Boys and girls diagnosed with attention-deficit/hyperactivity disorder (ADHD) face a significantly higher risk of developing a substance abuse problem — including cigarettes, alcohol and drugs, new research reveals.

“Our study, which is one of the largest set of longitudinal studies of this issue to date, supports the association between ADHD and substance abuse found in several earlier studies and shows that the increased risk cannot be accounted for by co-existing factors such as other psychiatric disorders or family history of substance abuse,” lead author Dr. Timothy Wilens, an associate professor of psychiatry at Harvard Medical School, said in a news release from Massachusetts General Hospital.

“Overall, study participants diagnosed with ADHD had a one-and-a-half times greater risk of developing substance abuse than did control participants,” he added.

Wilens, who is also with the Massachusetts General Hospital Pediatric Psychopharmacology Unit in Boston, and his colleagues reported the findings in the June issue of the Journal of the American Academy of Child & Adolescent Psychiatry.

The current observations stem from a fresh look at data that had been previously collected by two studies exploring psychiatric and behavioral problems among a total of 268 children diagnosed with ADHD. One of the studies had focused on boys, while the other looked at the experience of ADHD girls.

The research team found that nearly one-third of the children developed some form of substance abuse problem over the course of a decade of tracking.

Among a similar number of children who did not have ADHD, only about one-quarter of the children developed similar issues with cigarettes, alcohol or drugs.

Although neither gender nor a family history of substance abuse played a role in risk elevation, “conduct disorder” did boost the risk threefold, the investigators found.

“Anyone with ADHD needs to be counseled about the risk for substance abuse, particularly if they have any delinquency,” advised Wilens, in the news release. “We still need to understand why some kids with ADHD develop substance abuse and others don’t, whether particular treatment approaches can prevent substance problems and how best to treat young adults that have both ADHD and substance abuse.”

More information

For more on ADHD, visit the U.S. National Institute of Mental Health.

ROCKVILLE, Md., Dec. 28 — Voluven, an intravenous synthetic starch solution, won FDA approval as a blood volume expander for use during and after surgery.

In clinical trials that tested Voluven (6% hydroxyethyl starch 130/0.4 in 0.9% sodium chloride injection) in orthopedic surgery, the product was as safe and effective as Hespan, a starch solution already in use to expand blood volume.

The FDA said that Voluven also demonstrated safety and efficacy when used in newborns and infants undergoing major surgery. In the pediatric studies, the product was compared with an albumin-based blood volume expander.

Moreover, the FDA said, Voluven demonstrated safety in European trials that tested the product in patients ages two to 75.

Blood volume expanders are commonly administered to quickly restore some of the volume lost during surgery so that remaining red blood cells can continue to deliver oxygen to the body’s tissues.

Voluven contains a synthetic starch that does not dissolve in water. It is made by linking individual starch molecules and combining them with a salt solution, similar to the salt concentration typically found in blood. Voluven expands the volume of blood plasma and thus draws fluid into capillaries.

The most common side effects from Voluven were nausea and itching.

Voluven is not recommended for patients with known abnormal sensitivity to the synthetic starch used in the product, those experiencing fluid overload, patients on dialysis, and patients with kidney failure not related to low blood volume.

Nor is it recommended for patients with intracranial bleeding or those with severe increases in serum sodium or chloride.

Voluven was not studied in patients with sepsis but the FDA said a post-market clinical trial involving such patients was planned.

Voluven is manufactured by Fresenius Kabi, Bad Homburg, Germany.

SAN FRANCISCO, March 3 – The experience of a prostate cancer surgeon influences the likelihood of disease relapse, researchers reported here, and the prostatectomy learning curve is steep.

“It takes about 250 operations before a surgeon starts to reach a plateau in his skill level,” said Peter T. Scardino M.D., of Memorial Sloan-Kettering Cancer Center in New York, “and even after that it seems to keep climbing.”

Previous studies have shown that the skill a surgeon has in the operating room affects the likelihood a patient will have acute or long-term complications, said Dr. Scardino.

However, he said at the ASCO Prostate cancer Symposium, this is the first study to examine whether an individual surgeon’s experience performing radical prostatectomies has an impact on disease recurrence in prostate cancer patients.

The five-year progression-free survival was 88% for the patients of surgeons who had performed 250 or more radical prostatectomies, compared with 79% for surgeons who had performed only 10. Thus the risk of recurrence was halved by an experienced surgeon.

The results may not be surprising, “but the implications are really quite significant for long-term outcomes,” said Howard I. Scher, M.D., a medical oncologist at Memorial Sloan-Kettering.

The team looked at follow-up data from 7,849 men who underwent radical prostatectomy between 1987 and 2003 at one of four tertiary care centers, Cleveland Clinic, Wayne State University in Detroit, Baylor College of Medicine in Houston, and Memorial Sloan-Kettering. Patients included in the analysis did not have chemotherapy, hormonal, or radiation therapy at the time of surgery or prior to PSA above 0.4 ng/ml, which was the definition for biochemical disease recurrence in this study.

With a median follow-up of 50 months, 1,281 patients (17%) have had a significant increase in PSA. The likelihood of a rise in PSA differed substantially between patients treated by the 74 different surgeons included in the study, with some having a significantly lower rate of recurrence and others having a higher rate.

Using a statistical calculation developed to determine what part of such variability is due to true heterogeneity versus chance, the team found that 54% of the variation was real and due to heterogeneity among surgeons. This variation remained after adjustment for tumor and patient characteristics.

Moreover, there was significant variation even when the researchers considered only the 29 surgeons who had performed more than 40 radical prostatectomies or the 17 who had done the procedure more than 100 times.

Dr. Scardino said that physicians referring their patient for prostate cancer surgery should think about these issues when they choose the surgical referral. He also said that the data show that surgical training for such procedures needs to be increased, and that the different techniques in the procedure should be evaluated.

“This is very stressful for patients and for physicians referring patients,” said Dr. Scardino. He said he would have a hard time knowing how best to evaluate a surgeon for referral without such an analysis, though the number of radical prostatectomies completed is a good starting point.

Some experts in the field videotape individual procedures and subsequently review the films to see what could be done better or how they can improve their overall technique.

Primary source: ASCO/ASTRO Prostate Cancer Symposium

Source reference:
Bianco, FJ, et al. 2006. Outcomes Measurement Influence of the Surgeon on Cancer Control After Radical Prostatectomy. ASCO/ASTRO Prostate Cancer Symposium. Abstract 272.

The duration of red blood cell storage did not adversely affect outcomes in ventilated patients receiving transfusions, according to a small randomized trial.
There was no difference in short-term pulmonary, immunologic, or coagulation status between 50 patients who received fresh red blood cells (median storage of four days) and 50 who received standard-issue red blood cells (median storage duration of 26.5 days), reported Daryl Kor, MD, from the Mayo Clinic in Rochester, Minn., and colleagues in the American Journal of Respiratory and Critical Care Medicine.
Specifically, there was no difference in the primary outcome of change in pulmonary gas exchange — assessed by the partial pressure of arterial oxygen to fraction of inspired oxygen concentration ratio — at 2.5 ± 49.3 for fresh cells versus -9.0 ± 69.8 for standard-issue cells (P=0.22).

The duration of red blood cell storage has been linked to an increased risk of transfusion-related pulmonary complications, Kor’s group wrote. Mechanistic data have outlined alterations in red blood cells during storage.

“These alterations have been purported to potentially influence the recipient’s respiratory and immunologic response to the transfused blood product,” they wrote.

To test this theory, the researchers conducted a double-blind clinical trial in which they enrolled 100 patients and randomized them to a single unit of either fresh red blood cells or standard-issue red blood cells. The majority of patients in the standard-issue group received a red blood cell unit that had been stored for more than 21 days.

Most of the patients received an ABO-and-Rh-identical red blood cell unit, while the reminder received an ABO-and-Rh-compatible unit. There was no difference in the proportion of patients who received nonidentical, ABO-compatible red blood cells (18% for fresh cohort versus 12% for standard issue cohort, P=0.40).

The mean standard deviation from the initiation of intervention red blood cell transfusion to the post-transfusion measurements was 1.8 ± 0.46 hours for the fresh blood cohort and 1.9 ± 0.63 hours for the standard-issue group (P=0.59).

In addition to the lack of difference in the primary outcome, there were no significant differences seen for immunologic status, including interleukin-8 and C-reactive protein, or coagulation status.

The authors noted that median tidal volumes following red blood cell transfusion were similar in the two groups: 7.7 ml/kg per predicted body weight (PBW) for the fresh cohort, versus 7.5 ml/kg per PBW for the standard-issue group (P=0.23).

Finally, there were no significant differences in intermediate outcomes, such as new or progressive transfusion-related acute lung injury (P=0.62) or organ failures (P=0.80). However, the authors cautioned that the study was not sufficiently powered to adequately evaluate these particular endpoints.

The study had other limitations: It was done at a single center, tertiary-care facility in a small patient population. Also, the follow-up period was short, so delayed responses to the transfused red blood cell units were not identified.

The investigators noted that their results differed from earlier study results that have found storage duration and adverse clinical outcomes; one possible reason is that patients in this study received a similar red blood cell dose, while earlier researchers did not adjust for dose, they suggested.

Also, pre-storage leukocyte reduction was used for all red blood cell units transfused — including fresh ones — in this study, and this has been shown to lessen the accumulation of bioactive substances, they explained.

The study offers proof that larger clinical trials randomizing patients to fresh red blood cell units or prolonged storage units are ethical and possible, the authors concluded.

The study was funded by grants from the National Institutes of Health and the department of critical care medicine at the Mayo Clinic College of Medicine. No author disclosures were provided.

SAN ANTONIO, Dec. 14 — Even after the end of treatment, anastrozole (Arimidex), an aromatase inhibitor, outperforms tamoxifen in women with hormone-receptor-positive early breast cancer, a researcher said here.

The finding came after a median of 100 months of follow-up of the 5,216 postmenopausal women with localized invasive breast cancer in the landmark Arimidex, Tamoxifen, Alone, or In Combination (ATAC) trial, according to John Forbes, M.D., of the University of Newcastle in Australia.

At the median 100-month follow-up, time to recurrence, time to distant recurrence, and contralateral breast cancer were improved significantly in the intent-to-treat and hormone-receptor-positive populations, the investigators found.

More than three years, on average, after women in the study stopped taking the medications, those in the anastrozole arm had a 15% lower risk of recurrence than those in the tamoxifen arm, Dr. Forbes told an oral session at the San Antonio Breast Cancer Symposium. The full results of the study were reported simultaneously online in Lancet Oncology.

The absolute difference between the two arms in the proportion of women who relapsed nearly doubled in the four years after the end of treatment, Dr. Forbes said — from 2.8% to 4.8%.

“This is the first demonstration of a carry-over effect for aromatase inhibitors,” he said.

One new element after 100 months was the discovery that the increased rate of fractures associated with anastrozole — a well-known side effect of the aromatase inhibitor — vanished once the treatment drug was stopped after five years, he said.

The study’s North American leader, Aman Buzdar, M.D., of M. D. Anderson Cancer Center in Houston, said that finding “is totally new.”

“The downside of anastrozole was the increased risk of fractures,” he said in an interview. But “once you stop taking the drug, the risk of fractures drops very quickly.”

During the five years of active treatment, the researchers said, the annual fracture rate for women getting anastrozole was 2.93% versus 1.9% for those on tamoxifen and the incidence rate ratio was 1.55, which was significant at P

MUNICH, Germany, Aug. 25 — In the first three years of life, sensitization to indoor allergens, such as dust mites and cat and dog dander, may lead to allergic airway inflammation, impaired lung function, and asthma, according to researchers here.

On the other hand, 90% of children with wheezing but no atopy grew out of their symptoms by school age and retained normal lung function at puberty, showed results of the German Multicenter Allergy Study reported in the Aug. 26 issue of The Lancet.

In a birth cohort of 1,314 children in five German cities followed up to age 13, 499 newborns had risk factors for allergen sensitivity (raised cord blood IgE or at least two atopic family members), and 815 newborns had none of these risk factors, said Sabina Illi, Ph.D., of University Children’s Hospital and colleagues.

Dr. Illi noted that in Germany the prevalence of cockroach sensitization was estimated to be low and unlikely to contribute much to perennial allergic sensitization.

Early sensitization to perennial allergens affected lung function at school age, whereas later sensitization to these allergens had a less pronounced effect. By contrast, sensitization to food allergens and seasonal allergens had no significant effect on lung function at ages seven, 10, and 13, the researchers reported.

Lung function was significantly reduced in children sensitized early in life and exposed to high levels of allergens in the first three years of life, compared with non-sensitized and sensitized but less exposed children.

The ratio of forced expiratory volume (FEV1) to forced vital capacity (FVC) ratio was 87.4 (SD 7.4) for those sensitized and with high exposure compared with 92.6 (SD 6.0) for those not sensitized (P

Although the powerful sedative propofol (Diprivan) was implicated in singer Michael Jackson’s death in June, administration of the drug by a nonanesthesiologist is safe in trained hands, four major gastroenterology and hepatology societies asserted today.

The singer’s death reignited an old turf battle over who should administer the drug during endoscopies, with anesthesiologists insisting that one of their specialists should do it and gastroenterologists arguing the opposite.

An anesthesiologist can double the cost of elective GI endoscopy without improving patient safety or procedural outcome, according to today’s joint position statement from the gastroenterology and hepatology societies.

The document is appears in the December issues of Hepatology, the American Journal of Gastroenterology, Gastroenterology, and GIE: Gastrointestinal Endoscopy.

A propofol overdose, leading to respiratory depression and cardiac arrest, and aggravated by benzodiazepines and other drugs, caused Michael Jackson’s death on June 25, his autopsy found.

Although Jackson’s personal physician has allegedly admitted administering the drug, the appropriateness of its use by nonanesthesiologists has been debated for more than a decade.

Indeed, deliberations on today’s position statement began about 18 months ago, Sedation Task Force chairman Lawrence B. Cohen, MD, of Mount Sinai School of Medicine in New York City, told MedPage Today.

On one hand, anesthesiology guidelines say there isn’t enough evidence to support safe use by nonanesthesiologists.

In fact, at its October meeting, the American Society of Anesthesiologists reiterated its long held position, in a statement that the group “unequivocally maintains that Diprivan, or its generic name propofol, is a drug meant only for use in a medical setting by professionals trained in the provision of general anesthesia.”

Indeed, the drug’s product label says it should be administered only by “persons trained in the administration of general anesthesia.”

Positioning itself as patient safety advocate, the group cited its specialists’ technological advances, “most notably the pulse oximeter,” as well as standardization of equipment and changes in training for anesthesiologists.

Propofol’s product label also says it should be administered only by “persons trained in the administration of general anesthesia.”

On the other hand, Cohen argued that in recent years, tens of thousands of published cases from every continent have supported the efficacy and safety of administration by trained nonanesthesiologists.

“The data speak quite clear clearly,” he declared in an interview.

The gastroenterologists statement said the group conducted a systematic review and found more than 460,000 published endoscopy cases in which propofol was administered by a nonanesthesiologist — typically a nurse.

Altogether, three deaths were reported, all in esophagogastroduodenoscopy cases considered high-risk for sedation due to the patients’ significant comorbidities, the statement said. One generalized seizure was reported without permanent injury to the patient.

This low rate of serious adverse events suggested safety equivalent to that reported for endoscopists administering standard sedation with regard to risk of hypoxemia, hypotension, and bradycardia for upper endoscopy and colonoscopy, according to the statement.

Nurse-administered case series also showed safety comparable to that of general anesthesia and monitored anesthesia care, it said.

But propofol appeared to have some advantages over standard sedation with a narcotic and a benzodiazepine, Cohen’s group wrote.

Sedation was induced faster, recovery time was shorter, and patient satisfaction was at least as good or slightly superior to standard sedation, based on the reviewed studies.

Nonanesthesiologist-administered propofol was also more cost effective than standard sedation or anesthesiologist administration, and more efficient, the statement asserted.

The position paper recommended that any healthcare professional — nurse or endoscopist — should be formally trained in a program that includes didactic training, an airway management workshop, simulation training, and preceptorship.

It recommended periodic retraining in an airway workshop or human simulation laboratory, as well.

Some state nursing boards specifically exclude propofol administration by nurses, but trained nurses in those jurisdictions should still be able to monitor patients after the endoscopist starts the drug, Cohen said.

A more tricky issue is reimbursement, he said.

“A lot of the current practice of sedation for endoscopy today is driven by the economics,” he told MedPage Today, noting that there is no coding or compensation for administration of propofol by physicians or gastroenterologists.

“That has been a significant deterrent to physicians who would otherwise be interested in using propofol.”

On the other hand, bringing an anesthesiologist into the practice can generate revenue for the GI practice, since the bill generated by the anesthesiologist is often larger than that for the endoscopy itself, he said.

The statement noted that the cost of having an anesthesiologist present in the endoscopy suite for administration ranges from $150 to $1,500 or more.

“This is, I think, one of those examples where spending more for healthcare does not necessarily get you better care,” Cohen said in an interview.

Cohen reported being a consultant for Ethicon EndoSurgery and Eisai Pharmaceuticals. A co-author reported consulting for Ethicon EndoSurgery as well.

Revascularization using a paclitaxel-eluting balloon dramatically improved outcomes in patients with critical lower-limb ischemia — a condition with notoriously high rates of restenosis — a single-center European study found.
In the first trial of angioplasty with drug-eluting balloons for lengthy occluded or stenosed infrapopliteal arteries, the restenosis rate at three months was 27.4%, Andrej Schmidt, MD, of Park Hospital Leipzig in Germany, and colleagues reported in the Sept. 6 Journal of the American College of Cardiology.
In contrast, in a previous series by the same authors using uncoated balloons, the three-month restenosis rate for these large lesions was very high, at 69%.

“This particular study demonstrated impressive results with much longer anatomic lesions in the most challenging of arterial beds, the infrapopliteal arteries,” commented Michael R. Jaff, DO, of Massachusetts General Hospital in Boston in an accompanying editorial.

Conventional management of critical limb ischemia has involved surgical reconstruction, but because of the high degree of comorbidities in these patients, serious complications including infections and myocardial infarctions have remained problematic.

Drug-eluting stents have been tried in patients with these below-the-knee occlusions, but stents are more suitable for small lesions.

To see if angioplasty using a newly-approved paclitaxel-eluting balloon would be more successful in long segments of the infrapopliteal arteries, Schmidt’s team inserted balloons coated with 3.0 μg mm2 of paclitaxel (FreePac) into 109 limbs in 104 patients.

The patients’ mean age was 74, and two-thirds were men. Almost three-quarters had diabetes, more than 90% were hypertensive, and 46% had coronary artery disease.

Critical limb ischemia was present in 82.6% of the limbs and the remainder had severe claudication.

The mean lesion length was 176 mm.

By three months, nine patients had died and one was lost to follow-up.

In the remaining 94 patients, improvements were seen in 75.8% of limbs, 2% had worsened, and the remainder had not changed clinically.

Three toe amputations were done at the time of the balloon placement, and three more were done during the subsequent three months.

In patients who had ulcerations or gangrene (Rutherford-Becker category 5 disease), complete wound resolution occurred in 41.9%.

A total of 74 patients underwent angiography at the three-month time point. In this group, 72.6% of 84 arteries had no significant restenosis.

Restenosis did occur in the remaining 27.4%, but involved less than 20% of the size of the original lesion in most cases.

In only 9.5% of the 84 arteries was the entire originally affected segment restenosed.

One year after balloon insertion, there were clinical improvements in 91.2%, and the limbs were salvaged in 95.6% of cases.

“The one-year clinical results are promising and seem to confer a durable benefit,” the authors observed.

At one year, gangrene and ulcers had healed fully in 74.2% of patients.

Two major limb amputations had occurred, along with one additional toe and a single forefoot amputation.

The one-year mortality rate was 16.3%.

“The three-month restenosis rate of 27% after treatment with [drug-eluting balloons] represents a dramatic reduction for restenosis of 61% from the 69% seen in the series using uncoated balloons,” wrote Schmidt and colleagues.

The authors noted that their study was not sufficiently large for sub-analyses examining factors that might be associated with poor outcomes.

It did appear, however, that when the arteries of the foot were affected the restenosis rate was higher, at 38.5%.

The procedure appeared to be safe, with only two arteries showing ectasis during the angiogram done at three months.

Limitations of the study included its small numbers and single-site design, according to the authors, who noted that future studies will need to take into consideration cost concerns.

The issue of cost also was cited by Jaff in his editorial comment.

“The authors highlight the potential advantage that drug-coated balloons require fewer repeat interventions when compared with [percutaneous transluminal angioplasty], and this may result in a cost advantage of this technology,” Jaff wrote.

However, it remains an open question “whether costs will favor this technology in the era of healthcare reform,” he noted.

The study did not receive industry financial support.

The lead author and one co-author are consultants for Medtronic.

Editorialist Jaff has consulted for several companies including Medtronic Vascular, Abbott Vascular, Boston Scientific, and Micell, and holds shares in Vascular Therapies.

SAN FRANCISCO — Once-daily dosing of the protease inhibitor darunavir (Prezista) appeared to be at least as effective as twice-a-day regimens among treatment-experienced patients with no darunavir-associated resistance mutations, researchers reported here.

Study subjects received an optimized nucleoside backbone regimen and were randomized to either once- or twice-daily darunavir boosted with ritonavir.

Some 72.1% achieved undetectable HIV viral load on once-daily therapy, compared with 70.9% of patients who were treated twice-a-day (P<0.001 for noninferiority), Pedro Cahn, MD, medical director at Fundación Huesped in Buenos Aires, reported at the Conference on Retroviruses and Opportunistic Infections.

“These findings suggest that once-daily darunavir/ritonavir (Norvir) could be considered an option for patients whose previous treatments are failing,” he said.

The outcomes — the percentage of patients who achieved undetectable viral loads — overlapped at all time points studied: four weeks, eight weeks, 12 weeks, 24 weeks, 36 weeks and when the trial ended at 48 weeks.

At the end of the trial, CD4-positive cell counts increased about 100 cells/mm3 over baseline in the once-daily group, compared with 94 cells/mm3 for those on the twice-daily regimen.

For their study, Cahn and colleagues recruited adult antiretroviral-experienced patients with more than 1,000 copies/mL of circulating HIV but who had at least a CD4-positive cell count of 50/mm3.

The patients’ viruses were required to be free of darunavir resistance-associated mutations, and the patients had to have been stable for at least 12 weeks on a highly active antiretroviral therapy.

The researchers assigned 296 patients to receive darunavir 800 mg once a day, along with a ritonavir 100 mg booster plus optimized background regimens.

Another 294 patients were assigned to receive darunavir 600 mg plus ritonavir 100 mg twice a day on top of an optimized background regimen.

Cahn said the researchers sought to build on previous work that suggested the long, 15-hour half-life of darunavir made it a candidate for once-daily dosing.

The primary objective of the treatment was to establish that the simplified treatment was noninferior to the twice-a-day dosing of darunavir, assessing efficacy by the percentage of patients who were able to achieve an undetectable viral load, using the 50 copy/mL assay at 48 weeks of treatment.

About 40% of the patients in the study were women, and the mean age was 40 years. About 35% of the patients were white, while 28% were black, and about 16% were Hispanic.

Some 26% of the patients had previously been exposed to the protease inhibitor lopinavir (Kaletra) and 21% had been exposed to the protease inhibitor indinavir (Crixivan). Cahn said that 45% of the study population had no protease inhibitor experience before entering the trial.

Responding to questions from the audience, Cahn said that follow-up studies might be able to determine if there were differences in outcomes based on previous protease inhibitor use.

Cahn said there were similar toxicities and discontinuations in both study arms.

In addition to showing similar effectiveness, the incidence of grade 2-4 lipid elevations with once-daily darunavir/ritonavir was about half that seen with the twice-daily therapy, Cahn said.

“Virologic failure rarely resulted in resistance,” he said. One patient in the study developed primary protease inhibitor resistance-associated mutations and darunavir resistance-associated mutations following virologic failure.

The study was supported by Tibotec.

Cahn disclosed financial relationships with Abbott, Avexa, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Pfizer, Pharmasset, Schering-Plough, and Tibotec.

PHILADELPHIA, April 2 — Reports of neurologic symptoms and abnormal behavior, including some deaths, in patients using neuraminidase inhibitors, prompted an update of the package insert for zanamivir (Relenza), GlaxoSmithKline announced in a letter to healthcare professionals.

The postmarketing reports, primarily from Japan, cited symptoms that included seizures, hallucinations, delirium, and abnormal behavior, GSK medical director Judith Ng-Cashin, M.D., said in the letter.

In November, an FDA panel recommended labeling changes for zanamivir and oseltamivir (Tamiflu), saying that package inserts did not adequately address safety concerns surrounding the neuropsychiatric events (See: FDA Panel Urges Stronger Warnings on Flu Drugs).

The new language should note that deaths have occurred as a result of those events, the panel said, and could note that the flu itself may cause such events and that it remains unclear if the drugs contribute to them.

The new Warnings and Precautions section of the zanamivir package insert now includes a subsection called “Neuropsychiatric Events,” providing that information and guidance to clinicians.

The new subsection includes the following:

Because these events were reported voluntarily during clinical practice, estimates of frequency cannot be made, but they appear to be uncommon based on usage data for Relenza. These events were reported primarily among pediatric patients and often had an abrupt onset and rapid resolution. The contribution of Relenza to these events has not been established.

The company also added cautionary information about neurologic and behavioral symptoms to the side effects section of the patient information for Relenza.

In November, the FDA’s adverse event reporting system found 115 events associated with zanamivir, 74 of them among patients 21 or younger, but no deaths.