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DAKLINZA(daclatasvir) tablets

2016-01-28 08:13:28 来源: 作者: 【大中小】浏览:302次评论:0条

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use DAKLINZA safely and effectively. See full prescribing information for DAKLINZA.
DAKLINZA™ (daclatasvir) tablets, for oral use
Initial U.S. Approval: 2015

INDICATIONS AND USAGE

DAKLINZA is a hepatitis C virus (HCV) NS5A inhibitor indicated for use with sofosbuvir for the treatment of chronic HCV genotype 3 infection. (1)

Limitations of Use:

•: Sustained virologic response (SVR) rates are reduced in patients with cirrhosis. (14)

DOSAGE AND ADMINISTRATION

•: 60 mg taken orally once daily with or without food in combination with sofosbuvir. (2.1)
•: Recommended treatment duration: 12 weeks. (2.1)
•: Dose modification: Reduce dosage to 30 mg once daily with strong CYP3A inhibitors and increase dosage to 90 mg once daily with moderate CYP3A inducers. (2.2)

DOSAGE FORMS AND STRENGTHS

•: Tablet: 60 mg and 30 mg (3)

CONTRAINDICATIONS

•: Strong inducers of CYP3A, including phenytoin, carbamazepine, rifampin, and St. John’s wort. (4)

WARNINGS AND PRECAUTIONS

•: Bradycardia When Coadministered with Sofosbuvir and Amiodarone: Serious symptomatic bradycardia may occur in patients taking amiodarone with sofosbuvir in combination with another HCV direct-acting agent, including DAKLINZA, particularly in patients also receiving beta blockers or those with underlying cardiac comorbidities and/or advanced liver disease. Coadministration of amiodarone with DAKLINZA in combination with sofosbuvir is not recommended. In patients with no alternative treatment options, cardiac monitoring is recommended. ( 5.2, 6.2, 7.3)

ADVERSE REACTIONS

Most common adverse reactions (≥10%) observed with DAKLINZA in combination with sofosbuvir were headache and fatigue. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

•: Drug Interactions: Coadministration of DAKLINZA can alter the concentration of other drugs and other drugs may alter the concentration of daclatasvir. Consult the full prescribing information before use for contraindicated drugs and other potential drug-drug interactions. ( 2.2, 4, 5.1, 7, 12.3)

See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

Revised: 7/2015

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

2.2 Dosage Modification Due to Drug Interactions

2.3 Discontinuation of Therapy

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

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

5.2 Serious Symptomatic Bradycardia When Coadministered with Sofosbuvir and Amiodarone

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 Potential for Other Drugs to Affect DAKLINZA

7.2 Potential for DAKLINZA to Affect Other Drugs

7.3 Established and Potentially Significant Drug Interactions

7.4 Drugs without Clinically Significant Interactions with DAKLINZA

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Renal Impairment

8.7 Hepatic Impairment

8.8 Liver Transplant Patients

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

12.4 Microbiology

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

16.2 Storage

17 PATIENT COUNSELING INFORMATION

*: Sections or subsections omitted from the full prescribing information are not listed.

1 INDICATIONS AND USAGE

DAKLINZA is indicated for use with sofosbuvir for the treatment of patients with chronic hepatitis C virus (HCV) genotype 3 infection [see Dosage and Administration (2) and Clinical Studies (14)].

Limitations of Use:

•: Sustained virologic response (SVR) rates are reduced in HCV genotype 3-infected patients with cirrhosis receiving DAKLINZA in combination with sofosbuvir for 12 weeks [ see Clinical Studies (14)].

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

The recommended dosage of DAKLINZA is 60 mg, taken orally, once daily in combination with sofosbuvir for 12 weeks. DAKLINZA may be taken with or without food.

The optimal duration of DAKLINZA and sofosbuvir for patients with cirrhosis has not been established [see Clinical Studies (14)].

For specific dosage recommendations for sofosbuvir, refer to the respective prescribing information.

2.2 Dosage Modification Due to Drug Interactions

Refer to the drug interactions and contraindication sections for other drugs before coadministration with DAKLINZA.

Strong inhibitors of cytochrome P450 enzyme 3A (CYP3A): Reduce the dosage of DAKLINZA to 30 mg once daily when coadministered with strong CYP3A inhibitors using the 30 mg tablet [see Drug Interactions (7)].

Moderate CYP3A inducers: Increase the dosage of DAKLINZA to 90 mg once daily using an appropriate combination of tablets (three 30 mg tablets or one 60 mg and one 30 mg tablet) when coadministered with moderate CYP3A inducers [see Drug Interactions (7)].

Strong CYP3A inducers: DAKLINZA is contraindicated in combination with strong CYP3A inducers [see Contraindications (4)].

Dosage reduction of DAKLINZA for adverse reactions is not recommended.

2.3 Discontinuation of Therapy

If sofosbuvir is permanently discontinued in a patient receiving DAKLINZA with sofosbuvir, then DAKLINZA should also be discontinued.

3 DOSAGE FORMS AND STRENGTHS

•: Tablets: 60 mg daclatasvir (equivalent to 66 mg daclatasvir dihydrochloride), light green, biconvex, pentagonal, and debossed with “BMS” on one side and “215” on the other side.
•: Tablets: 30 mg daclatasvir (equivalent to 33 mg daclatasvir dihydrochloride), green, biconvex, pentagonal, and debossed with “BMS” on one side and “213” on the other side.

4 CONTRAINDICATIONS

•: DAKLINZA is contraindicated in combination with drugs that strongly induce CYP3A and, thus, may lead to lower exposure and loss of efficacy of DAKLINZA. Contraindicated drugs include, but are not limited to, those listed in Table 1 [ see Drug Interactions (7) and Clinical Pharmacology (12.3)].

Table 1: Drugs that are Contraindicated with DAKLINZA
Mechanism of Interaction	Clinical Comment	Drugs that are Contraindicated with DAKLINZAa
a This table is not a comprehensive list of all drugs that strongly induce CYP3A.
Strong induction of CYP3A by coadministered drug	May lead to loss of virologic response to DAKLINZA	Anticonvulsants phenytoin, carbamazepine
		Antimycobacterial agents rifampin
		Herbal products St. John’s wort (Hypericum perforatum)

5 WARNINGS AND PRECAUTIONS

5.1 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)]:

•: loss of therapeutic effect of DAKLINZA and possible development of resistance,
•: dosage adjustments of concomitant medications or DAKLINZA,
•: possible clinically significant adverse reactions from greater exposures of concomitant drugs or DAKLINZA.

See Table 1 for drugs contraindicated with DAKLINZA due to loss of efficacy and possible development of resistance [see Contraindications (4)]. See Table 3 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.