药品名称

英文药名: Atripla (Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate Tablets)
中文药名: 依法韦恩茨/恩曲他滨/替诺福韦富马酸片
此药生产商:Bristol-Myers-Squibb 和 Gilead Sciences, LLC.
药品介绍

艾滋病即获得性免疫缺陷综合征(AIDS),是由艾滋病病毒(HIV)引起的一种传染病,其特征是HIV特异性攻击辅助性T淋巴细胞,造成免疫系统功能进行性破坏,导致各种机会性感染和相关肿瘤的发生。艾滋病已成为威胁全人类的重大传染病,从1981年美国报道第1例艾滋病到至今的25年间,艾滋病病毒在全世界迅速蔓延。联合国艾滋病规划署(UNAIDS)2006年12月的最新流行报告显示,目前全球现存HIV/AIDS患者3950万例,仅2006年1年间,就有430万新感染病例,290万人死于艾滋病。
 
艾滋病药Atripla含3种药物：依法韦恩茨(efavirenz)、恩曲他滨(emtricitabine)和富马酸替诺福韦酯（tenofovir disoproxil fumarate），服用剂量为每日一片。
FDA批准首个治疗1型人类免疫缺陷病毒(HIV-1)感染的复方片剂Atripla(含固定剂量依法韦仑、恩曲他滨和替诺福韦3种广泛使用的抗逆转录病毒药),可单独应用或与其他抗逆转录病毒药合用治疗HIV-1感染成年患者。Atripla也是第一种每次1片、每日只需服用1次治疗HIV/AIDS的药物,它符合推荐的HIV感染治疗原则??开始治疗时至少使用3种高效抗逆转录病毒药。
Atripla简化了HIV-1感染的治疗方法,患者更易坚持治疗,而且有助于减少耐药性的产生,以达到长期控制HIV-1感染的目的。一项纳入244例HIV-1感染患者的为期48周的临床研究证明,联合应用依法韦仑、恩曲他滨和替诺福韦这3种药物安全、有效,80%的患者HIV显著减少,CD4细胞数显著增多。
Atripla的标签包括一个警告框,即该药可导致乳酸酸中毒。慢性乙型肝炎患者在停用Atripla(FDA没有批准这个适应证)后可加剧乙肝感染。其他可能导致的严重不良事件包括严重肝毒性、肾损伤和重症抑郁。最常见的不良反应有头痛、头晕、腹痛、恶心、呕吐和皮疹。
任何疑问，请遵医嘱！

VIRADAY (generic ATRIPLA)
Is an antiviral combination of 3 reverse transcriptase inhibitors. It works by slowing the growth of HIV, the virus that causes AIDS.

Important Patient Information

VIRADAY (generic ATRIPLA™) (uh TRIP luh) Tablets

Generic name: efavirenz, emtricitabine and tenofovir disoproxil fumarate (eh FAH vih renz, em tri SIT uh bean and te NOE’ fo veer dye soe PROX il FYOU mar ate)
 
VIRADAY: efavirenz and Emtricitabine and Tenofovir Disoproxil Fumarate Tablet 
 
COMPOSITION
VIRADAY
Each film-coated tablet contains:
Efavirenz ..................................................... 600 mg
Emtricitabine ...............................................200 mg
Tenofovir disoproxil fumarate ..................... 300 mg
e quivalent to Tenofovir disoproxil ............... 245 mg
 
INDICATIONS
VIRADAY is indicated for use alone as a complete regimen or in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults.
 
DOSAGE AND ADMINISTRATION
Adults
The dose of VIRADAY is one tablet once daily taken on an empty stomach. Dosing at bedtime may improve the tolerability of nervous system symptoms.

Pediatrics
VIRADAY is not recommended for use in patients <18 years of age.

Renal Impairment
Because VIRADAY is a fixed-dose combination, it should not be prescribed for patients requiring dosage adjustment such as those with moderate or severe renal impairment (creatinine clearance <50 mL/min).
 
CONTRAINDICATIONS
Hypersensitivity
VIRADAY is contraindicated in patients with previously demonstrated clinically significant hypersensitivity (e.g., Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to efavirenz, a component of VIRADAY.

Contraindicated Drugs
For some drugs, competition for CYP3A by efavirenz could result in inhibition of their metabolism and create the potential for serious and/or life-threatening adverse reactions (eg, cardiac arrhythmias, prolonged sedation, or respiratory depression). Drugs that are contraindicated with VIRADAY are listed in Table1.

Table 1: Drugs that are contraindicated or not recommended for use with VIRADAY 

Drug Class: Drug Name	Clinical Comment
Antifungal Voriconazole	Efavirenz significantly decreases voriconazole plasma concentrations, and co-administration may decrease the therapeutic effectiveness of voriconazole. Also, voriconazole significantly increases efavirenz plasma concentrations, which may increase the risk of efavirenz-associated side effects. Because VIRADAY is a fixed-dose combination product, the dose of efavirenz cannot be altered.
Ergot derivatives (Dihydroergotamine, ergonovine, ergotamine, methylergonovine)	Potential for serious and/or life-threatening reactions such as acute ergot toxicity characterized by peripheral vasospasm and ischemia of the extremities and other tissues.
Benzodiazepines: Midazolam, triazolam	Potential for serious and/or life-threatening reactions such as prolonged or increased sedation or respiratory depression.
Calcium channel blocker: Bepridil	Potential for serious and/or life-threatening reactions such as cardiac arrhythmias.
GI motility agent Cisapride	Potential for serious and/or life-threatening reactions such as cardiac arrhythmias.
Neuroleptic Pimozide	Potential for serious and/or life-threatening reactions such as cardiac arrhythmias.
St. John`s wort(Hypericum perforatum)	May lead to loss of virologic response and possible resistance to efavirenz or to the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs).

PACKAGING INFORMATION
VIRADAY………………………Container of 30 tablets

ATRIPLA

Information that comes with ATRIPLA before you start taking it and each time you get a refill since there may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. You should stay under a healthcare provider's care when taking ATRIPLA. Do not change or stop your medicine without first talking with your healthcare provider. Talk to your healthcare pr ovider or pharmacist if you have any questions about ATRIPLA.

What is the most important information I should know about ATRIPLA?

Some people who have taken medicine like ATRIPLA (which contains nucleoside analogs) have developed a serious condition called lactic acidosis (build up of an acid in the blood). Lactic acidosis can be a medical emergency and may need to be treated in the hospital. Call your healthcare provider right away if you get the following signs or symptoms of lactic acidosis:

You feel very weak or tired.
You have unusual (not normal) muscle pain.

You have trouble breathing.
You have stomach pain with nausea and vomiting.
You feel cold, especially in your arms and legs.
You feel dizzy or lightheaded.
You have a fast or irregular heartbeat.
Some people who have taken medicines like ATRIPL A have developed serious liver problems called hepatotoxicity, with liver enlargement (hepatomegaly) and fat in the liver (steatosis). Call your healthcare provider right away if you get the following signs or symptoms of liver problems:

Your skin or the white part of your eyes turns yellow (jaundice).
Your urine turns dark.
Your bowel movements (stools) turn light in color.
You don't feel like eating food for several days or longer.
You feel sick to your stomach (nausea).
You have lower stomach area (abdominal) pain.
Y ou may be more likely to get lactic acidosis or liver problems if you are female, very overweight (obese), or have been taking nucleoside analog-containing medicines, like ATRIPLA, for a long time.

If you also have Hepatitis B Virus (HBV) infection and you stop taking ATRIPLA, you may get a "flare-up" of your hepatitis. A "flare-up" is when the disease suddenly returns in a worse way than before. Patients with HBV who stop taking ATRIPLA need close medical follow-up for several months, including medical exams and blood tests to check for hepatitis that could be getting worse. ATRIPLA is not approved for the treatment of HBV, so you must discuss your HBV therapy with your heal thcare pro vider.

What is ATRIPLA?

ATRIPLA contains 3 medicines, SUSTIVA® (efavirenz), EMTRIVA® (emtricitabine) and VIREAD® (tenofovir disoproxil fumarate also called tenofovir DF) combined in one pill. EMTRIVA and VIREAD are HIV (human immunodeficiency virus) nucleoside analog reverse transcriptase inhibitors (NRTIs) and SUSTIVA is an HIV non-nucleoside analog reverse transcriptase inhibitor (NNRTI). VIREAD and EMTRIVA are the components of TRUVADA®. ATRIPLA can be used alone as a complete regimen, or in combination with other anti-HIV medicines to treat people with HIV infection. ATRIPLA is for adults age 18 and over. ATRIPLA has not been studi ed in children under age 18 or adults over age 65.

HIV infection destroys CD4 (T) cells, which are important to the immune system. The immune system helps fight infection. After a large number of T cells are destroyed, acquired immune deficiency syndrome (AIDS) develops.

ATRIPLA helps block HIV reverse transcriptase, a viral chemical in your body (enzyme) that is needed for HIV to multiply. ATRIPLA lowers the amount of HIV in the blood (viral load). ATRIPLA may also help to increase the number of T cells (CD4 cells), allowing your immune system to improve. Lowering the amount of HIV in the blood lowers the chance of death or infections that happen when your immune system is weak (opportunistic infections).

Does ATRIPLA cure HIV-1 or AIDS?

ATRIPLA does not cure HIV infection or AIDS. The long-term effects of ATRIPLA are not known at this time. People taking ATRIPLA may still get opportunistic infections or other conditions that happen with HIV infection. Opportunistic infections are infections that develop because the immune system is weak. Some of these conditions are pneumonia, herpes virus infections, and Mycobacterium avium complex (MAC) infection. It is very important that you see your healthcare provider regularly while taking ATRIPLA.

Does ATRIPLA reduce the risk of passing HIV-1 to others?

ATRIPLA has not been shown to lower your chance of passing HIV to other people through sexual contact, sharing needles, or being exposed to your blood.

Do not share needles or other injection equipment.
Do not share personal items that can have blood or body fluids on them, like toothbrushes or razor blades.
Do not have any kind of sex without protection. Always practice safer sex by using a latex or polyurethane condom or other barrier to reduce the chance of sexual contact with semen, vaginal secretions, or blood.
Who should not take ATRIPLA?

Together with your healthcare provider, you need to decide whether ATRIPLA is right for you.

Do not take ATRIPLA if you are allergic to ATRIPLA or any of its ingredients. The active ingredients of ATRIPLA are efavirenz, emtricitabine, and tenofovir DF. See the end of this leaflet for a complete list of ingredients.

What should I tell my healthcare provider before taking ATRIPLA?

Tell your healthcare provider if you:
Are pregnant or planning to become pregnant (see "What should I avoid while taking ATRIPLA?").
Are breastfeeding (see "What should I avoid while taking ATRIPLA?").
Have kidney problems or are undergoing kidney dialysis treatment.
Have bone problems.
Have liver problems, including Hepatitis B Virus infection. Your healthcare provider may want to do tests to check your liver while you take ATRIPLA.
Have ever had mental illness or are using drugs or alcohol.
Have ever had seizures or are taking medicine for seizures.
What important information should I know about taking other medicines with ATRIPLA?

ATRIPLA may change the effect of other medicines, including the ones for HIV, and may cause serious side effects. Your healthcare provider may change your other medicines or change their doses. Other medicines, including herbal products, may affect ATRIPLA. For this reason, it is very important to let all your healthcare providers and pharmacists know what medications, herbal supplements, or vitamins you are taking.

MEDICINES YOU SHOULD NOT TAKE WITH ATRIPLA

The following medicines may cause serious and life-threatening side effects when taken with ATRIPLA. You should not take any of these medicines while taking ATRIPLA: Hismanol® (astemizole), Propulsid® (cisapride), Versed® (midazolam), Halcion®(triazolam), ergot medications (for example, Wigraine® and Cafergot®).

ATRIPLA also should not be used with COMBIVIR®, EMTRIVA, EPIVIR®, EPIVIR-HBV®, EPZICOM™, TRIZIVIR®, SUSTIVA, TRUVADA, or VIREAD.

Vfend® (voriconazole) should not be taken with ATRIPLA since it may lose its effect or may increase the chance of having side effects from ATRIPLA.

It is also important to tell your healthcare provider if you are taking any of the following:

Fortovase®, Invirase® (saquinavir), or Biaxin® (clarithromycin); these medicines may need to be replaced with another medicine when taken with ATRIPLA.

Crixivan® (indinavir); Methadone; Mycobutin® (rifabutin); Rifampin; cholesterol-lowering medicines such as Lipitor® (atorvastatin), PRAVACHOL® (pravastatin), and Zocor® (simvastatin); or Zoloft® (sertraline); these medicines may need to have their dose changed when taken with ATRIPLA.

Videx®, Videx® EC (didanosine); tenofovir DF (a component of ATRIPLA) may increase the amount of didanosine in your blood, which could result in more side effects. You may need to be monitored more carefully if you are taking ATRIPLA and didanosine together. Also, the dose of didanosine may need to be changed.

Reyataz® (atazanavir sulfate) or Kaletra® (lopinavir/ritonavir); these medicines may increase the amount of tenofovir DF (a component of ATRIPLA) in your blood, which could result in more side effects. You may need to be monitored more carefully if you are taking ATRIPLA and either Reyataz or Kaletra together. Also, the dose of Reyataz or Kaletra may need to be changed.

Medicine for seizures [for example, Dilantin® (phenytoin), Tegretol® (carbamazepine), or phenobarbital]; your healthcare provider may want to switch you to another medicine or check drug levels in your blood from time to time.

Taking St. John's wort (Hypericum perforatum), or products containing St. John's wort with ATRIPLA is not recommended. St. John's wort is an herbal product sold as a dietary supplement. Talk with your healthcare provider if you are taking or are planning to take St. John's wort. Taking St. John's wort may decrease ATRIPLA levels and lead to increased viral load and possible resistance to ATRIPLA or cross-resistance to other anti-HIV drugs.

These are not all the medicines that may cause problems if you take ATRIPLA. Be sure to tell your healthcare provider about all medicines that you take.

Keep a complete list of all the prescription and nonprescription medicines as well as any herbal remedies that you are taking, how much you take, and how often you take them. Make a new list when medicines or herbal remedies are added or stopped, or if the dose changes. Give copies of this list to all of your healthcare providers and pharmacists every time you visit your healthcare provider or fill a prescription. This will give your healthcare provider a complete picture of the medicines you use. Then he or she can decide the best approach for your situation.

How should I take ATRIPLA?

Take the exact amount of ATRIPLA your healthcare provider prescribes. Never change the dose on your own. Do not stop this medicine unless your healthcare provider tells you to stop.

You should take ATRIPLA on an empty stomach.

Swallow ATRIPLA with water.

Taking ATRIPLA at bedtime may make some side effects less bothersome.

Do not miss a dose of ATRIPLA. If you forget to take ATRIPLA, take the missed dose right away, unless it is almost time for your next dose. Do not double the next dose. Carry on with your regular dosing schedule. If you need help in planning the best times to take your medicine, ask your healthcare provider or pharmacist.

If you believe you took more than the prescribed amount of ATRIPLA, contact your local poison control center or emergency room right away.

Tell your healthcare provider if you start any new medicine or change how you take old ones. Your doses may need adjustment.

When your ATRIPLA supply starts to run low, get more from your healthcare provider or pharmacy. This is very important because the amount of virus in your blood may increase if the medicine is stopped for even a short time. The virus may develop resistance to ATRIPLA and become harder to treat.

Your healthcare provider may want to do blood tests to check for certain side effects while you take ATRIPLA.

What should I avoid while taking ATRIPLA?

Women taking ATRIPLA should not become pregnant. Serious birth defects have been seen in the babies of animals and women treated with efavirenz (a component of ATRIPLA) during pregnancy. It is not known whether efavirenz caused these defects. Tell your healthcare provider right away if you are pregnant. Also talk with your healthcare provider if you want to become pregnant.

Women should not rely only on hormone-based birth control, such as pills, injections, or implants, because ATRIPLA may make these contraceptives ineffective. Women must use a reliable form of barrier contraception, such as a condom or diaphragm, even if they also use other methods of birth control.

Do not breast-feed if you are taking ATRIPLA. The Centers for Disease Control and Prevention recommend that mothers with HIV not breast-feed because they can pass the HIV through their milk to the baby. Also, ATRIPLA may pass through breast milk and cause serious harm to the baby. Talk with your healthcare provider if you are breast-feeding. You should stop breast-feeding or may need to use a different medicine.

Taking ATRIPLA with alcohol or other medicines causing similar side effects as ATRIPLA, such as drowsiness, may increase those side effects.

Do not take any other medicines, including prescription and nonprescription medicines and herbal products, without checking with your healthcare provider.

Avoid doing things that can spread HIV infection since ATRIPLA does not stop you from passing the HIV infection to others.

What are the possible side effects of ATRIPLA? 

ATRIPLA may cause the following serious side effects:

Lactic acidosis (buildup of an acid in the blood). Lactic acidosis can be a medical emergency and may need to be treated in the hospital. Call your healthcare provider right away if you get signs of lactic acidosis. (See "What is the most important information I should know about ATRIPLA?")

Serious liver problems (hepatotoxicity), with liver enlargement (hepatomegaly) and fat in the liver (steatosis). Call your healthcare provider right away if you get any signs of liver problems. (See "What is the most important information I should know about ATRIPLA?")

"Flare-ups" of Hepatitis B Virus (HBV) infection, in which the disease suddenly returns in a worse way than before, can occur if you have HBV and you stop taking ATRIPLA. Your healthcare provider will monitor your condition for several months after stopping ATRIPLA if you have both HIV and HBV infection and may recommend treatment for your HBV.

Serious psychiatric problems. A small number of patients may experience severe depression, strange thoughts, or angry behavior while taking ATRIPLA. Some patients have thoughts of suicide and a few have actually committed suicide. These problems may occur more often in patients who have had mental illness. Contact your healthcare provider right away if you think you are having these psychiatric symptoms, so your healthcare provider can decide if you should continue to take ATRIPLA.

Kidney problems. If you have had kidney problems in the past or take other medicines that can cause kidney problems, your healthcare provider should do regular blood tests to check your kidneys.

Changes in bone mineral density (thinning bones). It is not known whether long-term use of ATRIPLA will cause damage to your bones. If you have had bone problems in the past, your healthcare provider may need to do tests to check your bone mineral density or may prescribe medicines to help your bone mineral density.

Common side effects:

Patients may have dizziness, headache, trouble sleeping, drowsiness, trouble concentrating, and/or unusual dreams during treatment with ATRIPLA. These side effects may be reduced if you take ATRIPLA at bedtime on an empty stomach. They also tend to go away after you have taken the medicine for a few weeks. If you have these common side effects, such as dizziness, it does not mean that you will also have serious psychiatric problems, such as severe depression, strange thoughts, or angry behavior. Tell your healthcare provider right away if any of these side effects continue or if they bother you. It is possible that these symptoms may be more severe if ATRIPLA is used with alcohol or mood altering (street) drugs.

If you are dizzy, have trouble concentrating, or are drowsy, avoid activities that may be dangerous, such as driving or operating machinery.

Rash may be common. Rashes usually go away without any change in treatment. In a small number of patients, rash may be serious. If you develop a rash, call your healthcare provider right away.

Other common side effects include tiredness, upset stomach, vomiting, gas, and diarrhea.

Other possible side effects with ATRIPLA include:

Changes in body fat. Changes in body fat develop in some patients taking anti-HIV medicine. These changes may include an increased amount of fat in the upper back and neck ("buffalo hump"), in the breasts, and around the trunk. Loss of fat from the legs, arms, and face may also happen. The cause and long-term health effects of these fat changes are not known.

Skin discoloration (small spots or freckles) may also happen with ATRIPLA.

Tell your healthcare provider or pharmacist if you notice any side effects while taking ATRIPLA.

Contact your healthcare provider before stopping ATRIPLA because of side effects or for any other reason.

This is not a complete list of side effects possible with ATRIPLA. Ask your healthcare provider or pharmacist for a more complete list of side effects of ATRIPLA and all the medicines you will take.

How do I store ATRIPLA?

Keep ATRIPLA and all other medicines out of reach of children.
Store ATRIPLA at room temperature 77°F (25°C).
Keep ATRIPLA in its original container and keep the container tightly closed.
Do not keep medicine that is out of date or that you no longer need. If you throw any medicines away make sure that children will not find them.
General information about ATRIPLA:

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use ATRIPLA for a condition for which it was not prescribed. Do not give ATRIPLA to other people, even if they have the same symptoms you have. It may harm them.

This leaflet summarizes the most important information about ATRIPLA. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about ATRIPLA that is written for health professionals.

Do not use ATRIPLA if the seal over bottle opening is broken or missing.

What are the ingredients of ATRIPLA?

Active Ingredients: efavirenz, emtricitabine, and tenofovir disoproxil fumarate

Inactive Ingredients: croscarmellose sodium, hydroxypropyl cellulose, microcrystalline cellulose, magnesium stearate, sodium lauryl sulfate. The film coating contains black iron oxide, polyethylene glycol, polyvinyl alcohol, red iron oxide, talc, and titanium dioxide.

加拿大批准第一个一日1片的Atripla用于HIV感染的治疗
10月17日，百时美施贵宝公司(Bristol-Myers Squibb)和吉利德公司(Gilead Sciences)宣布，加拿大卫生当局已经批准了Atripla(依法韦仑600mg/恩曲他滨200mg/富马酸替诺福韦酯300mg，efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg)用于治疗成人HIV-1感染。至此，本品成为在加拿大批准的第一个一日1片的HIV疗法，单用或与其它抗逆转录病毒药物联用。
本品由两家公司的一个合资公司开发，于2006年7月获得美国FDA批准，在美国已经成为处方最大的药物用于HIV患者开始治疗。加拿大约有6万HIV患者，每年新确诊的约为2500人。
临床研究数据支持了本品用于未接受过治疗的HIV患者使用这一三联疗法。

一项随机开放活性对照的多中心非劣效性研究(研究934)，在未接受过治疗的HIV患者中，就一日1次Viread(富马酸替诺福韦酯), Emtriva(恩曲他滨)和Sustiva(依法韦仑)(本品的组成成分)，与一日2次Combivir(拉米夫定/齐多夫定，lamivudine/zidovudine)和一日1次Sustiva联用疗法行了比较。48周后， Viread/Emtriva/Sustiva组(244例)84%的患者、Combivir/Sustiva组(243例)73%的患者达到并保持病毒负荷低于400/ml。这一差异主要是由于因不良反应所致的较高比例的停药(Combivir/Sustiva组为9%，Viread/Emtriva/Sustiva组为4%)。其它原因还包括失访、患者停止用药、不顺应和违反研究草案(对照组为14%，Viread/Emtriva/Sustiva组为10%)。
此外，在48周里，Viread/Emtriva/Sustiva组80%，Combivir/Sustiva组70%的患者达到和保持病毒负荷低于50/ml。48周里，Viread/Emtriva/Sustiva组达到5%及以上的治疗相关的不良反应(2～4级)包括头晕、恶心、腹泻、疲劳、头痛和皮疹。
本品是由3种抗逆转录病毒药物组成的，因此其不良反应、与其它药物的配伍、禁忌等注意事项与其它抗逆转录病毒药物相似，详情参见本品说明书。