simeprevir (Rx)

Brand and Other Names:Olysio
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 150mg
more...

Chronic Hepatitis C

Indicated for treatment of chronic hepatitis C genotype 1 or 4 infection as a component of a combination antiviral treatment regimen

150 mg PO qDay in combination with peginterferon alfa and ribavirin, or in combination with sofosbuvir

See content below for specific treatment regimens and duration

Combination with peginterferon alfa and ribavirin (Genotype 1 or 4 HCV monoinfection or HIV/HIV-1 coinfection)

  • Treatment-naïve and prior relapsed patients (with or without cirrhosis; not coinfected with HIV): 12 weeks of treatment with simeprevir, peginterferon alfa, and ribavirin FOLLOWED by an additional 12 weeks of peginterferon alfa and ribavirin (total treatment duration of 24 wk)
  • Treatment-naïve and prior relapsed patients (without cirrhosis; coinfected with HIV): 12 weeks of treatment with simeprevir, peginterferon alfa, and ribavirin FOLLOWED by an additional 12 weeks of peginterferon alfa and ribavirin (total treatment duration of 24 wk)
  • Treatment-naïve and prior relapsed patients (with cirrhosis; coinfected with HIV): 12 weeks of treatment with simeprevir, peginterferon alfa, and ribavirin FOLLOWED by an additional 36 weeks of peginterferon alfa and ribavirin (total treatment duration of 48 wk)
  • All prior nonresponders (including partial and null-responders; with or without cirrhosis): 12 weeks of treatment with simeprevir, peginterferon alfa, and ribavirin FOLLOWED by an additional 36 weeks of peginterferon alfa and ribavirin (total treatment duration of 48 wk)

Discontinue if inadequate virologic response in combination with Peg-INF-alfa and RBV

  • Monitor HCV RNA levels to determine virologic response
  • 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
  • -HCV-RNA levels at week 4 ≥25 IU/mL: Discontinue simeprevir, peginterferon alfa, and ribavirin
  • -HCV-RNA levels at week 12 ≥25 IU/mL: Discontinue peginterferon alfa and ribavirin (treatment with simeprevir completed at week 12)
  • -HCV-RNA levels at week 24 ≥25 IU/mL: Discontinue peginterferon alfa and ribavirin

Combination with sofosbuvir (Genotype 1 HCV monoinfection)

  • Treatment-naïve or experienced: 150 mg PO qDay plus sofosbuvir 400 mg qDay x12 weeks (without cirrhosis) or x24 weeks (with cirrhosis)
  • No treatment stopping rules apply when combined with sofosbuvir

Dosage Modifications

To prevent treatment failure, the dose must not be reduced or interrupted

If treatment is discontinued because of adverse reactions or inadequate on-treatment virologic response, simeprevir must not be reinitiated

If adverse reactions potentially related to peginterferon alfa and/or ribavirin occur which require dosage adjustment or interruption of either medicine, refer to the instructions outlined in the respective prescribing information for these medicines

East Asian ancestry: Higher simeprevir exposure exhibited; insufficient safety data to recommend an appropriate dosage adjustment

Renal impairment (mild, moderate, or severe): No dose adjustment required

Hepatic impairment

  • Mild (Child-Pugh A): No dose adjustment required
  • Moderate or severe (Child-Pugh B or C): Not recommended

Dosing Considerations

Must not be used as monotherapy; if sofosbuvir, peginterferon alfa, or ribavirin is discontinued for any reason, simeprevir must also be discontinued

Efficacy in combination with peginterferon alfa and ribavirin is substantially reduced in patients infected with HCV genotype 1a with an NS3 Q80K polymorphism at baseline compared to patients without the Q80K polymorphism

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

Not recommended in patients who have previously failed therapy with a treatment regimen that included simeprevir or other HCV protease inhibitors (eg, boceprevir, telaprevir)

Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with HCV direct acting antivirals (DDAs)

Safety and efficacy not established

Next:

Interactions

Interaction Checker

and simeprevir

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 
            Previous
            Next:

            Adverse Effects

            >10%

            Rash; including photosensitivity (28%)

            Hyperbilirubinemia, grade 1 (27%)

            Pruritus (22%)

            Nausea (22%)

            Hyperbilirubinemia, grade 2 (18%)

            Myalgia (16%)

            Dyspnea (12%)

            1-10%

            Hyperbilirubinemia, grade 3 (4%)

            Alkaline phosphatase elevation, grade 1 (3%)

            <1%

            Hyperbilirubinemia, grade 4

            Alkaline phosphatase elevation, grade 2

            Postmarketing reports

            Serious symptomatic bradycardia (patients taking amiodarone who initiate treatment with sofosbuvir in combination with another HCV direct acting antiviral, including simeprevir

            Hepatic decompensation and hepatic failure, including fatal cases reported in patients receiving therapy in combination with peginterferon alfa and ribavirin or in combination with sofosbuvir

            Previous
            Next:

            Warnings

            Black Box Warnings

            Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with HCV direct acting antivirals (DDAs)

            HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with DDAs 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 post-treatment follow-up

            Initiate appropriate patient management for HBV infection as clinically indicated

            Contraindications

            Hypersensitivity

            Also consider contraindications to peginterferon alfa and ribavirin

            Because ribavirin may cause birth defects and fetal death, simeprevir in combination with peginterferon alfa and ribavirin is contraindicated in pregnant women and in men whose female partners are pregnant

            Cautions

            Hepatitis B virus (HBV) reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV DDAs, and who were not receiving HBV antiviral therapy; HBV reactivation is characterized as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA level (see Black Box Warnings and Dosing Considerations)

            Serious symptomatic bradycardia in patients taking amiodarone with sofosbuvir in combination with simeprevir reported, especially in patients receiving beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease; coadministration of amiodarone with simeprever in combination with sofosbuvir not recommended; in patients without alternative treatment options, cardiac monitoring is recommended

            Hepatic decompensation and hepatic failure, including fatal cases, reported when coadministered with peginterferon alfa and ribavirin 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; monitor liver chemistry tests before and during simeprevir combination therapy

            Photosensitivity reported, including serious reactions which resulted in hospitalization

            Rash may occur, most frequently within the first 4 weeks; mild-to-moderate rashes should be followed for possible progression of rash, including the development of mucosal signs (eg, oral lesions, conjunctivitis) or systemic symptoms; discontinue if rash becomes severe

            Contains a sulfonamide moiety; in subjects with a history of sulfa allergy (n=16), no increased incidence of rash or photosensitivity reactions was observed; however, insufficient data exist

            Must NOT be used as monotherapy

            Drug interaction overview

            • Avoid coadministering with moderate or strong CYP3A inhibitors; simeprevir AUC increased >7-fold
            • Avoid coadministering with moderate or strong CYP3A inducers; simeprevir trough levels decreased >90%
            Previous
            Next:

            Pregnancy & Lactation

            Pregnancy

            Simeprevir is coadministered with ribavirin and peginterferon alfa; extreme caution must be taken to avoid pregnancy in female patients and female partners of male patients while taking this combination (see Contraindications)

            Significant teratogenic and/or embryocidal effects have been demonstrated in all animal species exposed to ribavirin; and therefore ribavirin is contraindicated

            Women of childbearing potential and their male partners should not receive ribavirin unless they are using effective contraception (2 reliable forms) during treatment with ribavirin and for 6 months after treatment

            Ribavirin may cause birth defects and fetal death; avoid pregnancy in female patients and female partners of male patients; patients must have a negative pregnancy test prior to therapy; use 2 or more forms of contraception, 1 of these forms of contraception can be a combined oral contraceptive product containing at least 1 mg of norethindrone (lower doses of norethindrone and other forms of hormonal contraception have not been studied or are contraindicated)

            Lactation

            Unknown if distributed in human breast milk; because of the potential for adverse reaction, breastfeeding is not recommended

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

            more...
            Previous
            Next:

            Pharmacology

            Mechanism of Action

            In a biochemical assay simeprevir inhibited the proteolytic activity of recombinant genotype 1a and 1b HCV NS3/4A proteases, with median Ki values of 0.5 nM and 1.4 nM, respectively

            NS3/4A protease is needed for proteolytic cleavage of the HCV encoded polyprotein into mature forms

            Absorption

            Food increases systemic exposure by 60-70%

            Peak plasma time: 4-6 hr

            Predose plasma concentration: 1936 ng/mL

            AUC: 57,469 ng•hr/mL

            Distribution

            Protein bound: >99.9%

            Metabolism

            Substrate: CYP3A (major); CYP2C8 (minor) and CYP2C19 (minor)

            Inhibits OATP1B1/3 and P-gp transporters

            Mildly inhibits CYP1A2 and intestinal CYP3A, but does not affect hepatic CYP3A4 activity

            Elimination

            Half-life: 41 hr (HC- infected); 10-13 hr (HCV-uninfected)

            Excretion: Hepatobiliary; 91% feces (31% unchanged); <1% urine

            Pharmacogenomics

            Efficacy is substantially reduced in patients infected with HCV genotype 1a with an NS3 Q80K polymorphism at baseline; screening patients for the presence of virus with the NS3 Q80K polymorphism at baseline is strongly recommended

            Simeprevir exposures are higher in populations with lower amounts of CYP3A and/or OATP1B1/3 including patients of East Asian ancestry

            IL28B genetic variant

            • A genetic variant near the gene encoding interferon-lambda-3 (IL28B rs12979860, a C to T change) is a strong predictor of response to peginterferon alfa and ribavirin
            • Overall, sustained viral response rates were lower in subjects with the CT and TT genotypes compared to those with the CC genotype
            Previous
            Next:

            Administration

            Instructions

            Take with food (bioavailability improved)

            Swallow capsule whole

            Previous
            Next:

            Images

            Previous
            Next:

            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous
            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.