FDA Hepatitis Update - Labeling changes to Tyzeka (telbivudine) 600 mg tablets and oral solution 100 mg/5 mL reflect risk of resistance-associated substitutions

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FDA hepatitis electronic list serve. The purpose of the list serve is to relay

important information about viral hepatitis-related products and issues,

including product approvals, significant labeling changes, safety warnings,

notices of upcoming public meetings and alerts to proposed regulatory guidances

for comment.

Please do not reply to this message.

FDA has approved changes in product labeling for Tyzeka® (telbivudine) 600 mg

tablets and Tyzeka® (telbivudine) oral solution 100 mg/5 mL related to a higher

risk of developing resistance-associated substitutions in treated patients.

Indications and Usage-Under Section 1.1 Chronic Hepatitis B

The following points should be considered when initiating therapy with Tyzeka”:

• For HBeAg-positive patients, Tyzeka should only be initiated in patients with

HBV DNA less than 9 log10 copies/mL and ALT greater than or equal to 2x Upper

Limit of Normal (ULN) prior to treatment.

• For HBeAg-negative patients, Tyzeka should only be initiated in patients with

HBV DNA less than 7 log10 copies/mL prior to treatment.

• On-treatment response should guide continued therapy [see Dosage and

Administration (2.1) and Microbiology (12.4)].

Dosage and Administration-Under Section 2.1 Adults and Adolescents (16 years of

age and older):

Due to higher rates of resistance that may develop with longer term treatment

among patients with incomplete viral suppression, treatment should only be

initiated, if pre-treatment HBV DNA and ALT measurements are known, in the

following patient populations:

For HBeAg-positive patients, HBV DNA should be less than 9 log10 copies/mL and

ALT should be greater than or equal to 2x ULN prior to treatment with Tyzeka.

For HBeAg-negative patients, HBV DNA should be less than 7 log10 copies/mL prior

to treatment with Tyzeka.

HBV DNA levels should be monitored at 24 weeks of treatment to assure complete

viral suppression (HBV DNA less than 300 copies/mL). Alternate therapy should be

initiated for patients who have detectable HBV DNA after 24 weeks of treatment.

Optimal therapy should be guided by further resistance testing.

Dosage and Administration-Under Section 2.4-Duration of Therapy:

For patients with incomplete viral suppression (HBV DNA greater than or equal to

300 copies/mL) after 24 weeks of treatment, alternate therapy should be

instituted. HBV DNA should be monitored every 6 months to assure continued

response. If patients test positive for HBV DNA at any time after their initial

response, alternate treatment should be instituted. Optimal therapy should be

guided by resistance testing.

For more information on the role of Tyzeka in the treatment of of hepatitis,

please see the American Association for the Study of Liver Diseases (AASLD)

Practice Guidelines for Management of Chronic Hepatitis B

Klein

Office of Special Health Issues

Food and Drug Administration

Struble

Division of Antiviral Drug Products

Food and Drug Administration

Manage your FDA Subscriptions:

Questions about this service? support@...

Other inquiries? webmail@...

U.S. Food & Drug Administration (FDA) · 10903 New Hampshire Ave · Silver Spring,

MD 20993 · 800-439-1420

[Guest guest]

FDA hepatitis electronic list serve. The purpose of the list serve is to relay

important information about viral hepatitis-related products and issues,

including product approvals, significant labeling changes, safety warnings,

notices of upcoming public meetings and alerts to proposed regulatory guidances

for comment.

Please do not reply to this message.

FDA has approved changes in product labeling for Tyzeka® (telbivudine) 600 mg

tablets and Tyzeka® (telbivudine) oral solution 100 mg/5 mL related to a higher

risk of developing resistance-associated substitutions in treated patients.

Indications and Usage-Under Section 1.1 Chronic Hepatitis B

The following points should be considered when initiating therapy with Tyzeka”:

• For HBeAg-positive patients, Tyzeka should only be initiated in patients with

HBV DNA less than 9 log10 copies/mL and ALT greater than or equal to 2x Upper

Limit of Normal (ULN) prior to treatment.

• For HBeAg-negative patients, Tyzeka should only be initiated in patients with

HBV DNA less than 7 log10 copies/mL prior to treatment.

• On-treatment response should guide continued therapy [see Dosage and

Administration (2.1) and Microbiology (12.4)].

Dosage and Administration-Under Section 2.1 Adults and Adolescents (16 years of

age and older):

Due to higher rates of resistance that may develop with longer term treatment

among patients with incomplete viral suppression, treatment should only be

initiated, if pre-treatment HBV DNA and ALT measurements are known, in the

following patient populations:

For HBeAg-positive patients, HBV DNA should be less than 9 log10 copies/mL and

ALT should be greater than or equal to 2x ULN prior to treatment with Tyzeka.

For HBeAg-negative patients, HBV DNA should be less than 7 log10 copies/mL prior

to treatment with Tyzeka.

HBV DNA levels should be monitored at 24 weeks of treatment to assure complete

viral suppression (HBV DNA less than 300 copies/mL). Alternate therapy should be

initiated for patients who have detectable HBV DNA after 24 weeks of treatment.

Optimal therapy should be guided by further resistance testing.

Dosage and Administration-Under Section 2.4-Duration of Therapy:

For patients with incomplete viral suppression (HBV DNA greater than or equal to

300 copies/mL) after 24 weeks of treatment, alternate therapy should be

instituted. HBV DNA should be monitored every 6 months to assure continued

response. If patients test positive for HBV DNA at any time after their initial

response, alternate treatment should be instituted. Optimal therapy should be

guided by resistance testing.

For more information on the role of Tyzeka in the treatment of of hepatitis,

please see the American Association for the Study of Liver Diseases (AASLD)

Practice Guidelines for Management of Chronic Hepatitis B

Klein

Office of Special Health Issues

Food and Drug Administration

Struble

Division of Antiviral Drug Products

Food and Drug Administration

Manage your FDA Subscriptions:

Questions about this service? support@...

Other inquiries? webmail@...

U.S. Food & Drug Administration (FDA) · 10903 New Hampshire Ave · Silver Spring,

MD 20993 · 800-439-1420

[Guest guest]

FDA hepatitis electronic list serve. The purpose of the list serve is to relay

important information about viral hepatitis-related products and issues,

including product approvals, significant labeling changes, safety warnings,

notices of upcoming public meetings and alerts to proposed regulatory guidances

for comment.

Please do not reply to this message.

FDA has approved changes in product labeling for Tyzeka® (telbivudine) 600 mg

tablets and Tyzeka® (telbivudine) oral solution 100 mg/5 mL related to a higher

risk of developing resistance-associated substitutions in treated patients.

Indications and Usage-Under Section 1.1 Chronic Hepatitis B

The following points should be considered when initiating therapy with Tyzeka”:

• For HBeAg-positive patients, Tyzeka should only be initiated in patients with

HBV DNA less than 9 log10 copies/mL and ALT greater than or equal to 2x Upper

Limit of Normal (ULN) prior to treatment.

• For HBeAg-negative patients, Tyzeka should only be initiated in patients with

HBV DNA less than 7 log10 copies/mL prior to treatment.

• On-treatment response should guide continued therapy [see Dosage and

Administration (2.1) and Microbiology (12.4)].

Dosage and Administration-Under Section 2.1 Adults and Adolescents (16 years of

age and older):

Due to higher rates of resistance that may develop with longer term treatment

among patients with incomplete viral suppression, treatment should only be

initiated, if pre-treatment HBV DNA and ALT measurements are known, in the

following patient populations:

For HBeAg-positive patients, HBV DNA should be less than 9 log10 copies/mL and

ALT should be greater than or equal to 2x ULN prior to treatment with Tyzeka.

For HBeAg-negative patients, HBV DNA should be less than 7 log10 copies/mL prior

to treatment with Tyzeka.

HBV DNA levels should be monitored at 24 weeks of treatment to assure complete

viral suppression (HBV DNA less than 300 copies/mL). Alternate therapy should be

initiated for patients who have detectable HBV DNA after 24 weeks of treatment.

Optimal therapy should be guided by further resistance testing.

Dosage and Administration-Under Section 2.4-Duration of Therapy:

For patients with incomplete viral suppression (HBV DNA greater than or equal to

300 copies/mL) after 24 weeks of treatment, alternate therapy should be

instituted. HBV DNA should be monitored every 6 months to assure continued

response. If patients test positive for HBV DNA at any time after their initial

response, alternate treatment should be instituted. Optimal therapy should be

guided by resistance testing.

For more information on the role of Tyzeka in the treatment of of hepatitis,

please see the American Association for the Study of Liver Diseases (AASLD)

Practice Guidelines for Management of Chronic Hepatitis B

Klein

Office of Special Health Issues

Food and Drug Administration

Struble

Division of Antiviral Drug Products

Food and Drug Administration

Manage your FDA Subscriptions:

Questions about this service? support@...

Other inquiries? webmail@...

U.S. Food & Drug Administration (FDA) · 10903 New Hampshire Ave · Silver Spring,

MD 20993 · 800-439-1420

[Guest guest]

FDA hepatitis electronic list serve. The purpose of the list serve is to relay

important information about viral hepatitis-related products and issues,

including product approvals, significant labeling changes, safety warnings,

notices of upcoming public meetings and alerts to proposed regulatory guidances

for comment.

Please do not reply to this message.

FDA has approved changes in product labeling for Tyzeka® (telbivudine) 600 mg

tablets and Tyzeka® (telbivudine) oral solution 100 mg/5 mL related to a higher

risk of developing resistance-associated substitutions in treated patients.

Indications and Usage-Under Section 1.1 Chronic Hepatitis B

The following points should be considered when initiating therapy with Tyzeka”:

• For HBeAg-positive patients, Tyzeka should only be initiated in patients with

HBV DNA less than 9 log10 copies/mL and ALT greater than or equal to 2x Upper

Limit of Normal (ULN) prior to treatment.

• For HBeAg-negative patients, Tyzeka should only be initiated in patients with

HBV DNA less than 7 log10 copies/mL prior to treatment.

• On-treatment response should guide continued therapy [see Dosage and

Administration (2.1) and Microbiology (12.4)].

Dosage and Administration-Under Section 2.1 Adults and Adolescents (16 years of

age and older):

Due to higher rates of resistance that may develop with longer term treatment

among patients with incomplete viral suppression, treatment should only be

initiated, if pre-treatment HBV DNA and ALT measurements are known, in the

following patient populations:

For HBeAg-positive patients, HBV DNA should be less than 9 log10 copies/mL and

ALT should be greater than or equal to 2x ULN prior to treatment with Tyzeka.

For HBeAg-negative patients, HBV DNA should be less than 7 log10 copies/mL prior

to treatment with Tyzeka.

HBV DNA levels should be monitored at 24 weeks of treatment to assure complete

viral suppression (HBV DNA less than 300 copies/mL). Alternate therapy should be

initiated for patients who have detectable HBV DNA after 24 weeks of treatment.

Optimal therapy should be guided by further resistance testing.

Dosage and Administration-Under Section 2.4-Duration of Therapy:

For patients with incomplete viral suppression (HBV DNA greater than or equal to

300 copies/mL) after 24 weeks of treatment, alternate therapy should be

instituted. HBV DNA should be monitored every 6 months to assure continued

response. If patients test positive for HBV DNA at any time after their initial

response, alternate treatment should be instituted. Optimal therapy should be

guided by resistance testing.

For more information on the role of Tyzeka in the treatment of of hepatitis,

please see the American Association for the Study of Liver Diseases (AASLD)

Practice Guidelines for Management of Chronic Hepatitis B

Klein

Office of Special Health Issues

Food and Drug Administration

Struble

Division of Antiviral Drug Products

Food and Drug Administration

Manage your FDA Subscriptions:

Questions about this service? support@...

Other inquiries? webmail@...

U.S. Food & Drug Administration (FDA) · 10903 New Hampshire Ave · Silver Spring,

MD 20993 · 800-439-1420