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Nebivolol; valsartan moderate monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with indinavir.

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Clinically significant adverse reactionspotentially leading to severelife-threateningor fatal events from greater exposures of concomitant medicationsClinically significant adverse reactions from greater exposures of CRIXIVANLoss of therapeutic effect of CRIXIVAN and possible development of resistance.

To explain how indinavir workswe need to first tell you some information about HIVWhen HIV infects a cellit takes control of that cellHIV then forces the cell to make many more copies of the virusTo make these copiesthe cell uses proteins called enzymesWhen the activity of these enzymes is reduced the production of HIV slows.

Midazolam is extensively metabolized by CYP3A4Co-administration with CRIXIVAN with or without ritonavir may cause a large increase in the concentration of this benzodiazepineNo drug interaction study has been performed for the co-administration of CRIXIVAN with benzodiazepinesBased on data from other CYP3A4 inhibitorsplasma concentrations of midazolam are expected to be significantly higher when midazolam is given orallyTherefore CRIXIVAN should not be co-administered with orally administered midazolamsee CONTRAINDICATIONSwhereas caution should be used with coadministration of CRIXIVAN and parenteral midazolamData from concomitant use of parenteral midazolam with other protease inhibitors suggest a possible 3-4 fold increase in midazolam plasma levelsIf CRIXIVAN with or without ritonavir is co-administered with parenteral midazolamit should be done in a setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedationDosage reduction for midazolam should be consideredespecially if more than a single dose of midazolam is administered.

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