Elizabeth Mechcatie

When enhancing a patient's lips, consider the patient's aesthetic goals and the natural anatomy of the lip, and remember to think aesthetically about the entire face, said Dr. Kimberly Butterwick.

"Take care to achieve a lip that does not look like it's been done," advised Dr. Butterwick, a cosmetic dermatologist in La Jolla, Calif. "We're not just correcting a defect, but making a patient look prettier, and we have to be mindful how the lips contribute" to the symmetry and proportions of the entire face.

The anatomy of the lip—the vermilion border, the red portion of the lip, the philtral columns, and the balance of the upper and lower lip—and its proportions are the elements that need to be considered to create a lip that is natural looking, "yet enhanced and more beautiful," she said in an interview.

The lip is divided into red and white segments, "at a well-defined and arched vermilion border." Think about the M-shaped cupid's bow of the upper lip, and the lower lip as shaped like a W, with two lateral lobes and a midline groove, she said at a cosmetic dermatology seminar sponsored by Skin Disease Education Foundation (SDEF).

The relationship to the nose and chin, and facial proportions also should be considered, with the width of the lip falling between a straight line drawn from each inner iris.

A mistake that can be made with the red portion of the lip is to create a fat lip all the way across the upper and lower lip, like a sausage instead of being attentive to the normal contours. There is also a tendency to overstress the upper lip in an attempt to get a pouty look. Ideally, the lower lip should be bigger by 10%-25%, Dr. Butterwick added, noting that often, physicians try to make the upper lip equal to or bigger than the lower lip, which appears unnatural.

Areas of the lips that should be fuller and emphasized to achieve a natural look include the two anatomic mounds of fullness at the highest point of the upper lip, right under the peak of the cupid's bow, as well as the two mounds of volume of the lower lip of the "four pillows." It also often helps to add a little volume to the midline tubercle of the upper lips and the philtral columns.

Hyaluronic acid is the main option used for lip correction and enhancement, "because it is safe, soft, and natural, and it lasts long enough in most cases," Dr. Butterwick said. Currently available hyaluronic acid products are Restylane, Hyalaform, Juvèderm Ultra or Ultra Plus, and Prevelle Silk.

Prevelle Silk is a good option for beginners because it is lightweight, contains anesthetic, and does not last as long as the others. It also can be used first, injected along the vermilion for its anesthetic effects, and can be followed by another hyaluronic acid product that provides for more volume and lasts longer, using the rest of Prevelle Silk for fine lines, she said.

Restylane and Juvèderm are similar, although Juvèderm causes a little less swelling and, therefore, "may be a little softer and more natural in the lips," she said, but a product that is a little thicker may be appropriate for those patients who want more pronounced lips, she added. "That's when you can strike a balance between what the patient wants and still achieve a natural look."

Fat augmentation of the lips provides a natural appearance, but does not last as long as it does in other locations. "I would not go out of my way to put fat in the lips, unless you are already using fat for other indications in the face," she advised.

Semipermanent or permanent injectables that are associated with a high rate of adverse reactions when used in the lips are Radiesse, Sculptra, Evolence, and Artefill, as well as silicone, which should be avoided in lips altogether, she said. Their labels state they should not be used in lips, "yet physicians think that they can get away with it, and wind up every so often having a problem, and it is a big problem."

An important element of lip correction is consideration of the way lips appear in motion: When Dr. Butterwick consults with a patient, she said she observes their lips while they are talking. Some people have vertical lip lines from excessive pursing while they talk, or they pull down the corners of their mouth while talking, which are excess movements that can be "softened" with Botox, she said. Botox also can address a gummy smile.

Treating the surrounding tissue to support volume loss—such as deep marionette lines, a jowl, or a deep nasolabial fold right near the lip—will also improve the appearance of the lips.

Dr. Butterwick disclosed receiving grant research support from Mentor Corp., and is a consultant for Medicis Pharmaceutical Corp., Allergan Inc., Sanofi-Aventis, and Neutrogena Corp.

SDEF and this news organization are owned by Elsevier.

Photo shows patient prior to injection of 1 cc of Hyalaform to the upper lip.

Two weeks post injection, the cupid's bow is narrowed and more defined.

Source Photos courtesy Dr. Kimberly Butterwick

'We have to be mindful how the lips contribute' to the symmetry and proportions of the entire face.

Source DR. BUTTERWICK

When enhancing a patient's lips, consider the patient's aesthetic goals and the natural anatomy of the lip, and remember to think aesthetically about the entire face, said Dr. Kimberly Butterwick.

"Take care to achieve a lip that does not look like it's been done," advised Dr. Butterwick, a cosmetic dermatologist in La Jolla, Calif. "We're not just correcting a defect, but making a patient look prettier, and we have to be mindful how the lips contribute" to the symmetry and proportions of the entire face.

The anatomy of the lip—the vermilion border, the red portion of the lip, the philtral columns, and the balance of the upper and lower lip—and its proportions are the elements that need to be considered to create a lip that is natural looking, "yet enhanced and more beautiful," she said in an interview.

The lip is divided into red and white segments, "at a well-defined and arched vermilion border." Think about the M-shaped cupid's bow of the upper lip, and the lower lip as shaped like a W, with two lateral lobes and a midline groove, she said at a cosmetic dermatology seminar sponsored by Skin Disease Education Foundation (SDEF).

The relationship to the nose and chin, and facial proportions also should be considered, with the width of the lip falling between a straight line drawn from each inner iris.

A mistake that can be made with the red portion of the lip is to create a fat lip all the way across the upper and lower lip, like a sausage instead of being attentive to the normal contours. There is also a tendency to overstress the upper lip in an attempt to get a pouty look. Ideally, the lower lip should be bigger by 10%-25%, Dr. Butterwick added, noting that often, physicians try to make the upper lip equal to or bigger than the lower lip, which appears unnatural.

Areas of the lips that should be fuller and emphasized to achieve a natural look include the two anatomic mounds of fullness at the highest point of the upper lip, right under the peak of the cupid's bow, as well as the two mounds of volume of the lower lip of the "four pillows." It also often helps to add a little volume to the midline tubercle of the upper lips and the philtral columns.

Hyaluronic acid is the main option used for lip correction and enhancement, "because it is safe, soft, and natural, and it lasts long enough in most cases," Dr. Butterwick said. Currently available hyaluronic acid products are Restylane, Hyalaform, Juvèderm Ultra or Ultra Plus, and Prevelle Silk.

Prevelle Silk is a good option for beginners because it is lightweight, contains anesthetic, and does not last as long as the others. It also can be used first, injected along the vermilion for its anesthetic effects, and can be followed by another hyaluronic acid product that provides for more volume and lasts longer, using the rest of Prevelle Silk for fine lines, she said.

Restylane and Juvèderm are similar, although Juvèderm causes a little less swelling and, therefore, "may be a little softer and more natural in the lips," she said, but a product that is a little thicker may be appropriate for those patients who want more pronounced lips, she added. "That's when you can strike a balance between what the patient wants and still achieve a natural look."

Fat augmentation of the lips provides a natural appearance, but does not last as long as it does in other locations. "I would not go out of my way to put fat in the lips, unless you are already using fat for other indications in the face," she advised.

Semipermanent or permanent injectables that are associated with a high rate of adverse reactions when used in the lips are Radiesse, Sculptra, Evolence, and Artefill, as well as silicone, which should be avoided in lips altogether, she said. Their labels state they should not be used in lips, "yet physicians think that they can get away with it, and wind up every so often having a problem, and it is a big problem."

An important element of lip correction is consideration of the way lips appear in motion: When Dr. Butterwick consults with a patient, she said she observes their lips while they are talking. Some people have vertical lip lines from excessive pursing while they talk, or they pull down the corners of their mouth while talking, which are excess movements that can be "softened" with Botox, she said. Botox also can address a gummy smile.

Treating the surrounding tissue to support volume loss—such as deep marionette lines, a jowl, or a deep nasolabial fold right near the lip—will also improve the appearance of the lips.

Dr. Butterwick disclosed receiving grant research support from Mentor Corp., and is a consultant for Medicis Pharmaceutical Corp., Allergan Inc., Sanofi-Aventis, and Neutrogena Corp.

SDEF and this news organization are owned by Elsevier.

Photo shows patient prior to injection of 1 cc of Hyalaform to the upper lip.

Two weeks post injection, the cupid's bow is narrowed and more defined.

Source Photos courtesy Dr. Kimberly Butterwick

'We have to be mindful how the lips contribute' to the symmetry and proportions of the entire face.

Source DR. BUTTERWICK

When enhancing a patient's lips, consider the patient's aesthetic goals and the natural anatomy of the lip, and remember to think aesthetically about the entire face, said Dr. Kimberly Butterwick.

"Take care to achieve a lip that does not look like it's been done," advised Dr. Butterwick, a cosmetic dermatologist in La Jolla, Calif. "We're not just correcting a defect, but making a patient look prettier, and we have to be mindful how the lips contribute" to the symmetry and proportions of the entire face.

The anatomy of the lip—the vermilion border, the red portion of the lip, the philtral columns, and the balance of the upper and lower lip—and its proportions are the elements that need to be considered to create a lip that is natural looking, "yet enhanced and more beautiful," she said in an interview.

The lip is divided into red and white segments, "at a well-defined and arched vermilion border." Think about the M-shaped cupid's bow of the upper lip, and the lower lip as shaped like a W, with two lateral lobes and a midline groove, she said at a cosmetic dermatology seminar sponsored by Skin Disease Education Foundation (SDEF).

The relationship to the nose and chin, and facial proportions also should be considered, with the width of the lip falling between a straight line drawn from each inner iris.

A mistake that can be made with the red portion of the lip is to create a fat lip all the way across the upper and lower lip, like a sausage instead of being attentive to the normal contours. There is also a tendency to overstress the upper lip in an attempt to get a pouty look. Ideally, the lower lip should be bigger by 10%-25%, Dr. Butterwick added, noting that often, physicians try to make the upper lip equal to or bigger than the lower lip, which appears unnatural.

Areas of the lips that should be fuller and emphasized to achieve a natural look include the two anatomic mounds of fullness at the highest point of the upper lip, right under the peak of the cupid's bow, as well as the two mounds of volume of the lower lip of the "four pillows." It also often helps to add a little volume to the midline tubercle of the upper lips and the philtral columns.

Hyaluronic acid is the main option used for lip correction and enhancement, "because it is safe, soft, and natural, and it lasts long enough in most cases," Dr. Butterwick said. Currently available hyaluronic acid products are Restylane, Hyalaform, Juvèderm Ultra or Ultra Plus, and Prevelle Silk.

Prevelle Silk is a good option for beginners because it is lightweight, contains anesthetic, and does not last as long as the others. It also can be used first, injected along the vermilion for its anesthetic effects, and can be followed by another hyaluronic acid product that provides for more volume and lasts longer, using the rest of Prevelle Silk for fine lines, she said.

Restylane and Juvèderm are similar, although Juvèderm causes a little less swelling and, therefore, "may be a little softer and more natural in the lips," she said, but a product that is a little thicker may be appropriate for those patients who want more pronounced lips, she added. "That's when you can strike a balance between what the patient wants and still achieve a natural look."

Fat augmentation of the lips provides a natural appearance, but does not last as long as it does in other locations. "I would not go out of my way to put fat in the lips, unless you are already using fat for other indications in the face," she advised.

Semipermanent or permanent injectables that are associated with a high rate of adverse reactions when used in the lips are Radiesse, Sculptra, Evolence, and Artefill, as well as silicone, which should be avoided in lips altogether, she said. Their labels state they should not be used in lips, "yet physicians think that they can get away with it, and wind up every so often having a problem, and it is a big problem."

An important element of lip correction is consideration of the way lips appear in motion: When Dr. Butterwick consults with a patient, she said she observes their lips while they are talking. Some people have vertical lip lines from excessive pursing while they talk, or they pull down the corners of their mouth while talking, which are excess movements that can be "softened" with Botox, she said. Botox also can address a gummy smile.

Treating the surrounding tissue to support volume loss—such as deep marionette lines, a jowl, or a deep nasolabial fold right near the lip—will also improve the appearance of the lips.

Dr. Butterwick disclosed receiving grant research support from Mentor Corp., and is a consultant for Medicis Pharmaceutical Corp., Allergan Inc., Sanofi-Aventis, and Neutrogena Corp.

SDEF and this news organization are owned by Elsevier.

Photo shows patient prior to injection of 1 cc of Hyalaform to the upper lip.

Two weeks post injection, the cupid's bow is narrowed and more defined.

Source Photos courtesy Dr. Kimberly Butterwick

'We have to be mindful how the lips contribute' to the symmetry and proportions of the entire face.

Source DR. BUTTERWICK

The antithyroid drug propylthiouracil (PTU) has been associated with severe liver injuries and deaths in patients and should be reserved for those in the first trimester of pregnancy or those who are intolerant of or allergic to methimazole, according to a warning by the Food and Drug Administration.

“If PTU therapy is chosen, the patient should be closely monitored for symptoms and signs of liver injury, especially during the first 6 months after initiating therapy,” Dr. Amy Egan, deputy director for safety at the FDA's division of metabolism and endocrinology products at the Center for Drug Evaluation and Research, said in a statement that was posted on the agency's MedWatch Web site. From 1969, when the agency's adverse event reporting program was established, through October 2008, 32 cases of serious liver injury associated with PTU were reported to the FDA. Of these cases, 22 were in adults, and included 12 fatalities and 5 liver transplants. Among the 10 pediatric cases, there was 1 fatality and 6 reports of liver transplants.

Based on an analysis of these reports, the FDA determined that the risk of hepatotoxicity is greater with PTU than with methimazole (MMI). Like PTU, MMI is indicated for the treatment of hyperthyroidism caused by Graves' disease. The FDA received only five reports of serious liver injury associated with MMI, which was approved in 1950.

PTU, approved in 1947, is considered a second-line therapy for patients with Graves' disease, with the exception of those who are intolerant of or allergic to MMI. But because of rare cases of embryopathy reported in association with MMI treatment during pregnancy, PTU “may be more appropriate” for treating women with Graves' disease in the first trimester of pregnancy, according to the FDA.

The FDA plans to change the prescribing information for PTU to reflect the hepatotoxicity warning, and said that the American Thyroid Association (ATA) plans to update its Graves' disease treatment guidelines.

In April, PTU-induced liver failure was among the topics on the agenda at a public meeting on the role of PTU in managing Graves' disease in adults. The ATA/American Association of Clinical Endocrinologists Hyperthyroidism Guidelines Task Force is finalizing recommendations on the use of antithyroid drugs, including during pregnancy and childhood, and will cover the role of monitoring hepatic function in patients on PTU, according to the ATA.

Hepatoxicity has been recognized as one of the more serious but rare side effects associated with PTU, Dr. David Cooper, professor of medicine at Johns Hopkins University, Baltimore, said in an interview. MMI also can be hepatotoxic, but is usually associated with cholestatic dysfunction, while PTU causes hepatocellular necrosis.

With input from the ATA, the FDA decided to issue the warning, said Dr. Cooper, who directs the Johns Hopkins thyroid clinic. He and Dr. Scott Rivkees of the Yale Pediatric Thyroid Center, New Haven, Conn., coauthored an editorial in which they wrote, “one could reasonably conclude that PTU should never be used as a first line agent in either children or adults, with the possible exception of pregnant women and patients with life-threatening thyrotoxicosis” (J. Clin. Endocrinol. Metab. 2009; 94:1881-2).

Dr. Cooper said that most patients who can't take MMI should be treated with radioactive iodine or surgery. Patients who develop jaundice, fatigue, or other symptoms should stop PTU immediately, and contact their physicians. White blood cell count and bilirubin, alkaline phosphatase, and transaminase levels should be checked in such patients, he said.?

A link to the FDA's alert is available at www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm162701.htmwww.fda.gov/MedWatch/report.htm

The antithyroid drug propylthiouracil (PTU) has been associated with severe liver injuries and deaths in patients and should be reserved for those in the first trimester of pregnancy or those who are intolerant of or allergic to methimazole, according to a warning by the Food and Drug Administration.

“If PTU therapy is chosen, the patient should be closely monitored for symptoms and signs of liver injury, especially during the first 6 months after initiating therapy,” Dr. Amy Egan, deputy director for safety at the FDA's division of metabolism and endocrinology products at the Center for Drug Evaluation and Research, said in a statement that was posted on the agency's MedWatch Web site. From 1969, when the agency's adverse event reporting program was established, through October 2008, 32 cases of serious liver injury associated with PTU were reported to the FDA. Of these cases, 22 were in adults, and included 12 fatalities and 5 liver transplants. Among the 10 pediatric cases, there was 1 fatality and 6 reports of liver transplants.

Based on an analysis of these reports, the FDA determined that the risk of hepatotoxicity is greater with PTU than with methimazole (MMI). Like PTU, MMI is indicated for the treatment of hyperthyroidism caused by Graves' disease. The FDA received only five reports of serious liver injury associated with MMI, which was approved in 1950.

PTU, approved in 1947, is considered a second-line therapy for patients with Graves' disease, with the exception of those who are intolerant of or allergic to MMI. But because of rare cases of embryopathy reported in association with MMI treatment during pregnancy, PTU “may be more appropriate” for treating women with Graves' disease in the first trimester of pregnancy, according to the FDA.

The FDA plans to change the prescribing information for PTU to reflect the hepatotoxicity warning, and said that the American Thyroid Association (ATA) plans to update its Graves' disease treatment guidelines.

In April, PTU-induced liver failure was among the topics on the agenda at a public meeting on the role of PTU in managing Graves' disease in adults. The ATA/American Association of Clinical Endocrinologists Hyperthyroidism Guidelines Task Force is finalizing recommendations on the use of antithyroid drugs, including during pregnancy and childhood, and will cover the role of monitoring hepatic function in patients on PTU, according to the ATA.

Hepatoxicity has been recognized as one of the more serious but rare side effects associated with PTU, Dr. David Cooper, professor of medicine at Johns Hopkins University, Baltimore, said in an interview. MMI also can be hepatotoxic, but is usually associated with cholestatic dysfunction, while PTU causes hepatocellular necrosis.

With input from the ATA, the FDA decided to issue the warning, said Dr. Cooper, who directs the Johns Hopkins thyroid clinic. He and Dr. Scott Rivkees of the Yale Pediatric Thyroid Center, New Haven, Conn., coauthored an editorial in which they wrote, “one could reasonably conclude that PTU should never be used as a first line agent in either children or adults, with the possible exception of pregnant women and patients with life-threatening thyrotoxicosis” (J. Clin. Endocrinol. Metab. 2009; 94:1881-2).

Dr. Cooper said that most patients who can't take MMI should be treated with radioactive iodine or surgery. Patients who develop jaundice, fatigue, or other symptoms should stop PTU immediately, and contact their physicians. White blood cell count and bilirubin, alkaline phosphatase, and transaminase levels should be checked in such patients, he said.?

A link to the FDA's alert is available at www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm162701.htmwww.fda.gov/MedWatch/report.htm

The antithyroid drug propylthiouracil (PTU) has been associated with severe liver injuries and deaths in patients and should be reserved for those in the first trimester of pregnancy or those who are intolerant of or allergic to methimazole, according to a warning by the Food and Drug Administration.

“If PTU therapy is chosen, the patient should be closely monitored for symptoms and signs of liver injury, especially during the first 6 months after initiating therapy,” Dr. Amy Egan, deputy director for safety at the FDA's division of metabolism and endocrinology products at the Center for Drug Evaluation and Research, said in a statement that was posted on the agency's MedWatch Web site. From 1969, when the agency's adverse event reporting program was established, through October 2008, 32 cases of serious liver injury associated with PTU were reported to the FDA. Of these cases, 22 were in adults, and included 12 fatalities and 5 liver transplants. Among the 10 pediatric cases, there was 1 fatality and 6 reports of liver transplants.

Based on an analysis of these reports, the FDA determined that the risk of hepatotoxicity is greater with PTU than with methimazole (MMI). Like PTU, MMI is indicated for the treatment of hyperthyroidism caused by Graves' disease. The FDA received only five reports of serious liver injury associated with MMI, which was approved in 1950.

PTU, approved in 1947, is considered a second-line therapy for patients with Graves' disease, with the exception of those who are intolerant of or allergic to MMI. But because of rare cases of embryopathy reported in association with MMI treatment during pregnancy, PTU “may be more appropriate” for treating women with Graves' disease in the first trimester of pregnancy, according to the FDA.

The FDA plans to change the prescribing information for PTU to reflect the hepatotoxicity warning, and said that the American Thyroid Association (ATA) plans to update its Graves' disease treatment guidelines.

In April, PTU-induced liver failure was among the topics on the agenda at a public meeting on the role of PTU in managing Graves' disease in adults. The ATA/American Association of Clinical Endocrinologists Hyperthyroidism Guidelines Task Force is finalizing recommendations on the use of antithyroid drugs, including during pregnancy and childhood, and will cover the role of monitoring hepatic function in patients on PTU, according to the ATA.

Hepatoxicity has been recognized as one of the more serious but rare side effects associated with PTU, Dr. David Cooper, professor of medicine at Johns Hopkins University, Baltimore, said in an interview. MMI also can be hepatotoxic, but is usually associated with cholestatic dysfunction, while PTU causes hepatocellular necrosis.

With input from the ATA, the FDA decided to issue the warning, said Dr. Cooper, who directs the Johns Hopkins thyroid clinic. He and Dr. Scott Rivkees of the Yale Pediatric Thyroid Center, New Haven, Conn., coauthored an editorial in which they wrote, “one could reasonably conclude that PTU should never be used as a first line agent in either children or adults, with the possible exception of pregnant women and patients with life-threatening thyrotoxicosis” (J. Clin. Endocrinol. Metab. 2009; 94:1881-2).

Dr. Cooper said that most patients who can't take MMI should be treated with radioactive iodine or surgery. Patients who develop jaundice, fatigue, or other symptoms should stop PTU immediately, and contact their physicians. White blood cell count and bilirubin, alkaline phosphatase, and transaminase levels should be checked in such patients, he said.?

A link to the FDA's alert is available at www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm162701.htmwww.fda.gov/MedWatch/report.htm

The Food and Drug Administration has approved an ophthalmic formulation of a fluoroquinolone antibiotic, besifloxacin, for the treatment of bacterial conjunctivitis.

Besifloxacin ophthalmic suspension will be marketed as Besivance 0.6%, by Bausch & Lomb Inc. The recommended dosage is one drop in the affected eye or eyes three times a day, 4–12 hours apart for 7 days. The prescribing information summarizes a randomized study of almost 400 patients (aged 1–98 years) with bacterial conjunctivitis who were treated with besifloxacin or received placebo drops for 5 days. Clinical symptoms resolved in 45% of those on besifloxacin, compared with 33% of those on the vehicle. The eradication rate for causative pathogens in the besifloxacin group was statistically significant at 91%, compared with 60% in the vehicle group.

The most commonly reported ocular adverse event reported in treated patients has been conjunctival redness in about 2% of patients. To collect more safety data on besifloxacin, the FDA is requiring that the company conduct a postmarketing study comparing the recommended dosage of besifloxacin to vehicle in at least 300 patients with signs and symptoms of bacterial conjunctivitis.

The Food and Drug Administration has approved an ophthalmic formulation of a fluoroquinolone antibiotic, besifloxacin, for the treatment of bacterial conjunctivitis.

Besifloxacin ophthalmic suspension will be marketed as Besivance 0.6%, by Bausch & Lomb Inc. The recommended dosage is one drop in the affected eye or eyes three times a day, 4–12 hours apart for 7 days. The prescribing information summarizes a randomized study of almost 400 patients (aged 1–98 years) with bacterial conjunctivitis who were treated with besifloxacin or received placebo drops for 5 days. Clinical symptoms resolved in 45% of those on besifloxacin, compared with 33% of those on the vehicle. The eradication rate for causative pathogens in the besifloxacin group was statistically significant at 91%, compared with 60% in the vehicle group.

The most commonly reported ocular adverse event reported in treated patients has been conjunctival redness in about 2% of patients. To collect more safety data on besifloxacin, the FDA is requiring that the company conduct a postmarketing study comparing the recommended dosage of besifloxacin to vehicle in at least 300 patients with signs and symptoms of bacterial conjunctivitis.

The Food and Drug Administration has approved an ophthalmic formulation of a fluoroquinolone antibiotic, besifloxacin, for the treatment of bacterial conjunctivitis.

Besifloxacin ophthalmic suspension will be marketed as Besivance 0.6%, by Bausch & Lomb Inc. The recommended dosage is one drop in the affected eye or eyes three times a day, 4–12 hours apart for 7 days. The prescribing information summarizes a randomized study of almost 400 patients (aged 1–98 years) with bacterial conjunctivitis who were treated with besifloxacin or received placebo drops for 5 days. Clinical symptoms resolved in 45% of those on besifloxacin, compared with 33% of those on the vehicle. The eradication rate for causative pathogens in the besifloxacin group was statistically significant at 91%, compared with 60% in the vehicle group.

The most commonly reported ocular adverse event reported in treated patients has been conjunctival redness in about 2% of patients. To collect more safety data on besifloxacin, the FDA is requiring that the company conduct a postmarketing study comparing the recommended dosage of besifloxacin to vehicle in at least 300 patients with signs and symptoms of bacterial conjunctivitis.

ADELPHI, MD. — The atypical antipsychotic ziprasidone is effective for the treatment of manic or mixed episodes associated with bipolar disorder in patients aged 10-17 years, a Food and Drug Administration panel advised.

At a meeting in June, the Psychopharmacologic Drugs Advisory Committee voted 12-2 on ziprasidone's efficacy, with 4 abstentions. However, many on the 18-member panel abstained from voting on whether the data had shown the drug was acceptably safe in treating this population. Eight panel members voted in favor of safety, and one panelist voted no on this question. Among the reasons the nine panelists cited for abstaining was that a large number of patients were lost to follow-up in the study.

They also cited ambiguous data on an increase in QTc intervals among children treated with the drug, and the need for more data overall. Study data were presented by Pfizer, which manufactures ziprasidone (Geodon). The drug is already approved for treating schizophrenia and bipolar disorder in adults.

The panel was not asked specifically to rule on whether to recommend approval for treatment of the pediatric population. The FDA usually follows the recommendations of its advisory panels.

At the meeting, study results were presented on 238 patients, aged 10-17 years, with bipolar disorder (manic or mixed episodes) treated with placebo or ziprasidone (40-80 mg/day for those under 45 kg; 80-160 mg/day for those 45 kg or more). Based on the primary efficacy end point—change from baseline in the Young Mania Rating Scale after 4 weeks—there was a highly significant treatment effect similar to the changes observed in studies of adults, according to Pfizer.

Ziprasidone was generally well tolerated over 4 weeks, and for up to 26 weeks in an open-label study. The adverse event profile was similar to that seen in adults, with the exception of sedation and somnolence, which were more common in the pediatric population.

The rate of extrapyramidal symptoms was 24% among those on ziprasidone, compared with almost 8% among placebo. There were no completed suicides, and no increase in suicidality among those on ziprasidone.

In the short-term pediatric study, 3.6% of those on ziprasidone had a QTc interval increase of more than 450 msecs vs. 1.2% of those on placebo, Pfizer said.

ADELPHI, MD. — The atypical antipsychotic ziprasidone is effective for the treatment of manic or mixed episodes associated with bipolar disorder in patients aged 10-17 years, a Food and Drug Administration panel advised.

At a meeting in June, the Psychopharmacologic Drugs Advisory Committee voted 12-2 on ziprasidone's efficacy, with 4 abstentions. However, many on the 18-member panel abstained from voting on whether the data had shown the drug was acceptably safe in treating this population. Eight panel members voted in favor of safety, and one panelist voted no on this question. Among the reasons the nine panelists cited for abstaining was that a large number of patients were lost to follow-up in the study.

They also cited ambiguous data on an increase in QTc intervals among children treated with the drug, and the need for more data overall. Study data were presented by Pfizer, which manufactures ziprasidone (Geodon). The drug is already approved for treating schizophrenia and bipolar disorder in adults.

The panel was not asked specifically to rule on whether to recommend approval for treatment of the pediatric population. The FDA usually follows the recommendations of its advisory panels.

At the meeting, study results were presented on 238 patients, aged 10-17 years, with bipolar disorder (manic or mixed episodes) treated with placebo or ziprasidone (40-80 mg/day for those under 45 kg; 80-160 mg/day for those 45 kg or more). Based on the primary efficacy end point—change from baseline in the Young Mania Rating Scale after 4 weeks—there was a highly significant treatment effect similar to the changes observed in studies of adults, according to Pfizer.

Ziprasidone was generally well tolerated over 4 weeks, and for up to 26 weeks in an open-label study. The adverse event profile was similar to that seen in adults, with the exception of sedation and somnolence, which were more common in the pediatric population.

The rate of extrapyramidal symptoms was 24% among those on ziprasidone, compared with almost 8% among placebo. There were no completed suicides, and no increase in suicidality among those on ziprasidone.

In the short-term pediatric study, 3.6% of those on ziprasidone had a QTc interval increase of more than 450 msecs vs. 1.2% of those on placebo, Pfizer said.

ADELPHI, MD. — The atypical antipsychotic ziprasidone is effective for the treatment of manic or mixed episodes associated with bipolar disorder in patients aged 10-17 years, a Food and Drug Administration panel advised.

At a meeting in June, the Psychopharmacologic Drugs Advisory Committee voted 12-2 on ziprasidone's efficacy, with 4 abstentions. However, many on the 18-member panel abstained from voting on whether the data had shown the drug was acceptably safe in treating this population. Eight panel members voted in favor of safety, and one panelist voted no on this question. Among the reasons the nine panelists cited for abstaining was that a large number of patients were lost to follow-up in the study.

They also cited ambiguous data on an increase in QTc intervals among children treated with the drug, and the need for more data overall. Study data were presented by Pfizer, which manufactures ziprasidone (Geodon). The drug is already approved for treating schizophrenia and bipolar disorder in adults.

The panel was not asked specifically to rule on whether to recommend approval for treatment of the pediatric population. The FDA usually follows the recommendations of its advisory panels.

At the meeting, study results were presented on 238 patients, aged 10-17 years, with bipolar disorder (manic or mixed episodes) treated with placebo or ziprasidone (40-80 mg/day for those under 45 kg; 80-160 mg/day for those 45 kg or more). Based on the primary efficacy end point—change from baseline in the Young Mania Rating Scale after 4 weeks—there was a highly significant treatment effect similar to the changes observed in studies of adults, according to Pfizer.

Ziprasidone was generally well tolerated over 4 weeks, and for up to 26 weeks in an open-label study. The adverse event profile was similar to that seen in adults, with the exception of sedation and somnolence, which were more common in the pediatric population.

The rate of extrapyramidal symptoms was 24% among those on ziprasidone, compared with almost 8% among placebo. There were no completed suicides, and no increase in suicidality among those on ziprasidone.

In the short-term pediatric study, 3.6% of those on ziprasidone had a QTc interval increase of more than 450 msecs vs. 1.2% of those on placebo, Pfizer said.

ADELPHI, MD. — The atypical antipsychotic quetiapine is safe and effective for treating schizophrenia in adolescents and bipolar mania in both children and adolescents between the ages of 10 and 17 years, according to a Food and Drug Administration advisory panel.

At a meeting in June, the FDA's Psychopharmacologic Drugs Advisory Committee voted 17-1 that data on quetiapine showed it was effective for treating schizophrenia in adolescents aged 13-17 years. The panel also voted 16-0, with 2 abstentions, that the drug was “acceptably safe” for treating schizophrenia in this population.

The panel voted 17-0, with 1 abstention, that the drug was effective in treating bipolar mania in children and adolescents aged 10-17 years, and voted 13-0, with 5 abstentions, that it was safe in this group. A concern among those abstaining was safety in children aged 10-12.

The FDA usually follows the recommendations of its advisory panels.

Quetiapine is marketed as Seroquel by AstraZeneca Pharmaceuticals LP. The company presented results of three studies: two short-term studies and a safety study that followed 505 of these patients for 6 months.

One study compared 400 mg or 600 mg of quetiapine per day with placebo in 284 patients aged 10-17 years who had bipolar I mania. The patients were treated for 3 weeks. Changes in the Young Mania Rating Scale from baseline to day 21, the primary efficacy end point, were significantly greater in those on quetiapine than in those on placebo.

The second study comprised 222 patients aged 13-17 years, who had schizophrenia and were treated with 400 mg or 800 mg per day of quetiapine or placebo for 6 weeks. Changes in the Positive and Negative Syndrome Scale, which measures the severity of different components of schizophrenia, were significantly greater in those taking quetiapine.

In the two short-term studies, somnolence was the most common adverse event, affecting almost half of the patients on quetiapine and lasting for a mean of 12 days.

ADELPHI, MD. — The atypical antipsychotic quetiapine is safe and effective for treating schizophrenia in adolescents and bipolar mania in both children and adolescents between the ages of 10 and 17 years, according to a Food and Drug Administration advisory panel.

At a meeting in June, the FDA's Psychopharmacologic Drugs Advisory Committee voted 17-1 that data on quetiapine showed it was effective for treating schizophrenia in adolescents aged 13-17 years. The panel also voted 16-0, with 2 abstentions, that the drug was “acceptably safe” for treating schizophrenia in this population.

The panel voted 17-0, with 1 abstention, that the drug was effective in treating bipolar mania in children and adolescents aged 10-17 years, and voted 13-0, with 5 abstentions, that it was safe in this group. A concern among those abstaining was safety in children aged 10-12.

The FDA usually follows the recommendations of its advisory panels.

Quetiapine is marketed as Seroquel by AstraZeneca Pharmaceuticals LP. The company presented results of three studies: two short-term studies and a safety study that followed 505 of these patients for 6 months.

One study compared 400 mg or 600 mg of quetiapine per day with placebo in 284 patients aged 10-17 years who had bipolar I mania. The patients were treated for 3 weeks. Changes in the Young Mania Rating Scale from baseline to day 21, the primary efficacy end point, were significantly greater in those on quetiapine than in those on placebo.

The second study comprised 222 patients aged 13-17 years, who had schizophrenia and were treated with 400 mg or 800 mg per day of quetiapine or placebo for 6 weeks. Changes in the Positive and Negative Syndrome Scale, which measures the severity of different components of schizophrenia, were significantly greater in those taking quetiapine.

In the two short-term studies, somnolence was the most common adverse event, affecting almost half of the patients on quetiapine and lasting for a mean of 12 days.

ADELPHI, MD. — The atypical antipsychotic quetiapine is safe and effective for treating schizophrenia in adolescents and bipolar mania in both children and adolescents between the ages of 10 and 17 years, according to a Food and Drug Administration advisory panel.

At a meeting in June, the FDA's Psychopharmacologic Drugs Advisory Committee voted 17-1 that data on quetiapine showed it was effective for treating schizophrenia in adolescents aged 13-17 years. The panel also voted 16-0, with 2 abstentions, that the drug was “acceptably safe” for treating schizophrenia in this population.

The panel voted 17-0, with 1 abstention, that the drug was effective in treating bipolar mania in children and adolescents aged 10-17 years, and voted 13-0, with 5 abstentions, that it was safe in this group. A concern among those abstaining was safety in children aged 10-12.

The FDA usually follows the recommendations of its advisory panels.

Quetiapine is marketed as Seroquel by AstraZeneca Pharmaceuticals LP. The company presented results of three studies: two short-term studies and a safety study that followed 505 of these patients for 6 months.

One study compared 400 mg or 600 mg of quetiapine per day with placebo in 284 patients aged 10-17 years who had bipolar I mania. The patients were treated for 3 weeks. Changes in the Young Mania Rating Scale from baseline to day 21, the primary efficacy end point, were significantly greater in those on quetiapine than in those on placebo.

The second study comprised 222 patients aged 13-17 years, who had schizophrenia and were treated with 400 mg or 800 mg per day of quetiapine or placebo for 6 weeks. Changes in the Positive and Negative Syndrome Scale, which measures the severity of different components of schizophrenia, were significantly greater in those taking quetiapine.

In the two short-term studies, somnolence was the most common adverse event, affecting almost half of the patients on quetiapine and lasting for a mean of 12 days.

ADELPHI, MD. — The majority of a Food and Drug Administration advisory panel agreed that the data on the atypical antipsychotic olanzapine indicated that it was effective and had an acceptable safety profile for treating two pediatric indications: schizophrenia and bipolar mania in patients aged 13-17 years.

At a meeting of the FDA's Psychopharmacologic Drugs Advisory Committee, the panel voted 11-5, with 2 abstentions, that olanzapine had been shown to be effective as a treatment for schizophrenia in this age group, with the majority—10 panelists—voting that it had been shown to be “acceptably safe” for this indication. However, four of the panelists voted no on the safety question and four abstained, citing concerns that included the well-known metabolic effects of olanzapine.

The panel also voted 17-0, with 1 abstention, that the drug had been shown to be effective for treating bipolar mania, and voted 11-4, with 3 abstentions, that it had been shown to be acceptably safe in this age group for this indication.

Those voting positively on safety and efficacy for both indications said that they considered the drug as a second-line treatment, because of its metabolic effects. If approved, the label would advise clinicians to consider drugs before this one, because of concerns over its metabolic effects, Dr. Thomas Laughren, director of the FDA's division of psychiatry products, said at the meeting.

Olanzapine is marketed as Zyprexa by Eli Lilly and Co., and is approved for treating schizophrenia and bipolar disorder in adults.

Eli Lilly presented the results of a short-term study of 107 patients aged 13-17 with schizophrenia, comparing 2.5 mg to 20 mg per day of olanzapine to placebo over 4 weeks. The primary efficacy end point—the changes in the Brief Psychiatric Rating Scale-for Children (BPRS-C) total score from baseline to end point—found a significantly greater effect among those on olanzapine, with an effect size comparable to that seen in adult studies, according to the company.

In another study of 161 patients aged 13-17 years with bipolar disorder who were in an acute manic or mixed episode, those who received 2.5 mg to 20 mg per day of olanzapine had reductions in the Young Mania Rating Scale (YMRS) total score (the primary efficacy end point) that were significantly greater than the reductions seen among those on placebo, after 3 weeks of treatment.

In the two studies combined, sedation-related events were the most common adverse events associated with treatment (44% among those on olanzapine, compared with 9% of those on placebo), followed by increases in weight (almost 30%, compared with almost 6%, respectively), and increased appetite (24%, compared with 5.6%, respectively). Among those on olanzapine, 8% had elevated liver enzymes, compared with 1% of those on placebo.

The differences in these adverse events were all significantly greater among the patients who were taking olanzapine.

In addition to weight gain, increases in fasting glucose, fasting total cholesterol, fasting triglycerides, and prolactin levels have been documented in adolescents treated with olanzapine for 12 weeks or less, and for longer durations, according to Eli Lilly.

The increased risks of weight gain, hyperlipidemia, hyperglycemia, and hyperprolactinemia associated with olanzapine use in adolescents are included in the drug's label, even though the drug has not been approved for this age group.

ADELPHI, MD. — The majority of a Food and Drug Administration advisory panel agreed that the data on the atypical antipsychotic olanzapine indicated that it was effective and had an acceptable safety profile for treating two pediatric indications: schizophrenia and bipolar mania in patients aged 13-17 years.

At a meeting of the FDA's Psychopharmacologic Drugs Advisory Committee, the panel voted 11-5, with 2 abstentions, that olanzapine had been shown to be effective as a treatment for schizophrenia in this age group, with the majority—10 panelists—voting that it had been shown to be “acceptably safe” for this indication. However, four of the panelists voted no on the safety question and four abstained, citing concerns that included the well-known metabolic effects of olanzapine.

The panel also voted 17-0, with 1 abstention, that the drug had been shown to be effective for treating bipolar mania, and voted 11-4, with 3 abstentions, that it had been shown to be acceptably safe in this age group for this indication.

Those voting positively on safety and efficacy for both indications said that they considered the drug as a second-line treatment, because of its metabolic effects. If approved, the label would advise clinicians to consider drugs before this one, because of concerns over its metabolic effects, Dr. Thomas Laughren, director of the FDA's division of psychiatry products, said at the meeting.

Olanzapine is marketed as Zyprexa by Eli Lilly and Co., and is approved for treating schizophrenia and bipolar disorder in adults.

Eli Lilly presented the results of a short-term study of 107 patients aged 13-17 with schizophrenia, comparing 2.5 mg to 20 mg per day of olanzapine to placebo over 4 weeks. The primary efficacy end point—the changes in the Brief Psychiatric Rating Scale-for Children (BPRS-C) total score from baseline to end point—found a significantly greater effect among those on olanzapine, with an effect size comparable to that seen in adult studies, according to the company.

In another study of 161 patients aged 13-17 years with bipolar disorder who were in an acute manic or mixed episode, those who received 2.5 mg to 20 mg per day of olanzapine had reductions in the Young Mania Rating Scale (YMRS) total score (the primary efficacy end point) that were significantly greater than the reductions seen among those on placebo, after 3 weeks of treatment.

In the two studies combined, sedation-related events were the most common adverse events associated with treatment (44% among those on olanzapine, compared with 9% of those on placebo), followed by increases in weight (almost 30%, compared with almost 6%, respectively), and increased appetite (24%, compared with 5.6%, respectively). Among those on olanzapine, 8% had elevated liver enzymes, compared with 1% of those on placebo.

The differences in these adverse events were all significantly greater among the patients who were taking olanzapine.

In addition to weight gain, increases in fasting glucose, fasting total cholesterol, fasting triglycerides, and prolactin levels have been documented in adolescents treated with olanzapine for 12 weeks or less, and for longer durations, according to Eli Lilly.

The increased risks of weight gain, hyperlipidemia, hyperglycemia, and hyperprolactinemia associated with olanzapine use in adolescents are included in the drug's label, even though the drug has not been approved for this age group.

ADELPHI, MD. — The majority of a Food and Drug Administration advisory panel agreed that the data on the atypical antipsychotic olanzapine indicated that it was effective and had an acceptable safety profile for treating two pediatric indications: schizophrenia and bipolar mania in patients aged 13-17 years.

At a meeting of the FDA's Psychopharmacologic Drugs Advisory Committee, the panel voted 11-5, with 2 abstentions, that olanzapine had been shown to be effective as a treatment for schizophrenia in this age group, with the majority—10 panelists—voting that it had been shown to be “acceptably safe” for this indication. However, four of the panelists voted no on the safety question and four abstained, citing concerns that included the well-known metabolic effects of olanzapine.

The panel also voted 17-0, with 1 abstention, that the drug had been shown to be effective for treating bipolar mania, and voted 11-4, with 3 abstentions, that it had been shown to be acceptably safe in this age group for this indication.

Those voting positively on safety and efficacy for both indications said that they considered the drug as a second-line treatment, because of its metabolic effects. If approved, the label would advise clinicians to consider drugs before this one, because of concerns over its metabolic effects, Dr. Thomas Laughren, director of the FDA's division of psychiatry products, said at the meeting.

Olanzapine is marketed as Zyprexa by Eli Lilly and Co., and is approved for treating schizophrenia and bipolar disorder in adults.

Eli Lilly presented the results of a short-term study of 107 patients aged 13-17 with schizophrenia, comparing 2.5 mg to 20 mg per day of olanzapine to placebo over 4 weeks. The primary efficacy end point—the changes in the Brief Psychiatric Rating Scale-for Children (BPRS-C) total score from baseline to end point—found a significantly greater effect among those on olanzapine, with an effect size comparable to that seen in adult studies, according to the company.

In another study of 161 patients aged 13-17 years with bipolar disorder who were in an acute manic or mixed episode, those who received 2.5 mg to 20 mg per day of olanzapine had reductions in the Young Mania Rating Scale (YMRS) total score (the primary efficacy end point) that were significantly greater than the reductions seen among those on placebo, after 3 weeks of treatment.

In the two studies combined, sedation-related events were the most common adverse events associated with treatment (44% among those on olanzapine, compared with 9% of those on placebo), followed by increases in weight (almost 30%, compared with almost 6%, respectively), and increased appetite (24%, compared with 5.6%, respectively). Among those on olanzapine, 8% had elevated liver enzymes, compared with 1% of those on placebo.

The differences in these adverse events were all significantly greater among the patients who were taking olanzapine.

In addition to weight gain, increases in fasting glucose, fasting total cholesterol, fasting triglycerides, and prolactin levels have been documented in adolescents treated with olanzapine for 12 weeks or less, and for longer durations, according to Eli Lilly.

The increased risks of weight gain, hyperlipidemia, hyperglycemia, and hyperprolactinemia associated with olanzapine use in adolescents are included in the drug's label, even though the drug has not been approved for this age group.

An intravenous formulation of ibuprofen was approved by the Food and Drug Administration in June for treating mild to moderate pain, as an adjunct to opioid analgesics, and for the reduction of fever in adults.

This is the first injectable formulation of ibuprofen available and is for use only in the hospital, according to the FDA statement announcing the approval. The product, which will be marketed as Caldolor, is expected to become available later this year, according to the manufacturer, Cumberland Pharmaceuticals Inc.

In phase III studies, patients who received Caldolor reported a significant reduction in pain intensity after surgery and used significantly less morphine in the 24 hours following surgery, according to Cumberland.

An FDA statement announcing the approval cited a study of 319 women who had undergone an elective abdominal hysterectomy. Those who received Caldolor were less likely to request morphine than those who did not. “An injectable ibuprofen product can provide patients with relief from pain and fever when they cannot take oral products,” Dr. Bob Rappaport, director of the FDA's division of anesthesia, analgesia, and rheumatology drug products, said in the statement. Until now, he noted, most NSAIDs have been available only in oral form.

For acute pain, the recommended dosage is 400-800 mg administered intravenously over 30 minutes, every 6 hours. For fever, the recommended dosage is 400 mg administered over 30 minutes, followed by 400 mg every 4-6 hours, or 100-200 mg every 4 hours, as needed, according to the FDA.

Nausea, flatulence, vomiting, and headache were the most common adverse reactions reported in clinical trials of Caldolor, which should be used with caution in patients with heart failure, renal impairment, or liver impairment; in those taking diuretics or ACE inhibitors; and in patients with a history of ulcers or gastrointestinal bleeding.

Caldolor is contraindicated in patients with asthma, urticaria, or allergic-type reactions to aspirin or other NSAIDs; during the perioperative period in patients undergoing coronary artery bypass surgery; and in patients with known hypersensitivity to ibuprofen or other NSAIDs, according to the manufacturer. Blood pressure should be monitored during treatment.

An intravenous formulation of ibuprofen was approved by the Food and Drug Administration in June for treating mild to moderate pain, as an adjunct to opioid analgesics, and for the reduction of fever in adults.

This is the first injectable formulation of ibuprofen available and is for use only in the hospital, according to the FDA statement announcing the approval. The product, which will be marketed as Caldolor, is expected to become available later this year, according to the manufacturer, Cumberland Pharmaceuticals Inc.

In phase III studies, patients who received Caldolor reported a significant reduction in pain intensity after surgery and used significantly less morphine in the 24 hours following surgery, according to Cumberland.

An FDA statement announcing the approval cited a study of 319 women who had undergone an elective abdominal hysterectomy. Those who received Caldolor were less likely to request morphine than those who did not. “An injectable ibuprofen product can provide patients with relief from pain and fever when they cannot take oral products,” Dr. Bob Rappaport, director of the FDA's division of anesthesia, analgesia, and rheumatology drug products, said in the statement. Until now, he noted, most NSAIDs have been available only in oral form.

For acute pain, the recommended dosage is 400-800 mg administered intravenously over 30 minutes, every 6 hours. For fever, the recommended dosage is 400 mg administered over 30 minutes, followed by 400 mg every 4-6 hours, or 100-200 mg every 4 hours, as needed, according to the FDA.

Nausea, flatulence, vomiting, and headache were the most common adverse reactions reported in clinical trials of Caldolor, which should be used with caution in patients with heart failure, renal impairment, or liver impairment; in those taking diuretics or ACE inhibitors; and in patients with a history of ulcers or gastrointestinal bleeding.

Caldolor is contraindicated in patients with asthma, urticaria, or allergic-type reactions to aspirin or other NSAIDs; during the perioperative period in patients undergoing coronary artery bypass surgery; and in patients with known hypersensitivity to ibuprofen or other NSAIDs, according to the manufacturer. Blood pressure should be monitored during treatment.

An intravenous formulation of ibuprofen was approved by the Food and Drug Administration in June for treating mild to moderate pain, as an adjunct to opioid analgesics, and for the reduction of fever in adults.

This is the first injectable formulation of ibuprofen available and is for use only in the hospital, according to the FDA statement announcing the approval. The product, which will be marketed as Caldolor, is expected to become available later this year, according to the manufacturer, Cumberland Pharmaceuticals Inc.

In phase III studies, patients who received Caldolor reported a significant reduction in pain intensity after surgery and used significantly less morphine in the 24 hours following surgery, according to Cumberland.

An FDA statement announcing the approval cited a study of 319 women who had undergone an elective abdominal hysterectomy. Those who received Caldolor were less likely to request morphine than those who did not. “An injectable ibuprofen product can provide patients with relief from pain and fever when they cannot take oral products,” Dr. Bob Rappaport, director of the FDA's division of anesthesia, analgesia, and rheumatology drug products, said in the statement. Until now, he noted, most NSAIDs have been available only in oral form.

For acute pain, the recommended dosage is 400-800 mg administered intravenously over 30 minutes, every 6 hours. For fever, the recommended dosage is 400 mg administered over 30 minutes, followed by 400 mg every 4-6 hours, or 100-200 mg every 4 hours, as needed, according to the FDA.

Nausea, flatulence, vomiting, and headache were the most common adverse reactions reported in clinical trials of Caldolor, which should be used with caution in patients with heart failure, renal impairment, or liver impairment; in those taking diuretics or ACE inhibitors; and in patients with a history of ulcers or gastrointestinal bleeding.

Caldolor is contraindicated in patients with asthma, urticaria, or allergic-type reactions to aspirin or other NSAIDs; during the perioperative period in patients undergoing coronary artery bypass surgery; and in patients with known hypersensitivity to ibuprofen or other NSAIDs, according to the manufacturer. Blood pressure should be monitored during treatment.

Cycloset, a quick-release oral formulation of bromocriptine mesylate, was recently approved by the Food and Drug Administration as a treatment for type 2 diabetes, either as monotherapy or as adjunctive therapy to currently marketed type 2 diabetes drugs, according to the drug's manufacturers.

Cycloset is the first diabetes drug to gain approval since the agency published new guidance for the cardiovascular safety of diabetes drugs last December. Drug makers VeroScience and S2 Therapeutics Inc., announced the approval on May 6. Cycloset is taken by mouth once daily in the morning, and results in a “brief pulse of dopamine agonist activity shortly after its administration,” which improves postprandial glucose without increasing plasma insulin concentrations, according to a statement issued by VeroScience.

Bromocriptine is a sympatholytic dopamine D2 receptor agonist that can “exert inhibitor effects on serotonin in the central nervous system,” according to a ClinicalTrials.gov

Cycloset is approved for monotherapy or as adjunctive therapy to currently marketed type 2 diabetes drugs. Postmarketing studies required by the FDA will assess bioavailability and feasibility in pediatric patients between ages 10 and 16, as well as a randomized, double-blind controlled safety and efficacy study in such patients. The FDA waived requirements for pediatric study in patients under age 10 due to the low number of potential participants.

Cycloset, a quick-release oral formulation of bromocriptine mesylate, was recently approved by the Food and Drug Administration as a treatment for type 2 diabetes, either as monotherapy or as adjunctive therapy to currently marketed type 2 diabetes drugs, according to the drug's manufacturers.

Cycloset is the first diabetes drug to gain approval since the agency published new guidance for the cardiovascular safety of diabetes drugs last December. Drug makers VeroScience and S2 Therapeutics Inc., announced the approval on May 6. Cycloset is taken by mouth once daily in the morning, and results in a “brief pulse of dopamine agonist activity shortly after its administration,” which improves postprandial glucose without increasing plasma insulin concentrations, according to a statement issued by VeroScience.

Bromocriptine is a sympatholytic dopamine D2 receptor agonist that can “exert inhibitor effects on serotonin in the central nervous system,” according to a ClinicalTrials.gov

Cycloset is approved for monotherapy or as adjunctive therapy to currently marketed type 2 diabetes drugs. Postmarketing studies required by the FDA will assess bioavailability and feasibility in pediatric patients between ages 10 and 16, as well as a randomized, double-blind controlled safety and efficacy study in such patients. The FDA waived requirements for pediatric study in patients under age 10 due to the low number of potential participants.

Cycloset, a quick-release oral formulation of bromocriptine mesylate, was recently approved by the Food and Drug Administration as a treatment for type 2 diabetes, either as monotherapy or as adjunctive therapy to currently marketed type 2 diabetes drugs, according to the drug's manufacturers.

Cycloset is the first diabetes drug to gain approval since the agency published new guidance for the cardiovascular safety of diabetes drugs last December. Drug makers VeroScience and S2 Therapeutics Inc., announced the approval on May 6. Cycloset is taken by mouth once daily in the morning, and results in a “brief pulse of dopamine agonist activity shortly after its administration,” which improves postprandial glucose without increasing plasma insulin concentrations, according to a statement issued by VeroScience.

Bromocriptine is a sympatholytic dopamine D2 receptor agonist that can “exert inhibitor effects on serotonin in the central nervous system,” according to a ClinicalTrials.gov

Cycloset is approved for monotherapy or as adjunctive therapy to currently marketed type 2 diabetes drugs. Postmarketing studies required by the FDA will assess bioavailability and feasibility in pediatric patients between ages 10 and 16, as well as a randomized, double-blind controlled safety and efficacy study in such patients. The FDA waived requirements for pediatric study in patients under age 10 due to the low number of potential participants.

Reports of severe liver injuries—including one fatality—associated with Hydroxycut brand dietary supplements have prompted a nationwide product recall, the Food and Drug Administration announced last month. The products are marketed as weight-loss aids, energy-enhancers, low-carbohydrate diet aids, and diuretics.

The 23 reports of hepatic injuries have been in people aged 21–51 years, with no other identifiable cause for liver diseases and who have not appeared to be related to duration of use or dose. Included are cases of asymptomatic hyperbilirubinemia, jaundice, liver damage, liver transplant, and one death—a 19-year-old previously healthy male in 2007 in the U.S. Southwest. The outcome of another patient with liver failure who was on a transplant list is not known, the FDA said in a press briefing to announce the recall. In some cases, stoppage of Hydroxycut consumption resulted in recovery of liver function.

“We urge you to review your cases of hepatitis in order to determine if any may be related to the use of dietary supplements in these patients,” the FDA advised in a letter to health care professionals. In most cases, people had no identifiable preexisting medical condition that would predispose them to liver injury. There also have been reports of people with nonhepatic serious side effects associated with use of the products, including seizures, cardiovascular disorders ranging from palpitations to a heart attack, and rhabdomyolysis.

The recall covers 14 different products with the Hydroxycut name, including Hydroxycut Regular Rapid-Release Capsules, Hydroxycut Hardcore Liquid Caplets, Hydroxycut Caffeine-Free Drink Packets, and Hydroxycut Carb Control. Two Hydroxycut products—Hydroxycut Cleanse and Hoodia—which have completely different ingredients, are not affected by the recall, the FDA said.

Although liver damage associated with use of these supplements “appears to be relatively rare,” the FDA is warning consumers to immediately stop using these products, which are sold widely in supermarkets, health food stores, online, and on television. Ontario-based manufacturer Iovate Health Sciences Inc. has told the FDA that 2008 sales totaled more than 9 million units of Hydroxycut products, the agency said.

The precise cause of liver damage has not been identified, because the products contain herbs, herbal extracts, chemicals and metals, and other “overlapping” ingredients, making it difficult to pinpoint the specific ingredient or combination of ingredients that cause liver damage, Dr. Linda Katz, interim chief medical officer at the FDA's Center for Food Safety and Applied Nutrition (CFSAN), said during the briefing.

While most of the other 23 reports of Hydroxycut-related liver injury were made known to the FDA before the passage of the legislation, the agency said the rule allowing the agency to inspect the company's adverse event reports directly has been helpful in its investigation. Such inspection is “something we could not do before,” said Vasilios Frankos, Ph.D., director of CSFAN's Division of Dietary Supplement Programs. For information, go to the FDA's Med Watch Web site at www.fda.gov/medwatch/safety/2009/safety09.htm#Hydroxycut

Reports of severe liver injuries—including one fatality—associated with Hydroxycut brand dietary supplements have prompted a nationwide product recall, the Food and Drug Administration announced last month. The products are marketed as weight-loss aids, energy-enhancers, low-carbohydrate diet aids, and diuretics.

The 23 reports of hepatic injuries have been in people aged 21–51 years, with no other identifiable cause for liver diseases and who have not appeared to be related to duration of use or dose. Included are cases of asymptomatic hyperbilirubinemia, jaundice, liver damage, liver transplant, and one death—a 19-year-old previously healthy male in 2007 in the U.S. Southwest. The outcome of another patient with liver failure who was on a transplant list is not known, the FDA said in a press briefing to announce the recall. In some cases, stoppage of Hydroxycut consumption resulted in recovery of liver function.

“We urge you to review your cases of hepatitis in order to determine if any may be related to the use of dietary supplements in these patients,” the FDA advised in a letter to health care professionals. In most cases, people had no identifiable preexisting medical condition that would predispose them to liver injury. There also have been reports of people with nonhepatic serious side effects associated with use of the products, including seizures, cardiovascular disorders ranging from palpitations to a heart attack, and rhabdomyolysis.

The recall covers 14 different products with the Hydroxycut name, including Hydroxycut Regular Rapid-Release Capsules, Hydroxycut Hardcore Liquid Caplets, Hydroxycut Caffeine-Free Drink Packets, and Hydroxycut Carb Control. Two Hydroxycut products—Hydroxycut Cleanse and Hoodia—which have completely different ingredients, are not affected by the recall, the FDA said.

Although liver damage associated with use of these supplements “appears to be relatively rare,” the FDA is warning consumers to immediately stop using these products, which are sold widely in supermarkets, health food stores, online, and on television. Ontario-based manufacturer Iovate Health Sciences Inc. has told the FDA that 2008 sales totaled more than 9 million units of Hydroxycut products, the agency said.

The precise cause of liver damage has not been identified, because the products contain herbs, herbal extracts, chemicals and metals, and other “overlapping” ingredients, making it difficult to pinpoint the specific ingredient or combination of ingredients that cause liver damage, Dr. Linda Katz, interim chief medical officer at the FDA's Center for Food Safety and Applied Nutrition (CFSAN), said during the briefing.

While most of the other 23 reports of Hydroxycut-related liver injury were made known to the FDA before the passage of the legislation, the agency said the rule allowing the agency to inspect the company's adverse event reports directly has been helpful in its investigation. Such inspection is “something we could not do before,” said Vasilios Frankos, Ph.D., director of CSFAN's Division of Dietary Supplement Programs. For information, go to the FDA's Med Watch Web site at www.fda.gov/medwatch/safety/2009/safety09.htm#Hydroxycut

Reports of severe liver injuries—including one fatality—associated with Hydroxycut brand dietary supplements have prompted a nationwide product recall, the Food and Drug Administration announced last month. The products are marketed as weight-loss aids, energy-enhancers, low-carbohydrate diet aids, and diuretics.

The 23 reports of hepatic injuries have been in people aged 21–51 years, with no other identifiable cause for liver diseases and who have not appeared to be related to duration of use or dose. Included are cases of asymptomatic hyperbilirubinemia, jaundice, liver damage, liver transplant, and one death—a 19-year-old previously healthy male in 2007 in the U.S. Southwest. The outcome of another patient with liver failure who was on a transplant list is not known, the FDA said in a press briefing to announce the recall. In some cases, stoppage of Hydroxycut consumption resulted in recovery of liver function.

“We urge you to review your cases of hepatitis in order to determine if any may be related to the use of dietary supplements in these patients,” the FDA advised in a letter to health care professionals. In most cases, people had no identifiable preexisting medical condition that would predispose them to liver injury. There also have been reports of people with nonhepatic serious side effects associated with use of the products, including seizures, cardiovascular disorders ranging from palpitations to a heart attack, and rhabdomyolysis.

The recall covers 14 different products with the Hydroxycut name, including Hydroxycut Regular Rapid-Release Capsules, Hydroxycut Hardcore Liquid Caplets, Hydroxycut Caffeine-Free Drink Packets, and Hydroxycut Carb Control. Two Hydroxycut products—Hydroxycut Cleanse and Hoodia—which have completely different ingredients, are not affected by the recall, the FDA said.

Although liver damage associated with use of these supplements “appears to be relatively rare,” the FDA is warning consumers to immediately stop using these products, which are sold widely in supermarkets, health food stores, online, and on television. Ontario-based manufacturer Iovate Health Sciences Inc. has told the FDA that 2008 sales totaled more than 9 million units of Hydroxycut products, the agency said.

The precise cause of liver damage has not been identified, because the products contain herbs, herbal extracts, chemicals and metals, and other “overlapping” ingredients, making it difficult to pinpoint the specific ingredient or combination of ingredients that cause liver damage, Dr. Linda Katz, interim chief medical officer at the FDA's Center for Food Safety and Applied Nutrition (CFSAN), said during the briefing.

While most of the other 23 reports of Hydroxycut-related liver injury were made known to the FDA before the passage of the legislation, the agency said the rule allowing the agency to inspect the company's adverse event reports directly has been helpful in its investigation. Such inspection is “something we could not do before,” said Vasilios Frankos, Ph.D., director of CSFAN's Division of Dietary Supplement Programs. For information, go to the FDA's Med Watch Web site at www.fda.gov/medwatch/safety/2009/safety09.htm#Hydroxycut

The approval of the oral anticoagulant rivaroxaban is on hold while the manufacturer evaluates a “complete response” letter issued by the Food and Drug Administration, according to the manufacturer, Ortho-McNeil.

The FDA has requested more information about rivaroxaban, which is under review for the prevention of venous thromboembolism in patients undergoing hip or knee replacement surgery. A statement issued by the company said that Ortho-McNeil was evaluating the FDA's letter, and would address the questions raised as soon as possible. The FDA has not requested that any new clinical or nonclinical studies of safety and efficacy, according to the statement, which did not provide further details.

If approved, rivaroxaban, a direct Factor Xa inhibitor, would be the first oral anticoagulant approved for the two indications under review, and the first approved since warfarin. The FDA does not comment on products that are under review for approval.

The agency issues a complete response letter to a company when the review of a product approval application has been completed and the product cannot be approved based on available information. This has replaced the “approvable” and “nonapprovable” letters that the FDA previously issued.

In March, the majority of the FDA's Cardiovascular and Renal Drugs Advisory Committee agreed that data from four clinical trials showed that the anticoagulant had a favorable risk-benefit profile for the proposed indications. Panel members were concerned about off-label use of the drug, and about the possibility that it might be used for longer periods than the duration studied in hip replacement patients (35 days) and knee replacement patients (14 days). Although the majority agreed that the potential hepatotoxicity of the drug should not preclude approval, the panel agreed that long-term data on the hepatotoxicity risk were needed (HOSPITALIST NEWS, April 2009, p. 1).

Ortho-McNeil is a division of Johnson & Johnson Pharmaceutical Research & Development LLC.

The approval of the oral anticoagulant rivaroxaban is on hold while the manufacturer evaluates a “complete response” letter issued by the Food and Drug Administration, according to the manufacturer, Ortho-McNeil.

The FDA has requested more information about rivaroxaban, which is under review for the prevention of venous thromboembolism in patients undergoing hip or knee replacement surgery. A statement issued by the company said that Ortho-McNeil was evaluating the FDA's letter, and would address the questions raised as soon as possible. The FDA has not requested that any new clinical or nonclinical studies of safety and efficacy, according to the statement, which did not provide further details.

If approved, rivaroxaban, a direct Factor Xa inhibitor, would be the first oral anticoagulant approved for the two indications under review, and the first approved since warfarin. The FDA does not comment on products that are under review for approval.

The agency issues a complete response letter to a company when the review of a product approval application has been completed and the product cannot be approved based on available information. This has replaced the “approvable” and “nonapprovable” letters that the FDA previously issued.

In March, the majority of the FDA's Cardiovascular and Renal Drugs Advisory Committee agreed that data from four clinical trials showed that the anticoagulant had a favorable risk-benefit profile for the proposed indications. Panel members were concerned about off-label use of the drug, and about the possibility that it might be used for longer periods than the duration studied in hip replacement patients (35 days) and knee replacement patients (14 days). Although the majority agreed that the potential hepatotoxicity of the drug should not preclude approval, the panel agreed that long-term data on the hepatotoxicity risk were needed (HOSPITALIST NEWS, April 2009, p. 1).

Ortho-McNeil is a division of Johnson & Johnson Pharmaceutical Research & Development LLC.

The approval of the oral anticoagulant rivaroxaban is on hold while the manufacturer evaluates a “complete response” letter issued by the Food and Drug Administration, according to the manufacturer, Ortho-McNeil.

The FDA has requested more information about rivaroxaban, which is under review for the prevention of venous thromboembolism in patients undergoing hip or knee replacement surgery. A statement issued by the company said that Ortho-McNeil was evaluating the FDA's letter, and would address the questions raised as soon as possible. The FDA has not requested that any new clinical or nonclinical studies of safety and efficacy, according to the statement, which did not provide further details.

If approved, rivaroxaban, a direct Factor Xa inhibitor, would be the first oral anticoagulant approved for the two indications under review, and the first approved since warfarin. The FDA does not comment on products that are under review for approval.

The agency issues a complete response letter to a company when the review of a product approval application has been completed and the product cannot be approved based on available information. This has replaced the “approvable” and “nonapprovable” letters that the FDA previously issued.

In March, the majority of the FDA's Cardiovascular and Renal Drugs Advisory Committee agreed that data from four clinical trials showed that the anticoagulant had a favorable risk-benefit profile for the proposed indications. Panel members were concerned about off-label use of the drug, and about the possibility that it might be used for longer periods than the duration studied in hip replacement patients (35 days) and knee replacement patients (14 days). Although the majority agreed that the potential hepatotoxicity of the drug should not preclude approval, the panel agreed that long-term data on the hepatotoxicity risk were needed (HOSPITALIST NEWS, April 2009, p. 1).

Ortho-McNeil is a division of Johnson & Johnson Pharmaceutical Research & Development LLC.