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VIEKIRA PAK（DASABUVIR SODIUM/OMBITASVIR/PARITAPREVIR/RITONAVIR）Tablets
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use VIEKIRA PAK safely and effectively. See full prescribing information for VIEKIRA PAK.
VIEKIRA PAK (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets), co-packaged for oral use
Initial U.S. Approval: 2014
RECENT MAJOR CHANGES
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Dosage and Administration, Recommended Dosage in Adults (2.1) |
3/2015 |
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Contraindications (4) |
7/2015 |
INDICATIONS AND USAGE
VIEKIRA PAK with or without ribavirin is indicated for the treatment of patients with genotype 1 chronic hepatitis C virus (HCV) infection including those with compensated cirrhosis. VIEKIRA PAK includes ombitasvir, a hepatitis C virus NS5A inhibitor, paritaprevir, a hepatitis C virus NS3/4A protease inhibitor, ritonavir, a CYP3A inhibitor and dasabuvir, a hepatitis C virus non-nucleoside NS5B palm polymerase inhibitor. (1)
Limitation of Use: VIEKIRA PAK is not recommended for use in patients with decompensated liver disease. (1)
DOSAGE AND ADMINISTRATION
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Recommended dosage: Two ombitasvir, paritaprevir, ritonavir 12.5/75/50 mg tablets once daily (in the morning) and one dasabuvir 250 mg tablet twice daily (morning and evening) with a meal without regard to fat or calorie content. (2.1)
Treatment Regimen and Duration by Patient Population
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Patient Population |
Treatment* |
Duration |
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Genotype 1a, without cirrhosis |
VIEKIRA PAK + ribavirin |
12 weeks |
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Genotype 1a, with cirrhosis |
VIEKIRA PAK + ribavirin |
24 weeks** |
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Genotype 1b, without cirrhosis |
VIEKIRA PAK |
12 weeks |
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Genotype 1b, with cirrhosis |
VIEKIRA PAK + ribavirin |
12 weeks |
*Note: Follow the genotype 1a dosing recommendations in patients with an unknown genotype 1 subtype or with mixed genotype 1 infection.
**VIEKIRA PAK administered with ribavirin for 12 weeks may be considered for some patients based on prior treatment history [See Clinical Studies (14.3)]. |
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HCV/HIV-1 co-infection: For patients with HCV/HIV-1 co-infection, follow the dosage recommendations in the table above. (2.1)
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Liver Transplant Recipients: In liver transplant recipients with normal hepatic function and mild fibrosis (Metavir fibrosis score ≤2), the recommended duration of VIEKIRA PAK with ribavirin is 24 weeks. (2.2)
DOSAGE FORMS AND STRENGTHS
Tablets:
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Ombitasvir, paritaprevir, ritonavir: 12.5/75/50 mg (3)
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Dasabuvir: 250 mg (3)
CONTRAINDICATIONS
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If VIEKIRA PAK is administered with ribavirin, the contraindications to ribavirin also apply to this combination regimen. (4)
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Patients with severe hepatic impairment. (4, 8.6, 12.3)
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Co-administration with drugs that are: highly dependent on CYP3A for clearance; moderate or strong inducers of CYP3A and strong inducers of CYP2C8; and strong inhibitors of CYP2C8. (4)
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Known hypersensitivity to ritonavir (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome). (4)
WARNINGS AND PRECAUTIONS
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ALT Elevations: Discontinue ethinyl estradiol-containing medications prior to starting VIEKIRA PAK (alternative contraceptive methods are recommended). Perform hepatic laboratory testing on all patients during the first 4 weeks of treatment. For ALT elevations on VIEKIRA PAK, monitor closely and follow recommendations in full prescribing information. (5.1)
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Risks Associated With Ribavirin Combination Treatment: If VIEKIRA PAK is administered with ribavirin, the warnings and precautions for ribavirin also apply to this combination regimen. (5.2)
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Drug Interactions: The concomitant use of VIEKIRA PAK and certain other drugs may result in known or potentially significant drug interactions, some of which may lead to loss of therapeutic effect of VIEKIRA PAK. (5.3)
ADVERSE REACTIONS
In subjects receiving VIEKIRA PAK with ribavirin, the most commonly reported adverse reactions (greater than 10% of subjects) were fatigue, nausea, pruritus, other skin reactions, insomnia and asthenia. In subjects receiving VIEKIRA PAK without ribavirin, the most commonly reported adverse reactions (greater than or equal to 5% of subjects) were nausea, pruritus and insomnia. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact AbbVie Inc. at 1-800-633-9110 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG INTERACTIONS
Co-administration of VIEKIRA PAK can alter the plasma concentrations of some drugs and some drugs may alter the plasma concentrations of VIEKIRA PAK. The potential for drug interactions must be considered before and during treatment. Consult the full prescribing information prior to and during treatment for potential drug interactions. (4, 5.3, 7, 12.3)
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
Revised: 7/2015
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
VIEKIRA PAK with or without ribavirin is indicated for the treatment of patients with genotype 1 chronic hepatitis C virus (HCV) infection including those with compensated cirrhosis.
Limitation of Use:
VIEKIRA PAK is not recommended for use in patients with decompensated liver disease [see Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)].
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dosage in Adults
VIEKIRA PAK is ombitasvir, paritaprevir, ritonavir fixed dose combination tablets copackaged with dasabuvir tablets.
The recommended oral dosage of VIEKIRA PAK is two ombitasvir, paritaprevir, ritonavir tablets once daily (in the morning) and one dasabuvir tablet twice daily (morning and evening). Take VIEKIRA PAK with a meal without regard to fat or calorie content [see Clinical Pharmacology (12.3)].
VIEKIRA PAK is used in combination with ribavirin (RBV) in certain patient populations (see Table 1). When administered with VIEKIRA PAK, the recommended dosage of RBV is based on weight: 1000 mg/day for subjects <75 kg and 1200 mg/day for those ≥75 kg, divided and administered twice-daily with food. For ribavirin dosage modifications, refer to the ribavirin prescribing information.
For patients with HCV/HIV-1 co-infection, follow the dosage recommendations in Table 1. Refer to Drug Interactions (7) for dosage recommendations for concomitant HIV-1 antiviral drugs.
Monitor liver chemistry tests before initiating and during therapy [see Warnings and Precautions (5.1)].
Table 1 shows the recommended VIEKIRA PAK treatment regimen and duration based on patient population.
2.2 Use in Liver Transplant Recipients
In liver transplant recipients with normal hepatic function and mild fibrosis (Metavir fibrosis score 2 or lower), the recommended duration of VIEKIRA PAK with ribavirin is 24 weeks, irrespective of HCV genotype 1 subtype [see Clinical Studies (14.6)]. When VIEKIRA PAK is administered with calcineurin inhibitors in liver transplant recipients, dosage adjustment of calcineurin inhibitors is needed [see Drug Interactions (7)].
2.3 Hepatic Impairment
No dosage adjustment of VIEKIRA PAK is required in patients with mild hepatic impairment (Child-Pugh A). VIEKIRA PAK is not recommended in patients with moderate hepatic impairment (Child-Pugh B). VIEKIRA PAK is contraindicated in patients with severe hepatic impairment (Child-Pugh C) [see Contraindications (4), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)].
3 DOSAGE FORMS AND STRENGTHS
VIEKIRA PAK is ombitasvir, paritaprevir, ritonavir fixed dose combination tablets copackaged with dasabuvir tablets.
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Ombitasvir, paritaprevir, ritonavir 12.5/75/50 mg tablets are pink-colored, film-coated, oblong biconvex shaped, debossed with “AV1” on one side.
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Dasabuvir 250 mg tablets are beige-colored, film-coated, oval-shaped, debossed with “AV2” on one side. Each tablet contains 270.3 mg dasabuvir sodium monohydrate equivalent to 250 mg dasabuvir.
4 CONTRAINDICATIONS
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If VIEKIRA PAK is administered with ribavirin, the contraindications to ribavirin also apply to this combination regimen. Refer to the ribavirin prescribing information for a list of contraindications for ribavirin.
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VIEKIRA PAK is contraindicated in patients with severe hepatic impairment due to risk of potential toxicity [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
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VIEKIRA PAK is contraindicated with:
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Drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events.
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Drugs that are moderate or strong inducers of CYP3A and strong inducers of CYP2C8 and may lead to reduced efficacy of VIEKIRA PAK.
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Drugs that are strong inhibitors of CYP2C8 and may increase dasabuvir plasma concentrations and the risk of QT prolongation.
Table 2 lists drugs that are contraindicated with VIEKIRA PAK [see Drug Interactions (7)].
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VIEKIRA PAK is contraindicated in patients with known hypersensitivity (e.g. toxic epidermal necrolysis (TEN) or Stevens-Johnson syndrome) to ritonavir.
5 WARNINGS AND PRECAUTIONS
5.1 Increased Risk of ALT Elevations
During clinical trials with VIEKIRA PAK with or without ribavirin, elevations of ALT to greater than 5 times the upper limit of normal (ULN) occurred in approximately 1% of all subjects [see Adverse Reactions (6.1)]. ALT elevations were typically asymptomatic, occurred during the first 4 weeks of treatment, and declined within two to eight weeks of onset with continued dosing of VIEKIRA PAK with or without ribavirin.
These ALT elevations were significantly more frequent in female subjects who were using ethinyl estradiol-containing medications such as combined oral contraceptives, contraceptive patches or contraceptive vaginal rings. Ethinyl estradiol-containing medications must be discontinued prior to starting therapy with VIEKIRA PAK [see Contraindications (4)]. Alternative methods of contraception (e.g, progestin only contraception or non-hormonal methods) are recommended during VIEKIRA PAK therapy. Ethinyl estradiol-containing medications can be restarted approximately 2 weeks following completion of treatment with VIEKIRA PAK.
Women using estrogens other than ethinyl estradiol, such as estradiol and conjugated estrogens used in hormone replacement therapy had a rate of ALT elevation similar to those not receiving any estrogens; however, due to the limited number of subjects taking these other estrogens, caution is warranted for co-administration with VIEKIRA PAK [see Adverse Reactions (6.1)].
Hepatic laboratory testing should be performed during the first 4 weeks of starting treatment and as clinically indicated thereafter. If ALT is found to be elevated above baseline levels, it should be repeated and monitored closely:
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Patients should be instructed to consult their health care professional without delay if they have onset of fatigue, weakness, lack of appetite, nausea and vomiting, jaundice or discolored feces.
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Consider discontinuing VIEKIRA PAK if ALT levels remain persistently greater than 10 times the ULN.
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Discontinue VIEKIRA PAK if ALT elevation is accompanied by signs or symptoms of liver inflammation or increasing conjugated bilirubin, alkaline phosphatase, or INR.
5.2 Risks Associated With Ribavirin Combination Treatment
If VIEKIRA PAK is administered with ribavirin, the warnings and precautions for ribavirin, in particular the pregnancy avoidance warning, apply to this combination regimen. Refer to the ribavirin prescribing information for a full list of the warnings and precautions for ribavirin.
5.3 Risk of Adverse Reactions or Reduced Therapeutic Effect Due to Drug Interactions
The concomitant use of VIEKIRA PAK and certain other drugs may result in known or potentially significant drug interactions, some of which may lead to:
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Loss of therapeutic effect of VIEKIRA PAK and possible development of resistance
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Possible clinically significant adverse reactions from greater exposures of concomitant drugs or components of VIEKIRA PAK.
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