Important Safety InformationExpand
Important Safety Information
There are no specific contraindications to OLYSIO®. The contraindications to other antiviral drugs administered with OLYSIO® for the treatment of CHC infection also apply to OLYSIO® combination treatment. Prescribers should consult the complete prescribing information for these drugs for a description of contraindications.
Warnings and Precautions:
Serious Symptomatic Bradycardia When Co‐administered with Sofosbuvir and Amiodarone: Postmarketing cases of symptomatic bradycardia and cases requiring pacemaker intervention have been reported when amiodarone is coadministered with sofosbuvir in combination with another HCV direct-acting antiviral, including OLYSIO®. A fatal cardiac arrest was reported in a patient receiving a sofosbuvir-containing regimen (ledipasvir/sofosbuvir). Bradycardia has generally occurred within hours to days, but cases have been observed up to 2 weeks after initiating HCV treatment. Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease, may be at increased risk for symptomatic bradycardia with co‐administration of amiodarone. Bradycardia generally resolved after discontinuation of HCV treatment. The mechanism for this bradycardia effect is unknown.
Co-administration of amiodarone with OLYSIO® in combination with sofosbuvir is not recommended. For patients taking amiodarone who have no other alternative treatment options, and who will be co-administered OLYSIO® and sofosbuvir:
- Counsel patients about the risk of serious symptomatic bradycardia.
- Cardiac monitoring in an in-patient setting for the first 48 hours of co-administration is recommended, after which outpatient or self-monitoring of the heart rate should occur on a daily basis through at least the first 2 weeks of treatment.
Patients who are taking sofosbuvir in combination with OLYSIO® who need to start amiodarone therapy due to no other alternative treatment options should undergo similar cardiac monitoring as outlined above.
Due to amiodarone’s long elimination half-life, patients discontinuing amiodarone just prior to starting sofosbuvir in combination with OLYSIO® should also undergo similar cardiac monitoring as outlined above.
Patients who develop signs or symptoms of bradycardia should seek medical evaluation immediately. Symptoms may include near‐fainting or fainting, dizziness or lightheadedness, malaise, weakness, excessive tiredness, shortness of breath, chest pain, confusion, or memory problems.
Hepatic Decompensation and Hepatic Failure: Hepatic decompensation and hepatic failure, including fatal cases, have been reported postmarketing in patients treated with OLYSIO® in combination with Peg-IFN-alfa and RBV or in combination with sofosbuvir. Most cases were reported in patients with advanced and/or decompensated cirrhosis who are at increased risk for hepatic decompensation or hepatic failure. Because these events have been reported voluntarily during clinical practice, estimates of frequency cannot be made and a causal relationship between treatment with OLYSIO® and these events has not been established.
OLYSIO® is not recommended for patients with moderate or severe hepatic impairment (Child-Pugh Class B or C).
In clinical trials of OLYSIO®, modest increases in bilirubin levels were observed without impacting hepatic function. Postmarketing cases of hepatic decompensation with markedly elevated bilirubin levels have been reported. Monitor liver chemistry tests before and as clinically indicated during OLYSIO® combination therapy. Patients who experience an increase in total bilirubin to greater than 2.5 times the upper limit of normal should be closely monitored:
- Patients should be instructed to contact their healthcare provider if they have onset of fatigue, weakness, lack of appetite, nausea and vomiting, jaundice, or discolored feces.
- Discontinue OLYSIO® if elevation in bilirubin is accompanied by liver transaminase increases or clinical signs and symptoms of hepatic decompensation.
Risk of Serious Adverse Reactions Associated with Combination Treatment: OLYSIO® should be used in combination with other antiviral drugs for the treatment of CHC infection. Therefore, consult the prescribing information for these drugs before starting therapy with OLYSIO®.
Photosensitivity: Photosensitivity reactions have been observed with OLYSIO® combination therapy. Serious photosensitivity reactions resulting in hospitalization have been observed with OLYSIO® in combination with Peg-IFN-alfa and RBV. Photosensitivity reactions occurred most frequently in the first 4 weeks of treatment, but can occur at any time during treatment. Photosensitivity may present as an exaggerated sunburn reaction, usually affecting areas exposed to light (typically the face, “V” area of the neck, extensor surfaces of the forearms, and dorsa of the hands). Manifestations may include burning, erythema, exudation, blistering, and edema.
Use sun protective measures and limit sun exposure during treatment with OLYSIO®. Avoid use of tanning devices during treatment with OLYSIO®. Discontinuation of OLYSIO® should be considered if a photosensitivity reaction occurs and patients should be monitored until the reaction has resolved. If a decision is made to continue OLYSIO® in the setting of a photosensitivity reaction, expert consultation is advised.
Rash: Rash has been observed with OLYSIO® combination therapy. Rash occurred most frequently in the first 4 weeks of treatment, but can occur at any time during treatment. Severe rash and rash requiring discontinuation of OLYSIO® have been reported in subjects receiving OLYSIO® in combination with Peg-IFN-alfa and RBV. Most of the rash events in OLYSIO®-treated patients were of mild or moderate severity. Patients with mild to moderate rashes should be followed for possible progression of rash, including the development of mucosal signs (e.g., oral lesions, conjunctivitis) or systemic symptoms. If the rash becomes severe, OLYSIO® should be discontinued. Patients should be monitored until the rash has resolved.
Sulfa Allergy: OLYSIO® contains a sulfonamide moiety. In subjects with a history of sulfa allergy (n=16), no increased incidence of rash or photosensitivity reactions has been observed. However, there are insufficient data to exclude an association between sulfa allergy and the frequency or severity of adverse reactions observed with the use of OLYSIO®.
Risk of Adverse Reactions or Reduced Therapeutic Effect Due to Drug Interactions: Co-administration of OLYSIO® with substances that are moderate or strong inducers or inhibitors of cytochrome P450 3A (CYP3A) is not recommended as this may lead to significantly lower or higher exposure of simeprevir, respectively, which may result in reduced therapeutic effect or adverse reactions.
Use With Peg-IFN-alfa and RBV: Adverse reactions (all grades, at least 3% higher frequency) for OLYSIO® with Peg-IFN-alfa and RBV vs. Peg-IFN-alfa and RBV alone in the first 12 weeks were rash (including photosensitivity) (28% vs. 20%), pruritus (22% vs. 15%), nausea (22% vs. 18%), myalgia (16% vs. 13%), and dyspnea (12% vs. 8%).
Use With Sofosbuvir: 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.
Use in Specific Populations:
Pregnancy Category C: Adequate and well-controlled trials with OLYSIO® have not been conducted in pregnant women. OLYSIO® should be used during pregnancy only if the potential benefit justifies the potential risk. Female patients of childbearing potential should use an effective contraceptive method.
Race: Patients of East Asian ancestry exhibit higher simeprevir exposures. In clinical trials, higher simeprevir exposures have been associated with increased frequency of adverse reactions, including rash and photosensitivity. There are insufficient safety data to recommend an appropriate dose for patients of East Asian ancestry. The potential risks and benefits of OLYSIO® should be carefully considered prior to use in patients of East Asian ancestry.
Renal Impairment: No dose adjustment of OLYSIO® is required in patients with mild, moderate, or severe renal impairment. The safety and efficacy of OLYSIO® have not been studied in HCV-infected patients with severe renal impairment (creatinine clearance below 30 mL/min) or end-stage renal disease, including patients requiring dialysis. Simeprevir is highly protein-bound; therefore, dialysis is unlikely to result in significant removal of simeprevir.
Hepatic Impairment: No dose adjustment of OLYSIO® is required in patients with mild hepatic impairment (Child-Pugh Class A). The safety and efficacy of OLYSIO® have not been established in HCV-infected patients with moderate or severe hepatic impairment (Child-Pugh Class B or C). OLYSIO® is not recommended for patients with moderate or severe hepatic impairment (Child-Pugh Class B or C). There have been postmarketing reports of hepatic decompensation, hepatic failure, and death in patients with advanced or decompensated cirrhosis receiving OLYSIO® combination therapy. Simeprevir exposures are increased in patients with moderate or severe hepatic impairment (Child-Pugh Class B or C). In clinical trials, higher simeprevir exposures have been associated with increased frequency of adverse reactions, including increased bilirubin, rash, and photosensitivity.
Liver Transplantation: The safety and efficacy of OLYSIO® have not been studied in liver transplant patients.
Not a complete list of Uses in Specific Populations.
Consult the PI for Peg-IFN-alfa and RBV or sofosbuvir before starting therapy with OLYSIO®. Safety information related to these drugs also applies to their use in OLYSIO® combination treatment.
Reference: 1. Data on file. Janssen Therapeutics, Division of Janssen Products, LP.