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Olysio

"The U.S. Food and Drug Administration today approved Olysio (simeprevir), a new therapy to treat chronic hepatitis C virus infection.

Hepatitis C is a viral disease that causes inflammation of the liver that can lead to diminished liver"...

Olysio

Warnings
Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

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. Warnings and Precautions related to these drugs also apply to their use in OLYSIO combination treatment.

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 [see ADVERSE REACTIONS]. 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 [see ADVERSE REACTIONS]. 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 [see ADVERSE REACTIONS]. 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 [see DRUG INTERACTIONS and CLINICAL PHARMACOLOGY].

Patient Counseling Information

OLYSIO should be used in combination with other antiviral drugs for the treatment of CHC infection, and thus contraindications and warnings for these drugs also apply to their use in OLYSIO combination treatment.

Pregnancy

Advise female patients to use an effective contraceptive method during treatment with OLYSIO. Advise patients to see the patient information for other antiviral drugs used in combination with OLYSIO regarding use in pregnancy [see Use In Specific Populations].

Photosensitivity

Advise patients of the risk of photosensitivity reactions related to OLYSIO combination treatment and that these reactions may be severe. Patients should be advised to contact their healthcare provider immediately if they develop a photosensitivity reaction. Patients should not stop OLYSIO due to photosensitivity reactions unless instructed by their healthcare provider [see WARNINGS AND PRECAUTIONS].

Patients should be advised to use sun protection measures (such as a hat, sunglasses, protective clothing, sunscreen) during treatment with OLYSIO. Patients should limit exposure to natural sunlight and avoid artificial sunlight (tanning beds or phototherapy) during treatment with OLYSIO.

Rash

Advise patients of the risk of rash related to OLYSIO combination treatment and that rash may become severe. Patients should be advised to contact their healthcare provider immediately if they develop a rash. Patients should not stop OLYSIO due to rash unless instructed by their healthcare provider [see WARNINGS AND PRECAUTIONS].

Administration

Advise patients that OLYSIO should be used only in combination with other antiviral drugs for the treatment of CHC infection. Advise patients to discontinue OLYSIO if any of the other antiviral drugs used in combination with OLYSIO are permanently discontinued for any reason.

Advise patients that the dose of OLYSIO must not be reduced or interrupted, as it may increase the possibility of treatment failure.

If the patient misses a dose of OLYSIO and remembers within 12 hours of the usual dosing time, advise the patient to take the missed dose of OLYSIO with food as soon as possible and then take the next dose of OLYSIO at the regularly scheduled time. If a patient misses a dose of OLYSIO by more than 12 hours after the usual dosing time, advise the patient not to take the missed dose of OLYSIO, but to resume the usual dosing of OLYSIO with food at the regularly scheduled time. Inform the patient that he or she should not take more or less than the prescribed dose of OLYSIO at any one time.

Hepatitis C Virus Transmission

Inform patients that the effect of treatment of hepatitis C infection on transmission is not known, and to take appropriate precautions to prevent transmission of the hepatitis C virus.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenesis and Mutagenesis

Simeprevir was not genotoxic in a series of in vitro and in vivo tests including the Ames test, the mammalian forward mutation assay in mouse lymphoma cells or the in vivo mammalian micronucleus test. Carcinogenicity studies with simeprevir have not been conducted.

If OLYSIO is administered in a combination regimen containing RBV, refer to the prescribing information for RBV for information on carcinogenesis and mutagenesis.

Impairment of Fertility

In a rat fertility study at doses up to 500 mg/kg/day, 3 male rats treated with simeprevir (2/24 rats at 50 mg/kg/day and 1/24 rats at 500 mg/kg/day) showed no motile sperm, small testes and epididymides, and resulted in infertility in 2 out of 3 of the male rats at approximately 0.2 times the mean AUC in humans.

If OLYSIO is administered with Peg-IFN-alfa and RBV, refer to the prescribing information for Peg-IFN-alfa and RBV for information on impairment of fertility.

Use In Specific Populations

Pregnancy

OLYSIO must be administered in combination with other antiviral drugs [see DOSAGE AND ADMINISTRATION]. Refer to prescribing information of the drugs used in combination with OLYSIO for information regarding use in pregnancy.

Pregnancy Category C

Risk Summary

Adequate and well-controlled trials with OLYSIO have not been conducted in pregnant women. In animal reproduction studies with simeprevir, embryofetal developmental toxicity was observed at drug exposures higher than human exposure at the recommended clinical dose. 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.

If OLYSIO is administered with Peg-IFN-alfa and RBV, refer to the prescribing information for Peg-IFN-alfa and RBV for information on use in pregnancy.

Animal Data

Simeprevir showed no teratogenicity in rats and mice at exposures 0.5 times (in rats) and 6 times (in mice) the mean area under the plasma concentration time curve (AUC) in humans at the recommended dose of 150 mg once daily.

In a mouse embryofetal study at doses up to 1000 mg/kg, simeprevir resulted in early and late in utero fetal losses and early maternal deaths at an exposure approximately 6 times higher than the mean AUC in humans at the recommended 150 mg daily dose. Significantly decreased fetal weights and an increase in fetal skeletal variations were seen at exposures approximately 4 times higher than the mean AUC in humans at the recommended daily dose.

In a rat pre-and postnatal study, maternal animals were exposed to simeprevir during gestation and lactation at doses up to 1000 mg/kg/day. In pregnant rats, simeprevir resulted in early deaths at 1000 mg/kg/day corresponding to exposures similar to the mean AUC in humans at the recommended 150 mg once daily dose. Significant reduction in body weight gain was seen at an exposure 0.7 times the mean AUC in humans at the recommended 150 mg once daily dose. The developing rat offspring exhibited significantly decreased body weight and negative effects on physical growth (delay and small size) and development (decreased motor activity) following simeprevir exposure in utero (via maternal dosing) and during lactation (via maternal milk to nursing pups) at a maternal exposure similar to the mean AUC in humans at the recommended 150 mg once daily dose. Subsequent survival, behavior and reproductive capacity were not affected.

Nursing Mothers

It is not known whether OLYSIO or its metabolites are present in human breast milk. When administered to lactating rats, simeprevir was detected in plasma of suckling rats likely due to excretion of simeprevir via milk. Because of the potential for adverse reactions from the drug in nursing infants, a decision must be made whether to discontinue nursing or discontinue treatment with OLYSIO, taking into account the importance of the therapy to the mother.

If OLYSIO is administered in a regimen containing RBV, the information for RBV with regard to nursing mothers also applies to this combination regimen [see prescribing information for RBV].

Pediatric Use

The safety and efficacy of OLYSIO in pediatric patients have not been established.

Geriatric Use

Clinical studies of OLYSIO did not include sufficient numbers of patients older than 65 years to determine whether they respond differently from younger patients. No dose adjustment of OLYSIO is required in geriatric patients [see CLINICAL PHARMACOLOGY].

Race

Patients of East Asian ancestry exhibit higher simeprevir exposures [see CLINICAL PHARMACOLOGY]. In clinical trials, higher simeprevir exposures have been associated with increased frequency of adverse reactions, including rash and photosensitivity [see ADVERSE REACTIONS]. 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 [see CLINICAL PHARMACOLOGY]. 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 [see CLINICAL PHARMACOLOGY].

Refer to the prescribing information for the other antiviral drug(s) used in combination with OLYSIO regarding their use in patients with renal impairment.

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 studied in HCV-infected patients with moderate or severe hepatic impairment (Child-Pugh Class B or C). No dosage recommendation can be given for patients with moderate hepatic impairment (Child-Pugh Class B) due to modest increases in simeprevir exposures. OLYSIO is not recommended for patients with severe hepatic impairment (Child-Pugh Class C) due to substantially higher simeprevir exposures [see CLINICAL PHARMACOLOGY].

In clinical trials, higher simeprevir exposures have been associated with increased frequency of adverse reactions, including rash and photosensitivity [see ADVERSE REACTIONS]. The potential risks and benefits of OLYSIO should be carefully considered prior to use in patients with moderate hepatic impairment.

Refer to the prescribing information for the antiviral drug(s) used in combination with OLYSIO regarding their use in patients with hepatic impairment. The combination of OLYSIO with Peg-IFN-alfa and RBV is contraindicated in patients with decompensated cirrhosis (moderate or severe hepatic impairment).

Other HCV Genotypes

The safety and efficacy of OLYSIO have not been established in patients infected with other HCV genotypes.

Liver Transplantation

The safety and efficacy of OLYSIO have not been studied in liver transplant patients.

Last reviewed on RxList: 11/14/2014
This monograph has been modified to include the generic and brand name in many instances.

Warnings
Precautions
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