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Rivaroxaban

Rivaroxaban

What is ritonavir?

Ritonavir is a prescription medicine approved by the U.S. Food and Drug Administration (FDA) for the treatment of HIV infection in adults and children older than 1 month. Ritonavir is always used in combination with other HIV medicines.

Although ritonavir is a protease inhibitor, it is used as a pharmacokinetic enhancer as recommended in the Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV and the Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. Pharmacokinetic enhancers are used in HIV treatment to increase the effectiveness of other HIV medicines. The guidelines include recommendations on using ritonavir to increase the effectiveness of other HIV medicines in an HIV regimen.

HIV medicines can’t cure HIV/AIDS, but taking a combination of HIV medicines (called an HIV regimen) every day helps people with HIV live longer, healthier lives. HIV medicines also reduce the risk of HIV transmission.

Taking full-dose ritonavir

The full adult dose of ritonavir, when taken as a single protease inhibitor, is 600mg twice a day. Patients taking this dose should begin at a lower dose, such as 300mg twice a day, before gradually building up to the full dose over two weeks.

Taking ritonavir within two hours of a meal reduces nausea and increases the amount of the drug that the body absorbs. It should be taken with food, if possible.

Liver disease may increase levels of ritonavir in the body substantially, although there is considerable individual variation. A dose reduction to 500mg twice a day may be considered for people with mild liver impairment. However, ritonavir should not be taken by people with severe liver problems.

The side-effects seen with the 600mg twice-daily dose of ritonavir have led some researchers and practitioners to consider dosing the drug at 400mg twice daily. Although preliminary results of a small study comparing the standard and low doses found similar proportions of people achieving undetectable viral loads, but with fewer side-effects in the lower dose, the trial design has been seriously criticised.1 The lower dose is not currently recommended.

How does ritonavir work?

Ritonavir can work in two different ways in managing HIV infection. It can be used as a protease inhibitor or it can be used as a drug ‘booster.’ Ritonavir may also be useful in the management of other types of infection.

1. Ritonavir as a protease inhibitor

When HIV infects a cell, it takes control of that cell. HIV then forces the cell to make many more copies of the virus. To make these copies, the cell uses proteins called enzymes. When the activity of these enzymes is reduced the production of HIV slows.

Ritonavir belongs to a group or class of drugs called protease inhibitors. This drug interferes with an enzyme called protease, which is used by HIV-infected cells to make new viruses. Since ritonavir inhibits, or reduces the activity of this enzyme, this drug causes HIV-infected cells to produce fewer viruses.

However, ritonavir is almost never prescribed as the only protease inhibitor in a treatment regimen today.

2. Ritonavir as a drug ‘booster’

The most common way that ritonavir is used today is as a booster for other protease inhibitors. Ritonavir causes this effect in two ways. First it helps to increase absorption of other protease inhibitors, mainly by inhibiting enzymes in the intestine that degrade this class of drug. Second, it also inhibits the activity of enzymes in the liver that break down protease inhibitors. As a result, ritonavir causes prolonged and high levels of other protease inhibitors in the blood, enabling ritonavir–protease inhibitor combinations to be taken once- or twice-daily.

3. Other uses for ritonavir

Ritonavir in combination with other antiviral agents—lopinavir and ribavirin—has been tested as a treatment for SARS (severe acute respiratory syndrome). Very preliminary results suggest that the combination may be useful in managing SARS, although more studies are needed before this can be confirmed.

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