Darunavir Approved for QD Dosing in Naive Patients

October 23, 2008

Dear HIV Providers,

The FDA has approved a new dosing regimen for darunavir in treatment-naive patients. The recommended dose for treatment-naive adult patients is darunavir 800 mg (two 400 mg tablets) taken with ritonavir 100 mg once daily, with food. The type of food does not affect exposure to darunavir.

The dosing regimen for treatment-experienced patients remains unchanged as darunavir 600 mg + ritonavir 100 mg twice daily, with food.

	The 400mg darunavir tablet is expected to be received by wholesalers sometime next week.
	The cost of the 400mg tablet will be the same as the 600mg tablet and is expected to be $570.32 for 30 days (increased from the $484.90 / 30 days for the 300mg tablets being phased out as of November 1st).

Once daily dosing was approved based on results of the ARTEMIS trial (TMC114-C211), a randomized, controlled, open-label Phase 3 study comparing darunavir/ritonavir 800/100 mg QD vs lopinavir/ritonavir 800/200 mg per day (given as BID or QD). Both arms used a fixed background regimen consisting of tenofovir+emtricitabine. The proportion of patients with HIV RNA < 50 copies/mL was 84% for darunavir/ritonavir and 78% for lopinavir/ritonavir (p=not statistically significant). The median change in CD4+ cell count from baseline was +137 cells/mm3 for darunavir/r and +141 cells/mm3 for lopinavir/r (p=not statistically significant).

Other darunavir labeling changes include the following:

	Pregnancy Category changed from B to C
	Postmarketing Experience includes rare events of hypersensitivity including facial edema and rhabdomyolysis associated with coadministration with HMG-CoA reductase inhibitors
	Dose of rifabutin should be decreased to a maximum of 150mg every other day when prescribed with darunavir/ritonavir; monitor for adverse events
	No dose adjustment required when darunavir is prescribed with carbamazepine; clinical monitoring of carbamazepine levels is recommended

Pam Belperio, PharmD, BCPS
National Public Health Clinical Pharmacist
Center for Quality Management in Public Health