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化療止吐藥 Aprepitant ( Emend ... - …

1 ( tsgh Pharmacy Newsletter) 76 75 12 96 11 Aprepitant ( Emend ) (emesis) ( Chemotherapy induced nausea and vomiting, CINV ) ( acute CINV ) serotonin 24 ( delayed CINV ) substance P 24 ( anticipatory CINV ) CINV ( 90% ) ( 30% 90% ) ( 10% 30% ) ( < 10% )( ) Aprepitant ( Emend ) 2 70 - 80 5-HT3 receptor antagonist ( Granisetron Ondansetron ) Dexamethasone cisplatin 5- HT3 receptor antagonist substance P neurokinin ( NK1 ) receptor Aprepitant ( Emend ) 2005 NK1 receptor antagonist Aprepitant neurokinin 1 ( NK1 ) receptors serotonin ( 5- HT3 ) dopami

三總藥訊96.11 1 (TSGH Pharmacy Newsletter) (76)國報字第 一號 三軍總醫院 臨床藥學部 藥物諮詢室 洪乃勻藥師主編

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Transcription of 化療止吐藥 Aprepitant ( Emend ... - …

1 1 ( tsgh Pharmacy Newsletter) 76 75 12 96 11 Aprepitant ( Emend ) (emesis) ( Chemotherapy induced nausea and vomiting, CINV ) ( acute CINV ) serotonin 24 ( delayed CINV ) substance P 24 ( anticipatory CINV ) CINV ( 90% ) ( 30% 90% ) ( 10% 30% ) ( < 10% )( ) Aprepitant ( Emend ) 2 70 - 80 5-HT3 receptor antagonist ( Granisetron Ondansetron ) Dexamethasone cisplatin 5- HT3 receptor antagonist substance P neurokinin ( NK1 ) receptor Aprepitant ( Emend ) 2005 NK1 receptor antagonist Aprepitant neurokinin 1 ( NK1 ) receptors serotonin ( 5- HT3 ) dopamine corticosteroid Aprepitant substance P neurokinin 1 ( NK1 ) receptors ( chemotherapy-induced nausea and vomiting, CINV ) ( postoperative nausea and vomiting, PONV ) Substance P tachykinin ( neurokinin )

2 Aprepitant neurokinin 1 ( NK1 ) receptors substance P Aprepitant neurokinin 1 ( NK1 ) receptors FDA 1. 2. 3. 3 (1) Aprepitant 125 mg PO 1 hr prior to chemotherapy 80 mg PO in the morning 80 mg PO in the morning 5- HT3 antagonist Ondansetron 32 mg IV 30 mins prior to chemotherapy Dexamethasone 12 mg PO 30 mins prior to chemotherapy 8 mg PO in the morning 8 mg PO in the morning 8 mg PO in the morning (2) Aprepitant 125 mg PO 1 hr prior to chemotherapy 80 mg PO in the morning 80 mg PO in the morning 5- HT3 antagonist Ondansetron (1) 8 mg PO 30 to 60 mins prior to chemotherapy (2) 8 mg PO 8 hours after the first dose Dexamethasone 12 mg PO 30 mins prior to chemotherapy (3) 40 mg Aprepitant ( 80 - 125mg )

3 60 - 65% 3 - 4 95% 70 Cytochrome P450 CYP3A4 CYP1A2 CYP2C19 4 Aprepitant 9 -13 ALT AST Aprepitant B Aprepitant CYP3A4 ( inducer ) CYP2C9 Aprepitant pimozide terfenadine astemizole cisapride ( ) Aprepitant CYP3A4 (1) CYP3A4 ( CYP3A4 ) corticosteroid ( dexamethasone methylprednisolone ) ( etoposide vinorelbine docetaxel paclitaxel ifosfamide irinotecan ) benzodiazepines ( midazolam alprazolam triazolam ) fentanyl Aprepitant CYP3A4 Aprepitant CYP3A4 (2) CYP2C9 warfarin tolbutamine Aprepitant CYP2C9 warfarin Aprepitant 2 ( 7 10 ) prothrombin time (3) CYP3A4 azole ( ketoconazole itraconazole ) clarithromycin diltiazem nefazodone nelfinavir ritonavir Aprepitant CYP3A4.

4 CYP3A4 Aprepitant (4) CYP3A4 carbamazepine rifampin phenytoin CYP3A4 Aprepitant CYP3A4 ( phenytoin) (5) Aprepitant Aprepitant (6) Paroxetine Aprepitant AUC CMAX 5 Neurokinin-1 receptor antagonist 5- HT3 recepteor antagonist Aprepitant Granisetron Ondansetron Emend cap 80mg Kytril 1mg tab Kytril 1mg/ml inj Zofran 2mg/ml inj Antiemetic Substance P/ Neurokinin-1 Receptor antagonist Antiemetic 5-HT3 receptor antagonists Antiemetic 5- HT3 receptor antagonists 1. 2. 1. 2. 3. 4. 1. 2. 3. 60 - 65% 4 hrs ( Vd ) 70 L 95% CYP3A4 (major) CYP1A2(minor) CYP2C19(minor) 9 - 13 hrs Duration 24hrs ( Vd ) 2 - 4 L/kg 65% CYP3A N-demethylation oxidation followed by conjugation (11 - 12% unchanged, 48 - 49% as metabolites) (34 - 38% as metabolites ) 5 - 9 hrs Onset ~ 30 mins ( Vd ) - L/kg ( ) - L/kg ( ) 70~76% hydroxylation followed by glucuronide or sulfate conjugation demethylation(minor) (44 - 60%) ( 25% ) 3 - hrs ( 18 - 22% ) ( 7 - 13% ) ( 9 - 12% ) ( 3 - 18% ) ( 11% ) ( 9 - 21% ) ( 3 - 18% ) ( 5 - 18% ) ( 9 - 27% ) / ( 9 - 13% ) ( 6 - 11% ) 6 Aprepitant Granisetron Ondansetron 1.

5 Aprepitant 2. pimozide terfenadine astemizole cisapride granisetron 5- HT3 receptor antagonists ondansetron 5-HT3 receptor antagonists (*) 1. dexamethasone 5-HT3 2. 5- HT3 1. 2. / (1) Ondansetron 8 - 32mg Granisetron 1 - 3mg Tropisetron 5mg (2) Ondansetron 8 - 32mg Granisetron 1 - 3mg Tropisetron 5mg dexamethasone metoclopramide dexamethasone metoclopramide 3. ondansetron granisetron (1) total body or half body irradiation (2) pelvis or upper abdominal region of single irradiation dose> 6 Gy (3) dexamethasone metoclopramide rochlorperazine 1. / ?

6 / B 2. ( 18 ) 3. Aprepitant CYP3A4 CYP2C9 1. / ?/ B 2. ( 2 ) 3. Granisetron 1. / ?/ B 2. ( 1 month) 3. Ondansetron 4. NT: $ 715 ( 80 mg TAB ) NT: $ 296 (TAB) NT: $ 450 (AMP) NT: $ 389 7 (*) ( ) 1. cisplatin ( > 50 mg/m2/day ) carmustine ( 250 mg/m2/day ) cyclophosphamide ( > 1500 mg/m2/day ) methotrexate ( gm/m2/day ) 2. cisplatin ( 30mg/m2/day 50mg/m2/day ) carmustine ( 250 mg/m2/day ) cyclophosphamide ( 1500 mg/m2/day ) Doxorubicin ( 45 mg/m2/day ) epirubicin ( 70 mg/m2/day ) CPT-11 idarubicin ( 10mg/m2/day ) daunorubicin ( 60 mg/m2/day ) Dactinomycin ( actinomycin-D ) Arsenic trioxide Melphalan ( 50 mg/m2/day ) Cytarabine Carboplatin oxaliplatin ifosfamide Mitoxantrone Dacarbazine 3.

7 2006 ASCO ( American Society of Clinical Oncology ) 5-HT3 antagonists dexamethasone Aprepitant anthracycline cyclophosphamide 5- HT3 antagonists dexamethasone cisplatin guideline dexamethasone Aprepitant ASCO 5-HT3 receptor antagonists dexamethasone ( ) Aprepitant 8 Summary of Recommendations for Antiemetics in Oncology: Antiemeitc Regimens American Society of Clinical Oncology Guideline for Antiemetics in Oncology: Update 2006 9 Emetic Risk of Intravenously Administered Antineoplastic Agents American Society of Clinical Oncology Guideline for Antiemetics in Oncology: Update 2006 10 References 1.

8 Ton M. Dando and Caroline : Aprepitant - A review of its use in the prevention of chemotherapy-induced nausea and vomiting. Drugs, 2004; 64(7): 777-94. 2. Jordan K, Sippel C, Schmoll HJ: Guidelines for antiemetic treatment of chemotherapy-induced nausea and vomiting: past, present, and future recommendations, Oncologist, 2007 Sep; 12(9): 1143-50 3. DRUGDEX Evaluations of Aprepitant . In Micromedex Healthcare Series. Vol 134. 4. Emend Prescribing information. Merck & Co., Inc. 5. Charles F. Lacy, Lora L. Armstrong, et al. :Drug information handbook,15th ed, 2007: pp152-153, pp865-866, pp1345-1347. 6. , p 48-49 7. Kris, Mark G; Hesketh, Paul J; et al.: American Society of Clinical Oncology Guideline for Antiemetics in Oncology: Update 2006. Journal of clinical oncology 2006 24(18): 2932-2947