Notable Rise In Adverse Drug Reactions

In This Issue:

NOTABLE RISE IN ADVERSE DRUG REACTIONS
Most notable: Painkillers and drugs used for arthritis modify the immune system.

According to the Archives of Internal Medicine, the number of serious adverse events and death attributed to prescription medications has TRIPLED since the FDA made it easier to report significant side effects:

20% of drugs accounted for 87.1 percent of adverse side effects and the largest element of these were painkillers and drugs used to treat arthritis.

Fiddling with statistics, one quarter of the increase could be attributed to an increase in prescriptions with another 15 percent to the introduction of new biotechnology drugs available since 1998, but the rest of the increase cannot be explained away.

Experts admit they are losing ground in terms of drug safety. Both the FDA and a trade group representing drug makers agreed that the number of adverse events had been increasing. Studies estimated that from as few as 3 percent of adverse events to a maximum of about 33 percent were reported to the FDA. What that means is that there are statistically significant large numbers of adverse effects that are unreported (67 to 97%!).

Must of the information has been gathered through the “Adverse Event Reporting System” available online from the FDA, commonly known as “MedWatch” reports. Physicians and the public submit reports to the FDA or to the drug makers who are required to forward them to the FDA.

Here’s the FDA site: http://www.fda.gov/medwatch/report/hcp.htm

If you take prescription drugs and wonder about combinations, a good resource to get information is: http://medlineplus.gov/

You can discover for yourself lots of information about unsafe drugs that now may be in class action-type litigation or recalled as “unsafe.” Use keys words that relate to prescription drug class action lawsuits, or use the drug by name. Oxycontin problems (underreported addiction by the manufacturer) recently made class action headlines.

Here are a few in the news:

• Avandia (resogilitazone)
Avandia, generically known as rosiglitazone, is a drug used to help Type 2 diabetes patients with insulin resistance. Manufactured by GlaxoSmithKline, Avandia is in the thiazolidinedione (TZD) class of drugs, which are the first class of medications designed to reverse the basic problem in Type 2 diabetes of resistance to insulin. In May 2007, the New England Journal of Medicine published an analysis linking Avandia to increased risk of heart attacks. The meta-analysis reviewed 42 studies and found patients taking Avandia to be at a 43% higher risk of heart attacks.

• Permax (pergolide), Dostinex
Permax and Dostinex are drugs from a class of medications called ergot-derived dopamine receptor agonists and used in the treatment of Parkinson’s, restless leg syndrome, and migraine headaches. Other ergot-derived dopamine receptor drugs include the now banned diet drug Fen-phen, and all are associated with heart valve disease. Permax (pergolide) has been found in studies to make a patient five to seven times more likely to have leaky heart valves than those patients who use other drug therapies for Parkinson’s. Dostinex (cabergoline) has only been approved for sale in the United States to treat hyperprolactinemia, a condition in which excessive amounts of the hormone prolactin enter the bloodstream due to benign tumors of the pituitary gland.

It has been shown in two studies that Permax and Dostinex interact with a receptor in the heart valve, causing the valve to overgrow and become floppy and leaky. Of the two, only Permax currently has a black box warning addressing the increased risk of heart valve problems in patients.

• Keteck (telithromycin)
Ketek® is a prescription antibiotic drug made by Aventis Pharmaceuticals and known generically as telithromycin. Ketek is in a class of drugs called ketolide antibiotics, and is used to treat bacterial infections in the lungs and sinuses. Ketek has been associated with adverse side effects such as liver damage, liver disease, liver failure, and hepatitis.

• Fosamax (alendronate)
Fosamax is Merck’s osteoporosis management drug, generically known as alendronate, which is part of a class of drugs known as bisphosphonates. Fosamax is used to treat osteoporosis and bone pain caused by some cancers. Recent studies have shown a possible link between using Fosamax for osteoporosis and developing osteonecrosis of the jaw. Osteonecrosis, or ONJ, is the destruction of bone tissue, sometimes associated with interference of the blood supply to bone. Osteonecrosis of the jaw can be very painful and may lead to other complications such as infection, breakdown of the jawbone, ulcerations in the mouth, non-healing wounds, and osteomyelitis (inflammation of bone marrow). Once necrosis begins, it is irreversible. Merck was advised by the FDA in 2004 to include a warning in the drug label but failed to comply until almost a year later.

• Tequin (gatifloxacin)
Tequin is an antibiotic in the fluoroquinolone class of antibiotics, generically known as gatifloxacin, and made by Bristol-Myers Squibb Co. Normally used to treat lung, sinus, and other bacterial infections, the label, or package insert, for Tequin has been changed several times to strengthen the warnings about associated risks of hypoglycemia (low blood sugar) and hyperglycemia (high blood sugar), which can lead to coma or seizure, and are potentially fatal.

• Bextra (Study Results Link COX-2 Painkillers Vioxx, Celebrex, and Bextra to Heart Attack and Stroke)
Bextra® is the name under which Pfizer markets a prescription pain medication generically called valdecoxib. Bextra has been under much scrutiny of late because studies have shown adverse reations with Bextra such as heart attack, stroke, sudden cardiac death, Erythema Multiforme (EM), Stevens-Johnson Syndrome (SJS), and Toxic Epidermal Necrolysis (TEN). Cases of Stevens-Johnson syndrome and toxic epidermal necrolysis caused by Bextra use have been reported to the FDA. Stevens-Johnson syndrome — commonly referred to as Stevens-Johnson or SJS — and toxic epidermal necrolysis, or TEN, are closely related serious skin reactions.

• Crestor (rosuvastatin)
Crestor® (rosuvastatin) is a statin drug used to lower cholesterol by inhibiting production of an enzyme in the liver, much like the recalled drug Baycol. Crestor is uniquely distinguished from the other five statins on the market because of its potential for kidney toxicity. During clinical trials, patients taking the 80 mg dose of Crestor began to show signs of muscle weakness, early symptoms of rhabdomyolysis, and kidney damage. A new analysis of post-marketing safety reports suggests that patients using Crestor (rosuvastatin) are more likely to develop serious side effects than patients taking Lipitor (atorvastatin), Zocor (simvastatin), or Pravachol (pravastatin).

Bottom line: We are all at risk taking any form of prescription drug. It is important to be informed of the potential problems involved with drug use, then to weigh the positives and negatives carefully.

But of course, not all dangers come from these newer drugs. One of the most dangerous, is available OTC (Over The Counter):

A major health issue which has been with us for many decades, is the toxic effects (primarily liver toxicity) of Acetaminophen (Tylenol®), and whether in non-prescription or prescription form, it can be deadly. When used as a component within common Hydrocodone/Oxycodone and similar narcotic prescription pain killers such as Lorcet®, Lortab®, Norco®, Vicodin®, and Percocet®, just to name a few, it helps boost the pain reducing effects, without having to use a more powerful narcotic dose. Typically, when used as prescribed, the Acetaminophen dose in these preparations remains below the levels which are considered hazardous. However, when these pain killers are abused, not only do they present obvious addiction problems, but also present a serious risk of poisoning. In abuse situations, the lower-level narcotic dose preparations, tend to present an even higher risk. This is because the abuser tends to take an even larger quantity of these low-dose preparations, in order to increase the narcotic dosage, but in doing so, they quickly overdose on Acetaminophen.

Of course, virtually any substance we ingest can become toxic in the right dose; salt, sugar, even water in excessive amounts, are dangerous or even deadly. One of the main problems with Acetaminophen, is that it has one of the narrowest thresholds of any OTC pain killer, meaning that the range between what is considered a safe dose, and what is considered toxic, is very small indeed. The maximum recommended dose is no more than 1000 mg every 4 hours – no more than 4000 mg per day.

In a prescription form, take Percocet® for example, a number of dose combinations are available, from Percocet 2.5 mg/325 mg, to Percocet 10 mg/650 mg, where the first number is the dose of Oxycodone, and the second number is the Acetaminophen dose. In all its variations, the highest dose of Acetaminophen actually comes in the mid-level preparation (the Percocet® 7.5 mg/500 mg preparation), where the 8 tablet maximum daily dose delivers 4000 mg of Acetaminophen, while the lowest and highest dose preparations max out at 3900 mg per day. Any abuse of these or similar Hydrocodone/Oxycodone and Acetaminophen preparations — TAKING JUST ONE PILL OVER THE RECOMMENDED DOSE — represents a significant hazard in Acetaminophen toxicity, while a 50-100% increase over the recommended dose can produce fatal consequences within a very short duration of abuse.

Acetaminophen is an alkoloid which is processed mainly by the liver, and overdose is one of the most common poisonings worldwide. People often think that Acetaminophen is safe, because it is commonly found in non-prescription OTC remedies, and generally speaking, it is safe when used as directed, but in higher doses (or when abused), whether as a component of a more powerful narcotic pain killer, or in its standard non-narcotic OTC version, it can cause irreversible liver damage with fatal consequences. Moreover, people who take Acetaminophen containing medications in conjunction with alcohol (which increases the strain on the liver), or for those with existing liver diseases like cirrhosis, the risk of further and more serious liver damage increases almost exponentially.

“Acetaminophen toxicity is the number one cause of hospital admission for liver failure in the United States”

Dr. David D. Moore – Baylor College of Medicine