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Invirase and Ritonavir Tablets

Determining the interaction of Invirase and Ritonavir Tablets and the possibility of their joint administration.

Check result:

Invirase <> Ritonavir Tablets

Relevance: 12.05.2022 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 saquinavir together with ritonavir may increase the effects of saquinavir. Contact your doctor if you experience increased urination or extreme thirst, easy bruising or bleeding, fever, chills, cough, nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes). 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 (RTV) may significantly increase the bioavailability of saquinavir (SQV) from both the hard gelatin capsule (HGC) and soft gelatin capsule (SGC) formulations. The mechanism is RTV inhibition of CYP450 3A4 metabolism of SQV in the intestine and liver. In seven HIV+ patients stabilized on their antiretroviral regimen, addition of RTV (300 mg orally twice a day for 4 days) increased the median peak plasma concentration (Cmax) and 8-hour area under the concentration-time curve (AUC) of SQV (HGC 600 mg three times a day) by 30-fold and 58-fold, respectively, compared to baseline. In 57 healthy volunteers, escalating single doses of SQV (HGC) and RTV yielded comparable results, but increasing RTV dosages tended to produce less than proportional increases in SQV Cmax and AUC. The magnitude of the interaction is considerably less with the SGC formulation but still substantial. In individual groups of 8 healthy volunteers, various regimens of SQV (SGC 800 mg twice a day) and RTV (200 to 400 mg twice a day) for 14 days led to an approximate overall 9.6-fold increase in SQV Cmax and 20-fold increase in SQV AUC. RTV tended to reduce intersubject variability in SQV plasma levels. SQV had negligible effect on the pharmacokinetics of RTV.

MANAGEMENT: Based on the magnitude of interaction, SQV dosage should be reduced when coadministered with RTV. A regimen of (SQV HGC or SGC:RTV) 400:400 mg or 1000:100 mg twice daily is usually recommended based on their convenience and favorable safety-to-efficacy profile. Limited data suggest that dosages of 1200 to 2000:100 mg once daily may also be feasible and warrant further investigation. Patients receiving the combination should be closely monitored for toxicity including elevations in liver function tests and neutropenia.

References

Angel JB, Kumar A, Parato K, Filion LG, DiazMitoma F, Daftarian P, Pham B, Sun E, Leonard JM, Cameron DW "Improvement in cell-mediated immune function during potent anti-human immunodeficiency virus therapy with ritonavir plus saquinavir." J Infect Dis 177 (1998): 898-904
Cooper CL, Van Heeswijk RP, Gallicano K, Cameron DW "A review of low-dose ritonavir in protease inhibitor combination therapy." Clin Infect Dis 36 (2003): 1585-92
Cameron DW, Japour AJ, Xu Y, Hsu A, Mellors J, Farthing C, Cohen C, Poretz D, Markowitz M, Follansbee S, Angel JB, McMahon D "Ritonavir and saquinavir combination therapy for the treatment of HIV infection." AIDS 13 (1999): 213-24
"Product Information. Fortovase (saquinavir)" Roche Laboratories, Nutley, NJ.
Deeks SG, Grant RM, Beatty GW, Horton C, Detmer J, Eastman S "Activity of a ritonavir plus saquinavir-containing regimen in patients with virologic evidence of indinavir or ritonavir failure." AIDS 12 (1998): f97-102
"Product Information. Invirase (saquinavir)." Roche Laboratories, Nutley, NJ.
Lu JF, Blaschke TF, Flexner C, Rosenkranz SL, Sheiner LB "Model-based Analysis of the Pharmacokinetic Interactions Between Ritonavir, Nelfinavir, and Saquinavir after Simultaneous and Staggered Oral Administration." Drug Metab Dispos 30 (2002): 1455-61
"Product Information. Norvir (ritonavir)." Abbott Pharmaceutical, Abbott Park, IL.
Hsu A, Granneman GR, Cao GL, Carothers L, ElShourbagy T, Baroldi P, Erdman K, Brown F, Sun E, Leonard JM "Pharmacokinetic interactions between two human immunodeficiency virus protease inhibitors, ritonavir and saquinavir." Clin Pharmacol Ther 63 (1998): 453-64
Fitzsimmons ME, Collins JM "Selective biotransformation of the human immunodeficiency virus protease inhibitor saquinavir by human small-intestinal cytochrome p4503a4 - potential contribution to high first-pass metabolism." Drug Metab Dispos 25 (1997): 256-66
Kirk O, Katzenstein TL, Gerstoft J, Mathiesen L, Nielsen H, Pedersen C, Lundgren JD "Combination therapy containing ritonavir plus saquinavir has superior short-term antiretroviral efficacy: a randomized trial." AIDS 13 (1999): f9-16
Tebas P, Patick AK, Kane EM, Klebert MK, Simpson JH, Erice A, Powderly WG, Henry K "Virologic responses to a ritonavir-saquinavir-containing regimen in patients who had previously failed nelfinavir." AIDS 13 (1999): f23-8
Merry C, Barry MG, Mulcahy F, Ryan M, Heavey J, Tjia JF, Gibbons SE, Breckenridge AM, Back DJ "Saquinavir pharmacokinetics alone and in combination with ritonavir in HIV-infected patients." AIDS 11 (1997): f29-33
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]):
Kilby JM, Sfakianos G, Gizzi N, et al "Safety and pharmacokinetics of once-daily regimens of soft-gel capsule saquinavir plus minidose ritonavir in human immunodeficiency virus-negative adults." Antimicrob Agents Chemother 44 (2000): 2672-8
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
Boffito M, Dickinson L, Hill A, et al "Saquinavir/ritonavir (SQV/r) pharmacokinetics (PKs) in HIV+ subjects: 1000/100 mg bid vs 1600/100 and 2000/100 mg once daily (OD) Available from: URL: http://www.natap.org/2003/ICAAC/day7_1.htm." ([2003 Sept ]):
Rathbun RC, Rossi DR "Low-dose ritonavir for protease inhibitor pharmacokinetic enhancement." Ann Pharmacother 36 (2002): 702-6
Buss N, Snell P, Bock J, Hsu A, Jorga K "Saquinavir and ritonavir pharmacokinetics following combined ritonavir and saquinavir (soft gelatin capsules) administration." Br J Clin Pharmacol 52 (2001): 255-64

Invirase

Generic Name: saquinavir

Brand name: Invirase, Fortovase

Synonyms: n.a.

What is Invirase?

Ritonavir Tablets

Generic Name: ritonavir

Brand name: Norvir, Norvir Soft Gelatin

Synonyms: Ritonavir

What is Ritonavir Tablets?

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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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