Daclatasvir

Class and Category

Pharmacologic Class: Hepatitis C virus NS5A inhibitor

Therapeutic Class: Anti-viral

Indications and Dosages

As an adjunct to treat chronic hepatitis C virus (HCV) genotype 1 or genotype 3 infection concomitantly with sofosbuvir therapy and with or without ribavirin therapy

TABLETS

Adults: 

60 mg once daily for 12 wk.

Dosage Adjustment:

For patients taking certain HIV antiviral agents such as atazanavir with ritonavir, indinavir, nelfinavir, or saquinavir and strong CYP3A inhibitors, the dosage is reduced to 30 mg once daily. For patients taking moderate CYP3A inducers or nevirapine, the dosage is increased to 90 mg once daily.

Mechanism of Action

Inhibits both viral RNA replication and virion assembly against the hepatitis C virus to destroy it.

Contraindications

Concurrent therapy with drugs that strongly induce CYP3A, such as carbamazepine, phenytoin, rifampin, or St. John’s wort; hypersensitivity to daclatasvir or its components.

Interactions

DRUGS

Amiodarone, Sofosbuvir: Increased risk of significant bradycardia

Buprenorphine, Buprenorphine/Naloxone: Possible increased risk of buprenorphine-associated adverse reactions dabigatran etexilate mesylate: Increased plasma dabigatran level with increased risk of adverse reactions

Digoxin: Increased risk of digitalis toxicity

HMG-CoA reductase inhibitors such as Atorvastatin, Fluvastatin, Pitavastatin, Pravastatin, Rosuvastatin, Simvastatin: Increased plasma concentration of HMGCoA reductase inhibitors with increased risk of adverse reactions. 

Moderate CYP3A inducers such as bosentan, dexamethasone, modafinil, nafcillin, rifapentine; non-nucleoside reverse transcriptase inhibitors (NNRTI) such as efavirenz, etravirine, nevirapine: Possibly decreased plasma daclatasvir level with possible decreased effectiveness.

Other Antiretrovirals such as atazanavir/ cobicistat, elvitegravir /cobicistat/ emtricitabine/ tenofovir disoproxil fumarate; protease inhibitors such as atazanavir with ritonavir, indinavir, nelfinavir, saquinavir; strong CYP3A inhibitors such as clarithromycin, itraconazole, ketoconazole, nefazodone, posaconazole, telithromycin, voriconazole: Possibly increased plasma daclatasvir level with possible increased risk of adverse reactions

Adverse Reactions

CNS: Dizziness, fatigue, headache, insomnia, somnolence

CV: Bradycardia

GI: Diarrhea, elevated liver and pancreatic enzymes, hyperbilirubinemia, nausea

HEME: Anemia

SKIN: Rash

Childbearing Considerations

PREGNANCY

• It is not known if drug causes fetal harm although when given in combination with sofosbuvir and ribavirin, it is contraindicated during pregnancy.
• Use with caution only if benefit to mother outweighs potential risk to fetus.

LACTATION

• It is not known if drug is present in breast milk.
• The patient should check with prescriber before breastfeeding.

REPRODUCTION

• Women of childbearing age should use effective contraception during combination therapy with sofosbuvir along with ribavirin and for 6 months after combination therapy has been discontinued.
• Known or suspected pregnancy should be reported immediately.

Nursing Considerations

• Know that patients should be tested for hepatitis B before starting daclatasvir therapy because HBV reactivation has occurred in HCV/HBV co-infected patients when given treatment with HCV direct-acting antivirals such as daclatasvir who were not receiving HBV antiviral therapy. Fulminant hepatitis, hepatic failure, and even death have occurred. Monitor co-infected patients for HBV reactivation or hepatitis flare during daclatasvir therapy. If HBV infection is detected, expect treatment to be given.
• Be aware that daclatasvir must be given with sofosbuvir, with or without ribavirin, in the treatment of chronic hepatitis C. If sofosbuvir is discontinued, know that daclatasvir should also be discontinued.

WARNING: Monitor the patient’s heart rate closely, as serious symptomatic bradycardia may occur because of coadministration with sofosbuvir and amiodarone. Bradycardia most often occurs during the first 2 weeks of daclatasvir therapy. Expect the patient to have cardiac monitoring in an inpatient setting for the first 48 hr of daclatasvir therapy, followed by patient monitoring of pulse for the first 2 weeks of therapy. Know that patients at greater risk for bradycardia include patients receiving amiodarone or beta-blocker therapy or patients who have advanced liver disease or underlying cardiac disease.

PATIENT TEACHING

• Tell the patient that daclatasvir is never prescribed alone to treat hepatitis C and will be combined with another drug called sofosbuvir and possibly a third drug called ribavirin.
• Instruct patient to take daclatasvir once daily at the same time every day after taking the pulse.
• Stress the importance of not stopping daclatasvir therapy without the prescriber's knowledge.
• Inform the patient that HBV reactivation can occur in patients co-infected with HBV during or after treatment of HCV infection. Tell the patient to inform the prescriber if she has a history of hepatitis B.
• Tell the patient to notify all prescribers of daclatasvir therapy, because significant drug interactions can occur between daclatasvir and many other drugs.

WARNING Instruct patient how to take a pulse. Stress is the importance of the patient seeking immediate medical attention if she develops signs or symptoms of bradycardia such as chest pain, confusion, dizziness, excessive tiredness, fainting, lightheadedness, malaise, shortness of breath, or weakness.

• Instruct female patients of childbearing age to avoid pregnancy during therapy and for 6 months after completion of treatment. Tell her to notify the prescriber if pregnancy occurs or is suspected.
• Advise mothers who wish to breastfeed to discuss the benefits and risks with the prescriber before doing so.