martes, 31 de enero de 2012



On January 30, 2012, the U. S. Food and Drug Administration approved vismodegib (ERIVEDGE Capsule, Genentech, Inc.) for the treatment of adults with metastatic basal cell carcinoma or with locally advanced basal cell carcinoma that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation.
Efficacy was demonstrated in a single-arm, parallel cohort trial enrolling 104 patients. Patients received 150 mg of vismodegib daily. Central pathologic review of archival or baseline tissue confirmed the diagnosis of basal cell carcinoma (BCC) in 96 patients: 33 patients with metastatic basal cell carcinoma (mBCC) and 63 patients with locally advanced basal cell carcinoma (laBCC).
Efficacy was evaluated in these 96 patients with confirmed BCC. The median age of this population was 62 years, 61% were male, and 97% had an ECOG performance status of 0 or 1. Twenty‑one percent of patients carried a diagnosis of Gorlin syndrome. Sixty-six percent had locally advanced disease; 34% had metastatic disease. Among those with mBCC, 97% were previously treated. Prior therapy included surgery (97%), radiotherapy (58%), and systemic therapies (30%). Among laBCC patients, 94% were previously treated. Prior therapies included surgery (89%), radiotherapy (27%), and systemic/topical therapies (11%).
The trial’s primary endpoint was objective response rate (ORR) assessed by an independent review facility. Tumor response criteria for laBCC included assessment of tumor size, the presence or absence of ulceration, and biopsy of local disease sites. The criteria for complete response in localized disease required tumor biopsy (ies) demonstrating no pathologic evidence of BCC. RECIST version 1.0 criteria were used to assess responses in the mBCC population.
The ORRs were 30.3% (95% CI: 15.6, 48.2) and 42.9% (95% CI: 30.5, 56.0) in patients with mBCC and laBCC, respectively. All responses in the mBCC cohort were partial responses. For the 63 evaluable patients with laBCC, 13 (20.6%) patients had complete responses and 14 (22.2%) had partial responses. The median response duration was 7.6 months (95% CI: 5.6, not estimable) and 7.6 months (95% CI: 5.6, 9.7) for patients with mBCC and laBCC, respectively.
Safety was evaluated in 138 patients who received vismodegib as monotherapy for laBCC or mBCC. Adverse reactions occurring in more than 10% of patients were muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, decreased appetite, constipation, arthralgias, vomiting, and ageusia. In clinical trials, a total of 3 of 10 pre-menopausal women developed amenorrhea. Grade 3 adverse reactions occurring in more than 1% of patients were weight loss, fatigue, muscle spasms, and decreased appetite.
Healthcare professionals should verify pregnancy status prior to the initiation of vismodegib, counsel pregnant women on the potential risks to the embryo/fetus, and advise non-pregnant women to use highly effective contraception during treatment with vismodegib and for up to 7 months after the last dose. To avoid exposing an embryo/fetus to vismodegib that may be contained in semen, male patients should use condoms with spermicide during treatment with vismodegib, and for 2 months after the last dose. Healthcare providers should report to Genentech any cases of exposure during pregnancy (either direct exposure in female patients or through seminal fluid from male patients), and should encourage pregnant women to participate in the Erivedge pregnancy pharmacogvigilance program to collect information on pregnancy outcomes.
Vismodegib inhibits the Hedgehog pathway, an important embryonic developmental pathway. Reproductive toxicology studies in rats demonstrated that vismodegib exposure during organogensis results in embryo-fetal death at higher exposures and severe birth defects at exposures within the range achieved with the recommended human dose.
The recommended dose and schedule for vismodegib is 150 mg orally daily. Vismodegib may be taken with or without food.
Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at:
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).

Brookings Roundtable​: Highlights from the Sentinel Initiative Public Workshop on 2/1/2012

Please join us for the upcoming webinar, "Highlights from the Sentinel Initiative Public Workshop" on Wednesday, February 1, 2012, from 4:00 p.m. to 5:00 p.m. EST.  If you missed the Fourth Annual Sentinel Initiative Public Workshop, which was held on January 18, 2012, or would like to re-visit the discussion, this webinar will summarize Mini-Sentinel's progress from the past year, its emerging role in drug safety and plans for the upcoming year.  The webinar will also discuss strategies for communicating expectations of, and findings from, Sentinel.  The roundtable will feature presentations by Richard Platt, Chair, Department of Population Medicine at Harvard Medical School and Harvard Pilgrim Health Care Institute and Ed Staffa, Writer and Editor, Office of Communications, Center for Drug Evaluation and Research, U.S. Food and Drug Administration.

The agenda can be found on the Brookings website at

Webinar log in and teleconference information can be found in your registration confirmation email.  You must register to obtain this information.

Register for the Brookings RoundtableTo learn more about the Brookings active surveillance roundtable webinar and teleconference series, visit our website at:

Event Summary

The Engelberg Center for Health Care Reform at Brookings hosted the Fourth Annual Sentinel Initiative Public Workshop on Wednesday, January 18, at the Washington Marriott in Washington, DC. This public workshop brought together the stakeholder community for a productive discussion on a variety of topics in active medical product surveillance, including an update on the U.S. Food and Drug Administration’s (FDA’s) Sentinel Initiative; efforts to support the advancement of safety science; and stakeholder perspectives on the Sentinel Initiative’s progress and future direction.

IV Acetaminophen Linked to More Child Overdoses: MedlinePlus

IV Acetaminophen Linked to More Child Overdoses: MedlinePlus

IV Acetaminophen Linked to More Child Overdoses

Confusion can arise over measurement guidelines, experts warn

URL of this page:
(*this news item will not be available after 04/26/2012)

Friday, January 27, 2012 HealthDay Logo
HealthDay news image FRIDAY, Jan. 27 (HealthDay News) -- Following the U.S. Food Drug Administration's approval last year of an intravenous formulation of acetaminophen for fever and pain in a hospital setting, researchers warn that use of the preparation could lead to serious overdoses, particularly among the youngest patients.

The problem: There is confusion over measurement guidelines -- milligrams vs. milliliters, to be specific -- that can result in the accidental administration of doses that are up to 10 times more than the proper amount.
"This product would be given in a health care facility," said study co-author Dr. Richard Dart, from the Rocky Mountain Poison and Drug Center at Denver Health in Colorado. "And thus, the overdose ends up being from a miscalculation by a health care provider."

"In theory, the risk to the child is that they could develop serious liver injury," Dart added. "Liver injury is avoided if the overdose is detected and the antidote [acetylcysteine] is administered within several hours. [But] the challenge in the case of an intravenous overdose is that the medication error needs to be detected by the health care provider because it doesn't produce identifiable symptoms," apart from nausea and vomiting.

Dart and his colleague, Dr. Barry Rumack, discuss their concerns in the February issue of Pediatrics.
The authors noted that dosages of IV-administered acetaminophen are calculated in milligrams, mixed at a ratio of 10 milligrams of the drug for every one milliliter of a non-drug solution. Problems arise if and when that drug ratio is improperly executed.

Since it came on the global market a decade ago, the IV option has been very popular, with roughly 500 million doses having already been distributed to patients of all ages worldwide.

The FDA approval, however, restricted the drug's use to American patients above the age of 2. But, given the inherent difficulty in administering oral versions of the drug to pediatric patients, the authors cautioned that so-called "off label" use of the drug among very young Americans is pretty much inevitable.

Despite the fact that overdosing (pediatric or otherwise) has not yet been widely reported in the United States, the authors pointed to dozens of pediatric overdose cases in Britain and elsewhere across Europe (most involving children under the age of 1).

Dart and Rumack advised that hospitals using IV acetaminophen work with pharmacy and nursing staff to raise awareness of the overdose dangers. They also suggest that clinicians watch for accidental poisonings and report overdoses.

"This type of error is unfortunately common in medicine, and affects many drugs," said Dart, who also works in the department of emergency medicine at the University of Colorado School of Medicine. "I think the wisest way of avoiding the problem is to make sure that all orders written in a hospital are reviewed by a pharmacist before they are implemented. This markedly reduces the opportunity for error."

Frank Federico, a pharmacist and executive director of the Institute for Healthcare Improvement in Cambridge, Mass., believes "there are ways to ensure or at least improve the safety of drug administration in a hospital setting for pediatrics."

"For example, when you have a drug like this one that is ordered in milligrams but administered in milliliters you need a good safeguard and system that ensures that the conversion is simple and easy to do," he said. "And so you have computers do the math for you, rather than a person. You eliminate human error and you use clearly printed labels."

Federico, who once served as director of pharmacy at Children's Hospital Boston, suggested that it is possible to put in place a labeling protocol that is straightforward and allows for multiple checks.

"Our labels listed the concentration of the product, with the most basic ratio in there," he noted. "It was clear. And that way not only was the technician who was preparing the product clear on how much liquid was necessary, but so were the pharmacists who would check and the nurses who would check."

Parents should also not be afraid to ask hospital staff to double check the dosing. "Asking is always appropriate," he added.
SOURCES: Richard Dart, M.D., Ph.D., Rocky Mountain Poison and Drug Center, Denver Health, and department of emergency medicine, University of Colorado School of Medicine, Denver; Frank Federico, RPh, pharmacist and executive director, Institute for Healthcare Improvement, Cambridge, Mass.; February 2012 Pediatrics
More Health News on:
Children's Health
Medication Errors
Pain Relievers

Blood Pressure Differences Between Arms Could Signal Heart Risk: MedlinePlus

Blood Pressure Differences Between Arms Could Signal Heart Risk: MedlinePlus

Blood Pressure Differences Between Arms Could Signal Heart Risk

Peripheral vascular disease may lead to stroke or early death, researchers say
(*this news item will not be available after 04/28/2012)

Sunday, January 29, 2012 HealthDay Logo
HealthDay news image
Related MedlinePlus Page
SUNDAY, Jan. 29 (HealthDay News) -- People whose systolic blood pressure -- the upper number in their reading -- is different in their left and right arms may be suffering from a vascular disease that could increase their risk of death, British researchers report.

The arteries under the collarbone supply blood to the arms, legs and brain. Blockage can lead to stroke and other problems, the researchers noted, and measuring blood pressure in both arms should be routine.

"This is an important [finding] for the general public and for primary care doctors," said Dr. William O'Neill, a professor of cardiology and executive dean of clinical affairs at the University of Miami Miller School of Medicine.

"Traditionally, most people just check blood pressure in one arm, but if there is a difference, then one of the arteries has disease in it," he said.

The arteries that run under the collarbone can get blocked, especially in smokers and diabetics, he noted. "If one artery is more blocked than the other, then there is a difference in blood pressure in the arms," O'Neill explained.

"Doctors should, for adults -- especially adult smokers and diabetics -- at some point check the blood pressure in both arms," he said. "If there is a difference it should be looked into further."

The report appears in the Jan. 30 online edition of The Lancet.

For the study, a team led by Dr. Christopher Clark, from the Peninsula College of Medicine and Dentistry at the University of Exeter in Devon, England, reviewed 28 studies that looked at differences in systolic blood pressure between arms.

This process is called a meta-analysis. It uses data from previously published studies to find trends that may not have surfaced in the original data.

This analysis found that a difference of 15 millimeters of mercury (mm Hg) or more between readings was linked with an increased risk of narrowing or hardening of the arteries supplying the lower limbs, called peripheral vascular disease.

The risk of reduced blood flow to the legs and feet was increased 2.5 times and the risk of decreased blood flow to the brain was increased 1.6 times, the researchers found.

The difference in blood pressure was also associated with a 70 percent increased risk of dying from cardiovascular disease and a 60 percent increased risk of death from any cause, the authors added.
The risk of having peripheral vascular disease was also increased with a 10 mm Hg difference in blood pressure between arms, the researchers noted.

It makes no difference which arm has the higher or lower pressure, it's the difference between them that matters, the study authors said.

Finding peripheral vascular disease early and treating it by lowering blood pressure and cholesterol as well as giving up smoking can help reduce the risk of death, Clark's group said.

"Our findings suggest that a difference in [systolic blood pressure] of 10 mm Hg or more, or 15 mm Hg or more, between arms could identify patients at high risk of asymptomatic peripheral vascular disease and mortality who might benefit from further assessment," the researchers concluded.

"Findings from our study should be incorporated into future guidelines for hypertension [high blood pressure] and blood pressure measurement," they added.

Another expert agreed that when it comes to blood pressure monitoring, both arms matter.

"These findings further reinforce blood pressure measurement guidelines of the American Heart Association, World Health Organization, International Society of Hypertension Guidelines and European Society of Hypertension, which recommend that blood pressure should be measured in both arms at initial assessment," said Dr. Gregg Fonarow, a professor of cardiology at the University of California, Los Angeles, and spokesman for the American Heart Association.

He believes that, "individuals found to have differences in systolic blood pressure in between arms of greater than 10 or 15 mm Hg should undergo further vascular assessment."
SOURCES: Gregg Fonarow, M.D., professor, cardiology, University of California, Los Angeles, and spokesman, American Heart Association; William O'Neill, M.D., professor, cardiology, and executive dean, clinical affairs, University of Miami Miller School of Medicine; Jan. 30, 2012, The Lancet, online


Martes 31 de ENERO de 2012

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