Interactions with raltegravir: with twice-daily atazanavir and standard dose lamotrigine
The pharmacokinetics of atazanavir and raltegravir were investigated in HIV-negative subjects receiving twice daily unboosted atazanavir (300 mg twice-daily) and raltegravir (400 mg twice daily). 
Coadministration decreased atazanavir AUC (17%), Cmax (11%) and Cmin (29%). Atazanavir Cmin was 817 ng/mL (GM, range 250-1550 ng/ml), which is well the above the 10-fold protein binding adjusted EC90 for atazanavir against wild type HIV, and was moderately lower than historical values obtained with atazanavir/ritonavir. When given with atazanavir, the AUC, Cmax and Cmin of raltegravir increased by 54%, 39% and 48%, respectively. Mean QRS and PR interval increases were observed and require further investigation.
A second study investigated the pharmacokinetics of lamotrigine (100 mg single dose) when given alone or with raltegravir (400 mg twice daily) to 24 HIV-negative subjects. 
Coadministration had no significant effect on lamotrigine AUC (1% decrease) or Cmax (6% decrease). The ratio of lamotrigine glucuronide to lamotrigine was similar when taken alone (0.35) or with raltegravir (0.36). These results suggest that raltegravir is not expected to alter the metabolism of drug metabolised by UGT1A4 or UGT2B7 (e.g. valproic acid, diclofenac, carvediol).
Combining raltegravir with atazanavir is one of several potential nucleoside-sparing combinations but it is complicated by a two-way drug interaction (atazanavir levels are reduced whille raltegravir levels increase). This study suggests that twice-daily atazanavir may overcome these problems without using ritonavir and matching the BID dosing required by raltegravir. However, current pricing of this option is likely to limit practical use, even if future clinical studies show good efficacy and tolerability.
- Zhu L, et al. Pharmacokinetics and safety of twice daily atazanavir and raltegravir in healthy subjects. 16th CROI, Montreal, 2009. Abstract 696.