Medical therapies for adult chronic sinusitis a systematic review

JAMA - Journal of the American Medical Association

Volumn 314, Issue 9, 2015, Pages 926-939

  Rudmik, Luke ^a   Soler, Zachary M ^b  

^a UNIVERSITY OF CALGARY   (Canada)

^b MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMOXICILLIN; AMOXICILLIN PLUS CLAVULANIC ACID; ANTIHISTAMINIC AGENT; BECLOMETASONE DIPROPIONATE; BUDESONIDE; CEFACLOR; CEFIXIME; CEFOTIAM; CEFPODOXIME; CEFPROZIL; CICLESONIDE; CIPROFLOXACIN; CORTICOSTEROID; DESLORATADINE; DEXAMETHASONE; DOXYCYCLINE; FLUNISOLIDE; FLUTICASONE FUROATE; FLUTICASONE PROPIONATE; LEUKOTRIENE RECEPTOR BLOCKING AGENT; MACROLIDE; METHYLPREDNISOLONE; MOMETASONE FUROATE; MONTELUKAST; OMALIZUMAB; PLACEBO; PREDNISOLONE; PREDNISONE; SODIUM CHLORIDE; UNINDEXED DRUG; ANTIFUNGAL AGENT; ANTIINFECTIVE AGENT;

ACNE; ADD ON THERAPY; ALLERGIC REACTION; ALLERGIC RHINITIS; AVASCULAR NECROSIS; CATARACT; CHRONIC SINUSITIS; COCHRANE LIBRARY; CORTICOSTEROID THERAPY; DAILY LIFE ACTIVITY; DISEASE EXACERBATION; DROWSINESS; DRUG ERUPTION; DRUG HYPERSENSITIVITY; ELECTROLYTE DISTURBANCE; EMBASE; EPISTAXIS; FATIGUE; FUNCTIONAL STATUS; GASTROINTESTINAL SYMPTOM; GLAUCOMA; HEADACHE; HEALTH CARE COST; HUMAN; HYPERGLYCEMIA; HYPERSENSITIVITY; HYPERTENSION; INFLAMMATION; INFORMATION RETRIEVAL; JAUNDICE; LIVER TOXICITY; MEDLINE; MOOD DISORDER; NASAL LAVAGE; NAUSEA; NOSE POLYP; OSTEOPOROSIS; PATIENT CARE; PRIORITY JOURNAL; QUALITY OF LIFE; REVIEW; SHORT COURSE THERAPY; SKIN BRUISING; SLEEP DISORDER; SYSTEMATIC REVIEW; TREATMENT DURATION; URTICARIA; XEROSTOMIA; ADULT; CHRONIC DISEASE; LAVAGE; MAINTENANCE CHEMOTHERAPY; NASAL POLYPS; PROCEDURES; SINUSITIS;

ADRENAL CORTEX HORMONES; ADULT; ANTI-BACTERIAL AGENTS; ANTIFUNGAL AGENTS; CHRONIC DISEASE; DOXYCYCLINE; HISTAMINE ANTAGONISTS; HUMANS; LEUKOTRIENE ANTAGONISTS; MACROLIDES; MAINTENANCE CHEMOTHERAPY; NASAL POLYPS; QUALITY OF LIFE; SINUSITIS; SODIUM CHLORIDE; THERAPEUTIC IRRIGATION;

EID: 84940773503     PISSN: 00987484     EISSN: 15383598     Source Type: Journal    
DOI: 10.1001/jama.2015.7544     Document Type: Review

References (101)

1. Desrosiers M, Evans GA, Keith PK, et al. Canadian clinical practice guidelines for acute and chronic rhinosinusitis. J Otolaryngol Head Neck Surg. 2011;40(suppl 2):S99-S193.
2. Fokkens WJ, Lund VJ, Mullol J, et al. EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012: a summary for otorhinolaryngologists. Rhinology. 2012;50(1):1-12.
3. Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, et al. Clinical practice guideline (update): adult sinusitis. J Otolaryngol Head Neck Surg. 2015;152(2 suppl):S1-S39.
4. Bhattacharyya N. The economic burden and symptom manifestations of chronic rhinosinusitis. Am J Rhinol. 2003;17(1):27-32.
5. Bhattacharyya N. Clinical and symptom criteria for the accurate diagnosis of chronic rhinosinusitis. Laryngoscope. 2006;116(7 Pt 2)(suppl 110):1-22.
6. Soler ZM, Mace J, Smith TL. Symptom-based presentation of chronic rhinosinusitis and symptom-specific outcomes after endoscopic sinus surgery. Am J Rhinol. 2008;22(3):297-301.
7. Dietz de Loos DA, Hopkins C, Fokkens WJ. Symptoms in chronic rhinosinusitis with and without nasal polyps. Laryngoscope. 2013;123(1):57-63.
8. Rudmik L, Smith TL. Quality of life in patients with chronic rhinosinusitis. Curr Allergy Asthma Rep. 2011;11(3):247-252.
9. Alt JA, Smith TL. Chronic rhinosinusitis and sleep: a contemporary review. Int Forum Allergy Rhinol. 2013;3(11):941-949.
10. Rudmik L, Smith TL, Schlosser RJ, Hwang PH, Mace JC, Soler ZM. Productivity costs in patients with refractory chronic rhinosinusitis. Laryngoscope. 2014;124(9):2007-2012.
11. Halawi AM, Smith SS, Chandra RK. Chronic rhinosinusitis: epidemiology and cost. Allergy Asthma Proc. 2013;34(4):328-334.
12. Tan BK, Kern RC, Schleimer RP, Schwartz BS. Chronic rhinosinusitis: the unrecognized epidemic. Am J Respir Crit Care Med. 2013;188(11):1275-1277.
13. Bhattacharyya N. Incremental health care utilization and expenditures for chronic rhinosinusitis in the United States. Ann Otol Rhinol Laryngol. 2011;120(7):423-427.
14. Mattos JL, Woodard CR, Payne SC. Trends in common rhinologic illnesses: analysis of US healthcare surveys 1995-2007. Int Forum Allergy Rhinol. 2011;1(1):3-12.
15. Smith KA, Orlandi RR, Rudmik L. Cost of adult chronic rhinosinusitis: a systematic review. Laryngoscope. 2015;125(7):1547-1556.
16. Van Crombruggen K, Zhang N, Gevaert P, Tomassen P, Bachert C. Pathogenesis of chronic rhinosinusitis: inflammation. J Allergy Clin Immunol. 2011;128(4):728-732.
17. Ocampo CJ, Grammer LC. Chronic rhinosinusitis. J Allergy Clin Immunol Pract. 2013;1(3):205-211; quiz 212-203.
18. Hsu J, Avila PC, Kern RC, Hayes MG, Schleimer RP, Pinto JM. Genetics of chronic rhinosinusitis: state of the field and directions forward. J Allergy Clin Immunol. 2013;131(4):977-993, 993 e971-975.
19. Bassiouni A, Naidoo Y, Wormald PJ. Does mucosal remodeling in chronic rhinosinusitis result in irreversible mucosal disease? Laryngoscope. 2012;122(1):225-229.
20. Lee RJ, Cohen NA. Taste receptors in innate immunity. Cell Mol Life Sci. 2015;72(2):217-236.
21. Lee RJ, Cohen NA. Role of the bitter taste receptor T2R38 in upper respiratory infection and chronic rhinosinusitis. Curr Opin Allergy Clin Immunol. 2015;15(1):14-20.
22. Adappa ND, Zhang Z, Palmer JN, et al. The bitter taste receptor T2R38 is an independent risk factor for chronic rhinosinusitis requiring sinus surgery. Int Forum Allergy Rhinol. 2014;4(1):3-7.
23. Adappa ND, Howland TJ, Palmer JN, et al. Genetics of the taste receptor T2R38 correlates with chronic rhinosinusitis necessitating surgical intervention. Int Forum Allergy Rhinol. 2013;3(3):184-187.
24. Akdis CA, Bachert C, Cingi C, et al. Endotypes and phenotypes of chronic rhinosinusitis: a PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol. 2013;131(6):1479-1490.
25. Anderson GP. Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease. Lancet. 2008;372(9643):1107-1119.
26. Lötvall J, Akdis CA, Bacharier LB, et al. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol. 2011;127(2):355-360.
27. Parnham MJ, Erakovic Haber V, Giamarellos-Bourboulis EJ, Perletti G, Verleden GM, Vos R. Azithromycin: mechanisms of action and their relevance for clinical applications. Pharmacol Ther. 2014;143(2):225-245.
28. van Drunen CM, Reinartz S, Wigman J, Fokkens WJ. Inflammation in chronic rhinosinusitis and nasal polyposis. Immunol Allergy Clin North Am. 2009;29(4):621-629.
29. Yoon BN, Choi NG, Lee HS, Cho KS, Roh HJ. Induction of interleukin-8 from nasal epithelial cells during bacterial infection: the role of IL-8 for neutrophil recruitment in chronic rhinosinusitis. Mediators Inflamm. 2010;2010:813610.
30. Ocampo CJ, Peters AT. Medical therapy as the primary modality for the management of chronic rhinosinusitis. Allergy Asthma Proc. 2013;34(2):132-137.
31. Oxford Centre for Evidence-based Medicine. Levels of evidence. http://www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/. Accessed February 1, 2015.
32. Manual for ACC/AHA Guideline Writing Committees. Section II: tools and methods for creating guidelines. http://circ.ahajournals.org/site/manual/manual-IIstep6.xhtml. Accessed December 28, 2014.
33. Higgins JP, Green S. Cochrane Handbook for Systematic Reviews of Interventions, version 5.1.0. http://www.cochrane-handbook.org. Accessed May 4, 2015.
34. Joe SA, Thambi R, Huang J. A systematic review of the use of intranasal steroids in the treatment of chronic rhinosinusitis. Otolaryngol Head Neck Surg. 2008;139(3):340-347.
35. Kalish LH, Arendts G, Sacks R, Craig JC. Topical steroids in chronic rhinosinusitis without polyps: a systematic review and meta-analysis. Otolaryngol Head Neck Surg. 2009;141(6):674-683.
36. Snidvongs K, Kalish L, Sacks R, Craig JC, Harvey RJ. Topical steroid for chronic rhinosinusitis without polyps. Cochrane Database Syst Rev. 2011;(8):CD009274.
37. Rudmik L, Schlosser RJ, Smith TL, Soler ZM. Impact of topical nasal steroid therapy on symptoms of nasal polyposis: a meta-analysis. Laryngoscope. 2012;122(7):1431-1437.
38. Kalish L, Snidvongs K, Sivasubramaniam R, Cope D, Harvey RJ. Topical steroids for nasal polyps. Cochrane Database Syst Rev. 2012;12:CD006549.
39. Fandiño M, Macdonald KI, Lee J, Witterick IJ. The use of postoperative topical corticosteroids in chronic rhinosinusitis with nasal polyps: a systematic review and meta-analysis. Am J Rhinol Allergy. 2013;27(5):e146-e157.
40. Harvey R, Hannan SA, Badia L, Scadding G. Nasal saline irrigations for the symptoms of chronic rhinosinusitis. Cochrane Database Syst Rev. 2007; (3):CD006394.
41. Rudmik L, Hoy M, Schlosser RJ, et al. Topical therapies in the management of chronic rhinosinusitis: an evidence-based review with recommendations. Int Forum Allergy Rhinol. 2013;3(4):281-298.
42. van den Berg JW, de Nier LM, Kaper NM, et al. Limited evidence: higher efficacy of nasal saline irrigation over nasal saline spray in chronic rhinosinusitis-an update and reanalysis of the evidence base. Otolaryngol Head Neck Surg. 2014;150(1):16-21.
43. Wentzel JL, Soler ZM, DeYoung K, Nguyen SA, Lohia S, Schlosser RJ. Leukotriene antagonists in nasal polyposis: a meta-analysis and systematic review. Am J Rhinol Allergy. 2013;27(6):482-489.
44. DeYoung K, Wentzel JL, Schlosser RJ, Nguyen SA, Soler ZM. Systematic review of immunotherapy for chronic rhinosinusitis. Am J Rhinol Allergy. 2014;28(2):145-150.
45. Vaidyanathan S, Barnes M, Williamson P, Hopkinson P, Donnan PT, Lipworth B. Treatment of chronic rhinosinusitis with nasal polyposis with oral steroids followed by topical steroids: a randomized trial. Ann Intern Med. 2011;154(5):293-302.
46. Thomas WW III, Harvey RJ, Rudmik L, Hwang PH, Schlosser RJ. Distribution of topical agents to the paranasal sinuses: an evidence-based review with recommendations. Int Forum Allergy Rhinol. 2013;3(9):691-703.
47. Rudmik L. High volume sinonasal budesonide irrigations for chronic rhinosinusitis: an update on the safety and effectiveness. http://omicsgroup.org/journals/high-volume-sinonasal-budesonide-irrigations-for-chronic-rhinosinusitis-2167-1052.1000148.pdf. Accessed December 27, 2014.
48. Pynnonen MA, Mukerji SS, Kim HM, Adams ME, Terrell JE. Nasal saline for chronic sinonasal symptoms: a randomized controlled trial. Arch Otolaryngol Head Neck Surg. 2007;133(11):1115-1120.
49. Pauli C, Fintelmann R, Klemens C, et al. Polyposis nasi-improvement in quality of life by the influence of leukotriene receptor antagonists [in German]. Laryngorhinootologie. 2007;86(4):282-286.
50. Schäper C, Noga O, Koch B, et al. Anti-inflammatory properties of montelukast, a leukotriene receptor antagonist in patients with asthma and nasal polyposis. J Investig Allergol Clin Immunol. 2011;21(1):51-58.
51. Stewart RA, Ram B, Hamilton G, Weiner J, Kane KJ. Montelukast as an adjunct to oral and inhaled steroid therapy in chronic nasal polyposis. Otolaryngol Head Neck Surg. 2008;139(5):682-687.
52. Vuralkan E, Saka C, Akin I, et al. Comparison of montelukast and mometasone furoate in the prevention of recurrent nasal polyps. Ther Adv Respir Dis. 2012;6(1):5-10.
53. Mostafa BE, Abdel Hay H, Mohammed HE, Yamani M. Role of leukotriene inhibitors in the postoperative management of nasal polyps. ORL J Otorhinolaryngol Relat Spec. 2005;67(3):148-153.
54. Dykewicz MS, Hamilos DL. Rhinitis and sinusitis. J Allergy Clin Immunol. 2010;125(2)(suppl 2):S103-S115.
55. Wilson KF, McMains KC, Orlandi RR. The association between allergy and chronic rhinosinusitis with and without nasal polyps: an evidence-based review with recommendations. Int Forum Allergy Rhinol. 2014;4(2):93-103.
56. Hellings PW, Fokkens WJ, Akdis C, et al. Uncontrolled allergic rhinitis and chronic rhinosinusitis: where do we stand today? Allergy. 2013;68(1):1-7.
57. Cox L, Nelson H, Lockey R, et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol. 2011;127(1)(suppl):S1-S55.
58. Martinez-Devesa P, Patiar S. Oral steroids for nasal polyps. Cochrane Database Syst Rev. 2011;(7):CD005232.
59. Lal D, Hwang PH. Oral corticosteroid therapy in chronic rhinosinusitis without polyposis: a systematic review. Int Forum Allergy Rhinol. 2011;1(2):136-143.
60. Poetker DM, Jakubowski LA, Lal D, Hwang PH, Wright ED, Smith TL. Oral corticosteroids in the management of adult chronic rhinosinusitis with and without nasal polyps: an evidence-based review with recommendations. Int Forum Allergy Rhinol. 2013;3(2):104-120.
61. Soler ZM, Oyer SL, Kern RC, et al. Antimicrobials and chronic rhinosinusitis with or without polyposis in adults: an evidenced-based review with recommendations. Int Forum Allergy Rhinol. 2013;3(1):31-47.
62. Piromchai P, Thanaviratananich S, Laopaiboon M. Systemic antibiotics for chronic rhinosinusitis without nasal polyps in adults. Cochrane Database Syst Rev. 2011;(5):CD008233.
63. Pynnonen MA, Venkatraman G, Davis GE. Macrolide therapy for chronic rhinosinusitis: a meta-analysis. Otolaryngol Head Neck Surg. 2013;148(3):366-373.
64. Pinto JM, Mehta N, DiTineo M, Wang J, Baroody FM, Naclerio RM. A randomized, double-blind, placebo-controlled trial of anti-IgE for chronic rhinosinusitis. Rhinology. 2010;48(3):318-324.
65. Gevaert P, Calus L, Van Zele T, et al. Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma. J Allergy Clin Immunol. 2013;131(1):110-116.e111.
66. Gevaert P, Lang-Loidolt D, Lackner A, et al. Nasal IL-5 levels determine the response to anti-IL-5 treatment in patients with nasal polyps. J Allergy Clin Immunol. 2006;118(5):1133-1141.
67. Gevaert P, Van Bruaene N, Cattaert T, et al. Mepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal polyposis. J Allergy Clin Immunol. 2011;128(5):989-995.e1-8.
68. Lim M, Citardi MJ, Leong JL. Topical antimicrobials in the management of chronic rhinosinusitis: a systematic review. Am J Rhinol. 2008;22(4):381-389.
69. Wei CC, Adappa ND, Cohen NA. Use of topical nasal therapies in the management of chronic rhinosinusitis. Laryngoscope. 2013;123(10):2347-2359.
70. Isaacs S, Fakhri S, Luong A, Citardi MJ. A meta-analysis of topical amphotericin B for the treatment of chronic rhinosinusitis. Int Forum Allergy Rhinol. 2011;1(4):250-254.
71. Sacks PL, Harvey RJ, Rimmer J, Gallagher RM, Sacks R. Topical and systemic antifungal therapy for the symptomatic treatment of chronic rhinosinusitis. Cochrane Database Syst Rev. 2011;(8):CD008263.
72. Wang T, Su J, Feng Y. The effectiveness topical amphotericin B in the management of chronic rhinosinusitis: a meta-analysis. Eur Arch Otorhinolaryngol. 2015;272(8):1923-1929.
73. Van Zele T, Gevaert P, Holtappels G, et al. Oral steroids and doxycycline: 2 different approaches to treat nasal polyps. J Allergy Clin Immunol. 2010;125(5):1069-1076.e4.
74. Hessler JL, Piccirillo JF, Fang D, et al. Clinical outcomes of chronic rhinosinusitis in response to medical therapy: results of a prospective study. Am J Rhinol. 2007;21(1):10-18.
75. Ikeda K, Sakurada T, Suzaki Y, Takasaka T. Efficacy of systemic corticosteroid treatment for anosmia with nasal and paranasal sinus disease. Rhinology. 1995;33(3):162-165.
76. Lal D, Scianna JM, Stankiewicz JA. Efficacy of targeted medical therapy in chronic rhinosinusitis, and predictors of failure. Am J Rhinol Allergy. 2009;23(4):396-400.
77. Subramanian HN, Schechtman KB, Hamilos DL. A retrospective analysis of treatment outcomes and time to relapse after intensive medical treatment for chronic sinusitis. Am J Rhinol. 2002;16(6):303-312.
78. Poetker DM, Reh DD. A comprehensive review of the adverse effects of systemic corticosteroids. Otolaryngol Clin North Am. 2010;43(4):753-768.
79. Dellamonica P, Choutet P, Lejeune JM, et al. Efficacy and tolerance of cefotiam hexetil in the super-infected chronic sinusitis: a randomized, double-blind study in comparison with cefixime [in French]. Ann Otolaryngol Chir Cervicofac. 1994;111(4):217-222.
80. Legent F, Bordure P, Beauvillain C, Berche P. A double-blind comparison of ciprofloxacin and amoxycillin/clavulanic acid in the treatment of chronic sinusitis. Chemotherapy. 1994;40(suppl 1):8-15.
81. Huck W, Reed BD, Nielsen RW, et al. Cefaclor vs amoxicillin in the treatment of acute, recurrent, and chronic sinusitis. Arch Fam Med. 1993;2(5):497-503.
82. Reiter J, Demirel N, Mendy A, et al. Macrolides for the long-term management of asthma-a meta-analysis of randomized clinical trials. Allergy. 2013;68(8):1040-1049.
83. Harvey RJ, Wallwork BD, Lund VJ. Anti-inflammatory effects of macrolides: applications in chronic rhinosinusitis. Immunol Allergy Clin North Am. 2009;29(4):689-703.
84. Soler ZM, Smith TL. What is the role of long-term macrolide therapy in the treatment of recalcitrant chronic rhinosinusitis? Laryngoscope. 2009;119(11):2083-2084.
85. Wallwork B, Coman W, Mackay-Sim A, Greiff L, Cervin A. A double-blind, randomized, placebo-controlled trial of macrolide in the treatment of chronic rhinosinusitis. Laryngoscope. 2006;116(2):189-193.
86. Videler WJ, Badia L, Harvey RJ, et al. Lack of efficacy of long-term, low-dose azithromycin in chronic rhinosinusitis: a randomized controlled trial. Allergy. 2011;66(11):1457-1468.
87. Chang TW, Shiung YY. Anti-IgE as a mast cell-stabilizing therapeutic agent. J Allergy Clin Immunol. 2006;117(6):1203-1212.
88. Bachert C, Zhang N. Chronic rhinosinusitis and asthma: novel understanding of the role of IgE "above atopy". J Intern Med. 2012;272(2):133-143.
89. Mepolizumab: 240563, anti-IL-5 monoclonal antibody-GlaxoSmithKline, anti-interleukin-5 monoclonal antibody-GlaxoSmithKline, SB 240563. Drugs R D. 2008;9(2):125-130.
90. Jervis-Bardy J, Boase S, Psaltis A, Foreman A, Wormald PJ. A randomized trial of mupirocin sinonasal rinses versus saline in surgically recalcitrant staphylococcal chronic rhinosinusitis. Laryngoscope. 2012;122(10):2148-2153.
91. Braun H, Buzina W, Freudenschuss K, Beham A, Stammberger H. "Eosinophilic fungal rhinosinusitis": a common disorder in Europe? Laryngoscope. 2003;113(2):264-269.
92. Ponikau JU, Sherris DA, Kern EB, et al. The diagnosis and incidence of allergic fungal sinusitis. Mayo Clin Proc. 1999;74(9):877-884.
93. Lanza DC, Dhong HJ, Tantilipikorn P, Tanabodee J, Nadel DM, Kennedy DW. Fungus and chronic rhinosinusitis: from bench to clinical understanding. Ann Otol Rhinol Laryngol Suppl. 2006;196:27-34.
94. IFI Claims Patent Services. Methods and materials for treating and preventing inflammation of mucosal tissue. http://www.google.com/patents/US6291500. Accessed January 30, 2015.
95. Scadding GK, Durham SR, Mirakian R, et al. BSACI guidelines for the management of rhinosinusitis and nasal polyposis. Clin Exp Allergy. 2008;38(2):260-275.
96. Rudmik L, Smith TL. Olfactory improvement after endoscopic sinus surgery. Curr Opin Otolaryngol Head Neck Surg. 2012;20(1):29-32.
97. Cervin A, Wallwork B. Efficacy and safety of long-term antibiotics (macrolides) for the treatment of chronic rhinosinusitis. Curr Allergy Asthma Rep. 2014;14(3):416.
98. Patel AM, Shariff S, Bailey DG, et al. Statin toxicity from macrolide antibiotic coprescription: a population-based cohort study. Ann Intern Med. 2013;158(12):869-876.
99. Ray WA, Murray KT, Hall K, Arbogast PG, Stein CM. Azithromycin and the risk of cardiovascular death. N Engl J Med. 2012;366(20):1881-1890.
100. Westphal JF. Macrolide-induced clinically relevant drug interactions with cytochrome P-450A (CYP) 3A4: an update focused on clarithromycin, azithromycin and dirithromycin. Br J Clin Pharmacol. 2000;50(4):285-295.
101. Yasui N, Otani K, Kaneko S, et al. A kinetic and dynamic study of oral alprazolam with and without erythromycin in humans: in vivo evidence for the involvement of CYP3A4 in alprazolam metabolism. Clin Pharmacol Ther. 1996;59(5):514-519.