| Potential side effects and toxicity: Mostly gastrointestinal-related: mild diarrhea, nausea, vomiting and fatigue. In clinical trials symptoms have been managed by having a light snack with the drug. Other side effects include headaches, dry mouth and dizziness. This dose of tipranavir was fairly well tolerated in Phase II studies, with few patients needing to discontinue this combination due to side effects, but full side effect profile isn’t usually determined until drugs move into Phase III. See Norvir for more details on potential side effects.
Potential drug interactions: Not yet finalized. Should not be given with other protease inhibitors because it greatly lowers their blood levels due to its mechanism of action (a reduction of 55% for Kaletra, 56% for Agenerase and 81% for Fortovase—expected to lower other PI levels as well). This drug is metabolized by the liver (same as most of the other protease inhibitors). It must be dosed with Norvir. No dose adjustments are likely to be necessary when given with Videx, Viread or Sustiva. See Norvir for the drug interactions possible.
Tips: Tipranavir is different from the other protease inhibitors currently approved. Its difference is how the drug is built. It’s the first in a new class (third generation) of protease inhibitors called non-peptidic protease inhibitors. Initial studies indicate that tipranavir may be active against strains of HIV that are already resistant to currently available peptidic protease inhibitors. As resistance becomes more and more an issue for treatment-experienced individuals, this type of drug offers hope.
The results furthest out in people are still preliminary, six months data from two studies called RESIST 1 and RESIST 2. In both studies, taking tipranavir at least doubled the odds of doing well. Adding Fuzeon to tipranavir further increased those odds. (This shows that—as usual for treatment-experienced people—you might really need another “new” drug to have the best chance of success with tipranavir.) It is important to note that the people in these studies had taken extensive HIV therapy before, including all of the first three classes of HIV drugs on the market and at least two protease inhibitors. It is difficult to significantly decrease viral load in a group like this. RESIST-1 enrolled 620 patients and RESIST-2 enrolled 863 patients. The large numbers enrolled were necessary to make sure the drug worked in these populations.
All people were taking an “optimized background.” This means that they were using a regimen that was expected to have the most success for them according to resistance test results. (These trials used genotype resistance testing.) The studies compared the people taking Norvir-boosted tipranavir to those taking a different protease inhibitor combination (Kaletra, Agenerase or Fortovase). In RESIST 1 the number of people going below 400 viral load was 34.7% (47% with Fuzeon) vs. 16.5% (21.9% with Fuzeon). Just looking at the people with one (or greater) log drop in their viral load—a significant decrease—the results were 41.5% for the entire tipranavir group vs. 22.3% for the group taking other PIs. In RESIST 2, the number of people on tipranavir going below 400 viral load was 33.6% (38.5% with Fuzeon) vs. 13.1% (13% with Fuzeon). Looking at one (or greater) log drop, results were 41% for the tipranavir group vs. 14.9% of the other group. T-cell increase was 31 vs. 1.
Tipranavir is expected to do less well for people with combinations of certain protease-related mutations. It’s all still being figured out. Although tipranavir has to be taken with 200 mg twice daily of Norvir, it actually lowers the blood levels of Norvir. So, you may not see as much of the gastrointestinal side effects as you might expect. —Reviewed by Patrick G. Clay, Pharm.D.
To learn about getting free tipranavir, call the Expanded Access Program at 1–888–524–8675 or visit www.tpv-eap.com. In private phone calls, Abbott reps promised higher booster dose free to people using it, but there’s no official word as of yet. |
