Which metoprolol succinate is best: a Cleveland Clinic doctor's advice

Since I discovered that the metoprolol succinate that I buy at my local pharmacy is made by Cadila Healthcare in a plant in India that has been warned repeatedly by the FDA to clean up its act I have been wondering what alternate supplier to specify.

Dr. Harry Lever is the Medical Director for the Hypertrophic Cardiomyopathy Clinic at the Cleveland Clinic. He published "A Physician’s Perspective on Generic Drug Quality" in the Journal of Managed Care & Specialty Pharmacy, May 2020.

An excerpt from his published piece follows. It turns out that Dr. Lever started noticing problems with metoprolol succinate in his practice years ago.

"Another problematic drug in my practice is the beta blocker metoprolol succinate, which is a sustained release drug for the treatment of patients with hypertrophic cardiomyopathy, as well as angina pectoris and hypertension. This drug is particularly hard to reproduce because it is a sustained release formulation and the proprietary information about the original formulation is not available to generic manufacturers. For many patients, I have found that only the authorized generic or the name brand drug work consistently.

As the physician responsible for the care of my patients, the question I am too often left with is this: Am I dealing with a patient whose disease is simply not responding to medical treatment or with a poor quality drug? In addition to putting patients unnecessarily at risk, this increases the cost of care, which would appear to be the antithesis of what managed are is supposedly all about. Case in point: hospitals in the United States pay fines to the Centers for Medicare & Medicaid Services when Medicare patients are readmitted within 30 days of discharge for heart failure.

When I recognized that there was a clinical problem with metoprolol succinate made by the Indian manufacturer Wockhardt, I reported it to the FDA. I was told they would investigate my concerns and get back to me. It took them 18 months to do so, and when they finally did, I was told there was no problem. After reading Bottle of Lies, however, I learned that an FDA inspector was in the plant 7 months after I wrote my letter and had found severe problems. About 3 months after I received the FDA letter, it was then reported in the press that indeed there was a problem with this generic version and it was removed from the market because of dissolution problems."

I found a video with Dr. Lever where he was asked (minute 32:42) what version of metoprolol succinate does he prescribe for his patients now? He said "I use Lannett, which is an authentic generic actually made by Astra Zeneca which is the originating drug company. The formula is exactly the same". He also said if you can find the Aralez version, that is one he would also use.

I have just started to learn to be wary of prescription drugs. I had not realized there were such things as "authentic generics", or "authorized generics". The FDA has a page that explains.

I was first prescribed Tambocor (flecainide) on demand in 2004, about the same time as it went off patent. As my usage was infrequent, I still had pills left after four years. I got more flec through a European Broker, goldpharma.cn (they broker through individual pharmacies in Europe). I would purchase "Apocard" which is made by Meda Pharma for sale in Spanish speaking countries. Meda sells it as Tambocor in English speaking countries. One thing I liked about is the pills came in a blister pack, so very little oxidation. In June of 2021, I tried some US sourced (but likely not produced) generic flec for an on-demand conversion. It took twice as long as the Apocard ever has. Now this could be a random event, but it convinced me to go to the effort of sourcing the branded product. As I pay cash, getting insurance to pay is not one of my priorities.

Susan.d has mentioned an Israeli pharmacy that sells Tambocor branded flec. I've not found that Tambocor is available in the US.

For me, getting branded Tambocor or Apocard is now a priority.

It seems the European Union is ahead of the US in attempting to deal with low quality imported prescription drugs. See: The European regulatory system for medicines.

"Every batch of medicines must be certified as having been manufactured and tested in accordance with GMP and in conformance with the marketing authorization before it can be released onto the market in the EU. If the product is manufactured outside the EU and has been imported, it needs to undergo full analytical testing in the EU, unless a mutual recognition agreement (MRA) is in place between the EU and the exporting country."

(GMP is Good Manufacturing Practices, the regulations drug manufacturers must follow to ensure the production of quality drugs. An MRA, or Mutual Recognition Agreement allows countries to accept other countries inspections of manufacturing facilities and products to be as good as their own. It depends on how they enforce their laws, of course. There is no MRA between the EU and India, or China. A Canadian Senate Committee issued a report stating they were intrigued when they heard about batch testing imports as practiced in the EU, and there is a pilot program going in Canada to see how difficult this would be for Canada to do.)

Thank you for this information, and the link to the FDA site explaining generics.

I found this to be interesting: "Because an authorized generic drug is marketed under the brand name drug’s New Drug Application (NDA), it is not listed in FDA’s Approved Drug Products With Therapeutic Equivalence Evaluations (the Orange Book)."

1. What reference source provides a list of authorized generics and its corresponding NDC number?
2. What reference source provides a list of the original manufacturer of a drug (brand name; patent holder)?
3. What is the most efficient and least time consuming way to find out which pharmacies carry Lannett or Aralez?
4. What reference source, FDA or otherwise, provides information on companies, manufacturers, and distributors, who have been in violation of FDA rules & regulations, with details on each situation and the resolution, i.e. fines, sanctions, cease & desist, etc...?

I appreciate any information you may be able to provide.

I found the answer to one of my questions within the same FDA page:

Listing of Authorized Generic Drugs

"As part of their required annual reports, NDA holders must notify the FDA of any authorized generic drugs marketed under their approved NDAs. FDA publishes a list of reported authorized generics and updates that list quarterly."

I found information on FDA warnings by typing into Google: "manufacturer's name, FDA warning" and looking at the webpages that came up. The easiest to digest information would be news articles. A news article about the impact on a drug manufacturing company of an FDA warning might discuss the history of the company in relation to the FDA, some details not contained in the FDA warning, also include a link to the FDA warning. If I wanted to confirm exactly what the FDA said I would go there.

To get the manufacturer's name I looked on the label on my bottle of pills. There is an NDC number on the label of every bottle of pills sold in the US. I then went to a National Library of Medicine webpage and entered the number in a search box, as described in this post.

I haven't figured out how to get an NDC number any other way other than to look on my bottles of pills, yet. I also haven't figured out an easy way to find out where to get a specific manufacturer's drug, except by calling around to pharmacies one by one.

For metoprolol succinate I decided to follow Dr. Lever's advice, i.e. get Lannett. But I haven't found a source yet - I haven't really been looking though. I've been looking for good source for synthetic thyroid hormone first.

Just FYI, a reply to my emailed question to the FDA re: metoprolol succinate:
_________________________

Thank you for writing to FDA. Your email was forwarded to the Division of Drug Information, in the FDA's Center for Drug Evaluation and Research, for assistance.

It appears from a search of our NDC Directory (https://www.accessdata.fda.gov/scripts/cder/ndc/index.cfm), labelers for the authorized generic of metoprolol succinate include A-S Medication Solutions and Aphena Pharma Solutions – Tennessee, LLC, Bryant Ranch Prepack, and Proficient Rx LP.

Best regards,


Drug Information Specialist
Division of Drug Information
Center for Drug Evaluation and Research
Tel: 855-543-DRUG (855-543-3784)
druginfo@fda.hhs.gov

I have been making a few calls about the following drugs: Rosuvastatin (generic Crestor), Metoprolol Succinate ER and Diltiazem extended release CD. I was not very successful finding a manufacture that was not in India.. This is so frustrating, isn’t it? I need refills soon. Any help on these 3 drugs would be appreciated.

Rob, I don’t completely understand what the Drug Information Specialist is telling you . Also, what FDA page are you referencing for the listing of authorized generic drugs you mention in your post.

My head is spinning thinking of all of this. I found the article from the Cleveland Clinic physician quite disturbing!

Oh, I reread the posts and found the FDA page regarding the authorized generic drugs.



Edited 1 time(s). Last edit at 01/25/2022 05:57PM by Pixie.