Ombitasvir, Paritaprevir and Ritonavir Tablets

Name: Ombitasvir, Paritaprevir and Ritonavir Tablets

Side effects

TECHNIVIE should be 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 [see WARNINGS AND PRECAUTIONS]
  • Increased Risk of ALT Elevations [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of ombitasvir, paritaprevir and ritonavir 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 of TECHNIVIE is based on data from a clinical study that included 135 HCV genotype 4-infected subjects without cirrhosis, 91 who received ombitasvir 25 mg, paritaprevir 150 mg and ritonavir 100 mg (administered as one ombitasvir 25 mg tablet, three paritaprevir 50 mg tablets and one ritonavir 100 mg capsule) once daily with ribavirin for 12 weeks and 44 subjects without cirrhosis who received ombitasvir 25 mg, paritaprevir 150 mg, and ritonavir 100 mg (administered as one ombitasvir 25 mg tablet, three paritaprevir 50 mg tablets and one ritonavir 100 mg capsule) once daily without ribavirin for 12 weeks (PEARL-I).

Adverse reactions that occurred in subjects treated with ombitasvir, paritaprevir and ritonavir with or without ribavirin for 12 weeks are listed in Table 3. The majority of adverse reactions in PEARL-I were mild in severity. None of the subjects who received ombitasvir, paritaprevir and ritonavir with ribavirin experienced a serious adverse reaction. None of the subjects receiving ombitasvir, paritaprevir and ritonavir with or without ribavirin discontinued treatment due to an adverse reaction.

Table 3: Selected Adverse Reactions (All Grades) with ≥ 5% Frequency Reported in Subjects Treated with Ombitasvir, Paritaprevir and Ritonavir with or without Ribavirin for 12 Weeks

Adverse Reaction PEARL-I
Ombitasvir, paritaprevir, ritonavir + RBV 12 Weeks
N = 91 %		 Ombitasvir, paritaprevir, ritonavir 12 Weeks
N = 44 %
Asthenia 29 25
Fatigue 15 7
Nausea 14 9
Insomnia 13 5
Pruritus* 7 5
Skin reactions$# 7 5
*Grouped term 'pruritus' includes the preferred terms pruritus and pruritus generalized.
$Grouped term 'skin reactions' includes the preferred 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 and urticaria.
#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

None of the 135 HCV GT4 infected subjects treated with TECHNIVIE experienced post-baseline serum ALT levels greater than 5 times the upper limit of normal (ULN) after starting treatment [see WARNINGS AND PRECAUTIONS].

Serum Bilirubin Elevations

Post-baseline elevations in bilirubin at least 2 times ULN were observed in 5% (7/134) of subjects receiving TECHNIVIE; all of whom were also receiving RBV. These bilirubin increases were predominately indirect and related to the inhibition of the bilirubin transporters OATP1B1/1B3 by paritaprevir and possibly ribavirin-induced hemolysis. Bilirubin elevations occurred early after initiation of treatment, peaked by study Week 1, and generally resolved with ongoing therapy. Bilirubin elevations were generally not associated with serum ALT elevations.

Anemia/Decreased Hemoglobin

The mean change from baseline in hemoglobin levels in subjects treated with TECHNIVIE in combination with ribavirin was -2.1 g/dL and the mean change in subjects treated with TECHNIVIE alone was -0.4 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. One subject treated with TECHNIVIE with ribavirin had a single hemoglobin level decrease to less than 8 g/dL during treatment. Four percent (4/91) of subjects treated with TECHNIVIE with ribavirin underwent ribavirin dose reductions to manage anemia/decreased hemoglobin levels; none received a blood transfusion or erythropoietin. No subjects treated with TECHNIVIE alone had a hemoglobin level less than 8 g/dL.

Post-Marketing Experience

The following adverse reactions have been identified during post approval use of TECHNIVIE. 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 [see WARNINGS AND PRECAUTIONS].

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