Note: This document contains side effect information about dasabuvir / ombitasvir / paritaprevir / ritonavir. Some dosage forms listed on this page may not apply to the brand name Viekira Pak.

Applies to dasabuvir / ombitasvir / paritaprevir / ritonavir: oral tablet.

Serious side effects of Viekira Pak

Along with its needed effects, dasabuvir/ombitasvir/paritaprevir/ritonavir may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking dasabuvir / ombitasvir / paritaprevir / ritonavir:

Less common

• Abdominal or stomach pain
• bloating of the abdomen or stomach
• dark urine
• light-colored stools
• nausea and vomiting
• yellow eyes or skin

Incidence not known

• Blistering, peeling, or loosening of the skin
• chills
• cough
• diarrhea
• itching
• joint or muscle pain
• red skin lesions, often with a purple center
• red, irritated eyes
• sore throat
• sores, ulcers, or white spots in the mouth or on the lips
• unusual tiredness or weakness

Other side effects of Viekira Pak

Some side effects of dasabuvir / ombitasvir / paritaprevir / ritonavir may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Itching skin or rash
• lack or loss of strength
• trouble sleeping

For Healthcare Professionals

Applies to dasabuvir / ombitasvir / paritaprevir / ritonavir: oral kit, oral tablet extended release.

General

In hepatitis C virus (HCV) genotype 1-infected patients without cirrhosis, the most common side effects reported with dasabuvir plus ombitasvir/paritaprevir/ritonavir with ribavirin were fatigue, nausea, pruritus, other skin reactions, insomnia, and asthenia; the most common side effects reported with dasabuvir plus ombitasvir/paritaprevir/ritonavir (without ribavirin) were nausea, pruritus, and insomnia. Most side effects were mild to moderate in severity.

In HCV genotype 1-infected patients (including those with cirrhosis), the most common side effects reported with dasabuvir plus ombitasvir/paritaprevir/ritonavir with ribavirin were fatigue and nausea.

In HCV genotype 1-infected patients with compensated cirrhosis, fatigue, skin reactions, and dyspnea were reported more often in those treated with dasabuvir plus ombitasvir/paritaprevir/ritonavir with ribavirin for 24 weeks; most side effects occurred during the first 12 weeks. In HCV genotype 1b-infected patients with compensated cirrhosis, the most common side effects reported with dasabuvir plus ombitasvir/paritaprevir/ritonavir (without ribavirin) were fatigue and diarrhea.

In HCV genotype 1/HIV-1-coinfected patients on stable antiretroviral therapy, the most common side effects reported with dasabuvir plus ombitasvir/paritaprevir/ritonavir with ribavirin were fatigue, insomnia, nausea, headache, pruritus, cough, irritability, and ocular icterus.

In post-liver transplant patients with recurrent HCV genotype 1 infection, the most common side effects reported with dasabuvir plus ombitasvir/paritaprevir/ritonavir with ribavirin were fatigue, headache, cough, diarrhea, insomnia, asthenia, nausea, anemia, muscle spasms, and rash.

If this product is used with ribavirin, the manufacturer product information for ribavirin should be consulted for associated side effects.^[Ref]

Hepatic

Grade 3 (greater than 3 to 10 times the upper limit of normal [3 to 10 x ULN]) and grade 4 (greater than 10 x ULN) total bilirubin elevations have been reported in up to 9.7% and 0.1% of patients, respectively. Grade 3 (greater than 5 to 20 x ULN) and grade 4 (greater than 20 x ULN) ALT elevations have been reported in up to 1.1% and up to 0.5% of patients, respectively.

Post-baseline bilirubin elevations (at least 2 x ULN) occurred in 15% of patients using dasabuvir plus ombitasvir/paritaprevir/ritonavir with ribavirin compared to 2% of those using dasabuvir plus ombitasvir/paritaprevir/ritonavir without ribavirin. These increases were primarily indirect and associated with inhibition of OATP1B1/1B3 (bilirubin transporters) by paritaprevir and ribavirin-induced hemolysis. Bilirubin elevations occurred after therapy initiation, peaked by week 1 of the study, and usually resolved with ongoing therapy. Elevated bilirubin was not associated with elevated serum ALT.

Grade 2 post-baseline total bilirubin increases were reported in 12 of 60 genotype 1b-infected patients with compensated cirrhosis using dasabuvir plus ombitasvir/paritaprevir/ritonavir (without ribavirin). No grade 3 or higher post-baseline total bilirubin increase occurred; 1 of 60 patients reported grade 3 ALT elevation.

In HCV/HIV-1-coinfected patients using dasabuvir plus ombitasvir/paritaprevir/ritonavir with ribavirin, elevations in total bilirubin greater than 2 x ULN and greater than 3 x ULN (mostly indirect) were reported in 34 (54%) and 17 (27%) patients, respectively. At the time of bilirubin elevation, 24 of these 34 patients and 15 of these 17 patients were also using atazanavir; 9 of the 17 patients also reported ocular icterus, jaundice, or hyperbilirubinemia. No concurrent elevations of aminotransferases occurred with hyperbilirubinemia.

About 1% of patients had post-baseline serum ALT levels greater than 5 x ULN during therapy; incidence increased to 25% (4/16) in women concurrently using a product containing ethinyl estradiol. Clinically relevant ALT elevations were reported in 2 of 59 women using estrogens other than ethinyl estradiol (e.g., estradiol, conjugated estrogens [hormone replacement therapy]).

ALT elevations were usually asymptomatic, occurred during the first 4 weeks of therapy (20 days [mean]; range: 8 to 56 days), and resolved with continued use. Most ALT elevations were assessed as drug-related liver injury. Elevated ALT was usually not associated with elevated bilirubin. Cirrhosis was not a risk factor for elevated ALT.

Hepatic decompensation and hepatic failure (including liver transplantation or fatal outcomes) have been reported in patients using ombitasvir/paritaprevir/ritonavir (with and without dasabuvir and with and without ribavirin). Most patients with these severe outcomes had evidence of advanced/decompensated cirrhosis before starting therapy. Cases were generally reported within 1 to 4 weeks of starting therapy and characterized by acute onset of rising direct serum bilirubin levels without increases in ALT together with clinical signs/symptoms of hepatic decompensation.^[Ref]

Very common (10% or more): Elevated total bilirubin (up to 54%), elevated ALT (up to 25%)

Frequency not reported: Drug-related liver injury, jaundice, hyperbilirubinemia

Postmarketing reports: Hepatic decompensation, hepatic failure, hepatitis B reactivation^[Ref]

Other

Very common (10% or more): Fatigue (up to 50%), asthenia (up to 24%)^[Ref]

Fatigue was reported in 48% of HCV/HIV-1 coinfected patients using dasabuvir plus ombitasvir/paritaprevir/ritonavir with ribavirin.

Fatigue (50%) and asthenia (24%) were reported in post-liver transplant patients using dasabuvir plus ombitasvir/paritaprevir/ritonavir with ribavirin.^[Ref]

Nervous system

Headache was reported in 16% of HCV/HIV-1 coinfected patients and 44.1% of post-liver transplant patients using dasabuvir plus ombitasvir/paritaprevir/ritonavir with ribavirin.^[Ref]

Very common (10% or more): Headache (up to 44.1%)

Common (1% to 10%): Dizziness^[Ref]

Respiratory

Very common (10% or more): Cough (up to 32.4%)

Common (1% to 10%): Dyspnea^[Ref]

Cough was reported in 11% of HCV/HIV-1 coinfected patients and 32.4% of post-liver transplant patients using dasabuvir plus ombitasvir/paritaprevir/ritonavir with ribavirin.^[Ref]

Gastrointestinal

Very common (10% or more): Diarrhea (26.5%), nausea (up to 24%)

Common (1% to 10%): Vomiting^[Ref]

Nausea was reported in 17% of HCV/HIV-1 coinfected patients using dasabuvir plus ombitasvir/paritaprevir/ritonavir with ribavirin.

Diarrhea (26.5%) and nausea (24%) were reported in post-liver transplant patients using dasabuvir plus ombitasvir/paritaprevir/ritonavir with ribavirin.^[Ref]

Psychiatric

Very common (10% or more): Insomnia (up to 26.5%), irritability (10%)

Common (1% to 10%): Sleep disorder^[Ref]

Insomnia (19%) and irritability (10%) were reported in HCV/HIV-1 coinfected patients using dasabuvir plus ombitasvir/paritaprevir/ritonavir with ribavirin.

Insomnia was reported in 26.5% of post-liver transplant patients using dasabuvir plus ombitasvir/paritaprevir/ritonavir with ribavirin.^[Ref]

Dermatologic

Very common (10% or more): Skin reactions (includes rash, erythema, eczema, maculopapular rash, macular rash, dermatitis, papular rash, skin exfoliation, pruritic rash, erythematous rash, generalized rash, allergic dermatitis, contact dermatitis, exfoliative rash, photosensitivity reaction, psoriasis, skin reaction, ulcer, urticaria; up to 24%), pruritus (includes pruritus, generalized pruritus; up to 18.7%)

Common (1% to 10%): Rash-related events, dry skin

Postmarketing reports: Erythema multiforme

Ritonavir:

-Postmarketing reports: Stevens-Johnson syndrome^[Ref]

Pruritus was reported in 13% of HCV/HIV-1 coinfected patients using dasabuvir plus ombitasvir/paritaprevir/ritonavir with ribavirin.

Rash was reported in 21% of post-liver transplant patients using dasabuvir plus ombitasvir/paritaprevir/ritonavir with ribavirin.^[Ref]

Musculoskeletal

Muscle spasms were reported in 21% of post-liver transplant patients using dasabuvir plus ombitasvir/paritaprevir/ritonavir with ribavirin.^[Ref]

Very common (10% or more): Muscle spasms (21%)^[Ref]

Hematologic

Very common (10% or more): Anemia (up to 20.6%)

Common (1% to 10%): Decreased hemoglobin (Hgb)

Frequency not reported: Decreased CD4+ T-cell counts^[Ref]

Grade 2 (8 to less than 10 g/dL), grade 3 (6.5 to less than 8 g/dL), and grade 4 (less than 6.5 g/dL) Hgb decreases have been reported in up to 7.9%, up to 0.8%, and up to 0.3% of patients, respectively.

In phase 3 trials, the change from baseline in Hgb levels averaged -2.4 g/dL in patients using dasabuvir plus ombitasvir/paritaprevir/ritonavir with ribavirin and -0.5 g/dL in patients using dasabuvir plus ombitasvir/paritaprevir/ritonavir without ribavirin. Hgb level decreased early in therapy (week 1 or 2) with further decreases through week 3. Low Hgb values persisted throughout therapy and returned towards baseline levels by 4 weeks after therapy. Less than 1% of patients using dasabuvir plus ombitasvir/paritaprevir/ritonavir with ribavirin had Hgb levels decrease to less than 8 g/dL during therapy and 7% had their ribavirin dose reduced due to decreased Hgb levels; 3 patients received a blood transfusion and 5 required erythropoietin. Therapy was discontinued due to anemia in 1 patient. No patients using dasabuvir plus ombitasvir/paritaprevir/ritonavir without ribavirin had Hgb levels less than 10 g/dL.

A grade 2 post-baseline Hgb decrease was reported in 1 of 60 genotype 1b-infected patients with compensated cirrhosis using dasabuvir plus ombitasvir/paritaprevir/ritonavir (without ribavirin). No grade 3 or higher post-baseline Hgb decrease occurred.

At least 1 post-baseline Hgb value less than 10 g/dL was reported in 7 of 63 HCV/HIV-1-coinfected patients using dasabuvir plus ombitasvir/paritaprevir/ritonavir with ribavirin. Ribavirin dose was modified in 6 of these patients; no patient required a blood transfusion or erythropoietin.

In HCV/HIV-1-coinfected patients using dasabuvir plus ombitasvir/paritaprevir/ritonavir with ribavirin, CD4+ T-cell count decreases averaged 47 cells/mm3 and 62 cells/mm3 by the end of 12 and 24 weeks of therapy, respectively; most returned to baseline levels posttreatment. During therapy, CD4+ T-cell counts decreased to less than 200 cells/mm3 (without a decrease in CD4%) in 2 patients. AIDS-related opportunistic infection occurred in 2 patients but was not considered therapy-related.

At least 1 post-baseline Hgb value less than 10 g/dL was reported in 10 of 34 post-liver transplant patients using dasabuvir plus ombitasvir/paritaprevir/ritonavir with ribavirin. Ribavirin dose was modified in 10 of these patients and interrupted in 1 patient; 5 patients received erythropoietin and no patient required a blood transfusion.

Anemia was reported in 20.6% of post-liver transplant patients using dasabuvir plus ombitasvir/paritaprevir/ritonavir with ribavirin.^[Ref]

Ocular

Ocular icterus was reported in 10% of HCV/HIV-1 coinfected patients using dasabuvir plus ombitasvir/paritaprevir/ritonavir with ribavirin.^[Ref]

Very common (10% or more): Ocular icterus (10%)^[Ref]

Hypersensitivity

Postmarketing reports: Anaphylactic reactions, other hypersensitivity reactions (including angioedema/tongue and lip swelling)^[Ref]

Metabolic

Common (1% to 10%): Decreased appetite