Interaction Checker
Do Not Coadminister
Lopinavir/ritonavir (LPV/r)
_ZZSaquinavir (SQV)
Quality of Evidence: Low
Summary:
Coadministration is contraindicated in the European SPC for Invirase due to the potential for life threatening cardiac arrhythmia. However, the US Prescribing Information for Invirase advises caution; the charts reflect the more cautious option. No change in AUC or Cmin of saquinavir or lopinavir (data from saquinavir 1000 mg twice daily soft gel). No proof of added clinical/virological benefit. The recommended dose for saquinavir is 1000 mg twice daily when coadministered with Kaletra 400/100 mg twice daily. Kaletra once-daily has not been studied in combination with saquinavir. As with other double-boosted PIs, monitor and use TDM if available. Caution should be exercised as both drugs have a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.
Description:
No change in saquinavir concentrations was observed when saquinavir (1000 mg twice daily) was coadministered with Kaletra. No dose adjustment necessary.
Kaletra Summary of Product Characteristics, Abbott Laboratories Ltd, February 2012.
Evidence from several clinical trials indicates that saquinavir concentrations achieved with saquinavir 1000 mg plus lopinavir/ritonavir 400/100 mg twice daily are similar to those achieved following saquinavir/ritonavir 1000/100 mg twice daily. Saquinavir had no effect on lopinavir concentrations, but ritonavir concentrations were decreased. The recommended dose for this combination is saquinavir 1000 mg plus lopinavir/ritonavir 400/100 mg twice daily. Lopinavir/ritonavir in combination with saquinavir should be used with caution. Additive effects on QT and/or PR interval prolongation may occur with saquinavir.
Invirase Prescribing Information, Genentech USA Inc, February 2012.
Pharmacokinetic data were collected from HIV+ patients receiving boosted saquinavir (1000 mg twice daily) with ritonavir (100 mg twice daily, n=32) or lopinavir/ritonavir (400/100 mg twice daily, n=45). There was no significant difference in median saquinavir exposure between the groups (Cmin 543 vs 427 ng/ml, Cmax 2300 vs 2410 ng/ml, AUC 16977 vs 15130 ng/ml.h, lopinavir vs alone). Ritonavir exposure was lower in the lopinavir group (Cmin 78 vs 194 ng/ml, Cmax 428 vs 683 ng/ml, AUC 2972vs 6506 ng/ml.h, lopinavir vs alone). Lopinavir median values obtained for Cmin, Cmax and AUC were 3310 ng/ml, 7130 ng/ml and 64940 ng/ml.h respectively and were similar to historical data.
Saquinavir drug exposure is not impaired by the boosted protease inhibitor combination of lopinavir/ritonavir. Stephan C, Von Hentig N, Kourbeti I, et al. AIDS, 2004, 18: 503-508.
Coadministration of lopinavir/ritonavir (400/100 mg twice daily) and saquinavir soft gel (1000 mg twice daily) was studied in 25 HIV+ patients and compared to data obtained from 15 HIV+ patients receiving lopinavir/ritonavir (400/100 mg twice daily) without saquinavir. Pharmacokinetic median values for lopinavir were similar in patients with or without saquinavir (AUC 85.1 vs 85.2 µg/ml.h; Cmax 10.0 vs 9.5 µg/ml; Ctrough 7.3 vs 6.6 µg/ml; with SQV vs alone). Saquinavir AUC, Cmax and Ctrough median values were 22.87 µg/ml.h, 2.89 µg/ml, 1.56 µg/ml respectively.
Steady-state pharmacokinetics of a double-boosting regimen of saquinavir soft gel plus lopinavir plus minidose ritonavir in human immunodeficiency virus-infected adults. Ribera E, Lopez RM, Diaz M, et al. Antimicrob Agents Chemother, 2004, 48: 4256-4262.
Saquinavir and lopinavir concentrations were determined in 7 HIV+ patients receiving saquinavir (sgc)/lopinavir/ritonavir (1000/400/100 mg twice daily) and compared to historical data for saquinavir/ritonavir (1000/100 mg twice daily) and lopinavir/ritonavir (400/100 mg twice daily). Median saquinavir AUC (9.8 mg/L.h, IQR 8.3-24.5) and Cmax (1.6 mg/L, IQR 1.4-3.9) were lower than previously reported, though Cmin (0.4 mg/L, IQR 0.22-0.93) was similar. Lopinavir AUC (88.0 mg/L.h, IQR 68.6-118.9), Cmax (9.9 mg/L, IQR 7.9-12.5) and Cmin (4.8 mg/L IQR 3.9-5.6) were all similar to values reported in the product information.
Lopinavir/ritonavir plus saquinavir in salvage therapy; pharmacokinetics, tolerability and efficacy. La Porte CJL, Wasmuth JC, Schneider K, et al. AIDS, 2003, 17: 1700-1701.
Saquinavir hard gel capsules (400, 600 and 800 mg twice daily) were coadministered to 12 HIV+ subjects receiving lopinavir/ritonavir 400/100 mg twice daily. Saquinavir 600 and 800 mg produced similar Cmax (2.4±1.4 vs 2.4±0.9 µg/ml), AUC (15.6±7.4 vs 17.5±7.1 µg/ml.h) and Cmin (0.51±0.28 vs 0.60±0.33 µg/ml) when given with lopinavir; values were similar to historical data obtained for saquinavir soft gel (800 or 1200 mg twice daily) with lopinavir/ritonavir, and for saquinavir/ritonavir (1000/100 mg twice daily). AUC and Cmin obtained with saquinavir 400 mg were 55% lower than those observed with saquinavir 800 mg. Lopinavir pharmacokinetics were similar with all three saquinavir doses and were comparable to historical data; lopinavir Cmax, AUC and Cmin with saquinavir 600 mg were 10.6±3.9 µg/ml. 99±39 µg/ml.h and 5.6±2.7 µg/ml respectively.
Assessment of steady state pharmacokinetics of three dosing regimens of saquinavir administered as hard gelatin capsules in combination with lopinavir/ritonavir to HIV-infected adults. Bertz R, Ashbrenner E, Foit C, et al. 5th International Workshop on Clinical Pharmacology of HIV Therapy, Rome, April 2004, abstract 18.
Coadministration of saquinavir hard gel (600 mg twice daily) and lopinavir/ritonavir (400/100 mg twice daily) was assessed in 8 HIV+ subjects. There were no statistically significant differences in lopinavir or saquinavir trough concentrations when given in combination and compared to a reference population receiving saquinavir/ritonavir (600/100 mg twice daily) or lopinavir/ritonavir (400/100 mg twice daily). Compared to patients receiving saquinavir/ritonavir, ritonavir trough concentrations were significantly decreased in patients receiving lopinavir/ritonavir or saquinavir/lopinavir/ritonavir.
Lack of drug-drug interaction between lopinavir and saquinavir based on their trough plasma concentrations in highly HIV-experienced patients treated with Kaletra and Invirase. Poirier JM, Zouai O, Meynard JL, et al. 4th International Workshop on Clinical Pharmacology of HIV Therapy, Cannes, April 2003, abstract 8.12.
The effect of lopinavir/ritonavir (400/100 mg) on saquinavir (800 mg twice daily) was studied in healthy subjects. When compared to saquinavir 1200 mg three times daily, the study regimen produced substantially higher saquinavir concentration with ratios of central values for Cmax, AUC and Cmin being 6.3, 9.6 and 16.7 respectively. Lopinavir concentrations were similar to historical data.
Assessment of the steady state pharmacokinetic interaction of lopinavir/ritonavir with either indinavir or saquinavir in healthy subjects. Bertz RJ, Foit C, Ashbrenner E, et al. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, September 2002, abstract A-1822.
A study was performed (n=48) combining lopinavir/r (400/100 mg twice daily) with saquinavir (1000 mg twice daily). It did not show a disadvantageous pharmacokinetic interaction on lopinavir/r or saquinavir. The low ritonavir plasma levels were effective at boosting both lopinavir and saquinavir levels.
A new strategy: boosted double protease inhibitor regimen lopinavir/r plus saquinavir without reverse transcriptase inhibitors. Staszewski S, Dauer B, Stephan C, et al. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, September 2002, Abstract H-176.
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