What is Aptivus

• Aptivus is an anti-HIV medication. It is in a category of HIV medicines called protease inhibitors (PIs). Aptivus prevents cells infected by HIV from producing new virus. This reduces the amount of virus in your body.

• Aptivus must be used in combination with Norvir (ritonavir) and at least two other anti-HIV drugs.

• Aptivus, manufactured by Boehringer Ingelheim, was approved for the treatment of HIV by the U.S. Food and Drug Administration (FDA) in June 2005. Aptivus/ritonavir is only approved for HIV-infected people who have tried and failed other anti-HIV drug regimens (including those containing protease inhibitors) in the past. It is not approved for HIV-infected people starting anti-HIV treatment, or a protease inhibitor, for the first time (unless they were infected with a strain of HIV resistant to multiple protease inhibitors).

What is known about Aptivus

• Aptivus has a different structure than other protease inhibitors and is active against strains of the virus that are resistant to the other protease inhibitors that are currently available.

• The correct dose of Aptivus is 500mg twice a day (two 250mg capsules twice daily) . To help keep levels of Aptivus high in the blood, which is very important for the drug to be effective, it is necessary to combine Aptivus with low doses (200mg twice daily) of the protease inhibitor Norvir (ritonavir).

• Aptivus/ritonavir should be taken with food, preferably a complete nutritious meal, to ensure proper absorption of the drug into the bloodstream.

• Aptivus 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 Aptivus 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.

• Aptivus/ritonavir 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 and failed several anti-HIV drug regimens in the past. Drug resistance tests, such as genotypic assays and phenotypic assays, can be very useful in figuring out which anti-HIV drugs the virus is still likely to respond to. Drug-resistance tests are recommended when putting together a regimen that contains Aptivus/ritonavir. In clinical trials, Aptivus/ritonavir worked best when it was combined with Fuzeon (enfuvirtide; T-20), particularly in people who had not been on Fuzeon in the past.

Drug and Food Interactions

• Absorption of tipranavir increases when taken with a high-fat meal. Antacids reduce absorption of tipranavir, requiring timing adjustments of antacid use.

• Tipranavir/ritonavir at the recommended dosage is an inhibitor of CYP 3A and may thus increase plasma concentrations of agents that are primarily metabolized by this enzyme. Coadministration of tipranavir/ritonavir with drugs that are highly dependent on CYP 3A for clearance are contraindicated. These drugs include amiodarone, bepridil, flecainide, propafenone, quinidine, rifampin, dihydroergotamine, ergonovine, ergotamine, methylergonamine, cisapride, St. John's wort, lovastatin, simvastatin, pimozide, midazolam, and triazolam. 

• When used with other antiretrovirals in vitro, tipranavir was shown to be additive to antagonistic with other PIs, generally additive with non nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs), and synergistic with the fusion inhibitor enfuvirtide (Fuzeon).

• Patients should tell their doctor about any other medications they are taking, including prescription, nonprescription (over-the-counter), or herbal medications. It is particularly important for doctor s to know if a patient is allergic to sulfa drugs, because people with sulfa allergies may be at a higher risk of having an allergic reaction to tipranavir.

Potential Adverse Events and Side Effects

WARNING APTIVUS CO-ADMINISTERED WITH 200 MG RITONAVIR HAS BEEN ASSOCIATED WITH REPORTS OF BOTH FATAL AND NON-FATAL INTRACRANIAL HEMORRHAGE. (SEE WARNINGS) APTIVUS CO-ADMINISTERED WITH 200 MG RITONAVIR HAS BEEN ASSOCIATED WITH REPORTS OF CLINICAL HEPATITIS AND HEPATIC DECOMPENSATION INCLUDING SOME FATALITIES. EXTRA VIGILANCE IS WARRANTED IN PATIENTS WITH CHRONIC HEPATITIS B OR HEPATITIS CO-INFECTION, AS THESE PATIENTS HAVE AN INCREASED RISK OF HEPATOTOXICITY. (SEE WARNINGS)

• Like all anti-HIV drugs, tipranavir may cause some unwanted side effects. The most common side effects are diarrhea, nausea, fatigue, headache, and vomiting.

• Adverse effects leading to discontinuation of treatment were reported in 7.8 percent of individuals receiving tipranavir. Other adverse effects include rash, elevated lipid levels, fat redistribution, and immune reconstitution syndrome.  Women using estrogens may have an increased risk of non serious rash. Individuals with hemophilia may have increased risk of bleeding.

• Tipranavir in combination with ritonavir has been associated clinical hepatitis (liver inflammation) and hepatic decompensation, including some fatalities. Extra vigilance is warranted in individuals with advanced HIV disease or those with chronic hepatitis B or hepatitis C co-infection [with HIV] as these individuals have an increased risk of hepatotoxicity. Symptoms of hepatitis include fatigue, malaise, anorexia, nausea, jaundice, bilirubinemia, acholic stools, liver tenderness, or hepatomegaly.

Dosing Information

• Tipranavir is available in 250 mg soft gel capsules and is taken with ritonavir. The recommended dosing regimen is 500 mg tipranavir taken with 200 mg ritonavir twice daily.