The Heptitis C tretment lndscpe is chnging in Pkistn 01
A new dwn hs emerged in ccess to HCV Cure Ferozsons is herlding the chnge in the Heptitis C lndscpe of Pkistn In prtnership with Giled Sciences, Ferozsons mde the Brekthrough ll-orl Heptitis C tretment Sovldi ville to ptients in Pkistn in August 201, within months of its pprovl y FDA in the United Sttes. Pkistn ecme the first country in the world where ptients egn to receive Sovldi tretment t frction of the interntionl cost under specil Access Progrm. Over 50,000 Heptitis C ptients enefited from tretment nd ccess to cure within yer of vilility. Mny more ptients re in need of more ffordle yet qulity-ssured tretment. Introducing A new dwn in ccess to HCV Cure in Pkistn The first uthorized generic of Sofosuvir produced in Pkistn under license from Giled Sciences. In n exemplry prtnership to ring rekthrough medicl tretments to the ptients of Pkistn, we re committed to expnding ccess to cure in criticl diseses t ll levels. 02 03
INDICATION: 1 Cure for All Sofosuvir (SAVERA) is heptitis C virus (HCV) nucleotide nlog NS5B polymerse inhiitor indicted for the tretment of chronic heptitis C (CHC) s component of comintion ntivirl tretment regimen. Sofosuvir (SAVERA) efficcy hs een estlished in sujects with HCV genotype 1, 2, 3,, 5 or 6 infection, including those with heptocellulr crcinom meeting Miln criteri (witing liver trnsplnttion) nd those with HCV/HIV-1 co-infection PRESCRIBING CONSIDERATIONS: 1 Monotherpy of Sofosuvir (SAVERA) is not recommended. Tretment regimen nd durtion re dependent on oth virl genotype nd ptient popultion. Tretment response vries sed on seline host nd virl fctors. References: 1. Sofosuvir Summry of Product Chrcteristics (Europe) http://www.em.europ.eu/docs/en_gb/document_lirry/epar_-_product_ Informtion/humn/002798/WC500160597.pdf 0 05
The first ll-orl, IFN-free regimen for HCV GT 3 ptients 1 In VALENCE, Sofosuvir + Rivirin delivered high cure (SVR) rtes in tretmentnïve nd experienced GT 3 sujects 1, Percent (%) Sujects 100 80 60 0 20 0 % SVR in GT 3 tretment-nïve nd tretmentexperienced sujects in VALENCE 1 8% Overll SVR 93% Tretment-nïve Sustined virologic response (SVR) ws the primry endpoint, which ws defined s HCV RNA <25 IU per ml t weeks fter the end of tretment. 1 Achieving SVR is considered virologic cure. 2 Cirrhosis ws defined s ny one of the following: liver-iopsy smple showing cirrhosis; trnsient elstogrphy (FiroScn ) showing cirrhosis or liver stiffness of more thn.5 kp; serum FiroTest score of more thn 0.75 (on scle of 0 to 1) plus rtio of sprtte minotrnsferse to pltelets of more thn 2 during screening. 3 n=250 n=105 77% n=15 Tretment-experienced GT 3 sujects with compensted cirrhosis in VALENCE chieved SVR with n ll-orl regimen of Sofosuvir + Rivirin 1, Percent (%) Sujects 100 80 60 0 20 0 67% n=58 Overll SVR % SVR in GT 3 sujects with compensted cirrhosis in VALENCE 1 92% Tretment-nïve References: 1. Sofosuvir Summry of Product Chrcteristics (Europe) http://www.em.europ.eu/docs/en_gb/document_lirry/epar_-_product_ Informtion/humn/002798/WC500160597.pdf 2. Ghny MG, Nelson DR, Strder DB, Thoms DL, Seeff LB. An updte on tretment of genotype 1 chronic heptitis C virus infection: 2011 prctice guideline y the Americn Assocition for the Study of Liver Diseses. Heptology. 2011;5:133-1. doi:10.1002/ hep.261. 3. Lwitz E, Mngi A, Wyles D, Rodriguez-Torres M, et l. Sofosuvir for previously untreted chronic heptitis C infection. N Engl J Med. 2013;368(20):1878-1887. n=13 60% n=5 Tretment-experienced Ptients witing liver trnsplnttion: study design 1, Sofosuvir + Rivirin Week 0 61 sujects dignosed with heptocellulr crcinom (HCC) witing liver trnsplnttion received Sofosuvir + Rivirin for up to 8 weeks to prevent post-trnsplnt HCV reinfection 1 Of these 61 sujects, 1 underwent liver trnsplnttion, with 37 hving HCV RNA <LLOQ t time of trnsplnttion 1 A single-rm, open-lel clinicl study in liver trnsplnttion cndidtes with HCV nd HCC meeting Miln criteri (n=61) 1,, Time of trnsplnt (2-8 weeks or until liver trnsplnttion, whichever occurred first) Study included HCV-infected sujects, regrdless of genotype, with HCC meeting the Miln criteri (defined s the presence of tumor 5 cm or less in dimeter in ptients with single HCCs [heptocellulr crcinoms] nd no more thn 3 tumor nodules, ech 3 cm or less in dimeter in ptients with multiple tumors nd no extrheptic mnifesttions of the cncer or evidence of vsculr invsion of tumor). 5 sujects hd HCV genotype 1; sujects hd seline CPT score less thn 7; nd ll sujects hd seline undjusted MELD score 1. 1 Sujects received 00 mg Sofosuvir nd weight sed 1000-00 mg RBV dily for 2-8 weeks or until the time of liver trnsplnttion, whichever occurred first. 1 ptvr = post-trnsplnt virologic response, defined s HCV RNA <LLOQ t weeks post-trnsplnt. References: 1. Sofosuvir Summry of Product Chrcteristics (Europe) http://www.em.europ.eu/docs/en_gb/document_lirry/epar_-_product_ Informtion/humn/002798/WC500160597.pdf. Curry MP, Forns X, Chung R, Terrult N, et l. Pretrnsplnt Sofosuvir nd Rivirin to Prevent Recurrence of HCV Infection After Liver Trnsplnttion. Astrct presented t: 6th Annul Meeting of the Americn Assocition for the Study of Liver Diseses (AASLD); Novemer 1 5, 2013; Wshington, DC. Assess ptvr Primry endpoint Sofosuvir + Rivirin ws effective in HCC sujects witing liver trnsplnttion to prevent post-trnsplnt reinfection 1 Percent (%) Sujects 100 80 60 0 20 0 % ptvr in HCV-infected sujects with HCC witing liver trnsplnttion 1 6% Sofosuvir + Rivirin 2-8 weeks or until liver trnsplnttion, whichever occurred first ptvr ws 6% mong the 36 of these 37 sujects who were evlule nd who reched the -week posttrnsplnt time point 1 n=36 06 07
Sofosuvir + Rivirin is the first nd only ll-orl regimen for ptients with HCC meeting the Miln criteri who re witing liver trnsplnttion to prevent post-trnsplnt reinfection 1 In ptients with heptocellulr crcinom (HCC) witing liver trnsplnttion, Sofosuvir in comintion with rivirin is recommended until the time of liver trnsplnttion. 1 Sofosuvir in comintion in Rivirin is recommended for 2 weeks in liver trnsplnt reciepient lso. 1 No response-guided therpy is required with Sofosuvir. 1 Recommended regimen nd tretment durtion for Sofosuvir comintion therpy in HCV-infected ptients with HCC witing liver trnsplnt 1 Tretment Regimen All Orl: Sofosuvir 00 mg + Rivirin Durtion until liver trnsplnttion Sofosuvir regimens hd low discontinution rtes cross clinicl trils in HCV mono-infected sujects 1 Discontinution rtes due to AEs y regimen cross five Phse 3 Sofosuvir clinicl trils 1 2% 1% <1% % Sofosuvir + Peg-IFN + Rivirin ( weeks) N=327 Sofosuvir + Rivirin ( weeks) N=650 Rivirin dose is weight-sed (<75 kg = 1000 mg; 75 kg = 00 mg), dministered dily in two divided doses tken orlly with food. Ptients with renl impirment (CrCl 50 ml/min) require Rivirin dose reduction; refer to Rivirin prescriing informtion. 1 Sujects received weight-sed Rivirin (1000 mg per dy if weighing <75 kg or 00 mg per dy if weighing 75 kg). n=13 Sofosuvir + Rivirin N=250 GT 1,, 5 nd 6 GT 2 nd 3 Plceo ( weeks) N=71 11% Peg-IFN + Rivirin c N=23 In BOSON, Sofosuvir + Peginterferon/Rivirin for weeks delivered high cure rte (SVR) in genotype 3 HCV infected ptients including tretment-experienced cirrhotic ptients 5 In GT3 ptients, including lrge proportion of tretmentexperienced ptients with cirrhosis, Sofosuvir + Peginterferon/Rivirin for weeks resulted in the highest SVR rtes oserved to dte in Phse 3 study. GT3 ptients receiving 2 weeks of Sofosuvir + Rivirin hd higher SVR rtes thn those receiving 16 weeks of tretment, confirming tht 2 weeks is the optiml durtion for this comintion in GT3 ptients. Sofosuvir + Peginterferon/ Rivirin for weeks ws well tolerted with high rte of tretment completion. c Sujects received 800 mg Rivirin per dy regrdless of weight. Reference: 1. Sofosuvir Summry of Product Chrcteristics (Europe) http://www.em.europ.eu/docs/en_gb/document_lirry/epar_-_product_ Informtion/humn/002798/WC500160597.pdf References: 5. Foster G R et l. Sofosuvir + Peginterferon/Rivirin For Weeks vs Sofosuvir + Rivirin for 16 or 2 Weeks in Genotype 3 HCV infected ptients nd tretment-experienced cirrhotic ptients with genotype 2 HCV: The Boson Study. J Heptol. 2015; 62 (N2): S259 S260 08 09
Sofosuvir drug interction profile 1 Sofosuvir is sustrte of intestinl drug trnsporter P-gp Sofosuvir is clered renlly nd is not metolized y the CYP50 pthwy Sofosuvir in comintion with Rivirin for 2 weeks cn e considered for ptients with genotype 1 infection who re Interferon ineligile. Liver Trnsplnt Ptients Sofosuvir in comintion with Rivirin is recommended for 2 weeks in liver trnsplnt recipients. A strting Rivirin dose of 00 mg dministered Concomitnt Drug Clss: Drug Nme Antimycocterils: rifmpin Herl Supplements: St. John s wort Antiretrovirls: tiprnvir/ritonvir Antirrhythmics: miodrone (in comintion with nother DAA) Anticonvulsnts: crmzepine, phenytoin, phenoritl, oxcrzepine Antimycocterils: rifutin, rifpentine Antiretrovirls: drunvir/ritonvir, emtricitine, efvirenz, rltegrvir, rilpivirine, tenofovir disoproxil fumrte Immunosuppressnts: cyclosporine, tcrolimus Should not e used with Sofosuvir orlly in two divided doses with food is recommended. If the strting dose of Rivirin is well-tolerted, the dose cn e titrted up to mximum of 1,000-1,200 mg dily. Sofosuvir use with select medictions 1, Codministrtion with Sofosuvir not recommended No cliniclly significnt interction with Sofosuvir c Opioids: methdone Sofosuvir offers simple dosing for ptients with HCV genotypes 1, 2, 3,, 5 & 6 1 This informtion is not ll-inclusive. Decrese in concentrtion of Sofosuvir, leding to reduced therpeutic effect. c No dosge djustment for Sofosuvir or concomitnt medictions is necessry. Recommended regimens nd tretment durtion for comintion therpy in HCV mono-infected nd HCV/HIV-1 co-infected ptients 1 Genotype Tretment Regimen Durtion GT 1,, 5 nd 6 d See Peginterferon Alf prescriing informtion for dosge recommendtion for ptients with genotype 1,, 5 & 6 HCV GT 2 GT 3 GT 3 Ptients with CHC witing liver trnsplnttion Sofosuvir 00 mg + Peg-IFN lf d + Rivirin e weeks f Sofosuvir 00 mg + Peg-IFN lf + Rivirin e Sofosuvir 00 mg + Rivirin e e Dosge of Rivirin is weight-sed (<75 kg = 1000 mg nd 75 kg = 00 mg). The dily dosge of Rivirin is dministered orlly in two divided doses with food. Ptients with renl impirment (CrCl 50 ml/min) require Rivirin dosge reduction; refer to Rivirin prescriing informtion. f Considertion should e given to potentilly extending the durtion of therpy eyond weeks nd up to 2 weeks; especilly for those sugroups who hve one or more fctors historiclly ssocited with lower response rtes to interferon-sed therpies (e.g. dvnced firosis/cirrhosis, high seline virl concentrtions, lck rce, IL28B non CC genotype, prior null response to Peginterferon lf nd Rivirin therpy). g Durtion of dministrtion of Sofosuvir in ptients witing liver trnsplnttion should e guided y n ssessment of the potentil enefits nd risks for the individul ptient. Reference: 1. Sofosuvir Summry of Product Chrcteristics (Europe) http://www.em.europ.eu/docs/en_gb/document_lirry/epar_-_product_ Informtion/humn/002798/WC500160597.pdf All orl: Sofosuvir 00 mg + Rivirine weeks f All orl: 2 Sofosuvir 00 mg + Rivirin e weeks weeks f Until Liver g Trnsplttion 8% SVR for GT3 ptients with Sofosuvir +Rivirin 1,5 93% SVR for GT3 ptients with Sofosuvir +Peginterferon Alf+Rivirin ( weeks) 5 Optiml qulity offered y Ferozsons only Giled licensee in Pkistn Brief Prescriing Informtion SAVERA (Sofosuvir 00mg) is Heptitis C Virus (HCV) nucleotide nlog NS5B polymerse inhiitor indicted for the tretment of Chronic Heptitis C (CHC) infection s component of comintion ntivirl tretment regimen. INDICATIONS AND USAGE: SAVERA (Sofosuvir 00mg) efficcy hs een estlished in sujects with HCV genotype 1, 2, 3,, 5 or 6 infection, including those with heptocellulr crcinom meeting Miln criteri (witing liver trnsplnttion) nd those with HCV/HIV-1 co-infection. DOSAGE AND ADMINISTRATION: One 00 mg tlet tken once dily with or without food. It should e used in comintion with Rivirin or in comintion with Pegylted Interferon nd Rivirin for the tretment of CHC. Recommended comintion therpy for Genotypes 1-6 chronic HCV & HCV/HIV co-infection: GT 1,, 5, 6: Sofosuvir + Peginterferon + Rivirin ( weeks), GT 2: Sofosuvir + Rivirin ( weeks) & GT 3: Sofosuvir + Rivirin or Sofosuvir+Peginterferon+Rivirin ( weeks). GT 1 (interferon ineligile): Sofosuvir + Rivirin & HCC nd witing trnsplnt Ptient: Sofosuvir + Rivirin (up to 8 weeks or until liver trnsplnttion, whichever occurs first.). A dose recommendtion cnnot e mde for ptients with severe renl impirment or end stge renl disese. CONTRAINDICATIONS: When used in comintion with Peginterferon Alf/ Rivirin or Rivirin lone, ll contrindictions to Peginterferon Alf nd/or Rivirin lso pply to SAVERA (Sofosuvir 00mg) comintion therpy. Becuse Rivirin my cuse irth defects nd fetl deth, SAVERA (Sofosuvir 00mg) in comintion with Peginterferon Alf/Rivirin or Rivirin is contrindicted in pregnnt women nd in men whose femle prtners re pregnnt. WARNINGS AND PRECAUTIONS: Brdycrdi with miodrone codministrtion: Serious symptomtic rdycrdi my occur in ptients tking miodrone nd SAVERA (Sofosuvir 00mg) in comintion with nother direct cting ntivirl (DAA), prticulrly in ptients lso receiving et lockers, or those with underlying crdic comoridities nd/or dvnced liver disese. Codministrtion of miodrone with SAVERA (Sofosuvir 00mg) in comintion with nother DAA is not recommended. In ptients without lterntive, vile tretment options, crdic monitoring is recommended. Use with other drugs contining Sofosuvir is not recommended. Rivirin my cuse irth defects nd fetl deth nd niml studies hve shown interferons hve ortifcient effects; void pregnncy in femle ptients nd femle prtners of mle ptients. Ptients must hve negtive pregnncy test prior to inititing therpy, use t lest 2 effective non-hormonl methods of contrception nd hve monthly pregnncy tests. ADVERSE REACTIONS: The most common dverse events (incidence greter thn or equl to 20%, ll grdes) oserved with SAVERA (Sofosuvir 00mg) in comintion with Rivirin were ftigue nd hedche. The most common dverse events oserved with SAVERA (Sofosuvir 00mg) in comintion with Peginterferon Alf nd Rivirin were ftigue, hedche, nuse, insomni nd nemi. DRUG INTERACTIONS: Codministrtion of miodrone with SAVERA (Sofosuvir 00mg) in comintion with nother DAA my result in serious symptomtic rdycrdi. Drugs tht re potent intestinl P-gp inducers (e.g., Rifmpin, St. John s Wort) my lter the concentrtions of Sofosuvir. Consult the full prescriing informtion prior to use for potentil drug-drug interctions. USE IN SPECIFIC POPULATIONS: Sfety nd efficcy hve een studied in Ptients with HCV/HIV-1 co-infection & heptocellulr crcinom witing liver trnsplnttion. HOW SUPPLIED/STORAGE: Store elow 30 C in dry nd drk plce. INSTRUCTIONS: Keep out of the rech of children. To e sold on the prescription of registered medicl prctitioner only. Dispensed only in originl continer. Do not use if sel over ottle opening is roken or missing. PRESENTATION: SAVERA (Sofosuvir 00mg) is ville s lue-colored, olong-shped, film-coted tlets contining 00mg Sofosuvir deossed with f on one side nd plin on other side. Ech white color HDPE ottle contins 28 film-coted tlets, silic gel desiccnt with child resistnce cp. Full Prescriing Informtion ville on request. Reference: 1. Sofosuvir Summry of Product Chrcteristics (Europe) http://www.em.europ.eu/docs/en_gb/document_lirry/epar_-_product_ Informtion/humn/002798/WC500160597.pdf 2. Ghny MG, Nelson DR, Strder DB, Thoms DL, Seeff LB. An updte on tretment of genotype 1 chronic heptitis C virus infection: 2011 prctice guideline y the Americn Assocition for the Study of Liver Diseses. Heptology. 2011;5:133-1. doi:10.1002/ hep.261. 5. Foster G R et l. Sofosuvir + Peginterferon/Rivirin For Weeks vs Sofosuvir + Rivirin for 16 or 2 Weeks in Genotype 3 HCV infected ptients nd tretment-experienced cirrhotic ptients with genotype 2 HCV: The Boson Study. J Heptol. 2015; 62 (N2): S259 S260 10 11
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