Ombitasvir, paritaprevir and ritonavir

You should not use Technivie if you are allergic to ombitasvir, paritaprevir, or ritonavir, or if you have:

• moderate to severe liver problems; or

• if you have ever had a severe skin rash after taking ritonavir (Norvir).

If you take Technivie with ribavirin: There may be other reasons you should not take this combination treatment. Tell your doctor about all your medical conditions.

Some medicines can interact with Technivie and should not be used at the same time. Your doctor may need to change your treatment plan if you use any of the following drugs:

• alfuzosin;

• colchicine;

• dronedarone;

• efavirenz;

• ranolazine;

• rifampin;

• sildenafil (Revatio), when taken for pulmonary artery hypertension (PAH);

• St. John's wort;

• oral midazolam (Versed), or triazolam;

• antipsychotic medicine--lurasidone, pimozide;

• birth control pills or patches--Lo Loestrin FE, Norinyl, Ortho Tri-Cyclen Lo, Ortho Evra, and others;

• hormone replacement therapy such as Fem HRT;

• a vaginal ring such as NuvaRing;

• cholesterol-lowering medicine--gemfibrozil, lovastatin, simvastatin (Zocor, Vytorin, Simcor);

• ergot medicine--dihydroergotamine, ergotamine, ergonovine, methylergonovine; or

• seizure medicine--carbamazepine, phenytoin, phenobarbital.

Before you start taking Technivie, you must stop using medicine that contains ethinyl estradiol. This includes certain birth control pills or hormone replacement medicines. Ask your doctor about using non-hormonal birth control (condom, diaphragm with spermicide) to prevent pregnancy while taking Technivie and for 2 weeks after your treatment ends.

To make sure Technivie is safe for you, tell your doctor if you have:

• a history of hepatitis B;

• liver problems other than hepatitis;

• heart disease;

• HIV (human immunodeficiency virus); or

• if you have received a liver transplant.

If you take Technivie with ribavirin: Avoid getting pregnant during treatment and for at least 6 months after you stop taking these medicines together. Ribavirin is known to cause birth defects or death in an unborn baby. You may need to have a negative pregnancy test before taking ribavirin.

While you are taking Technivie with ribavirin: Use birth control to prevent pregnancy whether you are a man or a woman. Ribavirin use by either parent may cause birth defects. Tell your doctor right away if a pregnancy occurs while either the mother or the father is taking ribavirin.

It is not known whether Technivie passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Technivie is not approved for use by anyone younger than 18 years old.

When you start or stop taking Technivie, your doctor may need to adjust the doses of any other medicines you take on a regular basis.

Many drugs can interact with Technivie. Not all possible interactions are listed here. Tell your doctor about all your medications and any you start or stop using during treatment with Technivie, especially:

• metformin;

• quetiapine;

• heart or blood pressure medicine;

• medicine to treat HIV or AIDS;

• narcotic pain medicine;

• antifungal medicine--ketoconazole, voriconazole;

• asthma or allergy medicine--including Flonase, Veramyst, Flovent, Advair, Arnuity Ellipta, Serevent Diskus, and others; or

• medicine to prevent organ transplant rejection--cyclosporine, tacrolimus.

Many drugs can interact with Technivie, and some drugs should not be used together. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide. Tell your doctor about all medicines you use, and those you start or stop using during your treatment with Technivie. Give a list of all your medicines to any healthcare provider who treats you.

Contraindications

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

• Known hypersensitivity to ritonavir (e.g., toxic epidermal necrolysis [TEN], Stevens-Johnson syndrome).1

• Moderate or severe hepatic impairment (Child-Pugh class B or C).1 (See Hepatic Impairment under Cautions.)

• When ombitasvir/paritaprevir/ritonavir used in conjunction with ribavirin, contraindications for ribavirin apply.1 (See Precautions Related to Fixed Combinations and Multiple-drug Treatment Regimens under Cautions.)

• Concomitant use with certain drugs (i.e., drugs highly dependent on CYP3A for clearance, potent or moderate inducers of CYP3A).1 (See Interactions.)

Warnings/Precautions

Hepatic Effects

Hepatic decompensation and hepatic failure, sometimes requiring liver transplantation or resulting in death, reported during postmarketing experience.1 14 Similar cases reported in patients receiving fixed combination of ombitasvir/paritaprevir/ritonavir with dasabuvir.14 180 Most patients with severe outcomes had evidence of advanced cirrhosis prior to receiving ombitasvir/paritaprevir/ritonavir with or without dasabuvir;1 14 some cases of hepatic failure occurred in patients for whom these drugs were contraindicated or not recommended.14 Reported cases typically occurred within 1–4 weeks after the drugs were initiated and were characterized by acute onset of increasing serum concentrations of direct bilirubin without increased ALT concentrations in association with clinical signs and symptoms of hepatic decompensation.1 14

Increased ALT concentrations (>5 times ULN) observed in approximately 1% of patients receiving ombitasvir/paritaprevir/ritonavir (with or without dasabuvir and with or without ribavirin) in clinical trials.1 These ALT elevations typically were asymptomatic, occurred during first 4 weeks of treatment, and declined within 2–8 weeks after onset despite continued use of the regimen.1

ALT elevations during ombitasvir/paritaprevir/ritonavir treatment occurred more frequently in women receiving ethinyl estradiol-containing preparations (e.g., oral contraceptives, contraceptive patches, contraceptive vaginal rings) than in other patients.1 In a limited number of women receiving estrogens other than ethinyl estradiol (e.g., estradiol, conjugated estrogens), rate of ALT elevations was similar to that reported in those not receiving estrogens.1

Because of increased incidence of elevated ALT concentrations, concomitant use of ethinyl estradiol-containing preparations (including combination oral contraceptives) is contraindicated.1 Ethinyl estradiol-containing preparations must be discontinued prior to initiation of ombitasvir/paritaprevir/ritonavir.1 Alternative methods of contraception (e.g., progestin-only or nonhormonal contraception) recommended.1 Caution recommended if other estrogens (e.g., estradiol, conjugated estrogens) used concomitantly with ombitasvir/paritaprevir/ritonavir.1 (See Interactions.)

Evaluate liver function using appropriate laboratory tests prior to initiation of ombitasvir/paritaprevir/ritonavir, during first 4 weeks of treatment, and as clinically indicated thereafter.1 If ALT concentrations increase above baseline levels, repeat laboratory tests and closely monitor;1 consider discontinuing ombitasvir/paritaprevir/ritonavir if ALT concentrations are persistently >10 times ULN.1

Discontinue ombitasvir/paritaprevir/ritonavir if ALT elevations are accompanied by signs or symptoms of liver inflammation or increasing serum concentrations of direct bilirubin or alkaline phosphatase or increasing INR.1 Discontinue the drugs if there is evidence of hepatic decompensation (with or without increased bilirubin or transaminase concentrations).1 14

Instruct patients to immediately contact a clinician if they experience onset of fatigue, weakness, lack of appetite, nausea, vomiting, jaundice, or discolored feces.1

Sensitivity Reactions

Hypersensitivity reactions, including angioedema, reported during postmarketing experience.1

Precautions Related to Fixed Combinations and Multiple-drug Treatment Regimens

Consider cautions, precautions, contraindications, and drug interactions associated with all drugs in the ombitasvir/paritaprevir/ritonavir fixed combination and all drugs in the multiple-drug regimen.1 Consider cautionary information applicable to specific populations (e.g., pregnant or nursing women, individuals with hepatic or renal impairment, geriatric patients) for each drug.1

When ombitasvir/paritaprevir/ritonavir is used in conjunction with ribavirin, consider that ribavirin may cause fetal toxicity and/or death.349 377 Extreme care must be taken to avoid pregnancy in female patients and female partners of male patients receiving a ribavirin-containing regimen.349 377 Obtain a negative pregnancy test for female patients of childbearing potential immediately prior to initiating ribavirin;349 377 perform pregnancy tests monthly during and for 6 months after ribavirin treatment is completed.1 Women of childbearing potential (and their male partners) and male patients (and their female partners) must use at least 2 forms of effective contraception during and for 6 months after ribavirin treatment is completed.349 377

Interactions

Concomitant use of ombitasvir/paritaprevir/ritonavir and certain drugs is contraindicated or requires particular caution.1 Concomitant use with some drugs may result in drug interactions leading to loss of therapeutic effect of ombitasvir/paritaprevir/ritonavir and possible development of resistance.1 Certain drug interactions may result in clinically important adverse effects due to higher exposures of the concomitant drugs or components of ombitasvir/paritaprevir/ritonavir.1

Consider potential drug interactions prior to initiating ombitasvir/paritaprevir/ritonavir.1 Review drugs used concomitantly with ombitasvir/paritaprevir/ritonavir during course of treatment;1 monitor patient for adverse effects associated with these drugs.1

Risk of HIV Protease Inhibitor Drug Resistance in Patients Coinfected with HCV and HIV

Ritonavir is included in the fixed combination of ombitasvir/paritaprevir/ritonavir since it is a potent CYP3A inhibitor and increases paritaprevir plasma concentrations and AUC;1 ritonavir is an HIV protease inhibitor and can select for HIV protease inhibitor resistance-associated substitutions.1 HCV-infected patients coinfected with HIV receiving ombitasvir/paritaprevir/ritonavir for treatment of HCV infection also should be receiving a suppressive antiretroviral drug regimen to reduce risk of HIV protease inhibitor resistance.1 119

Do not use ombitasvir/paritaprevir/ritonavir in HIV-infected patients who are not receiving antiretroviral therapy.119

Specific Populations

Category B.1

Use ombitasvir/paritaprevir/ritonavir during pregnancy only if clearly needed.1

No adequate and well-controlled studies using ombitasvir/paritaprevir/ritonavir in pregnant women;1 animal studies have not revealed evidence of teratogenicity with ombitasvir, paritaprevir or ritonavir at exposures higher than recommended clinical dosage.1

When used in conjunction with ribavirin, consider that ribavirin is contraindicated in pregnant women and male partners of pregnant women.1 (See Precautions Related to Fixed Combinations and Multiple-drug Treatment Regimens under Cautions.)

Not known whether components of ombitasvir/paritaprevir/ritonavir distributed into human milk.1 In lactating rats, unchanged ombitasvir, paritaprevir, and its metabolite (M13) distributed into milk without apparent effects on nursing pups.1

Consider benefits of breast-feeding and importance of ombitasvir/paritaprevir/ritonavir to the woman along with the potential adverse effects on the breast-fed child from the drugs or from the underlying maternal condition.1

When used in conjunction with ribavirin, consider potential for adverse reactions to ribavirin in nursing infants;1 decide whether to discontinue nursing or the ribavirin-containing regimen, taking into account the importance of the treatment regimen to the woman.349 377

Safety and efficacy not established in children and adolescents <18 years of age.1

No overall differences in safety and efficacy observed between patients ≥65 years of age and younger adults.1

Ombitasvir/paritaprevir/ritonavir contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh class B or C).1

Do not use in patients with cirrhosis.1

Studies in individuals with mild, moderate, or severe renal impairment (without HCV infection) indicate no overall differences in ombitasvir, paritaprevir, or ritonavir exposures expected compared with those reported in patients with normal renal function.1

Pharmacokinetic data not available regarding use of ombitasvir/paritaprevir/ritonavir in individuals with end-stage renal disease (ESRD).1

Common Adverse Effects

Ombitasvir/paritaprevir/ritonavir with or without ribavirin: Asthenia,1 2 fatigue,1 2 headache,2 irritability,2 nausea,1 2 diarrhea,2 insomnia,1 2 myalgia,2 nasopharyngitis,2 pruritus,1 2 rash or other skin reactions,1 increased serum bilirubin concentrations.1 2

Storage

Oral

≤30º C.1

It is very important that your doctor check your progress at regular visits to make sure ombitasvir, paritaprevir, and ritonavir is working properly. Blood tests may be needed to check for unwanted effects.

Using ombitasvir, paritaprevir, and ritonavir together with ribavirin while you are pregnant can harm your unborn baby. These medicines may also cause birth defects if the father is using it when his sexual partner becomes pregnant. Avoid pregnancy during treatment and within 6 months of stopping treatment with Technivie™ with ribavirin. If a pregnancy occurs while you are using these medicines, tell your doctor right away.

Do not use the following medicines while you are using ombitasvir, paritaprevir, and ritonavir: alfuzosin (Uroxatral®), cisapride (Propulsid®), colchicine (Colcrys®), dronedarone (Multaq®), efavirenz (Sustiva®), ethinyl estradiol (Norinyl®, Ortho Evra®), everolimus (Afinitor®), lurasidone (Latuda®), oral midazolam (Versed®), pimozide (Orap®), ranolazine (Ranexa®), rifampin (Rifadin®, Rimactane®), sildenafil (Revatio®), sirolimus (Rapamune®), St. John's wort, tacrolimus (Prograf®), triazolam (Halcion®), certain medicines to lower cholesterol (such as atorvastatin, lovastatin, simvastatin, Mevacor®, Zocor®), medicine to treat seizures (eg, carbamazepine, phenobarbital, phenytoin, Tegretol®), or ergot medicines (eg, dihydroergotamine, ergonovine, ergotamine, methylergonovine, Cafergot®, Ergomar®, Wigraine®). Using Technivie™ with any of these medicines can cause very serious medical problems.

Check with your doctor right away if you are weak or tired, have onset of confusion, have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, vomiting, or yellow eyes or skin. These could be symptoms of a serious liver problem.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

• If you have an allergy to ombitasvir, paritaprevir, and ritonavir or any part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have liver problems other than hepatitis C.
• If you have had a severe skin reaction after taking ritonavir.
• If you are taking a drug that contains ethinyl estradiol, like certain birth control pills. Do not take a drug that contains ethinyl estradiol while taking ombitasvir, paritaprevir, and ritonavir and for some time after stopping this medicine. Your doctor will tell you when you can start taking a drug that contains ethinyl estradiol again after stopping ombitasvir, paritaprevir, and ritonavir.
• If you take any drugs (prescription or OTC, natural products, vitamins) that must not be taken with this medicine, like certain drugs that are used for high cholesterol, HIV, or seizures. There are many drugs that must not be taken with ombitasvir, paritaprevir, and ritonavir.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take ombitasvir, paritaprevir, and ritonavir with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• This medicine interacts with many other drugs. The chance of ombitasvir, paritaprevir, and ritonavir's side effects may be raised or how well this medicine works may be lowered. The chance of the other drugs' side effects may also be raised. This may include very bad, life-threatening, or deadly side effects. Check with your doctor and pharmacist to make sure that it is safe for you to take ombitasvir, paritaprevir, and ritonavir with all of your other drugs (prescription or OTC, natural products, vitamins).
• It is not known if this medicine stops the spread of diseases like hepatitis that are passed through blood or having sex. Do not have any kind of sex without using a latex or polyurethane condom. Do not share needles or other things like toothbrushes or razors. Talk with your doctor.
• Drugs that contain ethinyl estradiol, like certain birth control pills, must not be used with ombitasvir, paritaprevir, and ritonavir. If you use a birth control that contains ethinyl estradiol, you will need to use another type of birth control. This may include a progestin-only birth control or condoms. You will need to do this while taking this medicine and for about 2 weeks after you stop taking it. Talk with the doctor.
• This medicine may be used with ribavirin. If you are also taking ribavirin, talk with the doctor about the risks and side effects that may happen.
• If you have HIV infection, talk with your doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using ombitasvir, paritaprevir, and ritonavir while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with a meal.
• Take ombitasvir, paritaprevir, and ritonavir at the same time of day.
• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.
• It is important that you do not miss or skip a dose of ombitasvir, paritaprevir, and ritonavir during treatment.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.
• If you are not sure what to do if you miss a dose, call your doctor.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time this medicine is refilled. If you have any questions about ombitasvir, paritaprevir, and ritonavir, please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about ombitasvir, paritaprevir, and ritonavir. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using ombitasvir, paritaprevir, and ritonavir.

Review Date: October 4, 2017

(om BIT as vir, par i TA pre vir, & ri TOE na vir)

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Technivie: Ombitasvir 12.5 mg, paritaprevir 75 mg, and ritonavir 50 mg

• Technivie

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

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.

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

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]

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%)
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[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.[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[Ref]

Hypersensitivity

Postmarketing reports: Hypersensitivity reactions (including angioedema)[Ref]

Some side effects of ombitasvir / paritaprevir / ritonavir may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.