Darunavir
Mechanism :
Darunavir is a HIV protease inhibitor which prevents HIV replication by binding to the enzyme's active site, thereby preventing the dimerization and the catalytic activity of the HIV-1 protease. Darunavir selectively inhibits the cleavage of HIV encoded Gag-Pol polyproteins in virus-infected cells, which prevents the formation of mature infectious virus particles. Structural analyses suggest that the close contact that darunavir has with the main chains of the protease active site amino acids (Asp-29 and Asp-30) is an important contributing factor to its potency and wide spectrum of activity against multi-protease inhibitor resistant HIV-1 variants. Darunavir can also adapt to the changing shape of a protease enzyme because of its molecular flexibility. Darunavir is known to bind to two distinct sites on the enzyme: the active site cavity and the surface of one of the flexible flaps in the protease dimer.
Indication :
Contraindications :
Co-administration of PREZISTA/ritonavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (narrow therapeutic index).
Dosing :
Under 3 years or under 10 kg: Safety and efficacy not established.
10 kg to <15 kg:
20 mg/kg orally twice a day (plus
ritonavir 3 mg/kg twice a day).
15 kg to <30 kg:
375 mg orally (+
ritonavir 50 mg) twice a day.
30 kg to <40 kg:
450 mg orally (+
ritonavir 60 mg) twice a day.
≥40 kg:
600 mg orally (+
ritonavir 100 mg) twice a day.
Adverse Effect :
Increased total cholesterol, increased triglycerides, diarrhea, pain, nausea, vomiting, acute pancreatitis, dyspepsia, flatulence, hepatotoxicity, hypersensitivity reactions, Diabetes mellitus, myalgia, osteonecrosis, abnormal dreams, angioedema, pruritus, Stevens-Johnson Syndrome, urticaria.
Interaction :
Certain azole fungal medications (ketoconazole, itraconazole, voriconazole), boceprevir, efavirenz, pimozide, telaprevir: May decrease the effectiveness of hormonal birth control such as pills, patch, or ring. This could cause pregnancy.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Dose as in normal renal function |
| 10-20 | Dose as in normal renal function |
| <10 | Dose as in normal renal function |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Unlikely to be dialysed. Dose as in normal renal function |
| HD | Unlikely to be dialysed. Dose as in normal renal function |
| HDF/High flux | Unlikely to be dialysed. Dose as in normal renal function |
| CAV/VVHD | Unlikely to be dialysed. Dose as in normal renal function |
Hepatic Dose :
Avoid in severe hepatic impairment.