10 Medications that were recalled by the FDA

Mohamad-Ali Salloum, PharmD • September 2, 2024

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The U.S. Food and Drug Administration (FDA) plays a crucial role in ensuring the safety and efficacy of medications. Despite rigorous testing, some drugs are recalled post-approval due to unforeseen adverse effects. This essay explores ten such medications, detailing the reasons behind their recalls.


1) Zantac (ranitidine): 


In April 2020, the FDA requested the recall of all prescription and over-the-counter (OTC) ranitidine drugs, including Zantac, due to the presence of a probable human carcinogen called N-nitrosodimethylamine (NDMA) in the medications. NDMA is a known environmental contaminant and found in water and foods, including meats, dairy products, and vegetables, but it is not expected to cause harm when ingested in low levels. However, when exposed to higher levels over long periods of time, it may increase the risk of cancer.


Story:


N-Nitrosodimethylamine (NDMA) was discovered in Zantac (ranitidine) during routine testing by the FDA and other regulatory agencies. The discovery process involved several key steps:


  1. Initial Detection: The FDA began testing ranitidine products after reports of NDMA contamination in other medications. The initial tests revealed that NDMA levels in ranitidine increased over time and with exposure to higher temperatures.
  2. Chemical Breakdown: It was found that the active ingredient in Zantac, ranitidine, can break down into smaller molecules under certain conditions. These smaller molecules can then combine to form NDMA.
  3. Advanced Testing Methods: Laboratories used advanced analytical methods, such as liquid chromatography-high resolution mass spectrometry (LC-HRMS), to detect and quantify NDMA levels in ranitidineSome tests involved heating the product to simulate conditions during storage and transport, which showed significant NDMA formation.


2) Metformin:


Several manufacturers of metformin, a medication used to treat type 2 diabetes, have issued voluntary recalls due to the presence of a possible carcinogen called N-Nitrosodimethylamine (NDMA) in the medication. The levels of NDMA found in the recalled medications were above the acceptable daily intake limit set by the FDA.


Story:


N-Nitrosodimethylamine (NDMA) was discovered in metformin during routine testing and investigations by the FDA. The agency began testing metformin products after reports of NDMA contamination in other medications. The testing revealed that NDMA was present in the finished metformin tablets, but not in the active pharmaceutical ingredients (API) themselves

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This suggests that NDMA may form during the manufacturing process or storage of the finished product1The FDA used advanced analytical methods, such as liquid chromatography-high resolution mass spectrometry (LC-HRMS), to detect and quantify NDMA levels in metforminAs a result, several lots of extended-release metformin were recalled to ensure patient safety.


3) Losartan:


In 2019, several lots of losartan, a medication used to treat high blood pressure, were recalled due to the presence of a possible carcinogen called N-Nitrosodiethylamine (NDEA) in the medication. The levels of NDEA found in the recalled medications were above the acceptable daily intake limit set by the FDA.


Story:


N-Nitrosodiethylamine (NDEA) was discovered in Losartan during routine testing and investigations by regulatory agencies like the FDA. This impurity, along with others like N-Nitrosodimethylamine (NDMA) and N-Nitroso-N-methyl-4-aminobutyric acid (NMBA), was found in the active pharmaceutical ingredient (API) used to manufacture the drug.


The contamination occurred due to a chemical reaction during the manufacturing process of the API. Specifically, suppliers in India and China inadvertently produced contaminated ingredients, which were then used by pharmaceutical companies to produce the final drug productsThis led to the recall of several lots of Losartan to ensure patient safety.


4) Valsartan:


In 2018, several lots of valsartan, another medication used to treat high blood pressure, were recalled due to the presence of N-nitrosodimethylamine (NDMA) and N-Nitrosodiethylamine (NDEA) in the medication. The levels of NDMA and NDEA found in the recalled medications were above the acceptable daily intake limits set by the FDA.


5) Ibuprofen:


In 2018, several lots of liquid ibuprofen for infants and children were recalled due to the potential risk of higher concentrations of the medication. The recall was initiated by the manufacturer, Tris Pharma, after receiving customer complaints about the medication having higher concentrations of ibuprofen than listed on the label. Parents and caregivers were advised to stop using the recalled product and to contact their healthcare provider if their child had experienced any adverse effects. They were also instructed to return the product to the place of purchase for a refund.


Story:


  1. Higher Concentration Levels: Some units from the recalled batches were found to contain ibuprofen levels up to 10% above the specified limit. This could lead to infants receiving a higher dose than intended.
  2. Health Risks: Overdosing on ibuprofen can cause several adverse effects, especially in infants, including:
  • Gastrointestinal Issues: Nausea, vomiting, and abdominal pain.
  • Renal Injury: Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen can cause kidney damage, particularly in young children.
  • Other Symptoms: Drowsiness, headache, and in severe cases, respiratory depression and coma.



6) Digoxin:


In 2017, several lots of digoxin, a medication used to treat heart failure and irregular heartbeats, were recalled due to the potential risk of incorrect dosing. The recall was initiated by the manufacturer, Westminster Pharmaceuticals, after discovering that some bottles may have contained tablets with twice the approved strength.


Story:


There was a Label Mix-Up, where ottles labeled as 0.125 mg contained 0.25 mg tablets, and vice versa.




This recall was a precautionary measure to ensure patient safety and prevent any adverse health effects.


7) OxyContin:


In 2015, OxyContin was not specifically recalled, but there were significant developments related to its formulation and regulatory scrutiny:


  1. Reformulation: Purdue Pharma, the manufacturer of OxyContin, had reformulated the drug to make it more abuse-deterrent. This new version was designed to be harder to crush, snort, or inject, which are common methods of abuse.
  2. Regulatory Review: In 2015, the FDA was supposed to review follow-up data on the effectiveness of this reformulated version in reducing abuse. However, Purdue Pharma pulled its application to update OxyContin’s label with new information on abuse, stating that they needed more time to analyze the data.



As of 2024, Purdue Pharma has not reapplied to the FDA to update OxyContin’s label with new information on abuse deterrence. The company has been involved in ongoing legal and regulatory challenges, including a recent Supreme Court decision rejecting a nationwide settlement related to the opioid crisis.


Public Health Concerns: There were ongoing concerns about the effectiveness of the reformulated OxyContin in actually reducing abuse and addiction rates. The FDA and other health experts were closely monitoring the situation.



8) Tamiflu (oseltamivir phosphate):


In 2013, several lots of Tamiflu, a medication used to treat the flu, were recalled due to potential packaging defects that could cause the medication to spoil. The recall was initiated by the manufacturer, Roche, after discovering that the Tamiflu capsules had a defect that allowed moisture to enter the packaging, potentially causing the medication to spoil.


9) Levothyroxine:


In 2013, several lots of levothyroxine, a medication used to treat hypothyroidism, were recalled due to a labeling error that resulted in the incorrect strength being listed on the packaging. The recall was initiated by the manufacturer, Lannett Company, after discovering that some bottles contained tablets with a different strength than listed on the label.


10) HydroChloroThiazide (HCT):


In 2018, there were two notable recalls involving hydrochlorothiazide:


  1. Label Mix-Up: Accord Healthcare issued a recall for one lot of Hydrochlorothiazide Tablets USP, 12.5 mg, because bottles labeled as hydrochlorothiazide were found to contain spironolactone tablets instead. This mix-up could lead to patients receiving the wrong medication, which could have serious health implications.
  2. Contamination with NDEA: Teva Pharmaceuticals recalled several lots of amlodipine/valsartan/hydrochlorothiazide combination tablets due to the detection of N-Nitrosodiethylamine (NDEA), a probable human carcinogen, in the valsartan component. This impurity was found in the active pharmaceutical ingredient (API) manufactured by Mylan India.


Conclusion:


The recall of these medications underscores the importance of continuous monitoring and post-marketing surveillance to ensure drug safety. While these recalls highlight the potential risks, they also demonstrate the FDA’s commitment to protecting public health.


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    ABOUT THE AUTHOR

    Mohamad-Ali Salloum, PharmD

    Mohamad Ali Salloum LinkedIn Profile

    Mohamad-Ali Salloum is a Pharmacist and science writer. He loves simplifying science to the general public and healthcare students through words and illustrations. When he's not working, you can usually find him in the gym, reading a book, or learning a new skill.

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    These strong rays have been used by doctors and scientists for almost a century to gaze into the mysteries of the human body and beyond. But did you know that X-rays were found entirely by chance ?  In 1895, Wilhelm Conrad Roentgen, a German physicist, was experimenting with cathode rays (aka electric currents) when he noticed an unusual glow coming from a nearby screen. He had no idea that this unintentional discovery would forever revolutionize the world of medicine! Radiation such as X-rays can travel through the body. They are invisible to the naked eye and cannot be felt. The energy from X-rays is absorbed in varying rates by different regions of the body as they move through the body. After the X-rays have passed through, a detector on the other side of the body collects them and converts them into an image. Dense portions of your body, such as bone, that X-rays find difficult to get through, appear as distinct white patches in the image. Softer tissues that X-rays can easily pass through, such as your heart and lungs, seem darker. So, what’s the true purpose of X-rays? They are commonly used for a variety of evaluations, of which we shall highlight a few: Dental X-rays are used in dentistry to obtain images of the teeth and surrounding tissues, which aid in the diagnosis of oral health concerns and treatment planning. Cancer Treatment: a type of radiation therapy that uses high doses of radiation to eliminate cancer cells in specific parts of the body. Veterinary Care: utilized in veterinary medicine to diagnose and treat animals, assisting veterinarians in the detection of fractures, cancers, and other health problems. Industrial inspection is used to inspect machinery and infrastructure in the industrial sector, assisting in the detection of flaws and the prevention of accidents. Forensic Science: a branch of forensic science that examines the evidence and reconstructs crime scenes to assist in identifying victims of crimes and accidents. Bone Density Testing: used to assess bone density and aid in the diagnosis of osteoporosis and other bone-related diseases. The chart below provides additional information about the medical applications of X-rays:
    By Mohamad-Ali Salloum, PharmD September 11, 2024
    I’ve always thought that our energy is limited (due to the physical laws of thermodynamics, where it states that energy is neither created nor destroyed, it’s only transformed) and that when we work around 10 hectic hours a day, there’s nothing to do more than go home, eat, watch some tiktoks/reels, and then sleep. I know that our bodies and minds can feel depleted after long periods of exertion, but this feeling is not always an indicator that we are out of energy. Little by little, I am now convinced with the contrary to this theory. It’s not that our energy is finite, but what we can really do is to refresh ourselves to access the energy in us that we always had but never used. Imagine your energy is 100%/day. All your life, you thought that you were using 90-95% of your energy by going to school and then studying after-school, or during the collage days, or even when you started working. The most hectic phase is the work phase, where you are now stuck in adulthood and you have no escape. But this phase will be the best one if you knew how to play it. You are actually using only 50% of your true energy. (ps: I made up this percentage… but let me explain) Now as I am writing this article, I was work-travelling, I woke up today at 4 am, worked on some urgent tasks before going to the hospital, went to the hospital at 8 am and then worked till 6:30 pm. Then I went to the hotel, took a 1-hour rest. And now I am eating lunch and writing this article. When I reached the hotel, I was tired as f**k. I just wanted to take a shower and then sleep, but then I remembered something that always motivated me. (I heard David Goggins talk about it in a Podcast) Imagine when you die, the angels at the gates go through a list of your traits and qualities that you had during your lifetime, and they mention a top tier qualities that you’ve never imagined you will ever have or even mention accomplishments you’ve never thought that you would achieve something near to them. You tell them that they are describing someone else, and this person is not you. They reply to you that this person is the one you would have been if you worked enough on yourself. CHILLS. Imagine not being able to be the best version of yourself, just because you didn’t choose to…you always have the choice, but somehow you find an excuse to not do anything to make yourself better. Or even convince yourself that sending some emails or doing some tasks during the work day is enough to make you excel or reach this version of yourself. So i got up, feeling a whole new energy in me (although I didn’t sleep). I went outside of the hotel to the nearest restaurant, and now i’m finishing this article. After that I will continue working on my Running V-log project that I am currently working on. Step by Step. But the most important thing is to know that you will reach what you want one day if you make enough effort to accomplish it and make less excuses to run from it. The key takeaway is that while our physical energy might have limits, our mental and emotional energy can be optimized through various strategies. By adopting a proactive approach to energy management and changing your perspective of how you see things, you can unlock your full potential and achieve greater productivity and fulfillment.
    By Mohamad-Ali Salloum, PharmD September 7, 2024
    Adjustment shock is what we feel when life throws us a curveball, causing both our minds and bodies to react. In today’s ever-changing world, this is something we all face. On the flip side, there’s the idea of anti-fragility, a term coined by Nassim Nicholas Taleb. It describes systems that don’t just survive stress but actually thrive because of it. Let’s dive into how our brains can be anti-fragile.
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