Brand name: Aptivus
Generic name: tipranavir, or TPV
Class: Protease inhibitor (PI)
Manufacturer: Boehringer Ingelheim, www.aptivus.com, (800) 542-6257
AWP: $1,420.09/month; $419.84 for 95 mL bottle of solution
Standard Dose: Two 250 mg capsules with two 100 mg capsules of Norvir, both twice daily. Must be taken with Norvir. Oral solution available; both formulations available for children ages 2 years and older. Must take with food when using Norvir tablets; no food restrictions with Norvir capsules, but preferably taken with food to improve Norvir tolerability. Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose.
Potential side effects and toxicity: Aptivus contains a sulfa component, so use cautiously in patients with sulfa allergies. Mostly gastrointestinal-related: mild diarrhea, nausea, vomiting, abdominal pain, and fatigue. Other side effects may include headache, fever, dry mouth, and dizziness. Rash, including sensitivity to the sun, has occurred (most commonly among children). Some patients who developed rash also had one or more of the following: joint pain or stiffness, throat tightness, generalized itching, muscle aches, fever, redness, blisters, or peeling skin. Women taking birth control pills may be at higher risk for rash. If a severe rash occurs, Aptivus should be discontinued. Stop using Aptivus if rash appears with the symptoms listed above, and call your medical provider right away. Caution should be used in people with mild liver impairment, and it cannot be taken by people with moderate to severe liver disease. Be sure to know your liver function status if you are about to or are taking this drug! Use with caution by people who may be at risk of increased bleeding from trauma, surgery, or other medical conditions, or who are taking medications known to increase the risk of bleeding. See chart for potential drug class side effects.
Potential drug interactions: PIs interact with many other drugs. See package insert for the most complete list. Tell your provider or pharmacist of the medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Do not take with alfuzosin, Revatio, Tambocor, Rythmol, Cordarone (amiodarone), quinidine, oral Versed (midazolam), Halcion (triazolam), pimozide (Orap), cisapride, or the herb St. John's wort. Do not use Advicor, Altoprev, Livalo, Mevacor (lovastatin), Simcor, Vytorin, or Zocor (simvastatin) for the treatment of high cholesterol. Cholesterol-lowering alternatives are Crestor, Lescol, Lipitor, and Pravacol (pravastatin), but should be used with caution and started at the lowest dose possible; you should monitor closely for increased side effects from them. Increases levels of fluticasone (found in Advair, Flonase, and Flovent); use with caution and only if the benefits outweigh the risks, and monitor for signs of Cushing's syndrome (increased fat in the abdomen, fatty hump between the shoulders, rounded face, red/purple stretch marks on the skin, bone loss, possible high blood pressure, and sometimes diabetes). Aptivus can lower blood levels of Intelence, Ziagen, Videx EC, and Retrovir (zidovudine) and they should not be combined. Take Videx EC and Aptivus two hours apart. Aptivus should not be taken with other protease inhibitors because it greatly lowers their blood levels. Lowest level of Aptivus is increased 45% with Fuzeon, but dose adjustments are not recommended. Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Effectiveness of birth control pills may be decreased; consider the use of alternative or additional contraception. Methadone doses may need to be increased. Buprenorphine/naloxone (Suboxone) can lower Aptivus levels significantly; consider monitoring Aptivus levels, but dose adjustments are not recommended. Trazodone concentrations may increase; a lower dose of trazodone is recommended. Calcium channel blockers should be monitored for side effects. Monitoring may be required when taking Coumadin (warfarin). Tegretol, Dilantin (phenytoin), or phenobarbital may decrease Aptivus levels, so alternate seizure medications should be used and monitoring of Aptivus levels is recommended. Caution should be used with valproic acid, which may be less effective due to decreased concentrations. Use caution when taking itraconazole or fluconazole. Rifampin should not be used; reduced dose and frequency of Mycobutin is the recommended alternative for the treatment of TB. Use with caution with bosentan, salmeterol, immunosuppressants (including transplant drugs), and colchicine (lower colchicine dose). Norvir and Aptivus capsules contain alcohol (but should not be enough to trigger relapse), so be cautious with Antabuse (disulfiram) or Flagyl. Oral solution contains vitamin E; do not take additional vitamin E beyond that found in a multivitamin. Antacids can decrease levels of Aptivus. Aptivus should be taken two hours before or one hour after antacids. Aptivus decreases Prilosec (omeprazole) concentrations and Prilosec dose may need to be increased. Use of the hepatitis C drug Victrelis (boceprevir) along with a Norvir-boosted PI can potentially reduce the effectiveness of both drugs -- combined use is not recommended.
More information: Due to its drug resistance profile, drug interactions, higher pill burden, and the need for refrigeration if the indoor temperature is too hot, Aptivus is not as popular as other PIs. It is only FDA approved for treatment-experienced patients. Take with food to minimize stomach problems. It actually lowers the blood levels of Norvir, so you may not see as many of the GI side effects. Refrigerate capsules before opening, though Aptivus can be stored at room temperature (up to 77˚F), but must be used within 60 days. See package insert for details.
Aptivus is a "second-generation" PI, meaning that it's often active against PI-resistant virus. However, it is not widely used, mainly because of the availability of Prezista, which is safer, better tolerated, and is active against a wider range of PI-resistant virus. Aptivus causes more lipid elevation and liver toxicity than other PIs, possibly because it requires a higher boosting dose of Norvir (200 mg twice a day). However, there are some situations in which Aptivus is a better choice than Prezista. People who developed resistance to Lexiva or the discontinued Agenerase, for example, may have Prezista cross-resistance but will still respond to Aptivus. For that reason, it's always important to make the choice of a second-line PI based on resistance testing.
-- Joel Gallant, M.D., M.P.H.
I hate to be brief, but this drug has a limited value in the HIV arsenal in this age of newer, less toxic pills. I don't know anyone on this drug at this time, and I don't think it is still being prescribed, unless there's someone with a long history of taking ARVs and who is in a deep salvage situation. The increased Norvir boosting is enough to send you back to the days of high dose Norvir's GI upsets and metallic tongue tastes. Next!
-- Joey Wynn