DESCRIPTION

OLYSIO (simeprevir) is an inhibitor of the HCV NS3/4A protease.

The chemical name for simeprevir is (2R,3aR,10Z,11aS,12aR,14aR)-N(cyclopropylsulfonyl)-2-[[2-(4-isopropyl-1,3-thiazol-2-yl)-7-methoxy-8-methyl-4quinolinyl]oxy]-5-methyl-4,14-dioxo-2,3,3a,4,5,6,7,8,9,11a,12,13,14,14atetradecahydrocyclopenta[c]cyclopropa[g][1,6]diazacyclotetradecine-12a(1H)carboxamide. Its molecular formula is C₃₈H₄₇N₅O₇S₂ and its molecular weight is 749.94. Simeprevir has the following structural formula:

Simeprevir drug substance is a white to almost white powder. Simeprevir is practically insoluble in water over a wide pH range. It is practically insoluble in propylene glycol, very slightly soluble in ethanol, and slightly soluble in acetone. It is soluble in dichloromethane and freely soluble in some organic solvents (e.g., tetrahydrofuran and N,N-dimethylformamide).

OLYSIO (simeprevir) for oral administration is available as 150 mg strength hard gelatin capsules. Each capsule contains 154.4 mg of simeprevir sodium salt, which is equivalent to 150 mg of simeprevir. OLYSIO (simeprevir) capsules contain the following inactive ingredients: colloidal anhydrous silica, croscarmellose sodium, lactose monohydrate, magnesium stearate and sodium lauryl sulphate. The white capsule contains gelatin and titanium dioxide (E171) and is printed with ink containing iron oxide black (E172) and shellac (E904).

DOSAGE AND ADMINISTRATION

Testing Prior To The Initiation Of Therapy

Testing For HBV infection

Test all patients for evidence of current or prior HBV infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before initiating HCV treatment with OLYSIO [see WARNINGS AND PRECAUTIONS].

Q80K Testing In HCV Genotype 1a-Infected Patients

OLYSIO in Combination with Sofosbuvir

In HCV genotype 1a-infected patients with compensated cirrhosis, screening for the presence of virus with the NS3 Q80K polymorphism may be considered prior to initiation of treatment with OLYSIO with sofosbuvir [see Clinical Studies].

OLYSIO in Combination with Peg-IFN-alfa and RBV

Prior to initiation of treatment with OLYSIO in combination 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 [see INDICATIONS AND USAGE and Microbiology].

Hepatic Laboratory Testing

Monitor liver chemistry tests before and during OLYSIO combination therapy [see WARNINGS AND PRECAUTIONS].

OLYSIO Combination Treatment

Administer OLYSIO in combination with other antiviral drugs for the treatment of chronic HCV infection. OLYSIO monotherapy is not recommended. The recommended dosage of OLYSIO is one 150 mg capsule taken orally once daily with food [see CLINICAL PHARMACOLOGY]. The capsule should be swallowed as a whole. For specific dosing recommendations for the antiviral drugs used in combination with OLYSIO, refer to their respective prescribing information.

OLYSIO can be taken in combination with sofosbuvir or in combination with Peg-IFN-alfa and RBV.

SIDE EFFECTS

Because OLYSIO is administered in combination with other antiviral drugs, refer to the prescribing information of the antiviral drugs used in combination with OLYSIO for a description of adverse reactions associated with their use.

The following serious and otherwise important adverse reactions are described below and in other sections of the labeling:

• Serious Symptomatic Bradycardia When Co-administered with Sofosbuvir and Amiodarone [see WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS]
• Hepatic Decompensation and Hepatic Failure [see WARNINGS AND PRECAUTIONS]
• Photosensitivity [see WARNINGS AND PRECAUTIONS]
• Rash [see WARNINGS AND PRECAUTIONS]

• DRUG INTERACTIONS

  Potential For OLYSIO To Affect Other Drugs

  Simeprevir mildly inhibits CYP1A2 activity and intestinal CYP3A4 activity, but does not affect hepatic CYP3A4 activity. Coadministration of OLYSIO with drugs that are primarily metabolized by CYP3A4 may result in increased plasma concentrations of such drugs (see Table 8).

  Simeprevir inhibits OATP1B1/3, P-glycoprotein (P-gp) and BCRP transporters, and does not inhibit OCT2 in vitro. Coadministration of OLYSIO with drugs that are substrates for OATP1B1/3, and P-gp and BCRP transport may result in increased plasma concentrations of such drugs (see Table 8).

  Potential For Other Drugs To Affect OLYSIO

  The primary enzyme involved in the biotransformation of simeprevir is CYP3A [see CLINICAL PHARMACOLOGY]. Clinically relevant effects of other drugs on simeprevir pharmacokinetics via CYP3A may occur. Coadministration of OLYSIO with moderate or strong inhibitors of CYP3A may significantly increase the plasma exposure of simeprevir. Coadministration with moderate or strong inducers of CYP3A may significantly reduce the plasma exposure of simeprevir and lead to loss of efficacy (see Table 8). Therefore, Coadministration of OLYSIO with substances that are moderate or strong inducers or inhibitors of CYP3A is not recommended [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].