Another McNeil OTC drug recall: quality control issues not just for generic drugs

Let me just say at the outset that I generally pay extra to purchase brand name medications, prescription or over-the-counter (OTC), because of concerns I have about federal oversight of generic drug manufacturers.
On April 30, McNeil Consumer Products issued a voluntary recall of a litany of children’s cold products under the Tylenol, Motrin, Zyrtec and Benadryl brand names.

McNeil Consumer Healthcare, Division of McNEIL-PPC, Inc., in consultation with the U.S. Food and Drug Administration (FDA), is voluntarily recalling all lots that have not yet expired of certain over-the-counter (OTC) Children’s and Infants’ liquid products manufactured in the United States [in Fort Washington, PA] and distributed in the United States, Canada, Dominican Republic, Dubai (UAE), Fiji, Guam, Guatemala, Jamaica, Puerto Rico, Panama, Trinidad & Tobago, and Kuwait.

The complete product list can be found at the bottom of the press release (here) from which the above quote was derived.
McNeil noted that “some of the products included in the recall may contain a higher concentration of active ingredient than is specified; others may contain inactive ingredients that may not meet internal testing requirements; and others may contain tiny particles.”
However, an ABC News story on the recall provides an FDA report (PDF) indicating that some of the remedies contained as-yet unidentified gram-negative bacteria.
Your humble blogger was contacted for this story and quoted therein but I had not known at the time of the bacterial contamination. All reports suggest that these problems are unlikely to present any risks to infants and children, pending identification of the bacteria, but this cannot be good – especially since this is the third recall by the manufacturer in the last eight months.
ABC News quoted a statement released Tuesday from Johnson & Johnson, the parent company of McNeil Consumer Healthcare:

“The quality issues that the FDA has observed, many of which we had recently identified in our own quality reviews and communicated to the FDA, are unacceptable to us, and not indicative of how McNeil Consumer Healthcare intends to operate,” the Johnson and Johnson statement read.

This recall is also yet another blow to the widely-held belief in the higher-quality of a brand name drug product over generic drugs, at least in the case of over-the-counter products:
“This recall provides compelling evidence that quality assurance is an issue for all drugmakers, and is not specific to generic products, as many have implied,” said Dr. Jerry Avorn, professor of medicine at Harvard Medical School and chief of the Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital.
What struck me was the report from the Associated Press and the FDA’s own Q&A site that until these products are back on the market, parents use alternative products with the same ingredients on the labels – i.e., generic versions of the McNeil products – rather than trying to calculate how much of an adult-strength product to use in an infant or child.
I wonder how many parents might switch to the generics, see the incredible price savings, and switch permanently to one of these products.
Commenters at several of the news site also note that there has been much ado about quality control issues at drug plants outside the US; that excuse can’t be invoked in this case.

Nzu: African morning sickness remedy in Texas contains lead and arsenic

The US FDA has released a statement based on finding from the Texas Department of State Health Services on December 23, 2009:

The Texas Department of State Health Services is warning consumers, especially pregnant or breastfeeding women, to avoid consuming a traditional product called “Nzu” because of the potential health risks from high levels of lead and arsenic.
Nzu, which is consumed as a traditional remedy for morning sickness, has been found by DSHS food inspectors at two African specialty stores – one in the Dallas area and one in Houston. It was also found at a distributor in Houston. The product generally resembles balls of clay or mud and also is called Calabash clay, Calabar stone, Mabele, Argile and La Craie.
Laboratory analysis by DSHS found high levels of lead and arsenic in this product.
Exposure to lead can result in a number of harmful effects, and a developing child is particularly at risk of effects on the brain and nervous system. Arsenic is a carcinogen, and excessive long-term exposure to it has been associated with a range of adverse health effects, including cancers of the urinary bladder, lung and skin.
The Nzu may be covered in a brown or white “dust” and is usually sold in small plastic bags with a handwritten label identifying it as “Nzu” or “Salted Nzu.”
Anyone who has been ingesting the product should contact their health care provider.
The source of the product in Texas is not yet known. Inspectors with DSHS are continuing to investigate.

Ingesting soil, particularly mineral-rich clay, is a practice called geophagy. Various kinds of earth have been a folk remedy common to many cultures, primarily for gastrointestinal complaints.
In fact, that is where the name “Terra Sigillata” is derived.
Terra Sigillata was a fatty clay harvested from the Greek isle of Lemnos and contained at least one component found in today’s Kaopectate diarrhea remedy. A special ceremony would be held to harvest the clay where it would be cut into planchets, embossed with an official seal, then dried and sold. Terra Sigillata stands in pharmacy history as the first trademarked medicine.
Geophagy is also why South Carolinians are sometimes called “sandlappers” and why this Nigerian remedy is often called “Calabash Clay” or “Calabash Chalk.” (Calabash is a coastal town right at the border between North and South Carolina. A style of spiced seafood, usually shrimp, is also known as Calabash.)
But as regards “nzu,” a warning similar to that in Texas came out in 2002 from the Northern Ireland Department of Health, Social Services, and Public Safety (PDF).
In trying to dig up some literature, I believe this may be the first time I have entered a search term in PubMed and come up with zero returns. A search for Calabash chalk comes up with a 2004 paper in Chemosphere for which I cannot obtain full text. The abstract is suggestive that samples were analyzed for several elements and environmental contaminants, with 40 mg/kg of lead being present as well as pesticides. I believe that I will have to consult my geology or Nigerian colleagues for more information on this as I anticipate there is far more literature available but perhaps in regional journals not abstracted by the US National Library of Medicine. I’m primarily curious as to where such samples might be taken from so as to have such high levels of Pb.
In the meantime, I’ll be interested to learn later what case(s) in Texas spurred the current FDA action but I hypothesize that it involved pre-natal, post-natal, or maternal neurological toxicity.

Dr Saul Schanberg: neuroscientist, physician, mentor, teacher, father, husband

Saul and Rachel.JPGAlthough I saw this obituary over the weekend, I didn’t get to posting it until today. I was reminded by a local friend, an outstanding young scientist in her own right, of the impact that Dr Schanberg had made on so, so many lives in science, medicine, and our larger community.
I only had the honor of meeting Dr Schanberg once, shortly after his cancer diagnosis, while we were at a Duke Cancer Patient Support Center fundraising dinner. His wife of over 50 years, Rachel, is founder and former director of the organization which they started following the loss of their own daughter.
Among the many scientists and physicians that were mentored by Dr Schanberg is my dear friend and colleagues, Dr Cindy Kuhn. I knew that Dr Kuhn had worked with Dr Schanberg extensively, having co-authored 83 publications. What I had not appreciated previously was that Cindy had also done her PhD work with Saul – so much for that rule of distancing oneself from one’s mentor.
I can’t do any better than the obituary that follows.

“Saul was a warm and wonderful, high-spirited, opinionated and good humored man much loved for his infectious enthusiasm for science, his love of Duke (and Duke basketball) and most importantly his commitment to his family and friends.”

And I couldn’t live a life any better than that.

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Nipple cream warning: harmful to nursing infants

I missed this FDA warning in my e-mail box this week. But given the use of such products by breast-feeding women we know, I think this warning is worth publicizing here – chlorphenesin is a centrally-active skeletal muscle relaxant that is for some reason used in cosmetics but is not intended for oral consumption:

FDA Warns Consumers Against Using Mommy’s Bliss Nipple Cream
Product can be harmful to nursing infants

The U.S. Food and Drug Administration is warning consumers not to use or purchase Mommy’s Bliss Nipple Cream, marketed by MOM Enterprises, Inc., because the product contains potentially harmful ingredients that may cause respiratory distress or vomiting and diarrhea in infants. The product is promoted to nursing mothers to help soothe and heal dry or cracked nipples. Product labeling specifically states that there is no need for mothers to remove the cream prior to nursing. However, the ingredients contained in the product may be harmful to nursing infants.
Potentially harmful ingredients in Mommy’s Bliss Nipple Cream are chlorphenesin and phenoxyethanol. Chlorphenesin relaxes skeletal muscle and can depress the central nervous system and cause respiratory depression (slow or shallow breathing) in infants. Phenoxyethanol is a preservative that is primarily used in cosmetics and medications. It also can depress the central nervous system and may cause vomiting and diarrhea, which can lead to dehydration in infants.
Mothers and caregivers should watch for a decrease in an infant’s appetite. More serious signs would be difficulty in awakening the child, limpness of extremities or a decrease in an infant’s strength of grip and a change in skin color. Please seek immediate medical attention if your child is showing these signs and symptoms.
“The FDA is particularly concerned that nursing infants are being unwittingly exposed by their mothers to this product with dangerous side effects,” said Janet Woodcock, M.D., director, FDA’s Center for Drug Evaluation and Research. “Additionally, these two ingredients may interact with one another to further compound and increase the risk of respiratory depression in nursing infants.”
Though the FDA has not received any reports of injury to infants, the agency is alerting the public because of the potential harm this product can have on a child.
Chlorphenesin can also harm the mother by causing dermatitis, a skin condition that can worsen the drying and cracking of nipple skin.
MOM Enterprises, Inc. is based in San Rafael, Calif. The company has stated that it has discontinued marketing the nipple cream with the potentially harmful ingredients. The FDA is advising consumers to discontinue use of Mommy’s Bliss Nipple Cream and to consult a health care professional if they experience problems or believe that their infant may have experienced problems due to this product. Nursing mothers with cracked, painful nipples, which is often a side effect of nursing, should speak with their health care professional or a certified lactation consultant if the problem is severe or for other treatment options.
Consumers are strongly encouraged to report adverse events related to this product or any FDA approved product to MedWatch, the agency’s voluntary reporting program, by e-mail at, or by phone at 800-332-1088, or by fax to 800-332-0178. Consumers may also mail reports of adverse events to MedWatch, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD, 20852-9787.

“You got lead in my marijuana. . .”

“. . .you got marijuana in my lead.”
Two great tastes that do not go great together (with apologies).
[Welcome readers on 12 Oct 2008 – I comment on the recent story here and you can read our other posts on drugs of abuse here. Thanks for stopping by – APB]
ResearchBlogging.orgA concise but fascinating medical detective story appears in the letters of this week’s (10 Apr 2008) issue of the New England Journal of Medicine (free full text at the time of this posting.).
An astute group of physicians at Leipzig Hospital in Germany noted a local surge of young people presenting with classic symptoms of lead poisoning – 29 patients aged 16 to 33 over the course of 3-4 months. Patients exhibited symptoms ranging from abdominal cramps, nausea, and “Burton’s line” to hematologic pathologies such as anemia and basophilic stippling (overview). Burton’s line, illustrated here in another NEJM image from a lead poisoning case, results from “the reaction of circulating lead with sulfur ions released by oral microbial activity [that] may cause the deposition of lead sulfide at the interface of the teeth and gums.”
In another hospital in Leipzig, one patient was so severely poisoned that they had severe encephalopathy with hallucinations and permanent palsy in one forearm.
None of the patients were in any industry, such as lead-smelting, where today’s rare cases of lead poisoning still occur. Instead, they were young smokers with body piercings, either students or unemployed.

The diagnosis was quickly established, and chelation therapy was effective, but despite great efforts by health authorities and police, the source of lead could not be identified.

Yes, this is the one evidence-based indication for chelation therapy, usually with aminocarboxylate (calcium EDTA) or sulfur-containing compounds (2,3-dimercaptosuccinic acid; DMSA; succimer; Chemet®) to complex the lead with very high affinity and enhance its urinary excretion.
What else was common to these patients?

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Childhood cancer chemotherapy pioneer, Dr Charlotte Tan, dies at 84

Charlotte%20Tan.jpgActinomycin D was the first antitumor antibiotic isolated from Streptomyces parvallus cultures by the lab of 1952 Nobel laureate, Dr Selman Waksman, at Rutgers University. However, it took a young Chinese physician and the confidence in her by a future US Surgeon General for this natural product drug to positively impact the lives of children with cancer.
An unusually engaging Boston Globe obituary by Gloria Negri caught my attention this week that announced the death of pediatric oncology pioneer, Charlotte Tan (Hsu), MD, of pneumonia on 1 April in Brookline, MA. Dr Tan’s 1959 paper in Pediatrics yielded our first insights on the potential benefit of actinomycin D in Wilms’ tumor and childhood leukemias and lymphomas (The structure below is taken from that paper).
Act%20D%201959%20Tan.jpgKnown often as dactinomycin, the drug also went on to be used in rhabdomyosarcoma. However, most researchers today probably only know the drug as a laboratory tool to inhibit RNA polymerase activity or in the form of its fluorescent DNA-intercalating analog, 7-amino-actinomycin D (7-AAD), used to stain DNA in microscopy and cellular flow cytometry-based apoptosis methods.
Regular readers may know how deeply I revere pioneers in basic and clinical and cancer research; many of these researchers just happen to be women, including my idol, 1988 Nobel laureate Gertrude (Trudy) Elion for her work on antimetabolite chemotherapy. I’m just thinking out loud here but I wonder if the pioneering work of women in the cancer field had something to do with that group of diseases attracting professionals possessing a greater depth of compassion than your average Y-chromosome bearer.
Be that as it may, Dr Tan’s story is fascinating:

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NPR’s The People’s Pharmacy on bisphenol A, endocrine disruptors

200px-Bisphenol_A.svg.pngBisphenol A (BPA) is currently one of the major lightning rods for controversy in consumer products and public health research. The compound is used in the manufacture of plastic bottles, polycarbonate (PC) in particular, as well as in the lining of many food and beverage cans. The compound has been recognized since the 1930s as having estrogenic activity but it appears to have developmental, carcinogenic, and neurotoxic effects at concentrations well below those at which it binds to the two forms of estrogen receptor.
US governmental advisory committees can’t even agree on BPA. Public health blogger revere at Effect Measure posted last October about two conflicting reports from the US National Toxicology Program on the developmental risks of BPA – the contentious comment thread following the post is illustrative of the confusion surround BPA even among scientists. This 2005 review in Environmental Health Perspectives makes for a good introduction before delving into the current literature.
So if the scientists are confused, well guess what the public thinks? To shed light on this topic, award-winning medical journalists Joe and Terry Graedon will focus the next two shows of their NPR-syndicated The People’s Pharmacy radio show on BPA and the larger issue of endocrine disruptors. This week’s (1 March) guests are:

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American Association of Pediatrics seeks to combat antivaccinationist misinformation

For more details on this story, you can go to Mark Chu-Carroll, Orac, Mike the Mad Biologist, or the Autism Blog. I just wanted to share my personal views on the need for childhood vaccinations and support a public information campaign from the AAP.
Until I started medical blogging, I had not realized quite how vocal was the community of individuals refusing to vaccinate their children, mostly at the urging of those who claimed that vaccines and related components caused illness in their own children. I will first say that no drug product, natural or otherwise, is completely and absolutely free of side effects. One can never predict with absolute certainty how individuals in a genetically-diverse population of 300 million Americans or some 6 billion people worldwide will respond to any product.
But as a society, we have decided that the good of the public’s health is more than offset by the risks to the few; vaccines save lives but the generation that experienced life, and death, before vaccines is increasingly dying off. My child is completely up-to-date on vaccines because I could not bear to lose her to a preventable childhood disease; we still have family and friends who survived polio with varying degrees of debilitation – and they are the lucky ones, from an era before vaccines.

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Dr. Flea on medblogging and malpractice

Via Berci Meskó at Science Roll, I learned that the medblogger-formerly-known-as Flea has just given his first detailed interview since shutting down his blog during his pediatric malpractice case. Fellow physician, Orac, had a characteristically complete commentary on the situation that included the admonition not to blog about one’s own ongoing malpractice trial. I also recall being shocked at the time that Flea would make off-color comments about the plaintiff attorney’s bedroom habits.
In his interview on Eric Turkewitz’s New York Personal Injury Law Blog, Dr Robert “Flea” Lindeman details the additional pain incurred by a lawsuit that drags on for five years after one loses a kid one has cared for:

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Children’s Cold Medicine Controversy

Perhaps you’ve stumbled on this post late at night while tending to a child suffering from a cold.
Well, I’ve been reading a fair bit lately about the 18-19 October meeting of the FDA’s joint meeting of their Nonprescription Drug and Pediatric Advisory Committees, trying to make sense about calls to restrict or prohibit the use of cough and cold medicines in children under age 6. There is so much material on the subject that I have hesitated to post on the issue until I received the following e-mail from an old friend, fellow scientist and parent, North of 49:

Okay, so I’m writing to you to in order to prod you to open up a discussion on Terra Sig about the FDA recommendation that cough and cold medicines not be administered to kids. As a pharmacologist, what are your thoughts on this? What about as a parent?
According to the FDA’s own report, only 11 [efficacy] studies (in humans) have been done on these compounds, and even they admit that many of these were scientifically flawed. Yet, the FDA panel voted (13-9) to recommend stopping the use of cough and cold meds for kids [aged 2 to 5 yrs]. My feeling is that this is likely because of the deaths that have resulted from their improper use – A quick check, however, reveals that since 1969, 123 kids have died. This sounds like a lot, but when you calculate the number of doses that must have been given in the 38 yr time period, and the fact that (according to the FDA) a number of deaths were the result of parental error (either overdose of using multiple meds with similar active ingredients), it seems to me (as a humble physiologist) that your chances of being struck by lightning are higher if the meds are used properly – In fact, your chance of being struck (and killed) by lightning are approximately 20-fold higher – In the USA every year, 73 people die after being struck by lightning!!! (source)
Damn you Mother Nature!! Perhaps the FDA will recommend that we never go outside.
Also, the odds of death by a spoonful of medicine don’t even come close to the matching the odds of what we would (rationally) consider highly, highly improbable events:
Odds of fatally slipping in bath or shower: 2,232 to 1
Odds of getting away with murder: 2 to 1
Odds of dating a supermodel: 88,000 to 1
Odds of being on plane with a drunken pilot: 117 to 1
Chance that Earth will experience a catastrophic collision with an asteroid in the next 100 years: 1 in 5,000
Please guide us in this important discussion, o wise one.

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