Antidepressant Gets FDA OK for Hot Flashes

- Menopause is not a disease. Is a normal step in a woman life.
- Paroxetin is an antidepressive drug, with many adverse effects.
- Another bussines in the FDA.

The FDA has approved paroxetine (Brisdelle), a selective serotonin reuptake inhibitor (SSRI), to treat moderate to severe hot flashes associated with menopause.
"Today's approval provides women with the first FDA-approved, nonhormonal therapeutic option to help ease the hot flashes that are so common in menopause," said Hylton Joffe, MD, director of the division of bone, reproductive, and urologic products at the FDA's Center for Drug Evaluation and Research.
The safety and efficacy of the drug in this condition was established in two randomized, double-blind, controlled studies in 1,175 postmenopausal women with moderate to severe hot flashes.
Women in the study had a minimum of seven to eight hot flashes per day or 50 to 60 per week.
Treatment lasted 12 weeks in one study and 24 weeks in another, and both trials showed that paroxetine reduced hot flashes better than placebo.
The most common side effects with the drug included headache, fatigue, and nausea or vomiting,
The dosage approved for use in hot flashes (7.5 mg) is far lower than that used in conditions such as major depressive disorder, obsessive-compulsive disorder, panic disorder, and generalized anxiety disorder.
Still, the medication will contain a boxed warning about suicidality given that this side effect is included in the label for the drug when it is used in higher doses in the other conditions.
Additional warnings that will be included in the label will note a possible reduction in the efficacy of tamoxifen if both medications are used together, an increased risk of bleeding, and a risk of developing serotonin syndrome – symptoms of which include confusion, rapid heart rate, and high blood pressure.
The drug will be marketed by Noven Therapeutics of Miami.

Cardiac Science Powerheart, CardioVive, CardioLife; GE Responder and Responder Pro; and Nihon-Kohden Automated External Defibrillator

Cardiac Science Powerheart, CardioVive, CardioLife; GE Responder and Responder Pro; and Nihon-Kohden Automated External Defibrillators (AEDs): Class I Recall - Defective Component

Affected Models include:

• Powerheart 9300A, 9300E, 9300P, 9390A, and 9390E
• CardioVive 92532, 92533
• CardioLife 9200G and 9231
• GE Responder and Responder Pro
• Nihon-Kohden AEDs 

AUDIENCE: Emergency Medicine, Cardiology, Risk Manager

ISSUE: FDA notified healthcare professionals and medical care organizations of the Class 1 recall of the listed AEDs which contain a component that may fail unexpectedly due to a defect. If the component were to fail during a rescue attempt, the AED may not deliver defibrillation therapy, causing serious adverse health consequences, including death. The unit’s self test may not detect the failure or impending failure of the component.

BACKGROUND: These products are used for emergency treatment of victims showing symptoms of sudden cardiac arrest who are unresponsive and not breathing. These AEDs were manufactured and distributed from July 1, 2011 through December 30, 2011.

RECOMMENDATION: Affected customers are advised to contact the firm to arrange for delivery of shipping materials for an immediate return of their AEDs for repair. The affected devices will receive a hardware correction, and the same serial number device will be returned to the customer in most cases.

Read the MedWatch safety alert, including links to the Recal Notice and Letter, at:

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm294538.htm

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To Ease Or Not To Ease: FDA Panel Votes To Loosen Avandia Restrictions

Fda (Photo credit: Wikipedia)

Source: Pharmalot » To Ease Or Not To Ease: FDA Panel Votes To Loosen Avandia Restrictions

Avandia = Rosiglitazone

  by Ed Silverman 1

avandia.jpg

avandia.jpg

After an intense two-day meeting that illustrated the challenges in determining drug safety, a divided FDA advisory panel voted to ease restrictions on the use of the controversial Avandia diabetes pill, which has been under the equivalent of regulatory lock and key for nearly three years.
Of the 26 panelists, 20 voted to either remove or somehow modify the existing REMS, or Risk Evaluation and Mitigation Strategy, which was established in 2010 following a protracted controversy over the extent to which the GlaxoSmithKline drug causes serious cardiovascular events. That debate emerged after a 2007 meta-analysis found a 43 percent greater risk of causing heart attacks and strokes (see this and this).
Despite the vote, uncertainty remains. The panelists were not in agreement on how to ease the REMS, one of many the FDA established in response to drug safety scandals. The Avandia program contains a medication guide and another component known as ETASU, or elements to assure safe use, which spells out terms for physician participation, patient enrollment and distribution requirements for pharmacies (here is the Avandia REMS).
“I do feel we should continue with the medication guide and communication strategy, and maybe it’s possible to eliminate the ETASU or soften it,” said Marvin Konstam, a panelist and director of the cardiovascular center at Tufts University School of Medicine. “This shifts the burden to physicians and allows him or her to use their judgment.” He was one of 13 panelists who voted to modify the REMS.
"I believe relaxing the REMS would put this on a more even playing ffield with other drugs with similar risks," said Elaine Morrato, an associated professor at the University of Colorado School of Public Health, who also voted to modify the REMS.
Several panelists also suggested that, given a re-adjudicated Glaxo (GSK) clinical trial suggesting the pill was not associated with a significantly increased risk of cardiovascular events, another study should be conducted to obtain outcomes data on adverse events. The FDA had ordered the re-adjudication of the so-called RECORD trial three years ago at the same time the REMS program was required.
There are, however, obstacles to running such a trial, including ethical considerations, given that REMS restrictions are in place which, combined with the negative publicity, drastically cut the population of patients who currently use Avandia. In the US, for instance, the number currently hovers somewhere around 3,000, down from 120,000 three years ago, according to Glaxo.
Moreover, there would appear to be little incentive for Glaxo to sponsor such a trial. The Avandia patent expired in 2011 and sales basically melted to less than $10 million last year, a far cry from the $3 billion or so in annual sales that the pill generated before the controversy erupted. Glaxo issued a bland statement about the vote and re-adjudication, but did not mention the possibility of another study.
“The train may have already left the station on this,” said David Oakes, another panelist, who is a professor in the department of biostatistics and computational biology at the University of Rochester Medical Center. “I’m not sure what the practical results of this will be.” He was one of seven panelists who voted to remove the REMS altogether.
Whatever direction the FDA takes will be closely watched, especially since the agency has been harshly criticized over its handling of the Avandia controversy. FDA officials, for instance, were made aware of undisclosed trial data, which became an issue for Glaxo and contributed to a $3 billion fine the drugmaker paid last year to the federal government to settle charges of bad corporate behavior. At one point, the FDA was also accused of suppressing a different Avandia study (back story).
More recently, one co-author of the 2007 meta-analysis, Steve Nissen of the Cleveland Clinic, accused the FDA of trying to save face by holding this week’s meeting and he noted that the FDA did not invite him to speak at the two-day meeting (back story). To some extent, though, he was vindicated in that some restrictions will remain in place and Avandia usage is unlikely to increase substantially.
But the re-adjudication, itself, became the focal point of some drama after FDA medical reviewer Tom Marciniak alleged that Duke Clinical Research Institute, which was tapped to review the RECORD trial, was biased because, he explained, the academic research organization relied on trial data that was supplied by Glaxo.
His remarks were contained in FDA briefing documents released earlier this week that revealed a remarkable spate of jousting between him and several of his supervisors. Not only did they tangle over the veracity of the re-adjudication process, but Marciniak was also chastised for “unprofessional language” he used to criticize Glaxo, the Duke team and some of his own colleagues at the agency (more here).
Despite the unusual clash, the FDA panelists largely felt that the re-adjudication process itself was credible (see Duke report here), even as they mostly agreed with FDA reviewers that the underlying RECORD trial contained design flaws. In fact, DCRI’s Ken Mahaffey, who was in charge of the re-adjudication, acknowledged the study did not provide strong evidence that Avandia is safe.
For this reason, FDA critics continue to maintain that Avandia restrictions should not be loosened. “The concern is that by lifting the restrictions, more people will get this drug and nothing that happened at the meeting today does anything to make the drug any safer,” says Sid Wolfe, who heads Public Citizen Health Research Group and who testified at the meeting. “I think it’s an unfortunate outcome. The FDA has been given a green flag, so to speak, and this could be to the detriment of some people.”
As for Glaxo, here part of the official statement: “We appreciate the committee’s thorough examination of the RECORD results and will continue to work with the FDA as it considers the recommendation of the committee,” says James Shannon, Glaxo's chief medical officer. "We continue to believe that Avandia is a safe and effective treatment option for type 2 diabetes when used for the appropriate patient and in accordance with labeling.”

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Magnesium Sulfate: against prolongued use in pre-term labor

Magnesium Sulfate: Drug Safety Communication - Recommendation Against Prolonged Use in Pre-term Labor

AUDIENCE: OB/GYN, Nursing, Risk Manager
ISSUE: FDA is advising health care professionals against using magnesium sulfate injection for more than 5-7 days to stop pre-term labor in pregnant women. Administration of magnesium sulfate injection to pregnant women longer than 5-7 days may lead to low calcium levels and bone problems in the developing baby or fetus, including thin bones (osteopenia), and fractures. The shortest duration of treatment that can result in harm to the baby is not known. See the Data Summary in the Drug Safety Communication for additional information.
BACKGROUND: This use of the drug is off-label, and is not an FDA-approved use of the drug. Magnesium sulfate is approved to prevent seizures in preeclampsia, a condition in which the pregnant woman develops high blood pressure and protein in the urine, and for control of seizures in eclampsia. Both preeclampsia and eclampsia are life-threatening complications that can occur during pregnancy. Preeclampsia can lead to eclampsia, seizures, stroke, multiple organ failure, and death of the woman and/or baby.
RECOMMENDATIONS: In light of this new safety information about low calcium levels and bone problems in the developing baby, the following information is being added to the drug label for Magnesium Sulfate Injection, USP 50%:

• A new Warning stating that continuous administration of magnesium sulfate injection beyond 5-7 days in pregnancy for the treatment of pre-term labor can cause low calcium levels and bone changes in the baby.
• A new Teratogenic Effects section conveying the potential harm to developing babies by changing the Pregnancy Category to D from A. Pregnancy Category D means there is positive evidence of human fetal risk, but the potential benefits from using the drug in pregnant women may be acceptable in certain situations despite its risks.
• A new Labor and Delivery section emphasizing that continuous administration of magnesium sulfate injection to treat pre-term labor is not approved and that the safety and efficacy of use for this indication are not established. When used in pregnant women for conditions other than its approved indication, magnesium sulfate injection should be administered only by trained obstetrical personnel in a hospital setting with appropriate obstetrical care facilities.

Pregnant women should discuss with their health care professional the possibility of going into labor before term and the risks and benefits of any treatments that may be used.
Read the MedWatch safety alert, including a link to the Drug Safety Communication, at:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm354603.htm

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Citalopram and abonarmal Heart Rhytms

Citalopram, happiness pills (Photo credit: Fran Simó)

Celexa (citalopram hydrobromide) - Drug Safety Communication: Revised Recommendations, Potential Risk of Abnormal Heart Rhythms

[Posted 03/28/2012]

AUDIENCE: Psychiatry, Cardiology

ISSUE: FDA is clarifying dosing and warning recommendations for the antidepressant Celexa (citalopram hydrobromide; also available in generic form). In August 2011, FDA issued a Drug Safety Communication (DSC) stating that citalopram should no longer be used at doses greater than 40 mg per day because it could cause potentially dangerous abnormalities in the electrical activity of the heart. Citalopram use at any dose is discouraged in patients with certain conditions because of the risk of QT prolongation, but because it may be important for some of those patients to use citalopram, the drug label has been changed to describe the particular caution that needs to be taken when citalopram is used in such patients. The revised drug label also describes lower doses that should be used in patients over 60 years of age.

Read the FDA Drug Safety Communication for additional information.

BACKGROUND: Celexa (citalopram hydrobromide; also available in generic form) is in a class of antidepressants called selective serotonin reuptake inhibitors (SSRIs).

RECOMMENDATIONS:

• Citalopram is not recommended for use at doses greater than 40 mg per day because such doses cause too large an effect on the QT interval and confer no additional benefit.
• Citalopram is not recommended for use in patients with congenital long QT syndrome, bradycardia, hypokalemia, or hypomagnesemia, recent acute myocardial infarction, or uncompensated heart failure. 
• Citalopram use is also not recommended in patients who are taking other drugs that prolong the QT interval.
• The maximum recommended dose of citalopram is 20 mg per day for patients with hepatic impairment, patients who are older than 60 years of age, patients who are CYP 2C19 poor metabolizers, or patients who are taking concomitant cimetidine (Tagamet) or another CYP2C19 inhibitor, because these factors lead to increased blood levels of citalopram, increasing the risk of QT interval prolongation and Torsade de Pointes.

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