Darunavir

Darunavir is a prescription drug used for the treatment of HIV infection. HIV is the virus that causes AIDS. The drug belongs to a family of antiviral drugs known as protease inhibitors. Other members of this family include nelfinavir (Viracept) and amprenavir (Agenerase).

Darunavir was approved by the FDA in June 2006 and is marketed as Prezista by Ortho Biotech. Approval was granted on an accelerated ("fast track") basis to allow the use of darunavir in combination with other antiretroviral agents for the treatment of HIV infection in treatment-experienced adults, such as those infected with HIV strains resistant to more than 1 protease inhibitor.

Uses

Darunavir, in combination with with other antiretroviral agents, is specifically indicated for the treatment of HIV infection in antiretroviral treatment-experienced adult patients.

How Darunavir is Taken

Darunavir is available in 300 and 600 mg tablets. The recommended dose is 600 mg taken twice daily with ritonavir 100 mg twice daily AND FOOD.

How Darunavir Works

Darunavir inhibits an enzyme called HIV-1 protease. By inhibiting this enzyme, Darunavir inhibits the cleavage of HIV's Gag-Pol proteins in infected cells. This action prevents the formation of mature virus particles.

How the Body Affects Darunavir

Darunavir reaches peak circulating levels approximately 2.5-4 hours post-dosing.

Darunavir is extensively metabolized by liver enzymes, primarily by CYP3A.

About 80% of the original dose is excreted in the feces and about 14% in the urine.

Side Effects

The most common side effects (occurring in >10% of treated patients) are:

• diarrhea
• nausea
• headache
• nasopharyngitis (cold symptoms)

Risks and Precautions

Darunavir does not reduce the risk of passing HIV to others through sexual contact, sharing needles, or being exposed to blood or other bodily fluids.

Drug Interactions

The following drugs should not be used with darunavir:

• Anticonvulsants: carbamazepine, phenobarbital, phenytoin
• Antihistamines: astemizole, terfenadine
• Antimycobacterial: rifampin
• Ergot Derivatives: dihydroergotamine, ergonovine, ergotamine, methylergonovine
• Gastrointestinal Motility Agent: cisapride
• Herbal Products: St. John's wort (Hypericum perforatum)
• HMG-CoA Reductase Inhibitors: lovastatin, simvastatin

The following drug classes are known or likely to produce significant drug interactions with darunavir:

• Other HIV-Protease Inhibitors (PIs)
• Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
• Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
• Antiarrhythmics
• Anticoagulants
• TCA Antidepressants
• Anti-infectives
• Antifungals
• Antimycobacterials
• Calcium Channel Blockers
• Corticosteroids
• HMG-CoA Reductase Inhibitors
• H2-Receptor Antagonists and Proton Pump Inhibitors
• Narcotic Analgesics
• Oral Contraceptives/estrogens
• PDE-5 inhibitors
• Selective Serotonin Reuptake Inhibitors (SSRIs)

Effectiveness

One study called the ARTEMIS trial showed that 84% of treatment-naïve patients receiving darunavir/ritonavir with tenofovir/emtricitabine achieved an undetectable HIV viral load at 48 weeks compared with only 78% of patients receiving lopinavir/ritonavir plus tenofovir/emtricitabine.^[1]

References

1. ↑ Ortiz R, Dejesus E, Khanlou H, et al. Efficacy and safety of once-daily darunavir/ritonavir versus lopinavir/ritonavir in treatment-naive HIV-1-infected patients at week 48. AIDS. 2008 Jul 31;22(12):1389-97. Abstract

External Links

• FDA: Patient Information Sheet