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Metoprolol Mess (Toprol XL) Reveals Serious Flaws With FDA’s Generic Process

We've been hearing about problems with generic metoprolol since 2007. They're still coming in. If you can't afford Toprol XL what can you do?
Metoprolol Mess (Toprol XL) Reveals Serious Flaws With FDA’s...

We have been writing about problems with generic metoprolol for more than a decade. This beta blocker is prescribed for patients with hypertension and heart problems such as angina pectoris, heart failure, rapid pulse and/or irregular heart rhythms. The drug was originally sold under the brand name Lopressor. A sustained-release formulation, Toprol XL, was introduced in the US by AstraZeneca in 1992.

The Secret of Sustained-Release Screwups:

What very few physicians, pharmacists or patients realize is that sustained-release formulations are unique. They are designed to gradually release the active pharmaceutical ingredient (API) over time.

We suspect that many health professionals think that when a drug loses its patent the secret sauce is revealed to the generic drug companies so they can duplicate the brand name product exactly. Au contraire.

The way the brand name manufacturer makes its pills is a deep, dark secret. Coca-Cola does not reveal its formula to other soft drink makers and brand name pharmaceutical manufacturers do not share their secrets with generic drug companies.

We learned about this because of the antidepressant Wellbutrin XL 300. This brand name medicine releases its active ingredient, bupropion, gradually over many hours. Even after the patent was lost on the API bupropion, the brand name manufacturer retained the patent on the special membrane formulation technology.

The generic products had to come up with a different kind of formulation. The matrix some companies developed released the active ingredient differently and that led to all sorts of complications. You can read about the scandal we uncovered at this link.

Generic Toprol XL (Metoprolol Succinate) Creates Confusion:

When AstraZeneca developed its brand of metoprolol succinate, it created a unique polymer microencapsulation process to deliver the active drug gradually. The XL in Toprol XL stands for extended release. We suspect that some generic drug manufacturers have had problems coming up with their own gradual release formulation.

In 2007, we started receiving messages from visitors to this website that generic metoprolol was not working as well as Toprol XL had. As more and more complaints poured in, we contacted the FDA about our concerns.

On October 21, 2007, we informed Gary Buehler (then 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.”

FDA Inaction on Generic Toprol XL (The Metoprolol Mess):

We heard nothing from the agency that year (or in following years) about its investigation into generic metoprolol. Nevertheless, over years we 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 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

Fast Forward to October, 2021:

We recently received this message from a visitor to this website:

Q. I’ve been taking metoprolol for about ten years. For a long time, I took one particular generic and it worked fine. Then the pharmacy switched suppliers. After a few doses, my arrhythmia and rapid heartbeat started to recur.

Now the cardiologist’s office is trying to get my insurance to authorize brand name Toprol XL, so I can take something that will work. Why are we expected to use generics that are low quality? I “Googled” the maker of my current generic metoprolol. They have had numerous recalls.

A. Over the years the FDA has announced numerous recalls of metoprolol succinate. At one point, the large Indian generic drug maker, Wockhardt, supplied roughly one-fourth of the metoprolol swallowed each year in the U.S.

We have continued to alert the FDA about serious problems 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.

Adverse Reports Around Metoprolol

A report from Bloomberg News noted that the agency had 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.

Perhaps even more worrisome was an acknowledgment by FDA spokesperson Sandy Walsh that the FDA was 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.

BOTTOM LINE:

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 20 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. That is especially true now that FDA inspectors have been curtailed in their foreign inspections due to COVID-19.

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.

Is There A Trustworthy Generic Metoprolol?

Because we have heard about many generic drug problems over the years we often recommend “authorized” generic products. These can be drugs that are made by the original brand name company on their own production lines but then licensed and sold to a particular generic drug distributor. In other situations the brand name company reveals the special sauce so that the generic company can duplicate the brand name formulation exactly.

A cardiologist colleague tells us that New American Therapeutics is selling generic metoprolol made by AstraZeneca, the original brand name manufacturer of Toprol XL. Getting your pharmacist to stock the New American Therapeutics metoprolol could be a challenge, though.

To learn more about authorized generic drugs and affordable brand name medicines from legitimate Canadian pharmacies, check out our eGuide to Saving Money on Medicines. This electronic resource is available under the Health eGuides tab.

Please 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.

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.” .
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