Important Safety InformationExpand
Important Safety Information
Contraindications to P/R also apply to OLYSIOTM (simeprevir) combination treatment with P/R. OLYSIOTM in combination with P/R is contraindicated in pregnant women and in men whose female partners are pregnant because of the risks for birth defects and fetal death associated with ribavirin. Refer to the respective prescribing information for a list of the contraindications for P/R.
Warnings and Precautions:
Embryo-Fetal Toxicity (Use with P/R): Ribavirin may cause birth defects and/or death of the exposed fetus and animal studies have shown that interferons have abortifacient effects. Therefore, extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin therapy should not be started unless a report of a negative pregnancy test has been obtained immediately prior to initiation of therapy. Refer also to the prescribing information for ribavirin.
Female patients of childbearing potential and their male partners, as well as male patients and their female partners, must use two effective contraceptive methods during treatment and for 6 months after completion of treatment. Routine monthly pregnancy tests must be performed during this time.
Photosensitivity: Photosensitivity reactions have been observed with OLYSIOTM in combination with P/R, including serious reactions which resulted in hospitalization. Photosensitivity reactions occurred most frequently in the first 4 weeks of treatment with OLYSIOTM in combination with P/R, 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 OLYSIOTM in combination with P/R. Avoid use of tanning devices during treatment with OLYSIOTM in combination with P/R. Discontinuation of OLYSIOTM 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 OLYSIOTM in the setting of a photosensitivity reaction, expert consultation is advised.
Rash: Rash has been observed in subjects receiving OLYSIOTM in combination with P/R. Rash occurred most frequently in the first 4 weeks of treatment with OLYSIOTM in combination with P/R, but can occur at any time during treatment. Severe rash and rash requiring discontinuation of OLYSIOTM have been reported. Most of the rash events in OLYSIOTM-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, OLYSIOTM should be discontinued. Patients should be monitored until the rash has resolved.
Sulfa Allergy: OLYSIOTM 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 OLYSIOTM.
Use with P/R: OLYSIOTM must not be used as monotherapy. OLYSIOTM should be used in combination with both P/R. Therefore the prescribing information for P/R must be consulted before starting therapy with OLYSIOTM. Contraindications and Warnings and Precautions related to P/R also apply to OLYSIOTM combination treatment with P/R.
Drug Interactions: Co-administration of OLYSIOTM 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.
In pooled Phase 3 studies, adverse reactions (all grades, at least 3% higher frequency) for OLYSIOTM with P/R vs. P/R 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 in Specific Populations:
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 OLYSIOTM should be carefully considered prior to use in patients of East Asian ancestry.
Renal Impairment: No dose adjustment of OLYSIOTM is required in patients with mild, moderate or severe renal impairment. The safety and efficacy of OLYSIOTM 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. Refer to the respective prescribing information for P/R regarding use in patients with renal impairment.
Hepatic Impairment: No dose adjustment of OLYSIOTM is required in patients with mild hepatic impairment (Child-Pugh Class A); no dose recommendation can be given for patients with moderate or severe hepatic impairment (Child-Pugh Class B or C) due to higher simeprevir exposures. In clinical trials, higher simeprevir exposures have been associated with increased frequency of adverse reactions, including rash and photosensitivity.
The safety and efficacy of OLYSIOTM have not been studied in HCV-infected patients with moderate or severe hepatic impairment (Child-Pugh Class B or C). The combination of P/R is contraindicated in patients with decompensated cirrhosis (moderate or severe hepatic impairment). The potential risks and benefits of OLYSIOTM should be carefully considered prior to use in patients with moderate or severe hepatic impairment.
Other HCV Genotypes: The safety and efficacy of OLYSIOTM in combination with P/R has not been established in patients with other HCV genotypes.
Liver Transplantation: The safety and efficacy of OLYSIOTM alone or in combination with P/R have not been studied in liver transplant patients.
Not a complete list of Uses in Specific Populations.
Please see full Prescribing Information and Patient Information for more details.
Reference: 1. Data on file. Janssen Therapeutics, Division of Janssen Products, LP.