CASE 3

• 62 yo man• Genotype 1b chronic hepatitis C• Cirrhosis• No previous ascites/encephalopathy• OGD revealed a few very small esophageal

varices

CASE 3

• Therapy was initiated with triple therapy including PEGINF/RBV/Telaprevir

• Baseline HCVRNA…3.6510E5

CASE 3

•Week 0 HCVRNA…3.65x10E5•Week 4 HCVRNA…<12

•Begins to develop swelling of ankles at week 5 and at week 6 develops hematemsis

CASE 3

•OGD arranged…prepared in the usual fashion

•Bleeding seemingly coming from esophagitis and not varices

CASE 3

•Patient noted to be unable to protect airway and develops apneic episodes …requires intubation/respiratory support for 24 hrs CAUSE??

Interactions with Midazolam• Midazolam is a CYP3A4 substrate• susceptible to interactions with inhibitors• 2.5 to 5-fold AUC with saquinavir• 5 to 9-fold AUC with boceprevir or telaprevir• case report of prolonged sedation with midazolam +

SQV requiring flumazenil• Midazolam is contraindicated with HIV and HCV protease inhibitors• Alternatives: lorazepam (Ativan) or propofol

(Diprivan) [AIDS 1997;11:268-9; Victrelis & Incivek Product Monographs, 2011]

Summary• High potential for pharmacokinetic interactions

between directly acting antivirals and other drug classes

• Steps to minimize/manage interactions:• ensure medication records are up to date at each visit

(medication reconciliation)• use a systematic approach to identify combinations of

potential concern• consult pertinent drug interaction resources,

pharmacology/pharmacy specialists• consider therapeutic drug monitoring (if available)• patient counselling & close monitoring