Victrelis 200 mg hard capsules

Each hard capsule contains 200 mg of boceprevir.

Excipient with known effect: each capsule contains 56 mg of lactose monohydrate.

For the full list of excipients, see section 6.1.

Hard capsule.

Each capsule has a yellowish-brown, opaque cap with an "MSD" logo imprinted in red ink and off-white, opaque body with the code "314" imprinted in red ink.

Victrelis is indicated for the treatment of chronic hepatitis C (CHC) genotype 1 infection, in combination with peginterferon alfa and ribavirin, in adult patients with compensated liver disease who are previously untreated or who have failed previous therapy.

See sections 4.4 and 5.1.

Treatment with Victrelis should be initiated and monitored by a physician experienced in the management of chronic hepatitis C.

Posology

Victrelis must be administered in combination with peginterferon alfa and ribavirin. The Summary of Product Characteristics of peginterferon alfa and ribavirin (PR) must be consulted prior to initiation of therapy with Victrelis.

The recommended dose of Victrelis is 800 mg administered orally three times daily (TID) with food (a meal or light snack). Maximum daily dose of Victrelis is 2,400 mg. Administration without food could be associated with a net loss of efficacy due to sub-optimal exposure.

Patients without cirrhosis who are previously untreated or who have failed previous therapy

The following dosing recommendations differ for some subgroups from the dosing studied in the Phase 3 trials (see section 5.1).

Table 1

Duration of therapy using Response-Guided Therapy (RGT) guidelines in patients without cirrhosis who are previously untreated or who have failed previous therapy to interferon and ribavirin therapy

All cirrhotic patients and null responders

- Recommended treatment duration is 48 weeks: 4 weeks of bitherapy with peginterferon alfa+ ribavirin + 44 weeks of tritherapy with peginterferon alfa + ribavirin + Victrelis. (Refer to the stopping rule in Table 1 for all patients.)

o The duration of the tritherapy after the first 4 weeks of bitherapy should not be less than 32 weeks. Given the incremental risk of adverse events with Victrelis (anaemia notably); in case the patient cannot tolerate the treatment, consideration could be given to pursue with 12 weeks of bitherapy for the final 12 weeks of treatment instead of tritherapy (see sections 4.8 and 5.1). For additional information on use of Victrelis in patients with advanced liver disease, see section 4.4.

Poorly interferon-responsive patients

In poorly interferon responsive patients (defined as < 1-log₁₀ decline in HCV-RNA at TW 4) the use of triple therapy should be considered on a case by case basis, as the likelihood of achieving sustained virologic response (SVR) with triple therapy is lower in these patients (see section 5.1).

Missed doses

If a patient misses a dose and it is less than 2 hours before the next dose is due, the missed dose should be skipped.

If a patient misses a dose and it is 2 or more hours before the next dose is due, the patient should take the missed dose with food and resume the normal dosing schedule.

Dose reduction

Dose reduction of Victrelis is not recommended.

If a patient has a serious adverse reaction potentially related to peginterferon alfa and/or ribavirin, the peginterferon alfa and/or ribavirin dose should be reduced. Refer to the Summary of Product Characteristics for peginterferon alfa and ribavirin for additional information about how to reduce and/or discontinue the peginterferon alfa and/or ribavirin dose. Victrelis must not be administered in the absence of peginterferon alfa and ribavirin.

Stopping rules

Discontinuation of therapy is recommended in all patients with 1) HCV-RNA levels of greater than or equal to 1,000 IU per mL at TW 8; or 2) HCV-RNA levels of greater than or equal to 100 IU per mL at TW 12; or 3) confirmed, detectable HCV-RNA levels at TW 24.

Special populations

Renal impairment

No dose adjustment of Victrelis is required in patients with any degree of renal impairment (see section 5.2).

Hepatic impairment

No dose adjustment of Victrelis is required for patients with mild, moderate or severe hepatic impairment. Victrelis has not been studied in patients with decompensated cirrhosis (see section 5.2). For additional information on use of Victrelis in patients with advanced liver disease, see section 4.4.

Paediatric population

The safety and efficacy of Victrelis in children aged below 18 years have not yet been established. No data are available.

Older people

Clinical studies of Victrelis did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other clinical experience has not identified differences in responses between the older and younger patients (see section 5.2).

Method of administration

To obtain the hard capsules the foil of the blister should be peeled off. Victrelis is to be taken orally with food (a meal or light snack).

Victrelis, in combination with peginterferon alfa and ribavirin, is contraindicated in:

• Patients with hypersensitivity to the active substance or any of the excipients listed in section 6.1.

• Patients with autoimmune hepatitis.

• Co-administration with medicines that are highly dependent on CYP3A4/5 for clearance, and for which elevated plasma concentrations are associated with serious and/or life-threatening events such as orally administered midazolam and triazolam, bepridil, pimozide, lumefantrine, halofantrine, tyrosine kinase inhibitors, simvastatin, lovastatin, quetiapine, alfuzosin, silodosin and ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine) (see section 4.5).

• Pregnancy (see section 4.6).

Refer to the Summary of Product Characteristics for peginterferon alfa and ribavirin for additional information.