Category: Drugs and Disease

July 27, 2016

Sanofi announced today that the U.S. Food and Drug Administration (FDA) approved Adlyxin (lixisenatide), a once-daily mealtime GLP-1 receptor agonist injection indicated as an adjunct to diet and exercise for the treatment of adults with type 2 diabetes.

The approval of Adlyxin was based on FDA review of results from the GetGoal clinical program and findings from the ELIXA trial, which successfully addressed the FDA’s request to demonstrate CV safety. The GetGoal clinical program, which included 13 clinical trials involving more than 5,000 adults with type 2 diabetes worldwide, evaluated the safety and efficacy of lixisenatide in adults with type 2 diabetes. All studies of the GetGoal program successfully met the primary efficacy endpoint of HbA1c reduction. The most common adverse events reported for Adlyxin included nausea, hypoglycemia and vomiting.

Adlyxin will be available in a disposable pre-filled pen in a single dose of 20 micrograms. Patients will also receive a disposable pre-filled pen in a single dose of 10 micrograms that they should initiate once daily for 14 days. On Day 15, patients will increase dosage to 20 micrograms once daily.

Adlyxin is approved under the proprietary name, Lyxumia® in more than 60 countries and marketed in over 40. Commercial launches include most EU countries, Japan, Brazil, Mexico and India. Adlyxin was in-licensed from Zealand Pharma A/S (NASDAQ OMX Copenhagen: ZEAL), www.zealandpharma.com.

About Adlyxin

Adlyxin is a once-daily glucagon-like peptide-1 receptor agonist (GLP-1 RA) for the treatment of adult patients with type 2 diabetes mellitus as an adjunct to diet and exercise. GLP-1 is a peptide hormone that is released within minutes after eating a meal. It is known to suppress glucagon secretion from pancreatic alpha cells and stimulate glucose-dependent insulin secretion by pancreatic beta cells. Adlyxin increases glucose-dependent insulin release, decreased glucagon secretion, and slows gastric emptying.

July 26, 2016

Limits use for acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis and uncomplicated urinary tract infections.

The U.S. Food and Drug Administration today approved safety labeling changes for a class of antibiotics, called fluoroquinolones, to enhance warnings about their association with disabling and potentially permanent side effects and to limit their use in patients with less serious bacterial infections.

“Fluoroquinolones have risks and benefits that should be considered very carefully,” said Edward Cox, M.D., director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research. “It’s important that both health care providers and patients are aware of both the risks and benefits of fluoroquinolones and make an informed decision about their use.”

Fluoroquinolones are antibiotics that kill or stop the growth of bacteria. While these drugs are effective in treating serious bacterial infections, an FDA safety review found that both oral and injectable fluroquinolones are associated with disabling side effects involving tendons, muscles, joints, nerves and the central nervous system. These side effects can occur hours to weeks after exposure to fluoroquinolones and may potentially be permanent.

Because the risk of these serious side effects generally outweighs the benefits for patients with acute bacterial sinusitis, acute exacerbation of chronic bronchitis and uncomplicated urinary tract infections, the FDA has determined that fluoroquinolones should be reserved for use in patients with these conditions who have no alternative treatment options. For some serious bacterial infections, including anthrax, plague and bacterial pneumonia among others, the benefits of fluoroquinolones outweigh the risks and it is appropriate for them to remain available as a therapeutic option.

FDA-approved fluoroquinolones include levofloxacin (Levaquin), ciprofloxacin (Cipro), ciprofloxacin extended-release tablets, moxifloxacin (Avelox), ofloxacin and gemifloxacin (Factive). The labeling changes include an updated Boxed Warning and revisions to the Warnings and Precautions section of the label about the risk of disabling and potentially irreversible adverse reactions that can occur together. The label also contains new limitation-of-use statements to reserve fluoroquinolones for patients who do not have other available treatment options for acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis and uncomplicated urinary tract infections. The patient Medication Guide that is required to be given to the patient with each fluoroquinolone prescription describes the safety issues associated with these medicines.

In November 2015, an FDA Advisory Committee discussed the risks and benefits of fluoroquinolones for the treatment of acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis and uncomplicated urinary tract infections based on new safety information. The new information focused on two or more side effects occurring at the same time and causing the potential for irreversible impairment. The advisory committee concluded that the serious risks associated with the use of fluoroquinolones for these types of uncomplicated infections generally outweighed the benefits for patients with other treatment options.

Today’s action also follows a May 12, 2016, drug safety communication advising that fluoroquinolones should be reserved for these conditions only when there are no other options available due to potentially permanent, disabling side effects occurring together. The drug safety communication also announced the required labeling updates to reflect this new safety information.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency is also responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

July 12, 2016

The U.S. Food and Drug Administration approved Xiidra (lifitegrast ophthalmic solution) for the treatment of signs and symptoms of dry eye disease, on Monday, July 11, 2016. Xiidra is the first medication in a new class of drugs, called lymphocyte function-associated antigen 1 (LFA-1) antagonist, approved by the FDA for dry eye disease.

“Normal tear production is needed for clear vision and eye health,” said Edward Cox, M.D., director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research. “This approval will provide a new treatment option for patients with dry eye disease.”

Dry eye disease includes a group of conditions in which the eye does not produce an adequate volume of tears or when the tears are not of the correct consistency. The chance of experiencing dry eye increases with age, affecting approximately five percent of the adult population age 30-40 and 10 to 15 percent of adults over age 65, and is more common among women. When severe and left untreated, this condition can lead to pain, ulcers or scars on the part of the eye called the cornea. Dry eye can make it more difficult to perform some activities, such as using a computer or reading for an extended period of time, and it can decrease tolerance for dry environments, such as the air inside an airplane.

The safety and efficacy of Xiidra was assessed in over a thousand patients, in four separate, randomized, controlled studies. These studies included patients 19–97 years of age, of which the majority were female (76 percent). Patients were randomized equally to receive either Xiidra eyedrops or placebo eyedrops, which were used twice a day for twelve weeks. The studies found that groups treated with Xiidra demonstrated more improvement in both the signs and the symptoms of eye dryness than the groups treated with placebo.

The most common side effects of Xiidra include eye irritation, discomfort or blurred vision and an unusual taste sensation (dysgeusia).

Dry eye disease does not routinely occur in children. Safety and efficacy in pediatric patients below the age of 17 years has not been studied.

Women with endometriosis, a painful uterus condition, may be at a higher risk for coronary heart disease (CHD), a new study suggests.

The link was found to be strongest among young women. Having had a hysterectomy or oophorectomy was also tied to a higher risk of CHD, which explained partially the association between endometriosis and CHD.

Researchers analysed the potential connection between laparoscopically confirmed endometriosis and subsequent CHD among 116,430 women in the Nurses’ Health Study II (1989–2009). Excluded from the study were those with a history of heart disease and stroke.

Women with endometriosis had a higher risk of myocardial infarction, angiographically confirmed angina, coronary artery bypass graft surgery/coronary angioplasty procedure/stent, or any of these CHD endpoint combined when compared with women without the gynecologic disease.

The result was independent of potential demographic, anthropometric, family history, reproductive, and lifestyle confounders.

Relative risk for the combined CHD endpoint was highest among women aged ≤40 years and decreased as age increased (40<age≤50 years, 50<age≤55 years and age >55 years.

Women who had hysterectomy/oophorectomy had a higher risk of combined CHD compared with those who had not undergone the procedure. Greater frequency of hysterectomy/oophorectomy and earlier age at surgery after endometriosis diagnosis explain the 42 percent association between the gynaecologic condition and CHD.

Dengue fever is caused by the dengue virus and borne by the Aedes mosquito. The disease is now endemic in over 100 countries, according to the World Health Organization, but is still most common in Southeast Asian and countries in the Western Pacific. The virus causes flu-like symptoms that generally resolve on their own with supportive care but severe cases require further management and possibly hospitalization. Primary care doctors are frequently the first point of contact for people with dengue fever.

 

Dengue fever is a mosquito borne infection caused by the dengue virus, the most common mosquito borne viral infection in the world. We no longer talk about dengue as a disease affecting Asian countries – at least half of the world population is at risk for dengue because of where they live and their exposure to the virus from mosquitoes bites.

Since 2013, the total number of dengue cases recorded in Singapore has remained high at more than 10,000 cases annually. This is likely the result of a combination of factors such as high mosquito population, warmer weather, increasing urban density and low herd immunity in the Singapore local resident population.

Primary care doctors probably play the biggest role in identifying and caring for patients with dengue fever. Most of the time patients will go to their family doctor to seek medical advice  first, as the symptoms of early dengue infection cannot be differentiated from other viral illnesses. If dengue is suspected, nonsteroidal anti-inflammatory drugs (NSAIDS) and intramuscular injections should be avoided due to the risk of bleeding. The family physician should monitor the patient regularly throughout the course of illness. If the doctor is concerned that the patient may be at risk for severe dengue, the doctor should then refer the patient to hospital for further medical evaluation.

Dengue fever: running the course

Dengue fever is a self-limiting illness. Once a person is bitten by a virus-carrying mosquito he/she will come down with flu-like symptoms after an incubation period of 3-7 days. The patient may experience high fever, body aches and pains, loss of appetite and, in some cases, nausea and vomiting. Most patients will recover from the infection after about a week of illness.

One of the hallmarks of dengue fever occurs around day 4-5 of illness – the fever begins to improve but the blood platelet count starts to fall. This might cause patients to present with petechial rashes, which are small capillary bleeds just under the skin that look like small red dots. They are harmless but can be alarming and usually send patients back to the doctor who, under suspicion of dengue fever, would refer the patient to a hospital or polyclinic for a blood test.

Depending on how low the platelet levels are, and if the patient is otherwise well (if they are young, healthy, and able to drink sufficient fluids), they can be sent home and instructed to rest. Polyclinic doctors can continue to monitor the patient without referring to a hospital.

However, if the platelets are low and the patient is unwell, has poor appetite, is not able to drink sufficient fluids, or  if there is a worry of dengue complications that may result in severe dengue,  doctors may refer the patient to hospital for further management.

Plasma leaks and bleeding

The most important thing about dengue virus is its ability to cause severe disease. It is not well understood how the virus interacts with the cell lining of blood vessels but in severe dengue, plasma leaks into the surrounding tissues and accumulates. Fluid can accumulate in the lungs as well, resulting in hypotension and shock if the person does not receive fluid resuscitation in time.

The other feared complication is bleeding. Bleeding can occur in the gut, gums, urinary tract and brain. Women may also experience heavy menstrual bleeds.

Patients over 65 years, those with other medical conditions such as diabetes, pregnant women, and young children may be at risk for more severe forms of dengue infection. However, who is at risk for bleeding is not well understood.

Some other clues that a patient might be experiencing severe dengue include restlessness, abdominal pain, persistent vomiting, and bleeding of the gums or blood in the vomitus or stool. These are important symptoms for a primary care doctor to look out for to decide if a patient can be sent home to rest or come to hospital attention. If in doubt, medical practitioners should refer the patient to the hospital for further assessment.

No “magic bullet” for dengue

There is no curative treatment for dengue infection. Rather, medications are given to alleviate the signs and symptoms. Aspirin should not be given to patients. It can cause severe bleeding. Paracetamol are usually prescribed to relieve fever, muscle and joint aches, and headache. Bed rest is essential and the patient should consume plenty of water which will help to alleviate the illness.

In general, dengue fever is self-limiting. Death rarely occurs in severe cases and most well developed countries have trained medical personnel and proper care facilities to manage severe disease. The fatality rate is less than 1 percent in such countries.

Theoretically, a person may contract dengue fever four times as there are four different serotypes of virus. It is not uncommon to get dengue fever at least twice in a lifetime for people living in endemic areas. However, patients cannot fall ill with the same serotype twice as they will have developed antibodies against that serotype.

Evaluation of the usefulness of the Sanofi Pasteur dengue vaccine is ongoing. It is currently not approved for use in Singapore. The vaccine was found to be safe and among individuals aged 9 years and older, efficacy was higher than in younger children with an overall efficacy against any of the four serotypes of 60 percent.

Conclusion

Dengue fever is the most common mosquito borne viral infection worldwide. Most of the time, it is a self-limiting illness though its presentation cannot be differentiated from other viral illnesses. Severe dengue can occur in a subgroup of patients at high risk and is characterized by plasma leakage and/or bleeding. It is important to recognize the symptoms of severe disease early so that patients can be referred for proper medical care at the critical stages of illness to prevent complications and death.

Antibiotic therapy after surgical drainage of abscesses improves cure rates, even in the presence of methicillin-resistant Staphylococcus aureus (MRSA), according to results of a recent US study.

Eighty percent of individuals given trimethoprim and sulfamethoxazole achieved clinical cure compared to 73.6 percent of patients given placebo after surgical drainage of a cutaneous abscess.

Adjunct antibiotic treatment also reduced the need for subsequent drainage (3.4 percent in the treatment group vs 8.6 percent in the placebo group), skin infections at a different site (3.1 vs 10.3 percent) and infections among household members (1.7 vs 4.1 percent) 7 to 14 days post-treatment.

There was a higher incidence of adverse events in the treatment arm, though these were mostly mild gastrointestinal problems.

“Adjunctive oral treatment with trimethoprim-sulfamethoxazole, which is inexpensive, appears to be safe, and is associated with a high cure rate of the primary lesion, offers the possibility of lower rates of costly subsequent medical visits, surgeries, and hospitalizations and of new infections among patients and their household contacts,” said the study authors.

Participants of this double-blind, randomized trial were 1,265 patients aged >12 years who presented at 5 US Emergency Departments (EDs) with uncomplicated cutaneous abscesses which were treated with drainage. Among them, 45.3 percent had wound cultures that were positive for MRSA. Participants were given a combination of trimethoprim (320 mg) and sulfamethoxazole (1600 mg) twice daily for 7 days or a placebo.

While previous small studies have shown that adjuvant therapy with trimethoprim-sulfamethoxazole helped prevent the formation of new lesions in the short-term, they were not recommended for widespread use.

“Traditional teaching has been that the only treatment needed for most skin abscesses is surgical drainage – and that antibiotics don’t provide an extra benefit,” said Dr. Gregory Moran, Clinical Professor of Emergency Medicine at the David Geffen School of Medicine, University of California, Los Angeles (UCLA), California, US, and one of the authors of the present study. He hoped that the results would help guide doctors in treating abscesses.

According to the authors, adjunctive antibiotics are recommended for patients with coexisting conditions such as diabetes and cellulitis and those who have infected lesions that are larger than 5 cm. In the case of this study, many participants met the criteria for the use of antibiotics, said the authors.

High levels of the atherosclerosis marker coronary artery calcium (CAC) may be a good predictor of mortality and coronary heart disease (CHD) risk as well as myocardial infarction in individuals aged 80 and older without cardiovascular disease (CVD), according to a US-based observational study.

Researchers looked at 532 participants to determine whether CAC levels correlated with death, dementia and CHD among the elderly. CAC was defined as deposits that can narrow arteries and increase heart attack risk.

Of the total number of participants, 36 percent had CAC scores that were greater than the highest level (>400). Women and African-Americans showed lower CAC scores than men. CAC score and number of coronary calcifications directly correlated to age-adjusted total mortality and CHD. Age-specific incidence of dementia was higher than of CHD.

About 25 percent of deaths were attributed to CHD and 16 percent to dementia. Of the total deaths reported, 64 percent were of individuals with prior diagnosis of dementia. White women with low CAC scores had a significantly decreased incidence of dementia.

The findings suggest that the prevalence of dementia in older populations will likely increase as prevention and treatment of CHD improve and increase the longevity of the general population. A zero or very low CAC score could be associated with a low risk of dementia and cardiovascular risk factors such as high blood pressure, diabetes, smoking and sedentary behaviour leading to the development of atherosclerosis and eventually CHD could also affect progression of brain pathology, such as dementia risk.

The study highlights that people who reach older ages can expect a significant increase in the risk of dementia, although the small sample size necessitates replication of the results in other studies of the elderly.