Category: Drugs and Disease

FDA is investigating the use of the pain medicine tramadol in children aged 17 years and younger, because of the rare but serious risk of slowed or difficult breathing. This risk may be increased in children treated with tramadol for pain after surgery to remove their tonsils and/or adenoids. FDA is evaluating all available information and will communicate final conclusions and recommendations to the public when the review is complete.

Tramadol is not FDA-approved for use in children; however, data show it is being used “off-label” in the pediatric population. Health care professionals should be aware of this and consider prescribing alternative FDA-approved pain medicines for children.

BACKGROUND: In the body, tramadol is converted in the liver to the active form of the opioid, called O-desmethyltramadol. Some people have genetic variations that cause tramadol to be converted to the active form of the opioid faster and more completely than usual. These people, called ultra-rapid metabolizers, are more likely to have higher-than-normal amounts of the active form of the opioid in their blood after taking tramadol, which can result in breathing difficulty that may lead to death. Recently, a 5-year-old child in France experienced severely slowed and difficult breathing requiring emergency intervention and hospitalization after taking a single prescribed dose of tramadol oral solution for pain relief following surgery to remove his tonsils and adenoids. The child was later found to be an ultra-rapid metabolizer and had high levels of O-desmethyltramadol in his body.

RECOMMENDATION: Parents and caregivers of children taking tramadol who notice any signs of slow or shallow breathing, difficult or noisy breathing, confusion, or unusual sleepiness should stop tramadol and seek medical attention immediately by taking their child to the emergency room. Parents and caregivers should talk with their child’s health care professional if they have any questions or concerns about tramadol or other pain medicines their child is taking.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program:

A significantly more tolerable approach than standard chemotherapy using the combination of lenalidomide and rituximab as initial therapy in mantle-cell lymphoma is highly active and produces durable responses in most patients, an observational cohort study suggests.

“Treatment of patients with mantle-cell lymphoma, who are frequently older (median age 65 years) and unsuitable candidates for intensive regimens, remains a clinical challenge,” Jia Ruan MD, PhD, of the Meyer Cancer Center at Weill Cornell Medical College and New York-Presbyterian Hospital in New York City and colleagues wrote in The New England Journal of Medicine.

“Our data show that a lower-intensity approach for initial therapy than that usually used in the case of patients with this cancer can be highly active, with durable responses observed in most patients.”

A total of 38 patients who had untreated, measurable mantle-cell lymphoma were enrolled in the study. The median age of the cohort was 65 years (range 42-86 years); 100% of the group had Ann Arbor stage III or IV disease, and 89% had bone marrow involvement.

Rituximab was administered at a dose of 375 mg/m² once weekly for the first 4 weeks and then once every other cycle until disease progression. During the maintenance phase, lenalidomide was given at a dose of 15 mg a day again on days one through to 21 of every 28-day cycle while rituximab was given once every 8 weeks.

Treatment was continued for at least 36 cycles or until disease progression or unacceptable AEs. For patients with creatinine clearance of 30 to 60 mL/min, lenalidomide was administered at a lower dose of 10 mg day during the induction phase, although the dose was again escalated to 15 mg a day if patients experienced no dose-limiting AEs. During the maintenance phase, lenalidomide was given at a dose of 5 mg a day.

“Patients received thromboprophylaxis with aspirin or low-molecular-weight heparin unless they required treatment for known thrombosis,” Ruan and colleagues added, “[while] asymptomatic carriers of hepatitis B virus received antiviral therapy.”

On the other hand, prophylactic growth factors were not administered empirically.

Grade 3 or 4 hematologic AEs included neutropenia, which occurred in half of the group, thrombocytopenia in 13% of patients, and anemia in 11% of the group. The likelihood that patients would develop hematologic toxicity was higher during the induction phase than in the maintenance phase. Similarly, grade 3 and 4 nonhematological toxicities were only reported during the induction phase and included rash in 29% of patients, tumor flare in 11% of patients, serum sickness associated with rituximab in 8%, and fatigue in another 8% of patients.

Grade 3 infections were reported during the maintenance phase but all resolved with the administration of antibiotics and supportive care.

“Among the 33 patients with normal renal function, 36% had no unacceptable side effects associated with the dose escalation from 20 mg to 25 mg,” Ruan and colleagues noted.

However, 42% of the group did require a reduction in the dose of lenalidomide from 20 mg to 15 mg or less. Of the eight patients who had disease progression while receiving treatment, all remained alive except for an 86-year-old patient who opted for palliation.

Seven patients responded to retreatment with generally favorable outcomes and no indication that prior receipt of the biologic doublet compromised subsequent treatment outcomes.

“The efficacy of lenalidomide plus rituximab in a broad patient population, including patients who were ineligible for intensive approaches, is particularly notable in the context of data reported on patients receiving inpatient-based regimens, including high-dose chemotherapy with autologous hematopoietic-cell transplantation,” Ruan and colleagues observed.

“However, the duration of maintenance therapy remains to be determined, and it is unclear whether the combination of lenalidomide and rituximab is more effective than rituximab alone as maintenance therapy.”

Many people who’ve been told they’re allergic to penicillin may be able to safely take the drug, a small study suggests. The research was scheduled to be presented at the annual meeting of the American College of Allergy, Asthma & Immunology, held from Nov. 5 to 9 in San Antonio.

The researchers examined the medical records of 15 people who tested negative for penicillin allergy after being told they were allergic. They were then treated with intravenous penicillin multiple times.

“Of the patients whose records we examined, there were no adverse drug reactions or evidence of recurrence of their penicillin allergy,” study author and allergist David Khan, M.D., said in a College news release. “There is often thought to be a higher risk in patients who get intravenous penicillin, but we did not find this to be the case.”

Previous reported reactions included rash, hives, and swollen lips, Khan said. But the study found none of those reactions after allergy testing and treatment with multiple courses of intravenous penicillins.

– Lack of sleep may be a gateway to kidney disease, at least for women, a new study suggests.

Researchers from Boston’s Brigham and Women’s Hospital evaluated the sleep habits of thousands of women and found too little shuteye was tied to a more rapid decline in kidney function.

Women who slept five hours or less a night had a 65 percent greater risk of rapid decline in kidney function, compared with women sleeping seven to eight hours a night, the investigators discovered.

“This is concerning because as a general population the amount of sleep we are getting has decreased over the last 20 years,” said lead researcher Dr. Ciaran McMullan, an instructor in medicine.

It’s not known whether sleeping longer improves kidney function or reverses damage caused by shortened sleep, he said.

McMullan cautioned that this study can only show that decreased kidney function is associated with less sleep, not that less sleep causes the decline in kidney function. For that, more research is needed, he said.

A connection between disrupted sleep and heart disease has been studied before.

A link between reduced sleep and diminished kidney function might be the result of medical conditions that affect kidney function, such as diabetes and high blood pressure, McMullan said.

“Diabetes occurs more often in people who sleep less, as does high blood pressure,” he said. “We know that two of the greatest factors that decrease kidney function are diabetes and high blood pressure.”

The body’s natural rhythms, or so-called circadian clock, might also play a role, McMullan said. The kidney is timed to work differently during the night than during the day because the demands on the body are different, he explained.

“Maybe short sleep changes the physiology of the kidney over the daily cycle, and these changes might damage the kidney,” McMullan suggested.

As the U.S. population ages and as more people suffer from diabetes and high blood pressure, the number of people with kidney disease will increase, and too little sleep may play a part, he added.

“We are a sleep-deprived society,” McMullan said. “The concern is that sleep deprivation will lead to a decline in kidney function.”

He said it’s likely the findings would also apply to men, but noted that would need to be studied.

The results of the study are scheduled for presentation Thursday at a meeting of the American Society of Nephrology in San Diego. The data and conclusions should be considered preliminary until published in a peer-reviewed medical journal.

For the study, McMullan’s team collected data on more than 4,200 women who took part in the Nurses’ Health Study. Over 11 years, the women’s kidney function was measured at least twice.

Dr. Kenar Jhaveri, a nephrologist at North Shore-LIJ Health System in Great Neck, N.Y., said the connection between sleep and kidney disease is new to him.

“At this point I would be very cautious about giving advice to patients based on this study,” he said. “I certainly wouldn’t change any sleep habits.”

Jhaveri said seven hours of sleep is good for health. “People who sleep too little or too much are at risk for certain disorders,” he added. “In terms of kidney disease, this is something that is going to be interesting in how it pans out.”

EAST HANOVER, N.J., Oct. 29, 2015 Novartis announced today that the US Food and Drug Administration (FDA) has approved Seebri Neohaler (glycopyrrolate) inhalation powder 15.6 mcg as a stand-alone monotherapy for COPD. Novartis expects that Seebri Neohaler will be available in the first quarter of 2016.

Seebri is delivered via the low resistance Neohaler inhaler, which makes it suitable for patients with different severities of airflow limitation.

About Seebri Neohaler

Seebri Neohaler, previously known as NVA237, is a twice-daily long-acting muscarinic antagonist (LAMA) for the long-term maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and/or emphysema.

Glycopyrrolate (also known as glycopyrronium bromide) was exclusively licensed to Novartis in April 2005 by Vectura and its co-development partner Sosei.

INDICATION

Seebri Neohaler ia a prescription medicine used to treat chronic obstructive pulmonary disease (COPD) in adults. COPD is a chronic lung disease that includes chronic bronchitis, emphysema, or both. Seebri is used long-term, inhaled twice a day, to improve symptoms of COPD for better breathing.

Seebri contains the anticholinergic glycopyrrolate. This medicine works by helping the muscles around the airways in your lungs stay relaxed to prevent symptoms, such as wheezing, cough, chest tightness, and shortness of breath.

Seebri is not used to treat sudden symptoms of COPD and won’t replace a rescue inhaler.

IMPORTANT SAFETY INFORMATION

Call your doctor or get emergency medical care if your breathing problems worsen quickly, if you need to use your rescue inhaler more often than usual, or if you use your rescue inhaler medicine but it does not relieve your breathing problems. Call your doctor if breathing problems worsen over time while using Seebri.

Do not use Seebri Neohaler if you are allergic to glycopyrrolate or any of the ingredients in Seebri. Ask your doctor if you are not sure.

Do not swallow Seebri capsules. Only use Seebri capsules with the Neohaler inhaler. Never place a capsule in the mouthpiece of the Neohaler inhaler.

Tell your doctor about kidney problems, eye problems such as glaucoma, prostate problems, bladder problems, problems passing urine, or other medical conditions, including if you are pregnant, planning to become pregnant or breastfeeding, before using Seebri.

Tell your doctor if you are allergic to Seebri or any of their ingredients, any other medicines, or food products. Seebri contains lactose (milk sugar) and small amounts of milk proteins. It is possible that allergic reactions may happen in people who have a severe milk protein allergy.

Tell your doctor about all the medicines you take, including prescription medicines, over-the-counter medicines, vitamins, and herbal supplements. Using Seebri with other medicines may cause serious side effects. Tell your doctor if you take anticholinergics (including umeclidinium, tiotropium, ipratropium, aclidinium, glycopyrrolate), because taking them together with Seebri can increase side effects.

Seebri may cause serious side effects, including life-threatening sudden shortness of breath immediately after use and serious allergic reactions including rash; hives; swelling of the tongue, lips, and face; difficulty breathing or swallowing. If you have any of these symptoms, stop taking Seebri and get immediate medical help.

Seebri can cause new or worsened eye problems, including acute narrow-angle glaucoma, which can cause permanent loss of vision if not treated. Symptoms may include: eye pain or discomfort, nausea or vomiting, blurred vision, seeing halos or bright colors around lights, or red eyes. If you have any of these symptoms, stop Seebri and call your doctor right away.

Seebri can cause new or worsened urinary retention. Symptoms of urinary retention may include: difficulty urinating, painful urination, urinating frequently, or urination in a weak stream or drips. If you have these symptoms, stop taking Seebri and call your healthcare provider right away.

Common side effects of Seebri include upper respiratory tract infection, sore throat, and runny nose.

 

 

Rheumatoid arthritis may raise the risk of early death by as much as 40 percent, with heart and respiratory problems the most common contributors to a shortened life span, a new study suggests.

And among those who died of respiratory causes, one of the main causes of death was chronic obstructive pulmonary disease (COPD), the researchers reported.

The findings provide new evidence to support previous research suggesting a link between rheumatoid arthritis and increased risk of early death, and they point to the need for doctors to closely monitor these patients, the study authors said.

However, the study only showed an association, and not a cause-and-effect relationship, between rheumatoid arthritis and risk of premature death.

Rheumatoid arthritis is an autoimmune disorder in which the body’s immune system attacks the joints, resulting in pain and swelling.

For the study, researchers from Brigham and Women’s Hospital in Boston analyzed data from 964 women with rheumatoid arthritis who were part of the Nurses’ Health Study, and compared them with women without the disease. The study has followed more than 100,000 registered nurses since 1976.

“Previous studies have suggested that rheumatoid arthritis may be associated with increased mortality, but were not able to control for other variables, such as smoking, that affect both rheumatoid arthritis and mortality risks,” study corresponding author Dr. Jeffrey Sparks said in a hospital news release. He is with the division of rheumatology, immunology and allergy at the hospital.

“Because the Nurses’ Health Study is so large and has been following participants for so long, we were able to gather much more information about our subjects — we could follow them before and after diagnosis, take their health behaviors into account and determine specific causes of death,” he said.

“By doing so, we found strong evidence of increased risk for respiratory, cardiovascular and overall mortality for patients with rheumatoid arthritis,” Sparks said.

The researchers also analyzed differences between the two types of rheumatoid arthritis: seropositive and seronegative. Those with seropositive rheumatoid arthritis — which typically causes more severe symptoms — were nearly three times more likely to die of respiratory causes than those with seronegative disease, according to the study. It was published Nov. 3 in the journal Arthritis Care & Research.

While many doctors know that rheumatoid arthritis patients are at increased risk of death from heart problems, the new findings highlight the need to watch for respiratory symptoms, even among patients who never smoked or are former smokers, Sparks added.

“We hope that this study will encourage patients and clinicians to be more aware that patients with rheumatoid arthritis are at increased risk of both respiratory and cardiovascular mortality, particularly patients with seropositive rheumatoid arthritis,” he said.

Children’s weight and physical activity levels may affect their thinking and learning skills, a new study suggests.

Researchers studied 45 normal-weight children, aged 7 to 11; 24 of them were active and the rest were not. Children were considered active if they took part in organized activities, such as swimming, gymnastics, soccer or dance for more than an hour a week.

The study also included 45 overweight and inactive children.

As expected, active, normal-weight kids had less body fat and a lower resting heart rate than overweight, inactive children. But the researchers also found that normal-weight active children did better on tests of mental skills — such as planning and paying attention — than their inactive counterparts.

The findings were published online recently in the journal Pediatric Exercise Science.

While the study found an association between physical activity and mental skills in children, it did not find a cause-and-effect relationship.

“Activity made a difference even among normal-weight kids. That verifies that physical activity makes a difference in brain function,” study author Catherine Davis, a clinical health psychologist at the Medical College of Georgia, in Augusta, said in a college news release.

The good news is that children — with the help of families and schools — can boost their physical activity levels, she added.

“If they can cut some of the empty calories out of their diet and pick up the pace on physical activity, they may grow into their weight,” Davis said.

In addition, Davis pointed out that the study focused on weight, but it is likely more accurate to look at the amount of body fat in children. For example, overweight kids in the study had more fat, rather than weighing more because of extra muscle mass.

The investigators suggested that future studies should also include overweight, active children to see if they also gain mental benefits from physical activity, and to learn more about how weight and exercise relate to kids’ brain health.

Medications commonly prescribed to treat heartburn and acid reflux may increase kidney disease risk, according to new research. Three new studies show that increased use of proton pump inhibitors may be contributing to a rise in chronic kidney disease.

In one study, researchers tracked the health of more than 10,000 adults with normal kidney function at the start. Those who took PPI medications were found to be between 20 and 50 percent more likely to develop chronic kidney disease than non-users. This finding was replicated in a second study, in which over 240,000 patients were tracked. The third study followed nearly 72,000 patients and also found that use of proton pump inhibitors was associated with increased risk of kidney disease and was also associated with an increased risk of dying prematurely. One of the authors says, “As a large number of patients are being treated with PPIs, health care providers need to be better educated about the potential side effects of these drugs.”

September 25, 2015
The US Food and Drug Administration (FDA) today approved two long-lasting insulin drugs from Novo Nordisk to improve blood glucose control in adults with diabetes mellitus after having rejected them in 2013 for lack of cardiovascular outcomes data.

The drugs, Tresiba and Ryzodeg 70/30, contain insulin degludec, which possesses a half-life of 25 hours and acts for least 42 hours.

Insulin degludecis the only active ingredient in Tresiba. Patients inject it subcutaneously once a day. Because of the drug’s extended coverage, patients do not need to take it the same time each day as with other basal insulins, leading some to call it the “Sunday-sleeping-in insulin.”

Ryzodeg 70/30 contains insulin aspart, a rapid-acting agent, as well as insulin degludec. Also an injectable, Ryzodeg is taken once or twice a day with any main meal, according to a news release from Novo Nordisk.

After its initial regulatory setback 2 years ago, Novo Nordisk launched a cardiovascular trial for insulin degludec called DEVOTE and submitted interim results to the FDA earlier this year when it reapplied for approval. The manufacturer expects the trial to wrap up in the second half of 2016.

In a news release, the FDA cited clinical trials showing that both Tresiba and Ryzodeg 70/30 reduced hemoglobin A1c in patients with type 1 and type 2 diabetes who had inadequate glycemic control at the outset. The reductions resembled those achieved by previously approved long-lasting insulin drugs.

The most common adverse effects reported for the two new drugs were hypoglycemia, allergic reactions, injection-site reactions, pitting at the injection site, itching, rash, edema, and weight gain. Patients who have increased ketones in their blood or urine should not take either drug, according to the FDA.