Midazolam with protease inhibitors

Merry C, Mulcahy F, Barry M, Gibbons S, Back D. Saquinavir interaction with midazolam pharmacokinetic considerations when prescribing protease inhibitors for patients with HIV disease (letter). AIDS 1997 11 268-9. 

Delavirdine should not be used in combination with drugs that are CYP3A4 substrates such as pimozide, midazolam, triazolam, amiodarone, propafenone and ergot derivatives. Inducers of the hepatic P-450 system, rifampin, rifabutin, pheno-barbital, phenytoin or carbamazepine, should not be used in combination with delaviridine. It also increases the plasma levels of HIV protease inhibitors. 

Saquinavir substantially potentiates the effects of midazolam by raising its blood concentrations, and this suggests that a parallel interaction could occur with other protease inhibitors (and no doubt certain other benzodiazepines) in similar combinations (59). 

Clinically important, potentially hazardous interactions with amiodarone, amprenavir, anisindione, antacids, anticoagulants, aprepitant, atazanavir, atovaquone, beclomethasone, buprenorphine, corticosteroids, cortisone, cyclosporine, cyproterone, dabigatran, dapsone, darunavir, delavirdine, dexamethasone, dicumarol, digoxin, eszopiclone, flunisolide, fosamprenavir, gadoxetate, gestrinone, halothane, imatinib, isoniazid, itraconazole, ketoconazole, lapatinib, lorcainide, methylprednisolone, midazolam, nelfinavir, nifedipine, oral contraceptives, phenylbutazone, prednisone, protease inhibitors, pyrazinamide, ramelteon, ritonavir, saquinavir, solifenacin, sunitinib, tacrolimus, telithromycin, temsirolimus, tipranavir, tolvaptan, trabectedin, triamcinolone, triazolam, voriconazole, warfarin, zaleplon... 

Of aU the HIV protease inhibitors, saquinavir is the least potent inhibitor of CYP3A4. Nonetheless, it is recommended that the drug not be coadministered with ergot derivatives, triazolam, midazolam, or other CYP3A4 substrates with a low therapeutic index. Saquinavir clearance is increased with CYP3A4 induction thus coadministration of rifampin, nevirapine, or efavirenz lowers saquinavir concentrations and should be avoided. The effect of nevirapine or efavirenz on saquinavir may be partially or completely reversed with ritonavir. 

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