Simeprevir

It is not known if simeprevir is secreted into breast milk.

Simeprevir is a prescription medication used with other antiviral medicines to treat chronic hepatitis C virus infection (a viral disease that causes inflammation of the liver that can lead to diminished liver function or liver failure). 

Simeprevir belongs to a group of drugs called protease inhibitors that block a specific protein needed by the hepatitis C virus to replicate.

This medication comes in capsule form and is taken once daily with food. Swallow simeprevir capsules whole. The recommended duration of treatment with simeprevir is 12 weeks in combination with peginterferon alfa and ribavirin. 

Simeprevir can also be given with sofosbuvir for the treatment of chronic hepatitis C virus infection.

The most common side effects of simeprevir in combination with peginterferon-alfa and ribavirin are rash (including photosensitivity), itching and nausea. Limit sun exposure and use sun protective measures during treatment.

Simeprevir may be found in some form under the following brand names:

• Olysio

Simeprevir is part of the drug class:

• Protease inhibitors

• Simeprevir, in combination with peginterferon alfa and ribavirin may cause birth defects or death of your unborn baby. See "Pregnancy" section.
• Simeprevir in combination with peginterferon alfa and ribavirin may cause rashes and skin reactions to sunlight. These rashes and skin reactions to sunlight can be severe and you may need to be treated in a hospital. Rashes and skin reactions to sunlight are most common during the first 4 weeks of treatment, but can happen at any time during treatment with simeprevir, peginterferon alfa, and ribavirin combination therapy.
  • Use sunscreen, and wear a hat, sunglasses, and protective clothing when you will be exposed to sunlight during treatment with simeprevir.
  • Limit sunlight exposure during treatment with simeprevir.
  • Avoid use of tanning beds, sunlamps, or other types of light therapy during treatment with simeprevir.
  • Call your healthcare provider right away if you get any of the following symptoms:
    • burning, redness, swelling or blisters on your skin
    • mouth sores or ulcers
    • red or inflamed eyes, like "pink eye" (conjunctivitis)

• Do not take simeprevir alone. Simeprevir should be used together with peginterferon alfa and ribavirin or used in combination with sofosbuvir to treat chronic hepatitis C infection.

Contact your healthcare provider immediately if you develop weakness, fatigue, nausea, vomiting, yellow eyes or skin, loss of appetite, or light-colored stools. These may be signs and symptoms of a serious liver problem. 

Tell your healthcare provider if you are breastfeeding. It is not known if simeprevir passes into your breast milk. You and your healthcare provider should decide if you will take simeprevir or breastfeed. You should not do both.

Simeprevir is an antiviral medicine that prevents certain viruses from multiplying in your body. Simeprevir is used in combination with peginterferon alfa and ribavirin, or with sofosbuvir to treat hepatitis C genotype 1 or 4 in adults.

Read the medication guide or patient instructions provided with each medication in your combination therapy. Do not change your doses or medication schedule without your doctor's advice. Every person with hepatitis C should remain under the care of a doctor.

Simeprevir may also be used for purposes not listed in this medication guide.

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Simeprevir must be given in combination with other antiviral medications and it should not be used alone.

Take with food.

Do not crush, chew, break, or open a simeprevir capsule. Swallow it whole.

You will need frequent blood tests to check your liver function.

Read the medication guide or patient instructions provided with each medication in your combination therapy. Do not change your doses or medication schedule without your doctor's advice. Every person with chronic hepatitis C should remain under the care of a doctor.

You should not stop using simeprevir suddenly. Stopping suddenly could make your condition harder to treat with hepatitis C antiviral medicine.

If you have ever had hepatitis B, simeprevir can cause this condition to come back or get worse. You will need liver function tests during treatment and for several months after you stop using this medicine.

Store at room temperature away from moisture, heat, and light.

In the U.S.

• Olysio

Available Dosage Forms:

• Capsule

Therapeutic Class: Antiviral

Pharmacologic Class: Protease Inhibitor

It is very important that your doctor check your progress at regular visits to make sure simeprevir is working properly. Blood tests may be needed to check for unwanted effects.

Using simeprevir together with ribavirin while you are pregnant can harm your unborn baby. These medicines may also cause birth defects if the father is using it when his sexual partner becomes pregnant. If a pregnancy occurs while you are using these medicines, tell your doctor right away.

To make sure you are not pregnant, your doctor may ask you to have a pregnancy test before you start using simeprevir. You must have a negative pregnancy test before you will be allowed to use simeprevir with ribavirin. Two forms of birth control must be used during treatment and for 6 months after treatment ends. You should test for pregnancy every month while you are using simeprevir, and for 6 months after your treatment ends.

Do not take Olysio® in combination with sofosbuvir together with amiodarone. Using these medicines together may slow your heartbeat (bradycardia). Symptoms include fainting, dizziness, lightheadedness, trouble breathing, chest pain, or tiredness or weakness.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, vomiting, or yellow eyes or skin. These could be symptoms of a serious liver problem.

simeprevir may cause rashes and skin reactions to sunlight, which can be severe and must be treated in the hospital. This usually occurs during the first 4 weeks of treatment with simeprevir, peginterferon alfa, and ribavirin combination. Stay out of the sun as much as possible. Use a sunscreen or sun-blocking lotion when you are outdoors. Wear protective clothing and hats. Avoid sunlamps and tanning beds.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, milk thistle, St. John's wort) or vitamin supplements.

• It is used to treat long-term hepatitis C infections.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Itching.
• Upset stomach.
• Muscle pain.
• Loose stools (diarrhea).
• Dizziness.
• Headache.
• Feeling tired or weak.
• Not able to sleep.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

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.

Refer to adult dosing.

Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: Per US labeling: reduce afatinib by 10mg if not tolerated. Per Canadian labeling: avoid combination if possible; if used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib. Consider therapy modification

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

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

Asunaprevir: OATP1B1/SLCO1B1 Inhibitors may increase the serum concentration of Asunaprevir. Avoid combination

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. Consider therapy modification

Betrixaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Betrixaban. Management: Decrease the betrixaban dose to an initial single dose of 80 mg followed by 40 mg once daily if combined with a P-glycoprotein inhibitor. Consider therapy modification

Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Management: Consider alternatives when possible; bilastine should be avoided in patients with moderate to severe renal insufficiency who are receiving p-glycoprotein inhibitors. Consider therapy modification

Brentuximab Vedotin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Monitor therapy

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

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

CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. 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: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Consider therapy modification

Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

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

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

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

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

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

CYP3A4 Substrates: Simeprevir may increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Management: Dabigatran dose reductions may be needed. Specific recommendations vary considerably according to US vs Canadian labeling, specific P-gp inhibitor, renal function, and indication for dabigatran treatment. Refer to full monograph or dabigatran labeling. Consider therapy modification

Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

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

Dexamethasone (Systemic): May decrease the serum concentration of Simeprevir. Avoid combination

Digoxin: Simeprevir may increase the serum concentration of Digoxin. Monitor therapy

DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-glycoprotein inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification

Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: See full monograph for details. Reduced doses are recommended for patients receiving edoxaban for venous thromboembolism in combination with certain inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation. Consider therapy modification

Eltrombopag: May increase the serum concentration of OATP1B1/SLCO1B1 Substrates. Monitor therapy

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

Escitalopram: May decrease the serum concentration of Simeprevir. Monitor therapy

Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Consider therapy modification

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

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Gemfibrozil: May increase the serum concentration of OATP1B1/SLCO1B1 Substrates. See separate drug interaction monographs for agents listed as exceptions. Monitor therapy

Grazoprevir: OATP1B1/SLCO1B1 Inhibitors may increase the serum concentration of Grazoprevir. Avoid combination

Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

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

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

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

Midazolam: Simeprevir may increase the serum concentration of Midazolam. Monitor therapy

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

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

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

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

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

Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

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

P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

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

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

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

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

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

Protease Inhibitors: May increase the serum concentration of Simeprevir. Simeprevir may increase the serum concentration of Protease Inhibitors. Avoid combination

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

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

RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. 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. Consider therapy modification

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

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

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

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

St John's Wort: May decrease the serum concentration of Simeprevir. Avoid combination

Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Tenofovir Disoproxil Fumarate: May decrease the serum concentration of Simeprevir. Simeprevir may increase the serum concentration of Tenofovir Disoproxil Fumarate. Monitor therapy

Teriflunomide: May increase the serum concentration of OATP1B1/SLCO1B1 Substrates. 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. Consider therapy modification

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

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

Triazolam: Simeprevir may increase the serum concentration of Triazolam. Monitor therapy

Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring these combinations. Consider therapy modification

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

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

Voxilaprevir: OATP1B1/SLCO1B1 Inhibitors may increase the serum concentration of Voxilaprevir. Avoid combination

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% (Limited to important or life-threatening): Hepatic failure, liver decompensation, reactivation of HBV (FDA Safety Alert Dec. 8, 2016)

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).