"The U.S. Food and Drug Administration today approved Olysio (simeprevir), a new therapy to treat chronic hepatitis C virus infection.
Hepatitis C is a viral disease that causes inflammation of the liver that can lead to diminished liver"...
OLYSIO® is a hepatitis C virus (HCV) NS3/4A protease inhibitor indicated for the treatment of chronic hepatitis C (CHC) genotype 1 infection as a component of a combination antiviral treatment regimen.
Limitations of Use
- OLYSIO monotherapy is not recommended.
- OLYSIO efficacy in combination with peginterferon alfa (Peg-IFN-alfa) and ribavirin (RBV) is substantially reduced in patients infected with HCV genotype 1a with an NS3 Q80K polymorphism at baseline compared to patients infected with hepatitis C virus (HCV) genotype 1a without the Q80K polymorphism. [See DOSAGE AND ADMINISTRATION and Microbiology]. Screening patients with HCV genotype 1a infection for the presence of virus with the NS3 Q80K polymorphism at baseline is strongly recommended. Alternative therapy should be considered for patients infected with HCV genotype 1a containing the Q80K polymorphism.
- OLYSIO is not recommended in patients with severe hepatic impairment (Child-Pugh Class C) due to substantial increases in simeprevir exposures, which have been associated with increased frequency of adverse reactions [see CLINICAL PHARMACOLOGY and ADVERSE REACTIONS].
- OLYSIO is not recommended in patients who have previously failed therapy with a treatment regimen that included OLYSIO or other HCV protease inhibitors [see Microbiology].
DOSAGE AND ADMINISTRATION
OLYSIO Combination Treatment
Administer OLYSIO in combination with other antiviral drugs for the treatment of CHC infection. For specific dosing recommendations for the antiviral drugs used in combination with OLYSIO, refer to their respective prescribing information. OLYSIO monotherapy is not recommended. Administer OLYSIO in combination with either:
- Peg-IFN-alfa and RBV: Table 1 displays the recommended dosage regimen and treatment duration of OLYSIO in combination with Peg-IFN-alfa and RBV. Refer to Table 3 for treatment stopping rules for OLYSIO combination therapy with Peg-IFN-alfa and RBV; or
- Sofosbuvir: Table 2 displays the recommended dosage regimen and treatment duration of OLYSIO in combination with sofosbuvir.
The recommended dosage of OLYSIO is one capsule taken orally once daily with food. The capsule should be swallowed as a whole.
Table 1: Recommended Dosage Regimens and Treatment
Duration for OLYSIO, Peg-IFN-alfa, and RBV Combination Therapy for Treatment of
|Patient Population*||Treatment Regimen and Duration|
|Treatment-naive patients and prior relapsers†||12 weeks of OLYSIO in combination with Peg-IFN-alfa and RBV followed by an additional 12 weeks of Peg-IFN-alfa and RBV (total treatment duration of 24 weeks)‡|
|Prior non-responders (including partial# and null responders§)||12 weeks of OLYSIO in combination with Peg-IFN-alfa and RBV followed by an additional 36 weeks of Peg-IFN-alfa and RBV (total treatment duration of 48 weeks)‡|
|* Includes patients with or without cirrhosis.
† Prior relapser: HCV RNA not detected at the end of prior IFN-based therapy and HCV RNA detected during follow-up [see Clinical Studies].
‡ Recommended duration of treatment if patient does not meet stopping rules (see Table 3).
# Prior partial responder: prior on-treatment ≥ 2 log 10 IU/mL reduction in HCV RNA from baseline at Week 12 and HCV RNA detected at end of prior IFN-based therapy [see Clinical Studies].
§ Prior null responder: prior on-treatment < 2 log 10 reduction in HCV RNA from baseline at Week 12 during prior IFN-based therapy [see Clinical Studies].
Table 2: Recommended Dosage
Regimen and Treatment Duration for OLYSIO and Sofosbuvir Combination Therapy
for Treatment of CHC Infection
|Patient Population||Treatment Regimen and Duration|
|* Treatment-naive and treatment-experienced patients without cirrhosis||12 weeks of OLYSIO + sofosbuvir|
|Treatment-naive and treatment-experienced* patients with cirrhosis||24 weeks of OLYSIO + sofosbuvir|
|* Treatment-experienced patients include prior relapsers, prior partial responders and prior null responders who failed prior IFN-based therapy.|
Testing Prior To Initiation Of OLYSIO In HCV Genotype 1a-Infected Patients
Prior to initiation of treatment with OLYSIO with Peg-IFN-alfa and RBV, screening patients with HCV genotype 1a infection for the presence of virus with the NS3 Q80K polymorphism is strongly recommended and alternative therapy should be considered for patients infected with HCV genotype 1a containing the Q80K polymorphism. Prior to initiation of treatment with OLYSIO with sofosbuvir, screening patients infected with HCV genotype 1a for the presence of virus with the NS3 Q80K polymorphism is not strongly recommended but may be considered. [See INDICATIONS AND USAGE].
Discontinuation Of Dosing
Use with Peg-IFN-Alfa and RBV
During treatment, HCV RNA levels should be monitored as clinically indicated using a sensitive assay with a lower limit of quantification of at least 25 IU/mL.
Because patients with an inadequate on-treatment virologic response (i.e., HCV RNA ≥ 25 IU/mL) are not likely to achieve a sustained virologic response (SVR), discontinuation of treatment is recommended in these patients. Table 3 presents treatment stopping rules for patients who experience an inadequate on-treatment virologic response at Weeks 4, 12, and 24.
Table 3: Treatment Stopping Rules in Patients
Receiving OLYSIO in Combination with Peg-IFN-alfa and RBV with Inadequate
On-Treatment Virologic Response
|Treatment Week||HCV RNA||Action|
|Week 4||≥ 25 IU/mL||Discontinue OLYSIO, Peg-IFN-alfa, and RBV|
|Week 12||Discontinue Peg-IFN-alfa, and RBV (treatment with OLYSIO is complete at Week 12)|
|Week 24||Discontinue Peg-IFN-alfa, and RBV (treatment with OLYSIO is complete at Week 12)|
Use with Sofosbuvir
No treatment stopping rules apply to the combination of OLYSIO with sofosbuvir [see Clinical Studies].
Dosage Adjustment Or Interruption
To prevent treatment failure, avoid reducing the dosage of OLYSIO or interrupting treatment. If treatment with OLYSIO is discontinued because of adverse reactions or inadequate on-treatment virologic response, OLYSIO treatment must not be reinitiated.
If adverse reactions potentially related to the antiviral drug(s) used in combination with OLYSIO occur, refer to the instructions outlined in their respective prescribing information for recommendations on dosage adjustment or interruption.
If any of the other antiviral drugs used in combination with OLYSIO for the treatment of CHC infection are permanently discontinued for any reason, OLYSIO should also be discontinued.
No dosage recommendation can be made for patients with moderate hepatic impairment (Child-Pugh Class B) due to modest increases in simeprevir exposures. OLYSIO is not recommended for patients with severe hepatic impairment (Child-Pugh Class C) due to substantially higher simeprevir exposures [see CLINICAL PHARMACOLOGY]. In clinical trials, higher simeprevir exposures have been associated with increased frequency of adverse reactions, including rash and photosensitivity [see ADVERSE REACTIONS].
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). Do not administer OLYSIO in combination with Peg-IFN-alfa and RBV in patients with decompensated cirrhosis (moderate or severe hepatic impairment) [see Peg-IFN-alfa prescribing information]. The potential risks and benefits of OLYSIO should be carefully considered prior to use in patients with moderate hepatic impairment.
Dosage Forms And Strengths
Capsules: 150 mg, white and marked with “TMC435 150” in black ink.
Storage And Handling
OLYSIO 150 mg capsules are white, marked with “TMC435 150” in black ink. The capsules are packaged into a bottle containing 28 capsules (NDC 59676-225-28) or a bottle of 7 capsules (emergency supply; NDC 59676-225-07).
Store OLYSIO capsules in the original bottle in order to protect from light at room temperature below 30°C (86°F).
Manufactured by: Janssen-Cilag SpA, Latina, Italy. Manufactured for: Janssen Therapeutics, Division of Janssen Products, LP, Titusville NJ 08560. Revised: April 2015
Last reviewed on RxList: 4/23/2015
This monograph has been modified to include the generic and brand name in many instances.
Additional Olysio Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
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