July 27, 2016
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Olysio

"The U.S. Food and Drug Administration today approved Harvoni (ledipasvir and sofosbuvir) to treat chronic hepatitis C virus (HCV) genotype 1 infection.

Harvoni is the first combination pill approved to treat chronic HCV genotype 1 infecti"...

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Olysio




Olysio Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

Last reviewed on RxList 4/23/2015

Olysio (simeprevir) is a protease inhibitor used to treat chronic hepatitis C (CHC) infection as a component of a combination antiviral treatment regimen. Common side effects of Olysio include skin rash, itching, nausea, muscle pain, and indigestion.

The recommended dose of Olysio is one capsule of 150 mg taken orally once daily with food. Olysio may interact with amiodarone, amlodipine, antibiotics, azole antifungals, statins, medications to treat erectile dysfunction, antiviral medications, carbamazepine, cisapride, cobicistat-containing medicine, cyclosporine, dexamethasone, digoxin, diltiazem, disopyramide, felodipine, flecainide, mexiletine, midazolam, milk thistle, nicardipine, nifedipine, nisoldipine, oxcarbazepine, phenobarbital, phenytoin, propafenone, quinidine, sirolimus, St. John's wort, tacrolimus, telithromycin, triazolam, verapamil , or warfarin. Tell your doctor all medications and supplements you use. Olysio must not be used by women who are pregnant or by men whose partners are pregnant. Women should have a negative pregnancy test before stating this medication. Consult your doctor about using two forms of birth control while taking Olysio. It is unknown if this drug passes into breast milk. Consult your doctor before breastfeeding.

Our Olysio (simeprevir) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is Prescribing information?

The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.

Olysio FDA Prescribing Information: Side Effects
(Adverse Reactions)

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:

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

OLYSIO In Combination With Sofosbuvir

The safety profile of OLYSIO in combination with sofosbuvir in patients with HCV genotype 1 infection with compensated cirrhosis (Child-Pugh A) or without cirrhosis is based on pooled data from the Phase 2 COSMOS trial and the Phase 3 OPTIMIST-1 and OPTIMIST-2 trials which included 317 subjects who received OLYSIO with sofosbuvir (without RBV) for 12 or 24 weeks [see Clinical Studies].

Table 4 lists adverse events (all grades) that occurred with at least 10% frequency among subjects receiving 12 or 24 weeks of treatment with OLYSIO 150 mg once daily in combination with sofosbuvir 400 mg once daily without RBV. The overall safety profile appeared similar among cirrhotic and non-cirrhotic subjects [see DOSAGE AND ADMINISTRATION].

The majority of the adverse events reported were Grade 1 or 2 in severity. Grade 3 or 4 adverse events were reported in 4% and 13% of subjects receiving 12 or 24 weeks of OLYSIO with sofosbuvir, respectively. Serious adverse events were reported in 2% and 3% of subjects receiving 12 or 24 weeks of OLYSIO with sofosbuvir, respectively. One percent and 6% of subjects receiving 12 or 24 weeks of OLYSIO with sofosbuvir, respectively, discontinued treatment due to adverse events.

Table 4: Adverse Events (all Grades) that Occurred ≥ 10% Frequency Among Subjects Receiving 12 or 24 Weeks of OLYSIO in Combination with Sofosbuvir±

Adverse Events 12 Weeks OLYSIO +Sofosbuvir
N=286% (n)
24 Weeks OLYSIO +Sofosbuvir
N=31% (n)
Headache 17 (49) 23 (7)
Fatigue 16 (47) 32 (10)
Nausea 14 (40) 13 (4)
Rash (including photosensitivity) 12 (34) 16 (5)
Diarrhea 6 (18) 16 (5)
Dizziness 3 (10) 16 (5)
± The 12 week group represents subjects pooled from COSMOS, OPTIMIST-1, and OPTIMIST-2 trials. The 24 week group represents subjects from COSMOS trial.

Rash And Photosensitivity

In trials of OLYSIO in combination with sofosbuvir, rash (including photosensitivity reactions) was observed in 12% of OLYSIO-treated subjects receiving 12 weeks of treatment compared to 16% of OLYSIO-treated subjects receiving 24 weeks of treatment.

Most of the rash events in OLYSIO-treated subjects were of mild or moderate severity (Grade 1 or 2). Among 317 subjects, Grade 3 rash was reported in one subject ( < 1%), leading to treatment discontinuation; none of the subjects experienced Grade 4 rash.

Most photosensitivity reactions were of mild severity (Grade 1); Grade 2 photosensitivity reactions were reported in 2 of 317 subjects ( < 1%). No Grade 3 or 4 photosensitivity reactions were reported and none of the subjects discontinued treatment due to photosensitivity reactions.

Laboratory Abnormalities

Among subjects who received OLYSIO in combination with sofosbuvir, the most common Grade 3 and 4 laboratory abnormalities were amylase and lipase elevations (Table 5). Most elevations in amylase and lipase were transient and of mild or moderate severity. Amylase and lipase elevations were not associated with pancreatitis.

Table 5: Laboratory Abnormalities (WHO Worst Toxicity Grades 1 to 4) in Amylase, Hyperbilirubinemia and Lipase in Subjects Receiving 12 or 24 Weeks of OLYSIO in Combination with Sofosbuvir±

Laboratory Parameter WHO Toxicity Range 12 Weeks OLYSIO + Sofosbuvir
N=286 %
24 Weeks OLYSIO + Sofosbuvir
N=31 %
Chemistry
Amylase*
  Grade 1 ≥ 1.1 to ≤ 1.5 x ULN† 12 26
  Grade 2 > 1.5 to ≤ 2.0 x ULN 5 6
  Grade 3 > 2.0 to ≤ 5.0 x ULN 5 10
Hyperbilirubinemia
  Grade 1 ≥ 1.1 to ≤ 1.5 x ULN 12 16
  Grade 2 > 1.5 to ≤ 3.0 x ULN 3 3
  Grade 3 > 3.0 to ≤ 5.0 x ULN < 1 0
  Grade 4 > 5.0 x ULN 0 3
Lipase
  Grade 1 ≥ 1.1 to ≤ 1.5 x ULN 5 3
  Grade 2 > 1.5 to ≤ 3.0 x ULN 8 10
  Grade 3 > 3.0 to ≤ 5.0 x ULN < 1 3
  Grade 4 > 5.0 x ULN < 1 3
± The 12 week group represents subjects pooled from COSMOS, OPTIMIST-1, and OPTIMIST-2 trials. The 24 week group represents subjects from COSMOS trial.
* No Grade 4 changes in amylase were observed.
† ULN = Upper Limit of Normal

OLYSIO In Combination With Peg-IFN-alfa And RBV

The safety profile of OLYSIO in combination with Peg-IFN-alfa and RBV in patients with HCV genotype 1 infection is based on pooled data from three Phase 3 trials (QUEST-1, QUEST-2 and PROMISE) [see Clinical Studies]. These trials included a total of 1178 subjects who received OLYSIO or placebo in combination with 24 or 48 weeks of Peg-IFN-alfa and RBV. Of the 1178 subjects, 781 subjects were randomized to receive OLYSIO 150 mg once daily for 12 weeks and 397 subjects were randomized to receive placebo once daily for 12 weeks.

In the pooled Phase 3 safety data, the majority of the adverse reactions reported during 12 weeks treatment with OLYSIO in combination with Peg-IFN-alfa and RBV were Grade 1 to 2 in severity. Grade 3 or 4 adverse reactions were reported in 23% of subjects receiving OLYSIO in combination with Peg-IFN-alfa and RBV versus 25% of subjects receiving placebo in combination with Peg-IFN-alfa and RBV. Serious adverse reactions were reported in 2% of subjects receiving OLYSIO in combination with Peg-IFN-alfa and RBV and in 3% of subjects receiving placebo in combination with Peg-IFN-alfa and RBV. Discontinuation of OLYSIO or placebo due to adverse reactions occurred in 2% and 1% of subjects receiving OLYSIO with Peg-IFN-alfa and RBV and subjects receiving placebo with Peg-IFN-alfa and RBV, respectively.

Table 6 lists adverse reactions (all Grades) that occurred with at least 3% higher frequency among subjects with HCV genotype 1 infection receiving OLYSIO 150 mg once daily in combination with Peg-IFN-alfa and RBV, compared to subjects receiving placebo in combination with Peg-IFN-alfa and RBV, during the first 12 weeks of treatment in the pooled Phase 3 trials in subjects who were treatment-na´ve or who had previously relapsed after Peg-IFN-alfa and RBV therapy.

Table 6: Adverse Reactions (all Grades) that occurred ≥ 3% Higher Frequency Among Subjects with HCV Genotype 1 Infection Receiving OLYSIO Combination with Peg-IFN-alfa and RBV Compared to Subjects Receiving Placebo in Combination with Peg-IFN-alfa and RBV During the First 12 Weeks of Treatment in Subjects with Chronic HCV Infection* (Pooled Phase 3†)

Adverse Reaction‡ OLYSIO 150 mg + Peg-IFN-alfa+ RBV First 12 Weeks
N=781 % (n)
Placebo + Peg-IFN-alfa+ RBV First 12 Weeks
N=397 % (n)
Rash (including photosensitivity) 28 (218) 20 (79)
Pruritus 22 (168) 15 (58)
Nausea 22 (173) 18 (70)
Myalgia 16 (126) 13 (53)
Dyspnea 12 (92) 8 (30)
* Subjects were treatment-na´ve or had previously relapsed after Peg-IFN-alfa and RBV therapy.
† Pooled Phase 3 trials: QUEST 1, QUEST 2, PROMISE.
‡ Adverse reactions that occurred at ≥ 3% higher frequency in the OLYSIO treatment group than in the placebo treatment group.

Rash And Photosensitivity

In the Phase 3 clinical trials of OLYSIO or placebo in combination with Peg-IFN-alfa and RBV, rash (including photosensitivity reactions) was observed in 28% of OLYSIO-treated subjects compared to 20% of placebo-treated subjects during the 12 weeks of treatment with OLYSIO or placebo in combination with Peg-IFN-alfa and RBV. Fifty-six percent (56%) of rash events in the OLYSIO group occurred in the first 4 weeks, with 42% of cases occurring in the first 2 weeks. Most of the rash events in OLYSIO-treated subjects were of mild or moderate severity (Grade 1 or 2). Severe (Grade 3) rash occurred in 1% of OLYSIO-treated subjects and in none of the placebo-treated subjects. There were no reports of life-threatening (Grade 4) rash. Discontinuation of OLYSIO or placebo due to rash occurred in 1% of OLYSIO-treated subjects, compared to less than 1% of placebo-treated subjects. The frequencies of rash and photosensitivity reactions were higher in subjects with higher simeprevir exposures.

All subjects enrolled in the Phase 3 trials were directed to use sun protection measures. In these trials, adverse reactions under the specific category of photosensitivity were reported in 5% of OLYSIO-treated subjects compared to 1% of placebo-treated subjects during the 12 weeks of treatment with OLYSIO or placebo in combination with Peg-IFN-alfa and RBV. Most photosensitivity reactions in OLYSIO-treated subjects were of mild or moderate severity (Grade 1 or 2). Two OLYSIO-treated subjects experienced photosensitivity reactions which resulted in hospitalization. No life-threatening photosensitivity reactions were reported.

Dyspnea

During the 12 weeks of treatment with OLYSIO or placebo in combination with Peg-IFN-alfa and RBV, dyspnea was reported in 12% of OLYSIO-treated subjects compared to 8% of placebo-treated subjects (all grades; pooled Phase 3 trials). All dyspnea events reported in OLYSIO-treated subjects were of mild or moderate severity (Grade 1 or 2). There were no Grade 3 or 4 dyspnea events reported and no subjects discontinued treatment with OLYSIO due to dyspnea. Sixty-one percent (61%) of dyspnea events occurred in the first 4 weeks of treatment with OLYSIO.

Laboratory Abnormalities

Among subjects who received OLYSIO or placebo plus Peg-IFN-alfa and RBV, there were no differences between treatment groups for the following laboratory parameters: hemoglobin, neutrophils, platelets, aspartate aminotransferase, alanine aminotransferase, amylase, or serum creatinine. Laboratory abnormalities that were observed at a higher incidence in OLYSIO-treated subjects than in placebo-treated subjects are listed in Table 7.

Table 7: Laboratory Abnormalities (WHO Worst Toxicity Grades 1 to 4) Observed at a Higher Incidence in OLYSIO-Treated Subjects (Pooled Phase 3*; First 12 Weeks of Treatment)

Laboratory Parameter WHO Toxicity Range OLYSIO 150 mg + Peg-IFN-alfa + RBV
N=781 %
Placebo + Peg-IFN-alfa + RBV
N=397 %
Chemistry
Alkaline phosphatase†
  Grade 1 > 1.25 to ≤ 2.50 x ULN‡ 3 1
  Grade 2 > 2.50 to ≤ 5.00 x ULN < 1 0
Hyperbilirubinemia
  Grade 1 > 1.1 to ≤ 1.5 x ULN 27 15
  Grade 2 > 1.5 to ≤ 2.5 x ULN 18 9
  Grade 3 > 2.5 to ≤ 5.0 x ULN 4 2
  Grade 4 > 5.0 x ULN < 1 0
* Pooled Phase 3 trials: QUEST 1, QUEST 2, PROMISE.
† No Grade 3 or 4 changes in alkaline phosphatase were observed.
‡ ULN = Upper Limit of Normal

Elevations in bilirubin were predominately mild to moderate (Grade 1 or 2) in severity, and included elevation of both direct and indirect bilirubin. Elevations in bilirubin occurred early after treatment initiation, peaking by study Week 2, and were rapidly reversible upon cessation of OLYSIO. Bilirubin elevations were generally not associated with elevations in liver transaminases. The frequency of elevated bilirubin was higher in subjects with higher simeprevir exposures.

Adverse Reactions In HCV/HIV-1 Co-infection

OLYSIO in combination with Peg-IFN-alfa and RBV was studied in 106 subjects with HCV genotype 1/HIV-1 co-infection (C212). The safety profile in HCV/HIV co-infected subjects was generally comparable to HCV mono-infected subjects.

Adverse Reactions In HCV Genotype 4 Infection

OLYSIO in combination with Peg-IFN-alfa and RBV was studied in 107 subjects with HCV genotype 4 infection (RESTORE). The safety profile of OLYSIO in subjects with HCV genotype 4 infection was comparable to subjects with HCV genotype 1 infection.

Adverse Reactions In East Asian Subjects

OLYSIO in combination with Peg-IFN-alfa and RBV was studied in a Phase 3 trial conducted in China and South Korea in treatment-na´ve subjects with chronic HCV genotype 1 infection (TIGER). The safety profile of OLYSIO in East Asian subjects was similar to that of the pooled Phase 3 population from global trials; however, a higher incidence of the laboratory abnormality hyperbilirubinemia was observed in patients receiving 150 mg OLYSIO plus Peg-IFN-alfa and RBV compared to patients receiving placebo plus Peg-IFN-alfa and RBV. Elevation of total bilirubin (all grades) was observed in 66% (99/151) of subjects treated with 150 mg OLYSIO plus Peg-IFN-alfa and RBV and in 26% (40/152) of subjects treated with placebo plus Peg-IFN-alfa and RBV. Bilirubin elevations were mainly Grade 1 or Grade 2. Grade 3 elevations in bilirubin were observed in 9% (13/151) of subjects treated with 150 mg OLYSIO plus Peg-IFN-alfa and RBV and in 1% (2/152) of subjects treated with placebo plus Peg-IFN-alfa and RBV. There were no Grade 4 elevations in bilirubin. The bilirubin elevations were not associated with increases in liver transaminases and were reversible after the end of treatment [see Use in Specific Populations and Clinical Studies].

Postmarketing Experience

The following adverse reactions have been reported during post approval use of OLYSIO. Because postmarketing reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship between drug exposure and these adverse reactions.

Cardiac Disorders: Serious symptomatic bradycardia has been reported in patients taking amiodarone who initiate treatment with sofosbuvir in combination with another HCV direct-acting antiviral, including OLYSIO [see WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS].

Hepatobiliary Disorders: hepatic decompensation, hepatic failure [see WARNINGS AND PRECAUTIONS].

Read the entire FDA prescribing information for Olysio (Simeprevir Hard Gelatin Capsules)

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


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