Applies to elbasvir / grazoprevir: oral tablet.

Serious side effects

Along with its needed effects, elbasvir / grazoprevir 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 elbasvir / grazoprevir:

Less common

• Discouragement
• feeling sad or empty
• irritability
• loss of appetite
• loss of interest or pleasure
• trouble concentrating
• trouble sleeping
• unusual tiredness

Incidence not known

• Dark urine
• fever with or without chills
• large, hive-like swelling on face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• light-colored stools
• nausea and vomiting
• upper stomach pain
• yellow eyes or skin

Other side effects

Some side effects of elbasvir / grazoprevir 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

• Headache

Less common

• Diarrhea
• stomach pain

For Healthcare Professionals

Applies to elbasvir / grazoprevir: oral tablet.

General

In clinical trials, the safety of this drug (with or without ribavirin) was assessed in patients with chronic hepatitis C virus (HCV) infection with compensated liver disease (with or without cirrhosis). Clinical trials included therapy-naive and therapy-experienced (peginterferon alfa/ribavirin-experienced, peginterferon alfa/ribavirin/HCV protease inhibitor-experienced) patients, with and without HCV/HIV-coinfection; at least 1 clinical trial included patients with severe renal dysfunction, including those on hemodialysis. The most common side effects reported with this drug were fatigue and headache.

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

Other

Very common (10% or more): Fatigue (up to 25%)

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

Nervous system

Very common (10% or more): Headache (up to 17%)

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

Hematologic

The change from baseline in hemoglobin (Hgb) levels averaged about -2.2 g/dL in patients using this drug with ribavirin for 16 weeks and -0.3 g/dL in patients using this drug alone for 12 weeks. Hgb level decreased during the first 8 weeks of therapy, stayed low during the remainder of therapy, and normalized to baseline levels during follow-up. Less than 1% of patients using this drug with ribavirin had Hgb levels decrease to less than 8.5 g/dL during therapy; no patients using this drug alone had Hgb levels less than 8.5 g/dL.

In therapy-naive and therapy-experienced HCV/HIV-coinfected patients treated with this drug alone for 12 weeks, increase of CD4+ T-cell counts (of about 31 and 32 cells/mm3, respectively) was observed at the end of therapy. In therapy-experienced HCV/HIV-coinfected patients treated with this drug with ribavirin for 16 weeks, CD4+ T-cell counts decreased about 135 cells/mm3 by the end of therapy.^[Ref]

Very common (10% or more): Anemia (up to 16%)

Common (1% to 10%): Decreased hemoglobin

Frequency not reported: CD4+ T-cell counts increased, CD4+ T-cell counts decreased^[Ref]

Gastrointestinal

Very common (10% or more): Nausea (up to 12%)

Common (1% to 10%): Diarrhea, abdominal pain, dyspepsia, vomiting, constipation, upper abdominal pain, dry mouth^[Ref]

Dermatologic

Common (1% to 10%): Pruritus, alopecia, rash

Postmarketing reports: Angioedema^[Ref]

Hepatic

Common (1% to 10%): Elevated bilirubin

Uncommon (0.1% to 1%): Elevated ALT

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

During clinical trials with this drug (with or without ribavirin), regardless of duration of therapy, elevated bilirubin (greater than 2.5 x ULN) was reported in 6% and less than 1% of patients using this drug with ribavirin and alone, respectively. These increases were primarily indirect and generally associated with ribavirin coadministration. Elevated bilirubin was usually not associated with elevated serum ALT.

Based on pooled data in patients using this drug without ribavirin for 12 weeks, ALT of 5.1 to 10 x ULN, ALT of greater than 10 x ULN, total bilirubin of 2.6 to 5 x ULN, and total bilirubin of greater than 5 x ULN were reported in 0.7%, 0.7%, 0.4%, and 0% of patients, respectively.

During clinical trials with this drug (with or without ribavirin), regardless of duration of therapy, ALT in 13 of 1690 patients increased from normal levels to greater than 5 times the upper limit of normal (5 x ULN), usually at or after 8 weeks of therapy (mean onset: 10 weeks; range: 6 to 12 weeks). These late ALT elevations were generally asymptomatic and most resolved with continued use or after completion of therapy. Late ALT elevations occurred more often in patients with higher grazoprevir plasma levels (e.g., female, Asian, age at least 65 years). Incidence of late ALT elevations was not affected by duration of therapy and cirrhosis was not a risk factor. Less than 1% of patients treated with this drug (with or without ribavirin) had ALT elevations greater than 2.5 to 5 x ULN during therapy; therapy was not discontinued in these patients.^[Ref]

Musculoskeletal

Common (1% to 10%): Arthralgia, myalgia^[Ref]

Psychiatric

Common (1% to 10%): Insomnia, depression, irritability, anxiety^[Ref]

Respiratory

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

Metabolic

Common (1% to 10%): Decreased appetite