英文药名: Tekturna(Aliskiren Tablets) 中文药名: 阿利吉仑片 生产厂家: Novartis 药品介绍 美国FDA最终于2007年3月批准了瑞士诺华公司研制的治疗高血压新药阿利吉仑（aliskiren）上市, 其商品名为Tekturna。 这是FDA批准的第一个肾素抑制剂类高血压治疗药物，可单独或与其他降压药联合治疗高血压。目前市场上出售的Tekturna为含阿利吉仑游离碱150 mg和300 mg的薄膜衣片。其片剂所用的辅料包括下列成分：胶性二氧化硅，交联PVP，羟丙甲纤维素（hypromellose），氧化铁着色剂，硬脂酸镁，微晶纤维素，聚乙二醇，聚维酮（povidone），滑石粉和二氧化钛。 阿利吉仑的药代动力学特点 阿利吉仑是一种口服有效的非肽类直接肾素抑制剂，化学名为：（2S，4S，5S，7S）-N-（2-氨甲酰基-2-甲基丙基）-5-氨基-4-羟基-2，7-二异丙基-8-［4-甲氧基-3-（3-甲氧基丙氧基）苯基］-辛胺半富马酸盐，分子量为609.8。阿利吉仑口服吸收差（生物利用度约2.7%），半衰期平均23.7小时（20～45小时），适合每天1次给药，口服后1～3小时内血浆浓度达峰，连续给药5～8天后血浆浓度达到稳定状态。阿利吉仑主要以原形物经胆道排泄，吸收后的阿利吉仑约1/4经尿液排泄。由于阿利吉仑不抑制或诱导CYP450系统, 故与华法林、洛伐他汀、地高辛、缬沙坦、氨氯地平、二甲双胍、塞来考昔、阿替洛尔、阿伐他汀、雷米普利及氢氯噻嗪等合用时，不影响这些药物的药代动力学。但阿利吉仑与伊贝沙坦联用时自身血药浓度可以降低50%，与阿拓伐他汀联用时则增加50%，与酮康唑合用增加80%，与环胞霉素A合用时自身血药浓度亦显著增加；而与呋塞米合用时会显著降低呋塞米的血药浓度。 阿利吉仑的临床试验 6项随机双盲，安慰剂对照、为期8周的临床试验在轻-中度高血压患者中评价了阿利吉仑单药治疗的降压效果。在这些试验中，共2 730例患者服用阿利吉仑75～600 mg/d，1 231例患者服用安慰剂。试验结果表明，在用药治疗2周内，血压下降85%～90%，150～300 mg/d的使用剂量呈现较好的降压效果，剂量增加到600 mg/d时并不能进一步增强降压疗效。连续使用阿利吉仑1年以上，其疗效与安慰剂组相比较仍有显著差异，停用药物后，患者的血压在几周内逐渐恢复至基线水平，并不会引起血压反跳。据统计，阿利吉仑在黑人患者中的降压效果似乎稍次于白人或亚洲人群。 在随后进行的一项随机、双盲临床试验中，有687名患者经过26周阿利吉仑及雷米普利治疗（两药均单独使用或与双氢克尿噻联用），两组相比平均收缩压下降分别是17.9与15.2 mmHg（P =0.003 6），平均舒张压下降分别是13.2 mmgHg与12.0 mmgHg（P =0.025）。同时，此研究还观察了停药后4周内血压变化情况，发现阿利吉仑组比雷米普利组降压效果更为持久。因此得出阿利吉仑可以长期降压，并且降压效果在停药后也可持续较长时间，为高血压治疗提供了一种新的选择。 用法用量 目前，阿利吉仑推荐起始用量为150 mg每天一次，当血压控制不佳时2周后可增至300 mg每天一次。剂量超过300 mg不仅不增加降压作用, 还可能增加胃肠道不良反应发生率。老年人、糖尿病、肥胖及轻中度肝肾功能不全患者对阿利吉仑均能较好地耐受，初始剂量一般无需调整。有研究表明高脂食物可使阿利吉仑的平均AUC和Cmax分别降低71%和85%，建议空腹服用且服药30分钟以上进食。阿利吉仑口服后，血浆肾素活性可在30分钟内被迅速抑制。 不良反应 临床研究表明，阿利吉仑的不良反应发生率与ARB和ACEI或安慰剂相当，不良反应发生率大都不会随着剂量的增加而增加。因阿利吉仑的作用机制是直接抑制肾素，所以不会像ACEI一样升高循环中缓激肽的水平，一般不会产生血管性水肿和干咳等使患者不易耐受的不良反应。目前，阿利吉仑的安全性已经在至少6 460例患者进行过评价，其中1 740例患者治疗时间超过6个月，1 250例患者超过1年。在许多临床研究中，最常见的不良反应是疲乏、头晕、头痛和腹泻，胃肠道不良反应可能与剂量相关，无严重不良反应。Vaidyanathan等研究比较阿利吉仑300 mg剂量对轻、中、重度肝损伤和健康受检者的安全性和药代动力学，结果显示阿利吉仑引起的肝损伤和健康受检者无显著差异，肝脏疾病患者服用阿利吉仑不需要调整剂量。但阿利吉仑可轻度增加咳嗽的发生率（1.1%，安慰剂组0.6%）。在与赖诺普利或雷米普利比较的研究中，阿利吉仑组的咳嗽发生率约为ACEI组的1/3或1/2。其它较常见的不良反应还包括皮疹（1%）、尿酸升高（0.47%）、痛风（0.2%）和肾结石（0.2%）等，面部、手或全身浮肿的发生率与安慰剂相当。高血钾症罕见，但有研究表明本品在糖尿病患者中与ACE I联用后高钾血症的发生率明显增加， 故对于合并肾功能不全、糖尿病和心衰的患者，同时使用保钾药物和钾补充剂时需注意监测血钾。 本品禁用于孕妇，因其可能增加胎儿、新生儿的发病率和死亡率，对于孕妇在怀孕的前3个月，被定为C类；而在怀孕后的4～9个月，被定为D类[10]。肾功能不全（即血清肌肝）>117mg/dl（女）、> 210 mg/dl（男），或GFR<30患者(除外有血滤史、肾病综合征、肾血管性高血压者)，在服用此药时需特别谨慎。 包装规格： ·150mg *28 片 ·300mg *28 片  FDA approved Tekturna (aliskiren) The idea of treating hypertension by blocking the actions of renin has been toyed with by pharmaceutical companies for over twenty years with little success. Aliskiren is the first agent with satisfactory pharmacologic properties to be tested for efficacy in phase III clinical trials. Renin is secreted by the kidney in response to low blood pressure and catalyzes the first and rate-limiting step along the renin-angiotensin system (RAS), the conversion of angiotensinogen to angiotensin I. Over activity of the RAS is known to play a role in the pathology of hypertension, cardiovascular disease, and chronic kidney disease via the actions of angiotensin II. Our current therapeutic options for blocking the actions of the RAS include angiotensin converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARBs). Aliskiren now offers the ability to block the actions of the RAS at its point of origin. Several industry sponsored randomized, double-blinded, placebo-controlled trials have studied the safety and efficacy of aliskiren for treatment of mild-to-moderate hypertension. One trial published in Circulation compared the blood pressure lowering effects of aliskiren (150mg or 300mg) compared to placebo and irbesartan (150mg). After 8 weeks of treatment, patients receiving aliskiren 150mg or 300mg had significantly larger reductions in both systolic and diastolic blood pressure versus placebo. The average decrease in blood pressure (SBP/DBP) for those taking aliskiren was 11.4/9.3 and 15.8/11.8 for 150mg and 300mg respectively. Reductions in blood pressure were similar between aliskiren and irbesartan however those taking 300mg of aliskiren had significantly lower diastolic blood pressure recordings. Of note, all the trials have shown smaller blood pressure reductions among African Americans than among Caucasian of Asian subjects. All told, safety data is available for over 6,500 subjects who have participated in various studies of aliskiren. It appears to be generally well tolerated and safe. The most commonly reported adverse effect is diarrhea. Cough and rash have also been noted but have occurred about half as frequently as with ACE-I. Hypotension has been rare but reported and two cases of angioedema have also occurred. Aliskiren will be available as a single daily dose pill in either 150mg or 300mg doses. It is approved for use both as mono-therapy and in combination with a thiazide diuretic or ARB. It’s clearance is largely hepatic (CYP3A4) and no renal dosing is recommended however patients with GFR <30 were excluded from study. No major drug/drug interactions are known however use of other drugs with similar metabolism may prolong the effects of aliskiren. Like ACE-I and ARBs, administration during pregnancy or nursing is contraindicated, and the manufacturers have recommended avoiding high fat meals at the time of administration as this lowers the absorption of aliskiren. Generic Name for TEKTURNA Aliskiren 150mg, 300mg; tabs. Legal Classification: Rx Pharmacological Class for TEKTURNA Direct renin inhibitor. Manufacturer of TEKTURNA Novartis Pharmaceuticals Corp Indications for TEKTURNA Hypertension. Adult dose for TEKTURNA ≥18yrs: initially 150mg once daily, may increase to 300mg once daily if BP not adequately controlled. May be given with other antihypertensives (see literature). Children's dosing for TEKTURNA <18yrs: not recommended. Warnings/Precautions for TEKTURNA Moderate to severe renal dysfunction; consider monitoring electrolytes. Correct salt/volume depletion before starting therapy or start under close supervision. History of dialysis. Nephrotic syndrome. Renovascular hypertension. Monitor for hyperkalemia (esp. in diabetics on ACE inhibitors). Pregnancy (Cat.C in 1st trimester; Cat.D 2nd and 3rd trimesters); discontinue as soon as pregnancy detected. Nursing mothers: not recommended. Interactions for TEKTURNA Concomitant cyclosporine: not recommended. Caution with K+ supplements, K+ sparing diuretics, K+ containing salt substitutes; may cause hyperkalemia. Decreases furosemide plasma levels; may have diminished effect. Potentiated by atorvastatin, ketoconazole. Antagonized by irbesartan, high fat meals. Caution with max doses of ACE inhibitors. Adverse Reactions for TEKTURNA Diarrhea, hypotension, cough, rash, edema, elevated uric acid, gout, renal stones; rare: angioedema (discontinue if occurs; do not restart). How is TEKTURNA supplied? Tabs—30, 90