Simeprevir warnings and precautions

# Warnings And Precautions

## Embryo-Fetal Toxicity (Use with Ribavirin and peginterferon alfa)
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 OLYSIO in combination with peginterferon alfa and Ribavirin, including serious reactions which resulted in hospitalization. Photosensitivity reactions occurred most frequently in the first 4 weeks of treatment with OLYSIO in combination with peginterferon alfa and Ribavirin, 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 in combination with peginterferon alfa and Ribavirin. Avoid use of tanning devices during treatment with OLYSIO in combination with peginterferon alfa and Ribavirin . 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 in subjects receiving OLYSIO in combination with peginterferon alfa and Ribavirin . Rash occurred most frequently in the first 4 weeks of treatment with OLYSIO in combination with peginterferon alfa and Ribavirin, but can occur at any time during treatment. Severe rash and rash requiring discontinuation of OLYSIO have been reported. 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.

## Use with peginterferon alfa and Ribavirin
OLYSIO must not be used as monotherapy. OLYSIO should be used in combination with both peginterferon alfa and Ribavirin. Therefore the prescribing information for peginterferon alfa and Ribavirin must be consulted before starting therapy with OLYSIO. Contraindications and Warnings and Precautions related to peginterferon alfa and Ribavirin also apply to OLYSIO combination treatment with peginterferon alfa and Ribavirin.

## 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 .