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In the treatment of chronic hepatitis C virus (HCV) genotype 1 infection, Take a closer look at your patient’s individual needs OLYSIO® + sofosbuvir: The only protease inhibitor + nucleotide polymerase inhibitor regimen • Does not contain an NS5A inhibitor, ritonavir, and is IFN- and RBV-free Regimen OLYSIO ® + sofosbuvir NS3/4A Protease Inhibitor EPCLUSA®3 NS5A Inhibitor Non-nucleoside Polymerase Inhibitor Nucleoside Analog sofosbuvir ledipasvir sofosbuvir +/- ribavirin2 velpatasvir sofosbuvir +/- ribavirin2 paritaprevir/ ritonavir ombitasvir grazoprevir elbasvir DAKLINZA™6 + sofosbuvir NS5B Nucleotide Polymerase Inhibitor daclatasvir dasabuvir +/- ribavirin2 +/- ribavirin2 sofosbuvir +/- ribavirin2 INDICATIONS OLYSIO® is indicated for the treatment of adults with chronic hepatitis C virus (HCV) infection in combination with sofosbuvir in patients with HCV genotype 1 without cirrhosis or with compensated cirrhosis; in combination with peginterferon alfa (Peg-IFN-alfa) and ribavirin (RBV) in patients with HCV genotype 1 without cirrhosis or with compensated cirrhosis. Limitations of Use: Efficacy of OLYSIO® in combination with Peg-IFN-alfa and RBV is substantially reduced in patients infected with HCV genotype 1a with an NS3 Q80K polymorphism at baseline compared to patients infected with HCV genotype 1a without the Q80K polymorphism. OLYSIO® is not recommended in patients who have previously failed therapy with a treatment regimen that included OLYSIO® or other HCV protease inhibitors. SELECT SAFETY INFORMATION WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN PATIENTS COINFECTED WITH HCV AND HBV Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with OLYSIO®. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct-acting antivirals and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and posttreatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated. IFN=interferon; RBV=ribavirin. Please see additional Important Safety Information on the following pages and full Prescribing Information, including Boxed Warning and Patient Information by visiting www.olysio.com. Identify MOA ZEPATIER™5 Mechanism of Action OLYSIO ® HARVONI®1 VIEKIRA PAK ®4 NS5A COSMOS AND OPTIMIST-1 Clinical Trials COSMOS (IFN-free) study design Week 12 Study arms Week 48 12-week, RBV-free arm (n=28) OLYSIO® + SOF Post-therapy follow-up 24-week, RBV-free arm (n=31) OLYSIO® + SOF Post-therapy follow-up Week 12 12-week, RBV-free arm (n=155) OLYSIO® + SOF COSMOS (n=59) OPTIMIST-1 (n=155) 57 (27-68) 59 (19-70) Median age, years (range) Patients aged over 65 years (%) 2 7 Sex, male (%) 53 53 White 76 78 Black or African American 24 20 Race/ethnicity (%) OPTIMIST-1 (IFN-free) study design Study arms Demographics Week 24 Week 36 Post-therapy follow-up The recommended treatment duration of OLYSIO® + SOF is 24 weeks in patients with compensated cirrhosis (Child-Pugh A) and 12 weeks in patients without cirrhosis Body mass index ≥30 kg/m2 (%) Median HCV RNA level (log10 IU/mL) COSMOS: open‑label, randomized Phase 2 trial to investigate the efficacy and safety of 12 or 24 weeks of OLYSIO® in combination with SOF without or with RBV in HCV genotype 1‑infected prior null responders with METAVIR fibrosis score F0‑F2, or treatment‑naïve subjects and prior null responders (to P/R therapy) with METAVIR fibrosis score F3‑F4 and compensated liver disease. OPTIMIST-1: open-label, randomized Phase 3 trial to investigate the efficacy and safety of 12 weeks of OLYSIO® in combination with SOF without RBV in HCV genotype1-infected subjects without cirrhosis. O LYSIO® 150 mg once daily + SOF 400 mg once daily P rimary endpoint: SVR12: sustained virologic response 12 weeks after planned (COSMOS) or actual (OPTIMIST-1) end of treatment [EOT]) 37 6.75 6.83 75 75 HCV genotype (%) G1a Presence of Q80K polymorphism in G1a population 41 40 25 25 CC 14 28 CT 64 55 TT 22 17 Treatment naïve 25 74 Treatment experienced 75 26† G1b IFN- and RBV-free treatment option = OLYSIO® + SOF 46 Review the OLYSIO® Clinical Profile The recommended treatment duration of OLYSIO® + sofosbuvir is 24 weeks for patients with cirrhosis and 12 weeks for patients without cirrhosis Week 24 Baseline demographics and disease characteristics in OLYSIO® + SOF without RBV arms IL28B genotype (%) Patient type (%) ‡ In COSMOS, 19%, 31% and 22% had METAVIR fibrosis scores F0-F1, F2 and F3, respectively, and 29% had METAVIR fibrosis score F4 (cirrhosis). ‡ Includes only null responders to prior Peg-IFN/RBV therapy. † Includes relapsers and non-responders to prior Peg-IFN-based therapy (with or without RBV), and IFN-intolerant subjects. IFN=interferon; P/R=peginterferon/ribavirin; RBV=ribavirin; SOF=sofosbuvir SELECT SAFETY INFORMATION Contraindications: Because OLYSIO® is used only in combination with other antiviral drugs (including Peg-IFN-alfa and RBV) for the treatment of chronic HCV infection, the contraindications to other drugs also apply to the combination regimen. Refer to the respective prescribing information for a list of contraindications. Warnings and Precautions: Risk of Hepatitis B Virus Reactivation in Patients Coinfected With HCV and HBV: HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct-acting antivirals and who were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who Please see additional Important Safety Information on the following pages and full Prescribing Information, including Boxed Warning and Patient Information by visiting www.olysio.com. Risk of Hepatitis B Virus Reactivation in Patients Coinfected With HCV and HBV (cont’d): are HBsAg positive and also in patients with serologic evidence of resolved HBV infection (i.e., HBsAg negative and anti-HBc positive). HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. HBV reactivation is characterized as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA level. In patients with resolved HBV infection, reappearance of HBsAg can occur. Reactivation of HBV replication may be accompanied by hepatitis; i.e., increases in aminotransferase levels and, in severe cases, increases in bilirubin levels, liver failure, and death can occur. Test all patients for evidence of current or prior HBV infection by measuring HBsAg and anti-HBc before initiating HCV treatment with OLYSIO®. In patients with serologic evidence of HBV infection, monitor for clinical and laboratory signs of hepatitis flare or HBV reactivation during HCV treatment with OLYSIO® and during posttreatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated. 3 OLYSIO® + sofosbuvir = IFN- and RBV-free treatment option Overall cure* rates in the 24-week group (10/10) 100 SVR12 * 100 % Viral relapse ‡ (10/10) % of patients of patients with cirrhosis achieved cure in the 24-week group 97% COSMOS Overall Cure* Rates in Treatment Naïve and Null Responders† with Cirrhosis in the 24-week Group 50 0% (0/10) 0 Patients with cirrhosis (F4) COSMOS and OPTIMIST-1 Overall Cure* Rates in Adults without Cirrhosis Receiving 12 Weeks of OLYSIO® with Sofosbuvir (170/176) of patients without cirrhosis achieved cure and 3% (5/175) experienced viral relapse in the 12-week group 100 SVR12* 97% Viral relapse ‡ (170/176) % of patients 100% Overall cure* rates in the 12-week group 50 3% (5/175) 0 Pooled data from OPTIMIST-1 and COSMOS trials Use with RBV Use with RBV Results from treatment arms containing RBV in addition to OLYSIO® and sofosbuvir in the COSMOS trial are not shown because efficacy was similar with or without RBV, and thus addition of RBV to OLYSIO® and sofosbuvir is not recommended. Results from treatment arms containing RBV in addition to OLYSIO® and sofosbuvir in the COSMOS trial are not shown because efficacy was similar with or without RBV, and thus addition of RBV to OLYSIO® and sofosbuvir is not recommended. *Virologic cure (SVR12) was defined as sustained virologic response 12 weeks after the planned end of treatment (EOT). † Null responders to prior P/R therapy. ‡ Viral relapse rates are calculated with a denominator of subjects with HCV RNA not detected at EOT and with at least 1 follow-up HCV RNA assessment. *Virologic cure (SVR12) was defined as sustained virologic response 12 weeks after actual (OPTIMIST-1) or planned (COSMOS) end of treatment (EOT). ‡ Viral relapse rates are calculated with a denominator of subjects with undetectable (or unconfirmed detectable) HCV RNA at EOT. In addition to five subjects with viral relapse, one subject failed to achieve SVR12 due to missing SVR12 data. No subjects experienced ontreatment virologic failure. SELECT SAFETY INFORMATION Serious Symptomatic Bradycardia When Coadministered With Sofosbuvir and Amiodarone: Postmarketing cases of symptomatic bradycardia and cases requiring pacemaker intervention have been reported when amiodarone was coadministered with a sofosbuvir containing regimen. A fatal cardiac arrest was reported in a patient taking amiodarone who was coadministered a sofosbuvircontaining regimen (ledipasvir/sofosbuvir). Bradycardia has generally occurred within hours to days, but cases have been observed up to 2 weeks after initiating HCV treatment. Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease, may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. Bradycardia generally resolved after discontinuation of HCV treatment. The mechanism for this effect is unknown. Coadministration of amiodarone with OLYSIO® in combination with sofosbuvir is not recommended. For patients taking amiodarone who have no other alternative treatment options, and who will be coadministered OLYSIO® and sofosbuvir: Counsel patients about the risk of serious symptomatic bradycardia. Cardiac monitoring in an in-patient setting for the first 48 hours of coadministration is recommended, after which outpatient or selfmonitoring of the heart rate should occur on a daily basis through at least the first 2 weeks of treatment. 4 Please see additional Important Safety Information on the following pages and full Prescribing Information, including Boxed Warning and Patient Information by visiting www.olysio.com. Serious Symptomatic Bradycardia When Coadministered With Sofosbuvir and Amiodarone (cont’d): Patients who are taking sofosbuvir in combination with OLYSIO® who need to start amiodarone therapy due to no other alternative treatment options should undergo similar cardiac monitoring as outlined above. Due to amiodarone’s long elimination half-life, patients discontinuing amiodarone just prior to starting sofosbuvir in combination with OLYSIO® should also undergo similar cardiac monitoring as outlined above. Patients who develop signs or symptoms of bradycardia should seek medical evaluation immediately. Symptoms may include near-fainting or fainting, dizziness or lightheadedness, malaise, weakness, excessive tiredness, shortness of breath, chest pain, confusion, or memory problems. Hepatic Decompensation and Hepatic Failure: Hepatic decompensation and hepatic failure, including fatal cases, have been reported postmarketing in patients treated with OLYSIO® in combination with Peg-IFN-alfa and RBV or in combination with sofosbuvir. Most cases were reported in patients with advanced and/or decompensated cirrhosis who are at increased risk for hepatic decompensation or hepatic failure. Because these events have been reported voluntarily during clinical practice, estimates of frequency cannot be made, and a causal relationship between treatment with OLYSIO® and these events has not been established. 5 OLYSIO® Safety Information OLYSIO® Drug-Drug Interactions (DDIs) DDIs of clinical relevance Adverse Events (all Grades) that Occurred ≥10% Frequency Among Subjects Receiving 12 or 24 Weeks of OLYSIO® in Combination with Sofosbuvir 12 Weeks OLYSIO® + Sofosbuvir (N=286)* 24 Weeks OLYSIO® + Sofosbuvir (N=31) † % (n) % (n) Headache 17 (49) 23 (7) Fatigue 16 (47) 32 (10) Nausea 14 (40) 13 (4) Rash (including photosensitivity) 12 (34) 16 (5) Diarrhea 6 (18) 16 (5) Dizziness 3 (10) 16 (5) *The 12 week group represents subjects pooled from COSMOS, OPTIMIST-1, and OPTIMIST-2 trials. †The 24 week group represents subjects from COSMOS trial. Laboratory Abnormalities Among subjects who received OLYSIO in combination with sofosbuvir, the most common Grade 3 and 4 laboratory abnormalities were amylase and lipase elevations. Most elevations in amylase and lipase were transient and of mild or moderate severity. Amylase and lipase elevations were not associated with pancreatitis. Please see Full Safety Section (www.olysio.com/hcp/safety-profile/side-effects) for more details. NNRTIs=non-nucleoside reverse-transcriptase inhibitors; NRTIs=nucleoside reverse-transcriptase inhibitors. These interactions have been studied in healthy adults with the recommended dose of OLYSIO® 150 mg once daily unless otherwise noted. § The dose of OLYSIO® in this interaction study was 200 mg once daily, both when given alone and when coadministered with rifampin 600 mg once daily. || The interaction between simeprevir and ledipasvir was evaluated in a pharmacokinetic study in HCV-infected patients by comparing simeprevir exposure following simeprevir + 90/400 mg ledipasvir/sofosbuvir dosing versus simeprevir + 400 mg sofosbuvir dosing and by comparing ledipasvir exposure following simeprevir + 90/400 mg ledipasvir/sofosbuvir dosing versus 90/400 mg ledipasvir/sofosbuvir dosing. ¶ The dose of OLYSIO® in this interaction study was 50 mg once daily when coadministered in combination with darunavir/ritonavir, compared with 150 mg once daily in the OLYSIO®-alone treatment group. # The dose of OLYSIO® in this interaction study was 200 mg once daily, both when given alone and coadministered in combination with ritonavir 100 mg given twice daily. **Studied in combination with daclatasvir and RBV in a Phase 2 trial in HCV-infected post-liver transplant patients. ‡ SELECT SAFETY INFORMATION Hepatic Decompensation and Hepatic Failure (cont’d): OLYSIO® is not recommended for patients with moderate or severe hepatic impairment (Child-Pugh B or C). In clinical trials of OLYSIO®, modest increases in bilirubin levels were observed without impacting hepatic function. Postmarketing cases of hepatic decompensation with markedly elevated bilirubin levels have been reported. Monitor liver chemistry tests before and as clinically indicated during OLYSIO® combination therapy. Patients who experience an increase in total bilirubin to greater than 2.5 times the upper limit of normal should be closely monitored: Patients should be instructed to contact their healthcare provider if they have onset of fatigue, weakness, lack of appetite, nausea and vomiting, jaundice, or discolored feces. Discontinue OLYSIO® if elevation in bilirubin is accompanied by liver transaminase increases or clinical signs and symptoms of hepatic decompensation. 6 Please see additional Important Safety Information on the following pages and full Prescribing Information, including Boxed Warning and Patient Information by visiting www.olysio.com. Coadministration of OLYSIO® with substances that are moderate or strong inducers or inhibitors of cytochrome P450 3A (CYP3A) is not recommended, as this may lead to significantly lower or higher exposure of OLYSIO®, respectively, which may result in loss of virologic response or result in serious adverse reactions. The following drugs are not recommended to be coadministered with OLYSIO® Anti-infectives Antibiotics (systemic administration): erythromycin,‡ clarithromycin, telithromycin; antifungals (systemic administration): itraconazole, ketoconazole, posaconazole, fluconazole, voriconazole; antimycobacterials§: rifampin,‡§ rifabutin, rifapentine HCV products Ledipasvir|| HIV products Cobicistat-containing products; NNRTI: efavirenz‡; other NNRTIs: delavirdine, etravirine, nevirapine; PI: darunavir/ ritonavir‡¶, ritonavir‡#; other HIV products (boosted or unboosted): atazanavir, fosamprenavir, lopinavir, indinavir, nelfinavir, saquinavir, tipranavir Antiarrhythmics Amiodarone (coadministered with sofosbuvir) Herbal products Milk thistle, St. John’s Wort Other drugs Anticonvulsants: carbamazepine, oxcarbazepine, phenobarbital, phenytoin; dexamethasone (systemic); cisapride; cyclosporine‡** The following require caution and/or clinical monitoring when coadministered with OLYSIO® Cardiovascular agents Digoxin‡; antiarrhythmics (oral administration) ( drugs): amiodarone (coadministered without sofosbuvir), disopyramide, flecainide, mexiletine, propafenone, quinidine; calcium channel blockers (oral administration) ( drugs): amlodipine, diltiazem, felodipine, nicardipine, nifedipine, nisoldipine, verapamil; statins ( drugs): pitavastatin, pravastatin, rosuvastatin,‡ atorvastatin,‡ simvastatin,‡ lovastatin, fluvastatin Immunosuppressants or sirolimus Other drugs Phosphodiesterase type 5 inhibitors for pulmonary arterial hypertension ( drugs): sildenafil, tadalafil, vardenafil; midazolam,‡ triazolam ( drugs; oral administration) No expected clinically relevant DDIs Interactions between OLYSIO® and the following drugs were evaluated in clinical studies.‡ No dose adjustments are needed for either drug Caffeine, daclatasvir, dextromethorphan, escitalopram, ethinyl estradiol/norethindrone, methadone, midazolam (intravenous administration), omeprazole, raltegravir, rilpivirine, sofosbuvir, tacrolimus, tenofovir disoproxil fumarate, warfarin No clinically relevant drug interactions expected when OLYSIO® is coadministered with Antacids, azithromycin, bedaquiline, corticosteroids (budesonide, fluticasone, methylprednisolone, and prednisone), dolutegravir, H2-receptor antagonists, narcotic analgesics (buprenorphine and naloxone), NRTIs (eg, abacavir, didanosine, emtricitabine, lamivudine, stavudine, zidovudine), maraviroc, methylphenidate, proton pump inhibitors 7 IMPORTANT SAFETY INFORMATION WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN PATIENTS COINFECTED WITH HCV AND HBV Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with OLYSIO®. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct-acting antivirals and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and posttreatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated. Contraindications: Because OLYSIO® is used only in combination with other antiviral drugs (including Peg-IFN-alfa and RBV) for the treatment of chronic HCV infection, the contraindications to other drugs also apply to the combination regimen. Refer to the respective prescribing information for a list of contraindications. Warnings and Precautions: Risk of Hepatitis B Virus Reactivation in Patients Coinfected With HCV and HBV: HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct-acting antivirals and who were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive and also in patients with serologic evidence of resolved HBV infection (i.e., HBsAg negative and anti-HBc positive). HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. HBV reactivation is characterized as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA level. In patients with resolved HBV infection, reappearance of HBsAg can occur. Reactivation of HBV replication may be accompanied by hepatitis; i.e., increases in aminotransferase levels and, in severe cases, increases in bilirubin levels, liver failure, and death can occur. Test all patients for evidence of current or prior HBV infection by measuring HBsAg and anti-HBc before initiating HCV treatment with OLYSIO®. In patients with serologic evidence of HBV infection, monitor for clinical and laboratory signs of hepatitis flare or HBV reactivation during HCV treatment with OLYSIO® and during posttreatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated. Serious Symptomatic Bradycardia When Coadministered With Sofosbuvir and Amiodarone: Postmarketing cases of symptomatic bradycardia and cases requiring pacemaker intervention have been reported when amiodarone was coadministered with a sofosbuvir containing regimen. A fatal cardiac arrest was reported in a patient taking amiodarone who was coadministered a sofosbuvir-containing regimen (ledipasvir/ sofosbuvir). Bradycardia has generally occurred within hours to days, but cases have been observed up to 2 weeks after initiating HCV treatment. Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease, may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. Bradycardia generally resolved after discontinuation of HCV treatment. The mechanism for this effect is unknown. Coadministration of amiodarone with OLYSIO® in combination with sofosbuvir is not recommended. For patients taking amiodarone who have no other alternative treatment options, and who will be coadministered OLYSIO® and sofosbuvir: Counsel patients about the risk of serious symptomatic bradycardia. Cardiac monitoring in an in-patient setting for the first 48 hours of coadministration is recommended, after which outpatient or selfmonitoring of the heart rate should occur on a daily basis through at least the first 2 weeks of treatment. Patients who are taking sofosbuvir in combination with OLYSIO® who need to start amiodarone therapy due to no other alternative treatment options should undergo similar cardiac monitoring as outlined above. Due to amiodarone’s long elimination half-life, patients discontinuing amiodarone just prior to starting sofosbuvir in combination with OLYSIO® should also undergo similar cardiac monitoring as outlined above. Patients who develop signs or symptoms of bradycardia should seek medical evaluation immediately. Symptoms may include near-fainting or fainting, dizziness or lightheadedness, malaise, weakness, excessive tiredness, shortness of breath, chest pain, confusion, or memory problems. Hepatic Decompensation and Hepatic Failure: Hepatic decompensation and hepatic failure, including fatal cases, have been reported postmarketing in patients treated with OLYSIO® in combination with Peg-IFN-alfa and RBV or in combination with sofosbuvir. Most cases were reported in patients with advanced and/or decompensated cirrhosis who are at increased risk for hepatic decompensation or hepatic failure. Because these events have been reported voluntarily during clinical practice, estimates of frequency cannot be made, and a causal relationship between treatment with OLYSIO® and these events has not been established. OLYSIO® is not recommended for patients with moderate or severe hepatic impairment (Child-Pugh B or C). In clinical trials of OLYSIO®, modest increases in bilirubin levels were observed without impacting hepatic function. Postmarketing cases of hepatic decompensation with markedly elevated bilirubin levels have been reported. Monitor liver chemistry tests before and as clinically indicated during OLYSIO® combination therapy. Patients who experience an increase in total bilirubin to greater than 2.5 times the upper limit of normal should be closely monitored: 8 Risk of Serious Adverse Reactions Associated With Combination Treatment: Because OLYSIO® is used in combination with other antiviral drugs for the treatment of chronic HCV infection, consult the prescribing information for these drugs before starting therapy with OLYSIO®. Warnings and precautions related to these drugs also apply to their use in OLYSIO® combination treatment. Photosensitivity: Photosensitivity reactions have been observed with OLYSIO® combination therapy. Serious photosensitivity reactions resulting in hospitalization have been observed with OLYSIO® in combination with Peg-IFN-alfa and RBV. Photosensitivity reactions occurred most frequently in the first 4 weeks of treatment, but can occur at any time during treatment. Photosensitivity may present as an exaggerated sunburn reaction, usually affecting areas exposed to light (typically the face, “V” area of the neck, extensor surfaces of the forearms, and dorsa of the hands). Manifestations may include burning, erythema, exudation, blistering, and edema. Use sun protective measures and limit sun exposure during treatment with OLYSIO®. Avoid use of tanning devices during treatment with OLYSIO®. Discontinuation of OLYSIO® should be considered if a photosensitivity reaction occurs and patients should be monitored until the reaction has resolved. If a decision is made to continue OLYSIO® in the setting of a photosensitivity reaction, expert consultation is advised. Rash: Rash has been observed with OLYSIO® combination therapy. Rash occurred most frequently in the first 4 weeks of treatment, but can occur at any time during treatment. Severe rash and rash requiring discontinuation of OLYSIO® have been reported in subjects receiving OLYSIO® in combination with Peg-IFN-alfa and RBV. Most of the rash events in OLYSIO®-treated patients were of mild or moderate severity. Patients with mild to moderate rashes should be followed for possible progression of rash, including the development of mucosal signs (e.g., oral lesions, conjunctivitis) or systemic symptoms. If the rash becomes severe, OLYSIO® should be discontinued. Patients should be monitored until the rash has resolved. Sulfa Allergy: OLYSIO® contains a sulfonamide moiety. In subjects with a history of sulfa allergy (n=16), no increased incidence of rash or photosensitivity reactions has been observed. However, there are insufficient data to exclude an association between sulfa allergy and the frequency or severity of adverse reactions observed with the use of OLYSIO®. Risk of Adverse Reactions or Reduced Therapeutic Effect Due to Drug Interactions: Coadministration of OLYSIO® with substances that are moderate or strong inducers or inhibitors of cytochrome P450 3A (CYP3A) is not recommended as this may lead to significantly lower or higher exposure of simeprevir, respectively, which may result in reduced therapeutic effect or adverse reactions. The potential for drug-drug interactions must be considered prior to and during treatment. Adverse Reactions: Use With Sofosbuvir: The most common (all grades, ≥10%) adverse events reported during 12 or 24 weeks of treatment with OLYSIO® in combination with sofosbuvir were headache (17% and 23%), fatigue (16% and 32%), nausea (14% and 13%), rash (including photosensitivity) (12% and 16%), diarrhea (6% and 16%), and dizziness (3% and 16%), respectively. Use With Peg-IFN-alfa and RBV: Adverse reactions (all grades, ≥3% higher frequency) for OLYSIO® with Peg-IFN-alfa and RBV vs. Peg-IFNalfa and RBV alone during the first 12 weeks of treatment were rash (including photosensitivity) (28% vs. 20%), pruritus (22% vs. 15%), nausea (22% vs. 18%), myalgia (16% vs. 13%), and dyspnea (12% vs. 8%). Use in Specific Populations: Pregnancy: If OLYSIO® is administered with RBV, the combination regimen is contraindicated in pregnant women and in men whose female partners are pregnant. Refer to prescribing information for RBV and for other drugs used in combination with OLYSIO® for information on use in pregnancy. No adequate human data are available to establish whether or not OLYSIO® poses a risk to pregnancy outcomes. Pregnant women should be advised of potential risk to the fetus. Race: Patients of East Asian ancestry exhibit higher plasma simeprevir exposures, but no dosage adjustment is required based on race. Renal Impairment: No dosage adjustment of OLYSIO® is required in patients with mild, moderate, or severe renal impairment. The safety and efficacy of OLYSIO® have not been studied in HCV-infected patients with severe renal impairment (creatinine clearance below 30 mL/min) or end-stage renal disease, including patients requiring dialysis. Simeprevir is highly protein-bound; therefore, dialysis is unlikely to result in significant removal of simeprevir. Hepatic Impairment: No dosage adjustment of OLYSIO® is required in patients with mild hepatic impairment (Child-Pugh A). Simeprevir exposures are increased in patients with moderate or severe hepatic impairment (Child-Pugh B or C). In clinical trials of OLYSIO® in combination with Peg-IFN-alfa and RBV, higher simeprevir exposures were associated with increased frequency of adverse reactions, including increased bilirubin, rash, and photosensitivity. There have been postmarketing reports of hepatic decompensation, hepatic failure, and death in patients with advanced or decompensated cirrhosis receiving OLYSIO® combination therapy. The safety and efficacy of OLYSIO® have not been studied in liver transplant patients. Patients should be instructed to contact their healthcare provider if they have onset of fatigue, weakness, lack of appetite, nausea and vomiting, jaundice, or discolored feces. Not a complete list of Uses in Specific Populations. Consult the PI for Peg-IFN-alfa and RBV or sofosbuvir before starting your patients on therapy with OLYSIO®. Safety information related to these drugs also applies to their use in OLYSIO® combination treatment. Please see full Prescribing Information, including Boxed Warning, and Patient Information for more details. Discontinue OLYSIO® if elevation in bilirubin is accompanied by liver transaminase increases or clinical signs and symptoms of hepatic decompensation. 041676-170517 9 Throughout their OLYSIO® treatment Journey The OLYSIO® Support program The OLYSIO® Savings Program: Your commercially eligible patients pay no more than $5 per fill –Subject to a $50,000 annual maximum benefit or 12 months from the card activation date, whichever comes first. Not valid for patients enrolled in Medicare, including Medicare Part D, or Medicaid. Other restrictions apply Visit OLYSIO.com for more helpful resources for you and your patients Encourage your patients to enroll OLYSIO.com 1-855-5-OLYSIO Patients with chronic hepatitis C virus (HCV) infection have individual needs. When appropriate, consider OLYSIO®. SELECT SAFETY INFORMATION Risk of Serious Adverse Reactions Associated With Combination Treatment: Because OLYSIO® is used in combination with other antiviral drugs for the treatment of chronic HCV infection, consult the prescribing information for these drugs before starting therapy with OLYSIO®. Warnings and precautions related to these drugs also apply to their use in OLYSIO® combination treatment. References: 1. HARVONI® [prescribing information]. Foster City, CA: Gilead Sciences, Inc.; 2015. 2. REBETOL® [prescribing information]. Whitehouse Station, NJ: Merck & Co., Inc.; 2013. 3. EPCLUSA® [prescribing information]. Foster City, CA: Gilead Sciences, Inc.; 2016. 4. VIEKIRA PAK® [prescribing information]. North Chicago, IL: AbbVie Inc.; 2015. 5. ZEPATIER™ [prescribing information]. Whitehouse Station, NJ: Merck & Co., Inc.; 2016. 6. DAKLINZA™ [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company; 2016. 7. Data on file. Janssen Therapeutics, Division of Janssen Products, LP. All third-party trademarks are the property of their respective owners. Janssen Therapeutics Division of Janssen Products, LP © Janssen Therapeutics, Division of Janssen Products, LP 2017 June 2017 040283-170526 Test for Resistance HCV resistance tests can help identify appropriate treatment Test detects mutations and interprets the HCV strain resistance (highlighted in red) or sensitivity (highlighted in green). All observed mutations are summarized. Disclaimer: These are adapted sample forms from Monogram Biosciences, Inc., and are not actual reports. Please consult Monogram Biosciences, Inc., if you have any questions about these tests. HCV resistance tests for GT1 are offered by major laboratory companies1-3 NS3/4A COMPANY TEST NAME Monogram Biosciences, Inc., A LabCorp Company HCV GenoSure® NS3/4A NS5A NS5B Quest Diagnostics™ Monogram Biosciences, Inc., A LabCorp Company Quest Diagnostics™ Monogram Biosciences, Inc., A LabCorp Company Quest Diagnostics™ Hepatitis C Viral RNA NS3 Genotype HCV NS5A Drug Resistance Assay Hepatitis C Viral RNA NS5A Drug Resistance HCV NS5B Drug Resistance Assay Hepatitis C Viral RNA NS5B Drug Resistance CPT CODE 87900; 87902 87902 87900; 87902 87902 87900; 87902 87902 TEST NUMBER C5000; 550540 90924 or 90924X (depending on location) C6200; 550325 92447X C6300; 550505 92204X CONTACT INFORMATION ADDITIONAL INFORMATION Monogram Biosciences, Inc.: 1-800-777-0177 Quest Diagnostics™: 1-866-697-8378 Monogram Biosciences, Inc. (Gateway coverage) benefit verification & patient assistance: 1-877-436-6243 Quest Diagnostics™ patient assistance: 1-866-697-8378 or the local Quest Diagnostics™ office References: 1. Monogram Biosciences, Inc. HCV Test Codes. www.monogrambio.com/hepatitis-tests/hcv-test-codes. Accessed March 28, 2016. 2. LabCorp HCV Specimen Collection Guide. http://www.labcorp.com/.EdosPortlet/TestMenuLibrary?libName=File+Library&compName=L12160. Accessed March 28, 2016. 3. Quest Diagnostics. Test Center. www.questdiagnostics.com/testcenter/TestCenterHome.action. Accessed March 28, 2016. Please see additional Important Safety Information on the following pages and full Prescribing Information, including Boxed Warning and Patient Information by visiting www.olysio.com. Janssen Therapeutics Division of Janssen Products, LP © Janssen Therapeutics, Division of Janssen Products, LP 2017 June 2017 040283-170526