Why Not to be an Early Adopter

(A 13 year old post about blockbuster drugs that came and went - and there have been many others since then!)

New medicines are like new fashions in clothing. They are introduced with great fanfare. Most turn out to seem fairly ordinary after a few years. Some are quickly forgotten or discarded and make us say: “What was I thinking?”

Evaluating a new drug is difficult, for the pharmaceutical and scientific communities as well as for us clinicians. It often takes years of general use before a drug can really prove its safety or usefulness.

As physicians with responsibility for our patients’ lives and well-being, we need to balance our desire to provide the best treatment with our obligation to avoid unnecessary risk. Unfortunately, many new drugs turn out to be less safe than we are told when they are first introduced. The increasingly common sources of drug information, advertisements and pharmaceutical representatives, also don’t tell you what the serious journals say about new medications. It is our duty as practicing physicians to keep up with the leading medical journals.

I may sound old-fashioned at times when I question new treatments or hold off on using them for a while, but I have seen enough new drugs hit the market and soon be withdrawn because of safety issues that were not known or understood when the medicines were first approved.

Most people still remember Vioxx, the arthritis medication that wouldn’t cause ulcers. Early on we heard about high blood pressures and fluid retention. The heart attack risk was apparently kept secret for a while before the drug was withdrawn.

I prescribed a fair amount of Vioxx, because all the other arthritis medications could also cause fluid retention and Vioxx seemed to work quite well. I had also almost lost a patient to a sudden intestinal hemorrhage from indomethacin once, so the stomach safety seemed like a valid selling point.

Before Vioxx, there was Duract, an anti-inflammatory pain medication for short-term use. It was eliminated through the liver instead of through the kidneys, like other anti-inflammatory medications. I never had time to prescribe it. I held off, because it was a new type of drug, and it was soon withdrawn amid reports of liver failure.

Some medications for Type 2 Diabetes bother me. Rezulin was the first drug in a new class, which makes the body more sensitive to its own insulin. Before I had warmed up to prescribing it, the drug was withdrawn. It was linked to liver toxicity. The two newer drugs in the same class, Avandia and Actos, seem safer on the liver, but from early on, there were concerns over fluid retention and heart failure risk. In 2007 Avandia was shown to increase heart attack risk by over 40%. Actos has so far looked safer, but I am still very nervous about it.

When the Scandinavian Simvastatin Survival Study (4-S) showed that deaths from heart attacks could be reduced by 30% with Zocor, I felt fairly comfortable prescribing it for patients with high cholesterol.  I had not really used the statin drugs that came before it, because there was no proof they reduced heart disease risk. I was still cautious with Zocor, because the cholesterol-lowering drug that came before the statins, Atromid-S, was associated with a surprising and unexplained increase in death rates by over 40%.

With every statin drug that came after Zocor, I stubbornly waited for “outcomes data” of some sort. One by one, the newer drugs proved themselves to fight atherosclerosis and heart disease, and I have ended up using all of them.

Baycol came along and made claims of having less risk for muscle damage, rhabdomyolysis, than the other members of the class. I tried it, but as it didn’t have outcomes data yet, I reserved my use of it to patients who couldn’t tolerate the other statins. Ironically, Baycol was taken off the market because it had a much higher risk of rhabdomyolysis than the other statin drugs.

I have seen many new drugs come and go, from diet pills like Redux to antibiotics like Omniflox, Tequin and Ketek during my thirty years in medicine. I also vividly remember the Thalidomide-induced limb deformities of my classmate in Junior High School in Sweden. Thalidomide was marketed there as a safe drug for morning sickness.

One of my professors in medical school said about medications for high blood pressure that they needed to have no serious or annoying side effects and be less dangerous than the condition for which they are intended. I have held on to his wisdom all these years.

A patient with an acute, life-threatening condition may be very willing to accept a certain risk if the treatment is effective. Even an unproven treatment may be the best option when older treatments are known to be risky or not very effective.

I question the value of being an early adopter of new drugs under normal circumstances, when slightly older drugs are still useful. Why use our patients for guinea pigs?

(Here’s a list of drugs withdrawn from the US market.)