The FDA has just announced that a maker of generic Toprol XL will have to recall 109,744 bottles of metoprolol succinate. That could represent a substantial number of pills.
Wockhardt is a large Indian drug maker and it has supplied roughly one-fourth of the metoprolol swallowed each year in the U.S. Although the FDA previously stated that all the generic metoprolol products it had tested passed initial dissolution testing, a new announcement released on May 14, 2014, reveals that Wockhardt’s metoprolol actually failed this crucial test. The implications are significant regarding FDA’s oversight of metoprolol in particular and generic drugs in general.
Let’s start at the beginning of this tale of woe and intrigue. In 2007 we started receiving messages from visitors to this website that a beta blocker heart and blood pressure medicine called Toprol XL was not working as well as expected in its generic form, metoprolol. As more and more complaints poured in, we contacted the FDA about our concerns.
On October 21, 2007, we informed Gary Buehler (the director of the Office of Generic Drugs) and other FDA executives that there was a problem with the generic formulation of this and certain other important medications.
Gary’s response: “We are investigating all aspects of this issue.”
We heard nothing from the agency that year (or in following years) about its investigation into generic metoprolol. Nevertheless, over the last seven years we have continued to receive complaints from patients who maintained that there were generic metoprolol formulations that were not working the same way the brand name Toprol XL did. Here are just a few examples:
“I had been taking Toprol XL for six years with no problems. When the generic (metoprolol succinate) came out, I was switched to that. All was well for a while but then my blood pressure shot way up. I started having dizziness & numbness on the left side of the face. I also had difficulty breathing and anxiety.
“The pharmacist told me that she has heard a ton of complaints about metoprolol succinate and that it is not the same as Toprol XL. She stated that Toprol XL is a time-release formula & metoprolol succinate is not.
“I had my cardiologist switch me back and I started feeling better right away. By the second day my BP was back to normal.” Roger, December 9, 2007
“Generic metoprolol ER is not the same as Toprol XL. My pharmacy gave me generic metoprolol in December and within two weeks I started having irregular heartbeats.” Stephanie, Feb. 12, 2007
“After taking Toprol XL with good results for three years to control cardiac arrhythmias, I was given a generic substitute three weeks ago when I switched pharmacies.
“After taking the daily dosage for five days, I began having more and more arrhythmias to the point of having to be admitted to the hospital. There were no other differences in my daily life.
“After discharge, I returned to the unused brand name drug (Toprol XL) and have had no further problems.” Nancy, March 20, 2007
“I have been taking brand name Toprol XL for quite some time without any problems. Last week, I ran out and my doctor phoned in the refill for a generic prescription. I received metoprolol ER.
“I took it for 7 days. This is absolutely NOT the same. I have a blood pressure cuff that records my last 100 readings. During about the first 12 hours after taking it, my blood pressure was way too low. During about the last 12 hours, my blood pressure was much higher than it ever was. I am on my way now to pick up a new prescription for the brand name, at an additional cost to me, of course.” Debbie, July 5, 2007
“I was recently taking Toprol XL for a heart rate problem called SVT and was doing fine. Our drug coverage changed and the mail order drug company sent me the generic metoprolol succinate ER tabs.
“About a week after starting the generic drug I was awakened at 5:00 am with a heart rate of 188. We went to emergency and they got it under control. This happened 3 times within a four week period and finally my husband and I told the doctor the only thing we could think of that had changed was the generic drug.
“She immediately wrote a new prescription for brand name Toprol XL. I never had another problem.
“I understand the generic is a immediate release and is in the system for about 6 hours and that the Toprol XL is 24 hour time release. I am 54 years old without a blood pressure problem, but someone elderly could have a real serious BP problem on this generic.” Linda, June 26, 2007
We could provide lots more stories about the problems patients have had with generic metoprolol over the last seven years, but by now you get the point.
We have continued to alert the FDA that there was a serious problem with various generic metoprolol products. For people with hypertension, irregular heart rhythms or hypertrophic cardiomyopathy, having a medication that does not work as anticipated could turn into a life-threatening situation. Nearly 40 million prescriptions of metoprolol are dispensed each year in the U.S.
Fast forward to 2014. The FDA recently announced that it would begin testing generic metoprolol succinate…after seven years of our badgering. A recent report from Bloomberg News notes that the agency has received 3,425 adverse incident reports for the drug including “lack of effectiveness,” as well as “troublesome side effects.” In this Bloomberg report the FDA made it clear that in initial tests, generic forms of metoprolol succinate dissolved properly. That seemed to suggest the FDA had tested various products and found they had all passed muster. The way a pill dissolves in a test solution provides some indication how well it will dissolve in a human body.
But that all changed on May 14, 2014. Without a lot of fanfare, the FDA noted that the Indian drug company Wockhardt had a problem with its metoprolol. That prompted the recall of 110,000 bottles of 50 mg metoprolol succinate. Goodness knows how patients and pharmacists will be able to determine which pill bottles need to be returned. Most pharmacies do not put a lot number on the prescription label. Even if you call your pharmacist you may not be able to discover if your metoprolol is part of this recall.
Perhaps even more worrisome is an acknowledgment by FDA spokesperson Sandy Walsh that the FDA is rethinking the criteria it has used for decades for approving generic drugs. We are gratified that the agency is rethinking its procedures, but we worry that there could be hundreds of products on pharmacy shelves that may not be working the way physicians, pharmacists and patients expect.
There was a famous phrase uttered aboard the Apollo 13 moon flight on April 14, 1970: “Okay, Houston, we’ve had a problem here.”
For 25 years we were among the country’s most stalwart supporters of generic drugs. But for the last ten years we have been telling the FDA that we have a problem with some generic drugs. We suspect that there are issues with the FDA’s approval process. We also suspect that there are serious problems with manufacturing quality, particularly in countries like India and China where the FDA does not have adequate personnel to carry out inspections. Over the last few years we have heard about problems with Wockhardt, Ranbaxy and Sun Pharmaceutical, to name just a few. Given that the overwhelming majority of our generic drugs now come from abroad, Americans have a right to be indignant.
If you would like to read more about the details of our investigation into the generic drug problem in America and the FDA’s inadequate oversight, we offer our book, Top Screwups Doctors Make and How to Avoid Them. You will discover the details behind the Budeprion XL 300 debacle and learn what steps you can take to avoid generic drug disasters.
Share your own generic drug experience (positive or negative) below. We are especially interested in metoprolol stories, but please let us know about any generic drug you have taken.