Liverpool HIV Interactions

No Interaction Expected

Raltegravir (RAL)

Darunavir + ritonavir (DRV/r)

Quality of Evidence: Very Low

Summary:

No dose adjustment is required when raltegravir 400 mg twice daily or 1200 mg once daily is coadministered. Population data from HIV+ subjects suggest that coadministration of raltegravir and darunavir/ritonavir is associated with lower darunavir trough concentrations. However, the effect of raltegravir on darunavir plasma concentrations did not appear to be clinically meaningful. Limited data from 6 healthy subjects indicate that coadministration of twice daily raltegravir with darunavir/ritonavir decreased raltegravir AUC (29%) and Cmax (33%), but increased Cmin by 38%. Darunavir pharmacokinetics were similar to historical data. Contrary to clinical experience in HIV+ patients, 8/18 subjects presented with a clinical adverse experience of rash, which progressed from mild/moderate to serious in one subject and only six subjects completed the PK study.

Description:

In some studies, co-administration of raltegravir 400 mg tablets twice daily with darunavir resulted in a modest but clinically insignificant decrease in darunavir plasma concentrations. Based on the magnitude of effect seen with raltegravir 400 mg tablets twice daily, it is expected that the effect of raltegravir 1,200 mg once daily on darunavir plasma concentrations is likely to be not clinically meaningful.

Isentress 600 mg Summary of Product Characteristics, Merck Sharp & Dohme Ltd, September 2021.

In drug interaction studies performed using raltegravir film-coated tablets 400 mg twice daily dose, raltegravir did not have a clinically meaningful effect on the pharmacokinetics of darunavir/ritonavir. Darunavir/ritonavir did not have a clinically meaningful effect on the pharmacokinetics of 400 mg twice daily raltegravir. No dose adjustment is required when raltegravir 400 mg twice daily or 1200 mg once daily is coadministered.

Isentress Prescribing Information, Merck & Co Inc, August 2021.

Some clinical studies suggest raltegravir may cause a modest decrease in darunavir plasma concentrations. At present the effect of raltegravir on darunavir plasma concentrations does not appear to be clinically relevant. Boosted darunavir and raltegravir can be used without dose adjustments.

Prezista Summary of Product Characteristics, Janssen-Cilag Ltd, September 2022.

No dosage adjustments are recommended when darunavir/ritonavir is co-administered with raltegravir.

Prezista Prescribing Information, Janssen Pharmaceuticals Inc, March 2023.

Coadministration of raltegravir (400 mg twice daily) and darunavir/ritonavir (600/100 mg twice daily) was studied in 18 subjects. Contrary to clinical experience in HIV+ patients, eight subjects presented with a clinical adverse experience of rash, which progressed from mild/moderate to serious in one subject. Only six subjects completed the study. Based on these limited pharmacokinetic data, raltegravir AUC decreased by 29%, Cmax decreased by 33% and Cmin increased by 38% (the latter parameter showing very marked variability). Darunavir pharmacokinetics were similar to historical data.

Pharmacokinetic evaluation of darunavir/ritonavir and raltegravir in healthy subjects. Anderson MS, Sekar V, Tomaka F, et al. 48th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, October 2008, abstract A-962.

Darunavir trough concentrations were determined in 117 samples from 55 HIV+ patients receiving darunavir containing regimens with either a NRTI or raltegravir. Mean (± sd) darunavir concentrations were higher in the NRTI subjects than in the raltegravir subjects (4.20 ± 2.35 vs 2.63 ± 84 mg/L). However, the proportion of subjects with undetectable viral loads (<50 copies/ml) was higher in the raltegravir group than in the NRTI group. After adjusting for time from last drug intake and concomitant drugs, a multivariate linear regression model confirmed raltegravir to be independently related to lower darunavir concentrations. The mechanism of this unexpected interaction remains to be determined, but it does not appear to be virologically significant.

Unexpected drug interaction between darunavir and raltegravir. Fabbiani M, Di Giambenedetto S, Ragazzoni E, et al. 12th European AIDS Conference (EACS), Cologne, November 2009, abstract PE4.3/4.

View all available interactions with Raltegravir (RAL) by clicking here.