Pharmacokinetic (PK) interactions among certain nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) can significantly affect serum levels of these antiretrovirals (ARVs). It has long been known that lopinavir/ritonavir (Kaletra) levels are lowered by certain ARVs, including the NNRTIs efavirenz and nevirapine as well as the PIs fosamprenavir and nelfinavir. Recently, however, PK studies of the tablet formulation of lopinavir/ritonavir have been conducted, and the findings have yielded new dosage recommendations for combination therapy using these agents.
For all adults (both ARV naive and ARV experienced) who are taking lopinavir/ritonavir tablets in combination with nevirapine or efavirenz, the new recommended dosage for lopinavir/ritonavir is 500/125 mg BID. This dosage can be achieved either by taking two 200/50 mg tablets BID plus one 100/25 mg tablet BID, or by taking 2.5 of the 200/50 mg tablets BID. For adults who take lopinavir/ritonavir oral solution, the recommended dosage continues to be 533/133 mg (6.5 mL) BID when used in combination with nevirapine or efavirenz. (These dosing recommendations also apply when lopinavir/ritonavir is used in combination with fosamprenavir or nelfinavir, but note that dual-PI therapy in general is not recommended.)
For children, the recommended dosage of lopinavir/ritonavir is 300/75 mg/m2 when used with nevirapine, efavirenz, fosamprenavir, or nelfinavir; see package insert for further dosage information.
As before, lopinavir/ritonavir should not be administered once daily in regimens that include nevirapine or efavirenz.