Dasabuvir, ombitasvir, paritaprevir, and ritonavir

Name: Dasabuvir, ombitasvir, paritaprevir, and ritonavir

What is the most important information I should know about this medicine?

Do not use this medicine together with ribavirin if you are pregnant, or if you are a man and your sexual partner is pregnant.

Before you start taking Viekira, you must stop using certain birth control pills or hormone replacement medicines. Ask your doctor about using non-hormonal birth control to prevent pregnancy.

If you have ever had hepatitis B, Viekira can cause this condition to come back or get worse. You will need frequent blood tests to check your liver function.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

This medicine side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • liver problems--nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Common side effects may include:

  • nausea;

  • itching, skin rash or redness;

  • sleep problems (insomnia); or

  • feeling weak or tired.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Commonly used brand name(s)

In the U.S.

  • Viekira XR

Available Dosage Forms:

  • Tablet, Extended Release

Therapeutic Class: Antiviral

Pharmacologic Class: Hepatitis C Virus NS5A Inhibitor

Usual Adult Dose for Chronic Hepatitis C

Dasabuvir: 250 mg orally twice a day (morning and evening)

Ombitasvir/paritaprevir/ritonavir fixed-dose combination tablet: 2 tablets orally once a day (in the morning)

Recommended Regimen and Duration of Therapy:
-Genotype 1a, without cirrhosis: Dasabuvir, ombitasvir/paritaprevir/ritonavir, and ribavirin for 12 weeks
-Genotype 1a, with cirrhosis: Dasabuvir, ombitasvir/paritaprevir/ritonavir, and ribavirin for 24 weeks (12 weeks may be considered for some patients based on prior treatment history)
-Genotype 1b, without cirrhosis: Dasabuvir and ombitasvir/paritaprevir/ritonavir for 12 weeks
-Genotype 1b, with cirrhosis: Dasabuvir, ombitasvir/paritaprevir/ritonavir, and ribavirin for 12 weeks

Liver transplant recipients with normal liver function and mild fibrosis (Metavir fibrosis score 2 or lower): Dasabuvir, ombitasvir/paritaprevir/ritonavir, and ribavirin for 24 weeks, regardless of HCV genotype 1 subtype

Comments:
-Before starting this product, patients should be assessed for laboratory and clinical evidence of hepatic decompensation.
-Recommended for therapy-naive or interferon-experienced patients, including those with HCV/HIV-1 coinfection
-The dosing recommendations for genotype 1a should be followed for patients with unknown genotype 1 subtype or with mixed genotype 1 infection.
-The manufacturer product information should be consulted for ribavirin dosing recommendations (if applicable), regarding dosing of concomitant HIV-1 antiviral drugs in HCV/HIV-1 coinfected patients, and regarding use with calcineurin inhibitors in liver transplant recipients.

Use: With or without ribavirin, for the treatment of patients with genotype 1 chronic HCV infection, including those with compensated cirrhosis

Uses for Dasabuvir, Ombitasvir, Paritaprevir, and Ritonavir

Chronic HCV Infection

Treatment of chronic HCV genotype 1 infection in adults without cirrhosis or with compensated cirrhosis (Child-Pugh class A) who are treatment-naive (previously untreated) or in whom previous treatment with an interferon-based regimen (e.g., peginterferon alfa in conjunction with ribavirin) failed, including liver transplant recipients and those with HIV coinfection.1 119 175

Multiple-drug regimen of dasabuvir, ombitasvir, paritaprevir, and ritonavir can be administered as dasabuvir/ombitasvir/paritaprevir/ritonavir (fixed combination)175 or as ombitasvir/paritaprevir/ritonavir with dasabuvir (copackaged).1 (See Dosage and Administration.)

Efficacy not evaluated for treatment of chronic HCV genotype 1 infection in patients in whom previous treatment with a regimen that contained an HCV NS5B polymerase inhibitor, HCV NS5A replication complex inhibitor, or HCV NS3/4A protease inhibitor failed.1 175

Contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh class B or C).1 175 (See Hepatic Impairment under Cautions.)

Treatment of chronic HCV infection is complex and rapidly evolving; consult a specialist to obtain the most up-to-date information.119 Information from the American Association for the Study of Liver Diseases (AASLD), Infectious Diseases Society of America (IDSA), and International Antiviral Society–USA (IAS–USA) regarding diagnosis and management of HCV infection, including recommendations for initial treatment, is available at .119

Dasabuvir, Ombitasvir, Paritaprevir, and Ritonavir Dosage and Administration

General

  • Prior to initiating HCV treatment, test all patients for evidence of current or prior HBV infection by measuring hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc).1 25 119 175 (See Risk of HBV Reactivation in Patients Coinfected with HCV and HBV under Cautions.)

  • Prior to and during treatment, perform appropriate laboratory tests and clinical evaluation to assess for evidence of hepatic decompensation.1 175 (See Hepatic Effects under Cautions.)

Administration

Oral Administration

Dasabuvir/ombitasvir/paritaprevir/ritonavir (fixed combination): Administer orally once daily with a meal.175 Swallow whole; do not split, crush, or chew.175 Do not consume alcohol until ≥4 hours after the dose.175

Ombitasvir/paritaprevir/ritonavir with dasabuvir (copackaged): Administer ombitasvir/paritaprevir/ritonavir component orally once daily (in the morning) with a meal;1 administer dasabuvir component orally twice daily (morning and evening) with a meal.1

Dosage

Dasabuvir component available as dasabuvir sodium; dosage expressed in terms of dasabuvir.1 175

Dasabuvir/ombitasvir/paritaprevir/ritonavir (fixed combination): Each fixed combination tablet contains dasabuvir 200 mg, ombitasvir 8.33 mg, paritaprevir 50 mg, and ritonavir 33.33 mg.175

Ombitasvir/paritaprevir/ritonavir with dasabuvir (copackaged): Each fixed-combination tablet of ombitasvir/paritaprevir/ritonavir contains ombitasvir 12.5 mg, paritaprevir 75 mg, and ritonavir 50 mg.1 Each tablet of dasabuvir sodium contains 250 mg of dasabuvir.1

Adults

Treatment of Chronic HCV Infection HCV Genotype 1 Infection Oral

Dasabuvir/ombitasvir/paritaprevir/ritonavir (fixed combination) in those without cirrhosis or with compensated cirrhosis (Child-Pugh class A): 3 tablets once daily (total of 600 mg of dasabuvir, 25 mg of ombitasvir, 150 mg of paritaprevir, and 100 mg of ritonavir).175 Duration of treatment is 12 or 24 weeks depending on patient type.175 For certain patients, treatment regimen also should include ribavirin.175 (See Table 1.)

Manufacturer states a treatment duration of 12 weeks can be considered for some patients based on prior treatment history.175

Table 1. Recommended Treatment Regimen and Duration of Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir (Fixed Combination) in Adults119175

Patient Type

Treatment Regimen

Duration of Treatment

HCV genotype 1a infection (without cirrhosis)

Dasabuvir/ombitasvir/paritaprevir/ritonavir (fixed combination) in conjunction with ribavirin

12 weeks

HCV genotype 1a infection (with compensated cirrhosis)

Dasabuvir/ombitasvir/paritaprevir/ritonavir (fixed combination) in conjunction with ribavirin

24 weeks

HCV genotype 1b infection (with or without compensated cirrhosis)

Dasabuvir/ombitasvir/paritaprevir/ritonavir (fixed combination)

12 weeks

Ombitasvir/paritaprevir/ritonavir with dasabuvir (copackaged) in those without cirrhosis or with compensated cirrhosis (Child-Pugh class A): 2 tablets of ombitasvir/paritaprevir/ritonavir once daily in the morning (total of 25 mg of ombitasvir, 150 mg of paritaprevir, and 100 mg of ritonavir) and 1 tablet of dasabuvir (250 mg) twice daily (morning and evening).1 Duration of treatment is 12 or 24 weeks depending on patient type.1 For certain patients, treatment regimen also should include ribavirin.1 (See Table 2.)

Manufacturer states a treatment duration of 12 weeks can be considered for some patients based on prior treatment history.1

Table 2. Recommended Treatment Regimen and Duration of Ombitasvir/Paritaprevir/Ritonavir with Dasabuvir (Copackaged) in Adults1119

Patient Type

Treatment Regimen

Duration of Treatment

HCV genotype 1a infection (without cirrhosis)

Ombitasvir/paritaprevir/ritonavir with dasabuvir (copackaged) in conjunction with ribavirin

12 weeks

HCV genotype 1a infection (with compensated cirrhosis)

Ombitasvir/paritaprevir/ritonavir with dasabuvir (copackaged) in conjunction with ribavirin

24 weeks

HCV genotype 1b infection (with or without compensated cirrhosis)

Ombitasvir/paritaprevir/ritonavir with dasabuvir (copackaged)

12 weeks

Adults with unknown genotype 1 subtype or mixed genotype 1 subtypes without cirrhosis or with compensated cirrhosis (Child-Pugh class A): Follow treatment recommendations for HCV genotype 1a infection.1 175 (See Table 1 and Table 2.)

HCV Genotype 1 Infection in Liver Transplant Recipients Oral

HCV genotype 1a or 1b infection in liver transplant recipients with normal hepatic function and Metavir score ≤2: Use usual dosage of dasabuvir/ombitasvir/paritaprevir/ritonavir (fixed combination) or ombitasvir/paritaprevir/ritonavir with dasabuvir (copackaged) in conjunction with ribavirin for 24 weeks.1 175

HCV Genotype 1 Infection in Individuals Coinfected with HIV Oral

Use same dosage of dasabuvir/ombitasvir/paritaprevir/ritonavir (fixed combination) or ombitasvir/paritaprevir/ritonavir with dasabuvir (copackaged) and same HCV genotype-specific multiple-drug regimen and treatment duration recommended for patients without HIV infection.1 175 (See Table 1 and Table 2.)

Special Populations

Hepatic Impairment

Mild hepatic impairment (Child-Pugh class A): Dosage adjustments not needed.1 175

Moderate or severe hepatic impairment (Child-Pugh class B or C): Contraindicated.1 175 (See Hepatic Impairment under Cautions.)

Renal Impairment

Mild, moderate, or severe renal impairment, including those on dialysis: Dosage adjustments not needed.1 175

Geriatric Patients

Dosage adjustments not needed based solely on age.1 175 (See Geriatric Use under Cautions.)

Interactions for Dasabuvir, Ombitasvir, Paritaprevir, and Ritonavir

Paritaprevir and ritonavir metabolized principally by CYP3A;1 175 dasabuvir metabolized principally by CYP2C8.1 175 Ritonavir inhibits CYP3A4.1 175

Ombitasvir, paritaprevir, and dasabuvir inhibit UGT1A1.1 175

Ombitasvir, paritaprevir, dasabuvir, and ritonavir are substrates of P-glycoprotein (P-gp) transport.1 175

Paritaprevir, ritonavir, and dasabuvir inhibit breast cancer resistance protein (BCRP);1 175 ombitasvir, paritaprevir, and dasabuvir are substrates of BCRP.1 175

Paritaprevir is a substrate and inhibitor of organic anion transporting polypeptide (OATP) 1B1 and 1B3.1 175

Ombitasvir, paritaprevir, ritonavir, and dasabuvir do not inhibit organic anion transporter (OAT) 1 and not expected to inhibit OAT3, organic cation transporter (OCT) 2, or multidrug and toxin extrusion protein (MATE) 1 or MATE2K at clinically important concentrations.1 175

Specific drug interaction studies not performed using dasabuvir/ombitasvir/paritaprevir/ritonavir (fixed combination).175 The following interactions are based on studies using ombitasvir/paritaprevir/ritonavir with dasabuvir (copackaged) or studies using the individual components alone.1 175 Consider interactions associated with each drug in the multiple-drug regimen.1 175

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Potent CYP3A inhibitors: Possible pharmacokinetic interactions with ombitasvir/paritaprevir/ritonavir with dasabuvir (increased paritaprevir and ritonavir concentrations).1 175

CYP3A4 substrates: Possible pharmacokinetic interactions with ombitasvir/paritaprevir/ritonavir with dasabuvir (increased concentrations of CYP3A4 substrate).1 175

CYP2C8 inhibitors: Possible pharmacokinetic interactions with ombitasvir/paritaprevir/ritonavir with dasabuvir (increased dasabuvir concentrations).1 175

Drugs Affecting or Metabolized by UGT1A1

UGT1A1 substrates: Possible pharmacokinetic interactions with ombitasvir/paritaprevir/ritonavir with dasabuvir (increased concentrations of UGT1A1 substrate).1 175

Drugs Affecting or Affected by P-glycoprotein Transport

P-gp inhibitors: Possible pharmacokinetic interactions (increased concentrations of various components of ombitasvir/paritaprevir/ritonavir with dasabuvir).1 175

Drugs Affecting or Affected by Breast Cancer Resistance Protein

BCRP substrates: Possible pharmacokinetic interactions with ombitasvir/paritaprevir/ritonavir with dasabuvir (increased concentrations of BCRP substrate).1 175

BCRP inhibitors: Possible pharmacokinetic interactions (increased concentrations of various components of ombitasvir/paritaprevir/ritonavir with dasabuvir).1 175

Drugs Affecting or Affected by Organic Anion Transport Polypeptides

OATP1B1 or OATP1B3 inhibitors: Possible pharmacokinetic interactions (increased concentrations of various components of ombitasvir/paritaprevir/ritonavir with dasabuvir).1 175

OATP1B1 or OATP1B3 substrates: Possible pharmacokinetic interactions with ombitasvir/paritaprevir/ritonavir with dasabuvir (increased concentrations of OATP1B1 or OATP1B3 substrate).1 175

Specific Drugs

Drug

Interaction

Comments

Abacavir

No clinically important interactions1 175

Dosage adjustments not needed1 175

Alfuzosin

Increased alfuzosin concentrations may occur and result in hypotension1 175

Concomitant use contraindicated1 175

Angiotensin II receptor antagonists (candesartan, losartan, valsartan)

Increased concentrations of the angiotensin II receptor antagonist1 175

Reduce dosage of the angiotensin II receptor antagonist and monitor for signs and symptoms of hypotension and/or worsening renal function;1 175 if such events occur, reduce dosage further or consider use of an alternative to the angiotensin II receptor antagonist1 175

Antiarrhythmic agents (amiodarone, bepridil, disopyramide, dronedarone, flecainide, lidocaine [systemic], mexiletine, propafenone, quinidine)

Amiodarone, bepridil, disopyramide, flecainide, lidocaine (systemic), mexiletine, propafenone, quinidine: Increased concentrations of the antiarrhythmic agent1 175

Dronedarone: May result in serious and/or life-threatening adverse effects, including cardiac arrhythmias1 175

Amiodarone, bepridil, disopyramide, flecainide, lidocaine (systemic), mexiletine, propafenone, quinidine: Use concomitantly with caution;1 therapeutic drug monitoring of antiarrhythmic agent recommended, if available1 175

Dronedarone: Concomitant use contraindicated1 175

Anticonvulsants (carbamazepine, phenobarbital, phenytoin)

Carbamazepine: Decreased dasabuvir, ombitasvir, paritaprevir, and ritonavir exposures;1 175 may lead to loss of therapeutic effect of the HCV treatment regimen1 175

Phenobarbital, phenytoin: Possible decreased dasabuvir, ombitasvir, paritaprevir, and ritonavir exposures;1 175 may lead to loss of therapeutic effect of the HCV treatment regimen1 175

Carbamazepine, phenobarbital, phenytoin: Concomitant use contraindicated1 175

Antifungals, azoles

Ketoconazole: Increased ketoconazole AUC1 175

Voriconazole: Possible decreased voriconazole concentrations1 175

Ketoconazole: If used concomitantly, do not exceed ketoconazole dosage of 200 mg daily1 175

Voriconazole: Concomitant use not recommended unless benefits justify risks1 175

Antimycobacterial agents (rifampin)

Rifampin: Possible decreased ombitasvir, paritaprevir, ritonavir, and dasabuvir exposures; may lead to loss of therapeutic effect of the HCV treatment regimen1 175

Rifampin: Concomitant use contraindicated1 175

Antipsychotics (lurasidone, pimozide, quetiapine)

Lurasidone or pimozide: May result in serious and/or life-threatening adverse effects1 175

Quetiapine: Increased quetiapine concentrations expected1 175

Lurasidone or pimozide: Concomitant use contraindicated1 175

Quetiapine: Consider alternative HCV treatment;1 175 if ombitasvir/paritaprevir/ritonavir with dasabuvir necessary in patient receiving quetiapine, reduce quetiapine dosage to one-sixth of original dosage and monitor for quetiapine efficacy and adverse effects;1 175 if quetiapine necessary in patient receiving ombitasvir/paritaprevir/ritonavir with dasabuvir, initiate and titrate quetiapine dosage based on manufacturer instructions1 175

Atazanavir

Ritonavir-boosted atazanavir: Increased paritaprevir concentrations and AUC;1 175 increased atazanavir AUC1 175

Cobicistat-boosted atazanavir: Data not available200

Unboosted atazanavir: Use atazanavir 300 mg once daily (give at same time as morning dose of HCV treatment)1 175 200

Ritonavir-boosted or cobicistat-boosted atazanavir: Do not use concomitantly with ombitasvir/paritaprevir/ritonavir with dasabuvir;1 175 200 may be substituted for unboosted atazanavir after HCV treatment regimen completed1 175 200

Benzodiazepines (alprazolam, diazepam, midazolam, triazolam)

Alprazolam: Increased alprazolam AUC;1 175 no clinically important effect on the HCV antivirals1 175

Diazepam: Decreased AUC of diazepam and nordiazepam (metabolite of diazepam)1 175

Oral midazolam or triazolam: Substantially increased midazolam or triazolam concentrations;1 175 may result in serious or life-threatening adverse effects (e.g., prolonged or increased sedation, respiratory depression)1 175

Alprazolam: Consider reducing alprazolam dosage;1 175 clinical monitoring recommended1 175

Diazepam: Increase diazepam dosage if clinically indicated1 175

Oral midazolam or triazolam: Concomitant use contraindicated1 175

Buprenorphine, buprenorphine/naloxone

Increased buprenorphine and norbuprenorphine AUCs1 175

Dosage adjustments not needed;1 175 closely monitor patient for sedation and cognitive effects1 175

Calcium-channel blockers (amlodipine, diltiazem, nifedipine, verapamil)

Amlodipine: Increased amlodipine AUC;1 175 no clinically important effects on the HCV antivirals1 175

Diltiazem, nifedipine, verapamil: Possible increased calcium-channel blocker concentrations1 175

Amlodipine: Reduce amlodipine dosage by at least 50%1 175

Diltiazem, nifedipine, verapamil: Reduce dosage of the calcium-channel blocker1 175

All calcium-channel blockers: Monitor clinically for edema and/or signs and symptoms of hypotension;1 175 if such events occur, further reduce dosage of calcium-channel blocker or consider alternative to the calcium-channel blocker1 175

Cisapride

May result in serious and/or life-threatening adverse effects, including cardiac arrhythmias1 175

Concomitant use contraindicated1 175

Colchicine

May result in serious and/or life-threatening adverse effects in patients with renal and/or hepatic impairment1 175

Concomitant use contraindicated1 175

Corticosteroids

Fluticasone (inhaled or intranasal): Increased fluticasone concentrations;1 175 may reduce serum cortisol concentrations1 175

Fluticasone (inhaled or intranasal): Consider alternative corticosteroid, particularly for long-term use1 175

Darunavir

Ritonavir-boosted darunavir: Decreased darunavir trough concentrations1 175

Cobicistat-boosted darunavir: Data not available200

Cobicistat-boosted darunavir: Concomitant use not recommended200

Darunavir in antiretroviral-naive patients or antiretroviral-experienced patients with no darunavir-associated resistance substitutions: Use darunavir 800 mg once daily (without ritonavir)1 175

Ritonavir-boosted darunavir in antiretroviral-experienced patients with ≥1 darunavir-associated resistance substitution or in patients with no baseline resistance information: Concomitant use with ritonavir-boosted darunavir (600 mg of darunavir and 100 mg of ritonavir) twice daily not recommended1 175

Digoxin

No clinically important interactions1 175

Dosage adjustments not needed1 175

Dolutegravir

No clinically important interactions1 175

Dosage adjustments not needed1 175

Duloxetine

No clinically important interactions1 175

Dosage adjustments not needed1 175

Efavirenz

Concomitant use with efavirenz-containing regimens poorly tolerated;1 175 liver enzyme elevations observed1 175

Concomitant use contraindicated1 175

Elvitegravir

Fixed combination of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide (EVG/c/FTC/TAF): Concomitant use not recommended200

Fixed combination of elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (EVG/c/FTC/TDF): Concomitant use not recommended200

Emtricitabine

Fixed combination of emtricitabine and tenofovir disoproxil fumarate (emtricitabine/tenofovir DF): No clinically important interactions1 175

Emtricitabine/tenofovir DF: Dosage adjustments not needed1 175

Ergot alkaloids (dihydroergotamine, ergonovine, ergotamine, methylergonovine)

May cause ergot alkaloid-associated toxicity (e.g., vasospasm, tissue ischemia)1 175

Concomitant use contraindicated1 175

Estrogens/progestins (ethinyl estradiol, norgestimate, progestin-only contraceptives)

Ethinyl estradiol-containing preparations (e.g., oral contraceptives, contraceptive patches, contraceptive vaginal rings): Increased ALT concentrations reported1 175

Oral contraceptives containing ethinyl estradiol and norgestimate: Increased concentrations and AUC of ethinyl estradiol and active metabolites of norgestimate (norelgestromin, norgestrel)1 175

Progestin-only contraceptives: No clinically important interactions1 175

Ethinyl estradiol-containing preparations (e.g., oral contraceptives, contraceptive patches, contraceptive vaginal rings): Concomitant use contraindicated;1 175 must be discontinued prior to initiation of the HCV treatment regimen;1 175 may be restarted approximately 2 weeks after completion of the HCV treatment regimen1 175

Other estrogens (e.g., estradiol, conjugated estrogens): Use concomitantly with caution1 175

Progestin-only contraceptives: Dosage adjustments not needed1 175

Etravirine

Possible decreased concentrations of the HCV antivirals200

Concomitant use not recommended200

Fosamprenavir

Fosamprenavir or ritonavir-boosted fosamprenavir: Concomitant use not recommended200

Furosemide

Increased furosemide concentrations1 175

Clinical monitoring recommended;1 175 individualize furosemide therapy based on patient response1 175

Gemfibrozil

Substantially increased dasabuvir AUC;1 175 may increase risk of QT interval prolongation1 175

Concomitant use contraindicated1 175

HMG-CoA reductase inhibitors (statins)

Atorvastatin, lovastatin, simvastatin: May result in myopathy and rhabdomyolysis1 175

Pravastatin: Increased pravastatin AUC1 175

Rosuvastatin: Increased rosuvastatin concentrations and AUC1 175

Atorvastatin, lovastatin, simvastatin: Concomitant use contraindicated1 175

Pravastatin: If used concomitantly, do not exceed pravastatin dosage of 40 mg daily1 175

Rosuvastatin: If used concomitantly, do not exceed rosuvastatin dosage of 10 mg daily1 175

Hydrocodone

Fixed combination of hydrocodone and acetaminophen (hydrocodone/acetaminophen): Increased hydrocodone concentrations;1 175 no effect on dasabuvir, ombitasvir, paritaprevir, ritonavir, or acetaminophen concentrations1 175

Hydrocodone/acetaminophen: Reduce hydrocodone dosage by 50% and frequently monitor for respiratory depression and sedation;1 175 after completion of HCV treatment, adjust dosage of hydrocodone and monitor for opiate withdrawal1 175

Immunosuppressants (cyclosporine, everolimus, sirolimus, tacrolimus)

Cyclosporine, everolimus, sirolimus, tacrolimus: Increased immunosuppressant AUC1 175

Cyclosporine: If initiating dasabuvir/ombitasvir/paritaprevir/ritonavir (fixed combination) or ombitasvir/paritaprevir/ritonavir with dasabuvir (copackaged) in patient receiving cyclosporine, reduce cyclosporine dosage by one-fifth and base subsequent dosage on cyclosporine blood concentrations;1 175 frequently assess renal function and monitor for cyclosporine-related adverse effects1 175

Everolimus, sirolimus, tacrolimus: Concomitant use contraindicated1 175

Lamivudine

No clinically important interactions1 175

Dosage adjustments not needed1 175

Lopinavir

Fixed combination of lopinavir and ritonavir (lopinavir/ritonavir): Increased paritaprevir concentrations and AUC1 175

Lopinavir/ritonavir: Concomitant use not recommended1 175 200

Maraviroc

Increased maraviroc concentrations expected200

Concomitant use not recommended200

Metformin

Pharmacokinetic interaction not expected1 175

Monitor for signs of lactic acidosis (e.g., respiratory distress, somnolence, nonspecific abdominal distress, worsening renal function)1 175

Concomitant use in patients with renal or hepatic impairment not recommended1 175

Methadone

No clinically important interactions1 175

Dosage adjustments not needed1 175

Nevirapine

Possible decreased concentrations of the HCV antivirals200

Concomitant use not recommended200

Proton-pump inhibitors

Omeprazole: Decreased omeprazole concentrations and AUC1 175

Omeprazole: Monitor patient for decreased omeprazole efficacy;1 175 consider increased omeprazole dosage if symptoms not well controlled;1 175 avoid omeprazole dosages >40 mg daily1 175

Raltegravir

No clinically important interactions1 175

Dosage adjustments not needed1 175

Ranolazine

May result in serious and/or life-threatening adverse effects1 175

Concomitant use contraindicated1 175

Rilpivirine

Increased rilpivirine AUC;1 175 may cause QT interval prolongation1 175

Concomitant use not recommended1 175

Ritonavir

Increases paritaprevir concentrations and AUC;1 175 used to therapeutic advantage in dasabuvir/ombitasvir/paritaprevir/ritonavir (fixed combination) and ombitasvir/paritaprevir/ritonavir with dasabuvir (copackaged)1 175

Salmeterol

May increase salmeterol concentrations and increase risk of adverse cardiovascular effects (e.g., QT interval prolongation, palpitations, sinus tachycardia)1 175

Concomitant use not recommended1 175

Saquinavir

Ritonavir-boosted saquinavir: Concomitant use not recommended200

Sildenafil

Sildenafil dosages used for treatment of pulmonary arterial hypertension (PAH): May increase risk of sildenafil-associated adverse effects (e.g., visual disturbances, hypotension, priapism, syncope)1 175

Sildenafil dosages used for treatment of PAH: Concomitant use contraindicated1 175

Skeletal muscle relaxants (carisoprodol, cyclobenzaprine)

Carisoprodol: Decreased carisoprodol concentrations;1 175 no effect on concentrations of dasabuvir, ombitasvir, paritaprevir, ritonavir, or meprobamate (metabolite of carisoprodol)1 175

Cyclobenzaprine: Decreased concentrations of cyclobenzaprine and norcyclobenzaprine (metabolite of cyclobenzaprine);1 175 no effect on concentrations of dasabuvir, ombitasvir, paritaprevir, or ritonavir1 175

Carisoprodol, cyclobenzaprine: Increase dosage of skeletal muscle relaxant if clinically indicated1

Sofosbuvir

No clinically important interactions1 175

Dosage adjustments not needed1 175

SSRIs

Escitalopram: No clinically important interactions1 175

Escitalopram: Dosage adjustments not needed1 175

St. John's wort (Hypericum perforatum)

May decrease ombitasvir/paritaprevir/ritonavir with dasabuvir concentrations;1 175 may lead to loss of therapeutic effect of the HCV treatment regimen1 175

Concomitant use contraindicated1 175

Sulfamethoxazole and trimethoprim

Sulfamethoxazole or trimethoprim: Clinically important interactions not expected1

Sulfamethoxazole or trimethoprim: Dosage adjustments not needed1

Tenofovir

Emtricitabine/tenofovir DF: No clinically important interactions1 175

Emtricitabine/tenofovir DF: Dosage adjustments not needed1 175

Tipranavir

Ritonavir-boosted tipranavir: Concomitant use not recommended200

Warfarin

Manufacturer states no clinically important interactions;1 175 subtherapeutic INRs reported when components of dasabuvir/ombitasvir/paritaprevir/ritonavir (fixed combination) or ombitasvir/paritaprevir/ritonavir with dasabuvir (copackaged) initiated in patients receiving warfarin27

Manufacturer states dosage adjustments not needed;1 175 some clinicians state closely monitor INR when the HCV antivirals initiated27

Zolpidem

No clinically important interactions1 175

Dosage adjustments not needed1 175

Advice to Patients

  • If dasabuvir/ombitasvir/paritaprevir/ritonavir (fixed combination) used, advise patients that the drug should be taken once daily with a meal at a regularly scheduled time.175 Advise patients to swallow the tablet whole and to not consume alcohol within 4 hours of taking the dose.175

  • If ombitasvir/paritaprevir/ritonavir (copackaged) used, advise patients that the ombitasvir/paritaprevir/ritonavir component is taken once daily (in the morning) with a meal and the dasabuvir component is taken twice daily (morning and evening) with a meal.1

  • Importance of not missing or skipping doses and importance of taking the drug for the duration recommended by their clinician.1 175

  • Inform patients that reactivation of HBV infection has occurred in coinfected patients being treated for HCV infection.1 25 175 Importance of informing clinician of any history of HBV infection or other liver problems (e.g., cirrhosis).1 25 175 Importance of immediately contacting a clinician if any signs or symptoms of serious liver injury (e.g., fatigue, weakness, loss of appetite, nausea and vomiting, yellowing of the eyes or skin, light-colored bowel movements) occur.1 25 175 (See Risk of HBV Reactivation in Patients Coinfected with HCV and HBV under Cautions.)

  • Advise patients to watch for early signs of liver inflammation or failure (e.g., fatigue, weakness, lack of appetite, nausea, vomiting) as well as later signs (e.g., jaundice, onset of confusion, abdominal swelling, discolored feces) and to immediately contact a clinician if such manifestations occur.1 14 175

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1 175

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 175 If dasabuvir/ombitasvir/paritaprevir/ritonavir (fixed combination) or ombitasvir/paritaprevir/ritonavir with dasabuvir (copackaged) is used in conjunction with ribavirin, advise men and women of the importance of avoiding pregnancy during and for 6 months after ribavirin therapy.1 175 Inform patients that contraceptives containing ethinyl estradiol are contraindicated during treatment with ombitasvir/paritaprevir/ritonavir with dasabuvir.1 175 (See Hepatic Effects under Cautions.)

  • Importance of informing patients of other important precautionary information.1 175 (See Cautions.)

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