Darunavir

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[edit] BRAND NAMES

[edit] STRUCTURE

Darunavir.jpg

[edit] MECHANISM OF ACTION

Darunavir, is a protease inhibitor. It blocks an enzyme required for the proteolytic cleavage of the viral polyprotein precursors to the individual proteins found in infectious HIV. The cleavage of these viral polyproteins is essential for the maturation of infectious virus.
Darunavir binds to the active site of HIV protease and prevents cleavage of the polyproteins, resulting in the formation of immature non-infectious viral particles.

Darunavir, taken in combination with other antiviral medicines, reduces the amount of HIV in the blood and keeps it at a low level.
Darunavir does not cure HIV infection or AIDS, but it may delay the damage to the immune system and the development of infections and diseases associated with AIDS.

Darunavir is used with Ritonavir, another protease inhibitor that is used as a ‘booster’. Ritonavir inhibits CYP3A4, that normally metabolizes protease inhibitors, therfore, it slows down the rate at which Darunavir is broken down, increasing its levels in the blood.

[edit] INDICATIONS

  • Darunavir is indicated in combination with ritonavir and other antiretroviral agents, to treat patients aged three years and over who are infected with human immunodeficiency virus type 1 (HIV-1), a virus that causes acquired immune deficiency syndrome (AIDS)

[edit] DOSAGE

European medicine agency approved dosage:

  • Antiretroviral-naïve adult patients: The recommended dose regimen is 800 mg once daily with ritonavir 100 mg once daily taken with food.


  • Antiretroviral-experienced adult patients:
    • The recommended dose regimen is 600 mg twice daily taken with ritonavir 100 mg twice daily taken with food.
    • For antiretroviral-experienced adults with no darunavir resistance associated mutations (DRV-RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V) and who have plasma HIV-1 RNA < 100,000 copies/ml and CD4+ cell count ≥ 100 cells x 106/l, a dose regimen of 800 mg once daily with ritonavir 100 mg once daily taken with food may be used.
    • If HIV-1 genotype testing is not available, the recommended dose is 600 mg twice daily taken with ritonavir 100 mg twice daily taken with food.


  • Antiretroviral-experienced paediatric patients (3 to 17 years of age and weighing at least 15 kg):
    • ≥ 15 kg to < 30 kg: 380 mg of Darunavir + 50 mg of Ritonavir
    • ≥ 30 kg to < 40 kg: 460 mg of Darunavir + 60 mg of Ritonavir
    • ≥ 40 kg: 600 mg of Darunavir + 100 mg of Ritonavir

[edit] CONTRAINDICATIONS

[edit] WARNINGS AND PRECAUTIONS

  • Drug-induced hepatitis (e.g., acute hepatitis, cytolytic hepatitis) has been reported with Darunavir/Ritonavir. Monitor liver function before and during therapy, especially in patients with underlying chronic hepatitis, cirrhosis, or in patients who have pre-treatment elevations of transaminases. Post-marketing cases of liver injury, including some fatalities, have been reported.
  • Skin reactions ranging from mild to severe, including Stevens-Johnson Syndrome, toxic epidermal necrolysis and acute generalized exanthematous pustulosis, have been reported. Discontinue treatment if severe reaction develops.
  • Use with caution in patients with a known sulfonamide allergy.
  • Patients may develop new onset diabetes mellitus or hyperglycemia. Initiation or dose adjustments of insulin or oral hypoglycemic agents may be required.
  • Patients may develop redistribution/accumulation of body fat or immune reconstitution syndrome.
  • Patients with hemophilia may develop increased bleeding events.
  • Darunavir/Ritonavir should not be used in pediatric patients below 3 years of age in view of toxicity and mortality observed in juvenile rats dosed with darunavir up to days 23 to 26 of age

[edit] INTERACTIONS

Co-administration of Darunavir/Ritonavir with other drugs can alter the concentration of other drugs and other drugs may alter the concentrations of Darunavir. The potential drug-drug concentrations must be considered prior to and during therapy

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category C (US): Darunavir should be used during pregnancy only if the potential benefit justifies the potential risk
  • Nursing Mothers: The Centers for Disease Control and Prevention recommend that HIV-infected mothers in the United States not breastfeed their infants to avoid risking postnatal transmission of HIV. Although it is not known whether darunavir is secreted in human milk, darunavir is secreted into the milk of lactating rats. Because of both the potential for HIV transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breastfeed if they are receiving Darunavir.

[edit] SIDE EFFECTS

The most common clinical adverse drug reactions to Darunavir/Ritonavir were diarrhea, nausea, rash, headache, abdominal pain and vomiting.

[edit] RELATED LINKS

[edit] BIBLIOGRAPHY

[edit] REFERENCES