Daklinza

Daclatasvir is an antiviral medicine that prevents hepatitis C virus (HCV) from multiplying in your body.

Daclatasvir is used to treat genotype 3 chronic hepatitis C in adults without cirrhosis. This medicine is given together with another drug called sofosbuvir.

Daclatasvir may also be used for purposes not listed in this medication guide.

Serious drug interactions can occur when certain medicines are used together with daclatasvir. Tell each of your healthcare providers about all medicines you use now, and any medicine you start or stop using.

You should not use daclatasvir if you are allergic to it. If you take daclatasvir with sofosbuvir: There may be other reasons you should not take this combination treatment. Tell your doctor about all your medical conditions.

Some medicines can interact with daclatasvir and should not be used at the same time. Your doctor may need to change your treatment plan if you use any of the following drugs:

• rifampin;
• St. John's wort; or
• seizure medicine--carbamazepine, phenytoin.

To make sure daclatasvir is safe for you, tell your doctor if you have:

• liver problems other than hepatitis C;
• heart disease;
• if you also use amiodarone (a heart rhythm medicine); or
• if you have received a liver transplant.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether daclatasvir passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Daclatasvir is not approved for use by anyone younger than 18 years old.

Daklinza is a prescription medication used to treat chronic hepatitis C virus (HCV) genotype 3 infection. It is given in combination with sofosbuvir for 12 weeks. It is not known if Daklinza is safe and effective in children under 18 years of age.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Serious side effects have been reported with Daklinza. See the "Daklinza Precautions" section. 

Common side effects of Daklinza include the following:

• tiredness (fatigue)
• headache
• nausea
• diarrhea

Do not drive or operate heavy machinery until you know how this medication will affect you.

This is not a complete list of Daklinza side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away. 

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Daclatasvir is an antiviral medicine that prevents hepatitis C virus (HCV) from multiplying in your body.

Daclatasvir is used to treat genotype 3 chronic hepatitis C in adults without cirrhosis. This medicine is given together with another drug called sofosbuvir.

Daclatasvir may also be used for purposes not listed in this medication guide.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Taking daclatasvir will not prevent you from passing hepatitis C to other people. Do not have unprotected sex or share razors or toothbrushes. Talk with your doctor about safe ways to prevent HCV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person.

General

• Must be used in conjunction with other antivirals;1 do not use alone.1

• Specific multiple-drug regimen and duration of treatment depend on HCV genotype and patient population.1 119

• If sofosbuvir is permanently discontinued in a patient receiving daclatasvir, also discontinue daclatasvir.1

• HCV genotype 1a infection in patients with cirrhosis: Consider screening for presence of NS5A polymorphisms at M28, Q30, L31, and Y93 prior to initiation of multiple-drug regimen of daclatasvir and sofosbuvir (with or without ribavirin).1

Administration

Oral Administration

Administer orally once daily without regard to food.1

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Available as daclatasvir dihydrochloride;1 dosage expressed in terms of daclatasvir.1

Daclatasvir dosage may need to be reduced if used concomitantly with certain CYP3A inhibitors or daclatasvir dosage may need to be increased if used with certain CYP3A inducers (see Specific Drugs under Interactions).1 Do not reduce daclatasvir dosage because of adverse effects.1

Adults

Noncirrhotic or with compensated cirrhosis (Child-Pugh class A): 60 mg once daily in conjunction with sofosbuvir for a duration of 12 weeks.1

Decompensated cirrhosis (Child-Pugh class B or C): 60 mg once daily in conjunction with sofosbuvir and ribavirin.1 Usual treatment duration is 12 weeks, but optimal duration not established in those with Child-Pugh class C cirrhosis.1 Some experts recommend duration of 24 weeks for treatment of genotype 1a or 1b infection in cirrhotic patients.119

Noncirrhotic: 60 mg once daily in conjunction with sofosbuvir for a duration of 12 weeks.1

Compensated cirrhosis (Child-Pugh class A) or decompensated cirrhosis (Child-Pugh class B or C): 60 mg once daily in conjunction with sofosbuvir and ribavirin.1 Usual treatment duration is 12 weeks, but optimal duration not established in those with Child-Pugh class C impairment.1 Some experts recommend duration of 24 weeks for treatment of genotype 3 infection in cirrhotic patients.119

Some experts recommend 60 mg once daily in conjunction with sofosbuvir for a duration of 12 weeks;119 some patients (e.g., those with cirrhosis) may benefit from treatment duration of 24 weeks.119

Chronic HCV genotype 1 or genotype 3 infection: 60 mg once daily in conjunction with sofosbuvir and ribavirin.1 Usual treatment duration is 12 weeks.1

Generally, use the same daclatasvir dosage recommended for treatment of HCV infection in patients without HIV infection;1 119 consider that daclatasvir dosage may need to be increased or decreased when used concomitantly with certain HIV antiretroviral agents.1 119 (See Specific Drugs under Interactions.)

Multiple-drug regimen and duration of treatment are the same as those for patients without HIV infection.1

Special Populations

Hepatic Impairment

Mild, moderate, or severe hepatic impairment (Child-Pugh class A, B, or C): Dosage adjustments not needed.1

Renal Impairment

Mild, moderate, or severe renal impairment: Dosage adjustments not needed.1

Geriatric Patients

Dosage adjustments not needed.1

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

• Importance of using daclatasvir in conjunction with sofosbuvir (with or without ribavirin);1 do not use alone.1

• Advise patient to take daclatasvir once daily with or without food.1

• If a regimen of daclatasvir in conjunction with sofosbuvir (with or without ribavirin) is used in a patient receiving amiodarone, advise the patient about the risk of serious symptomatic bradycardia and the importance of immediately contacting a clinician if signs or symptoms of bradycardia (e.g., near-fainting or fainting, dizziness, lightheadedness, malaise, weakness, excessive tiredness, shortness of breath, chest pain, confusion, memory problems) occur.1

• Inform patients that the effect of HCV treatment on transmission of HCV is unknown;1 appropriate precautions should be taken to prevent transmission of the virus during treatment or in the event of treatment failure.1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 If used in multiple-drug regimen that includes ribavirin, advise men and women of importance of using 2 forms of effective contraception during and for 6 months after ribavirin therapy.349 377 (See Precautions Related to Multiple-drug Treatment Regimens under Cautions.)

• Importance of informing patients of other important precautionary information.1 (See Cautions.)

Daclatasvir is used together with sofosbuvir and with or without ribavirin to treat chronic hepatitis C infection.

This medicine is available only with your doctor's prescription.

Daklinza is indicated for use with sofosbuvir, with or without ribavirin, for the treatment of patients with chronic hepatitis C virus (HCV) genotype 1 or genotype 3 infection [see Dosage and Administration (2) and Clinical Studies (14)].

Limitations of Use:

5.1 Risk of Hepatitis B Virus Reactivation in Patients Coinfected with HCV and HBV

Hepatitis B virus (HBV) reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct-acting antivirals, and who were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive and also in patients with serologic evidence of resolved HBV infection (i.e., HBsAg negative and anti-HBc positive). HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients.

HBV reactivation is characterized as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA level. In patients with resolved HBV infection, reappearance of HBsAg can occur. Reactivation of HBV replication may be accompanied by hepatitis, i.e., increases in aminotransferase levels and, in severe cases, increases in bilirubin levels, liver failure, and death can occur.

Test all patients for evidence of current or prior HBV infection by measuring HBsAg and anti-HBc before initiating HCV treatment with Daklinza. In patients with serologic evidence of HBV infection, monitor for clinical and laboratory signs of hepatitis flare or HBV reactivation during HCV treatment with Daklinza and during post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated.

Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions

The concomitant use of Daklinza and other drugs may result in known or potentially significant drug interactions, some of which may lead to [see Contraindications (4) and Drug Interactions (7)]:

See Table 3 for drugs contraindicated with Daklinza due to loss of efficacy and possible development of resistance [see Contraindications (4)]. See Table 7 for steps to prevent or manage other possible and known significant drug interactions [see Drug Interactions (7)]. Consider the potential for drug interactions before and during Daklinza therapy, review concomitant medications during Daklinza therapy, and monitor for the adverse reactions associated with the concomitant drugs.

Serious Symptomatic Bradycardia When Coadministered with Sofosbuvir and Amiodarone

Postmarketing cases of symptomatic bradycardia and cases requiring pacemaker intervention have been reported when amiodarone is coadministered with sofosbuvir in combination with another HCV direct-acting antiviral, including Daklinza. A fatal cardiac arrest was reported in a patient receiving a sofosbuvir-containing regimen (ledipasvir/sofosbuvir). Bradycardia has generally occurred within hours to days, but cases have been observed up to 2 weeks after initiating HCV treatment. Patients also taking beta blockers or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. Bradycardia generally resolved after discontinuation of HCV treatment. The mechanism for this bradycardia effect is unknown.

Coadministration of amiodarone with Daklinza in combination with sofosbuvir is not recommended. For patients taking amiodarone who have no alternative treatment options and who will be coadministered Daklinza and sofosbuvir:

Patients who are taking sofosbuvir in combination with Daklinza who need to start amiodarone therapy due to no other alternative treatment options should undergo similar cardiac monitoring as outlined above.

Due to amiodarone’s long elimination half-life, patients discontinuing amiodarone just prior to starting sofosbuvir in combination with Daklinza should also undergo similar cardiac monitoring as outlined above.

Patients who develop signs or symptoms of bradycardia should seek medical evaluation immediately. Symptoms may include near-fainting or fainting, dizziness or lightheadedness, malaise, weakness, excessive tiredness, shortness of breath, chest pain, confusion, or memory problems [see Adverse Reactions (6.2) and Drug Interactions (7.3), Table 7].

Risks Associated with Ribavirin Combination Treatment

If Daklinza and sofosbuvir are administered with ribavirin, the warnings and precautions for ribavirin, in particular the pregnancy avoidance warning, apply to this combination regimen. Refer to the ribavirin prescribing information for a full list of the warnings and precautions for ribavirin.

Daklinza™ (dak lin za)
(daclatasvir)
tablets

This Patient Information has been approved by the U.S. Food and Drug Administration.

1344554A3
Revised February 2017

Daklinza is usually taken for 12 weeks. Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Daklinza must be given in combination with sofosbuvir and it should not be used alone.

You may take Daklinza with or without food.

You will need frequent blood tests to check your liver function.

Read the medication guide or patient instructions provided with each medication in your combination therapy. Do not change your doses or medication schedule without your doctor's advice. Every person with chronic hepatitis C should remain under the care of a doctor.

You should not stop using daclatasvir suddenly. Stopping suddenly could make your condition harder to treat with hepatitis C antiviral medicine.

If you have ever had hepatitis B, daclatasvir cause this condition to come back or get worse. You will need liver function tests during treatment and for several months after you stop using this medicine.

Store at room temperature away from moisture and heat.

Taking Daklinza will not prevent you from passing hepatitis C to other people. Do not have unprotected sex or share razors or toothbrushes. Talk with your doctor about safe ways to prevent HCV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person.