This CE activity is co-sponsored by ProCE, Inc. and Hospital Pharmacy. ProCE, Inc. is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. ACPE Universal Activity Number 0221-9999-15-035-H01-P has been assigned to this knowledge-based home study CE activity (initial release date 03-01-2015). This CE activity is approved for 1.5 contact hours (0.15 CEUs) in states that recognize ACPE providers. This CE activity is provided at no cost to participants. Completion of the evaluation and the post-test with a score of 70% or higher are required to receive CE credit. No partial credit will be given.

Faculty: Dennis J. Cada, PharmD, FASHP, FASCP (Editor), Founder and Contributing Editor, The Formulary; Danial E. Baker, PharmD, FASHP, FASCP, Director, Drug Information Center, and Professor of Pharmacy Practice, College of Pharmacy, Washington State University; and Ross Jason Bindler, PharmD, Drug Information Resident, College of Pharmacy, Washington State University. The authors indicate no relationships that could be perceived as a conflict of interest. This activity is self-funded by Hospital Pharmacy.

Release Date: March 1, 2015

Expiration Date: March 1, 2017

Continuing Education for this activity is processed through the ProCE online CE Center. To receive CE credit, please go to: 

• www.ProCE.com/HPJFDR
• Click to access the activity page to enroll and complete the Post-Test and Evaluation

For questions related to registering for and obtaining CE credit, contact ProCE at 630-540-2848 or Info@ProCE.com.

1. The US Food and Drug Administration (FDA)−approved indication for ledipasvir/sofosbuvir is for the treatment of:
   1. Adult patients with chronic hepatitis C (HCV) infections of any genotype.
   2. Adult patients with chronic HCV genotype 1 infections.
   3. Adult patients with chronic HCV genotype 1 infections in combination with at least 2 other direct-acting antiviral agents.
   4. Adult patients with chronic HCV infections of any genotype in combination with at least 1 other direct-acting antiviral agent.
      
      
2. Ledipasvir inhibits the activity of HCV genotype 1 by:
   1. Binding to the NS5A protein.
   2. Inhibiting NS5B RNA polymerase.
   3. Binding to the NS3/4A protein.
   4. Modulating the host’s natural immune syste­m.
      
      
3. Sofosbuvir inhibits the activity of HCV by:
   1. Binding to the NS5A protein.
   2. Inhibiting NS5B RNA polymerase.
   3. Binding to the NS3/4A protein.
   4. Modulating the host’s natural immune syste­m. 
      
      
4. Each tablet of ledipasvir/sofosbuvir contains how many milligrams of ledipasvir?
   1. 90 mg
   2. 180 mg
   3. 200 mg
   4. 400 mg
      
      
5. Which of the following is a contraindication to therapy with ledipasvir/sofosbuvir?
   1. Chronic compensated cirrhosis
   2. Coinfection with human immunodeficiency virus (HIV) 
   3. Failure of a previous course of HCV therapy 
   4. Hypersensitivity to ledipasvir, sofosbuvir, or any other tablet components
      
      
6. Ledipasvir/sofosbuvir is in which of the following Pregnancy Categories?
   1. .A
   2. B
   3. C
   4. X
      
      
7. Which of the following HIV antiretrovirals could be administered with ledipasvir/sofosbuvir in a patient with an HIV-HCV coinfection without a change in the pharmacokinetics of either medication?
   1. Tenofovir
   2. Ritonavir  
   3. Tipranavir
   4. Raltegravir
      
      
8. The most common side effects associated with the use of ledipasvir/sofosbuvir include: 
   1. Fatigue and headache.
   2. Nausea and diarrhea.
   3. Diarrhea and insomnia.
   4. Nausea and abnormal liver function tests.
      
      
9. What is the recommended duration of ledipasvir/sofosbuvir treatment for a patient who has previously failed an HCV genotype 1 treatment regimen and is diagnosed with compensated cirrhosis?
   1. 8 weeks
   2. 12 weeks 
   3. 24 weeks 
   4. 48 weeks
      
      

Case History

M.M. is a 42-year-old male patient with gastroesophageal reflux disease, bipolar disorder with major depressive disorder, and a history of illicit intravenous drug use. His current medications include famotidine 20 mg daily, lithium carbonate 300 mg every 8 hours, fluoxetine 40 mg per day, and methadone 40 mg once daily. His physician has just diagnosed him with a chronic HCV genotype 1b infection and would like to start treatment immediately. M.M.’s current laboratory values of note include an initial viral load of 6,390,000 IU/mL, an alanine aminotransferase (ALT) level of 84 IU/mL, and an aspartate aminotransferase (AST) level of 77 IU/mL, and genetic testing reveals his interleukin (IL)-28B genotype is TT, non-wild-type. Due to his history of serious mental health conditions and genetics, the treatment of his HCV genotype 1b infection with interferon alfa−containing regimens is not indicated, so his physician thinks he may benefit from the use of ledipasvir/sofosbuvir.

10. The recommended dose of ledipasvir/sofosbuvir for M.M. would be:
    1. 180 mg of ledipasvir/800 mg of sofosbuvir once daily.
    2. 180 mg of ledipasvir/800 mg of sofosbuvir twice daily.
    3. 90 mg of ledipasvir/400 mg of sofosbuvir twice daily.
    4. 90 mg of ledipasvir/400 mg of sofosbuvir once daily.
       
       
11. Based on the FDA-approved dosing schedule, how many total tablets of ledipasvir/sofosbuvir would make up the complete treatment period for M.M.?
    1. 42 tablets
    2. .56 tablets
    3. 84 tablets
    4. 168 tablets
       
       
12. M.M. should be instructed to take ledipasvir/sofosbuvir:
    1. On an empty stomach.
    2. With a large meal.
    3. With an 8 oz glass of milk.
    4. At the same time every day.
       
       
13. Which of the following medications should M.M. take at a different time than his ledipasvir/sofosbuvir?
    1. Famotidine
    2. Lithium carbonate
    3. Fluoxetine
    4. Methadone
       
       
14. Which of the following mutations in the specific HCV strain affecting M.M. may result in a reduced susceptibility to ledipasvir?
    1. Q23E
    2. Y93H
    3. P57R
    4. No mutations reduce HCV’s susceptibility to ledipasvir. 
       
       
15. Which of the following initial HCV genotype 1 viral loads would have qualified M.M. for the 8-week ledipasvir/sofosbuvir treatment regimen?
    1. 3,000,000 IU/mL
    2. 6,000,000 IU/mL 
    3. 9,000,000 IU/mL
    4. M.M. would not qualify for the 8-week treatment regimen with any initial viral load.