Prezista (darunavir)

October 2007     View PDF     En español
Reprinted from www.aidsmeds.com, US

What is Prezista?
Prezista is an anti-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 at least two other anti-HIV drugs.

Prezista, manufactured by Tibotec (a division of Ortho Biotech Products), was approved for the treatment of HIV by the U.S. Food and Drug Administration (FDA) on June 23, 2006. Prezista, combined with Norvir, is only approved for HIV-infected adults who have tried other anti-HIV drug regimens in the past. This includes people who have HIV that is resistant to more than one protease inhibitor. It is not approved for HIV-infected people starting anti-HIV treatment for the first time.

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What is known about Prezista?
Prezista has a different structure than other protease inhibitors and is active against strains of the virus resistant to other protease inhibitors that are currently available.

The correct dose of Prezista is 600mg twice a day (two 300mg tablets twice daily) plus 100mg Norvir twice a day (one 100mg capsule twice a day). Norvir is necessary to help keep levels of Prezista high in the blood, which is very important for the drug to be effective.

At the present time, Prezista is only approved for HIV-positive people who have tried other anti-HIV medications in the past. However, once-daily Prezista is currently being studied in clinical trials for HIV-positive people starting treatment for the first time (two 400mg tablets combined with one 100mg Norvir capsule once a day). In one study reported to date, Prezista was comparable to Kaletra (lopinavir/ritonavir) after 48 weeks among patients starting therapy for the first time, with a possible efficacy advantage among those starting treatment with HIV viral loads above 100,000 copies.

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.

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 is not recommended 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 anti-HIV medications that a patient’s virus is still at least partially sensitive to.

Prezista works best when it is combined with anti-HIV drugs that the virus is still sensitive to. However, this can be challenging for HIV-positive people who have tried several anti-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 anti-HIV drugs the virus is still likely to respond to.

Prezista is not approved for use in HIV-positive children.

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What about drug interactions?
Because of the ways Prezista and Norvir are metabolized (broken down) in the body, they can interact with many other medications used to treat HIV, AIDS-related complications, and other diseases. Prezista/Norvir may cause blood levels of other medications 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 your medicines 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:

Antifungals: Vfend (voriconazole)
Anti-seizure medications: Tegretol (carbamazepine), Luminal (phenobarbital), Dilantin ( phenytoin)
Acid reflux/heartburn medications: Propulsid (cisapride)
Antibiotics: Rifadin (rifampin)
Antimigraine medications: Methergine, Methylergometrine (methylergonovine); Ergostat, Cafergot, Ercaf, Wigraine (ergotamine); Ergotrate, Methergine (ergonovine); or D.H.E. 45, Migranal (dihydroergotamine)
Antihistamines: Hismanal (astemizole) or Seldane (terfenadine)
Cholesterol-lowering drugs (statins): Zocor (simvastatin), Mevacor (lovastatin), and Pravachol (pravastatin)
Heart medications: Cordarone (amiodarone), Vascor (bepridil), Tambocor (flecainide), Rythmol (propafenone), or Quinaglute/Quinidex (quinidine)
Antipsychotics: Orap (pimozide)
Sedatives: Versed (midazolam) and Halcion (triazolam)
Enlarged prostate: Uroxatral (alfuzosin)
Herbal products: St. John’s wort

Anti-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.

Anti-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 regimen as Prezista/Norvir, it should be taken one hour before or two hours after Prezista/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 anti-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) levels in the bloodstream. The dose of Biaxin does not need to be decreased, although this may be necessary in people with altered kidney function. Prezista/Norvir can also increase Mycobutin (rifabutin) levels in the bloodstream (Mycobutin can also decrease 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 may interact with calcium channel blockers, medications used to treat heart disease. Studies of Prezista/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 should not be combined with Vascor (bepridil).

Prezista/Norvir can decrease levels of the blood thinner Coumadin (warfarin) in the bloodstream. Monitoring Coumadin levels in the bloodstream is 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,” can interact with Prezista/Norvir. There are three statins that should not be used with Prezista/Norvir: Zocor (simvastatin), Pravachol (pravastatin), and Mevacor (lovastatin). Levels of these two drugs can become significantly increased in the bloodstream if they are combined with Prezista/Norvir, which increases the risk of side effects. The statin believed to be the safest in combination with Prezista/Norvir is Lescol (fluvastatin). It is also possible to take Prezista/Norvir with Lipitor (atorvastatin), although Prezista/Norvir can increase the level of this drug in the bloodstream (if Lipitor is prescribed, it’s best to begin treatment with the lowest possible dose of the drug and then increase the dose if necessary.) Little is known about the newest statin, Crestor (rosuvastatin), in combination with Prezista/Norvir.

Neoral, Sandimmune, Gengraf (cyclosporine), Prograf (tacrolimus), Rapamune (sirolimus) are all examples of immune-suppressants, 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. 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 the bloodstream 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.

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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 inflammation of the nose and throat. Some patients on this combination 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 may occur in people who take Prezista or other protease inhibitors.

Anti-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 anti-HIV drug therapy are reviewed in our lesson on lipodystrophy.

Anti-HIV medications, such as Prezista, can increase the risk of bleeding in hemophiliacs.

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Who should not 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 anti-HIV treatment to help protect their babies from 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.

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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.

Another useful service for finding clinical trials is AIDSinfo.nih.gov, a site run by the U.S. National Institutes of Health. They have “health information specialists” you can talk to at their toll-free number at 1-800-HIV-0440 (1-800-448-0440).

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