Note: This document contains side effect information about simeprevir. Some dosage forms listed on this page may not apply to the brand name Olysio.

Applies to simeprevir: oral capsule.

Serious side effects of Olysio

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Shortness of breath.
• Red, blistered, or swollen skin.
• Very bad skin irritation.
• Mouth sores.
• Eye irritation.
• Very bad and sometimes deadly liver problems have happened with this drug. Call your doctor right away if you have signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.

Other side effects of Olysio

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.
• 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 1-800-332-1088. You may also report side effects at https://www.fda.gov/medwatch.

For Healthcare Professionals

Applies to simeprevir: oral capsule.

General

In clinical trials, most side effects reported in hepatitis C virus (HCV) genotype 1-infected patients with compensated cirrhosis (Child-Pugh A) or without cirrhosis using this drug with sofosbuvir (without ribavirin) for 12 or 24 weeks were grade 1 or 2 in severity; grade 3 or 4 side effects were reported in 4% and 13% of patients receiving this therapy for 12 and 24 weeks, respectively. Serious side effects were reported in 2% (12 weeks therapy) and 3% (24 weeks therapy) of patients, respectively. The most common side effects reported in patients using this drug plus sofosbuvir for 12 or 24 weeks were fatigue, headache, rash (including photosensitivity reaction), diarrhea, dizziness, nausea, constipation, and pruritus. Therapy was discontinued due to side effects in 1% (12 weeks therapy) and 6% (24 weeks therapy) of patients, respectively.

In clinical trials, most side effects reported in HCV genotype 1-infected patients using this drug with peginterferon alfa and ribavirin for 12 weeks were grade 1 to 2 in severity; grade 3 or 4 side effects were reported in up to 23% of patients using this drug with peginterferon alfa and ribavirin and in up to 25% using placebo with peginterferon alfa and ribavirin. Serious side effects were reported in up to 2% of patients using this drug with peginterferon alfa and ribavirin and in up to 3% using placebo with peginterferon alfa and ribavirin. During the first 12 weeks of therapy with this drug plus peginterferon alfa and ribavirin, the most common side effects were rash (including photosensitivity), nausea, pruritus, myalgia, dyspnea, increased blood bilirubin, and photosensitivity reaction. This drug was discontinued due to side effects in up to 2% of patients using this drug with peginterferon alfa and ribavirin.

The manufacturer product information for coadministered HCV antiviral drugs should be consulted for associated side effects.^[Ref]

Hepatic

Very common (10% or more): Increased blood bilirubin (term included increased conjugated bilirubin, increased blood bilirubin, increased unconjugated blood bilirubin, hyperbilirubinemia; up to 66%)

Postmarketing reports: Hepatic decompensation, hepatic failure^[Ref]

Grade 1, 2, and 3 hyperbilirubinemia were reported in 12%, 3%, and less than 1% of patients using this drug plus sofosbuvir for 12 weeks, respectively. Grade 1, 2, and 4 hyperbilirubinemia were reported in 16%, 3%, and 3% of patients using this drug plus sofosbuvir for 24 weeks, respectively. In 1 trial, increased bilirubin was reported in no patients using this drug plus sofosbuvir (without ribavirin) for 12 weeks versus 9.3% of patients using this drug plus sofosbuvir and ribavirin for 12 weeks.

During the 12 weeks of therapy with this drug plus peginterferon alfa and ribavirin, grade 1, 2, 3, and 4 hyperbilirubinemia were reported in 26.7%, 18.3%, 4.1%, and 0.4% of patients, respectively. Bilirubin elevations were mostly mild to moderate in severity, and included elevation of both direct and indirect bilirubin. Bilirubin elevations occurred soon after therapy started, peaked by the second week, and reversed quickly after this drug was stopped. In general, bilirubin elevations (direct and indirect) were not associated with liver transaminase elevations. The incidence of increased bilirubin was higher in patients with increased simeprevir exposures (e.g., patients with severe liver dysfunction); such bilirubin increases were not associated with any adverse liver safety finding.

Compared to a pooled phase 3 population from global trials, East Asian patients using this drug with peginterferon alfa and ribavirin had a higher incidence of hyperbilirubinemia; elevated total bilirubin (all grades) was reported in up to 66% of patients. Bilirubin elevations were primarily grade 1 or 2; grade 3 bilirubin elevations were reported in up to 9% of patients. Bilirubin elevations were not associated with liver transaminase elevations and were reversible after therapy ended.

Hepatic decompensation and hepatic failure (including fatalities) have been reported with this drug coadministered with peginterferon alfa and ribavirin or with sofosbuvir. Most reports occurred in patients with advanced and/or decompensated cirrhosis.^[Ref]

Dermatologic

In trials of this drug plus sofosbuvir, rash (including photosensitivity reactions) was reported in 12% and 16% of patients receiving therapy for 12 and 24 weeks, respectively; pruritus was reported in 8.4% (12 weeks therapy) and 3.2% (24 weeks therapy) of patients. Most rash events were of mild or moderate severity (grade 1 or 2); most photosensitivity reactions were of mild severity (grade 1). Grade 3 rash was reported in 1 patient; therapy was discontinued. In 1 trial, rash was reported in 10.7% of patients using this drug plus sofosbuvir (without ribavirin) for 12 weeks versus 20.4% of patients using this drug plus sofosbuvir and ribavirin for 12 weeks.

Photosensitivity reactions (all grades) were reported in 3.1% (12 weeks therapy) and 6.5% (24 weeks therapy) of patients using this drug plus sofosbuvir. Most photosensitivity reactions were of mild severity (grade 1); grade 2 photosensitivity reactions were reported in 2 patients (12 weeks therapy). In 1 trial, photosensitivity reactions were reported in 7.1% of patients using this drug plus sofosbuvir (without ribavirin) for 12 weeks versus 5.6% of patients using this drug plus sofosbuvir and ribavirin for 12 weeks.

In trials of this drug plus peginterferon alfa and ribavirin, rash (including photosensitivity reactions) and pruritus were reported in up to 28% and 21.9% of patients, respectively, during the 12 weeks with this drug. Fifty-six percent (56%) of rash events occurred in the first 4 weeks; 42% in the first 2 weeks. Most rash and pruritus events were of mild or moderate severity (grade 1 or 2); severe rash and pruritus (grade 3) were reported in up to 1% and 0.1% of patients, respectively. This drug was discontinued due to rash and pruritus in up to 1% and 0.1% of patients, respectively. The frequencies of rash and photosensitivity reactions were higher in those with higher simeprevir (the active ingredient contained in Olysio) exposures.

All trial subjects were directed to use sun protection measures. In these trials, photosensitivity (specifically) was reported in 5% of patients during the 12 weeks of therapy with this drug plus peginterferon alfa and ribavirin. Most photosensitivity reactions were of mild or moderate severity (grade 1 or 2). Photosensitivity reactions requiring hospitalization occurred in 2 patients.^[Ref]

Very common (10% or more): Rash (including photosensitivity; term included rash, erythema, eczema, maculopapular rash, macular rash, dermatitis, papular rash, skin exfoliation, pruritic rash, erythematous rash, urticaria, generalized rash, drug eruption, allergic dermatitis, dermatosis, vasculitic rash, toxic skin eruption, exfoliative rash, generalized erythema, exfoliative dermatitis, cutaneous vasculitis, photosensitivity reaction, polymorphic light eruption, solar dermatitis, photodermatosis, sunburn, blister, macule, erythema of eyelid, palmar erythema, papule, pityriasis rosea, follicular rash, morbilliform rash, pustular rash, scrotal erythema, skin irritation, skin reaction, umbilical erythema; up to 28%), pruritus (term included pruritus, generalized pruritus, eyelids pruritus, prurigo; up to 22%)

Common (1% to 10%): Photosensitivity reaction^[Ref]

Other

Very common (10% or more): Fatigue (up to 32%)

Common (1% to 10%): Increased alkaline phosphatase

During the 12 weeks of therapy with this drug plus peginterferon alfa and ribavirin, grade 1 and 2 alkaline phosphatase elevations were reported in 3.3% and 0.1% of patients, respectively.

Gastrointestinal

Very common (10% or more): Elevated amylase (up to 26%), nausea (up to 22%), diarrhea (up to 16%)

Common (1% to 10%): Constipation, elevated lipase^[Ref]

Grade 1, 2, and 3 amylase elevations were reported in 11.9%, 5.2%, and 4.5% of patients using this drug plus sofosbuvir for 12 weeks, respectively. Grade 1, 2, and 3 amylase elevations were reported in 25.8%, 6.5%, and 9.7% of patients using this drug plus sofosbuvir for 24 weeks, respectively.

Grade 1, 2, 3, and 4 lipase elevations were reported in 4.5%, 7.7%, 0.3%, and 0.3% of patients using this drug plus sofosbuvir for 12 weeks, respectively. Grade 1, 2, 3, and 4 lipase elevations were reported in 3.2%, 9.7%, 3.2%, and 3.2% of patients using this drug plus sofosbuvir for 24 weeks, respectively.

Most amylase and lipase elevations were transient and of mild or moderate severity; such elevations were not associated with pancreatitis.^[Ref]

Nervous system

Very common (10% or more): Headache (up to 23%), dizziness (up to 16%)

Musculoskeletal

Very common (10% or more): Myalgia (up to 16%)^[Ref]

Psychiatric

Very common (10% or more): Insomnia (14%)

Hematologic

Very common (10% or more): Anemia (up to 13%)

Anemia was reported in 13% of patients using this drug with sofosbuvir and ribavirin and 0% using this drug with sofosbuvir.

A higher incidence of anemia was reported in patients with advanced fibrosis using this drug plus peginterferon alfa and ribavirin.

Respiratory

Very common (10% or more): Dyspnea (term included dyspnea, exertional dyspnea; up to 12%)^[Ref]

During the 12 weeks of therapy with this drug plus peginterferon alfa and ribavirin, dyspnea was reported in 12% of patients. All dyspnea events were of mild or moderate severity (grade 1 or 2). Sixty-one percent (61%) of dyspnea events occurred in the first 4 weeks. In patients older than 45 years, dyspnea was reported in 16.4% of patients using this drug compared to 9.1% using placebo with peginterferon alfa and ribavirin.^[Ref]

Cardiovascular

Postmarketing reports: Symptomatic bradycardia (including cases requiring pacemaker intervention)

Bradycardia has been reported when this drug was used with sofosbuvir and concomitant amiodarone. Serious symptomatic bradycardia has been reported in patients taking amiodarone who started therapy with a regimen containing sofosbuvir.