RapidRx

Major implicated agents include anabolic steroids, green tea, multi-ingredient nutritional supplements

Herbal and dietary supplement (HDS)-induced liver injury accounts for 20 percent of cases of hepatotoxicity in the United States, according to research published online Sept. 27 inHepatology.

Victor Navarro, M.D., from Einstein Healthcare Network in Philadelphia, and colleagues examine the current challenges in the diagnosis and management of HDS-induced liver injury.

The researchers note that HDS-induced liver injury accounts for one in five cases of hepatotoxicity in the United States. Anabolic steroids, green tea extract, and multi-ingredient nutritional supplements (MINS) are the major implicated agents. Anabolic steroids, which are marketed as bodybuilding supplements, tend to induce a prolonged cholestatic, self-limiting liver injury, characterized by a distinctive biochemical and histological phenotype. In contrast, green tea extracts and other products cause an acute hepatitis-like injury. MINS account for most cases of HDS-associated liver injury; the causative agent is usually unknown or can only be suspected.

“The confident identification of injurious ingredients within HDS will require strategic alignments among clinicians, chemists, and toxicologists,” the authors write. “The ultimate goal should be to prohibit or more closely regulate potentially injurious ingredients and thus promote public safety.”

The US Food and Drug Administration (FDA) has approved a new version of a recombinant, egg-free influenza vaccine called Flublok (Protein Sciences) that will protect against four strains of the virus, the manufacturer announced today.

The current version of Flublok, available during the 2016-2017 flu season, is designed for three strains: an A/California/7/2009 (H1N1)-like virus, an A/Hong Kong /4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008-like virus (B/Victoria lineage). The new formulation, Flublok Quadrivalent, protects against these as well as the B/Phuket/3073/2013-like virus (B/Yamagata lineage). Both are injectables.

A company spokesperson told Medscape Medical News that  Flublok Quadrivalent would be available for the 2017-2018 flu. Like its trivalent predecessor, Flublok Quadrivalent is indicated for adults 18 years of age and older.

Approved in 2013, trivalent Flublok is the only influenza vaccine on the market fashioned through recombinant DNA technology. The manufacturer isolates a hemagglutinin (HA) protein found on the surface of a naturally occurring flu virus that, as an antigen, triggers an immune response. These HA proteins are combined with portions of another virus, and the mix is grown in insect cells. The HA protein is then harvested and purified.

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention recommended trivalent Flublok in 2013 as a vaccine alternative for individuals who have an egg allergy. The two other current ways of making flu vaccines involve eggs. In egg-based manufacturing, inactivated or live attenuated vaccine viruses are grown in eggs. In the cell-based process, vaccine viruses first are grown in eggs and then combined with mammalian cells to replicate. Vaccine antigen is purified from this mix.

In a news release, Protein Sciences called Flublok Quadrivalent a “good choice” for seniors and individuals with compromised immune systems because it contains three times more active ingredient than other quadrivalent flu vaccines, compensating for a weaker immune response.

A clinical study of 9000 adults 50 years of age and older showed that individuals who received Flublok Quadrivalent were more than 40% less likely to come down with a confirmed case of influenza than those who received Fluarix Quadrivalent (Glaxo SmithKline), according to the manufacturer.

Injection-site tenderness and pain, headache, and fatigue are among the most common adverse events associated with Flublok Quadrivalent.

Antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), can significantly disrupt sleep architecture in elderly patients and may contribute to early signs of neurodegeneration that can progress to dementia, new research shows.

“We take into account other side effects of antidepressants, including weight gain and sexual side effects, but we are less concerned about sleep, especially when we use the SSRIs,” Muhammad Tahir, MD, psychiatry resident, SUNY Upstate Medical University, Syracuse, New York, told Medscape Medical News.

“But the SSRIs increase sleep latency in the elderly and decrease REM [rapid eye movement] sleep duration and are also associated with REM sleep behavioral disorders, including nightmares,” he added.

“So our literature review suggests that we should be careful about using SSRIs in the elderly population and not underestimate the effectiveness of psychotherapy and other holistic care approaches for the elderly,” Dr Tahir said.

The study was presented here at the Institute of Psychiatric Services (IPS): The Mental Health Services 2016 Conference.

The literature review included 10 studies published within the past 5 years. The studies included systemic reviews, retrospective studies, and prospective studies, and patients had to be at least 50 years of age and receiving an antidepressant, largely an SSRI, for the treatment of depression.

Analyses revealed that not only did the SSRIs in particular change sleep architecture in older patients, they also appeared to increase the risk for REM behavioral disorders.

REM sleep behavioral disorders are characterized by normal brain activity, but the body is agitated and is not sleeping. This may be an early sign of neurodegeneration, said Dr Tahir.

Changes in the sleep architecture brought on by antidepressant therapy may result in agitation, Dr Tahir noted, which may prompt further treatment with further side effects.

Unfortunately, there is little evidence to support the use of any treatment other than the SSRIs for depression in the elderly.

Both the tricyclic antidepressants and the monoamine oxidase inhibitors are associated with too many side effects, especially in the elderly, and are generally not used in older patients.

Benzodiazepines in turn are associated with an increased risk for falls and again are inappropriate for use in the elderly.

Dr Tahir suggested that psychiatrists screen their elderly patients for any signs and symptoms of neurodegenerative disorders and, if an SSRI is prescribed, ask detailed questions about sleep quality on all follow-up visits.

SSRI Dosing Important

Commenting on the findings for Medscape Medical News, Peter Yellowlees, MD, professor of psychiatry, University of California, Davis, said the analysis, though interesting, does not include information on the doses of the SSRIs used in the studies that were included for review.

“In the elderly, these doses should be a maximum of half of the usual dose prescribed for younger patients,” Dr Yellowlees observed.

As for the possible association between SSRI use and neurodegenerative disease, Dr Yellowlees also noted that SSRIs are not necessarily causative.

“Rather, it may simply be that in the early stages of these diseases, depression and agitation are more common, and hence antidepressants are more commonly prescribed,” he noted.

In fact, the same association has been reported between the benzodiazepines and neurodegenerative disease that has been reported in the new study with respect to SSRIs, Dr Yellowlees pointed out.

“The jury is definitely out on the connection between degenerative disorders and medications, but in my view, there is not a lot of evidence to suggest that there is a causative link, although there does seem to be an association,” Dr Yellowlees suggested.

“The key issue here is that depression in the elderly is common and can be debilitating and is very treatable with both medications in lower doses than usually prescribed in younger patients along with behavioral interventions.”

U.S. Food and Drug Administration (FDA) has approved Stelara (ustekinumab) for the treatment of moderately to severely active Crohn’s disease in adults (18 years or older) who have failed or were intolerant to treatment with immunomodulators or corticosteroids but never failed treatment with a tumor necrosis factor (TNF) blocker, or who failed or were intolerant to treatment with one or more TNF blockers. Stelara is the first biologic therapy for Crohn’s disease targeting interleukin (IL)-12 and IL-23 cytokines, which play a key role in inflammatory and immune responses.

“Crohn’s disease is a complex condition to treat, and not all therapies work for every patient,” said William J. Sandborn, MD, Chief, Division of Gastroenterology, and Professor of Medicine, UC San Diego School of Medicine, and study investigator. “The FDA approval of Stelara represents an important advancement in treating patients with Crohn’s disease, as this therapy offers an alternate mechanism of action to induce and maintain clinical remission over time. Based on the results of the clinical development program, Stelara has the potential to benefit many adults living with Crohn’s disease.”

In clinical studies of patients who were either new to, experienced with, or failed biologic therapy (TNF blockers), between 34% (UNITI-1 study) and 56% (UNITI-2 study) of patients experienced relief from their Crohn’s disease symptoms in just six weeks after receiving the one-time intravenous (IV) infusion of Stelara. Noticeable improvement was observed as early as three weeks. Additionally, the majority of those who responded to induction dosing and continued treatment with Stelara subcutaneous maintenance doses every 8 weeks were in remission at the end of 44 weeks (52 weeks from initiation of the induction dose).

Stelara is the only treatment for Crohn’s disease that starts with a weight-based, one-time intravenous (IV) infusion induction dose (260 mg [55 kg or less], 390 mg [more than 55 kg to 85 kg], or 520 mg [more than 85 kg]) to help reduce symptoms, followed by 90 mg subcutaneous maintenance injections every 8 weeks to help keep the symptoms under control. The first dose of Stelara is an induction dose, administered intravenously, under the supervision of a healthcare professional. Subsequent maintenance doses are administered as a subcutaneous injection every 8 weeks, either by a healthcare professional or self-injected by the patient after proper training.

About Crohn’s Disease

Crohn’s disease is a chronic inflammatory condition of the gastrointestinal tract that affects approximately 700,000 Americans. Symptoms of Crohn’s disease can vary but often include abdominal pain and tenderness, frequent diarrhea, rectal bleeding, weight loss, and fever. Hospitalization is at times required for severe disease, to treat certain complications, and for surgery. There is currently no cure for Crohn’s disease.¹

About Stelara (ustekinumab)

Stelara is a prescription medicine used to treat moderately to severely active Crohn’s disease in adult patients (18 years and older) who have already taken other medicine that did not work well enough or they could not tolerate it.

SOURCE Janssen Biotech, Inc.

September 23, 2016 — The U.S. Food and Drug Administration today approved Amjevita (adalimumab-atto) as a biosimilar to Humira (adalimumab) for multiple inflammatory diseases. Amjevita is approved for the following indications in adult patients:

• moderately to severely active rheumatoid arthritis;
• active psoriatic arthritis;
• active ankylosing spondylitis (an arthritis that affects the spine);
• moderately to severely active Crohn’s disease;
• moderately to severely active ulcerative colitis; and
• moderate to severe plaque psoriasis.

Amjevita is also indicated for moderately to severely active polyarticular juvenile idiopathic arthritis in patients four years of age and older.

Health care professionals should review the prescribing information in the labeling for detailed information about the approved uses.

“This is the fourth FDA-approved biosimilar. The biosimilar pathway is still a new frontier and one that we expect will enhance access to treatment for patients with serious medical conditions,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research.

Biological products are generally derived from a living organism and can come from many sources, including humans, animals, microorganisms or yeast. A biosimilar is a biological product that is approved based on a showing that it is highly similar to an already-approved biological product and has no clinically meaningful differences in terms of safety, purity and potency (i.e., safety and effectiveness) from the reference product, in addition to meeting other criteria specified by law.

The FDA’s approval of Amjevita is based on review of evidence that included structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data and other clinical safety and effectiveness data that demonstrates Amjevita is biosimilar to Humira. It has been approved as a biosimilar, not as an interchangeable product.

The most serious known side effects with Amjevita are infections and malignancies. The most common expected adverse reactions with Amjevita are infections and injection site reactions.

Like Humira, the labeling for Amjevita contains a Boxed Warning to alert health care professionals and patients about an increased risk of serious infections leading to hospitalization or death. The Boxed Warning also notes that lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor blockers, including adalimumab products. The drug must be dispensed with a patient Medication Guide that describes important information about its uses and risks.

Amjevita is manufactured by Amgen, Inc., of Thousand Oaks, California. Humira was approved in December 2002 and is manufactured by AbbVie Inc. of North Chicago, Illinois.