Daclatasvir

• Tablets: 30 and 60 mg

• Daclatasvir should be stored at room temperature, between 20 C to 25 C (68 F to 77 F).

• Daclatasvir directly blocks replication of HCV by interfering with a hepatitis C virus protein called nonstructural protein 5A (NS5A). Daclatasvir interferes with proteins and processes needed by hepatitis C virus to multiply and make new viruses, thus reducing the overall viral load. The efficacy of Daclatasvir has been established in subjects with hepatitis C virus genotypes 1 and 3.
• Daclatasvir is given with sofosbuvir and may be administered with or without ribavirin. In clinical studies, 95% of patients were cured after 12 weeks of treatment with daclatasvir plus sofosbuvir with or without ribavirin. Cure was defined as undetectable levels of hepatitis C virus in the blood when measured three months after the completion of treatment.

• The FDA approved daclatasvir in February 2016.

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Daclatasvir is part of the drug class:

• Other antivirals

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• medications that block a protein in the body (CYP3A4) such as some macrolide antibiotics (clarithromycin, telithromycin), some HIV protease inhibitors (indinavir, nelfinavir, ritonavir, saquinavir), some HCV protease inhibitors (boceprevir, telaprevir), some azole antifungals (ketoconazole, itraconazole, posaconazole, voriconazole), conivaptan (Vaprisol), delavirdine (Rescriptor), and nefazodone
• medications that increase the activity of the enzyme CYP3A4 such as carbamazepine (Tegretol, Equetro, Carbatrol), phenobarbital, phenytoin (Dilantin), rifampin (Rifadin), St John's wort, and nimodipine (Nimotop)
• anticoagulant (blood thinner) medications such as warfarin (Coumadin, Jantoven), heparin, enoxaparin (Lovenox), fondaparinux (Arixtra), rivaroxaban (Xarelto), and  apixaban (Eliquis), and dabigatran (Pradaxa)
• amiodarone (Cordarone, Pacerone)
• digoxin (Lanoxin)
• medications used to lower cholesterol known as "statins" such as simvastatin (Zocor) and atorvastatin (Lipitor)

This is not a complete list of daclatasvir drug interactions. Ask your doctor or pharmacist for more information. 

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if daclatasvir is excreted in human breast milk or if it will harm your nursing baby. Because many drugs are present in human milk and because of the potential for serious adverse reactions in nursing infants from daclatasvir, your doctor will determine the risk versus benefit of using this medication.

Take daclatasvir exactly as your healthcare provider tells you to.

• Do not change your dose unless your healthcare provider tells you to.
• Do not stop taking daclatasvir without first talking with your healthcare provider.
• Take daclatasvir 1 time each day with or without food.
• If you miss a dose of daclatasvir, take the missed dose as soon as you remember the same day. Take the next dose at your regular time. 
• If you miss a dose of daclatasvir and remember the next day, skip the missed dose. Take the next dose at your regular time. Do not take 2 doses of daclatasvir at the same time to make up for the missed dose.
• If you take too much daclatasvir, call your healthcare provider or go to the nearest hospital emergency room right away.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose and duration your doctor recommends may be based on the following:

• other medications you are taking
• how you respond to this medication
• the condition of your liver

The recommended usage of daclatasvir to treat chronic hepatitis C virus is 60 mg taken orally once daily with or without food in combination with sofosbuvir. The recommended treatment duration is 12 weeks.

• Dose modification: Reduce dosage to 30 mg once daily with strong CYP3A4 inhibitors and increase dosage to 90 mg once daily with moderate CYP3A4 inducers.

• Store daclatasvir at room temperature between 68°F and 77°F (20°C and 25°C).
• Keep this and all medications out of the reach of children. 

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.

Refer to adult dosing.

Concerns related to adverse effects:

• Bradycardia: When used in combination with sofosbuvir and amiodarone, symptomatic bradycardia (eg, near-fainting, dizziness, lightheadedness, malaise, weakness, excessive tiredness, shortness of breath, chest pain, confusion, memory problems) has been reported; pacemaker intervention may be required. Bradycardia generally occurs within hours or days but has been observed up to 2 weeks after treatment initiation. Risk factors include concomitant beta blocker use, underlying cardiac morbidities, and/or advanced hepatic disease. Patients receiving amiodarone (with no alternate treatment options) and initiating daclatasvir and sofosbuvir treatment, and patients on daclatasvir and sofosbuvir treatment who are initiating amiodarone therapy should have inpatient cardiac monitoring for the first 48 hours of amiodarone coadministration and daily outpatient self-monitoring through at least the first 2 weeks of treatment. Patients discontinuing amiodarone just prior to starting daclatasvir and sofosbuvir treatment should also undergo similar cardiac monitoring procedures. Bradycardia usually resolves after HCV treatment discontinuation.

Disease-related concerns:

• Cardiovascular disease: Patients with underlying cardiac morbidities and also taking concomitant amiodarone are at increased risk for symptomatic bradycardia; use with caution and monitor for bradycardia.

• Hepatic disease: Patients with advanced hepatic disease and also taking concomitant amiodarone are at increased risk for symptomatic bradycardia; use with caution. Sustained virologic response rates are reduced in HCV genotype 3-infected patients with cirrhosis. Optimal duration of treatment for HCV genotype 3-infected patients with cirrhosis or HCV genotype 1 patients with Child-Pugh class C cirrhosis has not been established.

• Hepatitis B virus reactivation: [US Boxed Warning]: Hepatitis B virus (HBV) reactivation has been reported in hepatitis C virus (HCV)/HBV coinfected patients who were receiving or had completed treatment with HCV direct-acting antivirals and were not receiving HBV antiviral therapy; some cases have resulted in fulminant hepatitis, hepatic failure, and death. Test all patients for evidence of current or prior HBV infection prior to initiation of daclatasvir; monitor HCV/HBV co-infected patients for hepatitis flare or HBV reactivation during treatment and post-treatment follow-up. Initiate treatment for HBV infection as clinically indicated. HBV reactivation has been reported in HBsAg positive patients and in patients with serologic evidence of resolved HBV infection (ie, HBsAg negative and anti-HBc positive) and is characterized by an abrupt increase in HBV replication manifested as a rapid increase in serum HBV DNA level; reappearance of HBsAg may occur in patients with resolved HBV infection. Risk of HBV reactivation may be increased in patients receiving certain immunosuppressants or chemotherapeutic agents.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Appropriate use: Do not use as monotherapy; use only in combination with other antihepatitis C virus drugs.

Applies to daclatasvir: oral tablet

Along with its needed effects, daclatasvir may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking daclatasvir:

• Chest pain or discomfort
• lightheadedness, dizziness, or fainting
• slow or irregular heartbeat
• unusual tiredness

Some side effects of daclatasvir may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Headache
• nausea

• Diarrhea

No adjustment recommended.

Comments:
-The manufacturer product information for sofosbuvir and ribavirin should be consulted regarding use in patients with renal dysfunction.

Administration advice:
-Before starting this drug, test all patients for evidence of current/prior HBV infection; measure hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc).
-Use in combination with sofosbuvir (with or without ribavirin); do not use alone.
-Before starting this drug and sofosbuvir (with or without ribavirin), consider screening HCV genotype 1a-infected patients with cirrhosis for nonstructural protein 5A (NS5A) polymorphisms at amino acid positions M28, Q30, L31, and Y93.
-May administer without regard to food
-Consult the manufacturer product information regarding missed doses.

General:
-Limitations of use: Sustained virologic response (SVR12) rates were reduced in HCV genotype 3-infected patients with cirrhosis using this drug with sofosbuvir for 12 weeks.
-Before starting therapy, the manufacturer product information for coadministered HCV antiviral drugs should be consulted for additional information.

Patient advice:
-Read the US FDA-approved patient labeling (Patient Information).
-Avoid missing doses and complete the entire course of therapy.

Amounts of this drug in breast milk are most likely very low as it is highly bound to maternal plasma proteins.

LactMed: If the mother requires this drug, it is not a reason to discontinue breastfeeding; some experts recommend against breastfeeding when this drug is used with ribavirin. -According to some authorities: Breastfeeding is not recommended during use of this drug. Excreted into human milk: Unknown Excreted into animal milk: Yes Comments: -This drug has not been studied in nursing mothers receiving treatment for hepatitis C virus infection. -Developmental and health benefits of breastfeeding should be considered as well as the mother's clinical need for this drug. -The effects in the nursing infant are unknown; potential side effects in the breastfed child due to this drug or the mother's underlying condition should be considered. -The manufacturer product information for ribavirin and/or peginterferon alfa should be consulted (if applicable).