ASTAGRAF XL
Generic Name and Formulations:
Tacrolimus 0.5mg, 1mg, 5mg; ext-rel caps.
安斯泰来（Astellas）美国子公司今天宣布，ASTAGRAF XL（他克莫司缓释胶囊，tacrolimus extended release capsules）获FDA批准，与霉酚酸酯（MMF）及皮质类醇联用、结合或无巴利昔单抗（basiliximab）诱导，用于预防成人肾移植受者中的 器官排斥。安斯泰来于2012年9月提交了该药的新药申请（NDA）。
在美国，ASTAGRAF XL是首个每日一次的他克莫司制剂，该药作为免疫抑制组合方案中的核心组成部分，为肾移植受者预防器官排斥反应提供了一个很有潜力的疗法。
该药的获批，是基于2项主要的、随机、比较III期临床研究，涉及美国、欧洲、加拿大、南美、澳大利亚、南非等国的1093例患者（545例他克莫司缓释胶囊治疗）。
在2007年，他克莫司缓释胶囊在欧洲获批以商品名Advagraf销售；2008年，该药在日本获批以商品名Graceptor销售。总体而言，他克莫司缓释胶囊已获得了全球73个国家的监管批准，每年经该药治疗的患者数超过14万人。
Company:
Astellas Pharma US, Inc.
Indications for ASTAGRAF XL:
Organ rejection prophylaxis in kidney transplant patients, in combination with mycophenolate mofetil (MMF) and corticosteroids, with or without basiliximab induction. Limitations of use: not interchangeable or substitutable with tacrolimus immediate-release caps. Do not use simultaneously with cyclosporine.
Adult Dose for ASTAGRAF XL:
Swallow whole. Take once daily in the morning, preferably on an empty stomach. If previously on Prograf IV infusion, initial oral dose may be given 8–12 hours after discontinuing infusion. ≥16yrs: with basiliximab induction: initially 0.15mg/kg/day; give first dose prior to or within 48 hours after transplantation; but may be delayed until renal function has recovered; without induction (pre-op): 0.1mg/kg/day; give dose within 12 hours prior to reperfusion when used with MMF and corticosteroids; without induction (post-op): 0.2mg/kg/day; give first dose within 12 hours after reperfusion but not less than 4 hours after pre-op dose when used with MMF and corticosteroids. Black patients may require higher doses. Renal or hepatic impairment: use lowest effective dose. Post-op oliguria: give initial dose no sooner than 6 hours and within 48 hours of transplantation, but may delay therapy until renal function recovers. See full labeling.
Children's Dose for ASTAGRAF XL:
<16yrs: not established.
Pharmacological Class:
Immunosuppressant (calcineurin-inhibitor).
Warnings/Precautions:
Not recommended for use in liver transplantation. Increased risk of infections (eg, bacterial, viral, fungal, protozoal, cytomegalovirus), opportunistic infections including polyoma virus. Increased risk of lymphomas and other malignancies (eg, skin). Avoid sun, UV light. Epstein Barr Virus seronegative. New-onset diabetes: monitor for hyperglycemia. Hepatic or renal impairment; monitor and consider dose reduction. Obtain tacrolimus whole blood concentrations, serum creatinine, potassium, and fasting glucose periodically. Pregnancy (Cat. C), nursing mothers: not recommended.
Interactions:
Concomitant sirolimus, live vaccines, cyclosporine: not recommended. Concomitant mycophenolic acid (MPA) products; monitor. Concomitant strong CYP3A4 inhibitors/inducers or substrates: must adjust dosing regimen, closely monitor tacrolimus blood concentrations and for QT prolongation. Caution with potassium-sparing diuretics, ACEIs, ARBs. Avoid grapefruit juice, nelfinavir, alcohol. Additive nephrotoxicity with aminoglycosides, ganciclovir, amphotericin B, cisplatin, tenofovir, ritonavir, indinavir. May be potentiated by calcium channel blockers (eg, verapamil, diltiazem, nifedipine), antifungals (eg, fluconazole, ketoconazole), macrolides (eg, troleandomycin, clarithromycin, erythromycin), metoclopramide, lansoprazole, omeprazole, bromocriptine, chloramphenicol, cimetidine, danazol, ethinyl estradiol, amiodarone, methylprednisolone, protease inhibitors (eg, telaprevir, boceprevir, ritonavir), nefazodone, magnesium-aluminum-hydroxide. May be antagonized by carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, caspofungin, St. Johns Wort.
Adverse Reactions:
Diarrhea, constipation, nausea, peripheral edema, tremor, anemia, headache, abdominal pain, insomnia, hypertension, renal dysfunction, infections (viral, cytomegalovirus, polyoma virus), hypophosphatemia, hyperkalemia, hypomagnesemia, hyperglycemia, nephrotoxicity or neurotoxicity (esp. in high doses), JC virus-associated progressive multifocal leukoencephalopathy, post-transplant diabetes mellitus, posterior reversible encephalopathy syndrome (consider reduced dose or discontinue), malignancies (lymphomas, skin), post-transplant lymphoproliferative disorder, pure red cell aplasia (consider discontinuation).
How Supplied:
Ext-rel caps—30, 50 |
