(dak LAT as vir)
Chronic hepatitis C: Treatment of chronic hepatitis C virus (HCV) genotype 1, 3 infection in combination with other antiviral therapy
Limitations of use: Sustained virologic response rates are reduced in HCV genotype 3-infected patients with cirrhosis receiving daclatasvir in combination with sofosbuvir for 12 weeks.
Concurrent use of strong CYP3A inducers (eg, carbamazepine, phenytoin, rifampin, St Johns wort). When used in combination with other agents (eg, ribavirin), the contraindications to those agents also apply (refer to respective labeling information).
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to daclatasvir or any component of the formulation; concurrent use with strong inducers of CYP3A4 and P-glycoprotein (P-gp)
Chronic hepatitis C (genotype 1 or 3): Oral: Note: Discontinue daclatasvir if other antihepaciviral therapy is permanently discontinued. Not indicated as monotherapy.
Genotype 1:
Without cirrhosis or with compensated (Child-Pugh class A) cirrhosis: 60 mg once daily with concomitant sofosbuvir for 12 weeks. Note: AASLD/IDSA 2015 guidelines recommend 24 weeks of therapy with concomitant sofosbuvir (with or without ribavirin) in patients with compensated cirrhosis and genotype 1; consult clinical guidelines for additional details (AASLD/IDSA 2015).
With decompensated (Child-Pugh class B or C) cirrhosis or post liver transplant: 60 mg once daily with concomitant sofosbuvir and ribavirin for 12 weeks
When used concomitantly with asunaprevir [Canadian product] for patients with genotype 1b (with or without compensated cirrhosis), the recommended duration of therapy is 24 weeks; when used concomitantly with asunaprevir, peginterferon alfa, and ribavirin in patients with genotypes 1 (with or without compensated cirrhosis), the recommended duration of therapy is 24 weeks. (Sunvepra Canadian labeling 2016). Note: Discontinuation of therapy is recommended for virologic breakthrough (>1 log10 IU/mL increase in HCV RNA from nadir).
Genotype 3:
Without cirrhosis: 60 mg once daily with concomitant sofosbuvir for 12 weeks
With compensated (Child-Pugh class A) or decompensated (Child-Pugh class B or C) cirrhosis or post liver transplant: 60 mg once daily with concomitant sofosbuvir and ribavirin for 12 weeks. Note: AASLD/IDSA 2015 guidelines recommend 24 weeks of therapy with concomitant sofosbuvir (with or without ribavirin in treatment-naive patients and with ribavirin in treatment-experienced patients) with compensated cirrhosis and genotype 3; consult clinical guidelines for additional details (AASLD/IDSA 2015).
Chronic hepatitis C (genotype 2):
Off-label use(AASLD/IDSA 2015): Oral:
Treatment-naive patients: 60 mg once daily with concomitant sofosbuvir for 12 weeks (only for patients unable to tolerate ribavirin)
Treatment-experienced patients in whom a previous regimen of sofosbuvir and ribavirin has failed: 60 mg once daily with concomitant sofosbuvir for 24 weeks with or without ribavirin (interferon-ineligible patients)
Hepatitis C virus (HCV) in patients co-infected with HIV (off-label use) (AASLD/IDSA 2015): Oral: 60 mg once daily with concomitant sofosbuvir with or without ribavirin (only when antiretroviral regimen changes cannot be made to accommodate alternate HCV direct-acting antivirals). Daclatasvir requires dosage adjustment for certain HIV antiretroviral agents.
Dosage adjustment with concomitant medications:
Strong inhibitors of CYP3A and certain HIV antiviral agents: 30 mg once daily
Moderate CYP3A inducers or nevirapine: 90 mg once daily
Strong CYP3A inducers: Concomitant use is contraindicated.
Refer to adult dosing.
No dosage adjustment necessary.
Child-Pugh class A, B, or C: No dosage adjustment necessary.
Oral: Administer with or without food.
Store at 25 ‚ °C (77 ‚ °F); excursions permitted between 15 ‚ °C and 30 ‚ °C (59 ‚ °F and 86 ‚ °F).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Daklinza: 30 mg, 60 mg, 90 mg [contains fd&c blue #2 aluminum lake]
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: Per US labeling: reduce afatinib by 10mg if not tolerated. Per Canadian labeling: avoid combination if possible; if used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib. Consider therapy modification
Amiodarone: Daclatasvir may enhance the bradycardic effect of Amiodarone. Avoid combination
Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Asunaprevir: OATP1B1/SLCO1B1 Inhibitors may increase the serum concentration of Asunaprevir. Avoid combination
Bosutinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bosutinib. Avoid combination
Brentuximab Vedotin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Monitor therapy
Buprenorphine: Daclatasvir may increase the serum concentration of Buprenorphine. Monitor therapy
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Consider therapy modification
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Daclatasvir. Management: Increase the daclatasvir dose to 90 mg once daily if used with a moderate CYP3A4 inducer. Consider therapy modification
CYP3A4 Inducers (Strong): May decrease the serum concentration of Daclatasvir. Avoid combination
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Daclatasvir. Management: Decrease the daclatasvir dose to 30 mg once daily if combined with a strong CYP3A4 inhibitor. No dose adjustment is needed when daclatasvir is used with darunavir/cobicistat. Consider therapy modification
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Management: Dabigatran dose reductions may be needed. Specific recommendations vary considerably according to US vs Canadian labeling, specific P-gp inhibitor, renal function, and indication for dabigatran treatment. Refer to full monograph or dabigatran labeling. Consider therapy modification
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Dexamethasone (Systemic): May decrease the serum concentration of Daclatasvir. Management: US labeling recommends increasing the daclatasvir dose to 90 mg once daily if used with dexamethasone. Canadian labeling states that the combination of daclatasvir and dexamethasone is contraindicated. Consider therapy modification
Digoxin: Daclatasvir may increase the serum concentration of Digoxin. Management: See full interaction monograph for details. Consider therapy modification
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-glycoprotein inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: See full monograph for details. Reduced doses are recommended for patients receiving edoxaban for venous thromboembolism in combination with certain inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation. Consider therapy modification
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Consider therapy modification
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Grazoprevir: OATP1B1/SLCO1B1 Inhibitors may increase the serum concentration of Grazoprevir. Avoid combination
HMG-CoA Reductase Inhibitors: Daclatasvir may increase the serum concentration of HMG-CoA Reductase Inhibitors. Monitor therapy
Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Monitor therapy
Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Nevirapine: May decrease the serum concentration of Daclatasvir. Management: Increase the daclatasvir dose to 90 mg once daily. Consider therapy modification
Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination
PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination
P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy
Prucalopride: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride. Monitor therapy
Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Monitor therapy
Rifapentine: May decrease the serum concentration of Daclatasvir. Management: US labeling recommends increasing the daclatasvir dose to 90 mg once daily if used with rifapentine. Canadian labeling states that the combination of daclatasvir and rifapentine is contraindicated. Consider therapy modification
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Monitor therapy
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Avoid combination
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
St Johns Wort: May decrease the serum concentration of Daclatasvir. Avoid combination
Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Avoid combination
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring these combinations. Consider therapy modification
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination
Manufacturer 's labeling: Prior to treatment initiation in genotype 1a patients, consider screening for the presence of NS5A polymorphisms at amino acid positions M28, Q30, L31, and Y93 in patients with cirrhosis. Liver enzymes and serum creatinine at baseline and periodically when clinically indicated. If used in combination with amiodarone or in patients who discontinued amiodarone just prior to initiating sofosbuvir in combination with daclatasvir, inpatient cardiac monitoring for the first 48 hours of coadministration, then outpatient self-monitoring of heart rate daily through at least the first 2 weeks of treatment.
Alternate recommendations (AASLD/IDSA 2015):
Baseline (within 12 weeks prior to starting antiviral therapy): CBC, INR, hepatic function panel (albumin, total and direct bilirubin, ALT, AST, and alkaline phosphatase), calculated GFR
Baseline (at any time prior to starting antiviral therapy): HCV genotype and subtype, quantitative HCV viral load
During therapy: CBC, serum creatinine, calculated GFR, hepatic function panel (after 4 weeks of therapy and as clinically indicated); quantitative HCV viral load testing (after 4 weeks of therapy and at 12 weeks after completion of therapy). If quantitative HCV viral load is detectable at treatment week 4, repeat testing is recommended after 2 additional weeks of treatment (treatment week 6).
All adverse drug reactions are from combination therapy trials with sofosbuvir.
>10%:
Central nervous system: Fatigue (14% to 15%), headache (12% to 14%)
Gastrointestinal: Nausea (8% to 15%)
Hematologic & Oncologic: Anemia (20%)
1% to 10%:
Central nervous system: Drowsiness (5%), insomnia (3%)
Dermatologic: Skin rash (8%)
Gastrointestinal: Diarrhea (3% to 5%), increased serum lipase (>3x ULN, transient)
Concerns related to adverse effects:
- Bradycardia: When used in combination with sofosbuvir and amiodarone, symptomatic bradycardia (eg, near-fainting, dizziness, lightheadedness, malaise, weakness, excessive tiredness, shortness of breath, chest pain, confusion, or memory problems) has been reported; pacemaker intervention may be required. Bradycardia generally occurs within hours or days but has been observed up to 2 weeks after treatment initiation. Risk factors include concomitant beta blocker use, underlying cardiac morbidities, and/or advanced hepatic disease. Patients receiving amiodarone (with no alternate treatment options) and initiating daclatasvir and sofosbuvir treatment, and patients on daclatasvir and sofosbuvir treatment who are initiating amiodarone therapy should have inpatient cardiac monitoring for the first 48 hours of amiodarone coadministration and daily outpatient self-monitoring through at least the first 2 weeks of treatment. Patients discontinuing amiodarone just prior to starting daclatasvir and sofosbuvir treatment should also undergo similar cardiac monitoring procedures. Bradycardia usually resolves after HCV treatment discontinuation.
Disease-related concerns:
- Cardiovascular disease: Patients with underlying cardiac morbidities and also taking concomitant amiodarone are at increased risk for symptomatic bradycardia; use with caution and monitor for bradycardia.
- Hepatic disease: Patients with advanced hepatic disease and also taking concomitant amiodarone are at increased risk for symptomatic bradycardia; use with caution. Sustained virologic response rates are reduced in HCV genotype 3-infected patients with cirrhosis. Optimal duration of treatment for HCV genotype 3-infected patients with cirrhosis or HCV genotype 1 patients with Child-Pugh class C cirrhosis has not been established.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Other warnings/precautions:
- Appropriate use: Do not use as monotherapy; use only in combination with other antivirals.
If used in combination with ribavirin, all warnings related to the use of ribavirin and pregnancy and/or contraception should be followed. Mother-to-child transmission of HCV does not occur if the woman is not viremic, therefore, HCV-infected women of childbearing potential should postpone pregnancy until therapy is complete. Treatment of HCV is not recommended for women who are already pregnant (AASLD/IDSA 2015).
Daclatasvir binds to the N-terminus within Domain 1 of HCV nonstructural protein 5A (NS5A) and inhibits viral RNA replication and virion assembly.
Vdss: 47 L
Primarily via CYP3A
Feces (88%, 53% unchanged); urine (6.6%, primarily unchanged)
Plasma: ≤2 hours
12 to 15 hours
~99%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience headache, loss of strength and energy, or nausea (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating, and advising patients.