Without evidence of benefit, an intervention should not be presumed to be beneficial or safe.

- Rogue Medic

FDA bans useless, possibly dangerous, antibacterial soap ingredients

antiseptic soaps safe - qm - WSJ and FDA logo

As of September 6, 2017, The FDA (Food and Drug Administration) will ban manufacturers from selling antiseptic soaps over the counter to consumers because the manufacturers could not provide evidence that they work and that they are safe. The list of ingredients is in the footnotes.[1],[2]

In 2013, the FDA gave manufacturers a deadline to provide information about the products they sell to consumers. After decades of use, the manufacturers finally needed to provide evidence that the ingredients in their products are GRAS/GRAE. What does GRAS/GRAE mean?

GRAS = Generally Recognized As Safe
GRAE = Generally Recognized As Effective
GRAS/GRAE = Generally Recognized As Safe and Effective

As a consumer, do we want to spend our money on something that is not safe, is not effective, or is both unsafe and is ineffective?

Does the absence of evidence prove that the ingredients are unsafe or that they are ineffective? No.

The failure to provide evidence shows one of the following –

A. The manufacturers cannot show that the ingredients are safe.
B. The manufacturers cannot show that the ingredients are effective.
C. The manufacturers cannot show that the ingredients are safe and effective.

Those three are the most obvious possibilities, but there are several more possibilities. For example –

D. The manufacturers don’t care enough to find out if the ingredients are safe or effective.

Is it a business decision that the amount of money to be made in this multi-billion dollar market is not worth the amount of money that would be lost, but would any money be lost? Is the failure to provide evidence essentially an admission that the antibacterial soaps are just a marketing gimmick? Have the manufacturers avoided providing evidence? No.

Is there an absence of information? No. There is plenty of evidence, but the evidence does not show benefit or safety.

Both sides in the debate have submitted reams of evidence to the FDA supporting their stance, offering up conflicting studies that make it a challenge for the average consumer to make informed decisions.[3]


The more conspiratorial would add some other possibilities –

E. The manufacturers can show that the ingredients are not safe.
F. The manufacturers can show that the ingredients are not effective.
G. The manufacturers can show that the ingredients are not safe and not effective.

These are not impossible, but should we assume that manufacturers are intentionally and maliciously marketing dangerous and useless products? Hanlon’s razor addresses this –

Never attribute to malice that which is adequately explained by stupidity.

Stupidity does not appear to be the right word for this situation. There is another version of Hanlon’s razor that seems to be written just for the those who think that a lack of evidence of harm is the same as safety and efficacy.

Don’t assume bad intentions over neglect and misunderstanding.

How different is this from medical treatments that have no evidence of efficacy or safety? We stopped using backboards to stabilize the spine, atropine for cardiac arrest, furosemide for CHF, . . . , and we may no longer be able to justify using amiodarone.


[1] FDA issues final rule on safety and effectiveness of antibacterial soaps – Rule removes triclosan and triclocarban from over-the-counter antibacterial hand and body washes
FDA (Food and Drug Administration)
For Immediate Release
September 2, 2016
FDA News Release

[2] Safety and Effectiveness of Consumer Antiseptics; Topical Antimicrobial Drug Products for Over-the-Counter Human Use
A Rule by the Food and Drug Administration on 09/06/2016
Final rule.

What ingredients are banned?

Thus, the following active ingredients are not GRAS/GRAE for use as a consumer antiseptic wash:
    *Iodophors (Iodine-containing ingredients)
○ Iodine complex (ammonium ether sulfate and polyoxyethylene sorbitan monolaurate)
○ Iodine complex (phosphate ester of alkylaryloxy polyethylene glycol)
○ Nonylphenoxypoly (ethyleneoxy) ethanoliodine
○ Poloxamer—iodine complex
○ Povidone-iodine 5 to 10 percent
○ Undecoylium chloride iodine complex
    *Methylbenzethonium chloride
    *Phenol (greater than 1.5 percent)
    *Phenol (less than 1.5 percent)
    *Secondary amyltricresols
    *Sodium oxychlorosene
    *Triple dye
Accordingly, OTC consumer antiseptic wash drug products containing these active ingredients are misbranded, and are new drugs for which approved new drug applications are required for marketing.

IV. Ingredients Not Generally Recognized as Safe and Effective

[3] Are Antibacterial Soaps Safe? Companies say there’s no cause for alarm, but studies suggest they may be dangerous. Now the FDA is preparing to rule.
Wall Street Journal
By Laura Landro
Updated Feb. 15, 2016 11:01 p.m. ET


FDA takes steps to improve reliability of automated external defibrillators


Why improve the reliability of AEDs (Automated External Defibrillators)?

AEDs are important, much more important than the epinephrine I wrote about yesterday, because AEDs actually work – at least when the AEDs work as they are supposed to.

AEDs fail much more often than they should.

From January 2005 through September 2014, the FDA received approximately 72,000 medical device reports associated with the failure of these devices. Since 2005, manufacturers have conducted 111 recalls, affecting more than two million AEDs. The problems associated with many of these recalls and reports included design and manufacturing issues, such as inadequate control of components purchased from other suppliers.[1]


72,000 reports over ten years. In the US, there are about 300,00 cardiac arrests a year where treatment is considered and an AED might be applied. Out of those, how many times is an AED applied? 1/3?

If I use that ballpark number guess, then 72,000 out of 1,000,000 is 0.72%. The reporting of problems that are identified during equipment checks and maintenance should also decrease the rate of failure in the treatment of real patients. Maybe I decrease that guess at a failure rate during cardiac arrest treatment/assessment to 0.5% or 0.1%?

A decrease to 0.1% is one out of every 1,000 uses. Is that a tolerable level of failure for a device that has only two tasks, but has to remain ready to perform those tasks at all times? The two tasks are to differentiate between ventricular fibrillation/ventricular tachycardia and any other cardiac rhythm and to deliver a shock to the patient after ventricular fibrillation or ventricular tachycardia has been identified.

Image credit.

There are only a few moving parts and the designs may vary from what I describe. The wire that is manually attached to the defibrillator pads. The lids that is opened, turns on the AED, and triggers the voice prompts. The buttons that are pressed to turn on the AEDs not turned on by opening the lid, to analyze the rhythm, and to deliver the shock.

Would Do we accept a similar failure rate from an ambulance, which has many more moving parts?

Do we accept similar failure rates from our personal vehicles, which have many more moving parts?

Do we accept similar failure rates from aircraft, which has many more moving parts?

Yes and no.

We deal with the failures in these vehicles by building in redundancies and paying attention to maintenance, but the result is that the failures rarely cause death, or the lack of resuscitation that could have occurred with a properly functioning AED.

For example, NASA management claimed that they had an isty-bitsy teeny-weeny failure rate. They were shown to be wrong in a very dramatic, and deadly, fashion. Twice.

If a reasonable launch schedule is to be maintained, engineering often cannot be done fast enough to keep up with the expectations of originally conservative certification criteria designed to guarantee a very safe vehicle. In these situations, subtly, and often with apparently logical arguments, the criteria are altered so that flights may still be certified in time. They therefore fly in a relatively unsafe condition, with a chance of failure of the order of a percent (it is difficult to be more accurate).

Official management, on the other hand, claims to believe the probability of failure is a thousand times less. One reason for this may be an attempt to assure the government of NASA perfection and success in order to ensure the supply of funds. The other may be that they sincerely believed it to be true, demonstrating an almost incredible lack of communication between themselves and their working engineers.

. . . .

For a successful technology, reality must take precedence over public relations, for nature cannot be fooled.[2]


We need to understand what the actual failure rates are. We also need to work on the failure rate that comes from operator error.

The reason people are able to lie to us with statistics (statistics do not lie, but statistics can be used by liars) is that we choose to remain ignorant of the appropriate use of statistics. We ask to be lied to.

What is an acceptable failure rate? It isn’t zero, because a zero failure rate is a lie.


[1] FDA takes steps to improve reliability of automated external defibrillators
January 28, 2015
Food and Drug Administration
FDA News Release

[2] Volume 2: Appendix F – Personal Observations on Reliability of Shuttle
Report of the Presidential Commission on the Space Shuttle Challenger Accident (Also known as The Rogers Commission Report)
by R. P. Feynman
NASA report


The FDA Gives Us Recalls and Label Changes for EMS Week

Image credit.

The FDA (Food and Drug Administration) has been busy with recalls and label changes this past week for EMS week.

Labetalol Hydrochloride Injection, USP, 100 mg/20 mL (5 mg/mL) 20 mL Multidose Vial, NDC 0409-2267-20, Lot 36-225-DD, Expiration 12/01/2015.[1]


This is worse than the usual particulate matter. Since this is often used to lower the blood pressure of patients with bad things happening in the brain or the heart, a bit of particulate matter could be the coup de grâce.

The embedded particulate was identified as stainless steel and the floating particulate as iron oxide. To date, Hospira has not received reports of any adverse events associated with this issue for this lot. Hospira has attributed the embedded particulate to a supplier’s glass defect.[1]


Image at DailyMed.

Dobutamine is another medication with a recall that is given to some of our less stable patients.

In general, injected particulate matter may result acutely in local inflammation, phlebitis, and/or low level allergic response through mechanical disruption of tissue or immune response to the particulate. Small capillaries may become obstructed.[2]


Dobutamine is supposed to improve circulation through small capillaries. 😳


Suppose you would like to ventilate a patient with a BVM (Bag Valve Mask) resuscitator (with the mask or connected to an endotracheal tube, a tracheostomy tube, and LMA, a King airway, . . . ). Some of them might not work properly.

voluntary medical device removal of a limited number of Ventlab™ Resuscitator Bags after becoming aware of complaints regarding a sticking duckbill valve that resulted in the resuscitation bags delivering no air through the patient valve, to the patient. The valves may stick due to incomplete curing during the manufacturing process. Resuscitation bags affected may not function properly and may result in a delay of treatment and life threatening health consequences that include hypoxia and hypoventilation.[3]


A sticking duckbill valve?

At 25 seconds of this video, there is a good view of the duckbill valve from the patient end.


There has been one report of injury requiring medical intervention due to the lack of a functional resuscitation bag and 31 reports of a delay in oxygenation due to the requirement to utilize a 2nd or 3rd device. The FDA has been notified of this voluntary action by Ventlab, LLC.[3]


If you are using injectable risperidone (Risperdal), watch out for anaphylaxis. It is rare, but it can make a bad situation worse and you probably were not injecting risperidone because the patient is being helpful.

6.8 Postmarketing Experience [for Risperdal Consta ]

  • added: Very rarely, cases of anaphylactic reaction after injection with RISPERDAL CONSTA have been reported during postmarketing experience in patients who have previously tolerated oral risperidone.[4]

    One of the new anticoagulants does not appear to increase the rate of stroke or heart attack (compared to warfarin [Coumadin]). Yay!

    But it does appear to increase the rate of GI bleed (GastroIntestinal bleed) (compared to warfarin [Coumadin]). Remember to pay attention to any signs of changes in bowel habits of signs of anemia in patients taking the newer anticoagulants.

    The new study included information from more than 134,000 Medicare patients, 65 years or older, and found that among new users of blood-thinning drugs, Pradaxa was associated with a lower risk of clot-related strokes, bleeding in the brain, and death, than warfarin. The study also found an increased risk of major gastrointestinal bleeding with use of Pradaxa as compared to warfarin. The MI risk was similar for the two drugs.[5]


    NTG (NiTroGlycerin – GTN GlycerylTriNitrate in Commonwealth countries) no longer has the following precaution –

    Drug Interactions

    deleted: “Patients receiving antihypertensive…..concomitantly”


    That was the good news.

    NTG is still discouraged if a patient is taking a PDE-5 (PhosphoDiEsterase-5) inhibitor.


    [1] Hospira Announces Voluntary Nationwide Recall Of One Lot Of Labetalol Hydrochloride Injection, USP, 100 MG/20 ML (5MG/ML), 20 ML, Multidose Vial, Due To Visible Particulates
    May 16, 2014
    Recalls, Market Withdrawals, & Safety Alerts

    [2] Hospira Announces Voluntary Nationwide Recall Of One Lot Of Dobutamine Injection, USP, 250 MG, 20 ML, Single-Dose Fliptop Vial, Due To Visible Particulates
    May 16, 2014
    Recalls, Market Withdrawals, & Safety Alerts

    [3] Ventlab, LLC. Issues a Nationwide Recall of Ventlab Resuscitator Bags Due to Possible Health Risk
    May 16, 2014
    Recalls, Market Withdrawals, & Safety Alerts

    [4] Risperdal (risperidone) tablets, oral solution, Risperdal M-Tab (risperidone) orally disintegrating tablets, and Risperdal Consta (risperidone) long-acting injection.
    Page Last Updated: 05/16/2014
    Safety information
    Label change

    [5] Pradaxa (dabigatran): Drug Safety Communication – Lower Risk for Stroke and Death, but Higher Risk for GI Bleeding Compared to Warfarin
    [Posted 05/13/2014]
    Safety information
    Label change

    [6] Nitrostat (nitroglycerin, USP) Sublingual Tablets
    Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)

    Page Last Updated: 05/16/2014
    Safety information
    Label change


    Homeopathic Product Recalled for Containing Real Medicine


    Homeopathic products are supposed to be diluted down to where they contain nothing.

    They definitely are not supposed to contain antibiotics, since antibiotics were not understood when Samuel Hahnemann made up the idea of homeopathy.

    FDA has determined that these products have the potential to contain penicillin or derivatives of penicillin, which may be produced during the fermentation process. In patients who are allergic to beta-lactam antibiotics, even at low levels, exposure to penicillin can result in a range of allergic reactions from mild rashes to severe and life-threatening anaphylactic reactions.[1]


    The law of similars. Find a poison that produces similar symptoms, preferably not the cause of the illness (not that a homeopath would know) and dilute the poison down to nothing.

    The water (or alcohol) is expected to remember the poison, but forget everything else that has been in the water, and magically cure the illness by doing the opposite of what the poison would do.

    The water is diluted to 1% of what was in it enough times that there should not be any poison left. The homeopath also hits the water a lot to teach the water to remember the poison. This is the magic memory of water.

    The result is nothing.

    Image credit.

    When blood-letting was a common treatment, this was better than going to a doctor, but still not as good as staying at home and saving your money, because who needs to go buy nothing?

    The idea that the more dilute the solution, the more potent the “medicine” is ridiculous. Somebody would be able to demonstrate the differences in strengths, but homeopathy is just another placebo with just another excuse to scam people.

    At what concentration of nothing does it start to work?

    At what concentration of nothing does it become dangerous?

    Is it still a solution when there is nothing in it?


    Hover text –

    Dear editors of Homeopathy Monthly: I have two small corrections for your July issue. One, it’s spelled “echinacea”, and two, homeopathic medicines are no better than placebos and your entire magazine is a sham.[2]


    One of the problems with dealing with a fraud is the inability to tell the difference between incompetence and intentional fraud.

    Homeopath X is a true believer. He believes that homeopathy works, but is too incompetent to keep real medicine out of his nothing.

    Homeopath XX is willing to sell anything that pays. He knows that homeopathy is nonsense, but wants to add real medicine to make it seem that the water is having some sort of effect beyond a placebo effect. He adds real medicine after the dilution for that effect. This is not rare.

    Homeopaths claim that their medicines are safe and that real medicines are dangerous, so why add medicine?

    Since homeopathy is all lies, should we believe anything a homeopath says?

    If you dilute a lie enough times, does it become truth?

    We have enough problems with believing in magic with real medicines without adding the problems of homeopathy, where there is nothing real except fraud.


    [1] Pleo Homeopathic Drug Products by Terra-Medica: Recall – Potential for Undeclared Penicillin – Includes Pleo-FORT, Pleo-QUENT, Pleo-NOT, Pleo-STOLO, Pleo-NOTA-QUENT, and Pleo-EX
    Posted 03/20/2014
    Safety Alert

    [2] dilution


    Etomidate Recall


    Etomidate, sold as generic etomidate (not the brand name Amidate, although at least one site is erroneously reporting that Amidate is being recalled), is being recalled by the manufacturer.

    All of the products bear a Pfizer label.[1]


    Image credits.


    Above are the images from the FDA (Food and Drug Administration) label for the lot numbers affected. Unless the package design has changed, this is what the packages should look like.

    due to the potential for small black particles, identified as paper shipper labels, to be present in individual vials; the potential for missing lot number and/or expiry date on the outer carton, and the potential for illegible/missing lot number and expiry on individual vials.[1]


    No adverse events have been reported, yet, according to the manufacturer, but injecting a medication that is suspected of having contaminants very bad patient care.

    For example –

    Intravenous administration of particles may lead to impairment of microcirculation, phlebitis, infection, embolism and subsequent infarction.[1]


    Here are the lot numbers to look for. If the lot number is not legible, then it is included in the recall. If the expiration date is not legible, then it is included in the recall.


    Remember that giving etomidate does not relieve pain, it only sedates, so we need to give something for pain if we are doing something that causes pain. Intubation is the most common example.

    the immediate recovery period will usually be shortened in adult patients by the intravenous administration of approximately 0.1 mg of intravenous fentanyl, one or two minutes before induction of anesthesia, probably because less etomidate is generally required under these circumstances (consult the package insert for fentanyl before using).[2]


    Etomidate is a hypnotic drug without analgesic activity.[1]


    The dose is 0.3 mg/kg, so there is no maximum dose because of weight. If there is a maximum dose permitted by protocol, consider using a medication that does not have an inappropriate limit.

    The patients most likely to present problems with intubation are the heaviest patients. These are the patients most likely to be inappropriately prevented from getting an effective dose by a bad protocol.

    If the maximum dose is 30 mg, then no patient over 100 kg (220 pounds) will receive an appropriate dose if you follow the protocol limit. That is not a very big patient. How difficult should we make airway management in order to appease medical directors? We used to be giving 2 mg of morphine with extreme caution because of the same inappropriate fantasy of caution.

    Overdosage may occur from too rapid or repeated injections. Too rapid injection may be followed by a fall in blood pressure. No adverse cardiovascular or respiratory effects attributable to etomidate overdose have been reported.


    Not from too large a dose?

    Not from an appropriate dose that is more than 30 mg, or more than 40 mg, or more than 50 mg, or more than 60 mg, or . . . ?

    The LD50 of etomidate administered intravenously to rats is 20.4 mg/kg.[2]


    The LD50 is the dose expected to kill about half of those receiving the dose. A little bit larger dose would probably kill more than half, while a little bit smaller dose would probably kill less than half.

    This is the dose that gives the patient about a 50/50 chance of survival/death. A Schrödinger dose.

    Not 20.4 mg.

    20.4 mg/kg, so there is a lot of flexibility in dosing, even in humans.

    The dose for induction of anesthesia in adult patients and in children above the age of ten (10) years will vary between 0.2 and 0.6 mg/kg of body weight, and it must be individualized in each case. The usual dose for induction in these patients is 0.3 mg/kg, injected over a period of 30 to 60 seconds.[2]


    Anywhere from 20 mg to 60 mg for a 100 kg patients would be an appropriate dose, according to the FDA, but the usual dose would be 30 mg.

    Anywhere from 40 mg to 120 mg for a 200 kg patients would be an appropriate dose, according to the FDA, but the usual dose would be 60 mg.

    One way to limit the dose of etomidate and decrease the amount of time etomidate is affect the patient is to give fentantl before the etomidate, according to the FDA.

    Make sure that intubation is followed by continuous sedation and pain management.[3]

    We need to better understand pharmacology for our patients’ sake.


    [1] Agila Specialties Private Limited Initiates Voluntary Nationwide Recall of 10 Lots of Etomidate Injection 2 mg/mL – 10 mL and 20 mL due to the Presence of Particulate Matter and/or Illegible and Missing Lot Number and/or Expiry Date
    February 19, 2014
    Page Last Updated: 02/19/2014
    Recall — Firm Press Release

    [2] ETOMIDATE injection
    [Pfizer Laboratories Div Pfizer Inc.]

    FDA label

    [3] Pain and Terror as Effective Pressors
    Dr. Scott Weingart
    May 16, 2011
    Podcast page.


    A Recalled AED is Better Than No AED

    Cardiac arrest. CPR in progress. Do not use the AED, because it has been recalled!



    HeartStart automated external defibrillators from Philips Healthcare have been recalled.

    What does the FDA (Food and Drug Administration) mean by recall?

    Well, why was the recall issued?

    Certain HeartStart automated external defibrillator (AED) devices made by Philips Medical Systems, a division of Philips Healthcare, may be unable to deliver needed defibrillator shock in a cardiac emergency situation, the U.S. Food and Drug Administration said today in a new safety communication for users of these previously recalled devices.[1]


    A shock might not be delivered.

    What does the FDA recommend?

    “The FDA advises keeping all recalled HeartStart AEDs in service until you obtain a replacement from Philips Healthcare or another AED manufacturer, even if the device indicates it has detected an error during a self-test,” said Steve Silverman, director of the Office of Compliance in the FDA’s Center for Devices and Radiological Health.[1]


    Do not take these AEDs out of service service until a replacement is present.


    What about the lawyers?

    But it’s defective!

    Thinking is dangerous!

    “Despite current manufacturing and performance problems, the FDA considers the benefits of attempting to use an AED in a cardiac arrest emergency greater than the risk of not attempting to use the defibrillator.”[1]


    The benefit is greater than the risk.

    There is risk with everything.

    Anyone who tells you otherwise is selling something.

    There is not benefit with everything.

    Since the detection of an error during the self-test does not guarantee that the AED will not deliver a shock when needed, removing the AED without a replacement is more dangerous than leaving the AED in service.

    These recalled AEDs are better than no AED.

    Of course, if needed for use in an emergency, make every attempt to clear the error and use the device normally, as described in the Owner’s Manual.[2]


    The manufacturer and the FDA agree that, in the case of these AEDs, something is better than nothing.

    Are we really going to make a dead patient more dead by using a defective AED?


    [1] FDA issues safety communication on HeartStart automated external defibrillators from Philips Healthcare
    FDA News Release
    For Immediate Release: Dec. 3, 2013
    Media Inquiries: Jennifer Rodriguez, 301-796-8232, jennifer.rodriguez@fda.hhs.gov
    Consumer Inquiries: 888-INFO-FDA
    News Release

    [2] Philips HeartStart FRx and OnSite (HS1) automated external defibrillators (AEDs)
    Phillips Healthcare
    Maintenance Advisory


    Is that Aspirin or Acetaminophen? Recall Due to Wrong Drug in Packages


    Last week the FDA (Food and Drug Administration) sent out a safety announcement about a recall of Rugby label Enteric Coated Aspirin Tablets, 81 mg, Lot 13A026.


    The package does not contain 81 mg aspirin, but actually contains 500 mg acetaminophen (Tylenol), which is a much larger dose and is in many other over the counter medicines, such as cough and cold medicines. Almost all of these medicines contain a full adult dose of acetaminophen in addition to whatever the active ingredient is (guaifenesin, dextromethorphan, et cetera).

    Consumers may be inadvertently taking Acetaminophen 500 mg instead of Enteric Coated Aspirin 81 mg which may cause severe liver damage to those who take other drugs containing acetaminophen, consumers who take 3 or more alcoholic drinks every day, or those who have liver disease. The labeled directions instructs patients to take 4-8 tablets every 4 hours, but not more than 48 tablets in 24 hours. Consumers who take 48 tablets daily of the defective product may be ingesting up to 24,000 mg of Acetaminophen, which is about six times the maximum recommended daily dose of acetaminophen (4,000 mg).[1]


    Taking more acetaminophen than needed is not safe because of this duplication of doses. The liver may be able to remove the current amount of acetaminophen we are consuming (intentionally and unintentionally), but an extra half gram of acetaminophen may result in a toxic dose.

    Some people only take 81 mg enteric coated aspirin on a daily basis for its antiplatelet effects, but the package recommends a lot more.


    “It’s not an uncommon overdose,” said Dr. Corey Slovis, who heads the department of emergent medicine at Vanderbilt University Medical Center in Tennessee. “We hate Tylenol overdose because they’re the silent overdoses.”

    Slovis said patients who overdose on acetaminophen often don’t feel sick right away, unless they’ve taken a massive dose that induces vomiting within six hours. Instead, many patients who overdose on acetaminophen don’t see a doctor for more than two days because they feel fine at first. When they finally get to Slovis, they’re often jaundiced and experiencing the early signs of liver failure.

    As such, this kind of overdose could result in liver failure, the need for a transplant or death, Slovis said.[2]


    The pills are probably larger than the normal aspirin pills, but if you are unfamiliar with the product, you would not recognize the difference. Taking a handful (4-8 tablets every 4 hours, but not more than 48 tablets in 24 hours) of pills at a time is probably not a good idea, regardless of the label instructions.

    “Did he take six pills or only five?” Well, to tell you the truth, in all this excitement I kind of lost track myself.[2]

    We have trouble counting beyond three.


    [1] Advance Pharmaceutical Inc. Issues Voluntary Recall of One Lot of Enteric Coated Aspirin Tablets, 81 mg, Due to Health Risk
    Recall – Firm Press Release
    Recall notice

    [2] Aspirin Recalled Over Bottle Mix-Up
    Sydney Lupkin (@slupkin)
    ABC News

    [3] Dirty Harry (1971)


    FDA Warning of Zyprexa Deaths – NOT With the Drug used by EMS or in the Emergency Department


    Today the FDA (Food and Drug Administration) sent out a safety announcement about long-acting olanzapine (Zyprexa Relprevv).

    This is not the form of olanzapine (Zyprexa) used by EMS or used in the ED (Emergency Department).

    Post-injection Delirium Sedation Syndrome (PDSS): Patients are at risk for severe drowsiness (including unconsciousness or coma) and/or confusion and disorientation after each injection and must stay at the doctor’s office or clinic for at least 3 hours after the injection is given. ZYPREXA RELPREVV is only prescribed by doctors who are enrolled in the ZYPREXA RELPREVV Patient Care Program to patients who are also enrolled.[1]


    The affected medication is packaged as Zyprexa Relprevv, the long-acting version of olanzepine.

    Image credit.[2]

    We would use olanzapine in its regular formulation, which has been available as a generic since 2011, when Eli lilly’s patent expired.

    The patent on Zyprexa Relprevv does not expire until September 30, 2018, so it is only available as an expensive version from Eli Lilly.[3]

    What happened?

    FDA is investigating two unexplained deaths in patients who received an intramuscular injection of the antipsychotic drug Zyprexa Relprevv (olanzapine pamoate). The patients died 3-4 days after receiving an appropriate dose of the drug, well after the 3-hour post-injection monitoring period required under the Zyprexa Relprevv Risk Evaluation and Mitigation Strategy (REMS). Both patients were found to have very high olanzapine blood levels after death.[4]


    Why 3 hours?

    Click on images to make them larger.

    Post-injection delirium/sedation syndrome events and time to initial onset, incapacitation, and hospitalization. The middle line inside the box is the median 50th percentile; left border of the box is the 25th percentile and right borders of the box is the 75th percentile; left whisker is the 10th percentile and right whisker is the 90th percentile.[5]


    All patients demonstrated symptoms within 5 hours of injection, so onset 3 to 4 days after injection seems unlikely. This medication can only be given in the clinic or doctor’s office, so an extra dose is improbable.

    How likely is it that the cause of death is the medication?

    It would seem unlikely, except that Both patients were found to have very high olanzapine blood levels after death.

    The FDA will investigate this and may find out the cause(s) of death, or may nor find out the cause(s) of death, but it does not appear to be something that affects emergency patients.

    These patients may present to EMS, or the ED, from a doctor’s office or clinic and we should be familiar with treatment.

    Symptoms appear to be less severe than with an overdose of olanzapine, so management should be just supportive care (assess blood sugar, vital signs, level of consciousness, . . .), only treating what truly needs to be treated (seizures, airway compromise, . . .).

    As discussed by McDonnell et al. [5], the probable mechanism most likely involves accidental entry of the medication into the blood stream following blood vessel injury during the injection process. The similarity in incidence of olanzapine LAI PDSS (0.07% of injections) to that of Hoigne’s syndrome following accidental intravascular injection of penicillin procaine G (0.08% of injections) [6] suggests that these findings may be approximating the naturally occurring background rate for accidental direct or indirect intravascular injection during any intramuscular injection process.[5]


    Accidental intravenous, or intra-arterial, injection does not seem to be a possible cause of deaths that happen several days later.

    We do not have other information on the patients, such as when they were last seen without any symptoms, what other medications they were taking, what other medical conditions were present, whether there were signs of trauma, . . . , so the only thing to do is wait for more information.

    If you carry olanzapine, there is no reason not to keep using it as before.

    If this encourages you to switch to ketamine, I do not see any problem with that decision.


    [1] Important Safety Information about ZYPREXA® RELPREVV™ (olanzapine) For Extended Release Injectable Suspension
    Eli Lilly
    Home page.

    [2] ZYPREXA RELPREVV (olanzapine pamoate) kit
    [Eli Lilly and Company]

    FDA Label

    [3] Generic Zyprexa Relprevv Availability
    Information page.

    [4] Zyprexa Relprevv (Olanzapine Pamoate): Drug Safety Communication – FDA Investigating Two Deaths Following Injection
    Posted 06/18/2013
    FDA Drug Safety Communication

    [5] Post-injection delirium/sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection, I: analysis of cases.
    Detke HC, McDonnell DP, Brunner E, Zhao F, Sorsaburu S, Stefaniak VJ, Corya SA.
    BMC Psychiatry. 2010 Jun 10;10:43. doi: 10.1186/1471-244X-10-43.
    PMID: 20537128 [PubMed – indexed for MEDLINE]

    Free Full Text from BMC Psychiatry.