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CASE 3

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

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CASE 3

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

  7. 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

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