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美国食品和药物管理局日前批准一种新药，用于治疗艾滋病。
这种药属于艾滋病病毒蛋白酶抑制剂类药物，通过抑制蛋白酶的作用，来阻碍艾滋病病毒的自我复制。
这种药名为“Prezista”，适用于感染了艾滋病病毒、但服用现有抗逆转录病毒药物未见疗效的成年人，至于那些感染艾滋病病毒、但从未接受过任何药物治疗的成年人及儿童是否也适用，目前还不清楚。
药管局批准这种新药可以和低剂量的另一种艾滋病药物“Norvir”同时用药，以提高药效。用药后的主要副作用表现为头痛、恶心、腹泻等。另外临床试验显示，7％的患者用药后还会出现不同程度的皮疹。
这一艾滋病新药由美国强生公司在比利时的一家医药子公司研制开发。据公司方面介绍，患者需每天两次、每次两片服用，每天用药需花费25美元。
2.3 达如那韦片
蒂泊特克制药（Tibotec Pharmaceuticals）公司的抗HIV药达如那韦（darunavir）薄膜包衣片（商品名：Prezista，原先称为TMC114），剂量规格：达如那韦300 mg/片。
达如那韦是一种新的HIV-1蛋白酶抑制药，其作用机制是选择性抑制感染细胞内的编码Gag-Pol多蛋白HIV卵裂，继而抑制形成成熟的病毒粒。
达如那韦适用于与小剂量利托那韦或其它抗HIV药合用治疗用其它抗HIV药治疗无效的成人HIV感染。利托那韦也是一种蛋白酶抑制药，可减缓达如那韦体内代谢，联合用药能使达如那韦血药浓度增加。推荐剂量：进食后服用达如那韦600 mg一日2次，加服利托那韦100 mg一日2次。
美国FDA加速批准了TibotecPharmaceuticals公司的抗HIV药达如那韦薄膜包衣片（darunavir，Prezista，原先称为TMC114）上市，商品名为本品剂量规格：达如那韦300mg/片。
达如那韦是一种新的HIV-1蛋白酶抑制药，其作用机制是选择性抑制感染细胞内的编码Gag-Pol多蛋白HIV卵裂，继而抑制形成成熟的病毒粒。
达如那韦适用于与小剂量利托那韦或其它抗HIV药合用治疗用其它抗HIV药治疗无效的成人HIV感染。利托那韦也是一种蛋白酶抑制药，可减缓达如那韦体内代谢，联合用药使达如那韦血药浓度增加。推荐剂量：进食后服用达如那韦600mg一日2次，加服利托那韦100mg一日2次。达如那韦最常见的不良反应为腹泻、恶心和头痛。
What is Prezista?
Prezista is an HIV medication. It is in a category of HIV medicines called protease inhibitors. Prezista prevents cells infected by HIV from producing new virus. This reduces the amount of virus in your body.
Prezista must be used with low-dose Norvir (ritonavir) and in combination with other HIV drugs.
Prezista, manufactured by Tibotec Therapeutics, a division of Centocor Ortho Biotech Products, LP, was initially approved by the U.S.
FoodandDrugAdministration (FDA) on June 23, 2006, for treatment-experienced HIV-positive adults. It was approved for HIV-positive people beginning treatment for the first time on October 22, 2008.
Tibotec Therapeutics has established a patient assistance program (PAP) for people living with HIV who do not have private or public health insurance and are unable to afford Prezista. To learn more about the PAP for Prezista, call 866-836-0114 or refer to Tibotec's website for more information. For those with private health insurance, Tibotec has established a program to help cover up to 80 percent of the amount of each Prezista co-payment, up to $100 every month. To learn more about this co-pay program, call 866-961-7169.
What is known about Prezista?
There are two approved adult doses for Prezista:
Treatment-naive patients:
Two 400 mg Prezista tablets plus one 100 mg Norvir capsule once a day.
Treatment-experienced patients : One 600 mg Prezista tablet plus one 100 mg Norvir capsule twice a day.
Prezista, combined with Norvir, should be taken with food. The type and amount of food is not important.
In other words, Prezista/Norvir can be taken with a full meal or a light snack.
For HIV-positive adults beginning HIV drug therapy for the first time, Prezista is listed as a "preferred" protease inhibitor option by the United States Department of Health and Human Services in its treatment guidelines. To learn more about these recommendations and options, click here.
Prezista is recommended by the U.S. Department of Health and Human Services (DHHS) for HIV-positive people who have tried and failed other protease inhibitors in the past. It has not yet been evalauted by the DHHS for patients who are new to anti-HIV treatment or starting a protease inhibitor for the first time.
Clinical trials have demonstrated that Prezista is an effective option for patients who are not likely to respond to older protease inhibitors, especially when it is combined with other HIV medications that a patient's virus is still at least partially sensitive to.
Prezista works best when it is combined with HIV drugs that the virus is still sensitive to. However, this can be challenging for HIV-positive people who have tried several HIV drug regimens in the past. Drug resistance tests, such as genotypic assays and phenotypic assays, and treatment history, can be very useful in figuring out which HIV drugs the virus is still likely to respond to.
Prezista is not approved for use in HIV-positive children under 6 years of age. To learn more about treatment options for children, click here.
What about drug interactions?
Because of the ways Prezista and Norvir are metabolized (broken down) in the body, they can interact withmanyothermedications used to treat HIV, AIDS-related complications, and other diseases. Prezista/Norvir may cause blood levels of othermedications to be become too low (which can decrease their effectiveness) or high (which can increase the risk of side effects). Similarly, other medications may cause blood levels of
Prezista and/or Norvir to become too low or high.
Tell your doctors and pharmacists about all medicines you take.
This includes those you buy over-the-counter and herbal or natural remedies, such as St. John's wort. Bring all yourmedicines when you see a doctor, or make a list of their names, how much you take, and how often you take them. Your doctor can then tell you if you need to change the dosages of any of your medications.
The following medications should not be taken while you are being treated with Prezista/Norvir (this list includesmedications that are contraindicated—should not be taken together—according to both the PrezistaandNorvirpackaginginformation):
Antifungals: Vfend (voriconazole)
Anti-seizure medications: Tegretol (carbamazepine), Luminal (phenobarbital), Dilant(phenytoinAcidreflux/heartburnmedications: Propulsid (cisapride)Antibiotics: Rifadin (rifampin)Antimigraine medications: Methergine, Methylergometrin(methylergonovine); Ergostat, Cafergot, Ercaf, Wigraine (ergotamine);
Ergotrate, Methergine (ergonovine); or D.H.E. 45, Migranal (dihydroergotamine)Antihistamines: Hismanal (astemizole) orSeldane (terfenadine)Cholesterol-lowering drugs (statins): Zocor (simvastatin) and Mevacor (lovastatin)Heart medications: Cordarone (amiodarone), Vascor (bepridil), Tambocor (flecainide), Rythmol (propafenone), or Quinaglute/Quinide(quinidineAntipsychotics: Orap (pimozide)Sedatives: Versed (midazolam) and Halcion (triazolamEnlargedprostate: Uroxatral (alfuzosin)Herbal products: St. John's wort
HIV protease inhibitors can interact with Prezista/Norvir. Kaletra (lopinavir/ritonavir) and Invirase (saquinavir) can significantly decrease blood levels of Prezista, hence it is not recommended that Prezista be combined with Kaletra or Invirase. Taking Prezista and Crixivan together can cause the levels of both drugs to increase in the bloodstream.
Prezista/Norvir does not appear to increase or decrease
blood levels of Reyataz (atazanavir), nor does Reyataz appear to increase or decrease blood levels of Prezista/Norvir. In turn, it may be possible to combine these two PIs.
HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs) can also interact with Prezista/Norvir. Prezista/Norvir can increase levels of Sustiva (efavirenz) [and to a lesser extent Viramune (nevirapine)] in the blood. Combining Prezista/Norvir with Sustiva should be done with caution.
Prezista/Norvir can increase levels of Viread (tenofovir), a nucleotide reverse transcriptase inhibitor, in the blood. However, these two drugs can be combined without any dose adjustments (although it may be necessary to watch carefully for kidney damage, a potential side effect of Viread). Videx/Videx EC (didanosine) must be taken on an empty stomach. In turn, if Videx/Videx EC is used in the same regimenasPrezista/Norvir,itshouldbetakenonehourbeforeortwohoursafterPrezista/Norvir (which should be taken with food).
Prezista/Norvir can interact with some medications used to treat thrush (candidiasis) and other fungal infections. Prezista/Norvir increases Nizoral (ketoconazole) and may increase Sporanox (itraconazole) levels in the bloodstream. For people taking Prezista/Norvir who also need to take Sporanox or Nizoral, the daily dose of Sporanox or Nizoral should not exceed 200mg. It is also possible that Prezista/Norvir decreases Vfend (voriconazole) levels in the blood (Vfend should not be taken if you are on an HIV drug regimen that contains Norvir).
Prezista/Norvir can interact with some medications used to treat TB, MAC, and other bacterial infections. Prezista/Norvir raises Biaxin (clarithromycin)levelsinthebloodstream. The dose of Biaxin does not need to be decreased, although this is recommended in people with altered kidney function. Prezista/Norvir can also increase Mycobutin (rifabutin) levels in the bloodstream (Mycobutin can also increase Prezista levels in the bloodstream). If Mycobutin is taken at the same time as Prezista/Norvir, it is recommended that the Mycobutin dose be reduced to 150mg every other day.
Prezista/Norvir should not be used with Rifadin (rifampin), a common antibiotic used to treat TB.
Prezista/Norvir may interact with calcium channel blockers, medications used to treat heart disease. StudiesofPrezista/Norvir combined with calcium channel blockers have not yet been conducted. Healthcare providers should be cautious when prescribing Prezista/Norvir with either Cardizem (diltiazem), Plendil/Lexxel (felodipine), Cardene (nicardipine), Sular (nisoldipine), or Calan/Verelan (verapamil).
Prezista/Norvir can increase the blood levels of the heart medications Vascor (bepridil), lidocaine, Quinidex (quinidine) and Cardarone (amiodarone).
These medications should be used with caution if taken with Prezista/Norvir and monitoring blood levels of these drugs is recommended, if available. Prezista/Norvir can also significantly increase blood levels of Lanoxin (digoxin). The lowest dose of Lanoxin should initially be used and monitoring Lanoxin blood levels is recommended.
Prezista/Norvir can decrease levels of the blood thinner Coumadin (warfarin) in the bloodstream. Conducting blood coagulation (clotting) testing may be necessary.
Prezista/Norvir may increase blood levels of Norpramin (desipramine), a drug used to treat depression. The dose of Norpramin may need to be decreased. Prezista/Norvir may also decrease levels of Zoloft (sertraline) and Paxil (paroxetine). It may be necessary to increase Zoloft of Paxil dosing if also using Prezista/Norvir.
Cholesterol-lowering drugs, also known as"statins,"caninteractwithPrezista/Norvir. There are two statins that should not be used withPrezista/Norvir: Zocor (simvastatin) andMevac(lovastatin).Levelsofthesetwodrugscanbecomesignificantly increased in the bloodstream if they are combinedwithPrezista/Norvir,whichincreases the risk of side effects. The statin believed to be the safestincombination with Prezista/Norvir is Lescol (fluvastatin).
It isalsopossibletotakePrezista/Norvir with Lipitor (atorvastatin), or Crestor (rosuvastatin) although Prezista/Norvir can increase the level of these drugs in the bloodstream (if Lipitor or Crestor are prescribed, it's best to begin treatment with the lowest possible dose of the drug and then increase the dose if necessary or else use a different drug.) While the FDA-approved packaging information for Prezista suggests that Pravachol (pravastatin) can also be used, Tibotec does not recommend combining Pravachol with Prezista/Norvir.
Neoral, Sandimmune, Gengraf (cyclosporine), Prograf (tacrolimus), Rapamune (sirolimus) are all examples ofimmunesuppressants, often prescribed for patients who have undergone an organ/tissue transplant.
Prezista/Norvir can increase levels of these drugs in the blood.
In turn, it is necessary to carefully monitor blood levels of these drugs if they are combined with Prezista/Norvir.
Prezista/Norvir can increase blood levels of Advair, Flovent, or Flonase (fluticasone), the inhalable medications that are used to treat allergies and asthma. In turn, these drugs may decrease blood levels of Prezista/Norvir. Alternatives to these drugs should be considered, especially for long-term use.
Another painkiller, methadone, commonly used to treat drug heroin addiction, can interact with Prezista/Norvir. Methadone levels in the bloodstream can decrease when combined with Prezista/Norvir. Because of this, it might be necessary to increase the dose of methadone.
Desyrel (trazodone) is used to treat depression. Prezista/Norvir can increase blood levels of this drug, leading to an increase risk of Desyrel side effects. Using a lower dose of Desyrel may be necessary.
Prezista/Norvir decreases the amount of oral contraceptives (taken by women to help avoid pregnancy) in the bloodstream. This means that there may be a higher risk of becoming pregnant if Prezista/Norvir and oral contraceptives are taken at the same time.
To reduce the risk of pregnancy, barrier protection (e.g., condoms) should be used.
Viagra (sildenafil), Levitra (vardenafil) and Cialis (tadalafil) levels in thebloodstream may increase when combined with Prezista/Norvir.
In turn, it is best to use a lower dose of these drugs in order to reduce the risk of side effects.
What is known about side effects?
The most common side effects reported by patients taking Prezista and Norvir in clinical trials included diarrhea, nausea, headache, and abdominal pain. Some patients receiving Prezista/Norvir experienced skin rashes; most were mild-to-moderate. If a severe rash occurs while taking Prezista/Norvir, patients should contact their healthcare providers immediately.
Prezista, a sulfa-containing drug, should be used with caution in patients with a known sulfa allergy.
Some people may experience large increases in their lipid levels (triglycerides and cholesterol) while being treated with protease inhibitors.
However, it is not yet known what effect, if any, Prezista will have on lipids. Click here for more information on HIV treatment and lipid increases.
Diabetes and high blood sugar mayoccurinpeoplewhotakePrezistaorotherprotease inhibitors.
HIV drug regimens containing protease inhibitors, including Prezista/Norvir, may cause abnormal body-shape changes (lipodystrophy; including increased fat around the abdomen, breasts, and back of the neck, as well as decreased fat in the face, arms, and legs). These side effects of HIV drug therapy are reviewed in our lesson on lipodystrophy.
HIV medications, such as Prezista, can increase the risk of bleeding inhemophiliacs.
Drug-induced hepatitis (liver injury) has been reported in people taking Prezista. This usually occured in people who had extremely low CD4 cells, were taking multiple other medications and who were also infected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV). People taking Prezista who are coinfected with HBV or HCV, or who have a history of liver damage, should have their liver function closely monitored by their healthcare providers. Stopping Prezista treatment may be necessary, in consultation with a healthcare provider, in the case of abnormal liver enzymes or symptoms of liver damage (i.e. fatigue, nausea, yellow eyes and skin, dark urine and liver tenderness).
Who should not take Prezista?
People with mild to moderate liver damage (hepatic impairment) may use Prezista without changing the dose. Prezista has not been studied in people with severe hepatic impairment and it is not recommended in people with severe hepatic impairment.
Can pregnant women take Prezista?
Prezista is classified by the FDA as a pregnancy category B drug.
Pregnancy category B means that animal studies have failed to demonstrate a risk to the fetus, but there are no adequate and well-controlled studies in pregnant women. HIV-positive women who become pregnant should discuss the benefits and possible side effects of HIV treatment to help protect their babies from HIV (see our lesson called FamilyPlanning,Pregnancy & HIV).
It is not known whether Prezista passes into breast milk and what effect it may have on a nursing baby.
To prevent transmission of the virus to uninfected babies, it is recommended that HIV-positive mothers not breast-feed.
Where can I learn more about clinical trials of Prezista?
If you would like to find out if you are eligible for any clinical trials that include Prezista, there is an interactive web site run by ACRIA, the AIDS Community Research Initiative of America.
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