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DPP-4 Inhibitors for Diabetes Can Cause Severe Joint Pain, FDA Says

August 28, 2015
Dipeptidyl peptidase-4 (DPP-4) inhibitors for type 2 diabetes may cause joint pain so intense it is disabling, the US Food and Drug Administration (FDA) warned today.

Fortunately, the pain goes away, usually in less than a month, once patients stop taking the medicine.

The agency said it identified 33 cases of severe arthralgia associated with DPP-4 inhibitors from October 16, 2006, through December 31, 2013, in its FDA Adverse Event Reporting System database. Twenty-eight of the cases involved sitagliptin (Januvia, Merck & Co, Inc). Sitagliptin accounts for more than 80% of all DPP-4 prescriptions in the country, according to a spokesperson for Merck.

Patients began experiencing joint pain anywhere from 1 day to years after they started taking the drugs. For 10 patients, disabling pain required hospitalization.

Clinicians prescribe DPP-4 inhibitors in conjunction with diet and exercise to reduce blood sugar levels in patients with type 2 diabetes. They are either combined with other diabetes drugs such as metformin or dispensed as stand-alone products.

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FDA OKs adapalene 0.3% and benzoyl peroxide 2.5% (Epiduo Forte) Gel for Acne

The US Food and Drug Administration (FDA) yesterday approved a topical gel combination of adapalene 0.3% and benzoyl peroxide 2.5% (Epiduo Forte, Galderma) for the treatment of acne vulgaris, the company has announced.

The approval was based on a phase 3 randomized double-blind study involving 217 patients, all aged 12 years and older, with an average patient age of 20 years. In the study, Epiduo Forte gel was superior to vehicle control gel in the overall study population of patients with moderate to severe acne at week 12 for the Investigator’s Global Assessment Success Rate and for changes in inflammatory and noninflammatory lesion count, the company notes in a news release announcing the approval.

In addition, half of the patients had severe acne at baseline, and more than half of this group (50.5%) saw marked improvement during the study, with results seen as early as 1 week, with continued improvement through week 12, according to the company.

“Acne is a challenging condition to manage. It can vary greatly from patient to patient, can have a significant physical and psychosocial impact on sufferers, and patients can find treatment adherence difficult to maintain,” Jonathan Weiss, MD, a board-certified dermatologist at Gwinnett Dermatology, PC, and lead investigator on the study, said in the news release.

“For many patients, rapid results are especially important, and some acne treatments take time to show effect. We were very excited to see in the clinical trial that people using Epiduo Forte gel saw results as early as 1 week, with efficacy continually improving through week 12,” Dr Weiss added.

Erythema, scaling, dryness, stinging/burning, and irritant and allergic contact dermatitis may occur with Epiduo Forte, requiring discontinuation in some cases.

Patients using Epiduo Forte gel should avoid exposure to sunlight and sunlamps and wear sunscreen when sun exposure cannot be avoided, the company said.

Epiduo Forte gel will be available by prescription beginning in September.

The formulation of adapalene 0.1% and benzoyl peroxide 2.5% (Epiduo) was approved by the FDA in 2009 for use in patients 12 and older.

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New drug to treat heart failure

The U.S. Food and Drug Administration today approved Entresto (sacubitril/valsartan) tablets for the treatment of heart failure. The drug has been shown to reduce the rate of cardiovascular death and hospitalization related to heart failure.

Entresto was studied in a clinical trial of more than 8,000 adults and was shown to reduce the rate of cardiovascular death and hospitalizations related to heart failure compared to another drug, enalapril. Most patients were also receiving currently approved heart failure treatments, including beta-blockers, diuretics, and mineralocorticoid antagonists.

The most common side effects in clinical trial participants being treated with Entresto were low blood pressure (hypotension), high blood potassium levels (hyperkalemia), and poor function of the kidneys (renal impairment).

Angioedema (an allergic reaction usually appearing as swelling of the lips or face) was also reported with Entresto; black patients and patients with a prior history of angioedema have a higher risk. Patients should be advised to get emergency medical help right away if they have symptoms of angioedema or trouble breathing while on Entresto. Health care professionals should advise patients not to use Entresto with any drug from the angiotensin converting enzyme (ACE) inhibitor class because the risk of angioedema is increased. When switching between Entresto and an ACE inhibitor, use of the two drugs should be separated by 36 hours.

Health care professionals should counsel patients about the risk of harm to an unborn baby. If pregnancy is detected, use of Entresto should be discontinued as soon as possible.

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Viberzi (eluxadoline) and Xifaxan (rifaximin), two new treatments, for irritable bowel syndrome with diarrhea

The U.S. Food and Drug Administration today approved Viberzi (eluxadoline) and Xifaxan (rifaximin), two new treatments, manufactured by two different companies, for irritable bowel syndrome with diarrhea (IBS-D) in adult men and women.

According to the National Institutes of Health, patients with irritable bowel syndrome (IBS) experience a number of signs and symptoms, including pain or discomfort in the abdomen and changes in bowel movement patterns. Studies estimate that IBS affects 10 to 15 percent of adults in the United States. IBS-D is a subtype characterized mainly by loose or watery stools at least 25 percent of the time.

“For some people, IBS can be quite disabling, and no one medication works for all patients suffering from this gastrointestinal disorder,” said Julie Beitz, M.D., director of the Office of Drug Evaluation III in FDA’s Center for Drug Evaluation and Research. “The approval of two new therapies underscores the FDA’s commitment to providing additional treatment options for IBS patients and their doctors.”

Viberzi, which contains a new active ingredient, is taken orally twice daily with food. Viberzi activates receptors in the nervous system that can lessen bowel contractions. Viberzi is intended to treat adults with IBS-D.

Xifaxan can be taken orally three times a day for 14 days, for the treatment of abdominal pain and diarrhea in patients with IBS-D. Patients who experience a recurrence of symptoms can be retreated with a 14 day treatment course, up to two times. Xifaxan, an antibiotic derived from rifampin, was previously approved as treatment for travelers’ diarrhea caused by E. coli and for reduction of the risk in adult patients of recurring overt hepatic encephalopathy, the changes in brain function that occur when the liver is unable to remove toxins from the blood. The exact mechanism of action of Xifaxan for treatment of IBS-D is not known, but is thought to be related to changes in the bacterial content in the gastrointestinal tract.

The most common side effects in patients treated with Viberzi include constipation, nausea and abdominal pain. The most serious known risk associated with Viberzi is the risk of spasm in the sphincter of Oddi, the smooth muscle that surrounds the end portion of the common bile and pancreatic ducts, which can result in pancreatitis. Viberzi should not be used in patients with a history of bile duct obstruction, pancreatitis, severe liver impairment, or severe constipation, and in patients who drink more than three alcoholic beverages per day.

The most common side effects in patients treated with Xifaxan for IBS-D include nausea and an increase in alanine aminotransferase (ALT), a liver enzyme measured in blood. If diarrhea does not improve or worsens after treatment with Xifaxan, then evaluation for development of a severe infectious diarrhea, C. difficile enterocolitis, should be performed. Caution should be used when using Xifaxan in patients with severe liver impairment or when combined with certain other drugs.

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New antibacterial drug Avycaz (ceftazidime-avibactam)

The U.S. Food and Drug Administration today approved Avycaz (ceftazidime-avibactam), a new antibacterial drug product, to treat adults with complicated intra-abdominal infections (cIAI), in combination with metronidazole, and complicated urinary tract infections (cUTI), including kidney infections (pyelonephritis), who have limited or no alternative treatment options.

Avycaz is a fixed-combination drug containing ceftazidime, a previously approved cephalosporin antibacterial drug, and avibactam, a new beta-lactamase inhibitor.

“It is important that the use of Avycaz be reserved to situations when there are limited or no alternative antibacterial drugs for treating a patient’s infection.”
Avycaz is the fifth approved antibacterial drug product designated as a Qualified Infectious Disease Product (QIDP). This designation is given to antibacterial products to treat serious or life-threatening infections under the Generating Antibiotic Incentives Now (GAIN) title of the FDA Safety and Innovation Act.
The most common side effects include vomiting, nausea, constipation and anxiety. Health care professionals should inform patients of these risks and also advise that decreased efficacy, seizures and other neurologic events were seen in patients with poor kidney function (renal impairment). Serious skin reactions and anaphylaxis may occur in patients with penicillin allergies.