Monday, June 23, 2014

Another Metoprolol Recall Reveals the Dark Side of Generic Drugs

Here we go again: another generic metoprolol recall from an Indian drug company. The FDA announced problems with Dr. Reddy's metoprolol succinate 25 mg extended release tablets and the company is in the process of recalling 1,356,000 pills.
What is going on with this heart medicine?
Toprol-XL (metoprolol) is a beta blocker in the same family as atenolol and propranolol. Tens of millions of people swallow beta blockers every day to control heart rate, reduce the risk of a second heart attack, prevent migraines and ease the pain of angina. These medications may also lower blood pressure.
The original brand name medicine was developed under the name Lopressor and was an immediate release product. That means it had to be taken up to four times daily. That was inconvenient for many people. The extended-release formulation, Toprol-XL, was approved in 1992 and was given once daily, making it far more patient friendly.
We first suspected that there might be problems with generic extended release metoprolol succinate in 2007. Readers of our newspaper column and visitors to our website began reporting therapeutic failures when they were switched from Toprol-XL to metoprolol succinate. Here are just a few of their reports:
"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


On October 21, 2007, we wrote to alert the FDA and its Office of Generic Drugs about the problems patients were reporting with this medication. We were told, in essence, "We'll get back to you." We heard nothing more.
Over the last several years there have been a number of recalls of generic metoprolol. In 2008 the FDA warned Sandoz that its formulation of metoprolol succinate had not been properly validated. There were dissolution problems. In other words, it didn't dissolve properly in a test solution. Sandoz recalled its generic formulation of metoprolol that year.
In 2009, Ethex, a subsidiary of KV Pharmaceutical, also got into trouble with its extended-release metoprolol. The company eventually pleaded guilty to felonies of failing to notify the FDA about manufacturing problems with a variety of medications.
Fast forward to 2014. In May, a large Indian drug manufacturer called Wockhardt had to recall 109,744 bottles of its metoprolol succinate. This company had two of its manufacturing plants shunned by FDA in 2013. Violations in manufacturing meant that products from these facilities could not be exported to the U.S. One of the plants made metoprolol succinate. Until these discoveries, Wockhardt provided one fourth of the metoprolol swallowed by Americans.
Now we are told that another Indian drug company, Dr. Reddy's Laboratories, also has problems with its metoprolol succinate. It is in the process of recalling 13,560 bottles from the U.S. market. This involves 25 mg tablets from lots C206578 and C207415 (NDC 55111-466-01). In both the Wockhardt and Dr. Reddy's recall of metoprolol the problem was dissolution. That is, the formulations were not releasing the active ingredient according to FDA specifications.
But here is the rub. Although the FDA considers the Dr. Reddy's recall important (Class II, which means "a situation in which use of or exposure to a violative product may cause temporary or medically reversible adverse health consequences") it is doing little to alert patients. Pharmacies are supposed to stop dispensing such products and return them to the company. But patients who have Dr. Reddy's metoprolol succinate 25 mg pills, even if they are in the recalled lots, are supposed to keep taking them. Huh? Does that make any sense?
Even if you wanted to check on your bottle of pills to see if it was included in the recall, the chances are very good that you would not find a lot number. That's because most state pharmacy rules do not require lot numbers on repackaged pill bottles. Why is it that there are lot numbers on all over-the-counter medications, soup cans and cereal boxes but rarely on a prescription bottle of generic pills? Does that make any sense to you?
Here are some more recent complaints about metoprolol from visitors to our website:
"My metoprolol was usually a small, white, tapered pill. My prescription was refilled with one that was white and aspirin-shaped. After taking only a couple, I experienced an irregular heartbeat.
"I called the pharmacist and she exchanged the round pills. The problem stopped. When I told my previous doctor what had happened, she said, 'That couldn't happen.' I said, 'The pharmacist said it could.'
"Later my drugstore ran out of the small white tapered pill. I was sent to another drug store to get it refilled. I told the pharmacist what had happened and he said, 'Of course that happened; the round pill is not time release.'"  E.T., May 16, 2014

"After having a bad reaction to a generic metoprolol in 2007, I began using the AstraZeneca original (Toprol-XL) and then switched to the PAR extended release generic, which is the one authorized by AstraZeneca. It's more expensive than other generics but I've always done well with it (50mg/day), so for me it's well worth the money. To my knowledge there's never been an issue with this generic, but I look forward to PP corroborating that." Gerald, May 16, 2014

"I too had cardiac problems after being on metoprolol for a few years. My GP refused to believe I had problems from the medication. Eventually I was hospitalized. The cardiologist stated that if I had not come to the hospital via 911, I would not have survived."Marjorie, RN, BA, May 26, 2014

Were this the only generic drug recall in recent years we would not be terribly worried. Unfortunately, dozens of different generic drugs have been recalled. We were instrumental in identifying the problems with generic versions of the antidepressant Wellbutrin XL 300. A generic product called Budeprion XL 300 was eventually withdrawn after we bugged the FDA for years because of reports of generic drug failures by visitors to this website. A different bupropion XL 300 was also withdrawn with little fanfare from the FDA.
To learn more about this tale of woe and intrigue, check out of book, Top Screwups Doctors Make and How to Avoid Them. It provides our "Top 10 Tips for Taking Generic Drugs," since insurance companies virtually force most Americans to buy generics. We're not against generic drugs, but we wish the FDA would do a better job both approving bioequivalency and monitoring foreign manufacturers. In the meantime, people will have to take steps to protect themselves. We hope our tips for using generic drugs safely will help.
Share you own generic drug story, positive or negative, below.

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