One year ago, I received a call from the mother of a young woman who said the matter was “urgent.” When I saw her daughter Abby a few days later, I met a 30-year-old woman who appeared much younger than her stated age. She was “terrified of everything,” and asked her mother to remain in my office during the evaluation. Abby said her primary care physician prescribed a generic antidepressant that kept her symptom-free for almost eight years. Five months ago, when she refilled her prescription, it was from a different manufacturer.
Abby said she “knew it looked different,” but when questioned, the pharmacist told her “All generics are the same.” Abby’s symptoms began within days of filling the prescription. In subsequent months, she developed mental slowing, fear of leaving her house, and a sense of overwhelming anxiety. The week prior to our appointment, her symptoms were so severe she could not go to work.
Abby’s current prescription was manufactured by Lupine, a company based in India. For the prior eight years, she took a generic version of the same medication made by TEVA, based in Israel. Unfortunately, the Teva version was discontinued.
The US has the world’s largest pharmaceutical drug market. The demand for generic drugs has grown substantially in the last few decades, due to a track record of safety, value, and low prices. In the current economic environment, concern about the high price of prescription drugs led the FDA to issue new guidance last month. Pharmacists and drug wholesalers can now import prescription medicines from Canada for up to two years as part of state programs aimed at bringing down costs.
Unfortunately, even if states allow Canadian imports, their market is too small to fill the massive requirements needed by Americans for their prescription medications. Pharmaceutical sales in Canada have only a 2.1 percent share of the global market. At present, China is the primary source of medicine imported into the US, with India and Mexico vying for second and third depending on the year.
What’s the problem? Not all generic manufacturers are the same, and unfortunately, most physicians and many pharmacists are not aware of the difference.
Last weekend, I called five pharmacies to find a non-Indian or Chinese-made equivalent for one of my patients. I finally found one who told me they carried an American brand. They were wrong, the product was made in Taiwan.
The pharmacist was not being dishonest. He looked at the product label and correctly noted that the medication is distributed by a US company. What he failed to realize, was where the product was actually manufactured. The name of the “American company” is Lupine.
The website for Lupine states it is headquartered in Baltimore, Maryland, which would understandably lead the consumer or pharmacist to believe it is made in America. Upon further investigation, I discovered Lupine is a multinational pharmaceutical company based in Mumbai, India.
The generic drug industry is facing a continuing problem in India, where many “copycat” medicines are manufactured. Katherine Eban’s excellent book, “Bottle of Lies,” focuses a spotlight on the most ignored transgressions of the Indian generic pharmaceutical industry both in the processes they follow or too often do not follow.
The US does not routinely inspect Indian pharmaceutical factories. FDA efforts to do so have been hampered by staffing shortages as well as aggressive drug companies that cover up potential problems. A yearlong investigation by Bloomberg News documented the findings of FDA inspections into manufacturing data pharmaceutical factories from West Virginia to China. Bloomberg reported, “some workers in India destroyed records to keep regulators in the dark about production issues.”
In 2021, the FDA reprimanded two Indian facilities operated by Lupine for ignoring tests showing that pills made there did not meet quality standards. The warning letter asserted that Lupine failed to properly investigate when samples of active pharmaceutical ingredients and the finished product had not passed inspection, choosing instead to test them repeatedly until they met standards or blame the failures on “laboratory errors.” The FDA also stated that the failures demonstrated Lupine’s inadequacy, and recommended an immediate and compressive manufacturing overhaul to comply with FDA requirements. Lupine continues to receive FDA rebukes, most recently this past April.
Although Lupine is the largest Indian pharmaceutical manufacturer, it is by no means the only one reprimanded. Aurobindo Pharma received nine citations from the US drug regulator for one of its sites in India. This is worrisome because it is a facility that manufactures injectable medications and is required to maintain the highest standards, and several of its drug approvals are currently pending in the US
To save my patients from paying exorbitant prices for brand medications not covered by insurance, I sometimes prescribe generic alternatives without concern for their safety and efficacy, because the FDA requires generic medications to be “bioequivalent” to their brand counterparts. This means that the generic drug will work the same way and be as safe and effective as the brand-name drug. They do not, however, have rules about what types of inactive ingredients the generics may contain.
Abby’s saga is but one example of similar stories my patients report almost every week. More often, insurance companies require physicians to complete prior authorizations to cover the cost of brand medications. When brand name options are denied, generic substitutions are the only viable option. However, because most generics imported to US pharmacies are manufactured in countries where FDA inspectors do not have authority, my concern over prescribing generics has grown. Primary care doctors prescribe most psychiatric medications in this country and do not have time to check on the origin of each prescription written. Many are not aware of the discrepancies between different generic brands.
It took several months, but Abby is back to work and feeling well. I appealed to the brand manufacturer who granted a generous coupon, so she could afford her medication. Most patients are unaware that prescriptions are made in countries with less than stellar facilities. Aside from the health implications for patients, there is also an economic burden. Some of my patients require medical leave or even accept short-term disability from work while waiting for a suitable generic alternative.
What can you do if you suspect your generic medication looks different, and you are experiencing new side effects or a recurrence of your original symptoms after you have been stable for a period of time?
- Call the pharmacy where you filled your prescription. Ask them to check the name of the manufacturer.
- Tell your prescriber about your suspicion. Ask him or her to track down the manufacturing site of the new pharmaceutical company. If they will not do it, you can find it yourself. On the prescription label, there is an abbreviation MGR or MFR. That usually stands for Manufacturer. Look up their website and find not where it is distributed, but where the factory is located.
- Sometimes, large chain pharmacies can not get the generic brand needed because they are part of a corporation that has limits on which generic manufacturers they can order from. It is helpful to find a pharmacy that is independently owned or is a compounding pharmacy. They are more client-focused and more likely to work with you.
- Consider using a Canadian pharmacy like Drug Mart. They are easy to work with, and their prices are competitive. The only drawback is time. Sometimes they have to source their supplies from the UK or Australia; shipping may take longer.
- Finally, consider contacting the manufacturer of the brand name of your prescription. They sometimes offer coupons that substantially lower your cost.