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 studies, with few patients needing to discontinue this combination due to side effects. Recent reports of liver problems in people taking it who also have hepatitis. Be sure to know your hepatitis status if you are about to or are taking this drug! See Norvir for more details on potential side effects.
Potential drug interactions: This drug is metabolized by the liver (same as most of the other protease inhibitors). It must be dosed with Norvir. 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). No dose adjustments are likely to be necessary when given with Videx, Viread or Sustiva. See Norvir for other drug interactions possible. Due to the presence of Norvir, do not use Zocor (simvastatin) or Mevacor (lovastatin); lipid-lowering alternatives are Lipitor (atorvastatin), Lescol, and Pravachol (pravastatin), but they should be used with caution due to potential for liver toxicity.
Norvir increases blood levels of Viagra (sidenafil citrate), Cialis (tadalafil) and Levitra (vardenafil). Use with caution. Initially the Viagra dose should be 12.5 mg (1/2 of 25 mg tablet) and increased as needed and tolerated. It’s recommended that people on PIs do not exceed 25 mg of Viagra in a 48-hour period because of potential for serious reaction. Use Cialis at reduced doses of 10 mg every 72 hours and Levitra at reduced doses of no more than 2.5 mg every 72 hours, with increased monitoring for adverse events.
Tips: Take with food to minimize stomach problems. Also, do not take at the same time as antacids. This drug does its best when used with T-20 (enfuvirtide, Fuzeon). Unlike adding 1+1 = 2, with Aptivus and Fuzeon, 1+1 = 3! This drug is only for experienced patients or those with extensive resistance.
Tipranavir is expected to do less well for people with combinations of certain protease-related mutations. It’s all still being figured out; see www.aptivus.com for a list of mutations. 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. —Patrick G. Clay, Pharm.D.
Doctor
Tipranavir (TPV) is the most recently FDA approved protease inhibitor. It has been long-awaited as a salvage agent that can be used when HIV becomes resistant to other PIs. Problems with absorption and large pill burdens mean this drug must be taken with fairly large booster doses of ritonavir (200 mg twice a day). Clinical trials are ongoing to assess its long-term efficacy, durability, and safety. Its ability to overcome known PI resistance is also not as dramatic as hoped, but it still provides an option for select patients with limited remaining options. Its main side effects are diarrhea and lipid problems, like most other PIs. Tolerability of the large booster dose of ritonavir may be an issue for some patients.—Chad J. Zawitz, MD
Activist
The first protease inhibitor exclusively approved for patients who have developed PI resistance. Two 250 mg capsules of Aptivus plus two 100 mg capsules of Norvir should be taken with food twice a day. Like Norvir, it requires refrigeration. It can cause diarrhea, increased cholesterol and triglycerides, and liver problems. Close monitoring of liver enzymes is imperative with this drug. It works a lot better if started with another drug that shows up as active in your genotype test. Those taking Fuzeon with it had a better response than those who started Aptivus with drugs that they had resistance to. One big problem with Aptivus is that it does not play well with others, so the list of contraindicated drugs is long. Aptivus should never be taken with another protease inhibitor, since it decreases PI blood levels. Aptivus is a complicated drug, but I welcome its introduction in the market for a population that has few to no options left. Too bad it is the most expensive protease inhibitor, with an annual wholesale cost (with Norvir) of $28,840 as of October 2005. If you use it with Truvada and Fuzeon, the total annual wholesale cost jumps up to $66,000, an exorbitant amount for salvage therapy.—Nelson Vergel
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