In search of cheaper and/or better drugs

I’ve been researching prescription drugs these days. My original idea was to come to some sort of understanding as to whether it was a good idea to buy a generic drug that is made in India from a Canadian online pharmacy.

Then my doctor called to say my TSH blood test for thyroid stimulating hormone showed something was wrong. She thought either I was taking the pills at the wrong time, or that the dose needed to be adjusted.

A wrong dose of levothyroxine can contribute to A-fib, or even cause it. After more than 3 years in remission, I’ve had two episodes of A-fib. I’m interested in doing whatever I can to avoid having to get involved with AADs or an ablation.

My research into prescription drugs had indicated that FDA inspectors are having trouble keeping up with a globalizing prescription drug industry. I wondered, maybe the pills are being shipped with an inconsistent active ingredient.

The US National Library of Medicine runs an online database of drug information where you can often find out where a drug is manufactured

I found the NDC number from the label on my bottle of levothyroxine:



I entered the NDC number into the search box. I clicked on the download PDF link on the page that came up. I searched the pdf using ctrl-F on “manufactured”.

My Levothyroxin is made by Lupin, in Pithampur, Madhya Pradesh, India.

I happened to have just read “Bottle of Lies” by Katherine Eban.

The book explains in gory detail why a very large Indian pharmaceutical company, Ranbaxy, was able to deceive and stall the FDA for many years, years ago. The book made it clear that it wasn’t just Ranbaxy, it was the entire pharmaceutical industry culture in India, combined with the inability of the FDA to deal with the situation.

From the inside cover of the book:

“Eban reveals an industry where fraud is rampant, companies routinely falsify data, and executives circumvent almost every principle of safe manufacturing to minimize cost and maximize profit, confident in their ability to fool inspectors. Meanwhile, patients unwittingly consume medicine with unpredictable and dangerous effects.”

Eban suggested that for maintenance drugs like a drug for hypothyroid, or an anticoagulant you may be taking every day for life, find out who makes it and put the name of that company and ‘FDA warning letter’ into google. “What has the FDA found out about this company? Has this company had drug recalls? You know, I mean, it is a bit of sleuthing, but if you're taking this medication day in and day out, it's worth it.”

I searched google on “FDA warning Lupin”. It didn’t take long to find that Lupin facilities in India have received repeated warnings of increasing severity from the FDA, in 2015, 2016, 2017, 2019, and 2021. The 2021 warning stated:

“Repeated violations at multiple sites demonstrate that your company’s corporate oversight and control over the manufacture of drugs is inadequate. You should further comprehensively assess your company’s global manufacturing operations to ensure that systems and processes, and ultimately, the drug products manufactured, conform to FDA requirements at all your sites.”

Similar warnings to comprehensively assess their entire global manufacturing operations were delivered to Lupin by the FDA in 2017 and 2019. Lupin has been promising to the FDA that it would comply, for years, and it has not. The FDA continues to inspect, find fault, and warn, but the FDA continues to allow Lupin drugs to be imported into the US.

It seems that not much has changed in India. I decided to find a supplier for levothyroxine manufactured almost anywhere else, preferably in the EU. And, I won’t be tempted to try a generic anticoagulant produced in India.

I’m married to a retired pharmacist. He taught me never to buy drugs from countries that have lax temperature control storage. India is top of the list.

[theprint.in]

Call your pharmacy and ask them for your rx to be from compliant countries. If you order online then you need to ask as well. I only buy drugs from countries that have strict guidelines. No tropical countries or India.

USA is not immune once the drugs leave its USA manufacturer and transported to big chain warehouses. They can’t control their distribution during a blizzard.

I was taking Tenormin, brand name from AstraZeneca before they stopped manufacturing it. My BP remained perfect even with a beta blocker until I started a new bottle and my BP jumped to 224/114. I called AstraZeneca and they asked for the lot number of the rx vial. I always ask for the manufacturer’s vial (not pharmacy vial) because it has the lot number and expiration date. Once I gave the lot number to the representative, she confirmed that entire lot was stuck 4 days in a truck in NY during a bad blizzard and it’s potency became compromised. Now I have a 4-6 month stockpile and order during mild weather.-no summers or freezing winters.

I recommend getting all your drugs in the original manufacturer’s vials and ask the pharmacist what country it was manufactured. Stay away from countries with poor compliance pharmaceutical distribution regulations and temperature storage.

Trivia:
Transport drugs regulations from non usa to usa guidelines:
[www.who.int]

Another concern is online pharmacies. I only buy from israelpharm because I know it’s strict. Check out where you get your rx.

[en.m.wikipedia.org]
Read discussion, risks and home delivery:

“Conventional 'bricks and mortar' pharmacies usually have controlled drug distribution systems from the manufacturer, sufficient validation, and follow good distribution practices. Home delivery of pharmaceuticals can be a desirable convenience, but sometimes it can lead to problems with uncontrolled distribution.

The shipment of drugs through the mail and parcel post is sometimes a concern for temperature-sensitive pharmaceuticals. Uncontrolled shipping conditions can include high and low temperatures outside the listed storage conditions for a drug. For example, the US FDA found the temperature in a mailbox in the sun could reach 136 °F (58 °C) while the ambient air temperature was 101 °F (38 °C).[1]

Shipment by express mail and couriers reduces transit time and often involves delivery to the door, rather than a mailbox. The use of insulated shipping containers also helps control drug temperatures, reducing risks to drug safety and efficacy.“

I also don’t buy mailed rx in extreme weather-winter or summer. I picked them up at the pharmacy. You know how hot/cold the usps mail Jeeps are in the hot months and freezing winters. Rx should be stored between 67-78 degrees F. At home our drugs are stored in a temperature controlled room (AC/heat on). Never store in a car or bathroom (humidity affects the potency. All my drugs I store in a insulated bag with a digital thermometer. When I travel (before the pandemic) I brought reusable ice bags to keep at the correct temperature. It came in handy in Spain during a hot August.

My bag: I don’t use ice in the inside. I lay it on the outside wrapped in an insulated material to keep my rx not too cold during a hot day:
[www.amazon.com]



Edited 2 time(s). Last edit at 01/13/2022 02:32AM by susan.d.

My insurance changed this year and I was just going to sign up for OptumRX as my mail order pharmacy. Diltiazem is a drug waiting for me to receive. After reading your info, Susan, about receiving drugs during summer and winter months, I am wondering what to do. I would save 30.00 for a 90 day supply having it mailed rather than picking it up at the pharmacy. More things to wonder about……..

I just read reviews about Optum mail order drugs and the ratings do not appear favorable! I guess time would tell how it would work for me!

Sherry



Edited 1 time(s). Last edit at 01/13/2022 10:48AM by Pixie.

Sherry: I also have OptumRX. Yes it is cheaper because in my plan my generic max is $12 regardless if I get a one month or three month supply. Brand is $30. With mail order I get 90 day supply automatically for $12/30 but with pharmacy pickup it’s 30 days for $12/30 unless I call up OptumRX, ask for a supervisor and ask for a price override…easier to do with the pandemic—I just say the truth that I would have less covid exposure picking up every 90 days than 30 days and I live in a desert and the temperatures get extreme for mail order. With pharmacy pickup I can ask the origin country of the rx manufacturer.

If you can financially afford the $30, I would splurge on your health. Any temperature affected drugs (lower potency) comes with an eventual price.

You may qualify with OptumRX to use manufacturer coupons. One coupon lasts a year and then you renew. An example Eliquis gives a monthly $20 coupon so I pay $10 ($30-20) and if you are in multaq, they offer $50 so that drug is free. Check the manufacturer websites for their savings plan.

There is a US mail order prescription pharmcy that tests every batch of every drug they sell prior to sending orders out to customers.

Given that synthetic thyroid hormone drugs such as Levothyroxin are “recognized to have a narrow toxic to therapeutic ratio with significant clinical consequences of excessive or inadequate treatment”, and that one of those significant consequences is atrial fibrillation, the Endocrine Society et.al. have issued a joint statement that doctors should warn patients that pharmacies can and will substitute different brands or generics any time they feel like it because of a mistaken belief everything is bioequivalent, so patients should ask their pharmacies to keep providing them what they’ve been accustomed to, or the patients may need to have their dose retitrated with TSH testing.

This warning doesn’t take into account the situation where a drug manufacturer routinely ships batches of drugs of inconsistent quality. But it would still apply. This would mean a blood test every time you filled a new prescription, unless you could verify that the new bottle came from the same batch as the last bottle.

I didn’t realize that when I had my prescription for Levothyroxin filled at my local US brick and mortar pharmacy, they would be supplying me with a drug produced by a company in India that had basically ignored repeated warnings by the FDA issued over many years that they needed to clean up their entire global operation.

Since these synthetic thyroid hormones are cheap, getting them from a pharmacy that will not only supply only the particular brand or generic that you want them to supply, but in addition they will test each batch they take your shipment from, seems like a good idea.

The pharmacy is Valisure.

The CEO testified to Congress recently:

At Valisure, our mission is to help ensure the safety, quality, and transparency of medications, and we do this with a very simple but novel approach: we check. Valisure is an online pharmacy attached to an analytical laboratory. We are the first and only pharmacy in America that chemically batch-validates every medication we sell, and we do it at no additional cost to consumers.

In response to rising concerns about medication quality, counterfeit medications, and overseas manufacturing, Valisure developed proprietary analytical technologies that we use in addition to the FDA’s standard assays to test every batch of every medication we dispense. Valisure tests medications for correct dosage, major inactive ingredients, proper dissolution, and the presence of carcinogens such as N-Nitrosodimethylamine (NDMA). Currently, we reject over 10% of on-market medication batches based on these testing standards. With roughly 80 percent of ingredients in U.S. medications manufactured in India and China, medication quality is constantly called into question. There are roughly three drug recalls in the U.S. every day and about 100 of those recalls every year are “Class I,” which are considered potentially life-threatening. These recalls can be attributed, at least in part, to the fact that the chemical quality of medications is primarily checked by manufacturers, which self-report the results. Most manufacturers are located overseas, where oversight by the FDA is difficult and fraud is commonplace.

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David_L
The pharmacy is Valisure.

There is an excellent Peter Attia podcast with David Light, the Valisure CEO: [peterattiamd.com]

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GeorgeN
There is an excellent Peter Attia podcast with David Light, the Valisure CEO: [peterattiamd.com]

Thanks for that link. I think Valisure is going to do well.

I have been wondering about mail order pharmacies and the temperature controls they have in place when transporting/delivering drugs. I am specifically thinking about the efficacy of drugs if the standard temperature control is not followed. I just got off the phone with Bristol-Myers’s Squibb, the manufacture of the Eliquis I take. It is manufactured in Switzerland. The person I talked to told me the standard temperature for Eliquis is between 68 and 77 degrees. The excursion/storage is 59 to 86 degrees. I live in Wisconsin with extreme cold and warm weather conditions. The person at Bristol- Myers told me the best I could do to get information is to call the pharmacy I use and ask about the temperature control they have in place. That would mean finding out the shipping company they use to get the drugs to their distribution centers and then to the individual pharmacies, the packaging used for each drug and the kind of truck used.

I just want my drugs to do what they are supposed to do!!

What are your thoughts on what I was told?

Susan, you mention you pick up your meds at the pharmacy during weather extremes. Do you know about that pharmacy’s distribution process, etc?

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susan.d
I’m married to a retired pharmacist. He taught me never to buy drugs from countries that have lax temperature control storage. India is top of the list.

[theprint.in]

I guess regulations in India regarding the transport of drugs need to be tightened, but the idea that doing that was an adequate response to the issues referred to in the article is laughable. The article mentioned the office of the United States Trade Representative (USTR) assertion that 20% of all drugs sold in India are counterfeit. The article also mentioned Katherine Eban's then recently published book, "Bottle of Lies" which describes a culture that pervades the entire Indian pharmaceutical industry that could not possibly produce good drugs combined with an FDA that has chosen not to enforce its regulations. It hardly matters how poorly manufactured, or counterfeit drugs are transported, they are still no good.

But that is an interesting point you make. I have been researching how to get the best cheapest drugs and I hadn't thought about the conditions during transport.

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susan.d
Another concern is online pharmacies. I only buy from israelpharm because I know it’s strict. Check out where you get your rx.

[en.m.wikipedia.org]

That article mentions organizations that put their stamp of approval on certain online pharmacies, i.e. PharmacyChecker, and the Canadian Internet Pharmacy Association, CIPA, stating that all drugs bought from online pharmacies credentialed by these organizations were legitimate. The thing is, I dug a little deeper and found that the study referred to only bought and tested brand name drugs from the credentialed pharmacies. Brand name drugs aren't the only drugs these businesses sell. The online pharmacies in question also act as fronts for other businesses in countries such as Turkey and India. I only looked at online pharmacies posing as "Canadian", or online pharmacies that actually are "Canadian", but those will "sell" you generic drugs by collecting your money and sending your order to India where a separate business not owned or controlled by them will ship whatever they feel like directly to you.

It turned out the local Costco pharmacy had Levothyroxin made for Lannett in stock:





Neolpharma appears to be a Mexican company that manufactures these tablets in Puerto Rico. Lannett is the distributor. I wrote Lannett to ask where does the API, the active pharmaceutical ingredient, come from.