部分中文利托那韦处方资料（仅供参考）

英文药名: Norvir (Ritonavir)

中文药名: 利托那韦

药品简介
雅培公司的利托那韦片获得美国FDA批准上市，用于单独或与抗逆转录病毒的核苷类药物合用治疗晚期或非进行性的艾滋病病人。
利托那韦为人免疫缺陷病毒-1（HIV-1）和人免疫缺陷病毒-2（HIV-2）天冬氨酸蛋白酶的口服有效抑制剂，阻断该酶促使产生形态学上成熟HIV颗粒所需的聚蛋白，使HIV颗粒因而保持在未成熟的状态，从而减慢HIV在细胞中的蔓延，以防止新一轮感染的发生和延迟疾病的发展。本品对齐多夫定敏感的和齐多夫定与沙喹那韦耐药的HIV株一般均有效。
利托那韦的剂量为600mg每日2次口服,可与进食同时进行。剂量从300mg每日2次在5天内逐渐递增至600mg每日2次,可减少腹泻的发生, 而这是一种主要的副作用。口服液如在30天内仍未服完必须放入冰箱。与吲哚那韦的交叉耐药常见；对其他蛋白酶抑制剂部分或完全耐药亦可见到。利托那韦是最强的细胞色素P-450酶抑制剂, 其他药物如某些非镇静类抗组胺药(如特非那定), 镇静类催眠药(如咪哒唑仑), 或抗心律失常药与之合用会使这些药物浓度升高达中毒水平及致病。所有合并用药都必须考虑其与利托那韦的可能的相互作用。促进P-450的药, 如利福平, 会降低利托那韦的血浓度, 而得不到预期疗效。副作用包括腹泻, 口周感觉异常, 味觉改变, 恶心, 肝炎和脂类异常。

分类名称
一级分类：皮肤科用药 二级分类：常用抗病毒药物 三级分类： 
 
药品英文名
Ritonavir
 
药品别名
利托那韦、雷托那韦、Norvir
 
药物剂型
1.胶囊：100mg，200mg；
2.口服液：10%，8%。
3.溶液剂：80mg(8ml)。
 
药理作用
利托那韦对人免疫缺陷病毒(HIV)有抑制活性。对HIV-1和HIV-2天门冬氨酸蛋白酶有抑制作用。本品为蛋白酶抑制剂，可阻止免疫缺陷病毒(HIV)蛋白酶，该酶影响病毒的终末形成。本品抑制HIV蛋白酶以致该酶不能加工多聚蛋白，从而不能产生形态成熟的HIV颗粒。由于该颗粒仍处于不成熟阶段，故HIV细胞之间的蔓延减缓。据此，蛋白酶抑制可阻止发生新的感染病灶，并延缓疾病的进展。本品是一种可口服的HIV-1和HIV-2天门冬氨酸蛋白酶多肽无机物抑制剂。在体外，它能拮抗所有HIV实验病毒株，同时具有抗齐多夫定敏感株或耐药病毒株的作用。本品对HIV蛋白酶有选择性亲和作用，其抗人天门冬氨酸蛋白酶抑制作用甚微。
 
药动学
口服吸收较好，生物利用度为60%以上，单剂量400mg顿服，血浆药物浓度达峰时间为2～4h，血药峰浓度53μg/ml。其剂量与血浆峰浓度和药-时曲线面积等参数呈非线性关系，可能与其可饱和的一过性代谢有关。进餐口服用血浆峰浓度和药-时曲线面积可升高63%，浓度达峰时间延迟1.6h。服用口服液1h后饮用巧克力奶不会影响其吸收程度和速率。在血浆和淋巴结浓度高，血浆半衰期为3～3.5h，血浆蛋白结合率为98%。主要在肝代谢，通过细胞色素P450氧化酶系统异构酶CYP3A和CYP2D6代谢，生成至少5种代谢物，主要代谢物也具抗毒活性，剂量的87%由粪便中排出，12%由尿液中排出，其中各含原形药物为36%和3.5%。
 
适应证
用于与抗逆病毒核苷类似物联合用于治疗HIV-1感染的晚期或进展性免疫缺陷患者。
 
禁忌证
1.严重肝疾病患者禁用。
2.妊娠及哺乳妇女禁用。
3.对本品过敏者禁用。
 
注意事项
1.慎用：
(1)轻或中度肝疾病、腹泻者慎用；
(2)12岁以下儿童慎用。
2.本品须在特殊监护下开始治疗。用于血友病患者治疗有自发性出血的现象，应注意对出血和血液变化的监测。单独应用本品或与核苷类反转录酶抑制剂联合应用，可使AST、ALT超出正常上限的5倍，发生肝炎或黄疸。对乙型或丙型肝炎患者有使转氨酶升高的可能，对既往患有肝疾病、肝酶异常、肝炎的患者在服用时尤应注意。服用本品的患者包括三酰甘油血症的患者有发生胰腺炎甚至死亡的危险，晚期HIV患者的发生率更大，如出现恶心、呕吐、腹部疼痛、血清脂肪酶和淀粉酶升高等症状者，应及时停药。对接受本品治疗的并发糖尿病者会引发或加重糖尿病，会出现高血糖、酮症酸中毒，应调整胰岛素和口服降糖药的剂量。
 
不良反应
1.常见发生胃肠不适、恶心、腹泻、腹痛、厌食、味觉异常、血管扩张、衰弱、无力、头痛、皮疹、荨麻疹、支气管痉挛、血管神经性水肿、出血或血肿、血液化学和血液学改变。2.偶见血浆三酰甘油、尿酸、AST、ALT升高、感觉异常、嗜酸粒细胞增多或过敏反应。
 
用法用量
口服：每次600mg，每天2次，宜与食物同服或餐后服用。或初始一次300mg，每天2次，每隔2天增加100mg，至一次600mg。
 
药物相应作用
1.本品有抑制细胞色素系统的作用，为细胞色素P450CYP3A及其他同工酶抑制剂，因此与许多具类似作用的药物有相互作用，可极大地提高被CYP3A及其他同工酶代谢药物的血浆浓度。
2.本品不能与利福喷汀、镇静剂、催眠剂、沙奎那韦或其他蛋白酶抑制剂药物联合应用。
3.本品不能与细胞色素P450代谢药物联用，因其可引起心律失常、血恶液质、癫痫样发作或其他严重不良反应。
4.本品与免疫抑制剂、非镇静组胺拮抗剂、大环内酯类抗生素、钙拮抗剂、抗抑郁药、神经肽类、西沙必利、艾司唑仑、右丙氧酚、恩卡尼、阿司咪唑、特非那丁、麦角胺、抗真菌药、美沙酮、芬太尼、卡马西平、华法林、甲苯磺丁脲、吗啡、地昔帕明、口服避孕药和氨茶碱等同时使用时应谨慎。5.如本品为口服液时，避免使用甲硝唑药物。6.本品可抑制其他HIV蛋白酶抑制剂的代谢，同时给予沙奎那韦、奈非那韦、茚地那韦，其血浆药-时曲线下面积分别增加36倍、10倍和8倍，另与沙奎那韦、茚地那韦具有交叉耐药性.

7.与麦角胺或二氢麦角胺联合应用可引起急性麦角中毒，其特征为外周血管痉挛或肢端缺血。
 
专家点评
本品为人免疫缺陷病毒蛋白酶的抑制剂，能使病毒负荷明显降低，CD4细胞计数显著增高。本品能单独应用或与核苷类似物合用来治疗晚期人免疫缺陷病毒感染。在研究本品的6个月中证明，本品能减缓患者疾病的进程50%以上。口服本品血浆蛋白的结合率约为98%。采取开始单用本品，2周后加入核苷的方法，可以提高患者对联合用药的耐受性。国外报道，两组随机、双盲、安慰剂对照的临床研究评介了本品抗HIV活性，一组口服安慰剂、利托那韦每次300～400mg，每天2次；另一组口服安慰剂、利托那韦每次500～600mg，每天2次，连续4周后进行盲性剂量延长治疗。结果所有经药物治疗患者的P24抗原滴度比基础值下降40%，多数患者的CD4细胞计数较基础值升高100%。另一试验评介本品治疗12周的抗HIV活性，患者随机分成2组，第一组口服安慰剂、利托那韦每次200～300mg，每天3次；第二组口服利托那韦每次200～300mg，每天4次。前4周为双盲对照，后8周均服用有效药物。结果经本品治疗后证实有明显的抗病毒活性，血浆HIV-RNA复制次数下降0.86～1.18自然对数值。
关于联合用药治疗，国外报道，本品为HIV强效抑制剂，对患有晚期疾病且经过广泛治疗的1090例HIV感染者随机分成2组，进行的为期6个月的安慰剂对照试验，发现在现行的疗法中增加本品能延缓病情的进展或降低死亡率。在两组患者中分别有26例和46例死亡。占病例总数的5%或8%。国外报道，本品与抗反转录病毒核苷类似物联合用于治疗HIV感染的晚期免疫缺陷患者，一项与安慰剂对照的临床研究证实，接受本品治疗的患者，其累积病死率为40%，连续口服6个月，患者的病程减缓50%。在大规模临床试验中，本品治疗组患者与对照组相比结果表明，其降低HIV-RNA浓度有明显的统计学差异，并明显增加CD4细胞细胞计数。首次临床试验统计证明，本品可延缓疾病的进展，并延长晚期HIV患者的生存时间。在多数晚期HIV-1感染的患者中，本品与齐多夫定联合治疗可降低病毒负荷和改善免疫状况。使用本品与齐多夫定和扎西他滨三联疗法，治疗时间长达60周，减少病毒负荷的结果与单用本品治疗类似，但联合治疗能减少耐药性。本品一般耐受良好，最常见的不良反应为胃肠道不适，在治疗的第2～4周，发生率最高，与本品最高血药浓度一致。 

Use
NORVIR® (ritonavir) is in a class of medicines called the HIV protease (PRO-tee-ase) inhibitors. NORVIR is used in combination with other anti-HIV medicines to treat people with human immunodeficiency virus (HIV) infection. NORVIR is for adults and for children age greater than 1 month and older.

NORVIR does not cure HIV infection or AIDS and does not reduce the risk of passing HIV to others. People taking NORVIR may still get opportunistic infections or other conditions that happen with HIV infection. Some of these conditions are pneumonia, herpes virus infections, and Mycobacterium avium complex (MAC) infections.

Important Safety Information
Do not take NORVIR if you have had a serious allergic reaction to NORVIR or any of its ingredients. Allergic reactions ranging from hives, asthma, severe breathing issues and mild to severe skin reactions have occurred.

Drug Interactions:
The below list of drug interactions is not complete. Before you take NORVIR, you must tell your doctor about all the medicines you are taking or are planning to take. These include other prescription and non-prescription medicines and herbal supplements.

Do not take the following medicines with NORVIR because they can cause serious or life-threatening problems such as irregular heartbeat, breathing difficulties or excessive sleepiness: Cordarone® (amiodarone); ergotamine, ergonovine, methylergonovine, and dihydroergotamine such as Cafergot®, Migranal®, D.H.E. 45® and others; Halcion® (triazolam); Orap® (pimozide); Propulsid® (cisapride); quinidine, also known as Quinaglute®, Cardioquin®, Quinidex® and others; Revatio® (sildenafil) only when used for the treatment of pulmonary arterial hypertension; Rythmol® (propafenone); Tambocor® (flecainide); Uroxatral® (alfuzosin hydrochloride); Vascor® (bepridil); Versed® (oral midazolam); and Vfend® (voriconazole).

Do not take NORVIR with St. John’s wort (Hypericum perforatum) as this may decrease NORVIR levels and lead to increased viral load and possible resistance to NORVIR or other antiretroviral medicines.

Do not take NORVIR with Mevacor® (lovastatin) or Zocor® (simvastatin) because of possible serious reactions. There is an increased risk of drug interactions between NORVIR and Lipitor® (atorvastatin) and Crestor® (rosuvastatin); you should talk to your doctor before you take any of these cholesterol-lowering medicines with NORVIR.

If you are taking Viagra® (sildenafil), Cialis® (tadalafil), or Levitra® (vardenafil) with NORVIR, your doctor may lower your dose of these medicines because you may be at risk of side effects such as low blood pressure, visual changes, and penile erection lasting more than 4 hours. Tell your doctor right away if you experience any of these side effects.

If you are taking Adcirca® (tadalafil) for pulmonary arterial hypertension, your doctor may change your dose of this medicine.

If you are taking oral contraceptives (“the pill”) or using the contraceptive patch to prevent pregnancy, you should use a different type of contraception since NORVIR may reduce the effectiveness of oral or patch contraceptives.

If you are taking Mycobutin® (rifabutin), your doctor will lower the dose of Mycobutin.

If you are taking Colcrys® (colchicine) or Tracleer® (bosentan), your doctor will tell you what dose to use.

NORVIR oral solution contains alcohol. Talk with your doctor if you are taking or planning to take Flagyl® (metronidazole) or Antabuse® (disulfiram). Severe nausea and vomiting can occur.

Rifampin, also known as Rimactane®, Rifadin®, Rifater®, or Rifamate®, may reduce blood levels of NORVIR. Be sure to tell your doctor if you are taking rifampin.

Rifampin and saquinavir should not be taken together with NORVIR. Be sure to tell your doctor if you are taking rifampin and saquinavir.

If you are taking or before you begin using inhaled Flonase® (fluticasone propionate), Serevent® (salmeterol), or Advair® (salmeterol in combination with fluticasone propionate), talk to your doctor about problems these medicines may cause when taken with NORVIR. Your doctor may choose not to keep you on inhaled Flonase, Serevent, or Advair.

Side Effects: (This list is not complete):
Blood tests in patients taking NORVIR may show possible liver problems. People with liver disease such as hepatitis B and C who take NORVIR may have worsening liver disease. Liver problems, including death, have occurred in people who take NORVIR and in people taking Aptivus® (tipranavir) with NORVIR. Tell your doctor right away if you have any of the following signs and symptoms: loss of appetite, yellowing of skin or eyes (jaundice), dark-colored urine, pale-colored stools, itchy skin and/or stomach area (abdominal) pain.

Pancreas problems (pancreatitis), which may cause death, have been reported in some people taking NORVIR. Tell your doctor if you have nausea, vomiting or abdominal pain as these may be signs of pancreatitis.

Large increases in triglycerides and cholesterol have occurred in some people taking NORVIR. The long-term chance of getting complications such as heart attacks or stroke due to increases in triglycerides and cholesterol caused by protease inhibitors is not known at this time.

Diabetes and high blood sugar (hyperglycemia), changes in body fat, and increased bleeding in people with hemophilia have occurred in some people taking protease inhibitors, including NORVIR. You should tell your doctor if you have diabetes or an increase in thirst or urinate often. The cause and long-term effects of body fat changes are not known at this time.

Changes in the electrocardiogram (EKG) can occur when taking NORVIR. Consult your doctor if you experience dizziness, lightheadedness, fainting spells or abnormal heartbeat. People with heart defects or conduction defects should avoid NORVIR.

Immune reconstitution syndrome may occur after starting anti-HIV medicines, including NORVIR. This happens when you develop signs and symptoms of serious infections you already have or had, which may require additional treatment.

The most commonly reported side effects are feeling weak/tired, nausea, vomiting, diarrhea, loss of appetite, abdominal pain, changes in taste, tingling feeling or numbness (in hands or feet or around the lips), headache, and dizziness.

If you are pregnant or planning to become pregnant, it is not known if NORVIR can harm your unborn baby. If you take NORVIR while you are pregnant, talk to your doctor about how you can take part in the Antiretroviral Pregnancy Registry. You should not breast-feed because you may pass HIV on to your baby or your baby could experience side effects from NORVIR.
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附件：

20118321591325.PDF    

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产地国家: 美国
原产地英文商品名:
NORVIR SOLUTION 80MG/ML 240MLS/BOTTLE
原产地英文药品名:
RITONAVIR
中文参考商品译名:
NORVIR溶液 80毫克/毫升 240毫升/瓶
中文参考药品译名:
利托那韦
生产厂家中文参考译名:
雅培
生产厂家英文名:
ABBOTT