prison [18:40 mg daily 1 175 Raltegravir No clinically important interactions 1 175 Dosage adjustments not needed 1 175 Ranolazine May result in serious and/or life-threatening adverse effects 1 175 Concomitant use contraindicated 1 175 Rilpivirine Increased rilpivirine AUC; 1 175 may cause QT interval prolongation 1 175 Concomitant use not recommended 1 175 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 recommended 1 175 Saquinavir Ritonavir-boosted saquinavir: Concomitant use not recommended 200 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 contraindicated 1 175 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 ritonavir 1 175 Carisoprodol, cyclobenzaprine: Increase dosage of skeletal muscle relaxant if clinically indicated 1 Sofosbuvir No clinically important interactions 1 175 Dosage adjustments not needed 1 175 SSRIs Escitalopram: No clinically important interactions 1 175 Escitalopram: Dosage adjustments not needed 1 175 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 regimen 1 175 Concomitant use contraindicated 1 175 Sulfamethoxazole and trimethoprim Sulfamethoxazole or trimethoprim: Clinically important interactions not expected 1 Sulfamethoxazole or trimethoprim: Dosage adjustments not needed 1 Tenofovir Emtricitabine/tenofovir DF: No clinically important interactions 1 175 Emtricitabine/tenofovir DF: Dosage adjustments not needed 1 175 Tipranavir Ritonavir-boosted tipranavir: Concomitant use not recommended 200 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 warfarin 27 Manufacturer states dosage adjustments not needed; 1 175 some clinicians state closely monitor INR when the HCV antivirals initiated 27 Zolpidem No clinically important interactions 1 175 Dosage adjustments not needed 1 175 Dasabuvir, Ombitasvir, Paritaprevir, and Ritonavir Pharmacokinetics Dasabuvir/ombitasvir/paritaprevir/ritonavir (fixed combination) tablets consist of an extended-release layer containing dasabuvir and an immediate-release layer containing ombitasvir, paritaprevir, and ritonavir. 175 Ombitasvir/paritaprevir/ritonavir with dasabuvir (copackaged) is a kit containing immediate-release, fixed-combination tablets containing ombitasvir, paritaprevir, and ritonavir (ombitasvir/paritaprevir/ritonavir) copackaged with immediate-release tablets containing dasabuvir. 1 Absorption Bioavailability Dasabuvir/ombitasvir/paritaprevir/ritonavir (fixed combination): Peak plasma concentrations of dasabuvir, ombitasvir, paritaprevir, and ritonavir occur at 8, 5, 5, and 4 hours, respectively, after a dose. 175 Ombitasvir/paritaprevir/ritonavir with dasabuvir (copackaged): Peak plasma concentrations of the drugs occur approximately 4 5 hours after a dose. 1 Absolute bioavailability of dasabuvir, ombitasvir, and paritaprevir is 70, 48, and 53%, respectively. 1 Food Dasabuvir/ombitasvir/paritaprevir/ritonavir (fixed combination): Dasabuvir AUC increased 5.92-fold, ombitasvir AUC increased 1.96-fold, paritaprevir AUC increased 4.6-fold, and ritonavir AUC increased 2.13-fold when administered with high-fat meal relative to administration in fasting state. 175 Ombitasvir/paritaprevir/ritonavir with dasabuvir (copackaged): Ombitasvir AUC increased 1.76-fold, paritaprevir AUC increased 2.8-fold, ritonavir AUC increased 1.44-fold, and dasabuvir AUC increased 1.22-fold when administered with high-fat meal relative to administration in fasting state. 1 Plasma Concentrations Dasabuvir: Exposures increase in dose-proportional manner with minimal accumulation. 1 Ombitasvir: Exposures increase in dose-proportional manner with minimal accumulation. 1 Paritaprevir: Exposures increase in more than dose-proportional manner with accumulation of approximately 1.5- to 2-fold. 1 Ritonavir: Exposures increase in more than dose-proportional manner with accumulation of approximately 1.5- to 2-fold. 1 Steady-state drug exposures of ombitasvir, paritaprevir, ritonavir, and dasabuvir occur after approximately 12 days. 1 175 Special Populations Mild hepatic impairment (Child-Pugh class A, score 5 6) without HCV infection: AUCs of ombitasvir, paritaprevir, and ritonavir decreased by 8, 29, and 34%, respectively, and AUC of dasabuvir increased by 17% compared with AUCs in those with normal hepatic function. 1 Moderate hepatic impairment (Child-Pugh class B, score 7 9) without HCV infection: AUCs of ombitasvir, paritaprevir, and dasabuvir decreased by 30, 30, and 16%, respectively, and AUC of paritaprevir increased by 62% compared with AUCs in those with normal hepatic function. 1 Severe hepatic impairment (Child-Pugh class C, score 10 15) without HCV infection: AUC of ombitasvir decreased by 54% and AUCs of paritaprevir, ritonavir, and dasabuvir increased by 945, 13, and 325%, respectively, compared with AUCs in those with normal hepatic function. 1 Mild renal impairment (Cl cr 60 89 mL/minute) without HCV infection: AUCs of paritaprevir, ritonavir, and dasabuvir increased by 19, 42, and 21%, respectively, and AUC of ombitasvir unchanged compared with AUCs in those with normal renal function. 1 Moderate renal impairment (Cl cr 30 59 mL/minute) without HCV infection: AUCs of paritaprevir, ritonavir, and dasabuvir increased by 33, 80, and 37%, respectively, and AUC of ombitasvir unchanged compared with AUCs in those with normal renal function. 1 Severe renal impairment (Cl cr 15 29 mL/minute) without HCV infection: AUCs of paritaprevir, ritonavir, and dasabuvir increased by 45, 114, and 50%, respectively, and AUC of ombitasvir unchanged compared with AUCs in those with normal renal function. 1 Distribution Plasma Protein Binding Ombitasvir: Approximately 99.9%. 1 Paritaprevir: Approximately 97 98.6%. 1 Ritonavir: Approximately 99%. 1 Dasabuvir: >99.5%. 1 Elimination Metabolism Ombitasvir: Principally by amide hydrolysis followed by oxidative metabolism. 1 Paritaprevir: Principally by CYP3A4 and, to lesser extent, by CYP3A5. 1 Ritonavir: Principally by CYP3A and, to lesser extent, by CYP2D6. 1 Dasabuvir: Principally by CYP2C8 and, to lesser extent, by CYP3A. 1 Elimination Route Ombitasvir: Approximately 90% of dose excreted in feces (88% as unchanged drug); 1 2% eliminated in urine. 1 Paritaprevir: Approximately 88% of dose excreted in feces (1% as unchanged drug); 1 8.8% eliminated in urine. 1 Ritonavir: Approximately 86% of dose excreted in feces; 11% eliminated in urine. 1 Dasabuvir: Approximately 94% of dose excreted in feces (26% as unchanged drug); 1 approximately 2% eliminated in urine. 1 Half-life Ombitasvir: Approximately 21 25 hours. 1 Paritaprevir: Approximately 5.5 hours. 1 Ritonavir: Approximately 4 hours when administered concomitantly with ombitasvir and paritaprevir. 1 Dasabuvir: Approximately 5.5 6 hours. 1 Stability Storage Oral Tablets Dasabuvir/ombitasvir/paritaprevir/ritonavir (fixed combination): 30º C. 175 Ombitasvir/paritaprevir/ritonavir with dasabuvir (copackaged): 30º C. 1 Actions and Spectrum Dasabuvir/ombitasvir/paritaprevir/ritonavir (fixed combination) and ombitasvir/paritaprevir/ritonavir with dasabuvir (copackaged) provide a multiple-drug regimen containing 3 direct-acting antivirals (DAAs) with activity against HCV. 1 175 Each antiviral (dasabuvir, ombitasvir, paritaprevir) has a different mechanism of action against HCV; 1 175 the drugs have non-overlapping resistance profiles. 1 175 No in vitro evidence of antagonistic anti-HCV effects between dasabuvir, ombitasvir, and paritaprevir in HCV replicon studies. 1 175 Ritonavir, a potent CYP3A inhibitor, is included in the fixed combination to increase paritaprevir plasma concentrations and AUC; 1 175 does not have activity against HCV. 1 175 Dasabuvir is a nonnucleoside NS5B polymerase inhibitor; 1 12 binds to HCV RNA-dependent RNA polymerase encoded by the NS5B gene targeting the palm domain and is referred to as a nonnucleoside NS5B palm polymerase inhibitor. 1 12 Biochemical assays indicate dasabuvir inhibits HCV genotype 1a and 1b NS5B polymerases; 1 has reduced activity against NS5B polymerases from HCV genotypes 2a, 2b, 3a, and 4a. 1 Certain amino acid substitutions in NS5B of HCV genotype 1a (e.g., C316Y, M414I/T, E446K/Q, Y448C/H, A553T, G554S, S556G/R, Y561H) and genotype 1b (e.g., C316H/N/Y, S368T, N411S, M414I/T, Y448C/H, A553V, S556G, D559G) selected in cell culture have been associated with reduced in vitro susceptibility to dasabuvir. 1 12 Ombitasvir is an HCV NS5A replication complex inhibitor (NS5A inhibitor). 1 9 10 11 13 Exact role of NS5A not fully elucidated, 9 10 11 but it is essential for viral replication and virion assembly. 1 9 10 11 Active against HCV genotype 1a and genotype 1b; 1 9 10 11 some activity against genotypes 2a, 3a, 4a, 5a, and 6a in vitro in cell-based replicon assays. 1 9 10 11 Certain amino acid substitutions in NS5A of HCV genotype 1a (e.g., M28T/V, Q30E/R, L31V, H58D, Y93C/H/L/N) and genotype 1b (e.g., L28T, L31F/V, Y93H) selected in cell culture have been associated with reduced in vitro susceptibility to ombitasvir. 1 Combinations of ombitasvir resistance-associated substitutions in HCV genotype 1a or 1b replicons further reduce ombitasvir antiviral activity. 1 Paritaprevir is an HCV NS3/4A protease inhibitor; 1 binds to active site of HCV NS3/4A protease, thereby blocking enzyme activity and formation of proteins essential for viral replication (i.e., NS3, NS4A, NS4B, NS5A, NS5B). 1 Active against HCV genotypes 1a and 1b; 1 may have activity against genotypes 2a, 2b, 3a, and 4a based on biochemical assays. 1 Certain amino acid substitutions in NS3 of HCV genotype 1a (e.g., F43L, R155G/K/S, A156T, D168A/E/F/H/N/V/Y, Q80K) and genotype 1b (e.g., A156T, D168A/H/V) selected in cell culture have been associated with reduced in vitro susceptibility to paritaprevir. 1 In HCV genotype 1a replicons, combinations of V36M, Y56H, or E357K with R155K or D168 substitutions reduced paritaprevir activity relative to the single R155K or D168 substitutions; 1 in HCV genotype 1b replicons, combination of Y56H and D168 substitutions reduced activity of paritaprevir relative to the single D168 substitution. 1 Cross-resistance expected within each HCV antiviral class (e.g., NS5A inhibitors, NS3/4A protease inhibitors, NS5B palm polymerase inhibitors). 1 Impact of prior treatment with dasabuvir, ombitasvir, or paritaprevir on efficacy of other HCV NS5B polymerase inhibitors, HCV NS5A inhibitors, or HCV NS3/4A protease inhibitors not evaluated. 1 175 Efficacy of dasabuvir/ombitasvir/paritaprevir/ritonavir (fixed combination) or ombitasvir/paritaprevir/ritonavir with dasabuvir (copackaged) not evaluated in patients in whom previous treatment with a regimen that contained an HCV NS5B polymerase inhibitor, HCV NS5A inhibitor, or HCV NS3/4A protease inhibitor failed. 1 175 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.) Preparations Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details. Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations. Dasabuvir Sodium, Ombitasvir, Paritaprevir, and Ritonavir Routes Dosage Forms Strengths Brand Names Manufacturer Oral Tablets, film-coated Dasabuvir Sodium 200 mg (of dasabuvir), Ombitasvir 8.33 mg, Paritaprevir 50 mg, and Ritonavir 33.33 mg Viekira XR AbbVie Ombitasvir, Paritaprevir, and Ritonavir with Dasabuvir Sodium Routes Dosage Forms Strengths Brand Names Manufacturer Oral Kit Ombitasvir 12.5 mg, Paritaprevir 75 mg, and Ritonavir 50 mg film-coated tablets Dasabuvir Sodium 250 mg (of dasabuvir) film-coated tablets Viekira Pak AbbVie AHFS DI Essentials. Copyright 2017, Selected Revisions October 2, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. References 1. AbbVie, Inc. Viekira Pak (ombitasvir, paritaprevir, and ritonavir copackaged with dasabuvir ) tablets prescribing information. North Chicago, IL; 2017 Mar. 2. Feld JJ, Kowdley KV, Coakley E et al. Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med . 2014; 370:1594-603. [PubMed 24720703] 3. Ferenci P, Bernstein D, Lalezari J et al. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med . 2014; 370:1983-92. [PubMed 24795200] 4. Poordad F, Hezode C, Trinh R et al. ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. N Engl J Med . 2014; 370:1973-82. [PubMed 24725237] 5. Zeuzem S, Jacobson IM, Baykal T et al. Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med . 2014; 370:1604-14. [PubMed 24720679] 6. Andreone P, Colombo MG, Enejosa JV et al. ABT-450, ritonavir, ombitasvir, and dasabuvir achieves 97% and 100% sustained virologic response with or without ribavirin in treatment-experienced patients with HCV genotype 1b infection. Gastroenterology . 2014; 147:359-365.e1. [PubMed 24818763] 7. Food and Drug Administration. Center for Drug Evaluation and Research: Application number 206619: Summary Review. From FDA website 8. Kwo PY, Mantry PS, Coakley E et al. An interferon-free antiviral regimen for HCV after liver transplantation. N Engl J Med . 2014; 371:2375-82. [PubMed 25386767] 9. Stirnimann G. Ombitasvir (ABT-267), a novel NS5A inhibitor for the treatment of hepatitis C. Expert Opin Pharmacother . 2014; 15:2609-22. [PubMed 25347030] 10. Gentile I, Buonomo AR, Borgia G. Ombitasvir: a potent pan-genotypic inhibitor of NS5A for the treatment of hepatitis C virus infection. Expert Rev Anti Infect Ther . 2014; 12:1033-43. [PubMed 25074011] 11. DeGoey DA, Randolph JT, Liu D et al. Discovery of ABT-267, a pan-genotypic inhibitor of HCV NS5A. J Med Chem . 2014; 57:2047-57. [PubMed 24400777] 12. Gentile I, Buonomo AR, Borgia G. Dasabuvir: A Non-Nucleoside Inhibitor of NS5B for the Treatment of Hepatitis C Virus Infection. Rev Recent Clin Trials . 2014; :. 13. Asselah T, Marcellin P. Optimal IFN-free therapy in treatment-naïve patients with HCV genotype 1 infection. Liver Int . 2015; 35 Suppl 1:56-64. [PubMed 25529088] 14. Food and Drug Administration. FDA drug safety communication: FDA warns of serious liver injury risk with hepatitis C treatments Viekira Pak and Technivie. Silver Spring, MD; 2015 Oct 22. From FDA website 15. Feld JJ, Moreno C, Trinh R et al. Sustained virologic response of 100% in HCV genotype 1b patients with cirrhosis receiving ombitasvir/paritaprevir/r and dasabuvir for 12weeks. J Hepatol . 2016; 64:301-7. [PubMed 26476290] 25. US Food and Drug Administration. FDA drug safety communication: FDA warns about the risk of hepatitis B reactivating in some patients treated with direct-acting antivirals for hepatitis C. 2016 Oct 4. From FDA website. 27. DeCarolis DD, Westanmo AD, Chen YC et al. Evaluation of a Potential Interaction Between New Regimens to Treat Hepatitis C and Warfarin. Ann Pharmacother . 2016; 50:909-917. [PubMed 27465881] 119. American Association for the Study of Liver Diseases (AASLD). Recommendations for testing, managing, and treating hepatitis C. From the AASLD website. Accessed 2017 May 8. 175. AbbVie, Inc. Viekira XR (dasabuvir, ombitasvir, paritaprevir, and ritonavir) extended-release tablets prescribing information. North Chicago, IL; 2017 Mar. 179. AbbVie, Inc. Technivie (ombitasvir, paritaprevir, and ritonavir) tablets prescribing information. North Chicago, IL; 2017 Mar. 200. Panel on Antiretroviral Guidelines for Adults and Adolescents, US Department of Health and Human Services (HHS). Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (July 14, 2016). Updates may be available at HHS AIDS Information (AIDSinfo) website. 349. Merck Sharp & Dohme Corporation. Rebetol (ribavirin) capsules and oral solution prescribing information. Whitehouse Station, NJ; 2013 Nov. 377. Genentech. Copegus (ribavirin) tablets prescribing information. South San Francisco, CA; 2013 Feb. Next Interactions Print this page Add to My Med List More about dasabuvir/ombitasvir/paritaprevir/ritonavir Side Effects During Pregnancy Dosage Information Drug Interactions Support Group En Español 10 Reviews Add your own review/rating Drug class: antiviral combinations Consumer resources Dasabuvir, ombitasvir, paritaprevir, and ritonavir ... +4 more Professional resources Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir (Wolters Kluwer) Other brands: Viekira Pak , Viekira XR Related treatment guides Hepatitis C]} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only B Pregnancy Category No proven risk in humans N/A CSA Schedule Not a controlled drug Drug Class Antiviral combinations Related Drugs Hepatitis C Harvoni , Epclusa , ribavirin , Zepatier , Mavyret , Sovaldi , sofosbuvir , ledipasvir / sofosbuvir , Vosevi , Viekira Pak , daclatasvir , Daklinza , Pegasys , Intron A , Ribasphere , Olysio , sofosbuvir / velpatasvir , Rebetol , simeprevir , PegIntron , Moderiba , glecaprevir / pibrentasvir , elbasvir / grazoprevir , More... Dasabuvir / ombitasvir / paritaprevir / ritonavir Rating 10 User Reviews 6.9 /10 10 User Reviews 6.9 Rate it!} } wind up
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