1. CASE 3 62 yo man Genotype 1b chronic hepatitis C Cirrhosis No previous ascites/encephalopathy OGD revealed a few very small esophageal varices

2. CASE 3 Therapy was initiated with triple therapy including PEGINF/RBV/Telaprevir Baseline HCVRNA…3.6510E5

3. 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

4. CASE 3 OGD arranged…prepared in the usual fashion Bleeding seemingly coming from esophagitis and not varices

5. CASE 3 Patient noted to be unable to protect airway and develops apneic episodes …requires intubation/respiratory support for 24 hrs CAUSE??

6. 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]

8. 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