Olysio

Treatment with OLYSIO should be initiated and monitored by a physician experienced in the management of CHC. Posology The recommended dosage of OLYSIO is one capsule of 150 mg once daily, taken with food. 1). 4). Refer also to the Summary of Product Characteristics of the medicinal products that are used in combination with OLYSIO.

4). 2 The daily dose of ribavirin is weight based (< 75 kg = 1,000 mg and ≥ 75 kg = 1,200 mg) and administered orally in two divided doses with food; also refer to the Summary of Product Characteristics of ribavirin.

Table 2:

Recommended treatment duration for OLYSIO combination therapy with peginterferon alfa and ribavirin1 in HCV genotype 1 or 4 Patient population Treatment duration Treatment-naïve and prior relapse patients2 with or without cirrhosis, who are not co-infected with HIV 24 weeks3 Treatment with OLYSIO must be initiated in combination with peginterferon alfa + ribavirin and administered for 12 weeks and then followed by an additional 12 weeks of peginterferon alfa + ribavirin.

without cirrhosis, who are co-infected with HIV with cirrhosis, who are co-infected with HIV 48 weeks3 Treatment with OLYSIO must be initiated in combination with peginterferon alfa + ribavirin and administered for 12 weeks and then followed by an additional 36 weeks of peginterferon alfa and + ribavirin.

Prior non-responder patients (including partial and null responders)2 with or without cirrhosis, with or without HIV co-infection 48 weeks3 Treatment with OLYSIO must be initiated in combination with peginterferon alfa + ribavirin and administered for 12 weeks and then followed by an additional 36 weeks of peginterferon alfa + ribavirin.

4). 1). 3 Recommended duration of treatment provided that patient does not meet a stopping rule (see table 3). Refer to table 3 for treatment stopping rules based on HCV RNA levels at weeks 4, 12 and 24 for patients receiving treatment with OLYSIO, peginterferon alfa and ribavirin.

Treatment discontinuation in patients with inadequate on-treatment virologic response OLYSIO in combination with sofosbuvir There are no virologic treatment stopping rules that apply to the combination of OLYSIO with sofosbuvir. , treatment stopping rules) are presented in table 3.

Summary of the safety profile The overall safety profile of simeprevir is based on data from 580 HCV genotype 1 infected patients who received simeprevir in combination with sofosbuvir with or without ribavirin (pooled data from the clinical phase 2 study HPC2002 and the clinical phase 3 studies HPC3017 and HPC3018) and 1,486 HCV genotype 1 infected patients who received simeprevir (or placebo) in combination with peginterferon alfa and ribavirin (pooled data from the clinical phase 2 studies C205 and C206 and the clinical phase 3 studies C208, C216 and HPC3007).

Medicinal product no longer authorised 18 Simeprevir in combination with sofosbuvir The safety profile of simeprevir in combination with sofosbuvir in patients with HCV genotype 1 infection with or without cirrhosis is based on pooled data from the phase 2 study HPC2002 and the phase 3 studies HPC3017 and HPC3018 which included 472 patients who received simeprevir with sofosbuvir without ribavirin (155, 286 and 31 patients received 8, 12 or 24 weeks of treatment, respectively) and 108 patients who received simeprevir with sofosbuvir and ribavirin (54 patients each received 12 or 24 weeks of treatment).

The majority of the adverse reactions reported were grade 1 in severity. 3% (n = 1) of patients, respectively, receiving 12 weeks simeprevir with sofosbuvir; no grade 4 adverse reactions were reported. 2%) experienced a grade 4 adverse reaction (‘blood bilirubin increased’).

No serious adverse reactions were reported. 4). 3%) and none of the patients in the 24-week treatment group discontinued treatment due to adverse reactions. Simeprevir in combination with peginterferon alfa and ribavirin The safety profile of simeprevir in combination with peginterferon alfa and ribavirin in patients with HCV genotype 1 infection is based on the pooled data from the phase 2 studies and phase 3 studies C205, C206, C208, C216 and HPC3007 which included 924 patients who received simeprevir 150 mg once daily for 12 weeks and 540 patients who received placebo with peginterferon alfa and ribavirin.

1). OLYSIO must not be administered as monotherapy and must be prescribed in combination with other medicinal products for the treatment of CHC. Consult the Summary of Product Characteristics of the co-prescribed medicinal products before starting therapy with OLYSIO.

Warnings and precautions related to these medicinal products also apply to their use in OLYSIO combination treatment. 3). Hepatic decompensation and hepatic failure Hepatic decompensation and hepatic failure, including fatal cases, have been reported post-marketing in patients treated with OLYSIO in combination with peginterferon alfa and ribavirin and in combination with sofosbuvir.

Medicinal product no longer authorised 6 Therefore, in patients who are at high risk for hepatic decompensation or hepatic failure, liver function tests should be monitored before and as clinically indicated during OLYSIO combination therapy.

2). Severe bradycardia and heart block Cases of bradycardia have been observed when OLYSIO is used in combination with sofosbuvir and concomitant amiodarone. The mechanism is not established. Cases are potentially life threatening, therefore amiodarone should only be used in patients on OLYSIO combination treatment with sofosbuvir when other alternative antiarrhythmic treatments are not tolerated or are contraindicated.

Should concomitant use of amiodarone be considered necessary, it is recommended that patients are closely monitored when initiating OLYSIO combination treatment with sofosbuvir. Patients who are identified as being at high risk of bradyarrhythmia should be continuously monitored for 48 hours in an appropriate clinical setting.

Due to the long elimination half-life of amiodarone, appropriate monitoring should also be carried out for patients who have discontinued amiodarone within the past few months and are to be initiated on OLYSIO combination treatment with sofosbuvir.

1.