After being withdrawn from the market for almost a year due to complications in the manufacturing process, ritonavir (Norvir®) is once again available. This eliminates the need to drink the unpleasant liquid form of the drug. The newly formulated soft gel capsules are already in pharmacies.
Abbott Laboratories, the manufacturer, recommends refrigeration of the new capsules but says it is not required if they are stored below 77°F (25°C) and used within 30 days. The new capsules are fairly large and contain 100mg of ritonavir. As with the old capsule formulation, ritonavir should be taken with food twice a day. Abbott believes that this new formulation behaves in the same manner as the old formulation. Therefore, the side effect profile and drug interactions should also be the same. For more information on drug interactions with ritonavir and other drugs, contact Project Inform's National HIV/AIDS Treatment Hotline and request the Drug Interactions Fact Sheet.
One of the great interests with ritonavir has been its ability to substantially raise and sustain the levels of other drugs in blood, especially other protease inhibitors. This often results in making it possible to take lower doses of both drugs and, in most cases, to reduce the number of times they must be taken each day. Because the drug levels are better sustained in the presence of ritonavir, it is unnecessary to take large initial doses of the drugs to get adequate long-term levels in the blood. Consequently, it is likely that some side effects may also be reduced by the use of such combinations.
One particular combination sparking a lot of interest is ritonavir and indinavir (Crixivan®). Results from several small studies suggest that this is a very potent combination, one that may 'overpower' some of the protease inhibitor resistant viruses because higher levels of indinavir can be achieved and sustained. Studies are now ongoing to determine the activity of this combination in people who have developed resistance to protease inhibitors.
Preliminary results in people starting therapy for the first time suggest very good anti-HIV activity, a reduction to twice daily dosing for indinavir, and the ability to take indinavir with food. There is even some suggestion that this combination may reduce a few kidney related side effects associated with indinavir. This may lessen the need to drink large amounts of water when taking the drug. These potentially important benefits, however, need to be confirmed in larger and longer studies.
Several dose combinations are currently being studied to determine the optimal dose. They include 100mg ritonavir/800mg indinavir, 200mg ritonavir/800mg indinavir and 400mg ritonavir/400mg indinavir, all of which are taken twice a day.
Back to the Project Inform Perspective September 1999 contents page.