Daklinza

NS5A Protein Inhibitor Antivirals for Hepatitis C

 
NOTE: Daclatasvir MUST be administered in combination with sofosbuvir; certain patients may also require treatment with ribavirin. If sofosbuvir is permanently discontinued, daclatasvir must also be discontinued.

Oral Administration

May be administered with or without food.

Severe

hepatic failure / Delayed / Incidence not known
hepatitis B exacerbation / Delayed / Incidence not known

Moderate

anemia / Delayed / 19.0-20.0
hyperbilirubinemia / Delayed / 5.0-8.0
elevated hepatic enzymes / Delayed / 2.0-3.0

Mild

headache / Early / 8.0-30.0
fatigue / Early / 14.0-17.0
nausea / Early / 6.0-15.0
rash / Early / 2.0-8.0
diarrhea / Early / 3.0-7.0
dizziness / Early / 6.0-6.0
insomnia / Early / 3.0-6.0

Hepatitis B exacerbation

Use of direct-acting antivirals (DAA), such as daclatasvir, to treat hepatitis C virus (HCV) infection in patients currently or previously infected with hepatitis B virus (HBV) has been associated with reactivation and hepatitis B exacerbation. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Hepatitis B reactivation has also occurred in patients receiving certain immunosuppressive or chemotherapeutic medications; the risk of HBV reactivation associated with DAA treatment may be increased in these patients. HBV reactivation is characterized as an abrupt increase in viral replication manifesting as a rapid increase in serum HBV DNA concentration. In patients with resolved HBV infection, the reappearance of HBsAg can occur. Reactivation of HBV replication may be accompanied by hepatitis (i.e., increases in aminotransferase concentrations) and, in severe cases, increases in bilirubin concentrations, liver failure, and death can occur. To decrease the risk of reactivating an HBV infection, screen all potential drug recipients for evidence of current or prior HBV infection by measuring the hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc). For those patients whose screening reveals serologic evidence of HBV infection, a baseline HBV DNA concentration should be obtained prior to starting daclatasvir. Continue to monitor coinfected patients during and after treatment for clinical and laboratory signs of hepatitis B exacerbation (i.e., HBsAg, HBV DNA, hepatic enzymes, bilirubin). In addition, instruct patients to immediately report any signs of liver toxicity (e.g., yellow eyes or skin, fatigue, weakness, loss of appetite, nausea, vomiting, or light-colored stools) to their health care provider. If a daclatasvir recipient develops signs of HBV reactivation, initiate appropriate treatment for HBV infection as clinically indicated.

Daklinza

Rx

Hepatitis C virus (HCV) NS5A inhibitor
For use with sofosbuvir and with or without ribavirin to treat genotypes 1 and 3 chronic HCV infections
Consider testing for NS5A resistance-associated polymorphisms prior to treating cirrhotic patients with HCV genotype 1a infections

For the treatment of chronic hepatitis C infection (HCV).
NOTE: Daclatasvir must be administered in combination with sofosbuvir; certain patients may also require treatment with ribavirin. If sofosbuvir is permanently discontinued, daclatasvir must also be discontinued.
For the treatment of chronic HCV genotype 1 infection.
NOTE: Cirrhotic patients infected with HCV genotype 1a should undergo testing for the presence of NS5A resistance-associated polymorphisms prior to initiating therapy; specifically, polymorphisms at amino acid positions M28, Q30, L31, and Y93.
NOTE: The optimal treatment duration has not been established for genotype 1 infected patients with decompensated (Child-Pugh C) cirrhosis. Oral dosage Adults without cirrhosis or who have compensated (Child-Pugh A) cirrhosis

60 mg PO once daily in combination with sofosbuvir 400 mg PO once daily for 12 weeks. Dosing includes patients coinfected with HIV.

Adults receiving strong CYP3A inhibitors who do not have cirrhosis or who have compensated (Child-Pugh A) cirrhosis

30 mg PO once daily in combination with sofosbuvir 400 mg PO once daily for 12 weeks. Dosing includes patients coinfected with HIV.

Adults receiving moderate CYP3A inducers who do not have cirrhosis or who have compensated (Child-Pugh A) cirrhosis

90 mg PO once daily in combination with sofosbuvir 400 mg PO once daily for 12 weeks. Dosing includes patients coinfected with HIV.

Adults who have decompensated (Child-Pugh B or C) cirrhosis and may or may not be candidates for liver transplantation, including those with hepatocellular carcinoma

60 mg PO once daily in combination with sofosbuvir (400 mg PO once daily) and ribavirin (600 mg PO once daily) for 12 weeks. Ribavirin must be administered with food, and the dose may be increased to 1000 mg PO daily if tolerated; consider decreasing ribavirin dose for abnormal hemoglobin or creatinine clearance. Dosing includes patients coinfected with HIV.

Adults receiving strong CYP3A inhibitors who have decompensated (Child-Pugh B or C) cirrhosis and may or may not be candidates for liver transplantation, including those with hepatocellular carcinoma

30 mg PO once daily in combination with sofosbuvir (400 mg PO once daily) and ribavirin (600 mg PO once daily) for 12 weeks. Ribavirin must be administered with food, and the dose may be increased to 1000 mg PO daily if tolerated; consider decreasing ribavirin dose for abnormal hemoglobin or creatinine clearance. Dosing includes patients coinfected with HIV.

Adults receiving moderate CYP3A inducers who have decompensated (Child-Pugh B or C) cirrhosis and may or may not be candidates for liver transplantation, including those with hepatocellular carcinoma

90 mg PO once daily in combination with sofosbuvir (400 mg PO once daily) and ribavirin (600 mg PO once daily) for 12 weeks. Ribavirin must be administered with food, and the dose may be increased to 1000 mg PO daily if tolerated; consider decreasing ribavirin dose for abnormal hemoglobin or creatinine clearance. Dosing includes patients coinfected with HIV.

Treatment-naive or experienced Adults with or without compensated (Child-Pugh A) cirrhosis who develop recurrent HCV genotype 1 after liver transplant

60 mg PO once daily in combination with sofosbuvir (400 mg PO once daily) and ribavirin (600 mg PO once daily) for 12 weeks. Ribavirin must be administered with food, and the dose may be increased to 1000 mg PO daily if tolerated; consider decreasing ribavirin dose for abnormal hemoglobin or creatinine clearance. Dosing includes patients coinfected with HIV.

Treatment-naive or experienced Adults receiving strong CYP3A inhibitors with or without compensated (Child-Pugh A) cirrhosis who develop recurrent HCV genotype 1 after liver transplant

30 mg PO once daily in combination with sofosbuvir (400 mg PO once daily) and ribavirin (600 mg PO once daily) for 12 weeks. Ribavirin must be administered with food, and the dose may be increased to 1000 mg PO daily if tolerated; consider decreasing ribavirin dose for abnormal hemoglobin or creatinine clearance. Dosing includes patients coinfected with HIV.

Treatment-naive or experienced Adults receiving moderate CYP3A inducers with or without compensated (Child-Pugh A) cirrhosis who develop recurrent HCV genotype 1 after liver transplant

90 mg PO once daily in combination with sofosbuvir (400 mg PO once daily) and ribavirin (600 mg PO once daily) for 12 weeks. Ribavirin must be administered with food, and the dose may be increased to 1000 mg PO daily if tolerated; consider decreasing ribavirin dose for abnormal hemoglobin or creatinine clearance. Dosing includes patients coinfected with HIV.

For the treatment of chronic HCV genotype 3 infection.
NOTE: The optimal treatment duration has not been established for genotype 3 infected patients with cirrhosis.
Oral dosage Adults without cirrhosis

60 mg PO once daily in combination with sofosbuvir 400 mg PO once daily for 12 weeks. Dosing includes patients coinfected with HIV.

Adults without cirrhosis receiving strong CYP3A inhibitors

30 mg PO once daily in combination with sofosbuvir 400 mg PO once daily for 12 weeks. Dosing includes patients coinfected with HIV.

Adults without cirrhosis receiving moderate CYP3A inducers

90 mg PO once daily in combination with sofosbuvir 400 mg PO once daily for 12 weeks. Dosing includes patients coinfected with HIV.

Adults with compensated (Child-Pugh A) cirrhosis

60 mg PO once daily in combination with sofosbuvir (400 mg PO once daily) and ribavirin for 12 weeks. Ribavirin must be administered with food in two divided doses, and the dose is based on weight as follows: less than 75 kg give 500 mg PO twice daily; 75 kg or more give 600 mg PO twice daily. Dosing includes patients coinfected with HIV.

Adults receiving strong CYP3A inhibitors who have compensated (Child-Pugh A) cirrhosis

30 mg PO once daily in combination with sofosbuvir (400 mg PO once daily) and ribavirin for 12 weeks. Ribavirin must be administered with food in two divided doses, and the dose is based on weight as follows: less than 75 kg give 500 mg PO twice daily; 75 kg or more give 600 mg PO twice daily. Dosing includes patients coinfected with HIV.

Adults receiving moderate CYP3A inducers who have compensated (Child-Pugh A) cirrhosis

90 mg PO once daily in combination with sofosbuvir (400 mg PO once daily) and ribavirin for 12 weeks. Ribavirin must be administered with food in two divided doses, and the dose is based on weight as follows: less than 75 kg give 500 mg PO twice daily; 75 kg or more give 600 mg PO twice daily. Dosing includes patients coinfected with HIV.

Adults with decompensated (Child-Pugh B or C) cirrhosis and may or may not be candidates for liver transplantation, including those with hepatocellular carcinoma

60 mg PO once daily in combination with sofosbuvir (400 mg PO once daily) and ribavirin (600 mg PO once daily) for 12 weeks. Ribavirin must be administered with food, and the dose may be increased to 1000 mg PO daily if tolerated; consider decreasing ribavirin dose for abnormal hemoglobin or creatinine clearance. Dosing includes patients coinfected with HIV.

Adults receiving strong CYP3A inhibitors who have decompensated (Child-Pugh B or C) cirrhosis and may or may not be candidates for liver transplantation, including those with hepatocellular carcinoma

30 mg PO once daily in combination with sofosbuvir (400 mg PO once daily) and ribavirin (600 mg PO once daily) for 12 weeks. Ribavirin must be administered with food, and the dose may be increased to 1000 mg PO daily if tolerated; consider decreasing ribavirin dose for abnormal hemoglobin or creatinine clearance. Dosing includes patients coinfected with HIV.

Adults receiving moderate CYP3A inducers who have decompensated (Child-Pugh B or C) cirrhosis and may or may not be candidates for liver transplantation, including those with hepatocellular carcinoma

90 mg PO once daily in combination with sofosbuvir (400 mg PO once daily) and ribavirin (600 mg PO once daily) for 12 weeks. Ribavirin must be administered with food, and the dose may be increased to 1000 mg PO daily if tolerated; consider decreasing ribavirin dose for abnormal hemoglobin or creatinine clearance. Dosing includes patients coinfected with HIV.

Treatment-naive or experienced Adults with or without cirrhosis (compensated or decompensated) who develop recurrent HCV genotypes 3 after liver transplant

60 mg PO once daily in combination with sofosbuvir (400 mg PO once daily) and ribavirin (600 mg PO once daily) for 12 weeks. Ribavirin must be administered with food, and the dose may be increased to 1000 mg PO daily if tolerated; consider decreasing ribavirin dose for abnormal hemoglobin or creatinine clearance. Dosing includes patients coinfected with HIV.

Treatment-naive or experienced Adults receiving strong CYP3A inhibitors with or without cirrhosis (compensated or decompensated) who develop recurrent HCV genotypes 3 after liver transplant

30 mg PO once daily in combination with sofosbuvir (400 mg PO once daily) and ribavirin (600 mg PO once daily) for 12 weeks. Ribavirin must be administered with food, and the dose may be increased to 1000 mg PO daily if tolerated; consider decreasing ribavirin dose for abnormal hemoglobin or creatinine clearance. Dosing includes patients coinfected with HIV.

Treatment-naive or experienced Adults receiving moderate CYP3A inducers with or without cirrhosis (compensated or decompensated) who develop recurrent HCV genotypes 3 after liver transplant

90 mg PO once daily in combination with sofosbuvir (400 mg PO once daily) and ribavirin (600 mg PO once daily) for 12 weeks. Ribavirin must be administered with food, and the dose may be increased to 1000 mg PO daily if tolerated; consider decreasing ribavirin dose for abnormal hemoglobin or creatinine clearance. Dosing includes patients coinfected with HIV.

Hepatic Impairment

No dosage adjustments are needed.

Renal Impairment

No dosage adjustments are needed.

Abacavir; Dolutegravir; Lamivudine: (Moderate) Systemic exposure of dolutegravir, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of dolutegravir; monitor patients for potential adverse effects.
Acarbose: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Acetohexamide: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Afatinib: (Moderate) If the concomitant use of daclatasvir and afatinib is necessary, consider reducing the afatinib dose by 10 mg per day if the original dose is not tolerated; resume the previous dose of afatinib as tolerated after discontinuation of daclatasvir. Afatinib is a P-glycoprotein (P-gp) substrate and inhibitor in vitro, and daclatasvir is a P-gp inhibitor; coadministration may increase plasma concentrations of afatinib. The ratio of digoxin Cmax, AUC, and Cmin when administered with daclatasvir (60 mg daily) or alone was 1.65, 1.27, and 1.18, respectively. Administration of another P-gp inhibitor, ritonavir (200 mg twice daily for 3 days), 1 hour before afatinib (single dose) increased the afatinib AUC and Cmax by 48% and 39%, respectively; there was no change in the afatinib AUC when ritonavir was administered at the same time as afatinib or 6 hours later. In healthy subjects, the relative bioavailability for AUC and Cmax of afatinib was 119% and 104%, respectively, when coadministered with ritonavir, and 111% and 105% when ritonavir was administered 6 hours after afatinib. The manufacturer of afatinib recommends permanent discontinuation of therapy for severe or intolerant adverse drug reactions at a dose of 20 mg per day, but does not address a minimum dose otherwise.
Albiglutide: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Aliskiren: (Moderate) Systemic exposure of aliskiren, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of aliskiren; monitor patients for potential adverse effects.
Aliskiren; Amlodipine: (Moderate) Systemic exposure of aliskiren, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of aliskiren; monitor patients for potential adverse effects.
Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Systemic exposure of aliskiren, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of aliskiren; monitor patients for potential adverse effects.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Systemic exposure of aliskiren, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of aliskiren; monitor patients for potential adverse effects.
Aliskiren; Valsartan: (Moderate) Systemic exposure of aliskiren, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of aliskiren; monitor patients for potential adverse effects. (Moderate) Systemic exposure of valsartan, a substrate of the drug transporter organic anion transporting polypeptides (OATP), may be increased when administered concurrently with daclatasvir, an OATP inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of valsartan; monitor patients for potential adverse effects.
Alogliptin: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Alogliptin; Metformin: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Alogliptin; Pioglitazone: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Alpelisib: (Major) Avoid coadministration of alpelisib with daclatasvir due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and daclatasvir is a BCRP inhibitor.
Amiodarone: (Major) Coadministration of amiodarone with daclatasvir plus sofosbuvir is not recommended due to the potential for serious symptomatic bradycardia. Cases of symptomatic bradycardia, some requiring pacemaker intervention, have been reported when amiodarone was administered with sofosbuvir and another direct-acting antiviral, including daclatasvir. One patient developed a fatal cardiac arrest after receiving amiodarone with ledipasvir; sofosbuvir. Bradycardia generally occurs within hours to days; however, cases have been observed up to 2 weeks after initiating the hepatitis C virus (HCV) treatment regimen. The mechanism of this effect is unknown. If coadministration is required, cardiac monitoring in an inpatient setting for the first 48 hours of coadministration is recommended, after which outpatient or self-monitoring of the heart rate should occur on a daily basis through at least the first 2 weeks of treatment. Due to the long half-life of amiodarone, patients discontinuing amiodarone just prior to starting the HCV regimen should also undergo similar cardiac monitoring as outlined above.
Amlodipine; Atorvastatin: (Moderate) Caution and close monitoring is advised if daclatasvir is administered with HMG-CoA reductase inhibitors (Statins). Use of these drugs together may result in elevated Statin serum concentrations, potentially resulting in adverse effects such as myopathy and rhabdomyolysis.
Amlodipine; Valsartan: (Moderate) Systemic exposure of valsartan, a substrate of the drug transporter organic anion transporting polypeptides (OATP), may be increased when administered concurrently with daclatasvir, an OATP inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of valsartan; monitor patients for potential adverse effects.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Systemic exposure of valsartan, a substrate of the drug transporter organic anion transporting polypeptides (OATP), may be increased when administered concurrently with daclatasvir, an OATP inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of valsartan; monitor patients for potential adverse effects.
Amoxicillin; Clarithromycin; Lansoprazole: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as clarithromycin. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects.
Amoxicillin; Clarithromycin; Omeprazole: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as clarithromycin. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects.
Antidiabetic Agents: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Apalutamide: (Contraindicated) Concomitant use of daclatasvir with apalutamide is contraindicated due to the potential for hepatitis C treatment failure. Coadministration may result in reduced systemic exposes to daclatasvir. Apalutamide is a potent inducer of the hepatic isoenzyme CYP3A4 and daclatasvir is a substrate of this isoenzyme.
Aprepitant, Fosaprepitant: (Moderate) Use caution if daclatasvir and aprepitant, fosaprepitant are used concurrently and monitor for an increase in daclatasvir-related adverse effects for several days after administration of a multi-day aprepitant regimen. Daclatasvir is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of daclatasvir. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Armodafinil: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be increased to 90 mg PO once daily when administered in combination with moderate CYP3A4 inducers, such as armodafinil. Taking these drugs together may decrease daclatasvir serum concentrations, potentially resulting in reduced antiviral efficacy and antimicrobial resistance. Conversely, the therapeutic effects of armodafinil, a P-glycoprotein (P-gp) substrate, may be increased by daclatasvir, a P-gp inhibitor.
Aspirin, ASA; Pravastatin: (Moderate) Caution and close monitoring is advised if daclatasvir is administered with HMG-CoA reductase inhibitors (Statins). Use of these drugs together may result in elevated Statin serum concentrations, potentially resulting in adverse effects such as myopathy and rhabdomyolysis.
Atazanavir: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with atazanavir, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. If these drugs are administered together, monitor patients for daclatasvir-related adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions. If atazanavir is boosted with cobicistat, the dose of daclatasvir must be reduced to 30 mg PO once daily.
Atazanavir; Cobicistat: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as cobicistat. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects. (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with atazanavir, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. If these drugs are administered together, monitor patients for daclatasvir-related adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions. If atazanavir is boosted with cobicistat, the dose of daclatasvir must be reduced to 30 mg PO once daily.
Atorvastatin: (Moderate) Caution and close monitoring is advised if daclatasvir is administered with HMG-CoA reductase inhibitors (Statins). Use of these drugs together may result in elevated Statin serum concentrations, potentially resulting in adverse effects such as myopathy and rhabdomyolysis.
Atorvastatin; Ezetimibe: (Moderate) Caution and close monitoring is advised if daclatasvir is administered with HMG-CoA reductase inhibitors (Statins). Use of these drugs together may result in elevated Statin serum concentrations, potentially resulting in adverse effects such as myopathy and rhabdomyolysis.
Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Contraindicated) Concomitant use of daclatasvir with phenobarbital is contraindicated due to the potential for hepatitis C treatment failure. Coadministration may result in reduced systemic exposes to daclatasvir. Phenobarbital is a potent inducer of the hepatic isoenzyme CYP3A4; daclatasvir is a substrate of this isoenzyme.
Belladonna Alkaloids; Ergotamine; Phenobarbital: (Contraindicated) Concomitant use of daclatasvir with phenobarbital is contraindicated due to the potential for hepatitis C treatment failure. Coadministration may result in reduced systemic exposes to daclatasvir. Phenobarbital is a potent inducer of the hepatic isoenzyme CYP3A4; daclatasvir is a substrate of this isoenzyme.
Berotralstat: (Major) Reduce the berotralstat dose to 110 mg PO once daily in patients chronically taking daclatasvir. Concurrent use may increase berotralstat exposure and the risk of adverse effects. Berotralstat is a P-gp and BCRP substrate and daclatasvir is a P-gp and BCRP inhibitor. Coadministration with another P-gp and BCRP inhibitor increased berotralstat exposure by 69%.
Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving daclatasvir. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving daclatasvir. Bleeding risk may be increased; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a substrate of P-gp; daclatasvir inhibits P-gp.
Bexarotene: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be increased to 90 mg PO once daily when administered in combination with moderate CYP3A4 inducers, such as bexarotene. Taking these drugs together may decrease daclatasvir serum concentrations, potentially resulting in reduced antiviral efficacy and antimicrobial resistance.
Boceprevir: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as boceprevir. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects. In addition, the therapeutic effects of boceprevir, a P-glycoprotein (P-gp) substrate, may be increased by daclatasvir, a P-gp inhibitor.
Bosentan: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be increased to 90 mg PO once daily when administered in combination with moderate CYP3A4 inducers, such as bosentan. Taking these drugs together may decrease daclatasvir serum concentrations, potentially resulting in reduced antiviral efficacy and antimicrobial resistance. Conversely, the therapeutic effects of bosentan, a substrate of the organic anion transporting polypeptides (OATP), may be increased by daclatasvir, an OATP inhibitor
Budesonide: (Moderate) Systemic exposure of budesonide, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of budesonide; monitor patients for potential adverse effects.
Budesonide; Formoterol: (Moderate) Systemic exposure of budesonide, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of budesonide; monitor patients for potential adverse effects.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Systemic exposure of budesonide, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of budesonide; monitor patients for potential adverse effects.
Buprenorphine: (Moderate) Systemic exposure of buprenorphine may be increased when administered concurrently with daclatasvir. Taking these drugs together could increase or prolong the therapeutic effects of buprenorphine. No dosage adjustments are recommended; however, close monitoring of patients for potential adverse effects is advised.
Buprenorphine; Naloxone: (Moderate) Systemic exposure of buprenorphine may be increased when administered concurrently with daclatasvir. Taking these drugs together could increase or prolong the therapeutic effects of buprenorphine. No dosage adjustments are recommended; however, close monitoring of patients for potential adverse effects is advised.
Canagliflozin: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Canagliflozin; Metformin: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Carbamazepine: (Contraindicated) Concomitant use of daclatasvir with carbamazepine is contraindicated due to the potential for hepatitis C treatment failure. Coadministration may result in reduced systemic exposes to daclatasvir. Carbamazepine is a potent inducer of the hepatic isoenzyme CYP3A4; daclatasvir is a substrate of this isoenzyme.
Carvedilol: (Moderate) Systemic exposure of carvedilol, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of carvedilol; monitor patients for potential adverse effects.
Cenobamate: (Major) Increase the dose of daclatasvir to 90 mg PO once daily if coadministered with cenobamate due to decreased daclatasvir exposure resulting in potential loss of virologic control. Daclatasvir is a CYP3A4 substrate; cenobamate is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer reduced the daclatasvir AUC by 63%.
Ceritinib: (Major) Reduce the daclatasvir dose to 30 mg PO once daily if coadministered with ceritinib due to increased daclatasvir exposure; exposure to ceritinib may also increase. Daclatasvir is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the daclatasvir AUC by 3-fold.
Chloramphenicol: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as chloramphenicol. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects.
Chlorpropamide: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Ciprofloxacin: (Moderate) According to the manufacturer, concurrent administration of daclatasvir, a CYP3A4 substrate, with ciprofloxacin, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. If these drugs are administered together, monitor patients for daclatasvir-related adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
Clarithromycin: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as clarithromycin. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects.
Cobicistat: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as cobicistat. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects.
Cobimetinib: (Minor) If concurrent use of cobimetinib and daclatasvir is necessary, use caution and monitor for a possible increase in cobimetinib-related adverse effects. Cobimetinib is a P-glycoprotein (P-gp) substrate, and daclatasvir is a P-gp inhibitor; coadministration may result in increased cobimetinib exposure. However, coadministration of cobimetinib with another P-gp inhibitor, vemurafenib (960 mg twice daily), did not result in clinically relevant pharmacokinetic drug interactions.
Colchicine: (Moderate) Systemic exposure of colchicine, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of colchicine; monitor patients for potential adverse effects.
Colchicine; Probenecid: (Moderate) Systemic exposure of colchicine, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of colchicine; monitor patients for potential adverse effects.
Conivaptan: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as conivaptan. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects.
Dabigatran: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with daclatasvir, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like daclatasvir in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with daclatasvir, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Dabrafenib: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be increased to 90 mg PO once daily when administered in combination with moderate CYP3A4 inducers, such as dabrafenib. Taking these drugs together may decrease daclatasvir serum concentrations, potentially resulting in reduced antiviral efficacy and antimicrobial resistance.
Danazol: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with danazol, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. If these drugs are administered together, monitor patients for daclatasvir-related adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
Dapagliflozin: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Dapagliflozin; Metformin: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Dapagliflozin; Saxagliptin: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Darunavir: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with darunavir, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. If these drugs are administered together, monitor patients for daclatasvir-related adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions. When darunavir is boosted with cobicistat, the dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily.
Darunavir; Cobicistat: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as cobicistat. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects. (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with darunavir, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. If these drugs are administered together, monitor patients for daclatasvir-related adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions. When darunavir is boosted with cobicistat, the dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as cobicistat. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects. (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with darunavir, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. If these drugs are administered together, monitor patients for daclatasvir-related adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions. When darunavir is boosted with cobicistat, the dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily.
Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Taking daclatasvir with dasabuvir may increase serum concentrations of dasabuvir, and potentially increase the risk for adverse effects. Dasabuvir is a P-glycoprotein (P-gp) substrates; daclatasvir is a P-gp inhibitor. (Major) Taking daclatasvir with ombitasvir may increase serum concentrations of ombitasvir, and potentially increase the risk for adverse effects. Ombitasvir is a P-glycoprotein (P-gp) substrates; daclatasvir is a P-gp inhibitor. (Major) Taking daclatasvir with paritaprevir may increase serum concentrations of paritaprevir, and potentially increase the risk for adverse effects. Paritaprevir is a P-glycoprotein (P-gp) substrates; daclatasvir is a P-gp inhibitor. (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as ritonavir. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects. In addition, the therapeutic effects of ritonavir, a P-glycoprotein (P-gp) substrate, may be increased by daclatasvir, a P-gp inhibitor.
Deferasirox: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be increased to 90 mg PO once daily when administered in combination with moderate CYP3A4 inducers, such as deferasirox. Taking these drugs together may decrease daclatasvir serum concentrations, potentially resulting in reduced antiviral efficacy and antimicrobial resistance.
Delavirdine: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as delavirdine. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects.
Dexamethasone: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be increased to 90 mg PO once daily when administered in combination with moderate CYP3A4 inducers, such as dexamethasone. Taking these drugs together may decrease daclatasvir serum concentrations, potentially resulting in reduced antiviral efficacy and antimicrobial resistance. Conversely, the therapeutic effects of dexamethasone, a P-glycoprotein (P-gp) substrate, may be increased by daclatasvir, a P-gp inhibitor.
Dextromethorphan; Quinidine: (Major) Systemic exposure of quinidine, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of quinidine; monitor patients for potential adverse effects.
Digoxin: (Major) Coadministration of daclatasvir with digoxin may increase digoxin exposure leading to increased or prolonged therapeutic effects and adverse events. If digoxin is initiated in a patients already receiving daclatasvir, start digoxin at the lowest appropriate dose followed by gradual and caution dose adjustments. If daclatasvir is started in a patients already receiving digoxin, obtain digoxin serum concentrations before giving daclatasvir and decrease the digoxin dose by 30% to 50%. Alternatively, the digoxin dose may be reduced by prolonging the dosing interval. Digoxin is a substrate for P-glycoprotein (P-gp); daclatasvir is a P-gp inhibitor.
Docetaxel: (Moderate) Systemic exposure of docetaxel, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of docetaxel; monitor patients for potential adverse effects.
Dolutegravir: (Moderate) Systemic exposure of dolutegravir, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of dolutegravir; monitor patients for potential adverse effects.
Dolutegravir; Lamivudine: (Moderate) Systemic exposure of dolutegravir, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of dolutegravir; monitor patients for potential adverse effects.
Dolutegravir; Rilpivirine: (Moderate) Systemic exposure of dolutegravir, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of dolutegravir; monitor patients for potential adverse effects.
Doxorubicin: (Moderate) Systemic exposure of doxorubicin, a substrate of the drug transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), may be increased when administered concurrently with daclatasvir, a P-gp and BCRP inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of doxorubicin; monitor patients for potential adverse effects.
Dronedarone: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with dronedarone, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. If these drugs are administered together, monitor patients for daclatasvir-related adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
Dulaglutide: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Efavirenz: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be increased to 90 mg PO once daily when administered in combination with moderate CYP3A4 inducers, such as efavirenz. Taking these drugs together may decrease daclatasvir serum concentrations, potentially resulting in reduced antiviral efficacy and antimicrobial resistance.
Efavirenz; Emtricitabine; Tenofovir: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be increased to 90 mg PO once daily when administered in combination with moderate CYP3A4 inducers, such as efavirenz. Taking these drugs together may decrease daclatasvir serum concentrations, potentially resulting in reduced antiviral efficacy and antimicrobial resistance.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be increased to 90 mg PO once daily when administered in combination with moderate CYP3A4 inducers, such as efavirenz. Taking these drugs together may decrease daclatasvir serum concentrations, potentially resulting in reduced antiviral efficacy and antimicrobial resistance.
Elagolix: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as daclatasvir is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Daclatasvir inhibits both OATP1B1 and P-gp. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density.
Elagolix; Estradiol; Norethindrone acetate: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as daclatasvir is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Daclatasvir inhibits both OATP1B1 and P-gp. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density.
Elbasvir; Grazoprevir: (Contraindicated) Concurrent administration of grazoprevir with daclatasvir is contraindicated. Use of these drugs together is expected to significantly increase the plasma concentrations of grazoprevir, and may result in adverse effects (i.e., elevated ALT concentrations). Daclatasvir is an inhibitor of the organic anion transporting polypeptide (OATP1B1/3). Grazoprevir is a substrate of OATP1B1/3.
Eletriptan: (Moderate) Systemic exposure of eletriptan, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of eletriptan; monitor patients for potential adverse effects.
Eluxadoline: (Major) Consider a reduction in the dose of eluxadoline to 75 mg twice daily and monitor for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity) if coadministered with daclatasvir. Coadministration may increase exposure of eluxadoline. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known. Eluxadoline is an OATP1B1 substrate and daclatasvir is a an OATP1B1 inhibitor. Coadministration with another OATP1B1 inhibitor increased the exposure of eluxadoline by 4.4-fold.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as cobicistat. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as cobicistat. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects.
Empagliflozin: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Empagliflozin; Linagliptin: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Empagliflozin; Linagliptin; Metformin: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Empagliflozin; Metformin: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Enzalutamide: (Contraindicated) Coadministration of daclatasvir and enzalutamide is contraindicated due to decreased daclatasvir exposure resulting in potential loss of virologic control. Daclatasvir is a CYP3A4 substrate; enzalutamide is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer reduced the daclatasvir AUC by 79%.
Ertugliflozin: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Ertugliflozin; Metformin: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Ertugliflozin; Sitagliptin: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Erythromycin: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with erythromycin, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. In addition, the therapeutic effects of erythromycin, a P-glycoprotein (P-gp) substrate, may be increased by daclatasvir, a P-gp inhibitor. If these drugs are administered together, monitor patients for adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
Erythromycin; Sulfisoxazole: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with erythromycin, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. In addition, the therapeutic effects of erythromycin, a P-glycoprotein (P-gp) substrate, may be increased by daclatasvir, a P-gp inhibitor. If these drugs are administered together, monitor patients for adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
Eslicarbazepine: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be increased to 90 mg PO once daily when administered in combination with moderate CYP3A4 inducers, such as eslicarbazepine. Taking these drugs together may decrease daclatasvir serum concentrations, potentially resulting in reduced antiviral efficacy and antimicrobial resistance.
Etravirine: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be increased to 90 mg PO once daily when administered in combination with moderate CYP3A4 inducers, such as etravirine. Taking these drugs together may decrease daclatasvir serum concentrations, potentially resulting in reduced antiviral efficacy and antimicrobial resistance.
Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate and watch for everolimus-related adverse reactions if coadministration with daclatasvir is necessary. The dose of everolimus may need to be reduced. Everolimus is a P-glycoprotein (P-gp) substrate and daclatasvir is a P-gp inhibitor. Coadministration with P-gp inhibitors may decrease the efflux of everolimus from intestinal cells and increase everolimus blood concentrations.
Exenatide: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Ezetimibe; Simvastatin: (Moderate) Caution and close monitoring is advised if daclatasvir is administered with HMG-CoA reductase inhibitors (Statins). Use of these drugs together may result in elevated Statin serum concentrations, potentially resulting in adverse effects such as myopathy and rhabdomyolysis.
Fexofenadine: (Minor) Systemic exposure of fexofenadine, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of fexofenadine; monitor patients for potential adverse effects.
Fexofenadine; Pseudoephedrine: (Minor) Systemic exposure of fexofenadine, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of fexofenadine; monitor patients for potential adverse effects.
Fluconazole: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with fluconazole, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. If these drugs are administered together, monitor patients for daclatasvir-related adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
Flutamide: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be increased to 90 mg PO once daily when administered in combination with moderate CYP3A4 inducers, such as flutamide. Taking these drugs together may decrease daclatasvir serum concentrations, potentially resulting in reduced antiviral efficacy and antimicrobial resistance.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) Systemic exposure of umeclidinium; vilanterol, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of umeclidinium; vilanterol; monitor patients for potential adverse effects.
Fluvastatin: (Moderate) Caution and close monitoring is advised if daclatasvir is administered with HMG-CoA reductase inhibitors (Statins). Use of these drugs together may result in elevated Statin serum concentrations, potentially resulting in adverse effects such as myopathy and rhabdomyolysis.
Fosamprenavir: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with fosamprenavir, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. In addition, the therapeutic effects of fosamprenavir, a P-glycoprotein (P-gp) substrate, may be increased by daclatasvir, a P-gp inhibitor. If these drugs are administered together, monitor patients for adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
Fosphenytoin: (Contraindicated) Concomitant use of daclatasvir with phenytoin or fosphenytoin is contraindicated due to the potential for hepatitis C treatment failure. Coadministration may result in reduced systemic exposes to daclatasvir. Phenytoin is a potent inducer of the hepatic isoenzyme CYP3A4; daclatasvir is a substrate of this isoenzyme.
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and daclatasvir as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of organic anion transporting polypeptide (OATP) 1B1/3, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP); daclatasvir is an inhibitor of all these drug transporters. (Moderate) Caution is advised with the coadministration of pibrentasvir and daclatasvir as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); daclatasvir is an inhibitor of P-gp and BCRP.
Glimepiride: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Glimepiride; Pioglitazone: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Glimepiride; Rosiglitazone: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Glipizide: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Glipizide; Metformin: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Glyburide: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Glyburide; Metformin: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Grapefruit juice: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as grapefruit juice. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects.
HMG-CoA reductase inhibitors: (Moderate) Caution and close monitoring is advised if daclatasvir is administered with HMG-CoA reductase inhibitors (Statins). Use of these drugs together may result in elevated Statin serum concentrations, potentially resulting in adverse effects such as myopathy and rhabdomyolysis.
Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Systemic exposure of valsartan, a substrate of the drug transporter organic anion transporting polypeptides (OATP), may be increased when administered concurrently with daclatasvir, an OATP inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of valsartan; monitor patients for potential adverse effects.
Idelalisib: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as idelalisib. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects.
Imatinib: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with imatinib, a moderate CYP3A4 inhibitor, may increase daclatasvir. In addition, the therapeutic effects of imatinib, a substrate for the breast cancer resistant protein (BCRP), may be increased by daclatasvir, a BCRP inhibitor. If these drugs are administered together, monitor patients for adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
Indinavir: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as indinavir. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects. In addition, the therapeutic effects of indinavir, a P-glycoprotein (P-gp) substrate, may be increased by daclatasvir, a P-gp inhibitor.
Insulin Aspart: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Insulin Aspart; Insulin Aspart Protamine: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Insulin Degludec; Liraglutide: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Insulin Detemir: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Insulin Glargine: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Insulin Glargine; Lixisenatide: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Insulin Glulisine: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Insulin Lispro: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Insulin Lispro; Insulin Lispro Protamine: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Insulin, Inhaled: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Isavuconazonium: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with isavuconazonium, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. If these drugs are administered together, monitor patients for daclatasvir-related adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Contraindicated) Concomitant use of daclatasvir with rifampin is contraindicated due to the potential for hepatitis C treatment failure. Coadministration reduces systemic exposes to daclatasvir by 79%. Rifampin is a potent inducer of the hepatic isoenzyme CYP3A4; daclatasvir is a substrate of this isoenzyme.
Isoniazid, INH; Rifampin: (Contraindicated) Concomitant use of daclatasvir with rifampin is contraindicated due to the potential for hepatitis C treatment failure. Coadministration reduces systemic exposes to daclatasvir by 79%. Rifampin is a potent inducer of the hepatic isoenzyme CYP3A4; daclatasvir is a substrate of this isoenzyme.
Isophane Insulin (NPH): (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Itraconazole: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as itraconazole. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects. In addition, the therapeutic effects of itraconazole, a P-glycoprotein (P-gp) substrate, may be increased by daclatasvir, a P-gp inhibitor.
Ketoconazole: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as ketoconazole. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects.
Lefamulin: (Moderate) Monitor for lefamulin-related adverse effects if oral lefamulin is administered with daclatasvir as concurrent use may increase exposure from lefamulin tablets; an interaction is not expected with intravenous lefamulin. Lefamulin is a CYP3A4 and P-gp substrate and daclatasvir is a P-gp inhibitor.
Lente Insulin: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in seriou

s symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of daclatasvir; monitor for potential reduction in efficacy. Daclatasvir is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of daclatasvir; monitor for potential reduction in efficacy. Daclatasvir is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Letermovir: (Moderate) Administering daclatasvir concurrently with letermovir may result in elevated concentrations of both drugs; dosage adjustments are not required for either drug. However in patients who are also receiving cyclosporine, the dose of daclatasvir should be reduced to 30 mg once daily. Closely monitor for adverse events, including tachycardia, atrial fibrillation, headache, tiredness, and gastrointestinal events. Daclatasvir is an inhibitor of the organic anion-transporting polypeptides (OATP1B1/3), and is primarily metabolized by CYP3A4. Letermovir is an OATP1B1/3 substrate and a moderate CYP3A4 inhibitor. When given with cyclosporine, the combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.
Linagliptin: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Linagliptin; Metformin: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Liraglutide: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Lixisenatide: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Lonafarnib: (Major) Reduce the daclatasvir dose to 30 mg PO once daily if coadministered with lonafarnib due to increased daclatasvir exposure. Daclatasvir is a CYP3A4 substrate; lonafarnib is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the daclatasvir AUC by 3-fold.
Loperamide: (Moderate) The plasma concentration of loperamide, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a potent inhibitor of P-gp. If these drugs are used together, monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest).
Loperamide; Simethicone: (Moderate) The plasma concentration of loperamide, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a potent inhibitor of P-gp. If these drugs are used together, monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest).
Lopinavir; Ritonavir: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as ritonavir. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects. In addition, the therapeutic effects of ritonavir, a P-glycoprotein (P-gp) substrate, may be increased by daclatasvir, a P-gp inhibitor.
Lorlatinib: (Major) Increase the dose of daclatasvir to 90 mg PO once daily if coadministered with lorlatinib due to decreased daclatasvir exposure resulting in potential loss of virologic control. Daclatasvir is a CYP3A4 substrate; lorlatinib is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer reduced the daclatasvir AUC by 63%.
Lovastatin: (Moderate) Caution and close monitoring is advised if daclatasvir is administered with HMG-CoA reductase inhibitors (Statins). Use of these drugs together may result in elevated Statin serum concentrations, potentially resulting in adverse effects such as myopathy and rhabdomyolysis.
Lovastatin; Niacin: (Moderate) Caution and close monitoring is advised if daclatasvir is administered with HMG-CoA reductase inhibitors (Statins). Use of these drugs together may result in elevated Statin serum concentrations, potentially resulting in adverse effects such as myopathy and rhabdomyolysis.
Maraviroc: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and daclatasvir as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp) and organic anion-transporting polypeptide (OATP1B1); daclatasvir is an inhibitor of P-gp and OATP1B1. The effects of these transporters on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
Mefloquine: (Moderate) Systemic exposure of mefloquine, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of mefloquine; monitor patients for potential adverse effects.
Metformin: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Metformin; Pioglitazone: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Metformin; Repaglinide: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Metformin; Rosiglitazone: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Metformin; Saxagliptin: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Metformin; Sitagliptin: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Methotrexate: (Minor) Systemic exposure of methotrexate, a substrate of the drug transporter breast cancer resistance protein (BCRP), may be increased when administered concurrently with daclatasvir, a BCRP inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of methotrexate; monitor patients for potential adverse effects.
Mifepristone: (Moderate) Administration of daclatasvir with mifepristone may increase daclatasvir serum concentrations. If these drugs are coadministered, monitor patients for daclatasvir-related adverse effects, such as headache, fatigue, nausea, and diarrhea. Daclatasvir is a CYP3A4 and P-gp substrate, and mifepristone is a known CYP3A4 inhibitor and possibly a P-gp inhibitor. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Miglitol: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Mitotane: (Contraindicated) Concomitant use of daclatasvir with mitotane is contraindicated due to the potential for hepatitis C treatment failure. Mitotane is a strong CYP3A4 inducer and daclatasvir is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of daclatasvir.
Mitoxantrone: (Moderate) Systemic exposure of mitoxantrone, a substrate of the drug transporter breast cancer resistance protein (BCRP), may be increased when administered concurrently with daclatasvir, a BCRP inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of mitoxantrone; monitor patients for potential adverse effects.
Modafinil: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be increased to 90 mg PO once daily when administered in combination with moderate CYP3A4 inducers, such as modafinil. Taking these drugs together may decrease daclatasvir serum concentrations, potentially resulting in reduced antiviral efficacy and antimicrobial resistance.
Morphine: (Moderate) Systemic exposure of morphine, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of morphine; monitor patients for potential adverse effects.
Morphine; Naltrexone: (Moderate) Systemic exposure of morphine, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of morphine; monitor patients for potential adverse effects.
Nafcillin: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be increased to 90 mg PO once daily when administered in combination with moderate CYP3A4 inducers, such as nafcillin. Taking these drugs together may decrease daclatasvir serum concentrations, potentially resulting in reduced antiviral efficacy and antimicrobial resistance.
Naldemedine: (Major) Monitor for potential naldemedine-related adverse reactions if coadministered with daclatasvir. The plasma concentrations of naldemedine may be increased during concurrent use. Naldemedine is a P-gp substrate; daclatasvir is a moderate P-gp inhibitor.
Nateglinide: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Nebivolol; Valsartan: (Moderate) Systemic exposure of valsartan, a substrate of the drug transporter organic anion transporting polypeptides (OATP), may be increased when administered concurrently with daclatasvir, an OATP inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of valsartan; monitor patients for potential adverse effects.
Nefazodone: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as nefazodone. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects.
Nelfinavir: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as nelfinavir. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects. In addition, the therapeutic effects of nelfinavir, a P-glycoprotein (P-gp) substrate, may be increased by daclatasvir, a P-gp inhibitor.
Netupitant, Fosnetupitant; Palonosetron: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with netupitant; palonosetron, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. If these drugs are administered together, monitor patients for daclatasvir-related adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
Nevirapine: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be increased to 90 mg PO once daily when administered in combination with moderate CYP3A4 inducers, such as nevirapine. Taking these drugs together may decrease daclatasvir serum concentrations, potentially resulting in reduced antiviral efficacy and antimicrobial resistance.
Niacin; Simvastatin: (Moderate) Caution and close monitoring is advised if daclatasvir is administered with HMG-CoA reductase inhibitors (Statins). Use of these drugs together may result in elevated Statin serum concentrations, potentially resulting in adverse effects such as myopathy and rhabdomyolysis.
Nicardipine: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with nicardipine, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. If these drugs are administered together, monitor patients for daclatasvir-related adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
Octreotide: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with octreotide, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. If these drugs are administered together, monitor patients for daclatasvir-related adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
Ombitasvir; Paritaprevir; Ritonavir: (Major) Taking daclatasvir with ombitasvir may increase serum concentrations of ombitasvir, and potentially increase the risk for adverse effects. Ombitasvir is a P-glycoprotein (P-gp) substrates; daclatasvir is a P-gp inhibitor. (Major) Taking daclatasvir with paritaprevir may increase serum concentrations of paritaprevir, and potentially increase the risk for adverse effects. Paritaprevir is a P-glycoprotein (P-gp) substrates; daclatasvir is a P-gp inhibitor. (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as ritonavir. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects. In addition, the therapeutic effects of ritonavir, a P-glycoprotein (P-gp) substrate, may be increased by daclatasvir, a P-gp inhibitor.
Omeprazole; Amoxicillin; Rifabutin: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be increased to 90 mg PO once daily when administered in combination with moderate CYP3A4 inducers, such as rifabutin. Taking these drugs together may decrease daclatasvir serum concentrations, potentially resulting in reduced antiviral efficacy and antimicrobial resistance.
Ondansetron: (Moderate) Systemic exposure of ondansetron, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of ondansetron; monitor patients for potential adverse effects.
Paclitaxel: (Moderate) Systemic exposure of paclitaxel, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of paclitaxel; monitor patients for potential adverse effects.
Panobinostat: (Major) Systemic exposure of panobinostat, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of panobinostat; monitor patients for potential adverse effects.
Pazopanib: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with pazopanib, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. In addition, the therapeutic effects of pazopanib, a substrate for P-glycoprotein (P-gp) and the breast cancer resistant protein (BCRP), may be increased by daclatasvir, a P-gp and BCRP inhibitor. If these drugs are administered together, monitor patients for adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
Pexidartinib: (Major) Increase the dose of daclatasvir to 90 mg PO once daily if coadministered with pexidartinib due to decreased daclatasvir exposure resulting in potential loss of virologic control. Daclatasvir is a CYP3A4 substrate; pexidartinib is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer reduced the daclatasvir AUC by 63%.
Phenobarbital: (Contraindicated) Concomitant use of daclatasvir with phenobarbital is contraindicated due to the potential for hepatitis C treatment failure. Coadministration may result in reduced systemic exposes to daclatasvir. Phenobarbital is a potent inducer of the hepatic isoenzyme CYP3A4; daclatasvir is a substrate of this isoenzyme.
Phenytoin: (Contraindicated) Concomitant use of daclatasvir with phenytoin or fosphenytoin is contraindicated due to the potential for hepatitis C treatment failure. Coadministration may result in reduced systemic exposes to daclatasvir. Phenytoin is a potent inducer of the hepatic isoenzyme CYP3A4; daclatasvir is a substrate of this isoenzyme.
Pioglitazone: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Pitavastatin: (Moderate) Caution and close monitoring is advised if daclatasvir is administered with HMG-CoA reductase inhibitors (Statins). Use of these drugs together may result in elevated Statin serum concentrations, potentially resulting in adverse effects such as myopathy and rhabdomyolysis.
Posaconazole: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as posaconazole. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects. In addition, the therapeutic effects of posaconazole, a P-glycoprotein (P-gp) substrate, may be increased by daclatasvir, a P-gp inhibitor.
Pramlintide: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Pravastatin: (Moderate) Caution and close monitoring is advised if daclatasvir is administered with HMG-CoA reductase inhibitors (Statins). Use of these drugs together may result in elevated Statin serum concentrations, potentially resulting in adverse effects such as myopathy and rhabdomyolysis.
Prednisone: (Moderate) Systemic exposure of prednisone, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of prednisone; monitor patients for potential adverse effects.
Primidone: (Contraindicated) Concomitant use of daclatasvir with primidone is contraindicated due to the potential for hepatitis C treatment failure. Coadministration may result in reduced systemic exposes to daclatasvir. Primidone is a potent inducer of the hepatic isoenzyme CYP3A4; daclatasvir is a substrate of this isoenzyme.
Quinidine: (Major) Systemic exposure of quinidine, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of quinidine; monitor patients for potential adverse effects.
Ranolazine: (Moderate) Systemic exposure of ranolazine, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of ranolazine; monitor patients for potential adverse effects.
Regular Insulin: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Regular Insulin; Isophane Insulin (NPH): (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Relugolix: (Major) Avoid concomitant use of relugolix and oral daclatasvir. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer daclatasvir at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate and daclatasvir is a P-gp inhibitor.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of relugolix and oral daclatasvir. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer daclatasvir at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate and daclatasvir is a P-gp inhibitor.
Repaglinide: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Revefenacin: (Major) Coadministration of revefenacin is not recommended with daclatasvir because it could lead to an increase in systemic exposure of the active metabolite of revefenacin and an increased potential for anticholinergic adverse effects.The active metabolite of revefenacin is a substrate of OATP1B1 and OATP1B3; daclatasvir is an inhibitor of OATP1B1 and OATP1B3.
Ribociclib: (Major) Reduce the daclatasvir dose to 30 mg PO once daily if coadministered with ribociclib due to increased daclatasvir exposure. Daclatasvir is a CYP3A4 substrate; ribociclib is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the daclatasvir AUC by 3-fold.
Ribociclib; Letrozole: (Major) Reduce the daclatasvir dose to 30 mg PO once daily if coadministered with ribociclib due to increased daclatasvir exposure. Daclatasvir is a CYP3A4 substrate; ribociclib is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the daclatasvir AUC by 3-fold.
Rifabutin: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be increased to 90 mg PO once daily when administered in combination with moderate CYP3A4 inducers, such as rifabutin. Taking these drugs together may decrease daclatasvir serum concentrations, potentially resulting in reduced antiviral efficacy and antimicrobial resistance.
Rifampin: (Contraindicated) Concomitant use of daclatasvir with rifampin is contraindicated due to the potential for hepatitis C treatment failure. Coadministration reduces systemic exposes to daclatasvir by 79%. Rifampin is a potent inducer of the hepatic isoenzyme CYP3A4; daclatasvir is a substrate of this isoenzyme.
Rifapentine: (Contraindicated) Coadministration of daclatasvir and rifapentine is contraindicated due to decreased daclatasvir exposure resulting in potential loss of virologic control. Daclatasvir is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer reduced the daclatasvir AUC by 79%.
Rifaximin: (Major) The dose of daclatasvir, a CYP3A4 substrate, may need to be increased to 90 mg PO once daily when administered in combination with rifaximin. Rifaximin is categorized as a moderate CYP3A4 inducer; however in patients with normal hepatic function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations. Taking these drugs together may decrease daclatasvir serum concentrations, potentially resulting in reduced antiviral efficacy and antimicrobial resistance. Conversely, the therapeutic effects of rifaximin, a substrate of P-glycoprotein (P-gp) and organic anion transporting polypeptides (OATP), may be increased by daclatasvir, a P-gp and OATP inhibitor.
Rimegepant: (Major) Avoid coadministration of rimegepant with daclatasvir; concurrent use may increase rimegepant exposure. Rimegepant is a substrate of P-gp and BCRP and daclatasvir is a P-gp and BCRP inhibitor.
Riociguat: (Minor) Systemic exposure of riociguat, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of riociguat; monitor patients for potential adverse effects.
Ritonavir: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as ritonavir. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects. In addition, the therapeutic effects of ritonavir, a P-glycoprotein (P-gp) substrate, may be increased by daclatasvir, a P-gp inhibitor.
Rivaroxaban: (Minor) Systemic exposure of rivaroxaban, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of rivaroxaban; monitor patients for potential adverse effects.
Romidepsin: (Moderate) Systemic exposure of romidepsin, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of romidepsin; monitor patients for potential adverse effects.
Rosiglitazone: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Rosuvastatin: (Moderate) Caution and close monitoring is advised if daclatasvir is administered with HMG-CoA reductase inhibitors (Statins). Use of these drugs together may result in elevated Statin serum concentrations, potentially resulting in adverse effects such as myopathy and rhabdomyolysis.
Rosuvastatin; Ezetimibe: (Moderate) Caution and close monitoring is advised if daclatasvir is administered with HMG-CoA reductase inhibitors (Statins). Use of these drugs together may result in elevated Statin serum concentrations, potentially resulting in adverse effects such as myopathy and rhabdomyolysis.
Sacubitril; Valsartan: (Moderate) Systemic exposure of valsartan, a substrate of the drug transporter organic anion transporting polypeptides (OATP), may be increased when administered concurrently with daclatasvir, an OATP inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of valsartan; monitor patients for potential adverse effects.
Saquinavir: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as saquinavir. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects. In addition, the therapeutic effects of saquinavir, a P-glycoprotein (P-gp) substrate, may be increased by daclatasvir, a P-gp inhibitor.
Saxagliptin: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Semaglutide: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Silodosin: (Moderate) Systemic exposure of silodosin, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of silodosin; monitor patients for potential adverse effects.
Simeprevir: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with simeprevir, a moderate CYP3A4 inhibitor, increases daclatasvir serum concentrations by 94%. In addition, the pharmacokinetic properties (i.e., Cmax, Cmin, and AUC) of simeprevir, a substrate of the drug transporters P-glycoprotein (P-gp) and organic anion transporting polypeptides (OATP), are increased by daclatasvir, a P-gp and OATP inhibitor. If these drugs are administered together, monitor patients for adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
Simvastatin: (Moderate) Caution and close monitoring is advised if daclatasvir is administered with HMG-CoA reductase inhibitors (Statins). Use of these drugs together may result in elevated Statin serum concentrations, potentially resulting in adverse effects such as myopathy and rhabdomyolysis.
Simvastatin; Sitagliptin: (Moderate) Caution and close monitoring is advised if daclatasvir is administered with HMG-CoA reductase inhibitors (Statins). Use of these drugs together may result in elevated Statin serum concentrations, potentially resulting in adverse effects such as myopathy and rhabdomyolysis. (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Sirolimus: (Moderate) Systemic exposure of sirolimus, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of sirolimus; monitor patients for potential adverse effects.
Sitagliptin: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Sofosbuvir; Velpatasvir: (Contraindicated) Do not coadminister velpatasvir with daclatasvir. Taking these drugs together is a duplication of therapy, and may result in adverse effects.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Contraindicated) Do not coadminister velpatasvir with daclatasvir. Taking these drugs together is a duplication of therapy, and may result in adverse effects. (Major) Avoid concurrent administration of voxilaprevir and daclatasvir. Taking these medications together may increase voxilaprevir plasma concentrations, potentially increasing the risk for adverse events. Voxilaprevir is a substrate for the drug transporter Organic Anion Transporting Polypeptides 1B1/1B3 (OATP1B1/1B3). Daclatasvir is an OATP1B1/1B3 inhibitor.
Sotorasib: (Major) Increase the dose of daclatasvir to 90 mg PO once daily if coadministered with sotorasib due to decreased daclatasvir exposure resulting in potential loss of virologic control. Daclatasvir is a CYP3A4 substrate; sotorasib is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer reduced the daclatasvir AUC by 63%.
St. John's Wort, Hypericum perforatum: (Contraindicated) Concomitant use of daclatasvir with St. John's Wort, Hypericum perforatum is contraindicated due to the potential for hepatitis C treatment failure. Coadministration may result in reduced systemic exposes to daclatasvir. St. John's Wort is a potent inducer of the hepatic isoenzyme CYP3A4; daclatasvir is a substrate of this isoenzyme.
Sulfasalazine: (Moderate) Systemic exposure of sulfasalazine, a substrate of the drug transporter breast cancer resistance protein (BCRP), may be increased when administered concurrently with daclatasvir, a BCRP inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of sulfasalazine; monitor patients for potential adverse effects.
Tacrolimus: (Moderate) Closely monitor tacrolimus serum concentrations if coadministration with a direct acting antiviral (DAA) agent, such as daclatasvir, is necessary; dosage adjustments may be required. Changes in liver function due to clearance of the hepatitis C virus by DAA therapy may alter tacrolimus serum concentrations.
Talazoparib: (Major) Avoid coadministration of daclatasvir with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP and P-glycoprotein (P-gp) substrate; daclatasvir is a BCRP and P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
Telithromycin: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as telithromycin. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects.
Temsirolimus: (Moderate) Monitor for an increase in temsirolimus-related adverse reactions if coadministration with daclatasvir is necessary. Temsirolimus is a P-glycoprotein (P-gp) substrate and daclatasvir is a P-gp inhibitor. Concomitant use is likely to lead to increased concentrations of temsirolimus.
Teniposide: (Moderate) Systemic exposure of teniposide, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of teniposide; monitor patients for potential adverse effects.
Tenofovir Alafenamide: (Minor) Caution is advised when administering tenofovir alafenamide concurrently with daclatasvir. Coadministration may result in increased tenofovir alafenamide plasma concentrations. Tenofovir alafenamide is a substrate of the drug transporters P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and the organic anion transport protein (OATP1B1 and 1B3); daclatasvir is an inhibitor all three transporters. If these drugs are administered together, closely monitor for tenofovir-associated adverse reactions. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Testosterone: (Minor) Systemic exposure of testosterone, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of testosterone; monitor patients for potential adverse effects.
Ticagrelor: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with ticagrelor, a moderate CYP3A4 inhibitor, increases daclatasvir serum concentrations. In addition, the therapeutic effects of ticagrelor, a P-glycoprotein (P-gp) substrate, may be increased by daclatasvir, a P-gp inhibitor. If these drugs are administered together, monitor patients for adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
Tipranavir: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as tipranavir boosted with ritonavir. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects. In addition, the therapeutic effects of tipranavir, a P-glycoprotein (P-gp) substrate, may be increased by daclatasvir, a P-gp inhibitor.
Tolazamide: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Tolbutamide: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Topotecan: (Major) Avoid coadministration of daclatasvir with oral topotecan due to increased topotecan exposure; daclatasvir may be administered with intravenous topotecan. Oral topotecan is a substrate of P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP); daclatasvir is a P-gp and BCRP inhibitor. Following escalating doses of a dual inhibitor of BCRP and P-gp, the AUC of topotecan lactone and total topotecan increased by approximately 2.5-fold compared to topotecan alone. Coadministration of a dual P-gp/BCRP inhibitor with intravenous topotecan increased total topotecan exposure by 1.2-fold and exposure to topotecan lactone by 1.1-fold.
Trandolapril; Verapamil: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with verapamil, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. In addition, the therapeutic effects of verapamil, a P-glycoprotein (P-gp) substrate, may be increased by daclatasvir, a P-gp inhibitor. If these drugs are administered together, monitor patients for adverse effects, such as hypotension, headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
Tucatinib: (Major) Reduce the daclatasvir dose to 30 mg PO once daily if coadministered with tucatinib due to increased daclatasvir exposure. Daclatasvir is a CYP3A4 substrate; tucatinib is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the daclatasvir AUC by 3-fold.
Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with daclatasvir. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a substrate of the BCRP and P-gp drug transporters; daclatasvir is a BCRP and P-gp inhibitor.
Ultralente Insulin: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Umeclidinium: (Moderate) Systemic exposure of umeclidinium; vilanterol, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of umeclidinium; vilanterol; monitor patients for potential adverse effects.
Umeclidinium; Vilanterol: (Moderate) Systemic exposure of umeclidinium; vilanterol, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of umeclidinium; vilanterol; monitor patients for potential adverse effects.
Valsartan: (Moderate) Systemic exposure of valsartan, a substrate of the drug transporter organic anion transporting polypeptides (OATP), may be increased when administered concurrently with daclatasvir, an OATP inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of valsartan; monitor patients for potential adverse effects.
Vemurafenib: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be increased to 90 mg PO once daily when administered in combination with moderate CYP3A4 inducers, such as vemurafenib. Taking these drugs together may decrease daclatasvir serum concentrations, potentially resulting in reduced antiviral efficacy and antimicrobial resistance. Conversely, the therapeutic effects of vemurafenib, a substrate of P-glycoprotein (P-gp), may be increased by daclatasvir, a P-gp inhibitor.
Venetoclax: (Major) Reduce the dose of venetoclax by at least 50% and monitor for venetoclax toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) if coadministered with daclatasvir due to the potential for increased venetoclax exposure. Resume the original venetoclax dose 2 to 3 days after discontinuation of daclatasvir. Venetoclax is a substrate of P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP); daclatasvir is an inhibitor of P-gp and BCRP. Coadministration with a single dose of another P-gp inhibitor increased venetoclax exposure by 78% in a drug interaction study.
Verapamil: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with verapamil, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. In addition, the therapeutic effects of verapamil, a P-glycoprotein (P-gp) substrate, may be increased by daclatasvir, a P-gp inhibitor. If these drugs are administered together, monitor patients for adverse effects, such as hypotension, headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
Voriconazole: (Moderate) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as voriconazole. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects.
Warfarin: (Moderate) Fluctuations in International Normalized Ratio (INR) have been observed in warfarin recipients who were also receiving treatment for hepatitis C virus (HCV) infections, including daclatasvir. It is recommended to closely monitor these patients for changes in INR both during and after discontinuation of the HCV treatment regimen.

Daklinza Oral Tab: 30mg, 60mg, 90mg

Adults

90 mg daily PO.

Geriatric

90 mg daily PO.

Adolescents

Safety and efficacy not established.

Children

Safety and efficacy not established.

Infants

Safety and efficacy not established.

Neonates

Safety and efficacy not established.

Daclatasvir is active against chronic infections caused by hepatitis C virus (HCV) genotypes 1 and 3. The drug prevents viral RNA replication and virion assembly by binding to the N-terminus of NS5A. This binding causes structural distortion, which results in impaired NS5A protein function.
 
HCV genotype 1a, 1b, and 3a replicons with reduced susceptibility to daclatasvir were selected in cell culture, and the genotype and phenotype of daclatasvir-resistant NS5A amino acid variants were identified. For genotype 1a, phenotypic analysis found single NS5A substitutions at M28T, Q30E, Q30H, Q30R, L31V, Y93C, Y93H, and Y93N resulted in 500-, 18,500-, 1,083-, 900-, 2,500-, 1,367-, 8,500-, and 34,833-fold reduced susceptibility to daclatasvir, respectively. For genotype 1b, single substitutions at L31V and Y93H, and combination substitutions at L31M/Y93H and L31V/y93H resulted in 33-, 30-, 16,000-, and 33,667-fold reductions in susceptibility to daclatasvir, respectively. Further, a P32-deletion (P32X) in genotype 1b reduced daclatasvir susceptibility by more than 1,000,000-fold. For genotype 3a, reductions in susceptibility to daclatasvir of 117-, 320-, 240-, and 3,733-fold were observed with single substitutions at A30K, L31F, L31I, and Y93H, respectively.
 
In clinical trials, 31 drug recipients were deem virologic failures (11 with genotype 1a, 1 with genotype 1b, 19 with genotype 3a). An analysis of these 31 patients found all harbored at least 1 NS5A resistance-associated substitution at the time of virologic failure. The most common substitution in genotype 3a-infected patients was Y93H, found in 17 of the 19 virologic failure subjects. For genotype 1a, the most common substitution occurred at position Q30 (Q30H/K/R; found in 8 of 11 patients). In addition to the NS5A substitutions, 6 patients were also found to have a virus with NS5B resistance-associated substitution deemed possibly associated with sofosbuvir resistance or exposure: A112T, L159F, E237G, Q355H (for genotype 1a) or S282T+Q355H (for genotype 3a).
 
Cross-resistance with other NS5A inhibitors is expected; however, resistance with other classes of direct-acting antiviral is not expected. The drug is NOT antagonistic with interferon alfa, NS3/4A protease inhibitors, NS5B nucleoside analogs inhibitors, or NS5B non-nucleoside inhibitors.

Daclatasvir is administered orally. Systemically absorbed daclatasvir has a steady state volume of distribution of approximately 47 L, and is extensively protein bound at 99%. Metabolism occurs via the hepatic isoenzymes CYP3A4. The feces are the main route of elimination, accounting for 88% of a radiolabeled dose, with urine accounting for only 6.6% of the dose. Daclatasvir has a terminal elimination half-life ranging from 12 to 15 hours.
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, P-glycoprotein (P-gp), organic anion transporting polypeptides (OATP1B1 and OATP1B3), breast cancer resistance protein (BCRP)
Daclatasvir is a substrate of the hepatic isoenzyme CYP3A4 and the drug transporter P-gp. The drug is also a P-gp inhibitor, and an inhibitor of the transporters OATP1B1, OATP1B3, and BCRP.

Oral Route

Based on in vitro data, the estimated absolute oral bioavailability of daclatasvir is 67%. Following oral administration, peak plasma concentrations are achieved within 2 hours, with steady state concentrations (AUC) reached after 4 days of once daily dosing. Pharmacokinetic parameters (i.e., AUC, Cmax, Cmin), increase in a dose proportional manner up to the recommended 60 mg dose. The drug may be administered with or without food. Low-fat, low-caloric meals do not alter the pharmacokinetic parameters; however, high-fat, high-caloric meals have been found to decrease the drugs AUC and Cmax by 23% and 28%, respectively, compared to fasting state.

Pregnancy

No human data are available regarding use of daclatasvir during pregnancy, and it is unknown if the drug poses a risk to the fetus or is associated with adverse reactions on the human reproductive system. The manufacturer advises caution and careful consideration when deciding if the drugs should be administered to a pregnant woman. In animal studies involving rat and rabbits, no evidence of fetal harm was observed following drug exposures during organogenesis that were 6- and 22-times, respectively, the recommended human dose of 60 mg. In certain patient populations, daclatasvir must be administered with ribavirin. Use of daclatasvir in combination with ribavirin is contraindicated in pregnant women. Ribavirin may cause birth defects and death of the exposed fetus; thus, the drug is contraindicated for use during pregnancy (FDA pregnancy risk category X) and in females who may become pregnant. Studies of ribavirin indicate teratogenic (e.g., malformations of skull, palate, eye, jaw, limbs, skeleton, and GI tract) or embryocidal properties in all of the animal species tested. To monitor maternal-fetal outcomes of pregnancies in female patients exposed to ribavirin during treatment and for 6 months following cessation of treatment, health care providers are encouraged to report any cases to the Ribavirin Pregnancy Registry; telephone (800) 593-2214. For patient who are also infected with HIV and taking concomitant antiretroviral agents, an Antiretroviral Pregnancy Registry is available at (800) 258-4263.

In certain patient populations, daclatasvir must be administered with ribavirin. Use of daclatasvir in combination with ribavirin is contraindicated in male partners of women who are pregnant. Ribavirin may cause birth defects and death of the exposed fetus. Ribavirin therapy also may cause male-mediated teratogenicity and is contraindicated for use in men whose female partners are pregnant. Studies of ribavirin indicate teratogenic (e.g., malformations of skull, palate, eye, jaw, limbs, skeleton, and GI tract) or embryocidal properties in all of the animal species tested. Patients and their partners are required use 2 reliable forms of effective contraception during treatment and for 6 months after use of the combination therapy. Patients who are not willing to practice strict contraception should not receive daclatasvir with ribavirin. Females must also undergo pregnancy testing immediately prior to initiation of therapy, monthly during therapy, and for 6 months post-therapy. To monitor maternal-fetal outcomes of pregnancies in female partners of male patients exposed to ribavirin during treatment and for 6 months following cessation of treatment, health care providers are encouraged to report any cases to the Ribavirin Pregnancy Registry; telephone (800) 593-2214. For patient who are also infected with HIV and taking concomitant antiretroviral agents, an Antiretroviral Pregnancy Registry is available at (800) 258-4263.