What is Viekira Pak (dasabuvir, ombitasvir, paritaprevir, and ritonavir)?

Viekira Pak (dasabuvir, ombitasvir, paritaprevir, and ritonavir) is a combination of antiviral drugs used to treat patients with hepatitis C virus (HCV) genotype 1. 

The drugs work in three different ways to help stop HCV from multiplying: 

  • They block the effect of proteases, which are enzymes HCV uses for making new virus, leading to reduced numbers of HCV copies in the body. 
  • Ombitasvir blocks HCV NS5A protease, while paritaprevir blocks HCV NS3/4A protease. 
  • Dasabuvir blocks a viral structure called NS5B palm polymerase which is also needed for replication of HCV. 

Ritonavir is not active against the HCV virus. It is used to increase blood levels of paritaprevir by inhibiting the breakdown of paritaprevir.

Common side effects of Viekira Pak when used with ribavirin include:

Common side effects of Viekira Pak when used without ribavirin include:

Serious side effects of Viekira Pak include:

Drug interactions of Viekira Pak include afluzosin hydrochloride, due to the risk of low blood pressure. Certain anti-seizure medications, rifampin, and St. John's wort may reduce the effectiveness of treatment with Viekira Pak. 

Ergot derivatives when used with Viekira Pak can result in ergot toxicity. 

Combination birth control pills that contain ethinyl estradiol should be avoided due to the potential for liver damage. 

Combining certain “statin” drugs with Viekira Pak can increase the risk for serious muscle pain and injury, including rhabdomyolysis. Combining Viekira Pak and pimozide may increase the risk for abnormal heart beats. 

Combining efavirenz and Viekira Pak may increase the risk of liver damage. 

Combining Viekira Pak with drugs used to treat erectile dysfunction may increase the risk of vision problems, low blood pressure, fainting, and priapism (painful, long-lasting erection). 

Viekira Pak increases blood levels of triazolam and midazolam, leading to increased sedation and respiratory depression

Viekira Pak has not been evaluated in pregnant women and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. When Viekira Pak is administered with ribavirin, the combination regimen should not be used in pregnant women and in men who can father children. Ribavirin is known to cause birth defects and should be avoided during pregnancy. 

There is an antiretroviral pregnancy registry that monitors the use of products such as Viekira Pak in HCV/HIV-1 co-infected women. Patients are advised to enroll in this program to help study and understand the safety of antiretroviral therapy during pregnancy. 

It is unknown if any of the drugs contained in Viekira Pak are excreted into human milk. Due to the lack of conclusive safety data, Viekira Pak should be used cautiously while breastfeeding

What are the important side effects of Viekira Pak (dasabuvir, ombitasvir, paritaprevir, and ritonavir)?

The most common side effects of Viekira Pak when used with ribavirin include:

  • tiredness,
  • nausea,
  • itching,
  • skin reactions such as redness or rash,
  • sleep problems (insomnia), and
  • feeling weak.

The most common side effects of Viekira Pak when used without ribavirin include:

  • nausea,
  • itching, and
  • problems sleeping.

Other side effects include:

  • allergic reactions,
  • anemia, and
  • increases in liver enzymes and bilirubin.

Viekira Pak (dasabuvir, ombitasvir, paritaprevir, and ritonavir) side effects list for healthcare professionals

If Viekira Pak is administered with ribavirin (RBV), refer to the prescribing information for ribavirin for a list of ribavirin-associated adverse reactions.

The following adverse reaction is described below and elsewhere in the labeling:

  • Risk of Hepatic Decompensation and Hepatic Failure in Patients with Cirrhosis
  • Increased Risk of ALT Elevations

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of Viekira Pak cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety assessment was based on data from seven clinical trials in more than 2,000 subjects who received Viekira Pak with or without ribavirin for 12 or 24 weeks.

Viekira Pak With Ribavirin In Placebo-Controlled Trials

The safety of Viekira Pak in combination with ribavirin was assessed in 770 subjects with chronic HCV genotype 1 (GT1) infection in two placebo-controlled trials (SAPPHIRE-I and -II). Adverse reactions that occurred more often in subjects treated with Viekira Pak in combination with ribavirin compared to placebo were fatigue, nausea, pruritus, other skin reactions, insomnia, and asthenia (see Table 3).

The majority of the adverse reactions were mild in severity. Two percent of subjects experienced a serious adverse event (SAE). The proportion of subjects who permanently discontinued treatment due to adverse reactions was less than 1%.

Table 3: Adverse Reactions with ≥ 5% Greater Frequency Reported in Subjects with Chronic HCV GT1 Infection Treated with Viekira Pak in Combination with Ribavirin Compared to Placebo for 12 Weeks

SAPPHIRE-I and -II
Viekira Pak + RBV
12 Weeks
N = 770 %
Placebo
12 Weeks
N = 255 %
Fatigue3426
Nausea2215
Pruritus*187
Skin reactions$169
Insomnia148
Asthenia147
*Grouped term 'pruritus' included the preferred terms pruritus and pruritus generalized.
$Grouped terms: rash, erythema, eczema, rash maculo-papular, rash macular, dermatitis, rash papular, skin exfoliation, rash pruritic, rash erythematous, rash generalized, dermatitis allergic, dermatitis contact, exfoliative rash, photosensitivity reaction, psoriasis, skin reaction, ulcer, urticaria.

Viekira Pak With And Without Ribavirin In Regimen-Controlled Trials

Viekira Pak with and without ribavirin was assessed in 401 and 509 subjects with chronic HCV infection, respectively, in three clinical trials (PEARL-II, PEARL-III and PEARL-IV). Pruritus, nausea, insomnia, and asthenia were identified as adverse events occurring more often in subjects treated with Viekira Pak in combination with ribavirin (see Table 4).

The majority of adverse events were mild to moderate in severity. The proportion of subjects who permanently discontinued treatment due to adverse events was less than 1% for both Viekira Pak in combination with ribavirin and Viekira Pak alone.

Table 4: Adverse Events with ≥ 5% Greater Frequency Reported in Subjects with Chronic HCV GT1 Infection Treated with Viekira Pak in Combination with Ribavirin Compared to Viekira Pak for 12 Weeks

PEARL-II, -III and-IV
Viekira Pak + RBV
12 Weeks
N = 401 %
Viekira Pak
12 Weeks
N = 509 %
Nausea168
Pruritus*137
Insomnia125
Asthenia94
*Grouped term 'pruritus' included the preferred terms pruritus and pruritus generalized.

Viekira Pak With Ribavirin In GT1-infected Subjects With Compensated Cirrhosis

Viekira Pak with ribavirin was assessed in 380 subjects with genotype 1 infection and compensated cirrhosis who were treated with Viekira Pak plus ribavirin for 12 (n=208) or 24 (n=172) weeks duration (TURQUOISE-II). The type and severity of adverse events in subjects with compensated cirrhosis was comparable to non-cirrhotic subjects in other phase 3 trials. Fatigue, skin reactions and dyspnea occurred at least 5% more often in subjects treated for 24 weeks.

The majority of adverse events occurred during the first 12 weeks of dosing in both treatment arms. Most of the adverse events were mild to moderate in severity. The proportion of subjects treated with Viekira Pak for 12 and 24 weeks with SAEs was 6% and 5%, respectively and 2% of subjects permanently discontinued treatment due to adverse events in each treatment arm.

Viekira Pak Without Ribavirin In GT1b-infected Subjects With Compensated Cirrhosis

Viekira Pak without ribavirin for 12 weeks was assessed in 60 subjects with genotype 1b infection and compensated cirrhosis (TURQUOISE-III). The type and severity of adverse events and laboratory abnormalities in genotype 1b-infected subjects with compensated cirrhosis were comparable to subjects in other trials without ribavirin.

Skin Reactions

In PEARL-II, -III and -IV, 7% of subjects receiving Viekira Pak alone and 10% of subjects receiving Viekira Pak with ribavirin reported rash-related events. In SAPPHIRE-I and -II 16% of subjects receiving Viekira Pak with ribavirin and 9% of subjects receiving placebo reported skin reactions. In TURQUOISE-II, 18% and 24% of subjects receiving Viekira Pak with ribavirin for 12 or 24 weeks reported skin reactions.

The majority of events were graded as mild in severity. There were no serious events or severe cutaneous reactions, such as Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), erythema multiforme (EM) or drug rash with eosinophilia and systemic symptoms (DRESS).

Laboratory Abnormalities

Serum ALT Elevations

Approximately 1% of subjects treated with Viekira Pak experienced post-baseline serum ALT levels greater than 5 times the upper limit of normal (ULN) after starting treatment. The incidence increased to 25% (4/16) among women taking a concomitant ethinyl estradiol containing medication. The incidence of clinically relevant ALT elevations among women using estrogens other than ethinyl estradiol, such as estradiol and conjugated estrogens used in hormone replacement therapy was 3% (2/59).

ALT elevations were typically asymptomatic, generally occurred during the first 4 weeks of treatment (mean time 20 days, range 8-57 days) and most resolved with ongoing therapy. The majority of these ALT elevations were assessed as drug-related liver injury. Elevations in ALT were generally not associated with bilirubin elevations. Cirrhosis was not a risk factor for elevated ALT.

Serum Bilirubin Elevations

Post-baseline elevations in bilirubin at least 2 x ULN were observed in 15% of subjects receiving Viekira Pak with ribavirin compared to 2% in those receiving Viekira Pak alone. These bilirubin increases were predominately indirect and related to the inhibition of the bilirubin transporters OATP1B1/1B3 by paritaprevir and ribavirin-induced hemolysis. Bilirubin elevations occurred after initiation of treatment, peaked by study Week 1, and generally resolved with ongoing therapy. Bilirubin elevations were not associated with serum ALT elevations.

Anemia/Decreased Hemoglobin

Across all Phase 3 studies, the mean change from baseline in hemoglobin levels in subjects treated with Viekira Pak in combination with ribavirin was -2.4 g/dL and the mean change in subjects treated with Viekira Pak alone was -0.5 g/dL. Decreases in hemoglobin levels occurred early in treatment (Week 1-2) with further reductions through Week 3. Hemoglobin values remained low during the remainder of treatment and returned towards baseline levels by post-treatment Week 4.

Less than 1% of subjects treated with Viekira Pak with ribavirin had hemoglobin levels decrease to less than 8.0 g/dL during treatment. Seven percent of subjects treated with Viekira Pak in combination with ribavirin underwent a ribavirin dose reduction due to a decrease in hemoglobin levels; three subjects received a blood transfusion and five required erythropoietin. One patient discontinued therapy due to anemia. No subjects treated with Viekira Pak alone had a hemoglobin level less than 10 g/dL.

Viekira Pak In HCV/HIV-1 Co-infected Subjects

Viekira Pak with ribavirin was assessed in 63 subjects with HCV/HIV-1 co-infection who were on stable antiretroviral therapy. The most common adverse events occurring in at least 10% of subjects were fatigue (48%), insomnia (19%), nausea (17%), headache (16%), pruritus (13%), cough (11%), irritability (10%), and ocular icterus (10%).

Elevations in total bilirubin greater than 2 x ULN (mostly indirect) occurred in 34 (54%) subjects. Fifteen of these subjects were also receiving atazanavir at the time of bilirubin elevation and nine also had adverse events of ocular icterus, jaundice or hyperbilirubinemia. None of the subjects with hyperbilirubinemia had concomitant elevations of aminotransferases. No subject experienced a grade 3 ALT elevation.

Seven subjects (11%) had at least one post-baseline hemoglobin value of less than 10 g/dL, and six of these subjects had a ribavirin dose modification; no subject in this small cohort required a blood transfusion or erythropoietin.

Median declines in CD4+ T-cell counts of 47 cells/mm³ and 62 cells/mm³ were observed at the end of 12 and 24 weeks of treatment, respectively, and most returned to baseline levels post-treatment. Two subjects had CD4+ T-cell counts decrease to less than 200 cells/mm³ during treatment without a decrease in CD4%. No subject experienced an AIDS-related opportunistic infection.

Viekira Pak In Selected Liver Transplant Recipients

Viekira Pak with ribavirin was assessed in 34 post-liver transplant subjects with recurrent HCV infection. Adverse events occurring in more than 20% of subjects included fatigue 50%, headache 44%, cough 32%, diarrhea 26%, insomnia 26%, asthenia 24%, nausea 24%, muscle spasms 21% and rash 21%.

Ten subjects (29%) had at least one post-baseline hemoglobin value of less than 10 g/dL. Ten subjects underwent a ribavirin dose modification due to decrease in hemoglobin and 3% (1/34) had an interruption of ribavirin. Five subjects received erythropoietin, all of whom initiated ribavirin at the starting dose of 1000 to 1200 mg daily. No subject received a blood transfusion.

Post-Marketing Adverse Reactions

The following adverse reactions have been identified during post approval use of Viekira Pak. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune System Disorders: Hypersensitivity reactions (including angioedema).

Hepatobiliary Disorders: Hepatic decompensation, hepatic failure.

What drugs interact with Viekira Pak (dasabuvir, ombitasvir, paritaprevir, and ritonavir)?

Potential For Viekira Pak To Affect Other Drugs

Ombitasvir, paritaprevir, and dasabuvir are inhibitors of UGT1A1, and ritonavir is an inhibitor of CYP3A4. Paritaprevir is an inhibitor of OATP1B1 and OATP1B3 and paritaprevir, ritonavir and dasabuvir are inhibitors of BCRP. Co-administration of Viekira Pak with drugs that are substrates of CYP3A, UGT1A1, BCRP, OATP1B1 or OATP1B3 may result in increased plasma concentrations of such drugs.

Potential For Other Drugs To Affect One Or More Components Of Viekira Pak

Paritaprevir and ritonavir are primarily metabolized by CYP3A enzymes. Co-administration of Viekira Pak with strong inhibitors of CYP3A may increase paritaprevir and ritonavir concentrations. Dasabuvir is primarily metabolized by CYP2C8 enzymes. Co-administration of Viekira Pak with drugs that inhibit CYP2C8 may increase dasabuvir plasma concentrations. Ombitasvir is primarily metabolized via amide hydrolysis while CYP enzymes play a minor role in its metabolism. Ombitasvir, paritaprevir, dasabuvir and ritonavir are substrates of P-gp. Ombitasvir, paritaprevir and dasabuvir are substrates of BCRP. Paritaprevir is a substrate of OATP1B1 and OATP1B3. Inhibition of P-gp, BCRP, OATP1B1 or OATP1B3 may increase the plasma concentrations of the various components of Viekira Pak.

Established And Other Potential Drug Interactions

If dose adjustments of concomitant medications are made due to treatment with Viekira Pak, doses should be re-adjusted after administration of Viekira Pak is completed. Dose adjustment is not required for Viekira Pak.

Table 5 provides the effect of co-administration of Viekira Pak on concentrations of concomitant drugs and the effect of concomitant drugs on the various components of Viekira Pak. Refer to the ritonavir prescribing information for other potentially significant drug interactions with ritonavir.

Table 5: Established Drug Interactions Based on Drug Interaction Trials

Concomitant Drug Class: Drug NameEffect on ConcentrationClinical Comments
ANGIOTENSIN RECEPTOR BLOCKERS e.g.
valsartan*
losartan*
candesartan*
↑ angiotensin receptor blockersDecrease the dose of the angiotensin receptor blockers and monitor patients for signs and symptoms of hypotension and/or worsening renal function. If such events occur, consider further dose reduction of the angiotensin receptor blocker or switching to an alternative to the angiotensin receptor blocker.
ANTIARRHYTHMICS
amiodarone*,
bepridil*,
disopyramide*,
flecainide*,
lidocaine (systemic)*,
mexiletine*,
propafenone ,
quinidine*
↑antiarrhythmicsTherapeutic concentration monitoring (if available) is recommended for antiarrhythmics when co-administered with Viekira Pak.
ANTIDIABETIC DRUGS
metformin↔ metforminMonitor for signs of onset of lactic acidosis such as respiratory distress, somnolence, and non-specific abdominal distress or worsening renal function. Concomitant metformin use in patients with renal insufficiency or hepatic impairment is not recommended. Refer to the prescribing information of metformin for further g uidanc e .
ANTIFUNGALS
ketoconazole↑ ketoconazoleWhen Viekira Pak is co-administered with ketoconazole, the maximum daily dose of ketoconazole should be limited to 200 mg per day.
voriconazole*↓ voriconazoleCo-administration of Viekira Pak with voriconazole is not recommended unless an assessment of the benefit-to-risk ratio justifies the use of voriconazole.
ANTIPSYCHOTICS
quetiapine*↑ quetiapine
  • Initiation of Viekira Pak in patients taking quetiapine: Consider alternative anti-HCV therapy to avoid increases in quetiapine exposures. If coadministration is necessary, reduce the quetiapine dose to 1/6th of the current dose and monitor for quetiapine-associated adverse reactions. Refer to the quetiapine prescribing information for the recommendations on adverse reaction monitoring.
  • Initiation of quetiapine in patients taking Viekira Pak: Refer to the quetiapine prescribing information for initial dosing and titration of quetiapine.
CALCIUM CHANNEL BLOCKERS
amlodipine
nifedipine*
diltiazem*
verapamil*
↑ calcium channel blockersDecrease the dose of the calcium channel blocker. The dose of amlodipine should be decreased by at least 50%. Clinical monitoring of patients is recommended for edema and/or signs and symptoms of hypotension. If such events occur, consider further dose reduction of the calcium channel blocker or switching to an alternative to the calcium channel blocker.
CORTICOSTEROIDS (INHALED/NASAL)
fluticasone*↑ fluticasoneConcomitant use of Viekira Pak with inhaled or nasal fluticasone may reduce serum cortisol concentrations. Alternative corticosteroids should be considered, particularly for long term use.
DIURETICS
furosemide↑ furosemide (Cmax)Clinical monitoring of patients is recommended and therapy should be individualized based on patient’s response.
HIV-ANTIVIRAL AGENTS
atazanavir/ritonavir once daily↑ paritaprevirWhen coadministered with Viekira Pak, atazanavir 300 mg (without ritonavir) should only be given in the morning.
darunavir/ritonavir↓ darunavir (Ctrough)Co-administration of Viekira Pak with darunavir/ritonavir is not recommended.
lopinavir/ritonavir↑ paritaprevirCo-administration of Viekira Pak with lopinavir/ritonavir is not recommended.
rilpivirine↑ rilpivirineCo-administration of Viekira Pak with rilpivirine once daily is not recommended due to potential for QT interval prolongation with higher concentrations of rilpivirine.
HMG CoA REDUCTASE INHIBITORS
rosuvastatin↑ rosuvastatinWhen Viekira Pak is co-administered with rosuvastatin, the dose of rosuvastatin should not exceed 10 mg per day.
pravastatin↑ pravastatinWhen Viekira Pak is co-administered with pravastatin, the dose of pravastatin should not exceed 40 mg per day.
IMMUNO SUPPRE SSANTS
cyclosporine↑ cyclosporineWhen initiating therapy with Viekira Pak, reduce cyclosporine dose to 1/5th of the patient’s current cyclosporine dose. Measure cyclosporine blood concentrations to determine subsequent dose modifications. Upon completion of Viekira Pak therapy, the appropriate time to resume pre-Viekira Pak dose of cyclosporine should be guided by assessment of cyclosporine blood concentrations. Frequent assessment of renal function and cyclosporine-related side effects is recommended.
tacrolimus↑ tacrolimusWhen initiating therapy with Viekira Pak, the dose of tacrolimus needs to be reduced. Do not administer tacrolimus on the day Viekira Pak is initiated. Beginning the day after Viekira Pak is initiated; reinitiate tacrolimus at a reduced dose based on tacrolimus blood concentrations. Typical tacrolimus dosing is 0.5 mg every 7 days. Measure tacrolimus blood concentrations and adjust dose or dosing frequency to determine subsequent dose modifications. Upon completion of Viekira Pak therapy, the appropriate time to resume pre-Viekira Pak dose of tacrolimus should be guided by assessment of tacrolimus blood concentrations. Frequent assessment of renal function and tacrolimus related side effects is recommended.
LONG ACTING BETA-ADRENOCEPTOR AGONIST
salmeterol*↑ salmeterolConcurrent administration of Viekira Pak and salmeterol is not recommended. The combination may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations and sinus tachycardia.
MUSCLE RELAXANTS
carisoprodol↓ carisoprodol
↔mepobramate (metabolite of carisoprodol)
Increase dose if clinically indicated.
cyclobenzaprine↓cyclobenzaprine
↓norcyclobenzaprine (metabolite of cyclobenzaprine)
Increase dose if clinically indicated.
NARCOTIC ANALGESICS
buprenorphine/ naloxone↑buprenorphine
↑norbuprenorphine (metabolite of buprenorphine)
Patients should be closely monitored for sedation and cognitive effects.
Acetaminophen/ hydro codone↑ hydrocodone
↔ acetaminophen
Reduce the dose of hydrocodone by 50% and monitor patients for respiratory depression and sedation at frequent intervals. Upon completion of Viekira Pak therapy, adjust the hydrocodone dose and monitor for signs of opioid withdrawal.
PROTON PUMP INHIBITORS
omeprazole↓ omeprazoleMonitor patients for decreased efficacy of omeprazole. Consider increasing the omeprazole dose in patients whose symptoms are not well controlled; avoid use of more than 40 mg per day of omeprazole.
SEDATIVES/HYPNOTICS
alprazolam↑ alprazolamClinical monitoring of patients is recommended. A decrease in alprazolam dose can be considered based on clinical response.
diazepam↓ diazepam
↓ nordiazepam (metabolite of diazepam)
Increase dose if clinically indicated.
The direction of the arrow indicates the direction of the change in exposures (Cmax and AUC) (↑ = increase of more than 20%, ↓ = decrease of more than 20%, ↔ = no change or change less than 20%).
*not studied.

Drugs Without Clinically Significant Interactions With Viekira Pak

No dose adjustments are recommended when Viekira Pak is co-administered with the following medications:

Summary

Viekira Pak (dasabuvir, ombitasvir, paritaprevir, and ritonavir) is a combination of antiviral drugs used to treat patients with hepatitis C virus (HCV) genotype 1. Common side effects of Viekira Pak when used with ribavirin include tiredness, nausea, itching, skin reactions such as redness or rash, sleep problems (insomnia), and feeling weak. Common side effects of Viekira Pak when used without ribavirin include nausea, itching, and problems sleeping. Serious side effects of Viekira Pak include allergic reactions, anemia, and increases in liver enzymes and bilirubin. Drug interactions of Viekira Pak include afluzosin hydrochloride, certain anti-seizure medications, rifampin, and St. John's wort. Viekira Pak has not been evaluated in pregnant women. It is unknown if any of the drugs contained in Viekira Pak are excreted into human milk.

Treatment & Diagnosis

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Medically Reviewed on 5/1/2020
References
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Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.
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