Recommended Topic Related To:

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

Included as part of the PRECAUTIONS section.

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 [see CONTRAINDICATIONS]. 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 [see ADVERSE REACTIONS]. 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 [see PATIENT INFORMATION]. 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 [see ADVERSE REACTIONS]. 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 [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.

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 [see DRUG INTERACTIONS and CLINICAL PHARMACOLOGY].

Patient Counseling Information

OLYSIO should be used in combination with peginterferon alfa and ribavirin, and thus contraindications and warnings for peginterferon alfa and ribavirin also apply to OLYSIO combination treatment.

Pregnancy

Ribavirin must not be used by female patients who are pregnant or by men whose female partners are pregnant. Ribavirin therapy should not be initiated until a report of a negative pregnancy test has been obtained immediately before starting therapy. OLYSIO in combination treatment with peginterferon alfa and ribavirin is contraindicated in women who are pregnant and in men whose female partners are pregnant (see also the prescribing information for ribavirin).

Female patients of childbearing potential and male patients with female partners of childbearing potential must be advised of the teratogenic/embryocidal risks of ribavirin and should be advised that extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients -both during treatment and for 6 months after the completion of all treatment. Women of childbearing potential and men must use at least two forms of effective contraception during treatment and for 6 months post-treatment. Women of childbearing potential and men must be counseled about use of effective contraception (two methods) prior to initiating treatment.

Patients (both male and female) should be advised to notify their healthcare provider immediately in the event of a pregnancy [see CONTRAINDICATIONS, WARNING AND PRECAUTIONS and Use in Specific Populations].

Photosensitivity

Patients should be advised of the risk of photosensitivity reactions related to the use of OLYSIO in combination with peginterferon and ribavirin 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 WARNING 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

Patients should be advised of the risk of rash related to the use of OLYSIO in combination with peginterferon and ribavirin 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 WARNING AND PRECAUTIONS].

Administration

Patients should be advised that OLYSIO should be administered in combination with both peginterferon alfa and ribavirin. If peginterferon alfa and/or ribavirin is discontinued for any reason, OLYSIO must also be discontinued.

Patients should be advised 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, the patient should 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, the patient should not take the missed dose of OLYSIO, but 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

Patients should be informed that the effect of treatment of hepatitis C infection on transmission is not known, and that appropriate precautions to prevent transmission of the hepatitis C virus should be taken.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenesis and Mutagenesis

Use with Ribavirin and Peginterferon alfa: Ribavirin is genotoxic in in vitro and in vivo assays. Ribavirin was not oncogenic in a 6-month p53+/-transgenic mouse study or a 2-year carcinogenicity study in rats. See the prescribing information for ribavirin.

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.

Fertility

Use with Ribavirin and Peginterferon alfa: Animal studies have shown that ribavirin induced reversible toxicity in males while peginterferon alfa may impair female fertility. See the prescribing information for ribavirin and peginterferon alfa.

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

Use In Specific Populations

Pregnancy

Pregnancy Category X: Use with Ribavirin and Peginterferon Alfa

Extreme caution must be taken to avoid pregnancy in female patients and female partners of male patients while taking this combination. Women of childbearing potential and their male partners should not receive ribavirin unless they are using effective contraception (two reliable forms) during treatment with ribavirin and for 6 months after treatment.

A Ribavirin Pregnancy Registry has been established to monitor maternal-fetal outcomes of pregnancies in female patients and female partners of male patients exposed to ribavirin during treatment and for 6 months following cessation of treatment. Healthcare providers and patients are encouraged to report such cases by calling 1-800-593-2214.

Animal Data

Animal studies have shown that ribavirin causes birth defects and/or fetal deaths while peginterferon alfa is abortifacient [see CONTRAINDICATIONS and WARNING AND PRECAUTIONS]. See the prescribing information for ribavirin. Significant teratogenic and/or embryocidal effects have been demonstrated in all animal species exposed to ribavirin; and therefore ribavirin is contraindicated in women who are pregnant and in the male partners of women who are pregnant [see CONTRAINDICATIONS, WARNING AND PRECAUTIONS and ribavirin prescribing information]. Interferons have abortifacient effects in animals and should be assumed to have abortifacient potential in humans [see peginterferon alfa prescribing information].

Pregnancy Category C: OLYSIO

There are no adequate and well-controlled studies with OLYSIO alone or in combination with peginterferon alfa and ribavirin in pregnant women.

Animal Data

Simeprevir showed no teratogenicity in rats and mice at exposures 0.5 times (in rats) and 6 times (in mice) the mean 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 clinical AUC. Significant reduction in body weight gain was seen from 500 mg/kg/day onwards at an exposure 0.7 times the mean clinical AUC. The developing rat offspring exhibited significant 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 clinical AUC at the recommended 150 mg once daily dose. Subsequent survival, behavior and reproductive capacity were not affected.

Nursing Mothers

It is not known whether simeprevir or its metabolites are excreted 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.

Pediatric Use

The safety and efficacy of OLYSIO in children and adolescents less than 18 years of age 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 respective prescribing information for peginterferon alfa and ribavirin regarding 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); 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 [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 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). The combination of peginterferon alfa and ribavirin is contraindicated in patients with decompensated cirrhosis (moderate or severe hepatic impairment). The potential risks and benefits of OLYSIO should be carefully considered prior to use in patients with moderate or severe hepatic impairment.

Other HCV Genotypes

The safety and efficacy of OLYSIO in combination with peginterferon alfa and ribavirin has not been established in patients with other HCV genotypes.

Liver Transplantation

The safety and efficacy of OLYSIO alone or in combination with peginterferon alfa and ribavirin have not been studied in liver transplant patients.

Last reviewed on RxList: 1/23/2014
This monograph has been modified to include the generic and brand name in many instances.

A A A

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.


Women's Health

Find out what women really need.