Simeprevir Dosage

Applies to the following strengths: 150 mg

Usual Adult Dose for:

Chronic Hepatitis C

Additional dosage information:

Renal Dose Adjustments
Liver Dose Adjustments
Dose Adjustments
Precautions
Dialysis
Other Comments

Usual Adult Dose for Chronic Hepatitis C

150 mg orally once a day with food

Recommended Regimen and Duration of Therapy:
Therapy-naive and therapy-experienced patients with HCV genotype 1 infection:

Without cirrhosis: Simeprevir plus sofosbuvir for 12 weeks
With compensated cirrhosis (Child-Pugh A): Simeprevir plus sofosbuvir for 24 weeks

Therapy-naive patients and prior relapsers with HCV genotype 1 or 4 infection:

HCV mono-infected patients without cirrhosis or with compensated cirrhosis (Child-Pugh A): Simeprevir plus peginterferon alfa plus ribavirin for 12 weeks
To be followed by: Peginterferon alfa plus ribavirin for 12 weeks
Total duration of therapy: 24 weeks (unless patient meets stopping rules)
HCV/HIV-1-coinfected patients without cirrhosis: Simeprevir plus peginterferon alfa plus ribavirin for 12 weeks
To be followed by: Peginterferon alfa plus ribavirin for 12 weeks
Total duration of therapy: 24 weeks (unless patient meets stopping rules)
HCV/HIV-1-coinfected patients with compensated cirrhosis (Child-Pugh A): Simeprevir plus peginterferon alfa plus ribavirin for 12 weeks
To be followed by: Peginterferon alfa plus ribavirin for 36 weeks
Total duration of therapy: 48 weeks (unless patient meets stopping rules)

Prior non-responders (including partial and null responders) with HCV genotype 1 or 4 infection:

HCV/HIV-1-coinfected or HCV mono-infected patients without cirrhosis or with compensated cirrhosis (Child-Pugh A): Simeprevir plus peginterferon alfa plus ribavirin for 12 weeks
To be followed by: Peginterferon alfa plus ribavirin for 36 weeks
Total duration of therapy: 48 weeks (unless patient meets stopping rules)

Treatment Stopping Rules for Patients with Inadequate On-Treatment Virologic Response during Treatment with Simeprevir, Peginterferon alfa, and Ribavirin:

HCV-RNA level at least 25 international units/mL at treatment week 4: Discontinue simeprevir, peginterferon alfa, and ribavirin.
HCV-RNA level at least 25 international units/mL at treatment week 12 or 24: Discontinue peginterferon alfa and ribavirin (simeprevir finished at week 12).

Comments:

Liver chemistry tests should be monitored before and during therapy.
Therapy-experienced patients include prior relapsers, prior partial responders, and prior null responders who failed prior interferon-based therapy.
Prior relapser: HCV RNA not detected at the end of prior interferon-based therapy and HCV RNA detected during follow-up.
Prior partial responder: Prior on-treatment reduction in HCV RNA at least 2 log10 international units/mL from baseline at week 12 and HCV RNA detected at end of prior interferon-based therapy.
Prior null responder: Prior on-treatment reduction in HCV RNA less than 2 log10 international units/mL from baseline at week 12 during prior interferon-based therapy.
Virologic treatment stopping rules not available for combination therapy with sofosbuvir.
HCV-RNA levels should be monitored during combination therapy with peginterferon alfa and ribavirin as clinically indicated. It is not likely that patients with inadequate on-treatment virologic response (i.e., HCV RNA at least 25 international units/mL) will achieve a sustained virologic response; therapy discontinuation recommended in such patients.

Use: For the treatment of chronic HCV infection

In combination with sofosbuvir: For HCV genotype 1 without cirrhosis or with compensated cirrhosis
In combination with peginterferon alfa and ribavirin: For HCV genotype 1 or 4 without cirrhosis or with compensated cirrhosis

Renal Dose Adjustments

Mild, moderate, or severe renal dysfunction: No adjustment recommended.

Comments:

Safety and efficacy have not been established in HCV-infected patients with severe renal dysfunction (CrCl less than 30 mL/min) or ESRD.
The manufacturer product information for coadministered HCV drugs should be consulted regarding use in patients with renal dysfunction.

Liver Dose Adjustments

Mild liver dysfunction (Child-Pugh A): No adjustment recommended.
Moderate or severe liver dysfunction (Child-Pugh B or C): Not recommended.

Comments:

Safety and efficacy have not been established in liver transplant recipients.
The manufacturer product information for peginterferon alfa should be consulted regarding its contraindication in patients with hepatic decompensation.

Dose Adjustments

To prevent treatment failure, reducing the dose of this drug or interrupting treatment should be avoided. If this drug is stopped due to side effects or inadequate on-treatment virologic response, it must not be restarted.

The manufacturer product information for coadministered HCV antiviral drugs should be consulted for appropriate dose adjustment or interruption due to side effects. If any of the coadministered HCV antiviral drugs are permanently stopped for any reason, this drug should also be discontinued.

Precautions

US BOXED WARNING:

RISK OF HBV REACTIVATION IN PATIENTS COINFECTED WITH HCV AND HBV: All patients should be tested for evidence of current/prior HBV infection before starting this drug. HBV reactivation has been reported during or after completion of HCV direct-acting antiviral therapy in HCV/HBV-coinfected patients who were not receiving HBV antiviral therapy; some cases resulted in fulminant hepatitis, hepatic failure, and death. HCV/HBV-coinfected patients should be monitored for hepatitis flare or HBV reactivation during HCV therapy and posttherapy follow-up; appropriate patient management for HBV infection should be started as clinically indicated.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Comments:

Safety and efficacy have not been established in HCV-infected patients with ESRD (including those requiring dialysis).
Significant removal via dialysis is not likely (highly protein bound).

Other Comments

Administration advice:

Before starting this drug, test all patients for evidence of current/prior HBV infection; measure hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc).
Use in combination with other antiviral drugs for the treatment of chronic HCV; do not use as monotherapy.
Before starting this drug with sofosbuvir, may consider screening HCV genotype 1a-infected patients with compensated cirrhosis for virus with the nonstructural protein 3 (NS3) Q80K polymorphism
Before starting this drug with peginterferon alfa and ribavirin, screen patients with HCV genotype 1a infection for virus with the NS3 Q80K polymorphism (strongly recommended); consider alternative therapy if the Q80K polymorphism is present.
Administer with food.
Swallow capsules whole.
If any of the coadministered HCV antiviral drugs are permanently stopped for any reason, discontinue this drug.
Consult the manufacturer product information regarding missed doses.

Storage requirements:

Store capsules in the original bottle to protect from light; store at room temperature below 30C (86F)

General:

Limitations of Use: Efficacy of this drug with peginterferon alfa and ribavirin is substantially reduced in patients infected with HCV genotype 1a with an NS3 Q80K polymorphism at baseline compared to those without the Q80K polymorphism. This drug is not recommended for patients who previously failed therapy with a regimen that included this or other HCV protease inhibitors.
The assay used to monitor HCV-RNA levels should be sensitive, with a lower limit of quantification of at least 25 international units/mL.
The manufacturer product information for coadministered HCV antiviral drugs should be consulted for additional information.

Monitoring:

General: HCV-RNA levels (at weeks 4 and 12 and as clinically indicated during combination therapy with peginterferon alfa and ribavirin)
Hepatic: Liver chemistry tests (before and as clinically indicated during therapy)

Patient advice:

Read the US FDA-approved patient labeling (Patient Information).
Avoid missing doses and complete the entire course of therapy.
Watch for signs of liver inflammation (e.g., early signs: fatigue, weakness, lack of appetite, nausea and vomiting; later signs: jaundice, discolored feces); consult healthcare provider immediately if these symptoms develop.
Use sun protection (e.g., hat, sunglasses, protective clothing, sunscreen), limit exposure to natural sunlight, and avoid artificial sunlight (e.g., tanning beds, phototherapy) during use of this drug.
Contact healthcare provider at once if photosensitivity reaction or rash occurs; do not stop this drug due to either event unless directed by healthcare provider.