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