INCIVEK was administered in combination with peginterferon alfa and ribavirin. The following table lists adverse drug reactions that occurred in INCIVEK-treated subjects with an incidence at least 5% greater than in subjects receiving peginterferon alfa and ribavirin alone (Table 4).

Table 4: Clinical Adverse Drug Reactions Reported with at Least 5% Higher Frequency Among Subjects Receiving INCIVEK   INCIVEK, peginterferon alfa, and ribavirin Combination Treatment
N=1797 Peginterferon alfa and ribavirin

N=493
*
Rash and anemia based on SSC (Special Search Category) grouped terms.
Rash* 56% 34%
Fatigue 56% 50%
Pruritus 47% 28%
Nausea 39% 28%
Anemia* 36% 17%
Diarrhea 26% 17%
Vomiting 13% 8%
Hemorrhoids 12% 3%
Anorectal discomfort 11% 3%
Dysgeusia 10% 3%
Anal pruritus 6% 1%
Description of Selected Adverse Drug Reactions
Rash
In controlled clinical trials, rash events (all grades) were reported in 56% of subjects who received INCIVEK combination treatment and in 34% of subjects who received peginterferon alfa and ribavirin. Rash most frequently began during the first 4 weeks, but could occur at any time during INCIVEK combination treatment. Improvement of rash occurs after INCIVEK dosing completion or discontinuation; however, rashes may take weeks for complete resolution.

Rash events led to discontinuation of INCIVEK alone in 6% of subjects and discontinuation of INCIVEK combination treatment in 1% of subjects.

For serious skin reactions and severe rash, see Warnings and Precautions (5.2 and 5.3).

Anemia
In controlled clinical trials, the overall incidence and severity of anemia increased with INCIVEK combination treatment compared to peginterferon alfa and ribavirin alone. The incidence of anemia adverse events was 36% with INCIVEK combination treatment compared to 17% with peginterferon alfa and ribavirin alone. A decrease in hemoglobin levels occurred during the first 4 weeks of treatment, with lowest values reached at the end of INCIVEK dosing. Hemoglobin values gradually returned to levels observed with peginterferon alfa and ribavirin after INCIVEK dosing was completed [see Warnings and Precautions (5.4)].

Anorectal Signs and Symptoms

In the controlled clinical trials, 29% of subjects treated with INCIVEK combination treatment experienced anorectal adverse events, compared to 7% of those treated with peginterferon alfa and ribavirin alone. The majority of these events (e.g., hemorrhoids, anorectal discomfort, anal pruritus, and rectal burning) were mild to moderate in severity; less than 1% led to treatment discontinuation and all resolved during or after completion of INCIVEK dosing.

Laboratory abnormalities

White Blood Cells: Treatment with peginterferon alfa is associated with decreases in mean values for total white blood cell, absolute neutrophil, and absolute lymphocyte cou