New Weight Loss Drug on the Market

OverweightFor the last 13 years there have been no new medications designed specifically for weight reduction that have received FDA (Food and Drug Administration) approval. The long drought came on the heels of the reported adverse effects of the successful weight reduction combination of phentaramine and fenfluramine. While patients lost weight successfully on this combination of medications plus diet they additionally risked developing disease of the heart valves and its consequences. In July the FDA approved Belviq or lorcasrin HCl for weight reduction. Pharmaceutical manufacturer Vivus received approval for its weight reduction product Qsymia recently which is a combination of phentermine and topiramate. Topiramate has been on the market as a medicine to treat vascular and migraine type headaches and to treat seizures.

Vivus submitted data to the FDA involving 756 obese subjects, which showed that over seven months of treatment obese patients lost 10% or more of their body weight 38% of the time among those taking Qsymmia 7.5 /46 mg and 43% of the time when they used the higher dose of 15/92 mg. Patients taking placebo plus diet lost 10% of their body weight only 6.8%. The dose of topiramate in this combination drug is significantly lower than the starting dose for that drug when treating neurological issues. When the researchers looked at statistical significance the lower dose combination was actually more successful than the higher dose combination.

Adverse effects were more common in the higher dose group and included parasthesia (23%), dry mouth in 18.5%, headache and constipation. The drug was released to a limited number of pharmacies in April but has been slow to catch on. Its use is cautioned in individuals with existing heart, liver and kidney disease.

Obesity is epidemic in this country. Increased activity and dietary intervention are always our first line of therapy. Dietary counseling, organized diet programs with meal replacement therapy and bariatric surgery are available to help. Adding new medications to a difficult treatment problem is always a welcome step but will require that we closely watch their risk and side effect profile as the drugs become more popular and are used more frequently.

Pradaxa: More Concerns. More Myocardial Infarctions?

Pradaxa is part of a new group of anticoagulants (thrombin X inhibitors) that eventually will allow anticoagulation by the pill route without requiring patients to alter their food and medication intake and avoid foods and medications that interfere with the anticoagulant as patients must do with Warfarin. Pradaxa additionally eliminates the need to take blood tests (INR/ PT) to monitor the dosage as one has to do with Warfarin (Coumadin).

There is a large commercial advertising campaign underway on TV and print media to encourage patients with atrial fibrillation to ask their doctors to switch them from Coumadin to Pradaxa (Dabigatrin).  The campaign bases its claims on the RE-LY trial of 18,000 patients at 80 medical centers throughout the world who took the 150 mg dosage and had significantly fewer strokes than patients taking Warfarin.  The original study was criticized because many of the patients in the Warfarin (Coumadin) group were not on enough Warfarin or at a therapeutic PT/INR to prevent embolic strokes so the comparison with Pradaxa may not be valid. Another criticism involved the fact that Pradaxa can cause major bleeding and there is no antidote to stop the bleeding. Patients on Pradaxa who are bleeding are advised to undergo hemodialysis to remove the drug from their system because there are no medications or treatments available to stop Pradaxa related bleeding.

One wonders how the Food and Drug Administration approved this product for general use under these circumstances without conducting further testing?  The issue becomes even more confusing with the addition of data presented by Ken Uchino, MD, and Adrian Hernandez MD, PhD of the Cleveland Clinic in the online version of the Archives of Internal Medicine. They claim that by reviewing the RE-LY data there is a 38% relative increase in the risk of a myocardial infarction (MI) or heart attack in the Pradaxa group. In an accompanying editorial in the same journal, clinicians at the Hadassah- Hebrew University Medical Center in Jerusalem wrote, “The robust finding that Dabigatran is associated with increased rates of MI (heart attack) is alarming and emphasizes the need for continued critical appraisal of new drugs after phase III trials.”

In my practice I generally will not switch to a new or controversial medication until it has been on the US market for at least one year. I make exceptions for orphan drugs, products to treat incurable diseases with no other choices available. The 12 months gives the medical and scientific community a chance to see how the medication performs and what unexpected adverse effects may be associated with it.

Thrombin X inhibitors are the wave of the future. With no way to stop the bleeding, and data on their safety and efficacy still accumulating, they are just not ready for prime time yet.

Higher Death Risk with Dietary Supplements

The vitamin, mineral and herbal supplement industry in the United States has been so effective in marketing that currently 50% of adults regularly consume their products.  Traditional health care advocates have believed that a well balanced varied diet rich in fresh fruits and vegetables, appropriately prepared, will provide all the nutrients, Co-enzymes and anti-oxidants that you need.

A recent article in Medpage Today cited the long-term study of Jaakko Mursu, PhD, of the University of Eastern Finland which states that dietary supplements are linked to a higher death risk. The use of multivitamins and vitamin B6, folic acid, iron, magnesium, zinc and copper supplements was associated with a greater “all cause mortality” during the 19 years the study was in progress.

Mursu evaluated the use of vitamin and mineral supplements among 38,772 post-menopausal women participating in the Iowa Women’s Health Study. Initiated in 1986, the average age of the participants in the study was 61.6 years.

“Based on existing evidence, we see little justification for the general and widespread use of dietary supplements.” stated Mursu.  “Calcium supplementation, on the other hand, was associated with a lower risk of death.”

The Food and Drug Administration does not require manufacturers of these products to reveal their efficacy or safety.  At this point I will continue to recommend a balanced, healthy and well prepared diet to my patients with avoidance of supplements unless we can demonstrate safety and efficacy.

Generic Drugs- Small Government and Less Regulation Lead to Lack of a Safety Net in Production

Years ago under pressure from consumer groups, Congress dramatically reduced the time a drug manufacturer could retain a patent on a brand drug.  The patent was reduced from 21 years from release of the product after FDA approval to 7 years from the time development begins. The extremely short window of opportunity to research and develop new medications led to extraordinarily high prices for the new medications. The law met its intended result of encouraging the rise of copy cat less expensive generic drugs.

At the same time under the Reagan Administration, the Food and Drug Administration closed its research and evaluation labs for testing new pharmaceutical products before they can be released to the American public. Under the new laws, pharmaceutical manufacturers now can contract with outside labs to test their products and the reports are then submitted to the FDA for review and approval.  No longer did a drug company have to submit its actual product to the FDA for their independent testing and approval or denial.

The results of these two pieces of government de-regulation was the rise of generic pharmaceutical manufacturing plants in remote regions of China , India and Asia with the most reliable and technologically advanced plants in Israel. Generics needed to prove to the FDA that they possessed 85% of the bioavailability of the brand product in reports generated by contracted labs and sent to the FDA for the products approval.

For years I suggested to my patients that if they could afford the brand name they were best served paying the higher price to obtain a product they knew was produced locally with relatively high standards.  The NY Times on Saturday August 13, 2011 ran a front page article noting that over 80% of generic products are produced in “shadowy” foreign factories that have never ever been inspected.  Several years ago 81 individuals perished because Chinese manufacturers substituted cheaper and tainted products in the making of the anti coagulant heparin. Counterfeit packaging and products originating with the Russian mob proliferate throughout the world market and are difficult for experts to distinguish from the real thing.

It appears that the Obama administration has finally reached an agreement with the generic drug industry for the industry to pay for government inspection of their facilities every few years. The legislation may pass through Congress this fall.

My suggestion to my patients remains the same. If you can afford the brand product purchase it. Know where your pills come from. Demand that your Congressional elected official works to fund the FDA so it can reopen its research and evaluation lab and be the independent agent determining the safety and efficacy of the drugs we are prescribed. Consider extending the length of a patent on new products in exchange for lower pricing on brand name drugs. It’s time to stop allowing only market forces to be watching out for the safety of our medications. That’s like asking the fox to watch the hen house.