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Tag Archives: FDA

How Long Before Zofran Gets Black Boxed?

It has been a few years, but the FDA’s war on antiemetics (medications for vomiting) continues. To review … Bendectin was the first antiemetic to be taken off the market after famous plaintiff attorney Melvin Belli sued Merrell Dow Pharmaceuticals. No credible evidence was ever found that Bendectin caused birth defects as the plaintiff attorneys alleged, yet Merrell Dow removed bendectin from the market to avoid further lawsuits. Droperidol was another great nausea medicine that got the FDA’s dreaded “black box” because it allegedly caused QT prolongation. See commentary here. Then the FDA went after Tigan suppositories. Remove them from the market, it demanded. Compazine was next to get the dreaded “black box” kiss of death. Then came Reglan, which joined the “black box” club due to a risk of tardive dyskinesia. Interesting that one of the medications that has been used to treat tardive dyskinesia is another antiemetic … Zofran. Phenergan was next. In Wyeth v. Levine, a Vermont jury decided that drug labeling warning against intra-arterial use wasn’t strong enough. The resulting black box warning struck fear into the hearts of hospital risk managers everywhere. By the way, how many of you knew that Phenergan is an antihistamine and, like Benadryl, can be used as a local anesthetic? It appears that not enough people were scared off by the previous FDA warning on Zofran, though. Now, the FDA has decided the 32 mg IV dose of Zofran has the “potential for serious cardiac risks” and is demanding removal of all 32 mg IV Zofran doses from the market. Those same cardiac risks – QT prolongation – were used to get droperidol black boxed, so it is only a matter of time until Zofran gets its scarlet letter from the FDA. Personally, I would like to see the FDA’s studies on Zofran … and all the other antiemetics for that matter. I seriously doubt many of the claims. In the meantime there’s always Aprepitant. That’s only $100/dose (in 2004). Plus … the FDA won’t determine that it’s bad for your health for at least another 10 years – about the time it goes off patent.

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FDA’s Latest Deadly Drug: Codeine

Get ready for more governmental regulation of opioids and maybe even some black box warnings added to the prescribing information for c0deine-containing drugs … just for everyone’s safety, of course. According to this FDA Special Bulletin on Safety Information, three pediatric deaths and one case of respiratory depression were documented in the medical literature after children took codeine-containing compounds. The etiology for the deaths was allegedly because the children had a variation in their cytochrome P450 enzyme that caused the codeine to break down faster into morphine, high levels of which, according to the FDA, “may be fatal.” If your child or your patient is an “ultra-rapid metabolizer” of codeine, he or she could DIE. The FDA also published a “Drug Safety Communication” that disclosed the studies on which its recommendations were based. One case cited by the FDA as “proof” that codeine can kill you involved a 2 year old child with sleep apnea who underwent tonsillectomy and adenoidectomy and who died three days after surgery. At autopsy, the child had elevated levels of codeine and morphine in his system, had aspirated food particles, and also had bilateral pneumonia. No mention of how much codeine the patient’s parents gave the child, only of the dose that was prescribed. No mention of how bilateral pneumonia or aspiration in a young child can be deadly. The researchers concluded that the elevated morphine levels “may” have contributed to the child’s death. The FDA wants you to believe that there was a causal connection there. Another article cited by the FDA was from the same authors who now found three additional cases of children who died after having tonsillectomy/adenoidectomy and were prescribed codeine. I didn’t purchase the article, but I also am assuming that there were no controls for dosing of the medication, only for prescription of the medication. In other words, I doubt that the researchers would be able to tell whether the parents accidentally just gave the child too much medication as opposed to whether some genetic variant caused higher than normal blood levels of the medication at normal doses. I also did a PubMed search for “children codeine p450” and also “pediatric codeine p450“. There was one Canadian case report of a mother who was an “ultra rapid metabolism phenotype” whose breastfed child had fatal opioid intoxication after the mother used codeine. There was another case report from Canada of a 5 year old girl who died from hydrocodone overdose when she was taking both clarithromycin for an ear infection and valproic acid for seizures. The medications decreased metabolism of the drug and she also had a genetic defect that decreased the metabolism of the drug. None of the other articles that I found mentioned pediatric death due to an interaction between opioids and cytochrome P450. Now, based on 4 deaths out of likely hundreds of millions of codeine prescriptions, the FDA is “currently conducting a safety review of codeine” and is recommending that doctors use low doses of codeine for patients in pain or that doctors just use another medication completely for children in pain. The FDA also recommends that caregivers monitor patients for signs of opioid toxicity. These recommendations are already in the prescribing information for Tylenol with Codeine. Oh, and the FDA also notes that doctors can always perform “FDA approved” genetic testing to see if children have the gene responsible for rapid metabolism of codeine. I can’t help wonder what motivation the FDA has to issue this warning about 4 deaths in tens or even hundreds of millions of prescriptions that were hypothesized to have been caused ...

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The FDA just issued a news release urging consumers to stop using HydroxyCut products, noting that some products were “associtated with” liver injuries. Iovate, the manufacturer, has agreed to recall all HydroxyCut products. Out of millions of doses of HydroxyCut sold, there were 23 reports of “serious health problems” “associated with” the use of the product, ranging from jaundice to elevated liver enzymes to permanent liver damage resulting in a liver transplant. There was also one death from liver failure. I keep putting the “associated with” in quotes because we have to be very careful about how we interpret the terms we use. Almost all people who die from asthma have probably used an inhaler shortly before their death. That means that use of asthma inhalers is “associated with” deaths from asthma. Can we say that asthma inhalers caused death in those patients? If so, we need to take asthma inhalers off the market. Many people who die in hospital emergency departments are brought by ambulances. Ambulance use is therefore “associated with” deaths in the hospital emergency department. Do ambulances cause death? Should we stop EMS transports immediately? Paying taxes is associated with increased … aww nevermind. You get the picture. So is this FDA warning a bunch of hooey or has Iovate been slipping the general public a Mickey all these years?

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Warning Labels – Just Don't Puke

In less than 24 hours, Phenergan will no longer be available in one of the largest teaching hospitals in our area. Because of the decision of 6 appointed justices in our US Supreme Court, the hospital is removing all of the Phenergan in the hospital’s stock. Thus continues the assault on many of the antiemetic stalwarts that we have been using for decades. Bendectin was the first antiemetic to go the way of the dodo bird after famous plaintiff attorney Melvin Belli sued Merrell Dow Pharmaceuticals. No credible evidence was ever found that Bendectin caused birth defects as the plaintiff attorneys alleged. Droperidol was another great nausea medicine that got the FDA’s dreaded “black box.” Then the FDA went after Tigan suppositories. Compazine was next to get the dreaded “black box” kiss of death. Just last week, Reglan joined the “black box” club due to a risk of tardive dyskinesia. Now Phenergan is going to take a hit. After the publicity, many doctors and hospitals will be afraid to use it. It’s just amazing that the medical profession has been poisoning patients with all of these medications for decades and just now we’re finding out about it. Luckily, we still have Zofran and other 5-HT3 receptor antagonists – if patients can afford it. I wrote a prescription for 12 Zofran ODT tablets for a patient who was vomiting last week. The pharmacist called me and said that the prescription would cost $260 and it wasn’t covered on the patient’s insurance. Could I change it to something else? I wasn’t willing to take the chance if the patient had a bad outcome. Defensive medicine strikes again. Avoid the bad outcome. I wrote about the Wyeth case here and here. I’m by no means a staunch drug manufacturer supporter, but pretend that you’re running a manufacturing company. What are you supposed to do with your drug labels now? Overlawyered.com has a summary of opinions about the Supreme Court’s decision as well as a link to the published opinion. The product labeling for Phenergan had the following language in it: I skimmed the 80 page US Supreme Court opinion and it appears that the majority believed that “Wyeth could have unilaterally added a stronger warning about IV-push administration.” Good thinking. Now you’ve just opened the legal floodgates to every Tom, Dick and Harry who has ever had a bad outcome from taking a medication. All they have to claim is that the warnings on the medication bottle “weren’t strong enough” and they’ve got the opinions of six Supreme Court justices to guide them on their quest for independent wealth at the expense of a drug manufacturer. Extending the Supreme Court’s logic puts every pharmaceutical manufacturer on notice that they must discover each and every way someone could possibly misuse their product and specifically warn the public not to use the product in that manner. Don’t pour Phenergan in electric sockets – it could start a fire and burn down your house Don’t feed Phenergan to your goldfish – it could burn their scales off and give you emotional distress Don’t gargle with Phenergan – it could cause caustic burns to your throat and you could get disfiguring burns and you could suffocate to death Don’t mix Phenergan with Frosted Flakes – it could cause an exothermic reaction with the Frosted Flakes, resulting in nasal irritation if you breathe the fumes Actually, I created a Supreme Court-approved label that all pharmaceutical companies could use when they decide to manufacture medications. I’ll bet that some companies will find it very helpful: If this label makes ...

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Wyeth v. Levine

There have been a lot of opinions rendered about the Wyeth v. Levine lawsuit. Want to read all the briefs? Click here. Including amicus briefs, there are about 30 of them. You can also read more about the case at this NY Times article. The case has been fought out in Vermont’s trial court and in the Vermont Supreme Court. Now the case is pending before the US Supreme Court. It’s a little odd when a drug company writes me to solicit my opinion. Last week I was invited to a conference call with several bloggers including TK from ER Stories and Michael Miller from Health Policy and Communications Blog along with one of the Wyeth representatives and a Wyeth attorney. Why did they want bloggers on a conference call about a pending Supreme Court case? They want to bring the facts and the issues to the public eye. Not sure why they picked me. Must be my charm … Before I start down this road, I’m a doctor, I’m not a legal scholar (but I did stay at a Holiday Inn Express). I’m not being paid by Wyeth or anyone else to discuss this. Just doing these posts because I think the issue is important. I’m also relying on Wyeth for some of the facts since the case is complex and I don’t have the time to read all of the briefs in this case. However, as far as I know, the “other” issues have been decided and the remaining issue before the US Supreme Court is one of “preemption.” I’ve tried to get the facts correct, but feel free to correct me if I have made a factual mistake. Today, I’ll focus on the history of the case and tomorrow I’ll get out my soapbox. The story began when a musician named Diana Levine went to the Northeast Washington County Community Health clinic with a migraine headache and vomiting. She received intramuscular injections of Demerol (meperidine) and Phenergan (promethazine) and was discharged. Her symptoms weren’t controlled. In fact, she began vomiting more and returned to the clinic. In order to improve her symptoms more quickly, the physician assistant gave Ms. Levine IV Demerol and IV Phenergan. Ms. Levine didn’t have an IV established, so the PA inserted a “butterfly” needle into the patient’s vein and injected the medication. Before I tell you about the outcome, you have to know a little more about the drug Phenergan. Phenergan is approved for use by the FDA. I have previously commented how the FDA doesn’t exactly do the best job investigating medications. Just think, the FDA approved all those cough and cold medications that the pediatricians are now decrying as a public health threat. Well, actually, the pediatricians are just saying that everyone is too dumb to take them correctly, but that’s another story. According to Wyeth’s brief, Wyeth had ongoing discussions over the years with the FDA to make sure that the FDA felt that the labeling was adequate. Even if we assume that the FDA had no idea what it was doing when it approved Phenergan for use, during the conference call the Wyeth rep stated that more than 220 million doses of Phenergan have been given around the world. Phenergan is an irritant. If you’ve ever gotten shots before, you know that some shots hurt like heck and that you can hardly even feel other shots. I commented in one of my previous posts that Phenergan produced “burning” sensation when it is injected into someone’s buttocks. The FDA has also approved Phenergan for intravenous use, and, just like ...

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Trusting The FDA

In a post I put up last September, I asked “What Is Going On With The FDA??” Thanks to a couple of articles I figured it out. There’s a reason it takes so many years for the FDA to take action against “dangerous” drugs like children’s cold meds, Rocephin, and Haldol. These drugs have all been on the market for more than 15 years and in just the past six months, the FDA came to the conclusion that they were all a threat to American lives. Enter the GAO. In a New York Times article, government investigators have just reported that the FDA is woefully understaffed. The article stated that at the FDA’s current staffing level, it would take more than 13 years to check every foreign drug manufacturing plant, and more than 1900 years to check every foreign food manufacturing plant. No, I didn’t have a nervous twitch on the “0” key. The article states “one thousand nine hundred” years to check all the foreign food manufacturing plants. In fact, the FDA computer systems are so bad that they can’t even create a list of which plants have been inspected and which have not. A Wall Street Journal article reported that the FDA can’t even keep up with inspection of domestic manufacturers of medical devices (like defibrillators and contact lenses). A former lawyer for the agency stated that “This is a fundamentally broken agency, and it needs to be repaired.” So it isn’t like Big Pharma is paying off the FDA to approve drugs while they are on patent and then put danger labels on them when they are off patent (and no longer earn the drug cartels companies any money). It’s just that the FDA is so overworked that 15 years is about how long it takes until they can review a drug’s safety profile. Doesn’t that make you feel better? Hat Tip to ACEP‘s Emergency Medicine Today

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