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Crixivan and Kaletra Oral Solution

Determining the interaction of Crixivan and Kaletra Oral Solution and the possibility of their joint administration.

Check result:

Crixivan <> Kaletra Oral Solution

Relevance: 25.10.2022 Reviewer: Shkutko P.M., M.D., in

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Consumer:

Using indinavir together with ritonavir may increase the effects of indinavir. Contact your doctor if your condition changes or you experience increased side effects such as kidney problems, including kidney stones or back pain with or without blood in your urine. If your doctor does prescribe these medications together, you may need a dose adjustment or special test to safely use both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Professional:

ADJUST DOSE: Coadministration with ritonavir may significantly increase the plasma concentrations of indinavir. The mechanism is ritonavir inhibition of indinavir metabolism via CYP450 3A4. In a study with healthy volunteers, ritonavir (200 mg to 400 mg every 12 hours) increased the peak plasma concentration (Cmax) and systemic exposure (AUC) of indinavir by up to 110% and 475%, respectively, compared to administration of indinavir alone. Increasing indinavir concentrations may increase the risk of urological complications, such as nephrolithiasis. However, increasing ritonavir dosage did not yield proportional increases in indinavir Cmax and AUC. Ritonavir reduced intersubject variability in indinavir plasma levels and has also been shown to eliminate food effects on the bioavailability of indinavir. Indinavir had negligible effect on the pharmacokinetics of ritonavir.

MANAGEMENT: Based on the magnitude of interaction, indinavir dosage should be reduced when coadministered with ritonavir. A regimen of (indinavir:ritonavir) 400:400 mg twice a day with food has been well tolerated in clinical trials and is recommended by some HIV experts. This dosing reportedly produces comparable indinavir AUC as standard indinavir (i.e., unboosted indinavir 800 mg three times a day) but increases plasma trough levels by 4-fold and reduces Cmax by over 50%, which may enhance dosing convenience as well as the safety-to-efficacy profile of indinavir. Lower doses of ritonavir (100 to 200 mg) plus 800 mg of indinavir twice daily with food are also recommended by HIV experts. These regimens appear to be equally effective as standard indinavir but may be somewhat less well tolerated, as indicated by an increased rate of treatment discontinuation and adverse effects such as nephrolithiasis, taste disturbances, and gastrointestinal intolerance in some studies. One trial also found that ritonavir-boosted indinavir (800:100 mg twice daily) had poorer tolerability and caused greater plasma lipid increases than ritonavir-boosted saquinavir (1000:100 mg twice daily), although virologic responses were similar. Limited data suggest that once-daily regimens with indinavir 1200 mg and ritonavir 200 to 400 mg may also be efficacious and warrant further investigation.

References

Rathbun RC, Rossi DR "Low-dose ritonavir for protease inhibitor pharmacokinetic enhancement." Ann Pharmacother 36 (2002): 702-6
vanHeeswijk RPG, Veldkamp AI, Hoetelmans RMW, Mulder JW, Schreij G, Hsu A, Lange JMA, Beijnen JH, Meenhorst PL "The steady-state plasma pharmacokinetics of indinavir alone and in combination with a low dose of ritonavir in twice daily dosing regimens in HIV-1-infected individuals." AIDS 13 (1999): f95-9
Aarnoutse RE, Wasmuth JC, Fatkenheuer G, et al. "Administration of indinavir and low-dose ritonavir (800/100 mg twice daily) with food reduces nephrotoxic peak plasma levels of indinavir." Antivir Ther 8 (2003): 309-14
Burger DM, Hugen PWH, vanderEnde ME, vanWijngaarden P, Aarnoutse RE, Reiss P, Lange JMA "Once-daily indinavir plus ritonavir: preliminary results of the PIPO study." Aids 14 (2000): 2621-3
Hsu A, Granneman GR, Cao GL, Carothers L, Japour A, ElShourbagy T, Dennis S, Berg J, Erdman K, Leonard JM, Sun EG "Pharmacokinetic interaction between ritonavir and indinavir in healthy volunteers." Antimicrob Agents Chemother 42 (1998): 2784-91
Developed by the panel of Clinical Practices for Treatment of HIV Infection convened by the Department of Health and Human Services (DHHS) "Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Available from: URL: http://AIDSinfo.nih.gov." ([2003 Nov 10]):
Cerner Multum, Inc. "Australian Product Information." O 0
Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
Kempf DJ, Marsh KC, Kumar G, et al "Pharmacokinetic enhancement of inhibitors of the human immunodeficiency virus protease by coadministration with ritonavir." Antimicrob Agents Chemother 41 (1997): 654-60
Burger D, Boyd M, Duncombe C, et al. "Pharmacokinetics and pharmacodynamics of indinavir with or without low-dose ritonavir in HIV-infected Thai patients." J Antimicrob Chemother 51 (2003): 1231-8
"Product Information. Norvir (ritonavir)." Abbott Pharmaceutical, Abbott Park, IL.

Crixivan

Generic Name: indinavir

Brand name: Crixivan

Synonyms: n.a.

What is Crixivan?

Kaletra Oral Solution

Generic Name: lopinavir / ritonavir

Brand name: Kaletra

Synonyms: Kaletra

What is Kaletra Oral Solution?

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In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.

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