Drug News
Simeprevir for hepatitis C virus By Shelley Hutcheson, and Olga M. Klibanov, PharmD, BCPS
The worldwide burden of hepatitis C virus (HCV) is significant. It is estimated that over 150 million people worldwide are infected with HCV, but the majority (up to 85%) are unaware of their status.1 Between 15% to 30% of chronically HCV-infected people will develop liver cirrhosis within 20 years, and the annual incidence of hepatocellular carcinoma in people with cirrhosis is 3% to 5% if the virus is untreated.1,2 Due to the serious complications of the disease and the availability of treatment, the CDC now recommends that HCV testing be performed at least once in everyone born between 1945 and 1965 and more frequently in those who have risk factors for acquiring HCV.2 Risk factors include: a history of injection drug use; receiving blood products that were not screened for HCV; being born to a mother infected with HCV; having had a sexual partner who was infected with HCV; a history of HIV infection; and tattoos or piercings.1,2 Six genotypes (1 to 6) of HCV have been identified (genotype 1 is the most common in the United States). Each genotype may respond differently to therapy. Prior to 2011, the combination of pegylated interferon alpha (Peg-IFNalpha) and ribavirin for 24 to 48 weeks was the standard of treatment for HCV infection (depending on the HCV genotype). However, there are many intolerable adverse events associated with this therapy that have resulted in suboptimal sustained virologic response (SVR) rates (or cure rates).3 Historically,
genotypes 2 and 3 have responded best to Peg-INF-alpha and ribavirin therapy, with an SVR rate of 70% to 80%; however, patients with all other genotypes achieved suboptimal SVR rates of 45% to 70% with this therapy.4 Over the last several years, new drugs have entered the market that target specific steps in the HCV replication cycle. In 2011, the approval of two novel HCV protease inhibitor agents (telaprevir and boceprevir) resulted in significantly improved SVR rates in HCV-infected patients and revolutionized the therapy landscape of HCV.4 Unfortunately, these agents still require the concomitant use of Peg-INF-alpha/ ribavirin, have a very high pill burden, a high incidence of adverse events, and may lead to resistance development. These drawbacks created a need for simpler, more tolerable regimens. Simeprevir (Olysio) is an HCV NS3/4A protease inhibitor that offers a novel option for treating HCV-infected individuals.5 It was studied in several phase III clinical trials (QUEST-1, QUEST-2, and PROMISE) involving over 1,100 HCV-infected patients.6-8 The drug was found to be effective and well-tolerated, which led to its FDA approval in December 2013. Simeprevir is manufactured and marketed by Janssen Therapeutics.5 ■ Indication Simeprevir is approved for the treatment of chronic hepatitis C, in combination with Peg-INF-alpha and ribavirin, in adults with compensated liver disease.5
■ Mechanism of action Simeprevir is a direct antiviral agent that exerts its effect by inhibiting HCV NS3/4A protease, an enzyme essential for hepatitis C viral replication.5 ■ Dosing and administration Simeprevir is available as an oral capsule and should be initiated at 150 mg once daily with food. Simeprevir must be given in combination with Peg-INF-alpha and ribavirin to be effective. The duration of simeprevir treatment depends on individual patient type and the response to therapy (see Patient counseling points).5 All patients should be started on simeprevir with Peg-INF-alpha and ribavirin for 12 weeks. Patients who are treatment-naive or prior relapsers, including those with cirrhosis, should receive an additional 12 weeks of Peg-INF-alpha and ribavirin (total duration is 24 weeks). Patients who are prior nonresponders, including those with cirrhosis, should receive an additional 36 weeks of peginterferon and ribavirin (total duration is 48 weeks). Because it is unlikely that patients who do not have an adequate on-treatment virologic response will achieve an SVR, simeprevir, peginterferon alfa, and ribavirin should be discontinued in anyone that meets the following criteria: HCV RNA greater than 25 international units (IU)/ mL at treatment week 4, 12, or 24 (stop Peg-INF-alpha and ribavirin; treatment with simeprevir is complete at week 12).5 Simeprevir has not been studied in patients with CrCL less than 30 mL/ min or those on hemodialysis; however, renal elimination is negligible, and no adjustments are needed
10 The Nurse Practitioner • Vol. 39, No. 9
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
www.tnpj.com
Drug News
in patients with renal impairment. Patients with moderate-to-severe liver disease (Child-Pugh score B and C) or decompensated liver disease should not use simeprevir.5 ■ Contraindications Because simeprevir must be used in combination with Peg-INF-alpha and ribavirin, any contraindications to these medications are also contraindications for the use of simeprevir.5 Simeprevir is considered a pregnancy category C drug when used alone and a pregnancy category X drug when used in combination with Peg-INFalpha and ribavirin. Because of these pregnancy category ratings, simeprevir is prohibited in pregnant women and male partners of pregnant women as well as women who are breastfeeding due to the unknown effects of simeprevir on the developing fetus. Female patients must have a negative pregnancy test before receiving treatment with simeprevir. All female patients and their partners are required to use at least two forms of contraception throughout treatment that do not include hormone therapy due to the ability of simeprevir to reduce their efficacy. Contraceptives should be continued 6 months posttreatment discontinuation, and monthly pregnancy tests should be given to ensure their efficacy.5 ■ Warnings and precautions Simeprevir should never be used as monotherapy for the treatment of hepatitis C.5 Patients with a sulfa allergy should exercise caution when considering simeprevir as a treatment option because it contains a sulfonamide moiety and may induce an allergic reaction in this patient population. Patients should also limit sun exposure and use sunscreen if there is anticipated sun exposure due to simeprevir’s ability to cause photosensitivity.5 www.tnpj.com
Patient counseling points5 • Simeprevir should always be used with other medications that treat hepatitis C virus • Before taking simeprevir tell your healthcare provider if you: – Have liver problems other than hepatitis C – Have taken the medicines telaprevir (Incivek) or boceprevir (Victrelis) – Had a liver transplant – Are receiving phototherapy – Have any other medical condition – Are of East Asian descent – Are breastfeeding • Inform your healthcare provider of any medications that you are taking • Take simeprevir exactly as prescribed • Take simeprevir once daily with food and swallow the capsule whole • The most common adverse reactions of simeprevir when used in combination with Peg-INF-alpha and ribavirin are skin rash, itching, and nausea • Avoid excessive sun exposure while taking simeprevir, and use sunscreen if sun exposure is anticipated
■ Adverse reactions Common adverse reactions of simeprevir include rash, pruritus, nausea, myalgia, dyspnea, and elevated liver functions tests and bilirubin. A small number of patients reported photosensitivity and elevated alkaline phosphatase levels. All of the adverse effects reported occurred during the first 4 weeks of treatment. Interestingly, patients of East Asian ancestry have higher simeprevir drug exposures and can experience a higher frequency of adverse events, including rash and photosensitivity. The potential risks and benefits should be carefully weighed prior to using simeprevir in this population.5 ■ Drug interactions Simeprevir has the potential to interact with many other drugs because it is mainly biotransformed by the liver CYP3A enzyme. Therefore, it is not recommended to administer simeprevir with medications that are CYP3A inhibitors or inducers due to their ability to alter simeprevir concentrations.5 Examples of the interacting
medications that are not recommended with simeprevir include the following: anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin), macrolide/ketolide antibiotics (erythromycin, clarithromycin, telithromycin), systemic antifungals (itraconazole, ketoconazole, posaconazole, fluconazole, voriconazole), antimycobacterials (rifampin, rifabutin, rifapentine), dexamethasone, cisapride, many anti-HIV agents, and herbal products (milk thistle, St. John’s wort).5 In addition to being a substrate for the CYP3A enzyme, simeprevir is also a mild inhibitor of CYP1A2 and CYP3A4, which can result in increased plasma concentrations of the drugs that are metabolized by those systems.5 Simeprevir also inhibits drug transport systems OATP1B1/3 and P-glycoprotein, resulting in increased plasma concentrations of drugs that are transported by those systems.5 Examples of drugs that may be affected by simeprevir include: HMG CoA reductase inhibitors (statins), immunosuppressants (cyclosporine, tacrolimus, sirolimus), The Nurse Practitioner • September 2014 11
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Drug News phosphodiesterase type 5 (PDE-5) inhibitors (sildenafil, tadalafil, vardenafil), and certain sedatives/anxiolytics (midazolam, triazolam). These medications should be used with extreme caution when given concomitantly with simeprevir, preferably started at lower doses and with careful dose titrations.5 ■ Pharmacokinetics Simeprevir’s bioavailability and exposure is increased by 60% to 70% when given with food. The maximum plasma concentration of the drug is achieved 4 to 6 hours after the dose, and steady-state is reached after 7 days of daily dosing. Simeprevir is highly bound to plasma proteins (greater than 99.9%). It is metabolized in the liver, mainly by the hepatic CYP3A system, and eliminated via biliary excretion. Pharmacokinetic studies indicated that simeprevir exposures are significantly (3.4-fold) higher in Asians compared with Whites, which can lead to a higher risk of adverse events, such as rash and photosensitivity.5 The potential risk and benefits of simeprevir in patients of East Asian ancestry should be carefully considered prior to starting treatment with this drug.
Stay y on the Leading Edge of Emergency Carre Deliver the best in patient care with the latest emergency nursing information: Ǧ Ongoing Departments Ǧ Tools for preventing medical errors, disaster preparation, and more Ǧ New drug updates, advances in procedures, and diagnostic techniques
Renal elimination of simeprevir is negligible; therefore, renal impairment is not expected to have any effects on the exposure of the drug. The terminal elimination half-life of simeprevir was 10 to 13 hours in healthy volunteers and 41 hours in HCV-infected subjects in pharmacokinetic studies.5 ■ Clinical pearls • Simeprevir provides an effective, well-tolerated addition to anti-HCV therapy. • Simeprevir should always be given in combination with Peg-INF-alpha and ribavirin. • Simeprevir is pregnancy category C; however, its use is contraindicated in pregnancy because it is used concomitantly with Peg-INF-alpha and ribavirin (ribavirin is pregnancy category X and can cause birth defects and fetal death). • Rash and photosensitivity have been observed with simeprevir. Sun exposure should be limited while the patient is on simeprevir, and the use of sunscreen should be encouraged. • Simeprevir has a sulfonamide moiety and should be used with caution in patients with a sulfa allergy. • The anti-HCV treatment protocol with simeprevir is dependent on the patient’s treatment history and response. • Patients’ medication profiles should be carefully screened for drug-drug interactions during treatment with simeprevir. REFERENCES 1. World Health Organization. Hepatitis C. 2014. http://www.who.int/ mediacentre/factsheets/fs164/en/. 2. The Centers for Disease Control and Prevention. Hepatitis C. 2014. http:// www.cdc.gov/hepatitis/HCV/GuidelinesC.htm. 3. AASLD, IDSA, IAS–USA. Recommendations for testing, managing, and treating hepatitis C. 2014. http://www.hcvguidelines.org. 4. Ghany MG, Nelson DR, Strader DB, et al. An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology. 2011;54(4):14331444. 5. OLYSIO® [package insert]. Titusville, NJ: Janssen Therapeutics; 2013. 6. Jacobson I, Dore GJ, Foster GR, et al. Simeprevir (TMC435) with peginterferon/ribavirin for treatment of chronic HCV genotype 1 infection in treatment-naïve patients: results from QUEST-1 a phase III trial. Presented at: The 48th Annual Meeting of the European Association for the Study of the Liver (EASL); April 24-28, 2013; Amsterdam.
Your perso onal sub bsccripti tio on incclu lude des: s ǦǦMobile view
7. Manns M, Marcellin P, Poordad F, et al. Simeprevir (TMC435) with peginterferon/ribavirin for treatment of chronic HCV genotype 1 infection in treatment-naive patients: results from QUEST-2 a phase III trial. Presented at: The 48th Annual Meeting of the European Association for the Study of the Liver (EASL); April 24-28, 2013; Amsterdam.
SUBSCRIBE TODAY AT LWW.COM or call 1-800-638-3030
8. Lawitz E, Forns X, Zeuzem S, et al. Simeprevir (TMC435) With peginterferon/ ribavirin for treatment of chronic HCV genotype 1 Infection in patients who relapsed after previous interferon-based therapy: results from PROMISE, a phase III trial. Presented at: Digestive Disease Week; May 18-21, 2013; Orlando.
Access the journal online at
www.AENJournal.com
Shelley Hutcheson is a pharmacy student and Olga M. Klibanov is a professor of pharmacy at Wingate University, Wingate, N.C. The authors have disclosed that they have no financial relationships related to this article. DOI-10.1097/01.NPR.0000452985.51256.53
12 The Nurse Practitioner • Vol. 39, No. 9
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
www.tnpj.com
Simeprevir for hepatitis C virus By Shelley Hutcheson, and Olga M. Klibanov, PharmD, BCPS
The worldwide burden of hepatitis C virus (HCV) is significant. It is estimated that over 150 million people worldwide are infected with HCV, but the majority (up to 85%) are unaware of their status.1 Between 15% to 30% of chronically HCV-infected people will develop liver cirrhosis within 20 years, and the annual incidence of hepatocellular carcinoma in people with cirrhosis is 3% to 5% if the virus is untreated.1,2 Due to the serious complications of the disease and the availability of treatment, the CDC now recommends that HCV testing be performed at least once in everyone born between 1945 and 1965 and more frequently in those who have risk factors for acquiring HCV.2 Risk factors include: a history of injection drug use; receiving blood products that were not screened for HCV; being born to a mother infected with HCV; having had a sexual partner who was infected with HCV; a history of HIV infection; and tattoos or piercings.1,2 Six genotypes (1 to 6) of HCV have been identified (genotype 1 is the most common in the United States). Each genotype may respond differently to therapy. Prior to 2011, the combination of pegylated interferon alpha (Peg-IFNalpha) and ribavirin for 24 to 48 weeks was the standard of treatment for HCV infection (depending on the HCV genotype). However, there are many intolerable adverse events associated with this therapy that have resulted in suboptimal sustained virologic response (SVR) rates (or cure rates).3 Historically,
genotypes 2 and 3 have responded best to Peg-INF-alpha and ribavirin therapy, with an SVR rate of 70% to 80%; however, patients with all other genotypes achieved suboptimal SVR rates of 45% to 70% with this therapy.4 Over the last several years, new drugs have entered the market that target specific steps in the HCV replication cycle. In 2011, the approval of two novel HCV protease inhibitor agents (telaprevir and boceprevir) resulted in significantly improved SVR rates in HCV-infected patients and revolutionized the therapy landscape of HCV.4 Unfortunately, these agents still require the concomitant use of Peg-INF-alpha/ ribavirin, have a very high pill burden, a high incidence of adverse events, and may lead to resistance development. These drawbacks created a need for simpler, more tolerable regimens. Simeprevir (Olysio) is an HCV NS3/4A protease inhibitor that offers a novel option for treating HCV-infected individuals.5 It was studied in several phase III clinical trials (QUEST-1, QUEST-2, and PROMISE) involving over 1,100 HCV-infected patients.6-8 The drug was found to be effective and well-tolerated, which led to its FDA approval in December 2013. Simeprevir is manufactured and marketed by Janssen Therapeutics.5 ■ Indication Simeprevir is approved for the treatment of chronic hepatitis C, in combination with Peg-INF-alpha and ribavirin, in adults with compensated liver disease.5
■ Mechanism of action Simeprevir is a direct antiviral agent that exerts its effect by inhibiting HCV NS3/4A protease, an enzyme essential for hepatitis C viral replication.5 ■ Dosing and administration Simeprevir is available as an oral capsule and should be initiated at 150 mg once daily with food. Simeprevir must be given in combination with Peg-INF-alpha and ribavirin to be effective. The duration of simeprevir treatment depends on individual patient type and the response to therapy (see Patient counseling points).5 All patients should be started on simeprevir with Peg-INF-alpha and ribavirin for 12 weeks. Patients who are treatment-naive or prior relapsers, including those with cirrhosis, should receive an additional 12 weeks of Peg-INF-alpha and ribavirin (total duration is 24 weeks). Patients who are prior nonresponders, including those with cirrhosis, should receive an additional 36 weeks of peginterferon and ribavirin (total duration is 48 weeks). Because it is unlikely that patients who do not have an adequate on-treatment virologic response will achieve an SVR, simeprevir, peginterferon alfa, and ribavirin should be discontinued in anyone that meets the following criteria: HCV RNA greater than 25 international units (IU)/ mL at treatment week 4, 12, or 24 (stop Peg-INF-alpha and ribavirin; treatment with simeprevir is complete at week 12).5 Simeprevir has not been studied in patients with CrCL less than 30 mL/ min or those on hemodialysis; however, renal elimination is negligible, and no adjustments are needed
10 The Nurse Practitioner • Vol. 39, No. 9
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
www.tnpj.com
Drug News
in patients with renal impairment. Patients with moderate-to-severe liver disease (Child-Pugh score B and C) or decompensated liver disease should not use simeprevir.5 ■ Contraindications Because simeprevir must be used in combination with Peg-INF-alpha and ribavirin, any contraindications to these medications are also contraindications for the use of simeprevir.5 Simeprevir is considered a pregnancy category C drug when used alone and a pregnancy category X drug when used in combination with Peg-INFalpha and ribavirin. Because of these pregnancy category ratings, simeprevir is prohibited in pregnant women and male partners of pregnant women as well as women who are breastfeeding due to the unknown effects of simeprevir on the developing fetus. Female patients must have a negative pregnancy test before receiving treatment with simeprevir. All female patients and their partners are required to use at least two forms of contraception throughout treatment that do not include hormone therapy due to the ability of simeprevir to reduce their efficacy. Contraceptives should be continued 6 months posttreatment discontinuation, and monthly pregnancy tests should be given to ensure their efficacy.5 ■ Warnings and precautions Simeprevir should never be used as monotherapy for the treatment of hepatitis C.5 Patients with a sulfa allergy should exercise caution when considering simeprevir as a treatment option because it contains a sulfonamide moiety and may induce an allergic reaction in this patient population. Patients should also limit sun exposure and use sunscreen if there is anticipated sun exposure due to simeprevir’s ability to cause photosensitivity.5 www.tnpj.com
Patient counseling points5 • Simeprevir should always be used with other medications that treat hepatitis C virus • Before taking simeprevir tell your healthcare provider if you: – Have liver problems other than hepatitis C – Have taken the medicines telaprevir (Incivek) or boceprevir (Victrelis) – Had a liver transplant – Are receiving phototherapy – Have any other medical condition – Are of East Asian descent – Are breastfeeding • Inform your healthcare provider of any medications that you are taking • Take simeprevir exactly as prescribed • Take simeprevir once daily with food and swallow the capsule whole • The most common adverse reactions of simeprevir when used in combination with Peg-INF-alpha and ribavirin are skin rash, itching, and nausea • Avoid excessive sun exposure while taking simeprevir, and use sunscreen if sun exposure is anticipated
■ Adverse reactions Common adverse reactions of simeprevir include rash, pruritus, nausea, myalgia, dyspnea, and elevated liver functions tests and bilirubin. A small number of patients reported photosensitivity and elevated alkaline phosphatase levels. All of the adverse effects reported occurred during the first 4 weeks of treatment. Interestingly, patients of East Asian ancestry have higher simeprevir drug exposures and can experience a higher frequency of adverse events, including rash and photosensitivity. The potential risks and benefits should be carefully weighed prior to using simeprevir in this population.5 ■ Drug interactions Simeprevir has the potential to interact with many other drugs because it is mainly biotransformed by the liver CYP3A enzyme. Therefore, it is not recommended to administer simeprevir with medications that are CYP3A inhibitors or inducers due to their ability to alter simeprevir concentrations.5 Examples of the interacting
medications that are not recommended with simeprevir include the following: anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin), macrolide/ketolide antibiotics (erythromycin, clarithromycin, telithromycin), systemic antifungals (itraconazole, ketoconazole, posaconazole, fluconazole, voriconazole), antimycobacterials (rifampin, rifabutin, rifapentine), dexamethasone, cisapride, many anti-HIV agents, and herbal products (milk thistle, St. John’s wort).5 In addition to being a substrate for the CYP3A enzyme, simeprevir is also a mild inhibitor of CYP1A2 and CYP3A4, which can result in increased plasma concentrations of the drugs that are metabolized by those systems.5 Simeprevir also inhibits drug transport systems OATP1B1/3 and P-glycoprotein, resulting in increased plasma concentrations of drugs that are transported by those systems.5 Examples of drugs that may be affected by simeprevir include: HMG CoA reductase inhibitors (statins), immunosuppressants (cyclosporine, tacrolimus, sirolimus), The Nurse Practitioner • September 2014 11
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Drug News phosphodiesterase type 5 (PDE-5) inhibitors (sildenafil, tadalafil, vardenafil), and certain sedatives/anxiolytics (midazolam, triazolam). These medications should be used with extreme caution when given concomitantly with simeprevir, preferably started at lower doses and with careful dose titrations.5 ■ Pharmacokinetics Simeprevir’s bioavailability and exposure is increased by 60% to 70% when given with food. The maximum plasma concentration of the drug is achieved 4 to 6 hours after the dose, and steady-state is reached after 7 days of daily dosing. Simeprevir is highly bound to plasma proteins (greater than 99.9%). It is metabolized in the liver, mainly by the hepatic CYP3A system, and eliminated via biliary excretion. Pharmacokinetic studies indicated that simeprevir exposures are significantly (3.4-fold) higher in Asians compared with Whites, which can lead to a higher risk of adverse events, such as rash and photosensitivity.5 The potential risk and benefits of simeprevir in patients of East Asian ancestry should be carefully considered prior to starting treatment with this drug.
Stay y on the Leading Edge of Emergency Carre Deliver the best in patient care with the latest emergency nursing information: Ǧ Ongoing Departments Ǧ Tools for preventing medical errors, disaster preparation, and more Ǧ New drug updates, advances in procedures, and diagnostic techniques
Renal elimination of simeprevir is negligible; therefore, renal impairment is not expected to have any effects on the exposure of the drug. The terminal elimination half-life of simeprevir was 10 to 13 hours in healthy volunteers and 41 hours in HCV-infected subjects in pharmacokinetic studies.5 ■ Clinical pearls • Simeprevir provides an effective, well-tolerated addition to anti-HCV therapy. • Simeprevir should always be given in combination with Peg-INF-alpha and ribavirin. • Simeprevir is pregnancy category C; however, its use is contraindicated in pregnancy because it is used concomitantly with Peg-INF-alpha and ribavirin (ribavirin is pregnancy category X and can cause birth defects and fetal death). • Rash and photosensitivity have been observed with simeprevir. Sun exposure should be limited while the patient is on simeprevir, and the use of sunscreen should be encouraged. • Simeprevir has a sulfonamide moiety and should be used with caution in patients with a sulfa allergy. • The anti-HCV treatment protocol with simeprevir is dependent on the patient’s treatment history and response. • Patients’ medication profiles should be carefully screened for drug-drug interactions during treatment with simeprevir. REFERENCES 1. World Health Organization. Hepatitis C. 2014. http://www.who.int/ mediacentre/factsheets/fs164/en/. 2. The Centers for Disease Control and Prevention. Hepatitis C. 2014. http:// www.cdc.gov/hepatitis/HCV/GuidelinesC.htm. 3. AASLD, IDSA, IAS–USA. Recommendations for testing, managing, and treating hepatitis C. 2014. http://www.hcvguidelines.org. 4. Ghany MG, Nelson DR, Strader DB, et al. An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology. 2011;54(4):14331444. 5. OLYSIO® [package insert]. Titusville, NJ: Janssen Therapeutics; 2013. 6. Jacobson I, Dore GJ, Foster GR, et al. Simeprevir (TMC435) with peginterferon/ribavirin for treatment of chronic HCV genotype 1 infection in treatment-naïve patients: results from QUEST-1 a phase III trial. Presented at: The 48th Annual Meeting of the European Association for the Study of the Liver (EASL); April 24-28, 2013; Amsterdam.
Your perso onal sub bsccripti tio on incclu lude des: s ǦǦMobile view
7. Manns M, Marcellin P, Poordad F, et al. Simeprevir (TMC435) with peginterferon/ribavirin for treatment of chronic HCV genotype 1 infection in treatment-naive patients: results from QUEST-2 a phase III trial. Presented at: The 48th Annual Meeting of the European Association for the Study of the Liver (EASL); April 24-28, 2013; Amsterdam.
SUBSCRIBE TODAY AT LWW.COM or call 1-800-638-3030
8. Lawitz E, Forns X, Zeuzem S, et al. Simeprevir (TMC435) With peginterferon/ ribavirin for treatment of chronic HCV genotype 1 Infection in patients who relapsed after previous interferon-based therapy: results from PROMISE, a phase III trial. Presented at: Digestive Disease Week; May 18-21, 2013; Orlando.
Access the journal online at
www.AENJournal.com
Shelley Hutcheson is a pharmacy student and Olga M. Klibanov is a professor of pharmacy at Wingate University, Wingate, N.C. The authors have disclosed that they have no financial relationships related to this article. DOI-10.1097/01.NPR.0000452985.51256.53
12 The Nurse Practitioner • Vol. 39, No. 9
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
www.tnpj.com
