Trade Names:Prezista- Tablets 75 mg (as base)- Tablets 150 mg (as base)- Tablets 300 mg (as base)- Tablets 400 mg (as base)- Tablets 600 mg (as base)
Inhibits HIV-1 protease, the enzyme required to form functional proteins in HIV-infected cells.
The T max of darunavir is approximately 2.5 to 4 h when administered with ritonavir 100 mg. Oral bioavailability is 37% and 82% when administered alone and with ritonavir, respectively. C max and AUC are approximately 30% higher when taken with food.
Protein binding is approximately 95%. Primarily bound to alpha-1 acid glycoprotein.
Extensively metabolized by CYP enzymes, primarily CYP3A. At least 3 active metabolites have been identified; all show activity that is at least 90% less than darunavir.
When coadministered with ritonavir, approximately 79.5% and 13.9% of the administered darunavir dose was eliminated in the feces and urine, respectively. Unchanged drug accounted for approximately 41.2% and 7.7% of the drug elimination in the feces and urine, respectively. Terminal elimination half-life is 15 h when combined with ritonavir. The Cl of darunavir administered alone and coadministered with ritonavir 100 mg was 32.8 and 5.9 L/h, respectively.
Pharmacokinetics not affected in patients with moderate renal function impairment (CrCl 30 to 60 mL/min). Pharmacokinetic data are not available for patients with severe renal function impairment or end-stage renal disease; however, a decrease in total body Cl of darunavir is not expected.Hepatic Function Impairment
No dose adjustment is needed for patients with mild or moderate hepatic function impairment. No pharmacokinetic data are available for use in patients with severe hepatic function impairment; however, administration is not recommended.Elderly
No significant differences in patients 18 to 75 years of age.Children
Pharmacokinetics of darunavir plus ritonavir in children 6 yr of age and older and weighing at least 20 kg (44 lb) are comparable with those of treatment-experienced adults.Gender
Mean exposure is higher in HIV-infected women compared with men; however, the difference is not clinically important.Race
Does not appear to affect the pharmacokinetics.
Treatment of HIV infection in adults and children in combination with ritonavir and other antiretroviral agents.
Coadministration with drugs that are highly dependent on CYP3A for Cl and drugs for which elevated plasma levels are associated with serious and/or life-threatening events (eg, cisapride, dihydroergotamine, ergonovine, ergotamine, lovastatin, methylergonovine, midazolam, pimozide, rifampin, simvastatin, St. John's wort, triazolam); hypersensitivity to any component of the product.
Darunavir 600 mg/ritonavir 100 mg twice daily.Children 6 to younger than 18 yr of age 20 kg (44 lb) to less than 30 kg (66 lb)
PO Coadminister darunavir 375 mg and ritonavir 50 mg twice daily with food.30 kg (66 lb) to less than 40 kg (88 lb)
PO Coadminister darunavir 450 mg and ritonavir 60 mg twice daily with food.40 kg (88 lb) or more
PO Coadminister darunavir 600 mg and ritonavir 100 mg twice daily with food.Children 3 to younger than 6 yr of age
Safety and efficacy have not been established in children 3 to younger than 6 yr of age.Children younger than 3 yr of age
Do not use in children younger than 3 yr of age.Treatment-Experienced PatientsAdults
PO 600 mg twice daily with ritonavir 100 mg twice daily with food.Treatment-Naive PatientsAdults
PO 800 mg with ritonavir 100 mg once daily with food.
Store at 59° to 86°F.
Plasma levels may be elevated by darunavir/ritonavir, increasing the risk of adverse reactions; careful monitoring and/or dosage adjustment are warranted.Carbamazepine
Carbamazepine levels may be elevated while darunavir levels may be decreased, resulting in antiretroviral treatment failure.Dexamethasone, lopinavir/ritonavir, omeprazole
Darunavir levels may be decreased. Do not administer lopinavir/ritonavir with darunavir/ritonavir.Didanosine
Because didanosine is administered on an empty stomach, give didanosine 1 h before or 2 h after darunavir/ritonavir.Drugs that are highly dependent on CYP3A for Cl and have a narrow therapeutic index (eg, cisapride, dihydroergotamine, ergonovine, ergotamine, lovastatin, methylergonovine, midazolam, pimozide, rifampin, simvastatin, St. John's wort, triazolam)
Coadministration with darunavir/ritonavir is contraindicated.Ethinyl estradiol, methadone, norethindrone, paroxetine, phenobarbital, phenytoin, sertraline
Plasma levels may be reduced by darunavir/ritonavir, decreasing the efficacy.Fluticasone inhalation
Fluticasone plasma levels may be increased. Consider alternative therapy.Food
When administered with food, the C max and AUC of darunavir, coadministered with ritonavir, are approximately 30% higher compared with the fasting state. Always administer darunavir, coadministered with ritonavir, with food.Indinavir
Indinavir and darunavir plasma levels may be elevated; however, appropriate doses in combination have not been established.Itraconazole, ketoconazole
Darunavir plasma levels may be elevated. Itraconazole and ketoconazole levels may be increased; do not increase the daily dose of itraconazole or ketoconazole above 200 mg.NRT/NNRT inhibitors
Coadministration may decrease darunavir plasma levels and clinical efficacy may be reduced. Efavirenz and nevirapine concentrations may be increased while etravine concentrations may be decreased.Rifabutin
Rifabutin and darunavir plasma levels may be elevated. Decrease the rifabutin dose by at least 75% of the usual dose.Saquinavir
Darunavir plasma levels may be decreased; therefore, coadministration is not recommended.Voriconazole
Do not coadminister with darunavir/ritonavir unless an assessment of the benefit/risk ratio justifies the use.Warfarin
Warfarin plasma levels may be decreased; INR monitoring is recommended.
None well documented.
Headache (5%); asthenia (3%); fatigue (1%).
Rash (6%); Stevens-Johnson syndrome.
Diarrhea (12%); nausea (7%); abdominal pain (adults, 5%; children, 10%); vomiting (adults, 4%; children, 13%); abdominal distension, dyspepsia (2%); anorexia (1%).
Hypersensitivity, including facial edema (postmarketing).
Increased total cholesterol (24%); increased LDL (13%); increased triglycerides (11%); increased glucose levels (8%); increased ALT and AST, increased pancreatic amylase (6%); increased pancreatic lipase (2%); increased hyperbilirubinemia, increased alkaline phosphatase (1%).
Myalgia (1%); rhabdomyolysis (postmarketing).
Assess liver function prior to starting therapy and monitor during treatment. Consider more frequent AST/ALT monitoring in patients with underlying chronic hepatitis or cirrhosis, or patients who have pretreatment elevations in transaminases.
Category C .
Undetermined. Per the CDC, HIV-infected women should not breast-feed.
Safety and efficacy not established in children younger than 6 yr of age. Do not administer in children younger than 3 yr of age.
Use with caution because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.
Pharmacokinetics not affected by moderate renal function impairment (CrCl of 30 to 60 mL/min). Pharmacokinetic data are not available for patients with severe renal function impairment or end-stage renal disease; however, a decrease in total body Cl is not expected.
No dose adjustment is needed for patients with mild or moderate hepatic function impairment. No pharmacokinetic data are available for use in patients with severe hepatic function impairment; however, administration is not recommended.
Darunavir contains a sulfonamide moiety; use with caution in patients with a sulfonamide allergy.
New-onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, and hyperglycemia have been reported.
Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and cushingoid appearance, have been observed in patients receiving antiretroviral therapy.
There have been reports of increased bleeding, including spontaneous skin hematomas and hemarthrosis, in patients with hemophilia types A and B treated with protease inhibitors.
Has been reported. During postmarketing experience, liver damage, including fatalities, has been reported. The risk may be increased in patients with preexisting liver dysfunction, including chronic active hepatitis B or C.
During initial phase of treatment, patients may develop an inflammatory response to indolent or residual opportunistic infections.
Skin rash accompanied by fever and/or elevated transaminases has been reported. Rarely, Stevens-Johnson syndrome has been reported. Discontinue treatment if severe rash occurs.
Oral doses of up to 3,200 mg have been administered without untoward effects.
Copyright © 2009 Wolters Kluwer Health.