Elizabeth Mechcatie

The Food and Drug Administration on April 6 approved vandetanib for the treatment of metastatic medullary thyroid cancer in adults – making it the first drug approved for this rare cancer.

Vandetanib is indicated for adults with metastatic medullary thyroid cancer, "who are ineligible for surgery and who have disease that is growing or causing symptoms," the agency said. It is administered orally once a day.

Approval was based on an international phase III study that compared treatment with oral vandetanib, 300 mg once a day, with placebo in 331 patients with unresectable locally advanced or metastatic medically thyroid cancer. The risk of progression with vandetanib was reduced by 54%, compared with placebo, a significant effect.

Among those on placebo, median progression-free survival was 16.4 months, compared with at least 22.6 months among those on vandetanib, according to the FDA statement, which added: "It is too early to determine the median progression-free survival in patients treated with vandetanib or to tell whether they will live longer (overall survival) compared to patients treated with placebo." Diarrhea, rash, nausea, high blood pressure, headache, fatigue, decreased appetite, and abdominal pain were among the adverse effects associated with treatment. In the study, serious adverse events resulted in five deaths in patients treated with vandetanib, according to the FDA; causes included breathing complications, heart failure, and sepsis.

Because vandetanib can cause QT interval prolongation, it is being approved with a Risk Evaluation and Mitigation Strategy (REMS) to inform health care professionals about cardiac risks and will be available through a restricted distribution program, so that only health care professionals and pharmacies certified through the vandetanib REMS program will be able to prescribe and dispense the product. Patients also will be given a medication guide that explains the risks of treatment.

An estimated 3%-5% of all thyroid cancers are medullary thyroid cancer, and the incidence of this cancer in the United States in 2010 was about 1,300-2,200 patients, according to the FDA.

There is no trade name yet for the drug, manufactured by AstraZeneca Pharmaceuticals.

The Food and Drug Administration on April 6 approved vandetanib for the treatment of metastatic medullary thyroid cancer in adults – making it the first drug approved for this rare cancer.

Vandetanib is indicated for adults with metastatic medullary thyroid cancer, "who are ineligible for surgery and who have disease that is growing or causing symptoms," the agency said. It is administered orally once a day.

Approval was based on an international phase III study that compared treatment with oral vandetanib, 300 mg once a day, with placebo in 331 patients with unresectable locally advanced or metastatic medically thyroid cancer. The risk of progression with vandetanib was reduced by 54%, compared with placebo, a significant effect.

Among those on placebo, median progression-free survival was 16.4 months, compared with at least 22.6 months among those on vandetanib, according to the FDA statement, which added: "It is too early to determine the median progression-free survival in patients treated with vandetanib or to tell whether they will live longer (overall survival) compared to patients treated with placebo." Diarrhea, rash, nausea, high blood pressure, headache, fatigue, decreased appetite, and abdominal pain were among the adverse effects associated with treatment. In the study, serious adverse events resulted in five deaths in patients treated with vandetanib, according to the FDA; causes included breathing complications, heart failure, and sepsis.

Because vandetanib can cause QT interval prolongation, it is being approved with a Risk Evaluation and Mitigation Strategy (REMS) to inform health care professionals about cardiac risks and will be available through a restricted distribution program, so that only health care professionals and pharmacies certified through the vandetanib REMS program will be able to prescribe and dispense the product. Patients also will be given a medication guide that explains the risks of treatment.

An estimated 3%-5% of all thyroid cancers are medullary thyroid cancer, and the incidence of this cancer in the United States in 2010 was about 1,300-2,200 patients, according to the FDA.

There is no trade name yet for the drug, manufactured by AstraZeneca Pharmaceuticals.

The Food and Drug Administration on April 6 approved vandetanib for the treatment of metastatic medullary thyroid cancer in adults – making it the first drug approved for this rare cancer.

Vandetanib is indicated for adults with metastatic medullary thyroid cancer, "who are ineligible for surgery and who have disease that is growing or causing symptoms," the agency said. It is administered orally once a day.

Approval was based on an international phase III study that compared treatment with oral vandetanib, 300 mg once a day, with placebo in 331 patients with unresectable locally advanced or metastatic medically thyroid cancer. The risk of progression with vandetanib was reduced by 54%, compared with placebo, a significant effect.

Among those on placebo, median progression-free survival was 16.4 months, compared with at least 22.6 months among those on vandetanib, according to the FDA statement, which added: "It is too early to determine the median progression-free survival in patients treated with vandetanib or to tell whether they will live longer (overall survival) compared to patients treated with placebo." Diarrhea, rash, nausea, high blood pressure, headache, fatigue, decreased appetite, and abdominal pain were among the adverse effects associated with treatment. In the study, serious adverse events resulted in five deaths in patients treated with vandetanib, according to the FDA; causes included breathing complications, heart failure, and sepsis.

Because vandetanib can cause QT interval prolongation, it is being approved with a Risk Evaluation and Mitigation Strategy (REMS) to inform health care professionals about cardiac risks and will be available through a restricted distribution program, so that only health care professionals and pharmacies certified through the vandetanib REMS program will be able to prescribe and dispense the product. Patients also will be given a medication guide that explains the risks of treatment.

An estimated 3%-5% of all thyroid cancers are medullary thyroid cancer, and the incidence of this cancer in the United States in 2010 was about 1,300-2,200 patients, according to the FDA.

There is no trade name yet for the drug, manufactured by AstraZeneca Pharmaceuticals.

The Food and Drug Administration on April 6 approved vandetanib for the treatment of metastatic medullary thyroid cancer in adults – making it the first drug approved for this rare cancer.

Vandetanib is indicated for adults with metastatic medullary thyroid cancer, "who are ineligible for surgery and who have disease that is growing or causing symptoms," the agency said. It is administered orally once a day.

Approval was based on an international phase III study that compared treatment with oral vandetanib, 300 mg once a day, with placebo in 331 patients with unresectable locally advanced or metastatic medically thyroid cancer. The risk of progression with vandetanib was reduced by 54%, compared with placebo, a significant effect.

Among those on placebo, median progression-free survival was 16.4 months, compared with at least 22.6 months among those on vandetanib, according to the FDA statement, which added: "It is too early to determine the median progression-free survival in patients treated with vandetanib or to tell whether they will live longer (overall survival) compared to patients treated with placebo." Diarrhea, rash, nausea, high blood pressure, headache, fatigue, decreased appetite, and abdominal pain were among the adverse effects associated with treatment. In the study, serious adverse events resulted in five deaths in patients treated with vandetanib, according to the FDA; causes included breathing complications, heart failure, and sepsis.

Because vandetanib can cause QT interval prolongation, it is being approved with a Risk Evaluation and Mitigation Strategy (REMS) to inform health care professionals about cardiac risks and will be available through a restricted distribution program, so that only health care professionals and pharmacies certified through the vandetanib REMS program will be able to prescribe and dispense the product. Patients also will be given a medication guide that explains the risks of treatment.

An estimated 3%-5% of all thyroid cancers are medullary thyroid cancer, and the incidence of this cancer in the United States in 2010 was about 1,300-2,200 patients, according to the FDA.

There is no trade name yet for the drug, manufactured by AstraZeneca Pharmaceuticals.

The Food and Drug Administration on April 6 approved vandetanib for the treatment of metastatic medullary thyroid cancer in adults – making it the first drug approved for this rare cancer.

Vandetanib is indicated for adults with metastatic medullary thyroid cancer, "who are ineligible for surgery and who have disease that is growing or causing symptoms," the agency said. It is administered orally once a day.

Approval was based on an international phase III study that compared treatment with oral vandetanib, 300 mg once a day, with placebo in 331 patients with unresectable locally advanced or metastatic medically thyroid cancer. The risk of progression with vandetanib was reduced by 54%, compared with placebo, a significant effect.

Among those on placebo, median progression-free survival was 16.4 months, compared with at least 22.6 months among those on vandetanib, according to the FDA statement, which added: "It is too early to determine the median progression-free survival in patients treated with vandetanib or to tell whether they will live longer (overall survival) compared to patients treated with placebo." Diarrhea, rash, nausea, high blood pressure, headache, fatigue, decreased appetite, and abdominal pain were among the adverse effects associated with treatment. In the study, serious adverse events resulted in five deaths in patients treated with vandetanib, according to the FDA; causes included breathing complications, heart failure, and sepsis.

Because vandetanib can cause QT interval prolongation, it is being approved with a Risk Evaluation and Mitigation Strategy (REMS) to inform health care professionals about cardiac risks and will be available through a restricted distribution program, so that only health care professionals and pharmacies certified through the vandetanib REMS program will be able to prescribe and dispense the product. Patients also will be given a medication guide that explains the risks of treatment.

An estimated 3%-5% of all thyroid cancers are medullary thyroid cancer, and the incidence of this cancer in the United States in 2010 was about 1,300-2,200 patients, according to the FDA.

There is no trade name yet for the drug, manufactured by AstraZeneca Pharmaceuticals.

The Food and Drug Administration on April 6 approved vandetanib for the treatment of metastatic medullary thyroid cancer in adults – making it the first drug approved for this rare cancer.

Vandetanib is indicated for adults with metastatic medullary thyroid cancer, "who are ineligible for surgery and who have disease that is growing or causing symptoms," the agency said. It is administered orally once a day.

Approval was based on an international phase III study that compared treatment with oral vandetanib, 300 mg once a day, with placebo in 331 patients with unresectable locally advanced or metastatic medically thyroid cancer. The risk of progression with vandetanib was reduced by 54%, compared with placebo, a significant effect.

Among those on placebo, median progression-free survival was 16.4 months, compared with at least 22.6 months among those on vandetanib, according to the FDA statement, which added: "It is too early to determine the median progression-free survival in patients treated with vandetanib or to tell whether they will live longer (overall survival) compared to patients treated with placebo." Diarrhea, rash, nausea, high blood pressure, headache, fatigue, decreased appetite, and abdominal pain were among the adverse effects associated with treatment. In the study, serious adverse events resulted in five deaths in patients treated with vandetanib, according to the FDA; causes included breathing complications, heart failure, and sepsis.

Because vandetanib can cause QT interval prolongation, it is being approved with a Risk Evaluation and Mitigation Strategy (REMS) to inform health care professionals about cardiac risks and will be available through a restricted distribution program, so that only health care professionals and pharmacies certified through the vandetanib REMS program will be able to prescribe and dispense the product. Patients also will be given a medication guide that explains the risks of treatment.

An estimated 3%-5% of all thyroid cancers are medullary thyroid cancer, and the incidence of this cancer in the United States in 2010 was about 1,300-2,200 patients, according to the FDA.

There is no trade name yet for the drug, manufactured by AstraZeneca Pharmaceuticals.

SILVER SPRING, MD. – A Food and Drug Administration advisory panel on April 5 voted 13-0 that fidaxomicin, a new orally administered macrolide antibiotic, is a safe and effective treatment for Clostridium difficile–associated diarrhea in adults, based on clinical trials.

At the meeting, members of the FDA’s Anti-Infective Drugs Advisory Committee agreed that the two phase III studies comparing the drug to vancomycin were rigorous and well done and that rates of leukopenia, neutropenia, and gastrointestinal bleeding in patients treated with the antibiotic should be followed after approval. Those adverse events were slightly higher among the patients treated with fidaxomicin in the studies.

The panel did not vote specifically on whether to recommend approval of fidaxomicin.

Fidaxomicin has a narrow spectrum of activity, with bactericidal activity against C. difficile, and is poorly absorbed and locally active in the gastrointestinal tract, according to its manufacturer, Optimer Pharmaceuticals Inc. The company has proposed that fidaxomicin be approved for the treatment of adults "with Clostridium difficile infection (CDI), also known as Clostridium difficile–associated diarrhea and for reducing the risk of recurrence when used for treatment of initial CDI."

In two phase III studies in the United States, Canada, and Europe of approximately 1,100 adults with C. difficile–associated diarrhea, treatment with fidaxomicin 200 mg twice daily for 10 days, compared with oral vancomycin 125 mg every 6 hours for 10 days. The clinical cure rate at the end of the treatment, the primary efficacy end point, was 88% in both trials, compared with 86%-87% among vancomycin-treated patients. (Clinical cure was defined as having three or fewer unformed bowel movements for 2 consecutive days or a marked reduction in the number of unformed bowel movements at the end of treatment plus no further treatment required within 2 days of stopping the medication.)

The recurrence rate over 30 days of follow-up was significantly lower among those treated with fidaxomicin (about 16% and 13% among those on fidaxomicin, vs. 25% and 27%, respectively, among those on vancomycin). How the recurrence data will be communicated to health care providers in the drug label and whether the indication will include the claim that treatment reduces recurrence (if the drug is approved) is unclear, however, since the panel voted 6-6 with 1 abstention on whether the lower recurrence rate associated with fidaxomicin was clinically significant.

In the United States, oral vancomycin is the only approved treatment for CDI and oral metronidazole is used off label.

The FDA is expected to make a decision by May 30. The drug, formulated in 200-mg tablets, is also being reviewed for approval in Europe. If approved, the company will market it as Dificid.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to meetings; occasionally, the FDA grants a waiver to a panelist with a conflict, but not at this meeting.

SILVER SPRING, MD. – A Food and Drug Administration advisory panel on April 5 voted 13-0 that fidaxomicin, a new orally administered macrolide antibiotic, is a safe and effective treatment for Clostridium difficile–associated diarrhea in adults, based on clinical trials.

At the meeting, members of the FDA’s Anti-Infective Drugs Advisory Committee agreed that the two phase III studies comparing the drug to vancomycin were rigorous and well done and that rates of leukopenia, neutropenia, and gastrointestinal bleeding in patients treated with the antibiotic should be followed after approval. Those adverse events were slightly higher among the patients treated with fidaxomicin in the studies.

The panel did not vote specifically on whether to recommend approval of fidaxomicin.

Fidaxomicin has a narrow spectrum of activity, with bactericidal activity against C. difficile, and is poorly absorbed and locally active in the gastrointestinal tract, according to its manufacturer, Optimer Pharmaceuticals Inc. The company has proposed that fidaxomicin be approved for the treatment of adults "with Clostridium difficile infection (CDI), also known as Clostridium difficile–associated diarrhea and for reducing the risk of recurrence when used for treatment of initial CDI."

In two phase III studies in the United States, Canada, and Europe of approximately 1,100 adults with C. difficile–associated diarrhea, treatment with fidaxomicin 200 mg twice daily for 10 days, compared with oral vancomycin 125 mg every 6 hours for 10 days. The clinical cure rate at the end of the treatment, the primary efficacy end point, was 88% in both trials, compared with 86%-87% among vancomycin-treated patients. (Clinical cure was defined as having three or fewer unformed bowel movements for 2 consecutive days or a marked reduction in the number of unformed bowel movements at the end of treatment plus no further treatment required within 2 days of stopping the medication.)

The recurrence rate over 30 days of follow-up was significantly lower among those treated with fidaxomicin (about 16% and 13% among those on fidaxomicin, vs. 25% and 27%, respectively, among those on vancomycin). How the recurrence data will be communicated to health care providers in the drug label and whether the indication will include the claim that treatment reduces recurrence (if the drug is approved) is unclear, however, since the panel voted 6-6 with 1 abstention on whether the lower recurrence rate associated with fidaxomicin was clinically significant.

In the United States, oral vancomycin is the only approved treatment for CDI and oral metronidazole is used off label.

The FDA is expected to make a decision by May 30. The drug, formulated in 200-mg tablets, is also being reviewed for approval in Europe. If approved, the company will market it as Dificid.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to meetings; occasionally, the FDA grants a waiver to a panelist with a conflict, but not at this meeting.

SILVER SPRING, MD. – A Food and Drug Administration advisory panel on April 5 voted 13-0 that fidaxomicin, a new orally administered macrolide antibiotic, is a safe and effective treatment for Clostridium difficile–associated diarrhea in adults, based on clinical trials.

At the meeting, members of the FDA’s Anti-Infective Drugs Advisory Committee agreed that the two phase III studies comparing the drug to vancomycin were rigorous and well done and that rates of leukopenia, neutropenia, and gastrointestinal bleeding in patients treated with the antibiotic should be followed after approval. Those adverse events were slightly higher among the patients treated with fidaxomicin in the studies.

The panel did not vote specifically on whether to recommend approval of fidaxomicin.

Fidaxomicin has a narrow spectrum of activity, with bactericidal activity against C. difficile, and is poorly absorbed and locally active in the gastrointestinal tract, according to its manufacturer, Optimer Pharmaceuticals Inc. The company has proposed that fidaxomicin be approved for the treatment of adults "with Clostridium difficile infection (CDI), also known as Clostridium difficile–associated diarrhea and for reducing the risk of recurrence when used for treatment of initial CDI."

In two phase III studies in the United States, Canada, and Europe of approximately 1,100 adults with C. difficile–associated diarrhea, treatment with fidaxomicin 200 mg twice daily for 10 days, compared with oral vancomycin 125 mg every 6 hours for 10 days. The clinical cure rate at the end of the treatment, the primary efficacy end point, was 88% in both trials, compared with 86%-87% among vancomycin-treated patients. (Clinical cure was defined as having three or fewer unformed bowel movements for 2 consecutive days or a marked reduction in the number of unformed bowel movements at the end of treatment plus no further treatment required within 2 days of stopping the medication.)

The recurrence rate over 30 days of follow-up was significantly lower among those treated with fidaxomicin (about 16% and 13% among those on fidaxomicin, vs. 25% and 27%, respectively, among those on vancomycin). How the recurrence data will be communicated to health care providers in the drug label and whether the indication will include the claim that treatment reduces recurrence (if the drug is approved) is unclear, however, since the panel voted 6-6 with 1 abstention on whether the lower recurrence rate associated with fidaxomicin was clinically significant.

In the United States, oral vancomycin is the only approved treatment for CDI and oral metronidazole is used off label.

The FDA is expected to make a decision by May 30. The drug, formulated in 200-mg tablets, is also being reviewed for approval in Europe. If approved, the company will market it as Dificid.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to meetings; occasionally, the FDA grants a waiver to a panelist with a conflict, but not at this meeting.

SILVER SPRING, MD. – A Food and Drug Administration advisory panel on April 5 voted 13-0 that fidaxomicin, a new orally administered macrolide antibiotic, is a safe and effective treatment for Clostridium difficile–associated diarrhea in adults, based on clinical trials.

At the meeting, members of the FDA’s Anti-Infective Drugs Advisory Committee agreed that the two phase III studies comparing the drug to vancomycin were rigorous and well done and that rates of leukopenia, neutropenia, and gastrointestinal bleeding in patients treated with the antibiotic should be followed after approval. Those adverse events were slightly higher among the patients treated with fidaxomicin in the studies.

The panel did not vote specifically on whether to recommend approval of fidaxomicin.

Fidaxomicin has a narrow spectrum of activity, with bactericidal activity against C. difficile, and is poorly absorbed and locally active in the gastrointestinal tract, according to its manufacturer, Optimer Pharmaceuticals Inc. The company has proposed that fidaxomicin be approved for the treatment of adults "with Clostridium difficile infection (CDI), also known as Clostridium difficile–associated diarrhea and for reducing the risk of recurrence when used for treatment of initial CDI."

In two phase III studies in the United States, Canada, and Europe of approximately 1,100 adults with C. difficile–associated diarrhea, treatment with fidaxomicin 200 mg twice daily for 10 days, compared with oral vancomycin 125 mg every 6 hours for 10 days. The clinical cure rate at the end of the treatment, the primary efficacy end point, was 88% in both trials, compared with 86%-87% among vancomycin-treated patients. (Clinical cure was defined as having three or fewer unformed bowel movements for 2 consecutive days or a marked reduction in the number of unformed bowel movements at the end of treatment plus no further treatment required within 2 days of stopping the medication.)

The recurrence rate over 30 days of follow-up was significantly lower among those treated with fidaxomicin (about 16% and 13% among those on fidaxomicin, vs. 25% and 27%, respectively, among those on vancomycin). How the recurrence data will be communicated to health care providers in the drug label and whether the indication will include the claim that treatment reduces recurrence (if the drug is approved) is unclear, however, since the panel voted 6-6 with 1 abstention on whether the lower recurrence rate associated with fidaxomicin was clinically significant.

In the United States, oral vancomycin is the only approved treatment for CDI and oral metronidazole is used off label.

The FDA is expected to make a decision by May 30. The drug, formulated in 200-mg tablets, is also being reviewed for approval in Europe. If approved, the company will market it as Dificid.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to meetings; occasionally, the FDA grants a waiver to a panelist with a conflict, but not at this meeting.

SILVER SPRING, MD. – A Food and Drug Administration advisory panel on April 5 voted 13-0 that fidaxomicin, a new orally administered macrolide antibiotic, is a safe and effective treatment for Clostridium difficile–associated diarrhea in adults, based on clinical trials.

At the meeting, members of the FDA’s Anti-Infective Drugs Advisory Committee agreed that the two phase III studies comparing the drug to vancomycin were rigorous and well done and that rates of leukopenia, neutropenia, and gastrointestinal bleeding in patients treated with the antibiotic should be followed after approval. Those adverse events were slightly higher among the patients treated with fidaxomicin in the studies.

The panel did not vote specifically on whether to recommend approval of fidaxomicin.

Fidaxomicin has a narrow spectrum of activity, with bactericidal activity against C. difficile, and is poorly absorbed and locally active in the gastrointestinal tract, according to its manufacturer, Optimer Pharmaceuticals Inc. The company has proposed that fidaxomicin be approved for the treatment of adults "with Clostridium difficile infection (CDI), also known as Clostridium difficile–associated diarrhea and for reducing the risk of recurrence when used for treatment of initial CDI."

In two phase III studies in the United States, Canada, and Europe of approximately 1,100 adults with C. difficile–associated diarrhea, treatment with fidaxomicin 200 mg twice daily for 10 days, compared with oral vancomycin 125 mg every 6 hours for 10 days. The clinical cure rate at the end of the treatment, the primary efficacy end point, was 88% in both trials, compared with 86%-87% among vancomycin-treated patients. (Clinical cure was defined as having three or fewer unformed bowel movements for 2 consecutive days or a marked reduction in the number of unformed bowel movements at the end of treatment plus no further treatment required within 2 days of stopping the medication.)

The recurrence rate over 30 days of follow-up was significantly lower among those treated with fidaxomicin (about 16% and 13% among those on fidaxomicin, vs. 25% and 27%, respectively, among those on vancomycin). How the recurrence data will be communicated to health care providers in the drug label and whether the indication will include the claim that treatment reduces recurrence (if the drug is approved) is unclear, however, since the panel voted 6-6 with 1 abstention on whether the lower recurrence rate associated with fidaxomicin was clinically significant.

In the United States, oral vancomycin is the only approved treatment for CDI and oral metronidazole is used off label.

The FDA is expected to make a decision by May 30. The drug, formulated in 200-mg tablets, is also being reviewed for approval in Europe. If approved, the company will market it as Dificid.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to meetings; occasionally, the FDA grants a waiver to a panelist with a conflict, but not at this meeting.

SILVER SPRING, MD. – A Food and Drug Administration advisory panel on April 5 voted 13-0 that fidaxomicin, a new orally administered macrolide antibiotic, is a safe and effective treatment for Clostridium difficile–associated diarrhea in adults, based on clinical trials.

At the meeting, members of the FDA’s Anti-Infective Drugs Advisory Committee agreed that the two phase III studies comparing the drug to vancomycin were rigorous and well done and that rates of leukopenia, neutropenia, and gastrointestinal bleeding in patients treated with the antibiotic should be followed after approval. Those adverse events were slightly higher among the patients treated with fidaxomicin in the studies.

The panel did not vote specifically on whether to recommend approval of fidaxomicin.

Fidaxomicin has a narrow spectrum of activity, with bactericidal activity against C. difficile, and is poorly absorbed and locally active in the gastrointestinal tract, according to its manufacturer, Optimer Pharmaceuticals Inc. The company has proposed that fidaxomicin be approved for the treatment of adults "with Clostridium difficile infection (CDI), also known as Clostridium difficile–associated diarrhea and for reducing the risk of recurrence when used for treatment of initial CDI."

In two phase III studies in the United States, Canada, and Europe of approximately 1,100 adults with C. difficile–associated diarrhea, treatment with fidaxomicin 200 mg twice daily for 10 days, compared with oral vancomycin 125 mg every 6 hours for 10 days. The clinical cure rate at the end of the treatment, the primary efficacy end point, was 88% in both trials, compared with 86%-87% among vancomycin-treated patients. (Clinical cure was defined as having three or fewer unformed bowel movements for 2 consecutive days or a marked reduction in the number of unformed bowel movements at the end of treatment plus no further treatment required within 2 days of stopping the medication.)

The recurrence rate over 30 days of follow-up was significantly lower among those treated with fidaxomicin (about 16% and 13% among those on fidaxomicin, vs. 25% and 27%, respectively, among those on vancomycin). How the recurrence data will be communicated to health care providers in the drug label and whether the indication will include the claim that treatment reduces recurrence (if the drug is approved) is unclear, however, since the panel voted 6-6 with 1 abstention on whether the lower recurrence rate associated with fidaxomicin was clinically significant.

In the United States, oral vancomycin is the only approved treatment for CDI and oral metronidazole is used off label.

The FDA is expected to make a decision by May 30. The drug, formulated in 200-mg tablets, is also being reviewed for approval in Europe. If approved, the company will market it as Dificid.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to meetings; occasionally, the FDA grants a waiver to a panelist with a conflict, but not at this meeting.

SILVER SPRING, MD. – A Food and Drug Administration advisory panel on April 5 voted 13-0 that fidaxomicin, a new orally administered macrolide antibiotic, is a safe and effective treatment for Clostridium difficile–associated diarrhea in adults, based on clinical trials.

At the meeting, members of the FDA’s Anti-Infective Drugs Advisory Committee agreed that the two phase III studies comparing the drug to vancomycin were rigorous and well done and that rates of leukopenia, neutropenia, and gastrointestinal bleeding in patients treated with the antibiotic should be followed after approval. Those adverse events were slightly higher among the patients treated with fidaxomicin in the studies.

The panel did not vote specifically on whether to recommend approval of fidaxomicin.

Fidaxomicin has a narrow spectrum of activity, with bactericidal activity against C. difficile, and is poorly absorbed and locally active in the gastrointestinal tract, according to its manufacturer, Optimer Pharmaceuticals Inc. The company has proposed that fidaxomicin be approved for the treatment of adults "with Clostridium difficile infection (CDI), also known as Clostridium difficile–associated diarrhea and for reducing the risk of recurrence when used for treatment of initial CDI."

In two phase III studies in the United States, Canada, and Europe of approximately 1,100 adults with C. difficile–associated diarrhea, treatment with fidaxomicin 200 mg twice daily for 10 days, compared with oral vancomycin 125 mg every 6 hours for 10 days. The clinical cure rate at the end of the treatment, the primary efficacy end point, was 88% in both trials, compared with 86%-87% among vancomycin-treated patients. (Clinical cure was defined as having three or fewer unformed bowel movements for 2 consecutive days or a marked reduction in the number of unformed bowel movements at the end of treatment plus no further treatment required within 2 days of stopping the medication.)

The recurrence rate over 30 days of follow-up was significantly lower among those treated with fidaxomicin (about 16% and 13% among those on fidaxomicin, vs. 25% and 27%, respectively, among those on vancomycin). How the recurrence data will be communicated to health care providers in the drug label and whether the indication will include the claim that treatment reduces recurrence (if the drug is approved) is unclear, however, since the panel voted 6-6 with 1 abstention on whether the lower recurrence rate associated with fidaxomicin was clinically significant.

In the United States, oral vancomycin is the only approved treatment for CDI and oral metronidazole is used off label.

The FDA is expected to make a decision by May 30. The drug, formulated in 200-mg tablets, is also being reviewed for approval in Europe. If approved, the company will market it as Dificid.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to meetings; occasionally, the FDA grants a waiver to a panelist with a conflict, but not at this meeting.

SILVER SPRING, MD. – A Food and Drug Administration advisory panel on April 5 voted 13-0 that fidaxomicin, a new orally administered macrolide antibiotic, is a safe and effective treatment for Clostridium difficile–associated diarrhea in adults, based on clinical trials.

At the meeting, members of the FDA’s Anti-Infective Drugs Advisory Committee agreed that the two phase III studies comparing the drug to vancomycin were rigorous and well done and that rates of leukopenia, neutropenia, and gastrointestinal bleeding in patients treated with the antibiotic should be followed after approval. Those adverse events were slightly higher among the patients treated with fidaxomicin in the studies.

The panel did not vote specifically on whether to recommend approval of fidaxomicin.

Fidaxomicin has a narrow spectrum of activity, with bactericidal activity against C. difficile, and is poorly absorbed and locally active in the gastrointestinal tract, according to its manufacturer, Optimer Pharmaceuticals Inc. The company has proposed that fidaxomicin be approved for the treatment of adults "with Clostridium difficile infection (CDI), also known as Clostridium difficile–associated diarrhea and for reducing the risk of recurrence when used for treatment of initial CDI."

In two phase III studies in the United States, Canada, and Europe of approximately 1,100 adults with C. difficile–associated diarrhea, treatment with fidaxomicin 200 mg twice daily for 10 days, compared with oral vancomycin 125 mg every 6 hours for 10 days. The clinical cure rate at the end of the treatment, the primary efficacy end point, was 88% in both trials, compared with 86%-87% among vancomycin-treated patients. (Clinical cure was defined as having three or fewer unformed bowel movements for 2 consecutive days or a marked reduction in the number of unformed bowel movements at the end of treatment plus no further treatment required within 2 days of stopping the medication.)

The recurrence rate over 30 days of follow-up was significantly lower among those treated with fidaxomicin (about 16% and 13% among those on fidaxomicin, vs. 25% and 27%, respectively, among those on vancomycin). How the recurrence data will be communicated to health care providers in the drug label and whether the indication will include the claim that treatment reduces recurrence (if the drug is approved) is unclear, however, since the panel voted 6-6 with 1 abstention on whether the lower recurrence rate associated with fidaxomicin was clinically significant.

In the United States, oral vancomycin is the only approved treatment for CDI and oral metronidazole is used off label.

The FDA is expected to make a decision by May 30. The drug, formulated in 200-mg tablets, is also being reviewed for approval in Europe. If approved, the company will market it as Dificid.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to meetings; occasionally, the FDA grants a waiver to a panelist with a conflict, but not at this meeting.

SILVER SPRING, MD. – A Food and Drug Administration advisory panel on April 5 voted 13-0 that fidaxomicin, a new orally administered macrolide antibiotic, is a safe and effective treatment for Clostridium difficile–associated diarrhea in adults, based on clinical trials.

At the meeting, members of the FDA’s Anti-Infective Drugs Advisory Committee agreed that the two phase III studies comparing the drug to vancomycin were rigorous and well done and that rates of leukopenia, neutropenia, and gastrointestinal bleeding in patients treated with the antibiotic should be followed after approval. Those adverse events were slightly higher among the patients treated with fidaxomicin in the studies.

The panel did not vote specifically on whether to recommend approval of fidaxomicin.

Fidaxomicin has a narrow spectrum of activity, with bactericidal activity against C. difficile, and is poorly absorbed and locally active in the gastrointestinal tract, according to its manufacturer, Optimer Pharmaceuticals Inc. The company has proposed that fidaxomicin be approved for the treatment of adults "with Clostridium difficile infection (CDI), also known as Clostridium difficile–associated diarrhea and for reducing the risk of recurrence when used for treatment of initial CDI."

In two phase III studies in the United States, Canada, and Europe of approximately 1,100 adults with C. difficile–associated diarrhea, treatment with fidaxomicin 200 mg twice daily for 10 days, compared with oral vancomycin 125 mg every 6 hours for 10 days. The clinical cure rate at the end of the treatment, the primary efficacy end point, was 88% in both trials, compared with 86%-87% among vancomycin-treated patients. (Clinical cure was defined as having three or fewer unformed bowel movements for 2 consecutive days or a marked reduction in the number of unformed bowel movements at the end of treatment plus no further treatment required within 2 days of stopping the medication.)

The recurrence rate over 30 days of follow-up was significantly lower among those treated with fidaxomicin (about 16% and 13% among those on fidaxomicin, vs. 25% and 27%, respectively, among those on vancomycin). How the recurrence data will be communicated to health care providers in the drug label and whether the indication will include the claim that treatment reduces recurrence (if the drug is approved) is unclear, however, since the panel voted 6-6 with 1 abstention on whether the lower recurrence rate associated with fidaxomicin was clinically significant.

In the United States, oral vancomycin is the only approved treatment for CDI and oral metronidazole is used off label.

The FDA is expected to make a decision by May 30. The drug, formulated in 200-mg tablets, is also being reviewed for approval in Europe. If approved, the company will market it as Dificid.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to meetings; occasionally, the FDA grants a waiver to a panelist with a conflict, but not at this meeting.

Changes have been made to the labeling of the antiviral drug telbivudine that are "related to a higher risk of developing resistance-associated substitutions in treated patients," according to the Food and Drug Administration.

The FDA-approved changes appear in the indications and usage section and in the dosage and administration section.

Telbivudine, marketed as Tyzeka by Novartis Pharmaceuticals, is a hepatitis B virus (HBV) nucleoside analogue reverse-transcriptase inhibitor. It is approved for the treatment of chronic hepatitis B in adults who have evidence of viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. Telbivudine is available in 600-mg tablets and in an oral solution containing 100 mg/5 mL.

The changes in the indications and usage section include the statement that in hepatitis B e antigen-positive (HBeAg-positive) patients, telbivudine "should only be initiated in patients with HBV DNA less than 9 log10 copies/mL and ALT greater than or equal to two times Upper Limit of Normal (ULN) prior to treatment." For patients who are HBeAg-negative, telbivudine "should only be initiated in patients with HBV DNA less than 7 log10 copies/mL prior to treatment," according to the modified label.

The dosage and administration section now states that because higher rates of resistance may develop with longer-term treatment in patients with incomplete viral suppression, "treatment should only be initiated if pre-treatment HBV DNA and ALT measurements are known," in the following groups of patients:

• For patients who are HbeAg positive, "HBV DNA should be less than 9 log10 copies/mL and ALT should be greater than or equal to two times ULN" before starting treatment with telbivudine.

• For patients who are HBeAg negative, "HBV DNA should be less than 7 log10 copies/mL," before starting treatment with telbivudine.

The label recommends that HBV DNA levels should be monitored at 24 weeks of treatment "to assure complete viral suppression (HBV DNA less than 300 copies/mL)," and that "alternate therapy should be initiated for patients who have detectable HBV DNA after 24 weeks of treatment." Changes have also been made to recommendations regarding duration of therapy.

The changes were made on March 29.

Information on the revised label is available at Drugs@FDA under Tyzeka or telbivudine at www.accessdata.fda.gov/scripts/cder/drugsatfda/.

Changes have been made to the labeling of the antiviral drug telbivudine that are "related to a higher risk of developing resistance-associated substitutions in treated patients," according to the Food and Drug Administration.

The FDA-approved changes appear in the indications and usage section and in the dosage and administration section.

Telbivudine, marketed as Tyzeka by Novartis Pharmaceuticals, is a hepatitis B virus (HBV) nucleoside analogue reverse-transcriptase inhibitor. It is approved for the treatment of chronic hepatitis B in adults who have evidence of viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. Telbivudine is available in 600-mg tablets and in an oral solution containing 100 mg/5 mL.

The changes in the indications and usage section include the statement that in hepatitis B e antigen-positive (HBeAg-positive) patients, telbivudine "should only be initiated in patients with HBV DNA less than 9 log10 copies/mL and ALT greater than or equal to two times Upper Limit of Normal (ULN) prior to treatment." For patients who are HBeAg-negative, telbivudine "should only be initiated in patients with HBV DNA less than 7 log10 copies/mL prior to treatment," according to the modified label.

The dosage and administration section now states that because higher rates of resistance may develop with longer-term treatment in patients with incomplete viral suppression, "treatment should only be initiated if pre-treatment HBV DNA and ALT measurements are known," in the following groups of patients:

• For patients who are HbeAg positive, "HBV DNA should be less than 9 log10 copies/mL and ALT should be greater than or equal to two times ULN" before starting treatment with telbivudine.

• For patients who are HBeAg negative, "HBV DNA should be less than 7 log10 copies/mL," before starting treatment with telbivudine.

The label recommends that HBV DNA levels should be monitored at 24 weeks of treatment "to assure complete viral suppression (HBV DNA less than 300 copies/mL)," and that "alternate therapy should be initiated for patients who have detectable HBV DNA after 24 weeks of treatment." Changes have also been made to recommendations regarding duration of therapy.

The changes were made on March 29.

Information on the revised label is available at Drugs@FDA under Tyzeka or telbivudine at www.accessdata.fda.gov/scripts/cder/drugsatfda/.

Changes have been made to the labeling of the antiviral drug telbivudine that are "related to a higher risk of developing resistance-associated substitutions in treated patients," according to the Food and Drug Administration.

The FDA-approved changes appear in the indications and usage section and in the dosage and administration section.

Telbivudine, marketed as Tyzeka by Novartis Pharmaceuticals, is a hepatitis B virus (HBV) nucleoside analogue reverse-transcriptase inhibitor. It is approved for the treatment of chronic hepatitis B in adults who have evidence of viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. Telbivudine is available in 600-mg tablets and in an oral solution containing 100 mg/5 mL.

The changes in the indications and usage section include the statement that in hepatitis B e antigen-positive (HBeAg-positive) patients, telbivudine "should only be initiated in patients with HBV DNA less than 9 log10 copies/mL and ALT greater than or equal to two times Upper Limit of Normal (ULN) prior to treatment." For patients who are HBeAg-negative, telbivudine "should only be initiated in patients with HBV DNA less than 7 log10 copies/mL prior to treatment," according to the modified label.

The dosage and administration section now states that because higher rates of resistance may develop with longer-term treatment in patients with incomplete viral suppression, "treatment should only be initiated if pre-treatment HBV DNA and ALT measurements are known," in the following groups of patients:

• For patients who are HbeAg positive, "HBV DNA should be less than 9 log10 copies/mL and ALT should be greater than or equal to two times ULN" before starting treatment with telbivudine.

• For patients who are HBeAg negative, "HBV DNA should be less than 7 log10 copies/mL," before starting treatment with telbivudine.

The label recommends that HBV DNA levels should be monitored at 24 weeks of treatment "to assure complete viral suppression (HBV DNA less than 300 copies/mL)," and that "alternate therapy should be initiated for patients who have detectable HBV DNA after 24 weeks of treatment." Changes have also been made to recommendations regarding duration of therapy.

The changes were made on March 29.

Information on the revised label is available at Drugs@FDA under Tyzeka or telbivudine at www.accessdata.fda.gov/scripts/cder/drugsatfda/.

Changes have been made to the labeling of the antiviral drug telbivudine that are "related to a higher risk of developing resistance-associated substitutions in treated patients," according to the Food and Drug Administration.

The FDA-approved changes appear in the indications and usage section and in the dosage and administration section.

Telbivudine, marketed as Tyzeka by Novartis Pharmaceuticals, is a hepatitis B virus (HBV) nucleoside analogue reverse-transcriptase inhibitor. It is approved for the treatment of chronic hepatitis B in adults who have evidence of viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. Telbivudine is available in 600-mg tablets and in an oral solution containing 100 mg/5 mL.

The changes in the indications and usage section include the statement that in hepatitis B e antigen-positive (HBeAg-positive) patients, telbivudine "should only be initiated in patients with HBV DNA less than 9 log10 copies/mL and ALT greater than or equal to two times Upper Limit of Normal (ULN) prior to treatment." For patients who are HBeAg-negative, telbivudine "should only be initiated in patients with HBV DNA less than 7 log10 copies/mL prior to treatment," according to the modified label.

The dosage and administration section now states that because higher rates of resistance may develop with longer-term treatment in patients with incomplete viral suppression, "treatment should only be initiated if pre-treatment HBV DNA and ALT measurements are known," in the following groups of patients:

• For patients who are HbeAg positive, "HBV DNA should be less than 9 log10 copies/mL and ALT should be greater than or equal to two times ULN" before starting treatment with telbivudine.

• For patients who are HBeAg negative, "HBV DNA should be less than 7 log10 copies/mL," before starting treatment with telbivudine.

The label recommends that HBV DNA levels should be monitored at 24 weeks of treatment "to assure complete viral suppression (HBV DNA less than 300 copies/mL)," and that "alternate therapy should be initiated for patients who have detectable HBV DNA after 24 weeks of treatment." Changes have also been made to recommendations regarding duration of therapy.

The changes were made on March 29.

Information on the revised label is available at Drugs@FDA under Tyzeka or telbivudine at www.accessdata.fda.gov/scripts/cder/drugsatfda/.

Changes have been made to the labeling of the antiviral drug telbivudine that are "related to a higher risk of developing resistance-associated substitutions in treated patients," according to the Food and Drug Administration.

The FDA-approved changes appear in the indications and usage section and in the dosage and administration section.

Telbivudine, marketed as Tyzeka by Novartis Pharmaceuticals, is a hepatitis B virus (HBV) nucleoside analogue reverse-transcriptase inhibitor. It is approved for the treatment of chronic hepatitis B in adults who have evidence of viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. Telbivudine is available in 600-mg tablets and in an oral solution containing 100 mg/5 mL.

The changes in the indications and usage section include the statement that in hepatitis B e antigen-positive (HBeAg-positive) patients, telbivudine "should only be initiated in patients with HBV DNA less than 9 log10 copies/mL and ALT greater than or equal to two times Upper Limit of Normal (ULN) prior to treatment." For patients who are HBeAg-negative, telbivudine "should only be initiated in patients with HBV DNA less than 7 log10 copies/mL prior to treatment," according to the modified label.

The dosage and administration section now states that because higher rates of resistance may develop with longer-term treatment in patients with incomplete viral suppression, "treatment should only be initiated if pre-treatment HBV DNA and ALT measurements are known," in the following groups of patients:

• For patients who are HbeAg positive, "HBV DNA should be less than 9 log10 copies/mL and ALT should be greater than or equal to two times ULN" before starting treatment with telbivudine.

• For patients who are HBeAg negative, "HBV DNA should be less than 7 log10 copies/mL," before starting treatment with telbivudine.

The label recommends that HBV DNA levels should be monitored at 24 weeks of treatment "to assure complete viral suppression (HBV DNA less than 300 copies/mL)," and that "alternate therapy should be initiated for patients who have detectable HBV DNA after 24 weeks of treatment." Changes have also been made to recommendations regarding duration of therapy.

The changes were made on March 29.

Information on the revised label is available at Drugs@FDA under Tyzeka or telbivudine at www.accessdata.fda.gov/scripts/cder/drugsatfda/.

Changes have been made to the labeling of the antiviral drug telbivudine that are "related to a higher risk of developing resistance-associated substitutions in treated patients," according to the Food and Drug Administration.

The FDA-approved changes appear in the indications and usage section and in the dosage and administration section.

Telbivudine, marketed as Tyzeka by Novartis Pharmaceuticals, is a hepatitis B virus (HBV) nucleoside analogue reverse-transcriptase inhibitor. It is approved for the treatment of chronic hepatitis B in adults who have evidence of viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. Telbivudine is available in 600-mg tablets and in an oral solution containing 100 mg/5 mL.

The changes in the indications and usage section include the statement that in hepatitis B e antigen-positive (HBeAg-positive) patients, telbivudine "should only be initiated in patients with HBV DNA less than 9 log10 copies/mL and ALT greater than or equal to two times Upper Limit of Normal (ULN) prior to treatment." For patients who are HBeAg-negative, telbivudine "should only be initiated in patients with HBV DNA less than 7 log10 copies/mL prior to treatment," according to the modified label.

The dosage and administration section now states that because higher rates of resistance may develop with longer-term treatment in patients with incomplete viral suppression, "treatment should only be initiated if pre-treatment HBV DNA and ALT measurements are known," in the following groups of patients:

• For patients who are HbeAg positive, "HBV DNA should be less than 9 log10 copies/mL and ALT should be greater than or equal to two times ULN" before starting treatment with telbivudine.

• For patients who are HBeAg negative, "HBV DNA should be less than 7 log10 copies/mL," before starting treatment with telbivudine.

The label recommends that HBV DNA levels should be monitored at 24 weeks of treatment "to assure complete viral suppression (HBV DNA less than 300 copies/mL)," and that "alternate therapy should be initiated for patients who have detectable HBV DNA after 24 weeks of treatment." Changes have also been made to recommendations regarding duration of therapy.

The changes were made on March 29.

Information on the revised label is available at Drugs@FDA under Tyzeka or telbivudine at www.accessdata.fda.gov/scripts/cder/drugsatfda/.

Changes have been made to the labeling of the antiviral drug telbivudine that are "related to a higher risk of developing resistance-associated substitutions in treated patients," according to the Food and Drug Administration.

The FDA-approved changes appear in the indications and usage section and in the dosage and administration section.

Telbivudine, marketed as Tyzeka by Novartis Pharmaceuticals, is a hepatitis B virus (HBV) nucleoside analogue reverse-transcriptase inhibitor. It is approved for the treatment of chronic hepatitis B in adults who have evidence of viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. Telbivudine is available in 600-mg tablets and in an oral solution containing 100 mg/5 mL.

The changes in the indications and usage section include the statement that in hepatitis B e antigen-positive (HBeAg-positive) patients, telbivudine "should only be initiated in patients with HBV DNA less than 9 log10 copies/mL and ALT greater than or equal to two times Upper Limit of Normal (ULN) prior to treatment." For patients who are HBeAg-negative, telbivudine "should only be initiated in patients with HBV DNA less than 7 log10 copies/mL prior to treatment," according to the modified label.

The dosage and administration section now states that because higher rates of resistance may develop with longer-term treatment in patients with incomplete viral suppression, "treatment should only be initiated if pre-treatment HBV DNA and ALT measurements are known," in the following groups of patients:

• For patients who are HbeAg positive, "HBV DNA should be less than 9 log10 copies/mL and ALT should be greater than or equal to two times ULN" before starting treatment with telbivudine.

• For patients who are HBeAg negative, "HBV DNA should be less than 7 log10 copies/mL," before starting treatment with telbivudine.

The label recommends that HBV DNA levels should be monitored at 24 weeks of treatment "to assure complete viral suppression (HBV DNA less than 300 copies/mL)," and that "alternate therapy should be initiated for patients who have detectable HBV DNA after 24 weeks of treatment." Changes have also been made to recommendations regarding duration of therapy.

The changes were made on March 29.

Information on the revised label is available at Drugs@FDA under Tyzeka or telbivudine at www.accessdata.fda.gov/scripts/cder/drugsatfda/.

Changes have been made to the labeling of the antiviral drug telbivudine that are "related to a higher risk of developing resistance-associated substitutions in treated patients," according to the Food and Drug Administration.

The FDA-approved changes appear in the indications and usage section and in the dosage and administration section.

Telbivudine, marketed as Tyzeka by Novartis Pharmaceuticals, is a hepatitis B virus (HBV) nucleoside analogue reverse-transcriptase inhibitor. It is approved for the treatment of chronic hepatitis B in adults who have evidence of viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. Telbivudine is available in 600-mg tablets and in an oral solution containing 100 mg/5 mL.

The changes in the indications and usage section include the statement that in hepatitis B e antigen-positive (HBeAg-positive) patients, telbivudine "should only be initiated in patients with HBV DNA less than 9 log10 copies/mL and ALT greater than or equal to two times Upper Limit of Normal (ULN) prior to treatment." For patients who are HBeAg-negative, telbivudine "should only be initiated in patients with HBV DNA less than 7 log10 copies/mL prior to treatment," according to the modified label.

The dosage and administration section now states that because higher rates of resistance may develop with longer-term treatment in patients with incomplete viral suppression, "treatment should only be initiated if pre-treatment HBV DNA and ALT measurements are known," in the following groups of patients:

• For patients who are HbeAg positive, "HBV DNA should be less than 9 log10 copies/mL and ALT should be greater than or equal to two times ULN" before starting treatment with telbivudine.

• For patients who are HBeAg negative, "HBV DNA should be less than 7 log10 copies/mL," before starting treatment with telbivudine.

The label recommends that HBV DNA levels should be monitored at 24 weeks of treatment "to assure complete viral suppression (HBV DNA less than 300 copies/mL)," and that "alternate therapy should be initiated for patients who have detectable HBV DNA after 24 weeks of treatment." Changes have also been made to recommendations regarding duration of therapy.

The changes were made on March 29.

Information on the revised label is available at Drugs@FDA under Tyzeka or telbivudine at www.accessdata.fda.gov/scripts/cder/drugsatfda/.

Changes have been made to the labeling of the antiviral drug telbivudine that are "related to a higher risk of developing resistance-associated substitutions in treated patients," according to the Food and Drug Administration.

The FDA-approved changes appear in the indications and usage section and in the dosage and administration section.

Telbivudine, marketed as Tyzeka by Novartis Pharmaceuticals, is a hepatitis B virus (HBV) nucleoside analogue reverse-transcriptase inhibitor. It is approved for the treatment of chronic hepatitis B in adults who have evidence of viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. Telbivudine is available in 600-mg tablets and in an oral solution containing 100 mg/5 mL.

The changes in the indications and usage section include the statement that in hepatitis B e antigen-positive (HBeAg-positive) patients, telbivudine "should only be initiated in patients with HBV DNA less than 9 log10 copies/mL and ALT greater than or equal to two times Upper Limit of Normal (ULN) prior to treatment." For patients who are HBeAg-negative, telbivudine "should only be initiated in patients with HBV DNA less than 7 log10 copies/mL prior to treatment," according to the modified label.

The dosage and administration section now states that because higher rates of resistance may develop with longer-term treatment in patients with incomplete viral suppression, "treatment should only be initiated if pre-treatment HBV DNA and ALT measurements are known," in the following groups of patients:

• For patients who are HbeAg positive, "HBV DNA should be less than 9 log10 copies/mL and ALT should be greater than or equal to two times ULN" before starting treatment with telbivudine.

• For patients who are HBeAg negative, "HBV DNA should be less than 7 log10 copies/mL," before starting treatment with telbivudine.

The label recommends that HBV DNA levels should be monitored at 24 weeks of treatment "to assure complete viral suppression (HBV DNA less than 300 copies/mL)," and that "alternate therapy should be initiated for patients who have detectable HBV DNA after 24 weeks of treatment." Changes have also been made to recommendations regarding duration of therapy.

The changes were made on March 29.

Information on the revised label is available at Drugs@FDA under Tyzeka or telbivudine at www.accessdata.fda.gov/scripts/cder/drugsatfda/.

Earlier this year, the majority of a Food and Drug Administration advisory panel voted in favor of expanding the approved use of a carotid stent to include patients who are at standard surgical risk in addition to the previously approved indication for revascularization in patients at high surgical risk.

The FDA's Circulatory System Devices Panel voted 7-3 with 1 abstention that the benefits of the Acculink Carotid Stent, a self-expanding stent made of nickel and titanium manufactured by Abbott Vascular, outweigh the risks when used for the proposed population of patients, at standard surgical risk.

The indication under review is for the treatment of patients at standard risk for adverse events from carotid endarterectomy who require carotid revascularization and meet the following criteria: patients who have neurological symptoms and at least 70% stenosis of the common or internal carotid artery by ultrasound or at least 50% stenosis by angiogram; or patients without neurological symptoms and at least 70% stenosis of the internal carotid artery by ultrasound or at least 60% stenosis by angiogram. Patients must also have a reference vessel diameter within the range of 4.0 mm and 9.0 mm at the target lesion.

In 2004, the Acculink Carotid Stent was approved for use for carotid revascularization in patients at high risk for adverse events from carotid endarterectomy who require carotid revascularization and meet slightly different criteria.

The company filed for approval of the expanded indication to include the lower surgical risk population based on the results of the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST), a randomized multicenter noninferiority study conducted in the United States and Canada comparing the outcomes of carotid artery stenting to the preferred method, carotid endarterectomy in patients who met the criteria in the proposed indication. At 1 year, the primary safety and effectiveness end point ? death, stroke, and myocardial infarction within 30 days of having the procedure plus the rate of ipsilateral stroke from 31 to 365 days after the procedure, was 7.1% among those who received the stent (1,131 patients) and 6.6% among those who underwent endarterectomy (1,176 patients), a difference that met the prespecified criteria for noninferiority.

Different components of the composite end point - periprocedural MIs and strokes -  were elevated among patients in the two arms: In the stent arm, the rate of strokes was 4.1%, compared with 1.9% in the surgical arm. MI at 30 days was 3.4% in the surgical arm, compared with 2% in the stent arm. Panelists varied on their opinions on the clinical significance of these differences.

The Acculink stent is approved in over 90 countries and more than 128,000 have been distributed worldwide, according to Abbott Vascular.

The CREST study was funded by Abbott Vascular, and was created by NIH and the New Jersey Medical School, Newark. The FDA usually follows the recommendations of its advisory panels.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to the meeting. Occasionally, the FDA grants a waiver to a panelist with a conflict but not at this meeting.

Commenting on this story, Dr. Linda Harris, vice chair, faculty development, department of surgery, Millard Fillmore Gates Hospital-Kaleida, Buffalo, N.Y. , stated: "While FDA approval is important to allow use of the carotid stent for average risk patients, this does not guarantee that Medicare or other insurances will reimburse for patients at average risk. Further, it is important to closely dissect the CREST data, which clearly show a higher rate of stroke for stenting than for endarterectomy, with a higher MI rate for open surgery."

In addition, "the goal of the procedure is to prevent stroke, so a higher stroke rate is a significant issue. They also noted that in a quality of life evaluation, as part of the CREST study, stroke had significantly greater impact on patient wellness than did MI. There is clearly a role for carotid stenting; however, physicians must weigh the benefits and disadvantages of each treatment methodology for a given patient. The role for any interventional therapy for asymptomatic patients is currently also being reevaluated in the era of improved medical management, with statins, plavix, and b-blockers in addition to aspirin," Dr. Harris concluded.

Earlier this year, the majority of a Food and Drug Administration advisory panel voted in favor of expanding the approved use of a carotid stent to include patients who are at standard surgical risk in addition to the previously approved indication for revascularization in patients at high surgical risk.

The FDA's Circulatory System Devices Panel voted 7-3 with 1 abstention that the benefits of the Acculink Carotid Stent, a self-expanding stent made of nickel and titanium manufactured by Abbott Vascular, outweigh the risks when used for the proposed population of patients, at standard surgical risk.

The indication under review is for the treatment of patients at standard risk for adverse events from carotid endarterectomy who require carotid revascularization and meet the following criteria: patients who have neurological symptoms and at least 70% stenosis of the common or internal carotid artery by ultrasound or at least 50% stenosis by angiogram; or patients without neurological symptoms and at least 70% stenosis of the internal carotid artery by ultrasound or at least 60% stenosis by angiogram. Patients must also have a reference vessel diameter within the range of 4.0 mm and 9.0 mm at the target lesion.

In 2004, the Acculink Carotid Stent was approved for use for carotid revascularization in patients at high risk for adverse events from carotid endarterectomy who require carotid revascularization and meet slightly different criteria.

The company filed for approval of the expanded indication to include the lower surgical risk population based on the results of the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST), a randomized multicenter noninferiority study conducted in the United States and Canada comparing the outcomes of carotid artery stenting to the preferred method, carotid endarterectomy in patients who met the criteria in the proposed indication. At 1 year, the primary safety and effectiveness end point ? death, stroke, and myocardial infarction within 30 days of having the procedure plus the rate of ipsilateral stroke from 31 to 365 days after the procedure, was 7.1% among those who received the stent (1,131 patients) and 6.6% among those who underwent endarterectomy (1,176 patients), a difference that met the prespecified criteria for noninferiority.

Different components of the composite end point - periprocedural MIs and strokes -  were elevated among patients in the two arms: In the stent arm, the rate of strokes was 4.1%, compared with 1.9% in the surgical arm. MI at 30 days was 3.4% in the surgical arm, compared with 2% in the stent arm. Panelists varied on their opinions on the clinical significance of these differences.

The Acculink stent is approved in over 90 countries and more than 128,000 have been distributed worldwide, according to Abbott Vascular.

The CREST study was funded by Abbott Vascular, and was created by NIH and the New Jersey Medical School, Newark. The FDA usually follows the recommendations of its advisory panels.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to the meeting. Occasionally, the FDA grants a waiver to a panelist with a conflict but not at this meeting.

Commenting on this story, Dr. Linda Harris, vice chair, faculty development, department of surgery, Millard Fillmore Gates Hospital-Kaleida, Buffalo, N.Y. , stated: "While FDA approval is important to allow use of the carotid stent for average risk patients, this does not guarantee that Medicare or other insurances will reimburse for patients at average risk. Further, it is important to closely dissect the CREST data, which clearly show a higher rate of stroke for stenting than for endarterectomy, with a higher MI rate for open surgery."

In addition, "the goal of the procedure is to prevent stroke, so a higher stroke rate is a significant issue. They also noted that in a quality of life evaluation, as part of the CREST study, stroke had significantly greater impact on patient wellness than did MI. There is clearly a role for carotid stenting; however, physicians must weigh the benefits and disadvantages of each treatment methodology for a given patient. The role for any interventional therapy for asymptomatic patients is currently also being reevaluated in the era of improved medical management, with statins, plavix, and b-blockers in addition to aspirin," Dr. Harris concluded.

Earlier this year, the majority of a Food and Drug Administration advisory panel voted in favor of expanding the approved use of a carotid stent to include patients who are at standard surgical risk in addition to the previously approved indication for revascularization in patients at high surgical risk.

The FDA's Circulatory System Devices Panel voted 7-3 with 1 abstention that the benefits of the Acculink Carotid Stent, a self-expanding stent made of nickel and titanium manufactured by Abbott Vascular, outweigh the risks when used for the proposed population of patients, at standard surgical risk.

The indication under review is for the treatment of patients at standard risk for adverse events from carotid endarterectomy who require carotid revascularization and meet the following criteria: patients who have neurological symptoms and at least 70% stenosis of the common or internal carotid artery by ultrasound or at least 50% stenosis by angiogram; or patients without neurological symptoms and at least 70% stenosis of the internal carotid artery by ultrasound or at least 60% stenosis by angiogram. Patients must also have a reference vessel diameter within the range of 4.0 mm and 9.0 mm at the target lesion.

In 2004, the Acculink Carotid Stent was approved for use for carotid revascularization in patients at high risk for adverse events from carotid endarterectomy who require carotid revascularization and meet slightly different criteria.

The company filed for approval of the expanded indication to include the lower surgical risk population based on the results of the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST), a randomized multicenter noninferiority study conducted in the United States and Canada comparing the outcomes of carotid artery stenting to the preferred method, carotid endarterectomy in patients who met the criteria in the proposed indication. At 1 year, the primary safety and effectiveness end point ? death, stroke, and myocardial infarction within 30 days of having the procedure plus the rate of ipsilateral stroke from 31 to 365 days after the procedure, was 7.1% among those who received the stent (1,131 patients) and 6.6% among those who underwent endarterectomy (1,176 patients), a difference that met the prespecified criteria for noninferiority.

Different components of the composite end point - periprocedural MIs and strokes -  were elevated among patients in the two arms: In the stent arm, the rate of strokes was 4.1%, compared with 1.9% in the surgical arm. MI at 30 days was 3.4% in the surgical arm, compared with 2% in the stent arm. Panelists varied on their opinions on the clinical significance of these differences.

The Acculink stent is approved in over 90 countries and more than 128,000 have been distributed worldwide, according to Abbott Vascular.

The CREST study was funded by Abbott Vascular, and was created by NIH and the New Jersey Medical School, Newark. The FDA usually follows the recommendations of its advisory panels.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to the meeting. Occasionally, the FDA grants a waiver to a panelist with a conflict but not at this meeting.

Commenting on this story, Dr. Linda Harris, vice chair, faculty development, department of surgery, Millard Fillmore Gates Hospital-Kaleida, Buffalo, N.Y. , stated: "While FDA approval is important to allow use of the carotid stent for average risk patients, this does not guarantee that Medicare or other insurances will reimburse for patients at average risk. Further, it is important to closely dissect the CREST data, which clearly show a higher rate of stroke for stenting than for endarterectomy, with a higher MI rate for open surgery."

In addition, "the goal of the procedure is to prevent stroke, so a higher stroke rate is a significant issue. They also noted that in a quality of life evaluation, as part of the CREST study, stroke had significantly greater impact on patient wellness than did MI. There is clearly a role for carotid stenting; however, physicians must weigh the benefits and disadvantages of each treatment methodology for a given patient. The role for any interventional therapy for asymptomatic patients is currently also being reevaluated in the era of improved medical management, with statins, plavix, and b-blockers in addition to aspirin," Dr. Harris concluded.

New data from a national pregnancy registry indicate an increased risk of oral clefts among infants exposed to topiramate monotherapy during the first trimester of pregnancy, which should be considered when prescribing the anticonvulsant to women of childbearing age, the Food and Drug Administration announced.

In the North American Antiepileptic Drugs Pregnancy Registry (NAAED), the prevalence of oral clefts (cleft lip or palate) was 1.4% among infants exposed in utero to topiramate monotherapy during the first trimester, compared with 0.38%-0.55% among infants exposed to other antiepileptic drugs (AEDs).

The rate was 0.07% among infants whose mothers did not have epilepsy or were not treated with other AEDs, according to an FDA statement.

In the NAAED registry, the relative risk of oral clefts among infants exposed to topiramate was 21.3 times that of the background risk among untreated women. The prevalence of oral clefts was also increased among infants exposed to topiramate monotherapy in a U.K. Epilepsy and Pregnancy Register: 3.2% among the infants exposed to topiramate monotherapy, compared with a background prevalence of 0.2% – a 16-fold increase in risk.

“Health care professionals should carefully consider the benefits and risks of topiramate when prescribing it to women of childbearing age,” and should consider alternative medications with a lower risk of birth defects, Dr. Russell Katz, director of the division of neurology products in the FDA's Center for Drug Evaluation and Research, said in the FDA statement.

The agency's announcement also notes that if the decision is made to prescribe topiramate to a woman of childbearing age, effective birth control should be used, “keeping in mind the potential for a decrease in hormonal exposure and a possible decrease in contraceptive efficacy when using estrogen-containing birth control with topiramate.”

The new information is being added to the prescribing information of topiramate, which is also being switched from a pregnancy risk category C (applied to drugs for which animal data suggest potential fetal risks, with no adequate data from human clinical trials or studies) to the pregnancy risk category D (applied to drugs for which there is evidence for human fetal risk based on human data, but potential benefits may be acceptable in certain situations, despite the risks).

Topiramate, which is marketed as Topamax and is also available in generic formulations, is approved as a treatment for epilepsy and for preventing migraine headaches.

Women who are on topiramate and become pregnant should be encouraged to register in the North American AED pregnancy registry by calling 888-233-2334.

New data from a national pregnancy registry indicate an increased risk of oral clefts among infants exposed to topiramate monotherapy during the first trimester of pregnancy, which should be considered when prescribing the anticonvulsant to women of childbearing age, the Food and Drug Administration announced.

In the North American Antiepileptic Drugs Pregnancy Registry (NAAED), the prevalence of oral clefts (cleft lip or palate) was 1.4% among infants exposed in utero to topiramate monotherapy during the first trimester, compared with 0.38%-0.55% among infants exposed to other antiepileptic drugs (AEDs).

The rate was 0.07% among infants whose mothers did not have epilepsy or were not treated with other AEDs, according to an FDA statement.

In the NAAED registry, the relative risk of oral clefts among infants exposed to topiramate was 21.3 times that of the background risk among untreated women. The prevalence of oral clefts was also increased among infants exposed to topiramate monotherapy in a U.K. Epilepsy and Pregnancy Register: 3.2% among the infants exposed to topiramate monotherapy, compared with a background prevalence of 0.2% – a 16-fold increase in risk.

“Health care professionals should carefully consider the benefits and risks of topiramate when prescribing it to women of childbearing age,” and should consider alternative medications with a lower risk of birth defects, Dr. Russell Katz, director of the division of neurology products in the FDA's Center for Drug Evaluation and Research, said in the FDA statement.

The agency's announcement also notes that if the decision is made to prescribe topiramate to a woman of childbearing age, effective birth control should be used, “keeping in mind the potential for a decrease in hormonal exposure and a possible decrease in contraceptive efficacy when using estrogen-containing birth control with topiramate.”

The new information is being added to the prescribing information of topiramate, which is also being switched from a pregnancy risk category C (applied to drugs for which animal data suggest potential fetal risks, with no adequate data from human clinical trials or studies) to the pregnancy risk category D (applied to drugs for which there is evidence for human fetal risk based on human data, but potential benefits may be acceptable in certain situations, despite the risks).

Topiramate, which is marketed as Topamax and is also available in generic formulations, is approved as a treatment for epilepsy and for preventing migraine headaches.

Women who are on topiramate and become pregnant should be encouraged to register in the North American AED pregnancy registry by calling 888-233-2334.

New data from a national pregnancy registry indicate an increased risk of oral clefts among infants exposed to topiramate monotherapy during the first trimester of pregnancy, which should be considered when prescribing the anticonvulsant to women of childbearing age, the Food and Drug Administration announced.

In the North American Antiepileptic Drugs Pregnancy Registry (NAAED), the prevalence of oral clefts (cleft lip or palate) was 1.4% among infants exposed in utero to topiramate monotherapy during the first trimester, compared with 0.38%-0.55% among infants exposed to other antiepileptic drugs (AEDs).

The rate was 0.07% among infants whose mothers did not have epilepsy or were not treated with other AEDs, according to an FDA statement.

In the NAAED registry, the relative risk of oral clefts among infants exposed to topiramate was 21.3 times that of the background risk among untreated women. The prevalence of oral clefts was also increased among infants exposed to topiramate monotherapy in a U.K. Epilepsy and Pregnancy Register: 3.2% among the infants exposed to topiramate monotherapy, compared with a background prevalence of 0.2% – a 16-fold increase in risk.

“Health care professionals should carefully consider the benefits and risks of topiramate when prescribing it to women of childbearing age,” and should consider alternative medications with a lower risk of birth defects, Dr. Russell Katz, director of the division of neurology products in the FDA's Center for Drug Evaluation and Research, said in the FDA statement.

The agency's announcement also notes that if the decision is made to prescribe topiramate to a woman of childbearing age, effective birth control should be used, “keeping in mind the potential for a decrease in hormonal exposure and a possible decrease in contraceptive efficacy when using estrogen-containing birth control with topiramate.”

The new information is being added to the prescribing information of topiramate, which is also being switched from a pregnancy risk category C (applied to drugs for which animal data suggest potential fetal risks, with no adequate data from human clinical trials or studies) to the pregnancy risk category D (applied to drugs for which there is evidence for human fetal risk based on human data, but potential benefits may be acceptable in certain situations, despite the risks).

Topiramate, which is marketed as Topamax and is also available in generic formulations, is approved as a treatment for epilepsy and for preventing migraine headaches.

Women who are on topiramate and become pregnant should be encouraged to register in the North American AED pregnancy registry by calling 888-233-2334.