Aptivus

Common Name: tipranavir (TPV)

Brand Name: Aptivus

Class: HIV protease inhibitor (PI)

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 formulas available for children and adults. Can be taken with or without food, with no food restrictions, but preferably with food to improve Norvir tolerability. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.

AWP: $1,187.27 / month for Aptivus only

Manufacturer contact: Boehringer-Ingelheim, www.aptivus.com, 1 (800) 542-6257

Potential side effects and toxicity: Mostly gastrointestinal-related; mild diarrhea, nausea, vomiting, abdominal pain, and fatigue. In clinical trials, symptoms have been managed by having a light snack with the drug. Rash, including sensitivity to the sun, has occurred with Aptivus. Rash was more common in children. Also, 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 joint pain or stiffness, throat tightness, generalized itching, muscle aches, fever, redness, blisters, or peeling of the skin, and call your health care provider right away. Other side effects may include headache, fever, dry mouth, and dizziness. Caution should be used in people with mild liver impairment, since Aptivus concentrations may be increased. Should not be taken by people with moderate to severe hepatitis. Be sure to know your hepatitis 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 such as antiplatelet drugs, anticoagulants, or supplemental high doses of vitamin E. Aptivus has a sulfa component to it, so it should be used cautiously in patients with sulfa allergies. Immune Reconstitution Inflammatory Syndrome (IRIS) may occur as the immune system regains strength; signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is initiated. Report symptoms of illness, such as shingles and TB, to a health care provider.

As seen with other protease inhibitors (except unboosted Reyataz), there can be increased levels of cholesterol and triglycerides which may be associated with an increased risk of heart disease. Other possible side effects seen with protease inhibitors are lipodystrophy (body fat changes, including thinning of the face, arms and legs, with or without fat accumulation in the stomach, breasts, and upper back), onset of new cases or worsening of diabetes (see your doctor promptly), and increased bleeding in hemophiliacs.

Potential drug interactions: Aptivus/Norvir interacts with many other drugs, so it is important to tell your health care professional of the medications you are taking. See the package insert. Aptivus lowers Intelence levels, and the two should not be combined. Do not take with Tambocor, Rythmol, quinidine, Versed (midazolam), Halcion, pimozide, ergot alkaloids (such as Cafergot, Wigraine, Methergine, and D.H.E. 45), or the herb St. John's wort. Do not use Advicor, Altoprev, Mevacor (lovastatin), Simcor, Vytorin, or Zocor (simvastatin) for the treatment of high lipids. Lipid-lowering alternatives are Crestor, Lescol, Lipitor and Pravacol (pravastatin), but should be used with caution. Increased levels of the inhaled and nasal sprays with fluticasone (found in Advair, Flonase, Flovent), can occur with Aptivus/Norvir and therefore should be used with caution. Aptivus can lower blood levels of Ziagen, Videx, and Retrovir (zidovudine, AZT). Take Videx and Aptivus 2 hours apart. The clinical significance of this interaction is not known. No significant changes were seen when combining Aptivus with Sustiva or Viramune. Should not be taken with other protease inhibitors because it greatly lowers their blood levels. Trough concentration (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.

Methadone doses may need to be increased. Blood levels of Aptivus decrease 40% with Suboxone, but dose adjustments are not recommended, and the effectiveness of Suboxone is not affected. Trazodone concentrations may increase; a lower dose of trazodone is recommended. Calcium channel blockers should be used with caution and monitored for side effects. Monitoring may be required when taking Coumadin or immunosuppressants. Carbamazepine, Dilantin (phenytoin), or phenobarbital may decrease Aptivus levels, so alternate seizure medications should be used and monitoring of Aptivus drug levels is recommended. Caution should be used with valproic acid, which may be less effective due to decreased concentrations when used with Aptivus. Caution must be exercised when using itraconazole or fluconazole. Rifampin should not be used; rifabutin (Mycobutin) is the recommended alternative for the treatment of TB. It requires a reduced dose and frequency. Norvir and Aptivus capsules contain alcohol (but should not be enough to trigger relapse), so be cautious with Antabuse or Flagyl. Oral solution contains vitamin E; do not take with additional vitamin E beyond that found in a standard multivitamin. Antacids can decrease levels of Aptivus. Aptivus should be taken 2 hours before or one hour after antacids. Drug levels of bupropion are lowered; titrate dose based on clinical response.

Tips: Due to its resistance profile and its drug interactions, Aptivus is not as popular as other PIs. Aptivus is only for treatment-experienced patients. Take with food to minimize stomach problems. Do not take at the same time as antacids. Aptivus is expected to do less well for people with combinations of certain protease-related mutations. See package insert. Although Aptivus 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 many of the GI side effects as you might expect. The capsules should be refrigerated prior to opening. Aptivus can be stored at room temperature (up to 77°F), but must be used within 60 days Please see package insert for more complete potential side effects and interactions.

Doctor

Aptivus (tipranavir) was approved in 2005 for combination antiretroviral treatment only in those individuals with HIV infection who have evidence of viral replication, are highly treatment-experienced, and/or have HIV strains resistant to multiple protease inhibitors. While Aptivus gives us an active drug choice in those who have resistance to multiple PIs, there are several reasons why this drug is minimally used currently. The main issue is that there are several possible side effects when using it, and side effects are considered to be more likely with this PI versus other options, primarily darunavir, given its activity against similarly resistant virus. Studies of this PI as a first regimen also demonstrated limitations to this drug, as it was not as successful as boosted lopinavir (Kaletra) in either how well it would establish control of HIV, or by its safely profile, as there were more side effects. -- Cal Cohen, M.D.

Activist

A lifesaving drug for patients with protease resistance when first released, Aptivus has been supplanted by newer PIs with improved resistance profiles, but without the debilitating GI problems -- mostly diarrhea. A host of drug interactions -- including other protease inhibitors -- makes this a tricky drug to balance in a regimen, especially for salvage patients already on a host of other meds. -- Jeff Taylor