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

Applies to ombitasvir / paritaprevir / ritonavir: oral tablet.

Serious side effects of Technivie

Along with its needed effects, 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 ombitasvir / paritaprevir / ritonavir:

Less common

• Abdominal or stomach pain
• chills
• clay-colored stools
• dark urine
• dizziness
• fever
• headache
• itching or rash
• loss of appetite
• nausea
• unpleasant breath odor
• unusual tiredness or weakness
• vomiting of blood
• yellow eyes or skin

Incidence not known

• Large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs

Other side effects of Technivie

Some side effects of 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

• Blistering, crusting, irritation, itching, or reddening of the skin
• cracked, dry, or scaly skin
• increased sensitivity of the skin to sunlight
• lack or loss of strength
• redness or other discoloration of the skin
• severe sunburn
• skin rash, encrusted, scaly, and oozing
• swelling
• trouble sleeping

For Healthcare Professionals

Applies to ombitasvir / paritaprevir / ritonavir: oral tablet.

General

The most common side effects reported in patients using this drug plus dasabuvir and ribavirin were fatigue and nausea. The most common side effects reported in genotype 4-infected patients without cirrhosis using this drug plus ribavirin were asthenia, fatigue, nausea, and insomnia; the most common side effect reported in such patients using this drug without ribavirin was asthenia. The most common side effects reported in genotype 4-infected patients with compensated cirrhosis using this drug plus ribavirin were fatigue, asthenia, headache, musculoskeletal pain/changes, pruritus, insomnia/sleep disorder, skin reactions, dyspnea, mood disorders, nausea, and dizziness.

The manufacturer product information for dasabuvir and/or ribavirin should be consulted.^[Ref]

Hepatic

Very common (10% or more): Elevated direct bilirubin levels

Common (1% to 10%): Elevated ALT, elevated total bilirubin, hyperbilirubinemia, clinical liver/bilirubin-related events (includes ascites, hepatic encephalopathy, jaundice, ocular icterus, esophageal varices hemorrhage, portal vein thrombosis)

Frequency not reported: Hepatic decompensation, hepatic failure, liver-related esophageal varices, liver-related ascites^[Ref]

Combination therapy with dasabuvir and ribavirin for 12 weeks: ALT greater than 5 to 20 times the upper limit of normal (5 to 20 x ULN), ALT greater than 20 x ULN, total bilirubin greater than 3 to 10 x ULN, and total bilirubin greater than 10 x ULN were reported in 0.8%, 0.4%, 2.5%, and 0.1% of patients, respectively.

Combination therapy with dasabuvir (without ribavirin) for 12 weeks: ALT greater than 5 to 20 x ULN and total bilirubin greater than 3 to 10 x ULN were reported in 0.2% and 0.4% of patients, respectively.

Combination therapy with dasabuvir and ribavirin for 12 or 24 weeks: ALT greater than 5 to 20 x ULN, ALT greater than 20 x ULN, and total bilirubin greater than 3 to 10 x ULN were reported in 1.1%, 0.5%, and 9.7% of cirrhosis patients, respectively.

In clinical trials with this drug and dasabuvir (with and without ribavirin), about 1% of patients had post-baseline serum ALT levels greater than 5 x ULN during therapy; incidence increased to 26% in women concurrently using a product containing ethinyl estradiol. No increase in incidence of ALT elevations was reported with estrogens other than ethinyl estradiol (e.g., estradiol, conjugated estrogens).

ALT elevations were usually asymptomatic, occurred during the first 4 weeks of therapy (20 days [mean]; range: 8 to 57 days), and resolved with continued use. Elevated ALT was usually not associated with elevated bilirubin. Cirrhosis was not a risk factor for elevated ALT.

Transient serum bilirubin elevations were reported in patients using this drug with dasabuvir and 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 aminotransferase elevations.

Transient elevations in total bilirubin greater than 3 x ULN (mostly indirect) were reported in 17 (27%) HCV/HIV-1 coinfected patients using combination therapy with dasabuvir and ribavirin; 15 of these patients were also using atazanavir. No concurrent elevations of aminotransferases occurred with hyperbilirubinemia.

None of the genotype 4-infected patients without cirrhosis (n=135) and 2 of the patients with compensated cirrhosis (n=120) reported post-baseline ALT levels greater than 5 x ULN and at least 2 times baseline after starting this drug.

Post-baseline bilirubin elevations (at least 2 x ULN) occurred in 5% of genotype 4-infected patients without cirrhosis using this drug with ribavirin. These increases were primarily indirect and associated with inhibition of OATP1B1/1B3 (bilirubin transporters) by paritaprevir and possibly ribavirin-induced hemolysis. Bilirubin elevations occurred soon after the start of therapy, peaked by week 1 of the study, and usually resolved with ongoing therapy. Elevated bilirubin was usually not associated with elevated serum ALT.

Total bilirubin and indirect bilirubin levels increased to about 3-fold from baseline during therapy in genotype 4-infected patients with compensated cirrhosis; direct bilirubin levels increased to about 2-fold during therapy. Elevated bilirubin occurred early, peaked by week 1 of the study, remained elevated during therapy, and normalized by 4 weeks after therapy; in general, elevated bilirubin was not associated with serum ALT elevations. Elevated direct bilirubin levels (greater than ULN) at or before 12 weeks of therapy were reported in 50 of 120 genotype 4-infected patients with compensated cirrhosis; 12% of these patients had clinical bilirubin/liver-related side effects (e.g., jaundice, ocular icterus, and portal vein thrombosis). At least 1 patient without elevated direct bilirubin reported liver-related esophageal varices and ascites.

Hepatic decompensation and hepatic failure (including liver transplantation or fatal outcomes) have been reported in patients using this drug (with and without dasabuvir and with and without ribavirin). Most patients with these severe outcomes had evidence of cirrhosis (including advanced or 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.

Compared to patients without cirrhosis, rate of indirect hyperbilirubinemia was increased in patients with compensated cirrhosis when ribavirin was part of the regimen.

Hepatic decompensation and hepatic failure have also been reported during postmarketing experience.^[Ref]

Other

Very common (10% or more): Asthenia (up to 29%), fatigue (up to 25%)

Common (1% to 10%): Edema (includes edema, peripheral edema)^[Ref]

Nervous system

Very common (10% or more): Headache (23%), dizziness (11%)

Common (1% to 10%): Altered mental status (includes disturbance in attention, memory impairment, somnolence)^[Ref]

Musculoskeletal

Very common (10% or more): Musculoskeletal pain/changes (includes arthralgia, arthritis, back pain, muscle injury muscle spasms, muscular weakness, musculoskeletal chest pain, myalgia, neck pain, pain in extremity; 17%)^[Ref]

Gastrointestinal

Very common (10% or more): Nausea (up to 14%), diarrhea

Common (1% to 10%): Abdominal pain (includes abdominal discomfort, abdominal pain, lower abdominal pain, upper abdominal pain), vomiting^[Ref]

Psychiatric

Very common (10% or more): Insomnia/sleep disorder (up to 14%), mood disorders (includes affective disorder, agitation, anxiety, depressed mood, depression, irritability, mania, suicide attempt; 11%)

Common (1% to 10%): Altered mental status (includes psychomotor retardation)^[Ref]

Dermatologic

Very common (10% or more): Pruritus (includes pruritus, generalized pruritus), skin reactions (includes bullous dermatitis, psoriasiform dermatitis, dry skin, asteatotic eczema, erythema, rash, skin exfoliation, skin lesion, skin toxicity; 13%)

Common (1% to 10%): 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)

Rare (0.01% to 0.1%): Angioedema

Postmarketing reports: Erythema multiforme^[Ref]

Respiratory

Very common (10% or more): Dyspnea (includes dyspnea, exertional dyspnea; 11%)

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

Hematologic

Common (1% to 10%): Anemia, decreased hemoglobin (Hgb)^[Ref]

Combination therapy with dasabuvir and ribavirin for 12 weeks: Hgb 8 to less than 10 g/dL and Hgb 6.5 to less than 8 g/dL were reported in 5.4% and 0.1% of patients, respectively.

Combination therapy with dasabuvir and ribavirin for 12 or 24 weeks: Hgb 8 to less than 10 g/dL, Hgb 6.5 to less than 8 g/dL, and Hgb less than 6.5 g/dL were reported in 7.9%, 0.8%, and 0.3% of cirrhosis patients, respectively.

At least 1 post-baseline Hgb value less than 10 g/dL was reported in 10 of 34 post-liver transplant patients using this drug with dasabuvir and ribavirin. Ribavirin dose was modified in 10 patients due to decreased Hgb; ribavirin was interrupted in 1 patient. Five patients (ribavirin starting dose of 1000 to 1200 mg/day) required erythropoietin; no patient required a blood transfusion.

The change from baseline in Hgb levels averaged -2.1 g/dL in genotype 4-infected patients without cirrhosis using this drug with ribavirin and -0.4 g/dL in patients using this drug alone. 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. At least 1 patient using this drug with ribavirin had a single Hgb level decrease to less than 8 g/dL during therapy and 4% had their ribavirin dose reduced due to anemia/decreased Hgb levels; no patient received a blood transfusion or erythropoietin. No patients using this drug alone had Hgb levels less than 8 g/dL.

Before starting therapy, 4 of 120 genotype 4-infected patients with compensated cirrhosis had anemia (Hgb less than the lower limit of normal). At or before 12 weeks of therapy, anemia and/or Hgb decrease of at least 2 g/dL occurred in 88 or 120 patients; at least 1 patient had a Hgb value less than 8 g/dL. Reduced Hgb were most likely mainly due to ribavirin in these patients. In 9 of 64 patients with history of cardiovascular disease or diabetes mellitus, Hgb decreased about 3.9 g/dL (range: 1.1 to 5.3 g/dL) from baseline and cardiac events occurred.

More genotype 1-infected patients (with or without cirrhosis) with severe renal dysfunction required intervention due to ribavirin-associated serum Hgb decreases than patients without renal dysfunction. The baseline Hgb level averaged 12.1 g/dL and the decline in Hgb at the end of therapy with ribavirin averaged 1.2 g/dL; 39 of the 50 patients who used ribavirin required interruption of ribavirin, and 11 of these patients were also treated with erythropoietin. Hgb level less than 8 g/dL was observed in 4 patients; 2 patients received a blood transfusion.^[Ref]

Cardiovascular

At or before 12 weeks of therapy, cardiac events were reported in 9 of 64 genotype 4-infected patients with compensated cirrhosis who had history of cardiovascular disease or diabetes mellitus. In these 9 patients, Hgb decreased about 3.9 g/dL from baseline and cardiac events (e.g., acute coronary syndrome, angina pectoris, chest pain, atrial fibrillation, palpitations, hypotension, and hypertension) occurred. A cardiac event (mild or moderate hypertension) was reported in 2 of 56 patients without history of cardiovascular disease or diabetes.^[Ref]

Common (1% to 10%): Cardiac events (includes acute coronary syndrome, angina pectoris, atrial fibrillation, chest pain, hypertension, hypotension, palpitations)^[Ref]

Metabolic

Common (1% to 10%): Decreased appetite

Uncommon (0.1% to 1%): Dehydration^[Ref]

Hypersensitivity

Postmarketing reports: Anaphylactic reactions, other hypersensitivity reactions (including angioedema)^[Ref]