Dr. Gustin's Blog

Breaking News: EMA suspends dozens of Drugs based on Flawed Studies

A committee of the European Medicines Agency (EMA) has just a few days ago recommended suspending the sale of roughly four dozen generic drugs that are used for conditions including diabetes, depression, and hypertension because they noted that their approvals were based on flawed clinical studies conducted only in India. The US Food and Drug Administration (FDA) has not yet taken action on the issue.  But they are in the process of reviewing this issue now.

Familiar names of commonly prescribe drugs on the list include candesartan, donepezil, escitalopram, esomeprazole, and metformin. The list extends more than 120 pages because the drugs are marketed individually in multiple European Union (EU) nations in various dosages, and therefore appear over and over.

Abbott Laboratories, Actavis, Dr Reddy's Laboratories, Mylan Pharmaceuticals, Sandoz, and Takeda Pharmaceuticals are some of the many well-known manufacturers involved in this scandel.  

The EMA recommendation to suspend the drugs would apply across the entire EU. Drug regulators in France, Germany, Belgium, and Luxembourg have already acted to stop the sales of 25 of these drugs.

The clinical studies in question were conducted by GVK Biosciences, a contract research organization in Hyderabad, India.

The recommendation of the EMA's Committee for Medicinal Products for Human Use to suspend the drugs was based on an independent French inspection of GVK Biosciences that revealed "data manipulations of electrocardiograms during the conduct of some studies of generic medicines," apparently over the course of at least 5 years. The systematic and prolonged nature of these manipulations and the number of staff involved "cast doubt" on the integrity of the trial methodology and the reliability of the data generated according to the EMA.

FDA Has Taken No Action After Its Own GVK Inspection

When queried the FDA said that some 40 drug applications received from 2007 to March 2012 contained GVK clinical data, and that some of these applications were approved.

The FDA declined to identify the drugs in question or indicate those that had been approved.

According to the FDA statement, the agency inspected GVK Biosciences in September 2014 on the heels of the French inspection in May 2014 and failed to find any evidence "that affects the safety or efficacy of drug products subject to pending applications or products approved in the US."

The agency promised to take "swift and appropriate action" to protect American consumers if it "identifies issues concerning GVK Biosciences that relate to products approved by the FDA."

Exceptions Can Be Made

The EMA investigation of drugs studied at GVK Biosciences encompassed more than 1000 individual generics in various forms and strengths as individually approved in 29 EU nations. Of this group, 300 generics had enough supporting clinical data from other sources to warrant staying on the market, according to the EMA.

That left roughly 700 generics — reiterations of the core four dozen or so drugs — that should be suspended, the EMA said. However, individual countries can make an exception for drugs that are critically important because there are no alternatives to meet patients' needs.

The EMA recommendation goes to the European Commission, the EU's executive agency, for a legally binding decision that will apply to all EU nations, including those that already have suspended the generics in question.

In the meantime, American physicians are waiting for the results of the independent FDA evaluation of this situation.  If the FDA concurs, then this will be the biggest debacle ever in U.S. pharmaceutical history.  

Stay tuned!

Statins: A new side effect

Statins are one of the most popular drugs.  They reduce serum lipids implicated in producing cardiac and vascular disease.  Statins have side effects and are well-known, such as liver disease and muscle pain.  Now a new side effect has been discovered.

Statin therapy significantly elevates the risk of developing cataracts severe enough to warrant surgery, suggests analyses of two distinct cohorts, one from Canada and another from the US.

For now, the possibility of such a risk from statins and its potential mechanisms should be explored in prospective trials, "especially in light of increased statin use for primary prevention of cardiovascular disease and the importance of acceptable vision in old age, when cardiovascular disease is common," according to the report, published in the December 2014 issue of the Canadian Journal of Cardiology with lead author Dr Stephanie J Wise (University of British Columbia, Vancouver).

"However, because the relative risk is low and because cataract surgery is effective and well tolerated, this association should be disclosed but not be considered a deterrent to use of statins when warranted for cardiovascular risk reduction," they write.

"For those of us who have prescribed high doses of statins for almost 3 decades, there is certainly no epidemic of cataracts among our longtime lipid-clinic patients," write Drs Steven E Gryn and Robert A Hegele (Western University, London, ON) in an accompanying editorial in the same journal.

"Nevertheless, if the findings of Wise et al are confirmed, physicians might need to factor in this potential risk when discussing statin use with patients," they continue.

And, in patients at high CV risk, "the prevention of CVD, stroke, and their associated morbidity and mortality vastly outweighs the risk of cataracts. Even among lower-risk patients, for whom the benefit/risk ratio is less dramatic, most patients would still probably prefer having to undergo earlier non–life-threatening cataract surgery over suffering a major vascular event."

Pain Meds Linked to Hypoglycemia

A popular pain medication called Tramadol (Ultram) has been found to cause serious hypoglycemia (low blood sugar).  This adverse reaction is potentially fatal.  Tramadol is not a narcotic.  It is used in lieu of narcotics.  The study can be found in JAMA.  

JAMA Intern Med. Published online December 8, 2014.

The authors of the study wrote:  "The increased prescribing of tramadol most likely reflects aggressive marketing coupled with the perception that it is a safe analgesic not prone to abuse. Whereas the drug's analgesic effects are at best moderate, its toxic effects are dangerous and merit respect, particularly when doses are escalated."

Other adverse effects include seizures, serotonin syndrome, and drug interactions, as well as well-known opiate adverse effects, namely respiratory depression.

New Synthetic Hallucinogens

A novel class of synthetic hallucinogens that is being sold as a cheaper, more readily available LSD substitute, or even as LSD itself, is emerging as a particularly deadly drug, especially for young males, new research shows.  A recent paper was published discussing the advent of this new class of drug.  See:   American Academy of Addiction Psychiatry (AAAP) 25th Annual Meeting and Symposium: Abstract 54, presented December 6, 2014.

This paper shows that a systematic review of published reports about use in humans of 251-NBOMe, or simply NBOMe, showed that doses as small as 50 µg can produce powerful effects ― and ingestion was associated with a variety of serious adverse events, from severe agitation and delirium that can last for days to seizures and even death.  In fact, several deaths have already been reported.  In fact, the drug is far more toxic and dangerous than prior hallucinogens like LSD.

Drug-related adverse events included severe agitation and aggression, delirium, tachycardia and hypertension, pyrexia, respiratory and metabolic acidosis, impaired renal function, elevation of creatine kinase levels, and elevated transaminase levels. A total of 40% of the patients presented with seizures; there was one case of status epilepticus.  This differs dramatically from the side effect profile of LSD which wore off with time and only required sedation in some cases.  These new drugs require ICU admission, and treatment of severe status epilepticus.

Popular Antipsychotic Medication Can be Fatal

A recent study revealed that the popular anti-psychotic, anti-bipolar, anti-depressant medication, Geodon when taken in normal doses can result in a fatal reaction.  Read on.

Antipsychotic Linked to Potentially Fatal Skin Reaction

 

 

The antipsychotic ziprasidone (Geodon, Pfizer Inc) and its generic counterparts have been linked to a rare but potentially fatal skin reaction, prompting the US Food and Drug Administration (FDA) to add a new warning to the drug's label.

Known as DRESS (drug reaction with eosinophilia and systemic syndromes), this serious condition can start with a fever and a rash and/or swollen lymph glands. DRESS can quickly spread to all parts of the body, causing inflammation in major organs, including the liver, kidneys, lungs, heart, or pancreas. DRESS can also increase eosinophils and lead to death.

Ziprasidone is used to treat schizophrenia and bipolar I disorder.

At the first sign of fever and rash, patients should seek immediate and urgent medical care, the FDA notes in a release. In addition, healthcare professionals should immediately stop treatment with ziprasidone if DRESS is suspected, but it also warns that patients should not discontinue the drug on their own, particularly in the absence of symptoms.

The FDA warning is based on a review of six patients in whom the signs and symptoms of DRESS appeared between 11 and 30 days after initiation of ziprasidone treatment. None of the patients died.

The FDA has required the drug's manufacturer to add a new warning for DRESS to the Warnings and Precautions section of the drug labels for the capsule, oral suspension, and injection formulations.

The FDA is urging healthcare professionals and patients to report side effects involving ziprasidone to the FDA MedWatch program at 1-800-332-1088 (P), 1-800-FDA-0178 (F), or MedWatch Online.

Ecstasy Use Increases Dramatically

As Emergency Departments swell while suffering the repercussions of the Affordable Healthcare Act, our nation's youth increase their use of mind-altering drugs, in particular, Ecstasy (Mollys).

The number of emergency department (ED) visits related to the use of Ecstasy (MDMA) (3,4-methylenedioxymethamphetamine) has increased by a staggering 128% in just 6 years, new research shows.

Also known as Ecstasy or Molly, a new report from the Substance Abuse and Mental Health Services Administration (SAMHSA) shows that MDMA-related visits among individuals younger than 21 years jumped from 4460 in 2005 to 10,176 in 2011.

In addition, 33% of ED visits involving MDMA use in this patient population also involved alcohol use.

"These findings raise concerns about the increase in popularity of this potentially harmful drug, especially in young people. Ecstasy is a street drug that can include other substances that can render it even more potentially harmful. We need to increase awareness about this drug's dangers and take other measures to prevent its use," Peter Delany, MD, SAMSHA's director of the Center for Behavioral Health and Statistics and Quality, said in a release.

MDMA has both stimulant and hallucinogenic properties. Although it is usually taken by mouth, it can also be snorted or smoked. The drug produces feelings of increased energy and euphoria and distorts users' sense and perception of time.

The report authors also note that the drug can produce a variety of negative health effects, including anxiety and confusion, that can last a week or longer. In addition, it has been associated with hypertension, as well as renal and cardiac failure.

The increase in this population is "a cause for concern due to the serious health risks involved with Ecstasy use and the higher potential for abuse when Ecstasy is mixed with alcohol," the report authors write.

The full report is available on the SAMSHA Web site.

Synthetic Cannabis Linked to Schizophrenia

Synthetic cannabis, often called spice, has become increasingly popular in high schools and on college campuses.  New research has demonstrated that the drug is capable of triggering schizophrenia/psychosis in a certain percentage of people using the drug, at virtually any dose. These episodes of schizophrenia pass when the effects of the drug has worn off, but the long-term effects of this drug remain to be seen. The public must be educated about the use of synthetic cannabis and the risk of developing serious mental illness.  The following newsbrief from Medscape summarizing a presentation from the American Academy of Addiction Psychiatry annual meeting summarizes these findings:

Read more: Synthetic Cannabis Linked to Schizophrenia

FDA approves "game-changer" Hepatitis C drug

Hepatitis C is a chronic, ultimately terminal liver condition.  Liver transplants are often necessary to prolong life.  The medical treatment for this condition is anti-viral drugs.  Recently, the FDA approved an entire new class of drugs to treat Hepatitis C, and it stands to dramatically improve patient outcome.  The following is a news report on this new class of drugs, and the specific drug, Sofosbuvir, the FDA has just approved.

Read more: FDA approves "game-changer" Hepatitis C drug

Raw Milk is Hazardous to Health

In your local health food store or chain market you might come across "raw milk" products.  Recent research has demonstrated that these products might be hazardous to human health.  The following article is a synopsis of a study published in December 2013 issue of Emerging Infectious Disease Journal.

Read more: Raw Milk is Hazardous to Health

Call Emergency Medicine Expert 510-549-1041
Copyright © 2016 - toxicologyexpert.net