 antihistamines in the treatment of chronic tamine/ decongestant for seasonal allergic rhinitis. J Allergy Clin idiopathic urticaria. Cutis. 2005; 76(2):118-26. Immunol. 1989; 83:1083-90. 44. Kozel MM, Sabroe RA. Chronic urticaria: aetiology, management 24. Grant JA, Fox R, Hampel F, Harris J, Gross G. Meta- analysis of and current and future treatment options. Drugs. 2004; 64(22):2515- Hismanal- D clinical trials in seasonal allergic rhinitis (SAR). Al- 36. lergy. 1992; 47(Suppl 12):242. 45. Kawashima M, Harada S, Tango T. Review of fexofenadine in the 25. Dockhorn RJ, Shellenberger MK, Moore MA, et al. Evaluation of treatment of chronic idiopathic urticaria. Int J Dermatol. 2002; + pseudoephedrine in seasonal allergic rhinitis. Ann Al- 41(10):701-6. lergy. 1995; 55:393. 46. Degonda M, Pichler WJ, Bircher A, Helbling A. Chronic idiopathic 26. Vermeeren A and O’Hanlon JF. Fexofenadine’s effects, alone and urticaria: effectiveness of fexofenadine. A double-blind, placebo with alcohol, on actual driving and psychomotor performance. J controlled study with 21 patients. Praxis. 2002; 91(15):637-43. Allergy Clin Immunol. 1998; 101(3): 306-311. 47. Nelson HS, Reynolds R, Mason J. Fexofenadine HCl is safe and 27. Tarnasky PR, Van Arsdel PP. Antihistamine therapy in allergic effective for treatment of chronic idiopathic urticaria. Ann Allergy rhinitis. J Fam Pract. 1990; 30:71-80. Asthma Immunol. 2000; 84(5):517-22. 28. Schäper C, Gustavus B, Koch B, Ewert R, Hanf G, Kunkel G, Noga O, 48. Simons FER and Simons KJ. Histamine and H1-antihistamines: Gläser S. Effects of fexofenadine on inflammatory mediators in celebrating a century of progress. Clinical reviews in allergy and nasal lavage fluid in intermittent allergic rhinitis. J Investig Allergol immunology. 2011; 1139-1150. Clin Immunol. 2009; 19 (6):459-64. 49. Komatsubara K, Miyoshi K, Kogure Y, Matsuhisa T, Eguchi H. 29. Simpson K, Jarvis B. Fexofenadine: a review of its use in the manage- Administration of premedication with fexofenadine for paclitaxel- ment of seasonal allergic rhinitis and chronic idiopathic urticaria. induced hypersensitive reactions in breast cancer patients compli- cated with closed-angle glaucoma. Gan To Kagaku Ryoho. 2010; Journal of Pharmacy Research Vol.5 Issue 3.March 2012 1646-1649 Farya Zafar / Journal of Pharmacy Research 2012,5(3),1646-1649 37(1):107-10. long-term administration of verapamil on the disposition of cyto- 50. Inui S, Nakajima T, Toda N, Itami S. Fexofenadine hydrochloride chrome P450 3A and P-glycoprotein substrates. Clin Pharmacol enhances the efficacy of contact immunotherapy for extensive Ther. 2006; 79:218-30. alopecia areata: Retrospective analysis of 121 cases. J Dermatol. 64. Yasui-Furukori N, Uno T, Sugawara K, Tateishi T. Different effects 2009; 36(6):323-7. of three transporting inhibitors, verapamil, , and 51. Meltzer EO, Gillman SA. Efficacy of fexofenadine versus probenecid, on fexofenadine pharmacokinetics. Clin Pharmacol desloratadine in suppressing histamine-induced wheal and flare. Al- Ther. 2005; 7:17-23. lergy Asthma Proc. 2007; 28(1):67-73. 65. Shon JH, Yoon YR, Hong WS, et al. Effect of itraconazole on the 52. Kawashima M, Tango T, Noguchi T, Inagi M, Nakagawa H, Harada pharmacokinetics and pharmacodynamics of fexofenadine in rela- S. Addition of fexofenadine to a topical corticosteroid reduces the tion to the MDR1 genetic polymorphism. Clin Pharmacol Ther. pruritus associated with atopic dermatitis in a 1-week randomized, 2005; 78:191-201. multicentre, double-blind, placebo-controlled, parallel-group study. 66. Shimizu M, Uno T, Sugawara K, Tateishi T. Effects of itraconazole Br J Dermatol. 2003; 148(6):1212-21. and diltiazem on the pharmacokinetics of fexofenadine, a substrate 53. Alexander M, Patel P, Allegro S, Hicks A. Supplementation of of P-glycoprotein. Br J Clin Pharmacol. 2006; 61:538-44. fexofenadine therapy with nedocromil sodium 2% ophthalmic solu- 67. Miura M and Uno T. Clinical pharmacokinetics o fexofenadine tion to treat ocular symptoms of seasonal allergic conjunctivitis. enantiomers. Expert Opin. Drug Metab. Toxicol. 2010; 6(1):69- Clin Experiment Ophthalmol. 2003; 31(3):206-12. 74. 54. Miyabe S, Koizuka I, Ochi K, Tanaka K, Kuroda H, Takatsu M, 68. Dresser GK, Bailey DG. The effects of fruit juices on drug disposi- Kinoshita H, Sugiyama Y. Effect of fexofenadine hydrochloride on tion: a new model for drug interactions. Eur J Clin Invest. 2003; cedar pollinosis. Auris Nasus Larynx. 2003; 30 Suppl:S61-8. 33:10-6. 55. Sheikh A, Ten Broek V, Brown SGA, Simons FER. H1-antihista- 69. Wang Z, Hamman MA, Huang SM, et al. Effect of St John’s wort on mines for the treatment of anaphylaxis: Cochrane systematic re- the pharmacokinetics of fexofenadine. Clin Pharmacol Ther. 2002; view. Allergy. 2007; 62:830-7. 71:414-20. 56. Kivisto KT, Kroemer HK. Use of probe drugs as predictors of drug 70. Simons FER. Advances in H1-antihistamines. N Engl J Med. 2004; metabolism in humans. J. Clin. Pharmacol. 1997; 37: 40S–48S. 351: 2203-17. 57. Frye RF. Probing the world of cytochrome P450 enzymes. Mol. 71. Milgrom H, Kittner B, Lanier R, et al. Safety and tolerability of Interv. 2004; 4:157–162. fexofenadine for the treatment of allergic rhinitis in children 2 to 5 58. Zhou H, Tong Z, McLeod JF. Cocktail approaches and strategies in years old. Ann Allergy Asthma Immunol. 2007; 99:358–63. drug development: valuable tool or flawed science? J. Clin. Pharmacol. 72. Kulthanan K, Gritiyarangsan P, Sitakalin C, et al. Multicenter study 2004; 44:120–134. of the effi cacy and safety of fexofenadine 60 mg. twice daily in 108 59. Wilkinson GR. In vivo probes for studying induction and inhibition Thai patients with chronic idiopathic urticaria. J Med Assoc Thai. of cytochrome P450 enzymes in humans, in: A.D. Rodrigues (Ed.), 2001; 84:153–9. Drug–Drug Interactions, Informa Healthcare, New York, 2008, pp. 73. Hamman MA, Bruce MA, Haehner-Daniels BD, Hall SD. The effect 581–641. of rifampin administration on the disposition of fexofenadine. Clin 60. Gupta S, Banfield C, Kantesariu B, Marino M, Clement R, Affrime Pharmacol Ther. 2001; 69:114-21. M and Batra V. Pharmacokinetic and Safety Profile of Desloratadine 74. Banfield C, Gupta S, Marino M, et al. Grapefruit juice reduces the and Fexofenadine When Coadministered with Azithromycin: A Ran- oral bioavailability of fexofenadine but not desloratadine. Clin domized, Placebo-Controlled, Parallel-Group Study. Clinical Thera- Pharmacokinet. 2002; 41:311–8. peutics. 2001; 23 (3): 451- 466. 75. Dresser GK, Kim RB, Bailey DG. Effect of grapefruit juice volume 61. Yamada S, Yasui-Furukori N, Akamine Y, Kaneko S, Uno T. Effects on the reduction of fexofenadine bioavailability: possible role of of the P-glycoprotein inducer carbamazepine on fexofenadine phar- organic anion transporting polypeptides. Clin Pharmacol Ther. 2005; macokinetics. Ther Drug Monit. 2009; 31(6):764-8. 77:170-7. 62. Ament PW, Paterson A. Drug interactions with the nonsedating 76. Axelrod D and Bielory L. Fexofenadine hydrochloride in the treat- antihistamines. Am Fam Physician. 1997; 56(1):223-31. ment of allergic disease: a review. Journal of Asthma and Allergy. 63. Lemma GL, Wang Z, Hamman MA, et al. The effect of short- and 2008; 1, 19:29.

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Journal of Pharmacy Research Vol.5 Issue 3.March 2012 1646-1649