Standard Dose: Two 250 mg capsules with two 100 mg capsules of Norvir, both twice daily. Must be taken with Norvir. Take with food. Take missed dose as soon as possible but do not double up on your next dose.
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, have occurred with Aptivus. If a rash occurs, Aptivus should be discontinued. Other side effects include headaches, dry mouth, and dizziness. 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! During clinical studies, bleeding in the brain occurred in people taking Aptivus/Norvir who had medical conditions or were receiving other medications that may have increased the risk of this. Use with caution by people who may be at risk of increased bleeding from trauma, surgery or other medical conditions, or who are receiving medications known to increase the risk of bleeding such as antiplatelet drugs or anticoagulants. 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; report symptoms of illness, such as shingles and TB, to health care provider.
As seen with other protease inhibitors, there can be increased levels of cholesterol and triglycerides (except possibly unboosted Reyataz) 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 sometimes the upper back), onset of new cases or worsening of diabetes (see your doctor promptly), and increased bleeding in hemophiliacs. See Norvir for more details on potential side effects.
Potential drug interactions:
Aptivus/Norvir interacts with many other drugs, so it is important to tell your healthcare professional of the medications you are taking. See the package insert. Do not take with Tambocor, Rythmol, Cordarone, quinidine, Versed, Halcion, rifampin, pimozide, ergot derivatives (such as Cafergot, Wigraine, Methergine, and D.H.E. 45), or the herb St. John's wort. Do not use simvastatin, Vytorin or lovastatin for the treatment of high lipids. It also increases the concentrations of Lipitor and Crestor, and the lowest possible dose should be used in combination with Aptivus. Other lipid lowering alternatives are Lescol and pravastatin, but they should be used with caution due to potential for liver toxicity. 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 zidovudine. The clinical significance of this interaction is not known. No significant changes were seen when combining Aptivus with Sustiva or Viramune. Should not be given with other protease inhibitors because it greatly lowers their blood levels. Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis per 72 hours, 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours.
Norvir may decrease levels of methadone, but withdrawal rarely occurs. Methadone doses may need to be increased. Trazodone concentrations may increase; a lower dose of trazodone is recommended. The blood pressure medications called calcium channel blockers should be 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 must be exercised when using Sporanax or fluconazole. Rifabutin requires a reduced dose. Norvir and Aptivus capsules contain alcohol (but should not be enough to trigger relapse), so be cautious with disulfiram or Flagyl (metronidazole).
Tips:
Received full FDA approval last year, based on 48 week data. Nevertheless, due to its resistance profile and its drug interactions, Aptivus is less popular than the other new PI, Prezista. Take with food to minimize stomach problems. Do not take at the same time as antacids. Aptivus did its best when used with Fuzeon. Aptivus is only for experienced patients. Aptivus is expected to do less well for people with combinations of certain protease-related mutations. See package insert or www.aptivus.com for a list of mutations. 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 much of the GI side effects as you might expect. The capsules should be refrigerated prior to opening. Once the bottle is opened, Aptivus can be stored at temperatures less than 77°F and must be used within 60 days. Please see package insert for more complete potential side effects and interactions.
Doctor
Aptivus was the first of what are sometimes called "second generation PIs," meaning that they work when resistance has developed to other PIs. The RESIST trials showed that Aptivus was more effective than other PIs in people with a lot of drug resistance. However, Aptivus never made a big splash, in part because of Prezista, which followed right behind, was better tolerated, less toxic, and more likely to be active against resistant virus. If you have a lot of PI mutations, you may be resistant to both drugs or to neither, but if you're only resistant to one, more often than not it's Aptivus. However, I've seen a few patients whose resistance tests show susceptibility only to Aptivus, which points out how important it is to do resistance testing before choosing drugs. Aptivus must be taken with two capsules of Norvir twice a day, and it's more likely to increase lipids or cause liver toxicity than other PIs. -- Joel Gallant, M.D.
Activist
Aptivus requires twice the normal dose of ritonavir, which adds substantially to the overall cost of using the drug, as well as making it cumbersome to use. Its value nearly disappeared when Prezista, and then Isentress, became available. Perhaps the only reason the drug is still on the market is that a small percentage (about 10%) of people who are resistant to all other protease inhibitors, and resistant to Prezista, still show some sensitivity to Aptivus. No one disputes the value of having a "last chance" drug available, even if it is needed only rarely. -- Martin Delaney
