Elizabeth Mechcatie

Reports have linked long-term use of proton pump inhibitors with hypomagnesemia, and discontinuation of the drug might be necessary for resolution of symptoms, the Food and Drug Administration announced on March 2.

"Consider PPIs as a possible cause of hypomagnesemia, particularly in patients who are clinically symptomatic," according to the FDA statement posted on the agency’s MedWatch site. In the statement, the agency recommended that health care professionals "should consider obtaining serum magnesium levels prior to initiation of prescription PPI treatment in patients expected to be on these drugs for long periods of time, as well as patients who take PPIs with medications such as digoxin, diuretics, or drugs that may cause hypomagnesemia." They should also consider periodically checking magnesium levels in these patients, the statement adds.

The alert was prompted by a review of 38 cases of hypomagnesemia in patients on prolonged PPI therapy reported to the FDA’s Adverse Event Reporting System and 23 cases reported in the medical literature (which included at least 8 of the AERS reports), which "suggests there is an association between serious adverse events related to hypomagnesemia and prolonged PPI use," the FDA said.

Some cases of hypomagnesemia have been reported in adults taking PPIs for at least 3 months, but most cases have been reported in people who have taken the PPI for more than a year. In some cases, treatment with magnesium supplements was not adequate and the patient has to stop taking the PPI to achieve resolution of symptoms, according to the FDA.

While the mechanism for hypomagnesemia is not known, long-term use of PPIs may affect intestinal absorption of magnesium, the statement said.

If over-the-counter PPIs are used as labeled, at low doses and only for 14 days of treatment up to three times a year, "FDA believes that there is very little risk of hypomagnesemia," the statement said.

Currently available prescription PPIs include esomeprazole magnesium (Nexium), dexlansoprazole (Dexilant), omeprazole (Prilosec), omeprazole and sodium bicarbonate (Zegerid), lansoprazole (Prevacid), pantoprazole sodium (Protonix), and rabeprazole sodium (AcipHex).

In 2009, about 21 million prescriptions for PPIs were filled at outpatient retail pharmacies in the United States, and people who take prescription PPIs usually continue treatment for an average of about 180 days, according to the FDA.

Serious adverse events associated with the use of PPIs and other drugs should be reported at the MedWatch Web site or by phoning 800-332-1088.

Reports have linked long-term use of proton pump inhibitors with hypomagnesemia, and discontinuation of the drug might be necessary for resolution of symptoms, the Food and Drug Administration announced on March 2.

"Consider PPIs as a possible cause of hypomagnesemia, particularly in patients who are clinically symptomatic," according to the FDA statement posted on the agency’s MedWatch site. In the statement, the agency recommended that health care professionals "should consider obtaining serum magnesium levels prior to initiation of prescription PPI treatment in patients expected to be on these drugs for long periods of time, as well as patients who take PPIs with medications such as digoxin, diuretics, or drugs that may cause hypomagnesemia." They should also consider periodically checking magnesium levels in these patients, the statement adds.

The alert was prompted by a review of 38 cases of hypomagnesemia in patients on prolonged PPI therapy reported to the FDA’s Adverse Event Reporting System and 23 cases reported in the medical literature (which included at least 8 of the AERS reports), which "suggests there is an association between serious adverse events related to hypomagnesemia and prolonged PPI use," the FDA said.

Some cases of hypomagnesemia have been reported in adults taking PPIs for at least 3 months, but most cases have been reported in people who have taken the PPI for more than a year. In some cases, treatment with magnesium supplements was not adequate and the patient has to stop taking the PPI to achieve resolution of symptoms, according to the FDA.

While the mechanism for hypomagnesemia is not known, long-term use of PPIs may affect intestinal absorption of magnesium, the statement said.

If over-the-counter PPIs are used as labeled, at low doses and only for 14 days of treatment up to three times a year, "FDA believes that there is very little risk of hypomagnesemia," the statement said.

Currently available prescription PPIs include esomeprazole magnesium (Nexium), dexlansoprazole (Dexilant), omeprazole (Prilosec), omeprazole and sodium bicarbonate (Zegerid), lansoprazole (Prevacid), pantoprazole sodium (Protonix), and rabeprazole sodium (AcipHex).

In 2009, about 21 million prescriptions for PPIs were filled at outpatient retail pharmacies in the United States, and people who take prescription PPIs usually continue treatment for an average of about 180 days, according to the FDA.

Serious adverse events associated with the use of PPIs and other drugs should be reported at the MedWatch Web site or by phoning 800-332-1088.

Reports have linked long-term use of proton pump inhibitors with hypomagnesemia, and discontinuation of the drug might be necessary for resolution of symptoms, the Food and Drug Administration announced on March 2.

"Consider PPIs as a possible cause of hypomagnesemia, particularly in patients who are clinically symptomatic," according to the FDA statement posted on the agency’s MedWatch site. In the statement, the agency recommended that health care professionals "should consider obtaining serum magnesium levels prior to initiation of prescription PPI treatment in patients expected to be on these drugs for long periods of time, as well as patients who take PPIs with medications such as digoxin, diuretics, or drugs that may cause hypomagnesemia." They should also consider periodically checking magnesium levels in these patients, the statement adds.

The alert was prompted by a review of 38 cases of hypomagnesemia in patients on prolonged PPI therapy reported to the FDA’s Adverse Event Reporting System and 23 cases reported in the medical literature (which included at least 8 of the AERS reports), which "suggests there is an association between serious adverse events related to hypomagnesemia and prolonged PPI use," the FDA said.

Some cases of hypomagnesemia have been reported in adults taking PPIs for at least 3 months, but most cases have been reported in people who have taken the PPI for more than a year. In some cases, treatment with magnesium supplements was not adequate and the patient has to stop taking the PPI to achieve resolution of symptoms, according to the FDA.

While the mechanism for hypomagnesemia is not known, long-term use of PPIs may affect intestinal absorption of magnesium, the statement said.

If over-the-counter PPIs are used as labeled, at low doses and only for 14 days of treatment up to three times a year, "FDA believes that there is very little risk of hypomagnesemia," the statement said.

Currently available prescription PPIs include esomeprazole magnesium (Nexium), dexlansoprazole (Dexilant), omeprazole (Prilosec), omeprazole and sodium bicarbonate (Zegerid), lansoprazole (Prevacid), pantoprazole sodium (Protonix), and rabeprazole sodium (AcipHex).

In 2009, about 21 million prescriptions for PPIs were filled at outpatient retail pharmacies in the United States, and people who take prescription PPIs usually continue treatment for an average of about 180 days, according to the FDA.

Serious adverse events associated with the use of PPIs and other drugs should be reported at the MedWatch Web site or by phoning 800-332-1088.

Reports have linked long-term use of proton pump inhibitors with hypomagnesemia, and discontinuation of the drug might be necessary for resolution of symptoms, the Food and Drug Administration announced on March 2.

"Consider PPIs as a possible cause of hypomagnesemia, particularly in patients who are clinically symptomatic," according to the FDA statement posted on the agency’s MedWatch site. In the statement, the agency recommended that health care professionals "should consider obtaining serum magnesium levels prior to initiation of prescription PPI treatment in patients expected to be on these drugs for long periods of time, as well as patients who take PPIs with medications such as digoxin, diuretics, or drugs that may cause hypomagnesemia." They should also consider periodically checking magnesium levels in these patients, the statement adds.

The alert was prompted by a review of 38 cases of hypomagnesemia in patients on prolonged PPI therapy reported to the FDA’s Adverse Event Reporting System and 23 cases reported in the medical literature (which included at least 8 of the AERS reports), which "suggests there is an association between serious adverse events related to hypomagnesemia and prolonged PPI use," the FDA said.

Some cases of hypomagnesemia have been reported in adults taking PPIs for at least 3 months, but most cases have been reported in people who have taken the PPI for more than a year. In some cases, treatment with magnesium supplements was not adequate and the patient has to stop taking the PPI to achieve resolution of symptoms, according to the FDA.

While the mechanism for hypomagnesemia is not known, long-term use of PPIs may affect intestinal absorption of magnesium, the statement said.

If over-the-counter PPIs are used as labeled, at low doses and only for 14 days of treatment up to three times a year, "FDA believes that there is very little risk of hypomagnesemia," the statement said.

Currently available prescription PPIs include esomeprazole magnesium (Nexium), dexlansoprazole (Dexilant), omeprazole (Prilosec), omeprazole and sodium bicarbonate (Zegerid), lansoprazole (Prevacid), pantoprazole sodium (Protonix), and rabeprazole sodium (AcipHex).

In 2009, about 21 million prescriptions for PPIs were filled at outpatient retail pharmacies in the United States, and people who take prescription PPIs usually continue treatment for an average of about 180 days, according to the FDA.

Serious adverse events associated with the use of PPIs and other drugs should be reported at the MedWatch Web site or by phoning 800-332-1088.

Reports have linked long-term use of proton pump inhibitors with hypomagnesemia, and discontinuation of the drug might be necessary for resolution of symptoms, the Food and Drug Administration announced on March 2.

"Consider PPIs as a possible cause of hypomagnesemia, particularly in patients who are clinically symptomatic," according to the FDA statement posted on the agency’s MedWatch site. In the statement, the agency recommended that health care professionals "should consider obtaining serum magnesium levels prior to initiation of prescription PPI treatment in patients expected to be on these drugs for long periods of time, as well as patients who take PPIs with medications such as digoxin, diuretics, or drugs that may cause hypomagnesemia." They should also consider periodically checking magnesium levels in these patients, the statement adds.

The alert was prompted by a review of 38 cases of hypomagnesemia in patients on prolonged PPI therapy reported to the FDA’s Adverse Event Reporting System and 23 cases reported in the medical literature (which included at least 8 of the AERS reports), which "suggests there is an association between serious adverse events related to hypomagnesemia and prolonged PPI use," the FDA said.

Some cases of hypomagnesemia have been reported in adults taking PPIs for at least 3 months, but most cases have been reported in people who have taken the PPI for more than a year. In some cases, treatment with magnesium supplements was not adequate and the patient has to stop taking the PPI to achieve resolution of symptoms, according to the FDA.

While the mechanism for hypomagnesemia is not known, long-term use of PPIs may affect intestinal absorption of magnesium, the statement said.

If over-the-counter PPIs are used as labeled, at low doses and only for 14 days of treatment up to three times a year, "FDA believes that there is very little risk of hypomagnesemia," the statement said.

Currently available prescription PPIs include esomeprazole magnesium (Nexium), dexlansoprazole (Dexilant), omeprazole (Prilosec), omeprazole and sodium bicarbonate (Zegerid), lansoprazole (Prevacid), pantoprazole sodium (Protonix), and rabeprazole sodium (AcipHex).

In 2009, about 21 million prescriptions for PPIs were filled at outpatient retail pharmacies in the United States, and people who take prescription PPIs usually continue treatment for an average of about 180 days, according to the FDA.

Serious adverse events associated with the use of PPIs and other drugs should be reported at the MedWatch Web site or by phoning 800-332-1088.

Reports have linked long-term use of proton pump inhibitors with hypomagnesemia, and discontinuation of the drug might be necessary for resolution of symptoms, the Food and Drug Administration announced on March 2.

"Consider PPIs as a possible cause of hypomagnesemia, particularly in patients who are clinically symptomatic," according to the FDA statement posted on the agency’s MedWatch site. In the statement, the agency recommended that health care professionals "should consider obtaining serum magnesium levels prior to initiation of prescription PPI treatment in patients expected to be on these drugs for long periods of time, as well as patients who take PPIs with medications such as digoxin, diuretics, or drugs that may cause hypomagnesemia." They should also consider periodically checking magnesium levels in these patients, the statement adds.

The alert was prompted by a review of 38 cases of hypomagnesemia in patients on prolonged PPI therapy reported to the FDA’s Adverse Event Reporting System and 23 cases reported in the medical literature (which included at least 8 of the AERS reports), which "suggests there is an association between serious adverse events related to hypomagnesemia and prolonged PPI use," the FDA said.

Some cases of hypomagnesemia have been reported in adults taking PPIs for at least 3 months, but most cases have been reported in people who have taken the PPI for more than a year. In some cases, treatment with magnesium supplements was not adequate and the patient has to stop taking the PPI to achieve resolution of symptoms, according to the FDA.

While the mechanism for hypomagnesemia is not known, long-term use of PPIs may affect intestinal absorption of magnesium, the statement said.

If over-the-counter PPIs are used as labeled, at low doses and only for 14 days of treatment up to three times a year, "FDA believes that there is very little risk of hypomagnesemia," the statement said.

Currently available prescription PPIs include esomeprazole magnesium (Nexium), dexlansoprazole (Dexilant), omeprazole (Prilosec), omeprazole and sodium bicarbonate (Zegerid), lansoprazole (Prevacid), pantoprazole sodium (Protonix), and rabeprazole sodium (AcipHex).

In 2009, about 21 million prescriptions for PPIs were filled at outpatient retail pharmacies in the United States, and people who take prescription PPIs usually continue treatment for an average of about 180 days, according to the FDA.

Serious adverse events associated with the use of PPIs and other drugs should be reported at the MedWatch Web site or by phoning 800-332-1088.

Reports have linked long-term use of proton pump inhibitors with hypomagnesemia, and discontinuation of the drug might be necessary for resolution of symptoms, the Food and Drug Administration announced on March 2.

"Consider PPIs as a possible cause of hypomagnesemia, particularly in patients who are clinically symptomatic," according to the FDA statement posted on the agency’s MedWatch site. In the statement, the agency recommended that health care professionals "should consider obtaining serum magnesium levels prior to initiation of prescription PPI treatment in patients expected to be on these drugs for long periods of time, as well as patients who take PPIs with medications such as digoxin, diuretics, or drugs that may cause hypomagnesemia." They should also consider periodically checking magnesium levels in these patients, the statement adds.

The alert was prompted by a review of 38 cases of hypomagnesemia in patients on prolonged PPI therapy reported to the FDA’s Adverse Event Reporting System and 23 cases reported in the medical literature (which included at least 8 of the AERS reports), which "suggests there is an association between serious adverse events related to hypomagnesemia and prolonged PPI use," the FDA said.

Some cases of hypomagnesemia have been reported in adults taking PPIs for at least 3 months, but most cases have been reported in people who have taken the PPI for more than a year. In some cases, treatment with magnesium supplements was not adequate and the patient has to stop taking the PPI to achieve resolution of symptoms, according to the FDA.

While the mechanism for hypomagnesemia is not known, long-term use of PPIs may affect intestinal absorption of magnesium, the statement said.

If over-the-counter PPIs are used as labeled, at low doses and only for 14 days of treatment up to three times a year, "FDA believes that there is very little risk of hypomagnesemia," the statement said.

Currently available prescription PPIs include esomeprazole magnesium (Nexium), dexlansoprazole (Dexilant), omeprazole (Prilosec), omeprazole and sodium bicarbonate (Zegerid), lansoprazole (Prevacid), pantoprazole sodium (Protonix), and rabeprazole sodium (AcipHex).

In 2009, about 21 million prescriptions for PPIs were filled at outpatient retail pharmacies in the United States, and people who take prescription PPIs usually continue treatment for an average of about 180 days, according to the FDA.

Serious adverse events associated with the use of PPIs and other drugs should be reported at the MedWatch Web site or by phoning 800-332-1088.

Reports have linked long-term use of proton pump inhibitors with hypomagnesemia, and discontinuation of the drug might be necessary for resolution of symptoms, the Food and Drug Administration announced on March 2.

"Consider PPIs as a possible cause of hypomagnesemia, particularly in patients who are clinically symptomatic," according to the FDA statement posted on the agency’s MedWatch site. In the statement, the agency recommended that health care professionals "should consider obtaining serum magnesium levels prior to initiation of prescription PPI treatment in patients expected to be on these drugs for long periods of time, as well as patients who take PPIs with medications such as digoxin, diuretics, or drugs that may cause hypomagnesemia." They should also consider periodically checking magnesium levels in these patients, the statement adds.

The alert was prompted by a review of 38 cases of hypomagnesemia in patients on prolonged PPI therapy reported to the FDA’s Adverse Event Reporting System and 23 cases reported in the medical literature (which included at least 8 of the AERS reports), which "suggests there is an association between serious adverse events related to hypomagnesemia and prolonged PPI use," the FDA said.

Some cases of hypomagnesemia have been reported in adults taking PPIs for at least 3 months, but most cases have been reported in people who have taken the PPI for more than a year. In some cases, treatment with magnesium supplements was not adequate and the patient has to stop taking the PPI to achieve resolution of symptoms, according to the FDA.

While the mechanism for hypomagnesemia is not known, long-term use of PPIs may affect intestinal absorption of magnesium, the statement said.

If over-the-counter PPIs are used as labeled, at low doses and only for 14 days of treatment up to three times a year, "FDA believes that there is very little risk of hypomagnesemia," the statement said.

Currently available prescription PPIs include esomeprazole magnesium (Nexium), dexlansoprazole (Dexilant), omeprazole (Prilosec), omeprazole and sodium bicarbonate (Zegerid), lansoprazole (Prevacid), pantoprazole sodium (Protonix), and rabeprazole sodium (AcipHex).

In 2009, about 21 million prescriptions for PPIs were filled at outpatient retail pharmacies in the United States, and people who take prescription PPIs usually continue treatment for an average of about 180 days, according to the FDA.

Serious adverse events associated with the use of PPIs and other drugs should be reported at the MedWatch Web site or by phoning 800-332-1088.

Reports have linked long-term use of proton pump inhibitors with hypomagnesemia, and discontinuation of the drug might be necessary for resolution of symptoms, the Food and Drug Administration announced on March 2.

"Consider PPIs as a possible cause of hypomagnesemia, particularly in patients who are clinically symptomatic," according to the FDA statement posted on the agency’s MedWatch site. In the statement, the agency recommended that health care professionals "should consider obtaining serum magnesium levels prior to initiation of prescription PPI treatment in patients expected to be on these drugs for long periods of time, as well as patients who take PPIs with medications such as digoxin, diuretics, or drugs that may cause hypomagnesemia." They should also consider periodically checking magnesium levels in these patients, the statement adds.

The alert was prompted by a review of 38 cases of hypomagnesemia in patients on prolonged PPI therapy reported to the FDA’s Adverse Event Reporting System and 23 cases reported in the medical literature (which included at least 8 of the AERS reports), which "suggests there is an association between serious adverse events related to hypomagnesemia and prolonged PPI use," the FDA said.

Some cases of hypomagnesemia have been reported in adults taking PPIs for at least 3 months, but most cases have been reported in people who have taken the PPI for more than a year. In some cases, treatment with magnesium supplements was not adequate and the patient has to stop taking the PPI to achieve resolution of symptoms, according to the FDA.

While the mechanism for hypomagnesemia is not known, long-term use of PPIs may affect intestinal absorption of magnesium, the statement said.

If over-the-counter PPIs are used as labeled, at low doses and only for 14 days of treatment up to three times a year, "FDA believes that there is very little risk of hypomagnesemia," the statement said.

Currently available prescription PPIs include esomeprazole magnesium (Nexium), dexlansoprazole (Dexilant), omeprazole (Prilosec), omeprazole and sodium bicarbonate (Zegerid), lansoprazole (Prevacid), pantoprazole sodium (Protonix), and rabeprazole sodium (AcipHex).

In 2009, about 21 million prescriptions for PPIs were filled at outpatient retail pharmacies in the United States, and people who take prescription PPIs usually continue treatment for an average of about 180 days, according to the FDA.

Serious adverse events associated with the use of PPIs and other drugs should be reported at the MedWatch Web site or by phoning 800-332-1088.

The Food and Drug Administration has issued a warning advising against the use of injectable terbutaline for preventing and for prolonged treatment of preterm labor and against any use of oral terbutaline in this setting, prompted by postmarketing reports of deaths and other serious cardiovascular events associated with the use of the drug in this setting.

“Death and serious adverse reactions, including increased heart rate, transient hyperglycemia, hypokalemia, cardiac arrhythmias, pulmonary edema, and myocardial ischemia have been reported after prolonged administration of oral or injectable terbutaline to pregnant women,” according to an FDA statement.

Based on these reports and a review of the medical literature, the agency “has concluded that the risk of serious adverse events outweighs any potential benefit to pregnant women receiving prolonged treatment with terbutaline injection (beyond 48–72 hours), or acute or prolonged treatment with oral terbutaline,” the FDA said.

This is not the first FDA warning issued about the obstetric-related risks of terbutaline, an FDA-approved treatment for bronchospasm that has been used off label to treat and prevent preterm labor and to treat uterine hyperstimulation. In 1997, the agency notified health care professionals in a letter about concerns over the safety of long-term administration of subcutaneous terbutaline and revised the drug's labeling about the risk of serious cardiovascular adverse events associated with this use. But despite studies reporting a lack of safety and efficacy of terbutaline for the treatment of recurrent preterm labor and professional association recommendations, “prolonged use of terbutaline continues, with serious and sometimes fatal consequences,” the FDA statement said.

Between 1976, when terbutaline was first marketed, and 2009, 16 maternal deaths associated with the obstetric use of terbutaline were reported to the FDA's Adverse Event Reporting System (AERS). Between January 1998, soon after the FDA issued the warning letter, and July 2009, 12 maternal cases of serious cardiovascular events associated with the use of terbutaline were reported.

While there are “certain obstetrical conditions” in which health care professionals “may decide that the benefit of terbutaline injection for an individual patient in a hospital setting clearly outweighs the risk,” the FDA statement said that terbutaline administered by injection or continuous infusion pump should not be used for more than 48–72 hours, and injectable terbutaline should not be used in outpatient settings. These warnings are being added to a new boxed warning in terbutaline labels.

In an interview, Dr. Washington Hill of Sarasota (Fla.) Memorial Hospital, welcomed the FDA warnings. Still, he cautioned that subcutaneous terbutaline should not be entirely abandoned because there are some obstetric situations where its use is beneficial, when used in the hospital setting and not in a pump. These include reducing contractions in a woman with tachysystole of the uterus due to pitocin or for intrauterine resuscitation, adjunct to external cephalic version, relaxing an inverted uterus or as an adjunct to managing inversion of the uterus, transporting a patient with contractions from one location to another, and rarely when delivering a second twin when the uterus needs to be relaxed.

Dr. Hill had no relevant financial disclosures.

The Food and Drug Administration has issued a warning advising against the use of injectable terbutaline for preventing and for prolonged treatment of preterm labor and against any use of oral terbutaline in this setting, prompted by postmarketing reports of deaths and other serious cardiovascular events associated with the use of the drug in this setting.

“Death and serious adverse reactions, including increased heart rate, transient hyperglycemia, hypokalemia, cardiac arrhythmias, pulmonary edema, and myocardial ischemia have been reported after prolonged administration of oral or injectable terbutaline to pregnant women,” according to an FDA statement.

Based on these reports and a review of the medical literature, the agency “has concluded that the risk of serious adverse events outweighs any potential benefit to pregnant women receiving prolonged treatment with terbutaline injection (beyond 48–72 hours), or acute or prolonged treatment with oral terbutaline,” the FDA said.

This is not the first FDA warning issued about the obstetric-related risks of terbutaline, an FDA-approved treatment for bronchospasm that has been used off label to treat and prevent preterm labor and to treat uterine hyperstimulation. In 1997, the agency notified health care professionals in a letter about concerns over the safety of long-term administration of subcutaneous terbutaline and revised the drug's labeling about the risk of serious cardiovascular adverse events associated with this use. But despite studies reporting a lack of safety and efficacy of terbutaline for the treatment of recurrent preterm labor and professional association recommendations, “prolonged use of terbutaline continues, with serious and sometimes fatal consequences,” the FDA statement said.

Between 1976, when terbutaline was first marketed, and 2009, 16 maternal deaths associated with the obstetric use of terbutaline were reported to the FDA's Adverse Event Reporting System (AERS). Between January 1998, soon after the FDA issued the warning letter, and July 2009, 12 maternal cases of serious cardiovascular events associated with the use of terbutaline were reported.

While there are “certain obstetrical conditions” in which health care professionals “may decide that the benefit of terbutaline injection for an individual patient in a hospital setting clearly outweighs the risk,” the FDA statement said that terbutaline administered by injection or continuous infusion pump should not be used for more than 48–72 hours, and injectable terbutaline should not be used in outpatient settings. These warnings are being added to a new boxed warning in terbutaline labels.

In an interview, Dr. Washington Hill of Sarasota (Fla.) Memorial Hospital, welcomed the FDA warnings. Still, he cautioned that subcutaneous terbutaline should not be entirely abandoned because there are some obstetric situations where its use is beneficial, when used in the hospital setting and not in a pump. These include reducing contractions in a woman with tachysystole of the uterus due to pitocin or for intrauterine resuscitation, adjunct to external cephalic version, relaxing an inverted uterus or as an adjunct to managing inversion of the uterus, transporting a patient with contractions from one location to another, and rarely when delivering a second twin when the uterus needs to be relaxed.

Dr. Hill had no relevant financial disclosures.

The Food and Drug Administration has issued a warning advising against the use of injectable terbutaline for preventing and for prolonged treatment of preterm labor and against any use of oral terbutaline in this setting, prompted by postmarketing reports of deaths and other serious cardiovascular events associated with the use of the drug in this setting.

“Death and serious adverse reactions, including increased heart rate, transient hyperglycemia, hypokalemia, cardiac arrhythmias, pulmonary edema, and myocardial ischemia have been reported after prolonged administration of oral or injectable terbutaline to pregnant women,” according to an FDA statement.

Based on these reports and a review of the medical literature, the agency “has concluded that the risk of serious adverse events outweighs any potential benefit to pregnant women receiving prolonged treatment with terbutaline injection (beyond 48–72 hours), or acute or prolonged treatment with oral terbutaline,” the FDA said.

This is not the first FDA warning issued about the obstetric-related risks of terbutaline, an FDA-approved treatment for bronchospasm that has been used off label to treat and prevent preterm labor and to treat uterine hyperstimulation. In 1997, the agency notified health care professionals in a letter about concerns over the safety of long-term administration of subcutaneous terbutaline and revised the drug's labeling about the risk of serious cardiovascular adverse events associated with this use. But despite studies reporting a lack of safety and efficacy of terbutaline for the treatment of recurrent preterm labor and professional association recommendations, “prolonged use of terbutaline continues, with serious and sometimes fatal consequences,” the FDA statement said.

Between 1976, when terbutaline was first marketed, and 2009, 16 maternal deaths associated with the obstetric use of terbutaline were reported to the FDA's Adverse Event Reporting System (AERS). Between January 1998, soon after the FDA issued the warning letter, and July 2009, 12 maternal cases of serious cardiovascular events associated with the use of terbutaline were reported.

While there are “certain obstetrical conditions” in which health care professionals “may decide that the benefit of terbutaline injection for an individual patient in a hospital setting clearly outweighs the risk,” the FDA statement said that terbutaline administered by injection or continuous infusion pump should not be used for more than 48–72 hours, and injectable terbutaline should not be used in outpatient settings. These warnings are being added to a new boxed warning in terbutaline labels.

In an interview, Dr. Washington Hill of Sarasota (Fla.) Memorial Hospital, welcomed the FDA warnings. Still, he cautioned that subcutaneous terbutaline should not be entirely abandoned because there are some obstetric situations where its use is beneficial, when used in the hospital setting and not in a pump. These include reducing contractions in a woman with tachysystole of the uterus due to pitocin or for intrauterine resuscitation, adjunct to external cephalic version, relaxing an inverted uterus or as an adjunct to managing inversion of the uterus, transporting a patient with contractions from one location to another, and rarely when delivering a second twin when the uterus needs to be relaxed.

Dr. Hill had no relevant financial disclosures.

Guanfacine has been approved by the Food and Drug Administration as an adjunct to stimulant medications for the treatment of attention-deficit/hyperactivity disorder in children and adolescents aged 6–17, the manufacturer announced in a statement.

The extended-release form of the drug, a selective alpha-2A adrenergic receptor agonist, previously had been approved as monotherapy for treating ADHD. The adjunctive therapy indication was based on a 9-week study of children and adolescents, according to the prescribing information for guanfacine, marketed as Intuniv by Shire PLC. The 9-week study included 455 patients with ADHD who had a suboptimal response to stimulant treatment.

Patients were randomized to receive a dose of guanfacine or placebo in the morning or evening or placebo in combination with the stimulant they had been receiving, with the dose of guanfacine starting at 1 mg titrated weekly over a 5-week period to a maximum of 4 mg/day, based on tolerability and clinical response.

At the end of 9 weeks, the mean reductions in total scores on the ADHD rating scale (ADHD-RS-IV) were significantly greater among those who received the combination than among those who continued on the psycho-stimulant alone.

The prescribing information states that it is indicated “as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, and social) for patients with this syndrome.”

Guanfacine has been approved by the Food and Drug Administration as an adjunct to stimulant medications for the treatment of attention-deficit/hyperactivity disorder in children and adolescents aged 6–17, the manufacturer announced in a statement.

The extended-release form of the drug, a selective alpha-2A adrenergic receptor agonist, previously had been approved as monotherapy for treating ADHD. The adjunctive therapy indication was based on a 9-week study of children and adolescents, according to the prescribing information for guanfacine, marketed as Intuniv by Shire PLC. The 9-week study included 455 patients with ADHD who had a suboptimal response to stimulant treatment.

Patients were randomized to receive a dose of guanfacine or placebo in the morning or evening or placebo in combination with the stimulant they had been receiving, with the dose of guanfacine starting at 1 mg titrated weekly over a 5-week period to a maximum of 4 mg/day, based on tolerability and clinical response.

At the end of 9 weeks, the mean reductions in total scores on the ADHD rating scale (ADHD-RS-IV) were significantly greater among those who received the combination than among those who continued on the psycho-stimulant alone.

The prescribing information states that it is indicated “as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, and social) for patients with this syndrome.”

Guanfacine has been approved by the Food and Drug Administration as an adjunct to stimulant medications for the treatment of attention-deficit/hyperactivity disorder in children and adolescents aged 6–17, the manufacturer announced in a statement.

The extended-release form of the drug, a selective alpha-2A adrenergic receptor agonist, previously had been approved as monotherapy for treating ADHD. The adjunctive therapy indication was based on a 9-week study of children and adolescents, according to the prescribing information for guanfacine, marketed as Intuniv by Shire PLC. The 9-week study included 455 patients with ADHD who had a suboptimal response to stimulant treatment.

Patients were randomized to receive a dose of guanfacine or placebo in the morning or evening or placebo in combination with the stimulant they had been receiving, with the dose of guanfacine starting at 1 mg titrated weekly over a 5-week period to a maximum of 4 mg/day, based on tolerability and clinical response.

At the end of 9 weeks, the mean reductions in total scores on the ADHD rating scale (ADHD-RS-IV) were significantly greater among those who received the combination than among those who continued on the psycho-stimulant alone.

The prescribing information states that it is indicated “as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, and social) for patients with this syndrome.”

In a study that identified independent risk factors for respiratory syncytial virus lower respiratory tract infections in a group of healthy term newborns, investigators in the Netherlands developed “a simple prediction rule” that they say can be used in clinical practice to identify healthy newborns at high risk for being treated as outpatients for these infections during the first year of life.

In the prospective birth cohort study of 298 healthy term babies born in two large urban Dutch hospitals between January 2006 and December 2008 who were followed for a year, the following were identified as independent predictors for respiratory syncytial virus (RSV) lower respiratory tract infections (LRTI): day-care attendance and/or having siblings, high parental education level, birth weight over 4 kg, and birth from April to September.

The risk of RSV LRTI was 10 times higher for children with these four factors, compared with children without these factors (Pediatrics 2011;127:35-41).

Using statistical analyses of the association between these predictors and the presence or absence of RSV LRTI, Dr. Michiel Houben of Wilhelmina Children's Hospital, Utrecht, the Netherlands, and his associates derived the prediction rule, with scores ranging from 0 to 5. The absolute risk of having an RSV LRTI ranged from 3% for a child with a score of 2 or less (20% of the children) to 32% for a child with a score of 5 and all four of these factors (8% of the children).

“Clinicians can use these features to differentiate between children with high and low risks of RSV LRTI and subsequently can target preventive and monitoring strategies to children at high risk,” he and his coauthors concluded.

They noted that to date, clinical prediction models have only been developed for predicting hospitalization in preterm infants, and as far as they know, theirs is the first study that “attempts to predict the risk of nonhospitalized RSV LRTI for healthy newborns by using molecular detection of RSV.”

The primary outcome measured in the study was RSV LRTI, which was based on a positive RSV polymerase chain reaction test result and symptoms of acute wheezing or a moderate/severe cough. Parents recorded their children's respiratory symptoms with daily logs and used nose and throat swabs when the child had a respiratory tract infection. During their first year of life, 42 (14%) of the 298 children had an RSV LRTI.

With the formula they derived, 1 point was assigned for a birth weight over 4 kg, 1 point for being born from April to September, 2 points for being in day care or having siblings, and 1 point for a high parental education level. In an example they provided, a baby born in July (1 point) and who is in day care (2 points), who weighed 4.2 kg at birth (1 point) and has parents who are not highly educated (0 points) would have a score of 4 points, corresponding to a “probability of developing a RSV LRTI of 23%,” they wrote.

Because of the “extremely high” incidence of medically attended RSV infection, “children classified as being at high risk could be monitored more closely and lifestyle changes that reduce exposure could be applied,” Dr. Houben and associates added.

One of the study authors received research funding and speaker's fees from Abbott International; the other authors indicated they had no relevant financial disclosures.

View on the News

Study: Well Done, but Raises Concerns

If clinicians used this type of prediction rule in their practices, Dr. Lance Chilton said it would be used to identify those at the highest risk – with scores of 4 or 5 – rather than using a low score as a basis to advise parents not to worry. Some of the factors that are in the formula are modifiable, he pointed out, noting that a score of 4 or 5 might influence parents to decide to take their children out of day care.

Dr. Chilton said that he is not aware of any clinicians who use a predictive scoring system to identify newborns at highest risk of RSV infection.

“If you asked a group of pediatricians what they used as a means of prediction as to who is at highest risk of RSV infection, most would come up with day-care attendance and older siblings, and none of them would have guessed that higher educational achievement would be positively correlated with risk of a medically attended RSV infection,” he said in an interview. “And most would say that they recommend that all babies stay away from coughing people and crowds of people during the winter virus season.”

While he thought the study appeared to be well done, he pointed out that there are major differences in hospitalization rates for RSV between United States and European epidemiologic studies, and that there are likely other differences, such as the use of emergency departments for treatment rather than general practices. One concern he had was that the study might be used “as a means to suggest” that newborns with a score of 4 or 5 be given palivizumab (Synagis), “which would markedly increase costs without any proof of effectiveness, let alone cost-effectiveness.”

DR. CHILTON is a pediatrician at the Young Children's Health Center at the University of New Mexico, Albuquerque. Dr. Chilton, formerly the chair of the Center for Disease Control and Prevention's working group on RSV immunoprophylaxis, said he had no relevant financial disclosures.

In a study that identified independent risk factors for respiratory syncytial virus lower respiratory tract infections in a group of healthy term newborns, investigators in the Netherlands developed “a simple prediction rule” that they say can be used in clinical practice to identify healthy newborns at high risk for being treated as outpatients for these infections during the first year of life.

In the prospective birth cohort study of 298 healthy term babies born in two large urban Dutch hospitals between January 2006 and December 2008 who were followed for a year, the following were identified as independent predictors for respiratory syncytial virus (RSV) lower respiratory tract infections (LRTI): day-care attendance and/or having siblings, high parental education level, birth weight over 4 kg, and birth from April to September.

The risk of RSV LRTI was 10 times higher for children with these four factors, compared with children without these factors (Pediatrics 2011;127:35-41).

Using statistical analyses of the association between these predictors and the presence or absence of RSV LRTI, Dr. Michiel Houben of Wilhelmina Children's Hospital, Utrecht, the Netherlands, and his associates derived the prediction rule, with scores ranging from 0 to 5. The absolute risk of having an RSV LRTI ranged from 3% for a child with a score of 2 or less (20% of the children) to 32% for a child with a score of 5 and all four of these factors (8% of the children).

“Clinicians can use these features to differentiate between children with high and low risks of RSV LRTI and subsequently can target preventive and monitoring strategies to children at high risk,” he and his coauthors concluded.

They noted that to date, clinical prediction models have only been developed for predicting hospitalization in preterm infants, and as far as they know, theirs is the first study that “attempts to predict the risk of nonhospitalized RSV LRTI for healthy newborns by using molecular detection of RSV.”

The primary outcome measured in the study was RSV LRTI, which was based on a positive RSV polymerase chain reaction test result and symptoms of acute wheezing or a moderate/severe cough. Parents recorded their children's respiratory symptoms with daily logs and used nose and throat swabs when the child had a respiratory tract infection. During their first year of life, 42 (14%) of the 298 children had an RSV LRTI.

With the formula they derived, 1 point was assigned for a birth weight over 4 kg, 1 point for being born from April to September, 2 points for being in day care or having siblings, and 1 point for a high parental education level. In an example they provided, a baby born in July (1 point) and who is in day care (2 points), who weighed 4.2 kg at birth (1 point) and has parents who are not highly educated (0 points) would have a score of 4 points, corresponding to a “probability of developing a RSV LRTI of 23%,” they wrote.

Because of the “extremely high” incidence of medically attended RSV infection, “children classified as being at high risk could be monitored more closely and lifestyle changes that reduce exposure could be applied,” Dr. Houben and associates added.

One of the study authors received research funding and speaker's fees from Abbott International; the other authors indicated they had no relevant financial disclosures.

View on the News

Study: Well Done, but Raises Concerns

If clinicians used this type of prediction rule in their practices, Dr. Lance Chilton said it would be used to identify those at the highest risk – with scores of 4 or 5 – rather than using a low score as a basis to advise parents not to worry. Some of the factors that are in the formula are modifiable, he pointed out, noting that a score of 4 or 5 might influence parents to decide to take their children out of day care.

Dr. Chilton said that he is not aware of any clinicians who use a predictive scoring system to identify newborns at highest risk of RSV infection.

“If you asked a group of pediatricians what they used as a means of prediction as to who is at highest risk of RSV infection, most would come up with day-care attendance and older siblings, and none of them would have guessed that higher educational achievement would be positively correlated with risk of a medically attended RSV infection,” he said in an interview. “And most would say that they recommend that all babies stay away from coughing people and crowds of people during the winter virus season.”

While he thought the study appeared to be well done, he pointed out that there are major differences in hospitalization rates for RSV between United States and European epidemiologic studies, and that there are likely other differences, such as the use of emergency departments for treatment rather than general practices. One concern he had was that the study might be used “as a means to suggest” that newborns with a score of 4 or 5 be given palivizumab (Synagis), “which would markedly increase costs without any proof of effectiveness, let alone cost-effectiveness.”

DR. CHILTON is a pediatrician at the Young Children's Health Center at the University of New Mexico, Albuquerque. Dr. Chilton, formerly the chair of the Center for Disease Control and Prevention's working group on RSV immunoprophylaxis, said he had no relevant financial disclosures.

In a study that identified independent risk factors for respiratory syncytial virus lower respiratory tract infections in a group of healthy term newborns, investigators in the Netherlands developed “a simple prediction rule” that they say can be used in clinical practice to identify healthy newborns at high risk for being treated as outpatients for these infections during the first year of life.

In the prospective birth cohort study of 298 healthy term babies born in two large urban Dutch hospitals between January 2006 and December 2008 who were followed for a year, the following were identified as independent predictors for respiratory syncytial virus (RSV) lower respiratory tract infections (LRTI): day-care attendance and/or having siblings, high parental education level, birth weight over 4 kg, and birth from April to September.

The risk of RSV LRTI was 10 times higher for children with these four factors, compared with children without these factors (Pediatrics 2011;127:35-41).

Using statistical analyses of the association between these predictors and the presence or absence of RSV LRTI, Dr. Michiel Houben of Wilhelmina Children's Hospital, Utrecht, the Netherlands, and his associates derived the prediction rule, with scores ranging from 0 to 5. The absolute risk of having an RSV LRTI ranged from 3% for a child with a score of 2 or less (20% of the children) to 32% for a child with a score of 5 and all four of these factors (8% of the children).

“Clinicians can use these features to differentiate between children with high and low risks of RSV LRTI and subsequently can target preventive and monitoring strategies to children at high risk,” he and his coauthors concluded.

They noted that to date, clinical prediction models have only been developed for predicting hospitalization in preterm infants, and as far as they know, theirs is the first study that “attempts to predict the risk of nonhospitalized RSV LRTI for healthy newborns by using molecular detection of RSV.”

The primary outcome measured in the study was RSV LRTI, which was based on a positive RSV polymerase chain reaction test result and symptoms of acute wheezing or a moderate/severe cough. Parents recorded their children's respiratory symptoms with daily logs and used nose and throat swabs when the child had a respiratory tract infection. During their first year of life, 42 (14%) of the 298 children had an RSV LRTI.

With the formula they derived, 1 point was assigned for a birth weight over 4 kg, 1 point for being born from April to September, 2 points for being in day care or having siblings, and 1 point for a high parental education level. In an example they provided, a baby born in July (1 point) and who is in day care (2 points), who weighed 4.2 kg at birth (1 point) and has parents who are not highly educated (0 points) would have a score of 4 points, corresponding to a “probability of developing a RSV LRTI of 23%,” they wrote.

Because of the “extremely high” incidence of medically attended RSV infection, “children classified as being at high risk could be monitored more closely and lifestyle changes that reduce exposure could be applied,” Dr. Houben and associates added.

One of the study authors received research funding and speaker's fees from Abbott International; the other authors indicated they had no relevant financial disclosures.

View on the News

Study: Well Done, but Raises Concerns

If clinicians used this type of prediction rule in their practices, Dr. Lance Chilton said it would be used to identify those at the highest risk – with scores of 4 or 5 – rather than using a low score as a basis to advise parents not to worry. Some of the factors that are in the formula are modifiable, he pointed out, noting that a score of 4 or 5 might influence parents to decide to take their children out of day care.

Dr. Chilton said that he is not aware of any clinicians who use a predictive scoring system to identify newborns at highest risk of RSV infection.

“If you asked a group of pediatricians what they used as a means of prediction as to who is at highest risk of RSV infection, most would come up with day-care attendance and older siblings, and none of them would have guessed that higher educational achievement would be positively correlated with risk of a medically attended RSV infection,” he said in an interview. “And most would say that they recommend that all babies stay away from coughing people and crowds of people during the winter virus season.”

While he thought the study appeared to be well done, he pointed out that there are major differences in hospitalization rates for RSV between United States and European epidemiologic studies, and that there are likely other differences, such as the use of emergency departments for treatment rather than general practices. One concern he had was that the study might be used “as a means to suggest” that newborns with a score of 4 or 5 be given palivizumab (Synagis), “which would markedly increase costs without any proof of effectiveness, let alone cost-effectiveness.”

DR. CHILTON is a pediatrician at the Young Children's Health Center at the University of New Mexico, Albuquerque. Dr. Chilton, formerly the chair of the Center for Disease Control and Prevention's working group on RSV immunoprophylaxis, said he had no relevant financial disclosures.

BETHESDA, MD. – The influenza vaccine for the 2011–2012 influenza season in the United States should include the same three strains that are in the current vaccine, a Food and Drug Administration Advisory Panel recommended.

The panel voted to recommend that the strains in the Northern Hemisphere 2010–2011 seasonal influenza vaccine – an A/California/7/2009 (H1N1)–like virus, an A/Perth/16/2009 (H3N2)–like virus, and a B/Brisbane/60/2008–like virus – compose the upcoming vaccine.

This is a preliminary recommendation that will be approved by the FDA in time for vaccine manufacturers to be able to produce an adequate supply for next season. The vaccines panel meets at this time annually to make preliminary recommendations on the components of the trivalent vaccine for the forthcoming influenza season. It considers presentations on the latest influenza surveillance, and epidemiology data; antigenic characteristics of recent virus isolates; serologic responses to current vaccines; and availability of candidate vaccine strains and reagents.

Influenza A(H3N2), A(H1N1), and B strains continue to circulate in the United States and globally, and recently characterized strains appear to be well matched to the components in the current seasonal vaccine, Dr. Lisa Grohskopf, a medical officer in the influenza division at the Centers for Disease Control and Prevention, Atlanta, said at the meeting. The H1N1 virus is a pandemic 2009 H1N1 virus and is the same vaccine virus as was used in the 2009 H1N1 monovalent vaccine.

Recently circulating viruses remain susceptible to neuraminidases, and in recent weeks, influenza activity has remained high, she said. An increase in the proportion of influenza A viruses identified as A(H1N1) have been identified since the beginning of the U.S. season. Of the viruses that have been tested at the CDC since Oct. 1, 2011, 13% have been influenza A(H1N1), 54% have been A(H3N2), and 33% have been influenza B.

The panel voted 15–0, with 1 abstention, in support of the H1N1 strain; the votes in favor of retaining the other two strains were unanimous. However, panelists expressed some concern about the B component, a B/Victoria lineage strain, because of the possibility that a B/Yamagata lineage strain could become an issue. As in past meetings, panelists observed that having a quadrivalent influenza vaccine, with both a B/Victoria and B/Yamagata component, would address these concerns. Although influenza vaccine manufacturers are conducting clinical studies of quadrivalent influenza vaccine, none would be ready for the next season, according to speakers at the meeting. One option discussed was to produce a monovalent vaccine to be used if needed to vaccinate susceptible groups, including children.

An industry representative who spoke at the meeting, Samson Lee, Ph.D., of Sanofi-Pasteur, said that there has been a significant increase in influenza immunization rates among different age groups during the current season, compared with last year: increases of about 18% in the pediatric population, 24% in adults, and 14% in the population aged 65 and older.

To date, 35 pediatric influenza-associated deaths have been reported in the United States this season, including 13 reportedly due to influenza B, 9 due to A(H3N2), and 7 due to A(H1N1). Subtypying was not performed for the remaining six cases, Dr. Grohskopf said.

Panel members reported having no relevant financial disclosures.

BETHESDA, MD. – The influenza vaccine for the 2011–2012 influenza season in the United States should include the same three strains that are in the current vaccine, a Food and Drug Administration Advisory Panel recommended.

The panel voted to recommend that the strains in the Northern Hemisphere 2010–2011 seasonal influenza vaccine – an A/California/7/2009 (H1N1)–like virus, an A/Perth/16/2009 (H3N2)–like virus, and a B/Brisbane/60/2008–like virus – compose the upcoming vaccine.

This is a preliminary recommendation that will be approved by the FDA in time for vaccine manufacturers to be able to produce an adequate supply for next season. The vaccines panel meets at this time annually to make preliminary recommendations on the components of the trivalent vaccine for the forthcoming influenza season. It considers presentations on the latest influenza surveillance, and epidemiology data; antigenic characteristics of recent virus isolates; serologic responses to current vaccines; and availability of candidate vaccine strains and reagents.

Influenza A(H3N2), A(H1N1), and B strains continue to circulate in the United States and globally, and recently characterized strains appear to be well matched to the components in the current seasonal vaccine, Dr. Lisa Grohskopf, a medical officer in the influenza division at the Centers for Disease Control and Prevention, Atlanta, said at the meeting. The H1N1 virus is a pandemic 2009 H1N1 virus and is the same vaccine virus as was used in the 2009 H1N1 monovalent vaccine.

Recently circulating viruses remain susceptible to neuraminidases, and in recent weeks, influenza activity has remained high, she said. An increase in the proportion of influenza A viruses identified as A(H1N1) have been identified since the beginning of the U.S. season. Of the viruses that have been tested at the CDC since Oct. 1, 2011, 13% have been influenza A(H1N1), 54% have been A(H3N2), and 33% have been influenza B.

The panel voted 15–0, with 1 abstention, in support of the H1N1 strain; the votes in favor of retaining the other two strains were unanimous. However, panelists expressed some concern about the B component, a B/Victoria lineage strain, because of the possibility that a B/Yamagata lineage strain could become an issue. As in past meetings, panelists observed that having a quadrivalent influenza vaccine, with both a B/Victoria and B/Yamagata component, would address these concerns. Although influenza vaccine manufacturers are conducting clinical studies of quadrivalent influenza vaccine, none would be ready for the next season, according to speakers at the meeting. One option discussed was to produce a monovalent vaccine to be used if needed to vaccinate susceptible groups, including children.

An industry representative who spoke at the meeting, Samson Lee, Ph.D., of Sanofi-Pasteur, said that there has been a significant increase in influenza immunization rates among different age groups during the current season, compared with last year: increases of about 18% in the pediatric population, 24% in adults, and 14% in the population aged 65 and older.

To date, 35 pediatric influenza-associated deaths have been reported in the United States this season, including 13 reportedly due to influenza B, 9 due to A(H3N2), and 7 due to A(H1N1). Subtypying was not performed for the remaining six cases, Dr. Grohskopf said.

Panel members reported having no relevant financial disclosures.

BETHESDA, MD. – The influenza vaccine for the 2011–2012 influenza season in the United States should include the same three strains that are in the current vaccine, a Food and Drug Administration Advisory Panel recommended.

The panel voted to recommend that the strains in the Northern Hemisphere 2010–2011 seasonal influenza vaccine – an A/California/7/2009 (H1N1)–like virus, an A/Perth/16/2009 (H3N2)–like virus, and a B/Brisbane/60/2008–like virus – compose the upcoming vaccine.

This is a preliminary recommendation that will be approved by the FDA in time for vaccine manufacturers to be able to produce an adequate supply for next season. The vaccines panel meets at this time annually to make preliminary recommendations on the components of the trivalent vaccine for the forthcoming influenza season. It considers presentations on the latest influenza surveillance, and epidemiology data; antigenic characteristics of recent virus isolates; serologic responses to current vaccines; and availability of candidate vaccine strains and reagents.

Influenza A(H3N2), A(H1N1), and B strains continue to circulate in the United States and globally, and recently characterized strains appear to be well matched to the components in the current seasonal vaccine, Dr. Lisa Grohskopf, a medical officer in the influenza division at the Centers for Disease Control and Prevention, Atlanta, said at the meeting. The H1N1 virus is a pandemic 2009 H1N1 virus and is the same vaccine virus as was used in the 2009 H1N1 monovalent vaccine.

Recently circulating viruses remain susceptible to neuraminidases, and in recent weeks, influenza activity has remained high, she said. An increase in the proportion of influenza A viruses identified as A(H1N1) have been identified since the beginning of the U.S. season. Of the viruses that have been tested at the CDC since Oct. 1, 2011, 13% have been influenza A(H1N1), 54% have been A(H3N2), and 33% have been influenza B.

The panel voted 15–0, with 1 abstention, in support of the H1N1 strain; the votes in favor of retaining the other two strains were unanimous. However, panelists expressed some concern about the B component, a B/Victoria lineage strain, because of the possibility that a B/Yamagata lineage strain could become an issue. As in past meetings, panelists observed that having a quadrivalent influenza vaccine, with both a B/Victoria and B/Yamagata component, would address these concerns. Although influenza vaccine manufacturers are conducting clinical studies of quadrivalent influenza vaccine, none would be ready for the next season, according to speakers at the meeting. One option discussed was to produce a monovalent vaccine to be used if needed to vaccinate susceptible groups, including children.

An industry representative who spoke at the meeting, Samson Lee, Ph.D., of Sanofi-Pasteur, said that there has been a significant increase in influenza immunization rates among different age groups during the current season, compared with last year: increases of about 18% in the pediatric population, 24% in adults, and 14% in the population aged 65 and older.

To date, 35 pediatric influenza-associated deaths have been reported in the United States this season, including 13 reportedly due to influenza B, 9 due to A(H3N2), and 7 due to A(H1N1). Subtypying was not performed for the remaining six cases, Dr. Grohskopf said.

Panel members reported having no relevant financial disclosures.

The approval of the quadrivalent meningococcal conjugate vaccine manufactured by Novartis has been expanded to include children aged 2–10 years, but does not yet include infants.

The Food and Drug Administration approved the use of the vaccine for preventing invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y, and W-135 in children aged 2–10 years of age, according to a statement issued by Novartis. The company markets the vaccine (Meningococcal [Groups A, C, Y and W-135] Oligosaccharide Diphtheria CRM ₁₉₇ Conjugate Vaccine) as Menveo. It was approved in 2010 for use in adolescents and adults aged 11–55 years.

Novartis' application for approval included children down to age 2 months. But the statement said that the FDA had not included this age group in the approval because of concerns raised that the company believes are of a “procedural nature,” and that the company plans to resubmit the application for approval with more clinical data on children 2 months to 2 years within a few months.

Approval for children aged 2–10 years was based on data in a phase III study of 5,297 children in that age group comparing the safety and immunogenicity against the four serogroups contained in the vaccine with those in the other meningococcal vaccine licensed in the United States, according to Novartis. The company said it has agreed to conduct postmarketing studies.

The other meningococcal conjugate vaccine approved in the United States is Menactra, manufactured by Sanofi Pasteur, which is also approved for immunizing people aged 2–55 years against invasive meningococcal disease caused by the four serogroups contained in the vaccine, the same included in Menveo.

In the European Union, where Menveo is known as Meningococcal Group A, C, W135 and Y Conjugate Vaccine, Novartis plans to submit data to support the use of the vaccine in children aged 0–10 years in the first half of 2011, according to the statement. In Canada, the application for use in children 2–10 years has been submitted.

The approval of the quadrivalent meningococcal conjugate vaccine manufactured by Novartis has been expanded to include children aged 2–10 years, but does not yet include infants.

The Food and Drug Administration approved the use of the vaccine for preventing invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y, and W-135 in children aged 2–10 years of age, according to a statement issued by Novartis. The company markets the vaccine (Meningococcal [Groups A, C, Y and W-135] Oligosaccharide Diphtheria CRM ₁₉₇ Conjugate Vaccine) as Menveo. It was approved in 2010 for use in adolescents and adults aged 11–55 years.

Novartis' application for approval included children down to age 2 months. But the statement said that the FDA had not included this age group in the approval because of concerns raised that the company believes are of a “procedural nature,” and that the company plans to resubmit the application for approval with more clinical data on children 2 months to 2 years within a few months.

Approval for children aged 2–10 years was based on data in a phase III study of 5,297 children in that age group comparing the safety and immunogenicity against the four serogroups contained in the vaccine with those in the other meningococcal vaccine licensed in the United States, according to Novartis. The company said it has agreed to conduct postmarketing studies.

The other meningococcal conjugate vaccine approved in the United States is Menactra, manufactured by Sanofi Pasteur, which is also approved for immunizing people aged 2–55 years against invasive meningococcal disease caused by the four serogroups contained in the vaccine, the same included in Menveo.

In the European Union, where Menveo is known as Meningococcal Group A, C, W135 and Y Conjugate Vaccine, Novartis plans to submit data to support the use of the vaccine in children aged 0–10 years in the first half of 2011, according to the statement. In Canada, the application for use in children 2–10 years has been submitted.

The approval of the quadrivalent meningococcal conjugate vaccine manufactured by Novartis has been expanded to include children aged 2–10 years, but does not yet include infants.

The Food and Drug Administration approved the use of the vaccine for preventing invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y, and W-135 in children aged 2–10 years of age, according to a statement issued by Novartis. The company markets the vaccine (Meningococcal [Groups A, C, Y and W-135] Oligosaccharide Diphtheria CRM ₁₉₇ Conjugate Vaccine) as Menveo. It was approved in 2010 for use in adolescents and adults aged 11–55 years.

Novartis' application for approval included children down to age 2 months. But the statement said that the FDA had not included this age group in the approval because of concerns raised that the company believes are of a “procedural nature,” and that the company plans to resubmit the application for approval with more clinical data on children 2 months to 2 years within a few months.

Approval for children aged 2–10 years was based on data in a phase III study of 5,297 children in that age group comparing the safety and immunogenicity against the four serogroups contained in the vaccine with those in the other meningococcal vaccine licensed in the United States, according to Novartis. The company said it has agreed to conduct postmarketing studies.

The other meningococcal conjugate vaccine approved in the United States is Menactra, manufactured by Sanofi Pasteur, which is also approved for immunizing people aged 2–55 years against invasive meningococcal disease caused by the four serogroups contained in the vaccine, the same included in Menveo.

In the European Union, where Menveo is known as Meningococcal Group A, C, W135 and Y Conjugate Vaccine, Novartis plans to submit data to support the use of the vaccine in children aged 0–10 years in the first half of 2011, according to the statement. In Canada, the application for use in children 2–10 years has been submitted.

Guanfacine has been approved by the Food and Drug Administration as an adjunct to stimulant medications for the treatment of attention-deficit/hyperactivity disorder in children and adolescents aged 6-17, the manufacturer announced Feb. 28 in a statement.

The extended-release form of the drug, a selective alpha-2A adrenergic receptor agonist, previously had been approved as monotherapy for treating ADHD. Approval of the monotherapy was based on two 8- to 9-week studies, and the adjunctive therapy indication was based on a 9-week study of children and adolescents, according to the prescribing information for guanfacine, marketed as Intuniv by Shire PLC. The 9-week study included 455 patients with ADHD who had a suboptimal response to stimulant treatment. Those who had no response to stimulant therapy were not included in the study.

Patients were randomized to receive a dose of guanfacine or placebo in the morning or evening or placebo in combination with the stimulant they had been receiving, with the dose of guanfacine starting at 1 mg titrated weekly over a 5-week period to a maximum of 4 mg/day, based on tolerability and clinical response. At the end of 9 weeks, the mean reductions in total scores on the ADHD rating scale (ADHD-RS-IV) were significantly greater among those who received the combination than among those who continued on the psychostimulant alone. The prescribing information states that "controlled adjunctive long-term efficacy studies over 9 weeks have not been conducted," and that it is indicated "as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, and social) for patients with this syndrome."

The most common adverse events, reported in 5% or more of patients at a rate of at least twice the placebo rate, were somnolence, fatigue, insomnia, dizziness, and abdominal pain. Most adverse events were mild to moderate, and the four serious adverse events reported in the study – which included syncope and poison ivy – were not considered to be related to the drug, by the investigator, according to the company statement. The discontinuation attributable to side effects was 3% among those on the combination, compared with 1% among those on the stimulant alone, according to the company statement.

Guanfacine is a known antihypertensive, and the labeling cautions about its use with antihypertensive drugs. (It is marketed as an antihypertensive as Tenex, by another manufacturer).

Guanfacine comes in 1-mg, 2-mg, 3-mg and 4-mg extended-release tablets. It should be taken once daily, and should not be taken with high-fat meals, which increases exposure to the drug, according to the prescribing information.

Guanfacine has been approved by the Food and Drug Administration as an adjunct to stimulant medications for the treatment of attention-deficit/hyperactivity disorder in children and adolescents aged 6-17, the manufacturer announced Feb. 28 in a statement.

The extended-release form of the drug, a selective alpha-2A adrenergic receptor agonist, previously had been approved as monotherapy for treating ADHD. Approval of the monotherapy was based on two 8- to 9-week studies, and the adjunctive therapy indication was based on a 9-week study of children and adolescents, according to the prescribing information for guanfacine, marketed as Intuniv by Shire PLC. The 9-week study included 455 patients with ADHD who had a suboptimal response to stimulant treatment. Those who had no response to stimulant therapy were not included in the study.

Patients were randomized to receive a dose of guanfacine or placebo in the morning or evening or placebo in combination with the stimulant they had been receiving, with the dose of guanfacine starting at 1 mg titrated weekly over a 5-week period to a maximum of 4 mg/day, based on tolerability and clinical response. At the end of 9 weeks, the mean reductions in total scores on the ADHD rating scale (ADHD-RS-IV) were significantly greater among those who received the combination than among those who continued on the psychostimulant alone. The prescribing information states that "controlled adjunctive long-term efficacy studies over 9 weeks have not been conducted," and that it is indicated "as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, and social) for patients with this syndrome."

The most common adverse events, reported in 5% or more of patients at a rate of at least twice the placebo rate, were somnolence, fatigue, insomnia, dizziness, and abdominal pain. Most adverse events were mild to moderate, and the four serious adverse events reported in the study – which included syncope and poison ivy – were not considered to be related to the drug, by the investigator, according to the company statement. The discontinuation attributable to side effects was 3% among those on the combination, compared with 1% among those on the stimulant alone, according to the company statement.

Guanfacine is a known antihypertensive, and the labeling cautions about its use with antihypertensive drugs. (It is marketed as an antihypertensive as Tenex, by another manufacturer).

Guanfacine comes in 1-mg, 2-mg, 3-mg and 4-mg extended-release tablets. It should be taken once daily, and should not be taken with high-fat meals, which increases exposure to the drug, according to the prescribing information.

Guanfacine has been approved by the Food and Drug Administration as an adjunct to stimulant medications for the treatment of attention-deficit/hyperactivity disorder in children and adolescents aged 6-17, the manufacturer announced Feb. 28 in a statement.

The extended-release form of the drug, a selective alpha-2A adrenergic receptor agonist, previously had been approved as monotherapy for treating ADHD. Approval of the monotherapy was based on two 8- to 9-week studies, and the adjunctive therapy indication was based on a 9-week study of children and adolescents, according to the prescribing information for guanfacine, marketed as Intuniv by Shire PLC. The 9-week study included 455 patients with ADHD who had a suboptimal response to stimulant treatment. Those who had no response to stimulant therapy were not included in the study.

Patients were randomized to receive a dose of guanfacine or placebo in the morning or evening or placebo in combination with the stimulant they had been receiving, with the dose of guanfacine starting at 1 mg titrated weekly over a 5-week period to a maximum of 4 mg/day, based on tolerability and clinical response. At the end of 9 weeks, the mean reductions in total scores on the ADHD rating scale (ADHD-RS-IV) were significantly greater among those who received the combination than among those who continued on the psychostimulant alone. The prescribing information states that "controlled adjunctive long-term efficacy studies over 9 weeks have not been conducted," and that it is indicated "as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, and social) for patients with this syndrome."

The most common adverse events, reported in 5% or more of patients at a rate of at least twice the placebo rate, were somnolence, fatigue, insomnia, dizziness, and abdominal pain. Most adverse events were mild to moderate, and the four serious adverse events reported in the study – which included syncope and poison ivy – were not considered to be related to the drug, by the investigator, according to the company statement. The discontinuation attributable to side effects was 3% among those on the combination, compared with 1% among those on the stimulant alone, according to the company statement.

Guanfacine is a known antihypertensive, and the labeling cautions about its use with antihypertensive drugs. (It is marketed as an antihypertensive as Tenex, by another manufacturer).

Guanfacine comes in 1-mg, 2-mg, 3-mg and 4-mg extended-release tablets. It should be taken once daily, and should not be taken with high-fat meals, which increases exposure to the drug, according to the prescribing information.

Guanfacine has been approved by the Food and Drug Administration as an adjunct to stimulant medications for the treatment of attention-deficit/hyperactivity disorder in children and adolescents aged 6-17, the manufacturer announced Feb. 28 in a statement.

The extended-release form of the drug, a selective alpha-2A adrenergic receptor agonist, previously had been approved as monotherapy for treating ADHD. Approval of the monotherapy was based on two 8- to 9-week studies, and the adjunctive therapy indication was based on a 9-week study of children and adolescents, according to the prescribing information for guanfacine, marketed as Intuniv by Shire PLC. The 9-week study included 455 patients with ADHD who had a suboptimal response to stimulant treatment. Those who had no response to stimulant therapy were not included in the study.

Patients were randomized to receive a dose of guanfacine or placebo in the morning or evening or placebo in combination with the stimulant they had been receiving, with the dose of guanfacine starting at 1 mg titrated weekly over a 5-week period to a maximum of 4 mg/day, based on tolerability and clinical response. At the end of 9 weeks, the mean reductions in total scores on the ADHD rating scale (ADHD-RS-IV) were significantly greater among those who received the combination than among those who continued on the psychostimulant alone. The prescribing information states that "controlled adjunctive long-term efficacy studies over 9 weeks have not been conducted," and that it is indicated "as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, and social) for patients with this syndrome."

The most common adverse events, reported in 5% or more of patients at a rate of at least twice the placebo rate, were somnolence, fatigue, insomnia, dizziness, and abdominal pain. Most adverse events were mild to moderate, and the four serious adverse events reported in the study – which included syncope and poison ivy – were not considered to be related to the drug, by the investigator, according to the company statement. The discontinuation attributable to side effects was 3% among those on the combination, compared with 1% among those on the stimulant alone, according to the company statement.

Guanfacine is a known antihypertensive, and the labeling cautions about its use with antihypertensive drugs. (It is marketed as an antihypertensive as Tenex, by another manufacturer).

Guanfacine comes in 1-mg, 2-mg, 3-mg and 4-mg extended-release tablets. It should be taken once daily, and should not be taken with high-fat meals, which increases exposure to the drug, according to the prescribing information.

Guanfacine has been approved by the Food and Drug Administration as an adjunct to stimulant medications for the treatment of attention-deficit/hyperactivity disorder in children and adolescents aged 6-17, the manufacturer announced Feb. 28 in a statement.

The extended-release form of the drug, a selective alpha-2A adrenergic receptor agonist, previously had been approved as monotherapy for treating ADHD. Approval of the monotherapy was based on two 8- to 9-week studies, and the adjunctive therapy indication was based on a 9-week study of children and adolescents, according to the prescribing information for guanfacine, marketed as Intuniv by Shire PLC. The 9-week study included 455 patients with ADHD who had a suboptimal response to stimulant treatment. Those who had no response to stimulant therapy were not included in the study.

Patients were randomized to receive a dose of guanfacine or placebo in the morning or evening or placebo in combination with the stimulant they had been receiving, with the dose of guanfacine starting at 1 mg titrated weekly over a 5-week period to a maximum of 4 mg/day, based on tolerability and clinical response. At the end of 9 weeks, the mean reductions in total scores on the ADHD rating scale (ADHD-RS-IV) were significantly greater among those who received the combination than among those who continued on the psychostimulant alone. The prescribing information states that "controlled adjunctive long-term efficacy studies over 9 weeks have not been conducted," and that it is indicated "as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, and social) for patients with this syndrome."

The most common adverse events, reported in 5% or more of patients at a rate of at least twice the placebo rate, were somnolence, fatigue, insomnia, dizziness, and abdominal pain. Most adverse events were mild to moderate, and the four serious adverse events reported in the study – which included syncope and poison ivy – were not considered to be related to the drug, by the investigator, according to the company statement. The discontinuation attributable to side effects was 3% among those on the combination, compared with 1% among those on the stimulant alone, according to the company statement.

Guanfacine is a known antihypertensive, and the labeling cautions about its use with antihypertensive drugs. (It is marketed as an antihypertensive as Tenex, by another manufacturer).

Guanfacine comes in 1-mg, 2-mg, 3-mg and 4-mg extended-release tablets. It should be taken once daily, and should not be taken with high-fat meals, which increases exposure to the drug, according to the prescribing information.

Guanfacine has been approved by the Food and Drug Administration as an adjunct to stimulant medications for the treatment of attention-deficit/hyperactivity disorder in children and adolescents aged 6-17, the manufacturer announced Feb. 28 in a statement.

The extended-release form of the drug, a selective alpha-2A adrenergic receptor agonist, previously had been approved as monotherapy for treating ADHD. Approval of the monotherapy was based on two 8- to 9-week studies, and the adjunctive therapy indication was based on a 9-week study of children and adolescents, according to the prescribing information for guanfacine, marketed as Intuniv by Shire PLC. The 9-week study included 455 patients with ADHD who had a suboptimal response to stimulant treatment. Those who had no response to stimulant therapy were not included in the study.

Patients were randomized to receive a dose of guanfacine or placebo in the morning or evening or placebo in combination with the stimulant they had been receiving, with the dose of guanfacine starting at 1 mg titrated weekly over a 5-week period to a maximum of 4 mg/day, based on tolerability and clinical response. At the end of 9 weeks, the mean reductions in total scores on the ADHD rating scale (ADHD-RS-IV) were significantly greater among those who received the combination than among those who continued on the psychostimulant alone. The prescribing information states that "controlled adjunctive long-term efficacy studies over 9 weeks have not been conducted," and that it is indicated "as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, and social) for patients with this syndrome."

The most common adverse events, reported in 5% or more of patients at a rate of at least twice the placebo rate, were somnolence, fatigue, insomnia, dizziness, and abdominal pain. Most adverse events were mild to moderate, and the four serious adverse events reported in the study – which included syncope and poison ivy – were not considered to be related to the drug, by the investigator, according to the company statement. The discontinuation attributable to side effects was 3% among those on the combination, compared with 1% among those on the stimulant alone, according to the company statement.

Guanfacine is a known antihypertensive, and the labeling cautions about its use with antihypertensive drugs. (It is marketed as an antihypertensive as Tenex, by another manufacturer).

Guanfacine comes in 1-mg, 2-mg, 3-mg and 4-mg extended-release tablets. It should be taken once daily, and should not be taken with high-fat meals, which increases exposure to the drug, according to the prescribing information.