"SILVER SPRING, MD â€” The US Food and Drug Administration (FDA) is updating labeling information for the hepatitis C antivirals ledipasvir/sofosbuvir (Harvoni, Gilead Sciences) and sofosbuvir (Sovaldi, Gilead Sciences) after th"...
Olysio Side Effects Center
Medical Editor: John P. Cunha, DO, FACOEP
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
OLYSIO should be 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 drug reactions (ADRs) are discussed in detail in another section of the labeling:
Clinical Trials Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice.
Adverse Reactions when Used 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 who were treatment-naïve or who had previously relapsed following interferon therapy with or without RBV is based on pooled data from three Phase 3 trials [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.
The following table lists adverse reactions (all Grades) that occurred with at least 3% higher frequency among subjects 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-naïve or who had previously relapsed after Peg-IFN-alfa and RBV therapy (see Table 4).
Table 4: Adverse Reactions (all Grades) that Occurred
with at Least 3% Higher Frequency Among Subjects 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 Subjects with CHC Infection*(Pooled Phase 3 Trials†)
|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-naïve 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, 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 Grade 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.
During the 12 weeks of treatment with OLYSIO, 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.
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 5.
Table 5: Laboratory Abnormalities (WHO Worst Toxicity
Grades 1 to 4) Observed at a Higher Incidence in OLYSIO-Treated Subjects
(Pooled Phase 3 Trials*; First 12 Weeks of Treatment)
|Laboratory Parameter||WHO Toxicity Range||OLYSIO 150 mg + Peg-IFN-alfa + RBV
|Placebo + Peg-IFN-alfa + RBV
|Grade 1||> 1.25 to ≤ 2.50 x ULN‡||3||1|
|Grade 2||> 2.50 to ≤ 5.00 x ULN||< 1||0|
|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.
Adverse Reactions when Used with Sofosbuvir
In the COSMOS trial, the most common ( > 10%) adverse reactions reported during 12 weeks treatment with OLYSIO in combination with sofosbuvir without RBV were fatigue (25%), headache (21%), nausea (21%), insomnia (14%) and pruritus (11%). Rash and photosensitivity were reported in 11% and 7% of subjects, respectively. During 24 weeks treatment with OLYSIO in combination with sofosbuvir, dizziness (16%), and diarrhea (16%) were also commonly reported.
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 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].
Read the entire FDA prescribing information for Olysio (Simeprevir Hard Gelatin Capsules)
Additional Olysio Information
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.
Find out what women really need.