Darunavir

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Darunavir
Systematic (IUPAC) name
[(1R,5S,6R)-2,8-dioxabicyclo[3.3.0]oct-6-yl] N-[(2S,3R)-4- [(4-aminophenyl)sulfonyl- (2-methylpropyl)amino]-3-hydroxy-1-phenyl- butan-2-yl] carbamate
Identifiers
CAS number	206361-99-1
ATC code	?
PubChem	213039
Chemical data
Formula	C27H37N3O7S
Mol. mass	547.665 g/mol
Pharmacokinetic data
Bioavailability	?
Protein binding	95%
Metabolism	hepatic (CYP)
Half life	15 hours
Excretion	?
Therapeutic considerations
Pregnancy cat.	B
Legal status
Routes	oral

Darunavir, sold as Prezista®, is a protease inhibitor used to treat HIV. It was approved by the Food and Drug Administration (FDA) on June 23, 2006.^[1]

PREZISTA™ (darunavir) is a protease inhibitor (PI), and when co-administered with 100mg ritonavir (PREZISTA/rtv) and with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus-1 (HIV) infection in antiretroviral treatment-experienced adult patients. In studies, the drug, co-administered with ritonavir in combination therapy, significantly reduced viral load and increased CD4 cell counts in this treatment-experienced patient population (Tibotec, 2006, Product Monograph, Prezista 2006)

Contents 1 Efficacy 2 Safety 3 Dosing and Administration 4 References 5 Notes 6 See also 7 External links

[edit] Efficacy

Efficacy of PREZISTA ™ is based on data from POWER 1 and POWER 2, two ongoing, randomized, controlled trials of the product boosted with ritonavir in treatment-experienced patients, together with supportive data from the POWER 3 analysis. The patients eligible for these studies had experience with at least one protease inhibitor, one non-nucleoside reverse transcriptase inhibitor and two nucleoside reverse transcriptase inhibitors, and had one or more primary protease inhibitor mutations.

A pooled analysis of results from POWER 1 and POWER 2 demonstrated that after 24 weeks:

- Significantly more treatment-experienced patients achieved a reduction in viral load at the 24-week primary endpoint with PREZISTA, compared with the investigator-selected PI (70% vs 21%, respectively).

- Almost four times as many treatment-experienced patients (45%) have achieved an undetectable viral load with the PREZISTA containing regimen, compared with the investigator-selected PI arm (12%).

- In treatment-experienced patients, the PREZISTA containing regimen increases CD4 cell counts five times more than the investigator-selected PI arm (92 cells/mm3 vs 17 cells/mm3, respectively) (Johnson & Johnson Press Release, 2006; Lazzarin, 2005)

The efficacy results of POWER 1 and POWER 2 are confirmed by data from a large, non-randomized, open-label analysis known as POWER 3. After 24 weeks:

- 65 percent of patients achieved a reduction in viral load of 1 log10 or more, versus baseline.

- 40 percent of patients reached undetectable virus levels (<50 HIV RNA copies/mL). (Molina, 2005)

[edit] Safety

PREZISTA ™ does not cure HIV infection or AIDS, and does not prevent passing HIV to others.

In studies, PREZISTA ™ was generally well tolerated. Mild to moderate rash was seen in 7% of patients. Some patients developed severe rash. In clinical studies, 0.3% of patients discontinued due to rash. The most common moderate to severe side effects associated with PREZISTA ™ include diarrhea (2.3%), headache (3.8%), abdominal pain (2.3%), constipation (2.3%), and vomiting (1.5%). Four percent of patients discontinued treatment due to adverse events. People who are allergic to PREZISTA ™ or any of its ingredients, or ritonavir (NORVIR) should not take PREZISTA ™ .

There were few relevant drug-drug interactions with other medications commonly used in HIV patient populations, such as other antiretroviral medications, proton pump inhibitors, and H2 receptor antagonists. Patients should talk to their healthcare provider about all the medicines they are taking or plan to take, including prescription and nonprescription medicines, vitamins, and herbal supplements.

Before taking PREZISTA ™ , patients should tell their healthcare provider if they have any medical conditions, including diabetes, liver problems, hemophilia, or allergy to sulfa medicines and should tell their doctor if they are pregnant or planning to become pregnant, or are nursing. PREZISTA ™ should be used with caution in patients with hepatic impairment.

High blood sugar, diabetes or worsening of diabetes, muscle pain, tenderness or weakness, and increased bleeding in people with hemophilia have been reported in patients taking protease inhibitor medicines like PREZISTA ™ . Changes in body fat have been seen in some patients taking anti-HIV medicines, including loss of fat from legs, arms and face, increased fat in the abdomen and other internal organs, breast enlargement and fatty lumps on the back of the neck. The cause and long-term health effects of these conditions are not known at this time.

Clinical laboratory safety observed in the PREZISTA ™ group was comparable to the control group. (Product Monograph, Prezista)

[edit] Dosing and Administration

The recommended oral dose of PREZISTA ™ tablets is 600 mg (two 300 mg tablets) twice daily (BID) taken with ritonavir 100mg BID and with food. The drug can be taken with any type of food.

Additional Studies Involving PREZISTA ™ - TMC114-C211: Investigating a dose of 800 mg of the drug boosted with 100 mg of ritonavir once daily in treatment-naïve patients.

- TMC114-C214: Investigating a dose of 600 mg of the drug boosted with 100 mg of ritonavir twice daily in moderately treatment-experienced patients.

- DUET trial: The drug is being studied with TMC125, an investigational non-nucleoside reverse transcriptase inhibitor, in one of the few HIV clinical trials to involve two investigational HIV treatments in treatment-experienced patients. (Tibotec 2006)

[edit] References

1. Lazzarin A, Queiroz-Telles F, Frank I, Rockstroh J, Walmsley S, De Paepe E, Vangeneugden T, Spinosa-Guzman S and Lefebvre E Lazzarin A, et al. XVI IAC 2006. Abstract TUAB0104

2. Johnson & Johnson FDA Approval Press Release, June 23 2006, http://www.jnj.com/news/jnj_news/20060623_191250.htm;jsessionid=NT1BC4RC4RHKYCQPCAOWU3YKB2IIWTT

3. Molina JM, Cohen C, Katlama C et al. TMC114/r in treatment-experienced HIV patients in power 3: 24-week efficacy and safety analysis. Poster abstract TUPE0060.

4. Janssen-Ortho, Prezista Mongraph information. Updated 2006. http://www.janssen-ortho.com/JOI/pdf_files/Prezista_E.pdf

5. Tibotec, http://www.tibotec.com/bgdisplay.jhtml?itemname=HIV_tmc114

[edit] Notes

[edit] See also

• Tibotec

[edit] External links

• Prezista FAQ at AIDSmeds.com
• Drug information in PDF

v • d • e Antivirals (primarily J05A, also S01AD and D06BB)
Anti-herpesvirus	Aciclovir, Cidofovir, Docosanol, Famciclovir, Fomivirsen, Foscarnet, Ganciclovir, Idoxuridine, Penciclovir, Trifluridine, Tromantadine, Valaciclovir, Valganciclovir, Vidarabine
Anti-influenza agents	Amantadine, Arbidol, Oseltamivir, Peramivir, Rimantadine, Zanamivir
Antiretrovirals: NRTIs	Abacavir, Didanosine, Emtricitabine, Lamivudine, Stavudine, Zalcitabine, Zidovudine
Antiretrovirals: NtRTIs	Tenofovir
Antiretrovirals: NNRTIs	Efavirenz, Delavirdine, Nevirapine, Loviride
Antiretrovirals: PIs	Amprenavir, Atazanavir, Darunavir, Fosamprenavir, Indinavir, Lopinavir, Nelfinavir, Ritonavir, Saquinavir, Tipranavir
Antiretrovirals: Fusion inhibitors	Enfuvirtide
Other antiviral agents	Adefovir, Fomivirsen, Imiquimod, Inosine, Interferon, Podophyllotoxin, Ribavirin, Viramidine