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 for 12 weeks, taken with food.
OLYSIO must not be administered as monotherapy. OLYSIO must be used in combination with other medicinal products for the treatment of CHC (see section 5.1). When considering OLYSIO combination treatment with peginterferon alfa and ribavirin in HCV genotype 1a patients, patients should be tested for the presence of virus with the NS3 Q80K polymorphism before starting treatment (see section 4.4).
Refer also to the Summary of Product Characteristics of the medicinal products that are used in combination with OLYSIO.
The recommended co-administered medicinal product(s) and treatment duration for OLYSIO combination therapy are provided in table 1.
Table 1: Recommended co-administered medicinal product(s) and treatment duration for OLYSIO combination therapy
|
Patient population
|
Treatment
|
Duration
|
|
Treatment-naïve and prior relapse patients with HCV genotype 1 or 41
|
OLYSIO + peginterferon alfa + ribavirin2
|
24 weeks3
Treatment with OLYSIO must be initiated in combination with peginterferon alfa and ribavirin and administered for 12 weeks and then followed by an additional 12 weeks of peginterferon alfa and ribavirin.
|
|
Prior non-responder patients (including partial and null responders) with HCV genotype 1 or 41
|
OLYSIO + peginterferon alfa + ribavirin2
|
48 weeks
Treatment with OLYSIO must be initiated in combination with peginterferon alfa and ribavirin and administered for 12 weeks and then followed by an additional 36 weeks of peginterferon alfa and ribavirin.
|
|
Patients with HCV genotype 1 or 4, regardless of prior treatment history4
|
OLYSIO + sofosbuvir
(+/- ribavirin)5
|
12 weeks (see sections 4.4, 4.8 and 5.1)
|
1 Includes patients with or without cirrhosis and those co-infected with human immunodeficiency virus (HIV). Relapse or non-response following prior treatment with interferon (pegylated or non-pegylated), with or without ribavirin (see section 5.1).
2 When considering OLYSIO combination treatment with peginterferon alfa and ribavirin in HCV genotype 1a patients, testing for NS3 Q80K polymorphism should be performed before starting treatment (see section 4.4).
3 Treatment-naïve and prior relapse patients with cirrhosis who are co-infected with HIV should receive 48 weeks of treatment. Treatment with OLYSIO must be initiated in combination with peginterferon alfa and ribavirin and administered for 12 weeks and then followed by an additional 36 weeks of peginterferon alfa and ribavirin. See Special patient populations - HCV/Human immunodeficiency virus type 1 (HIV-1) co-infection.
4 Includes treatment-naive patients or patients who failed prior treatment with peginterferon alfa and ribavirin with or without cirrhosis.
5 OLYSIO with sofosbuvir should only be used in patients who are intolerant to or ineligible for interferon therapy, and are in urgent need of treatment. Ribavirin could be added based on a clinical assessment of each individual patient (see sections 4.4, 4.8 and 5.1). The recommended treatment duration is 12 weeks. A longer treatment duration (up to 24 weeks) of OLYSIO with sofosbuvir (with or without ribavirin) could be considered based on an individual basis (see sections 4.4, 4.8 and 5.1).
Refer to table 2 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 during treatment with OLYSIO, peginterferon alfa and ribavirin
It is unlikely that patients with inadequate on-treatment virologic response will achieve a sustained virologic response (SVR), therefore discontinuation of treatment is recommended in these patients. The HCV RNA thresholds that trigger discontinuation of treatment (i.e., treatment stopping rules) are presented in table 2.
Table 2: Treatment stopping rules in patients receiving OLYSIO in combination with peginterferon alfa and ribavirin with inadequate on-treatment virologic response
|
HCV RNA
|
Action
|
|
Treatment week 4: ≥ 25 IU/ml
|
Discontinue OLYSIO, peginterferon alfa and ribavirin
|
|
Treatment week 12: detectable1
|
Discontinue peginterferon alfa and ribavirin (treatment with OLYSIO is complete at week 12)
|
|
Treatment week 24: detectable1
|
Discontinue peginterferon alfa and ribavirin
|
1 Re-eva luation of HCV RNA is recommended in case of detectable HCV RNA after previous undetectable HCV RNA to confirm HCV RNA levels prior to discontinuing HCV treatment.
There are no virologic treatment stopping rules that apply to the combination of OLYSIO with sofosbuvir.
Dosage adjustment or interruption of OLYSIO treatment
To prevent treatment failure, the dose of OLYSIO must not be reduced or interrupted. If treatment with OLYSIO is discontinued because of adverse reactions or inadequate on-treatment virologic response, OLYSIO treatment must not be reinitiated.
Dosage adjustment or interruption of medicinal products used in combination with OLYSIO for the treatment of CHC
If adverse reactions, potentially related to the medicinal products that are used in combination with OLYSIO for the treatment of CHC, require dosage adjustment or interruption of either medicinal product, refer to the instructions outlined in the respective Summary of Product Characteristics for these medicinal products.
If the other medicinal products that are used in combination with OLYSIO for the treatment of CHC are permanently discontinued for any reason, OLYSIO must also be discontinued.
Missed dose
If a dose of OLYSIO is missed, and the patient notices within 12 hours of the usual dosing time, the patient should take the missed dose of OLYSIO with food as soon as possible and then take the next dose of OLYSIO at the regularly scheduled time.
If a dose of OLYSIO is missed by more than 12 hours after the usual dosing time, the patient should not take the missed dose of OLYSIO and should resume dosing of OLYSIO with food at the regularly scheduled time.
Special populations
Elderly (over 65 years of age)
There are limited data on the safety and efficacy of OLYSIO in patients older than 65 years. There are no safety and efficacy data of OLYSIO in patients over the age of 75 years. No dose adjustment of OLYSIO is required in elderly patients (see section 5.2).
Renal impairment
No dose adjustment of OLYSIO is required in patients with mild or moderate renal impairment. Increased simeprevir exposures have been observed in individuals with severe renal impairment. OLYSIO has 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 haemodialysis. As exposure may be increased in HCV infected patients with severe renal impairment, caution is recommended when prescribing OLYSIO to these patients (see section 5.2).
Refer to the respective Summary of Product Characteristics of the medicinal products used in combination with OLYSIO regarding use in patients with renal impairment.
Hepatic impairment
No dose adjustment of OLYSIO is required in patients with mild or moderate hepatic impairment (Child-Pugh class A or B). Simeprevir exposure is significantly increased in subjects with severe hepatic impairment (Child-Pugh class C) and no dose recommendation can be given for those patients (see section 5.2). The safety and efficacy of OLYSIO have not been studied in HCV infected patients with moderate or severe hepatic impairment (Child-Pugh class B or C); therefore particular caution is recommended when prescribing OLYSIO to HCV infected patients with moderate or severe hepatic impairment.
Refer to the respective Summary of Product Characteristics of the medicinal products used in combination with OLYSIO regarding use in patients with decompensated cirrhosis (Child-Pugh class B or C).
Race
Given limited data, the potential risks and benefits of OLYSIO 150 mg should be carefully considered prior to use in East Asian patients (see section 5.2).
Paediatric population
The safety and efficacy of OLYSIO in children aged below 18 years have not yet been established. No data are available.
HCV/Human immunodeficiency virus type 1 (HIV-1) co-infection
No dose adjustment of OLYSIO is required in HCV/HIV-1 co-infected patients (see sections 4.8, 5.1 and 5.2).
HCV/HIV-1 co-infected patients, irrespective of prior HCV treatment history, should be treated in the same way as HCV mono-infected patients, except for co-infected patients with cirrhosis who should receive 36 weeks of treatment with peginterferon alfa and ribavirin after completing 12 weeks of treatment with OLYSIO, peginterferon alfa and ribavirin (total treatment duration of 48 weeks).
Please refer to sections 4.4 and 4.5 for relevant interactions with antiretroviral agents.
Method of administration
OLYSIO must be taken orally once a day with food (see section 5.2). The capsule should be swallowed as a whole.
General
The efficacy of OLYSIO has not been studied in patients with HCV genotypes 2, 3, 5 or 6; therefore OLYSIO should not be used in these patients (see section 5.1).
OLYSIO must not be administered as monotherapy and must be prescribed in combination with other medicinal products for the treatment of CHC.
If the other medicinal products that are used in combination with OLYSIO for the treatment of CHC are permanently discontinued, OLYSIO should also be discontinued (see section 4.2). 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.
There are no clinical data on the use of OLYSIO in re-treating patients who have failed an HCV NS3-4A protease inhibitor-based therapy (see sections 5.1 and 5.3).
Use of simeprevir in patients infected with HCV genotype 1a
Simeprevir efficacy in combination with peginterferon alfa and ribavirin is substantially reduced in patients infected with hepatitis C genotype 1a with the NS3 Q80K polymorphism at baseline compared to patients with hepatitis C genotype 1a without the Q80K polymorphism (see section 5.1). Testing for the presence of the Q80K polymorphism in patients with HCV genotype 1a is strongly recommended when considering therapy with OLYSIO in combination with peginterferon alfa and ribavirin. Alternative therapy should be considered for patients infected with HCV genotype 1a with the Q80K polymorphism or in cases where testing is not accessible.
Data are too limited to eva luate whether the presence of Q80K polymorphism in HCV genotype 1a patients reduces the efficacy of simeprevir when OLYSIO is used in combination with other direct acting antivirals against HCV (see section 5.1). Until confirmatory data becomes available, testing for the presence of the Q80K polymorphism should be considered before initiating OLYSIO in combination with sofosbuvir in patients infected with HCV genotype 1a.
Interferon-free therapy
Interferon-free regimens with OLYSIO have not been investigated in phase 3 studies (see section 5.1). The optimal regimen and treatment duration have not been established. Interferon-free therapy with OLYSIO should only be used in patients who are intolerant to or ineligible for interferon therapy, and are in urgent need of treatment.
Co-administration with other direct acting antivirals against HCV
OLYSIO should only be co-administered with other direct acting antiviral medicinal products if the benefits are considered to outweigh the risks based upon available data. There are no data to support the co-administration of OLYSIO and telaprevir or boceprevir. These HCV protease inhibitors are anticipated to be cross-resistant, and co-administration is not recommended (see also section 4.5).
OLYSIO in combination with peginterferon alfa-2b
In the clinical studies, patients randomised to simeprevir in combination with peginterferon alfa-2b and ribavirin obtained numerically lower SVR12 rates and also experienced viral breakthrough and viral relapse more frequently than those treated with simeprevir in combination with peginterferon alfa-2a and ribavirin (see section 5.1).
Pregnancy and contraception
OLYSIO should only be used during pregnancy or in women of childbearing potential if the benefit justifies the risk. Female patients of childbearing potential must use an effective form of contraception (see section 4.6).
The contraindications and warnings regarding pregnancy and contraception requirements applicable to the co-administered medicinal products also apply to their use in OLYSIO combination treatment.
Ribavirin may cause birth defects and/or death of the exposed foetus. Therefore, extreme care must be taken to avoid pregnancy in female patients
