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Simeprevir (United States: Not available): Drug information

Simeprevir (United States: Not available): Drug information
(For additional information see "Simeprevir (United States: Not available): Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Hepatitis B virus reactivation:

Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with simeprevir. HBV reactivation has been reported in hepatitis C virus (HCV)/HBV co-infected patients who were undergoing or had completed treatment with HCV direct-acting antivirals and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Monitor HCV/HBV co-infected 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.

Pharmacologic Category
  • Antihepaciviral, NS3/4A Protease Inhibitor (Anti-HCV);
  • NS3/4A Inhibitor
Dosing: Adult

Note: Olysio tablets have been discontinued in the United States for >1 year.

Note: If other concomitant treatment (eg, sofosbuvir) is discontinued for any reason, simeprevir must also be discontinued. Do not reduce simeprevir dosage or interrupt therapy; if therapy must be interrupted due to adverse reactions or inadequate response, do not reinitiate. In patients with genotype 1a and compensated cirrhosis, screening for hepatitis C virus (HCV) with the NS3 Q80K polymorphism may be considered prior to starting therapy. Screening is strongly recommended prior to initiation of combination treatment with peginterferon alfa and ribavirin in patients with genotype 1a; consider alternative therapy in patients infected with HCV genotype 1a containing the Q80K polymorphism.

Chronic hepatitis C, genotype 1

Chronic hepatitis C, genotype 1 (without cirrhosis or with compensated cirrhosis [Child-Pugh class A]): Oral: 150 mg once daily in combination with sofosbuvir for 12 weeks (without cirrhosis) or 24 weeks (with compensated cirrhosis). Note: The American Association for the Study of Liver Diseases/Infectious Diseases Society of America guidelines for testing, managing, and treating hepatitis C no longer include simeprevir as a component of recommended treatment regimens for HCV infection (AASLD/IDSA 2021).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

CrCl >30 mL/minute: No dosage adjustment necessary.

CrCl ≤30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

End-stage renal disease (ESRD), including hemodialysis patients: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Dialysis is unlikely to result in significant removal of simeprevir.

Dosing: Hepatic Impairment: Adult

Mild impairment (Child-Pugh class A): No dosage adjustment necessary.

Moderate or severe impairment (Child-Pugh class B or C): Use is not recommended.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Percentages reported for combination therapy with peginterferon alfa and ribavirin (Peg-IFN-alfa and RBV) unless otherwise noted.

>10%:

Central nervous system: Headache (with sofosbuvir 7% to 49%), fatigue (with sofosbuvir 10% to 47%), insomnia (with sofosbuvir 14%), dizziness (with sofosbuvir 5% to 10%)

Dermatologic: Skin photosensitivity (with sofosbuvir ≤5% to ≤34%; grade 3: ≤1%; with Peg-IFN-alfa and RBV ≤28%; grade 3: <1%), skin rash (with sofosbuvir ≤5% to ≤34%; grade 3: ≤1%; with Peg-IFN-alfa and RBV ≤28%; including erythema, eczema, maculopapular rash, urticaria, toxic skin eruption, dermatitis exfoliative, cutaneous vasculitis; grade 3: ≤1%), pruritus (with Peg-IFN-alfa and RBV 22%; with sofosbuvir 11%)

Endocrine & metabolic: Increased amylase (with sofosbuvir)

Gastrointestinal: Nausea (with sofosbuvir 4% to 40%; with Peg-IFN-alfa and RBV 22%), diarrhea (with sofosbuvir 5% to 18%)

Hepatic: Increased serum bilirubin (<66%), hyperbilirubinemia (with sofosbuvir)

Neuromuscular & skeletal: Myalgia (16%)

Respiratory: Dyspnea (12%)

1% to 10%:

Gastrointestinal: Increased serum lipase (with sofosbuvir)

Hepatic: Increased serum alkaline phosphatase

<1%, postmarketing, and/or case reports: Hepatic failure, liver decompensation, reactivation of HBV (FDA Safety Alert Dec. 8, 2016)

Contraindications

There are no contraindications listed in the manufacturer's labeling. When administered with ribavirin and peginterferon alfa, the contraindications to ribavirin and peginterferon alfa also apply. See Ribavirin and Peginterferon Alfa monographs.

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to simeprevir or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

• Hepatic decompensation/failure: Hepatic decompensation and failure (including fatal cases) have been reported in patients treated with simeprevir in combination with peginterferon alfa and ribavirin or sofosbuvir. Most cases occurred in patients with advanced and/or decompensated cirrhosis. Modest bilirubin level increases, not impacting hepatic function, have been reported; however, postmarketing cases of hepatic decompensation with markedly elevated bilirubin levels have also been reported. Monitor hepatic function at baseline and as clinically indicated; closely monitor patients who experience an increase in total bilirubin >2.5 times the ULN. Discontinue treatment if elevated bilirubin accompanied by liver transaminase increases or clinical signs or symptoms of hepatic decompensation (eg, fatigue, weakness, lack of appetite, nausea and vomiting, jaundice, discolored feces) occur.

• Photosensitivity: Photosensitivity reactions, including serious reactions resulting in hospitalization, have been reported when used in combination with peginterferon alfa and ribavirin. May present as an exaggerated sunburn reaction (burning, erythema, exudation, blistering, and edema), usually to areas exposed to light (face, “v” area of the neck, extensor surfaces of the forearms, dorsa of the hands); most frequently occurs within the first 4 weeks of treatment. Avoid excessive sunlight, tanning devices, and take precautions to limit exposure (eg, loose fitting clothing, sunscreen). Discontinue use if photosensitivity occurs and monitor until the reaction resolves. If therapy is to be continued in a patient who has experienced photosensitivity, expert consultation is advised.

• Skin reactions: Rash has been typically observed within first 4 weeks of therapy initiation, but can occur at any time during treatment. Severe rashes and rash requiring discontinuation have occurred in combination with peginterferon alfa and ribavirin. If a patient experiences a mild to moderate rash, follow for progression and/or development of mucosal signs (eg, oral lesions, conjunctivitis) or systemic symptoms. If rash becomes severe, discontinue simeprevir and monitor for rash resolution.

• Sulfa allergy: Contains a sulfonamide moiety. In patients with a history of sulfa allergy, no increased incidence of rash or photosensitivity has been reported, although the risk of reaction (or potential severity) cannot be excluded. Discontinue if signs of hypersensitivity are noted.

Disease-related concerns:

• Diabetes: Rapid reduction in hepatitis C viral load during direct-acting antiviral (DAA) therapy for hepatitis C may lead to improvement in glucose metabolism in patients with diabetes, potentially resulting in symptomatic hypoglycemia if antidiabetic agents are continued at the same dose. Monitor for changes in glucose tolerance and inform patients of the risk of hypoglycemia during DAA therapy, particularly within the first 3 months. Modification of antidiabetic therapy may be necessary (Ciancio 2018; Dawood 2017; Hum 2017).

• Hepatic impairment: Not recommend in patients with moderate or severe hepatic impairment (Child-Pugh class B or C).

• Hepatitis B virus reactivation: [US Boxed Warning]: Hepatitis B virus (HBV) reactivation has been reported in hepatitis C virus (HCV)/HBV co-infected patients who were receiving or had completed treatment with HCV direct-acting antivirals and were not receiving HBV antiviral therapy; some cases have resulted in fulminant hepatitis, hepatic failure, and death. Test all patients for evidence of current or prior HBV infection prior to initiation of simeprevir; monitor HCV/HBV co-infected patients for hepatitis flare or HBV reactivation during treatment and post-treatment follow-up. Initiate treatment for HBV infection as clinically indicated. HBV reactivation has been reported in HBsAg positive patients and in patients with serologic evidence of resolved HBV infection (ie, HBsAg negative and anti-HBc positive) and is characterized by an abrupt increase in HBV replication manifested as a rapid increase in serum HBV DNA level; reappearance of HBsAg may occur in patients with resolved HBV infection. Risk of HBV reactivation may be increased in patients receiving certain immunosuppressants or chemotherapeutic agents.

Concurrent drug therapy issues:

• Amiodarone: Symptomatic bradycardia (some requiring pacemaker intervention) has occurred in patients receiving amiodarone and sofosbuvir in combination with another direct acting antiviral, including simeprevir. Fatal cardiac arrest occurred in a patient receiving a sofosbuvir (eg, ledipasvir/sofosbuvir) combination product. Bradycardia generally occurred within hours to days following coadministration; however, some cases have occurred 2 weeks following the initiation of HCV treatment. The risk of bradycardia may be increased in patients taking beta blockers or patients with underlying cardiac comorbidities and/or advanced liver disease. Bradycardia generally resolves following discontinuation of HCV treatment. Coadministration of amiodarone with simeprevir and sofosbuvir in combination is not recommended. However, if patients have no treatment alternatives, patients should be counseled about the interaction and have in-patient cardiac monitoring for the first 48 hours of coadministration followed by daily outpatient or self-monitoring of heart rate for at least the first 2 weeks of treatment. Due to the long half-life of amiodarone, cardiac monitoring (as described) is also recommended if amiodarone was discontinued just prior to beginning treatment with sofosbuvir and simeprevir. Patients should seek medical attention immediately if they experience fainting or near-fainting, dizziness, lightheadedness, malaise, weakness, excessive tiredness, shortness of breath, chest pains, confusion, or memory problems.

Other warnings/precautions:

• Appropriate use: Do not use as monotherapy; use only as part of a multiple-drug regimen for treatment of HCV.

• Resistance: Reduced sustained virologic response (SVR) rates of simeprevir in combination with sofosbuvir were observed in patients infected with hepatitis C genotype 1a with an NS3 Q80K polymorphism compared to patients without the polymorphism; consider alternative therapy in these patients. Patients with compensated cirrhosis and hepatitis C genotype 1a should be evaluated for the presence of the Q80K polymorphism; alternative regimens should be used if Q80K variant is present (Lawitz 2016).

Product Availability

Olysio tablets have been discontinued in the US for more than 1 year.

Generic Equivalent Available: US

Yes

Pricing: US

Capsules (Olysio Oral)

150 mg (28): $26544.00

Disclaimer: The pricing data provide a representative AWP and/or AAWP price from a single manufacturer of the brand and/or generic product, respectively. The pricing data should be used for benchmarking purposes only, and as such should not be used to set or adjudicate any prices for reimbursement or purchasing functions. Pricing data is updated monthly.

Administration: Adult

Oral: Administer with food. Swallow capsules whole; do not chew, crush, break, cut, or dissolve the capsule.

Use: Labeled Indications

Chronic hepatitis C: Treatment of genotype 1 chronic hepatitis C in combination with sofosbuvir in adults without cirrhosis or with compensated cirrhosis.

Limitations of use: Not recommended for use in patients who have previously failed a simeprevir-containing regimen or another regimen containing hepatitis C virus (HCV) protease inhibitors.

Note: The American Association for the Study of Liver Diseases/Infectious Diseases Society of America guidelines for testing, managing, and treating hepatitis C no longer include simeprevir as a component of recommended treatment regimens for HCV infection (AASLD/IDSA 2021).

Metabolism/Transport Effects

Substrate of CYP3A4 (major), OATP1B1/1B3 (SLCO1B1/1B3), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BCRP/ABCG2, CYP1A2 (weak), CYP3A4 (weak), OATP1B1/1B3 (SLCO1B1/1B3), P-glycoprotein/ABCB1

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Risk D: Consider therapy modification

Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Aliskiren. Risk C: Monitor therapy

Alpelisib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Alpelisib. Management: Avoid coadministration of BCRP/ABCG2 inhibitors and alpelisib due to the potential for increased alpelisib concentrations and toxicities. If coadministration cannot be avoided, closely monitor for increased alpelisib adverse reactions. Risk D: Consider therapy modification

ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ALPRAZolam. Risk C: Monitor therapy

Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination

Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy

Antidiabetic Agents: Direct Acting Antiviral Agents (HCV) may enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Asciminib: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy

Asunaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Asunaprevir. Risk X: Avoid combination

Atogepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Atogepant. Management: For episodic migraine, the recommended atogepant dose is 10 mg or 30 mg once daily if given with OATP1B1/1B3 inhibitors. For chronic migraine, the recommended atogepant dose is 30 mg once daily with OATP1B1/1B3 inhibitors. Risk D: Consider therapy modification

Atorvastatin: Simeprevir may increase the serum concentration of Atorvastatin. Management: The maximum atorvastatin dose should not exceed 40 mg/day with concurrent use of simeprevir, and use of the lowest necessary atorvastatin dose is recommended. Monitor for atorvastatin toxicity with concomitant use. Risk D: Consider therapy modification

Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Risk X: Avoid combination

Brincidofovir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Brincidofovir. Management: Consider alternatives to OATP1B/1B3 inhibitors in patients treated with brincidofovir. If coadministration is required, administer OATP1B1/1B3 inhibitors at least 3 hours after brincidofovir and increase monitoring for brincidofovir adverse reactions. Risk D: Consider therapy modification

Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Risk C: Monitor therapy

Cisapride: Simeprevir may increase the serum concentration of Cisapride. Risk X: Avoid combination

Cladribine: BCRP/ABCG2 Inhibitors may increase the serum concentration of Cladribine. Management: Avoid concomitant use of BCRP inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider dose reduction of the BCRP inhibitor and separation in the timing of administration. Risk D: Consider therapy modification

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy

Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: This combination is often contraindicated, but combined use may be permitted with dose adjustment and monitoring. Recommendations vary based on brand, indication, use of CYP3A4 inhibitors, and hepatic/renal function. See interaction monograph for details. Risk D: Consider therapy modification

CycloSPORINE (Systemic): Simeprevir may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Simeprevir. Risk X: Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Simeprevir. Risk X: Avoid combination

CYP3A4 Inducers (Strong): May decrease the serum concentration of Simeprevir. Risk X: Avoid combination

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Simeprevir. Risk X: Avoid combination

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Simeprevir. Risk X: Avoid combination

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Risk C: Monitor therapy

Darolutamide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy

Delavirdine: May increase the serum concentration of Simeprevir. Risk X: Avoid combination

DexAMETHasone (Systemic): May decrease the serum concentration of Simeprevir. Risk X: Avoid combination

Digoxin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Digoxin. Management: Measure digoxin serum concentrations before initiating treatment with these P-glycoprotein (P-gp) inhibitors. Reduce digoxin concentrations by either reducing the digoxin dose by 15% to 30% or by modifying the dosing frequency. Risk D: Consider therapy modification

Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Risk C: Monitor therapy

DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination

DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor therapy

Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Risk C: Monitor therapy

Elagolix: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix. Risk X: Avoid combination

Elagolix, Estradiol, and Norethindrone: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix, Estradiol, and Norethindrone. Specifically, concentrations of elagolix may be increased. Risk X: Avoid combination

Elbasvir and Grazoprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination

Eltrombopag: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy

Eluxadoline: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with OATP1B1/1B3 inhibitors and monitor patients for increased eluxadoline effects/toxicities. Risk D: Consider therapy modification

Erythromycin (Systemic): May increase the serum concentration of Simeprevir. Simeprevir may increase the serum concentration of Erythromycin (Systemic). Risk X: Avoid combination

Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide. Risk C: Monitor therapy

Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide Phosphate. Risk C: Monitor therapy

Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Risk C: Monitor therapy

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Fezolinetant: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Fezolinetant. Risk X: Avoid combination

Finerenone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Finerenone. Risk C: Monitor therapy

Flecainide: Simeprevir may increase the serum concentration of Flecainide. Risk C: Monitor therapy

Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Risk C: Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Gemfibrozil: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy

Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor therapy

Ixabepilone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ixabepilone. Risk C: Monitor therapy

Lapatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lapatinib. Risk C: Monitor therapy

Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib. Risk C: Monitor therapy

Ledipasvir: Simeprevir may increase the serum concentration of Ledipasvir. Ledipasvir may increase the serum concentration of Simeprevir. Risk X: Avoid combination

Leflunomide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy

Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider therapy modification

Leniolisib: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination

Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider therapy modification

Lovastatin: Simeprevir may increase the serum concentration of Lovastatin. Risk C: Monitor therapy

Methoxsalen (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy

Mexiletine: Simeprevir may increase the serum concentration of Mexiletine. Risk C: Monitor therapy

Midazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Midazolam. Risk C: Monitor therapy

Milk Thistle: May increase the serum concentration of Simeprevir. Risk X: Avoid combination

Momelotinib: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Momelotinib. Risk C: Monitor therapy

Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Risk C: Monitor therapy

Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Nadolol. Risk C: Monitor therapy

Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. Risk C: Monitor therapy

Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Risk C: Monitor therapy

Nevirapine: May decrease the serum concentration of Simeprevir. Risk X: Avoid combination

NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy

OXcarbazepine: May decrease the serum concentration of Simeprevir. Risk X: Avoid combination

PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination

PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination

Phosphodiesterase 5 Inhibitors: Simeprevir may increase the serum concentration of Phosphodiesterase 5 Inhibitors. Risk C: Monitor therapy

Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination

Pitavastatin: Simeprevir may increase the serum concentration of Pitavastatin. Risk C: Monitor therapy

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy

Pralsetinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider therapy modification

Pravastatin: Simeprevir may increase the serum concentration of Pravastatin. Risk C: Monitor therapy

Pretomanid: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy

Propafenone: Simeprevir may increase the serum concentration of Propafenone. Risk C: Monitor therapy

Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Risk C: Monitor therapy

Red Yeast Rice: Simeprevir may increase the serum concentration of Red Yeast Rice. Risk C: Monitor therapy

Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider therapy modification

Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider therapy modification

Repotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Repotrectinib. Risk X: Avoid combination

Revefenacin: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentrations of the active metabolite(s) of Revefenacin. Risk X: Avoid combination

RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Risk C: Monitor therapy

Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rimegepant. Management: Avoid administration of another dose of rimegepant within 48 hours if given concomitantly with a P-glycoprotein (P-gp) inhibitor. Risk D: Consider therapy modification

RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RisperiDONE. Risk C: Monitor therapy

RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RomiDEPsin. Risk C: Monitor therapy

Rosuvastatin: Simeprevir may increase the serum concentration of Rosuvastatin. Management: Limit initial rosuvastatin dose to 5 mg/day when being started in a patient who is also being treated with simeprevir. The maximum rosuvastatin dose should not exceed 10 mg/day with concurrent use of simeprevir. Risk D: Consider therapy modification

Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Risk C: Monitor therapy

Simvastatin: Simeprevir may increase the serum concentration of Simvastatin. Risk C: Monitor therapy

Sirolimus (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with P-glycoprotein (P-gp) inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Monitor for increased sirolimus concentrations/toxicity if combined. Risk D: Consider therapy modification

Sirolimus (Protein Bound): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination

Tacrolimus (Systemic): Simeprevir may decrease the serum concentration of Tacrolimus (Systemic). Tacrolimus (Systemic) may increase the serum concentration of Simeprevir. Risk C: Monitor therapy

Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy

Talazoparib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy

Taurursodiol: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Taurursodiol. Risk X: Avoid combination

Tegaserod (Withdrawn from US Market): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod (Withdrawn from US Market). Risk C: Monitor therapy

Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Teniposide. Risk C: Monitor therapy

Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy

Teriflunomide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy

Theophylline Derivatives: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy

TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Risk D: Consider therapy modification

Topotecan: BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination

Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination

Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Risk C: Monitor therapy

Trofinetide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Avoid concurrent use with OATP1B1/1B3 substrates for which small changes in exposure may be associated with serious toxicities. Monitor for evidence of an altered response to any OATP1B1/1B3 substrate if used together with trofinetide. Risk D: Consider therapy modification

Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Risk D: Consider therapy modification

Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of a P-gp inhibitor. Risk D: Consider therapy modification

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy

VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination

Vitamin K Antagonists (eg, warfarin): Direct Acting Antiviral Agents (HCV) may diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Voclosporin: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy

Voxilaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Voxilaprevir. Risk X: Avoid combination

Zavegepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Zavegepant. Risk X: Avoid combination

Reproductive Considerations

Patients with hepatitis C virus (HCV) infection should be treated before considering pregnancy to optimize maternal health and reduce the risk of HCV transmission (AASLD/IDSA 2021).

Simeprevir is not used as monotherapy; when used in combination with ribavirin, all warnings related to the use of ribavirin and contraception should be followed. Also refer to the ribavirin monograph for additional information.

Pregnancy Considerations

Simeprevir is not used as monotherapy; combination therapy with ribavirin is contraindicated in pregnant patients and males whose partners are pregnant. If used in combination with ribavirin, all warnings related to the use of ribavirin and pregnancy should be followed. Refer to the ribavirin monograph for additional information.

Outcome data following maternal use of direct-acting antiviral (DAA) medications during pregnancy are limited. Use of a DAA is not currently recommended for the purpose of reducing mother to child transmission of hepatitis C virus due to a lack of safety and efficacy data. The decision to continue treatment in a patient who becomes pregnant while taking a DAA should be individualized after considering the potential benefits and risks of therapy. DAA medications should not be initiated during pregnancy outside of clinical trials until safety and efficacy data are available (AASLD/IDSA 2021; SMFM [Dotters-Katz 2021]).

Breastfeeding Considerations

It is not known if simeprevir is present in breast milk.

According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Breastfeeding is not linked to the spread of hepatitis C virus; however, if nipples are cracked or bleeding, breastfeeding is not recommended (milk should be expressed and discarded) (AASLD/IDSA 2021; SMFM [Dotters-Katz 2021]).

Monitoring Parameters

Baseline (obtain any time prior to treatment initiation) quantitative hepatitis C virus (HCV) RNA; HCV genotype and subtype (if a non–pan-genotypic direct-acting antiviral [DAA] will be prescribed); staging of fibrosis. Baseline (within 6 months prior to treatment initiation) CBC, INR, hepatic function (albumin, total and direct bilirubin, ALT, AST, alkaline phosphatase), calculated GFR. Before initiating DAA therapy, serum pregnancy test (women of childbearing age) and assessment for HIV coinfection. During treatment, monitor CBC, serum creatinine, calculated GFR, hepatic function panel as clinically indicated. Quantitative HCV viral load testing ≥12 weeks after completion of therapy. Hepatitis B virus (HBV) surface antigen, HBV core antibody, and HBV surface antibody prior to initiation (AASLD/IDSA 2021). Screen patients infected with HCV genotype 1a for the presence of virus with the NS3 Q80K polymorphism prior to the initiation of treatment.

In patients with serologic evidence of HBV infection, monitor for clinical and laboratory signs of hepatitis flare or HBV reactivation during treatment and during posttreatment follow-up.

In patients with diabetes, monitor blood glucose and for signs/symptoms of hypoglycemia (AASLD/IDSA 2021; Ciancio 2018; Dawood 2017; Hum 2017); in patients taking warfarin, monitor INR during and post-therapy (AASLD/IDSA 2021).

Mechanism of Action

Simeprevir is an inhibitor of HCV NS3/4A protease, a protease that is essential for viral replication. It is considered a direct-acting antiviral treatment for HCV, also called a specifically targeted antiviral therapy for HCV (STAT-C).

Pharmacokinetics (Adult Data Unless Noted)

Absorption: Food enhances absorption.

Protein binding: >99.9% (albumin and alpha 1-acid glycoprotein)

Metabolism: Primarily oxidative metabolism by CYP3A4 (and possibly CYP2C8 and CYP2C19) to unchanged drug and metabolites (minor).

Bioavailability: 62% (single dose under fed conditions)

Half-life elimination: Plasma: 10 to 13 hours (healthy volunteers); 41 hours (HCV-infected patients)

Time to peak, serum: 4 to 6 hours

Excretion: Feces (~91%); urine (<1%)

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Hepatic function impairment: Mean steady-state AUC of simeprevir was 2.4-fold higher in HCV-uninfected subjects with moderate hepatic impairment (Child-Pugh class B) and 5.2-fold higher in HCV-uninfected subjects with severe hepatic impairment (Child-Pugh class C) compared with HCV-uninfected subjects with normal hepatic function.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Olysio;
  • (AR) Argentina: Olysio;
  • (AT) Austria: Olysio;
  • (AU) Australia: Olysio;
  • (BE) Belgium: Olysio;
  • (BR) Brazil: Olysio;
  • (CH) Switzerland: Olysio;
  • (CO) Colombia: Olysio;
  • (CZ) Czech Republic: Olysio;
  • (DE) Germany: Olysio;
  • (EE) Estonia: Olysio;
  • (EG) Egypt: Olysio;
  • (ES) Spain: Olysio;
  • (FR) France: Olysio;
  • (GB) United Kingdom: Olysio;
  • (GR) Greece: Olysio;
  • (HU) Hungary: Olysio;
  • (ID) Indonesia: Olysio;
  • (IE) Ireland: Olysio;
  • (IT) Italy: Olysio;
  • (KW) Kuwait: Olysio;
  • (LT) Lithuania: Olysio;
  • (LV) Latvia: Olysio;
  • (MX) Mexico: Olysio;
  • (NL) Netherlands: Olysio;
  • (NO) Norway: Olysio;
  • (PE) Peru: Olysio;
  • (PL) Poland: Olysio;
  • (PT) Portugal: Olysio;
  • (RO) Romania: Olysio;
  • (RU) Russian Federation: Sovriad;
  • (SA) Saudi Arabia: Olysio;
  • (SE) Sweden: Olysio;
  • (SG) Singapore: Olysio;
  • (SI) Slovenia: Olysio;
  • (SK) Slovakia: Olysio;
  • (TR) Turkey: Olysio
  1. American Association for the Study of Liver Diseases (AASLD), Infectious Diseases Society of America (IDSA). HCV guidance: recommendations for testing, managing, and treating hepatitis C. https://www.hcvguidelines.org. Updated October 5, 2021. Accessed March 24, 2022.
  2. Chastain CA, Naggie S. Treatment of Genotype 1 HCV Infection in the HIV Coinfected Patient in 2014. Curr HIV/AIDS Rep. 2013;10(4):408-419. [PubMed 24272069] 10.1007/s11904-013-0182-8
  3. Ciancio A, Bosio R, Bo S, et al. Significant improvement of glycemic control in diabetic patients with HCV infection responding to direct-acting antiviral agents. J Med Virol. 2018;90(2):320-327. doi:10.1002/jmv.24954 [PubMed 28960353]
  4. Dawood AA, Nooh MZ, Elgamal AA. Factors associated with improved glycemic control by direct-acting antiviral agent treatment in Egyptian type 2 diabetes mellitus patients with chronic hepatitis C genotype 4. Diabetes Metab J. 2017;41(4):316-321. doi:10.4093/dmj.2017.41.4.316 [PubMed 28868829]
  5. Dienstag JL, McHutchison JG. American Gastroenterological Association medical position statement on the management of hepatitis C. Gastroenterology. 2006;130(1):225-230. [PubMed 16401485]
  6. Dotters-Katz SK, Kuller JA, Hughes BL. Society for Maternal-Fetal Medicine Consult Series #56: hepatitis C in pregnancy-updated guidelines: replaces Consult Number 43, November 2017. Am J Obstet Gynecol. 2021;225(3):B8-B18. doi:10.1016/j.ajog.2021.06.008 [PubMed 34116035]
  7. FDA Safety Alert. MedWatch. Direct-acting antiviral for hepatitis C: drug safety communication – risk of hepatitis B reactivating. Food and Drug Administration website. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm523690.htm. Accessed December 8, 2016.
  8. Fried MW, Buti M, Dore GJ, et al. Once-daily simeprevir (TMC435) with pegylated interferon and ribavirin in treatment-naïve genotype 1 hepatitis C: The randomized PILLAR study. Hepatology. 2013;58(6):1918-1929. [PubMed 23907700]
  9. Galexos (Simeprevir) [product monograph]. Toronto, Ontario, Canada: Janssen Inc; July 2017.
  10. Hoofnagle JH, Seeff LB. Peginterferon and ribavirin for chronic hepatitis C. N Engl J Med. 2006;355(23):2444-2451. [PubMed 17151366]
  11. Hum J, Jou JH, Green PK, et al. Improvement in glycemic control of type 2 diabetes after successful treatment of hepatitis C virus. Diabetes Care. 2017;40(9):1173-1180. doi:10.2337/dc17-0485 [PubMed 28659309]
  12. Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med. 2001;345(1):41-52. [PubMed 11439948]
  13. Lawitz E, Matusow G, DeJesus E, et al. Simeprevir plus sofosbuvir in patients with chronic hepatitis C virus genotype 1 infection and cirrhosis: a phase 3 study (OPTIMIST-2). Hepatology. 2016;64(2):360-369. doi: 10.1002/hep.28422. [PubMed 26704148]
  14. Olysio (simeprevir) [prescribing information]. Titusville, NJ: Janssen Therapeutics; November 2017.
  15. Zeuzem S, Berg T, Gane E, et al. Simeprevir Increases Rate of Sustained Virologic Response Among Treatment-Experienced Patients With HCV Genotype-1 Infection: A Phase IIb Trial [published online ahead of print November 1, 2013]. Gastroenterology. [PubMed 24184810]
Topic 91660 Version 260.0

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