Cumulative Use of Strong Anticholinergics and Incident Dementia
Shelly L. Gray, PharmD, MS1; Melissa L. Anderson, MS2; Sascha Dublin, MD, PhD2,3; Joseph T. Hanlon, PharmD, MS4; Rebecca Hubbard, PhD2,5,6; Rod Walker, MS2; Onchee Yu, MS2; Paul K. Crane, MD, MPH7; Eric B. Larson, MD, MPH2,7
Importance Many medications have anticholinergic effects. In general, anticholinergic-induced cognitive impairment is considered reversible on discontinuation of anticholinergic therapy. However, a few studies suggest that anticholinergics may be associated with an increased risk for dementia.
Objective To examine whether cumulative anticholinergic use is associated with a higher risk for incident dementia.
Design, Setting, and Participants Prospective population-based cohort study using data from the Adult Changes in Thought study in Group Health, an integrated health care delivery system in Seattle, Washington. We included 3434 participants 65 years or older with no dementia at study entry. Initial recruitment occurred from 1994 through 1996 and from 2000 through 2003. Beginning in 2004, continuous replacement for deaths occurred. All participants were followed up every 2 years. Data through September 30, 2012, were included in these analyses.
Exposures Computerized pharmacy dispensing data were used to ascertain cumulative anticholinergic exposure, which was defined as the total standardized daily doses (TSDDs) dispensed in the past 10 years. The most recent 12 months of use was excluded to avoid use related to prodromal symptoms. Cumulative exposure was updated as participants were followed up over time.
Main Outcomes and Measures Incident dementia and Alzheimer disease using standard diagnostic criteria. Statistical analysis used Cox proportional hazards regression models adjusted for demographic characteristics, health behaviors, and health status, including comorbidities.
Results The most common anticholinergic classes used were tricyclic antidepressants, first-generation antihistamines, and bladder antimuscarinics. During a mean follow-up of 7.3 years, 797 participants (23.2%) developed dementia (637 of these [79.9%] developed Alzheimer disease). A 10-year cumulative dose-response relationship was observed for dementia and Alzheimer disease (test for trend, P < .001). For dementia, adjusted hazard ratios for cumulative anticholinergic use compared with nonuse were 0.92 (95% CI, 0.74-1.16) for TSDDs of 1 to 90; 1.19 (95% CI, 0.94-1.51) for TSDDs of 91 to 365; 1.23 (95% CI, 0.94-1.62) for TSDDs of 366 to 1095; and 1.54 (95% CI, 1.21-1.96) for TSDDs greater than 1095. A similar pattern of results was noted for Alzheimer disease. Results were robust in secondary, sensitivity, and post hoc analyses.
Conclusions and Relevance Higher cumulative anticholinergic use is associated with an increased risk for dementia. Efforts to increase awareness among health care professionals and older adults about this potential medication-related risk are important to minimize anticholinergic use over time.
Note: drugs include - antihistamines sold over the counter as sleep aids, such as diphenhydramine (Benadryl, McNeil-PPC Inc), or for allergy relief, such as chlorpheniramine; oxybutynin and tolterodine for overactive bladder; and the tricyclic antidepressants, such as doxepin or amitriptyline, even when used at low doses for migraine prevention or neuropathic pain.
Source : JAMA (Jan 2015)
J&J sales plunge as new drug recall announced
Sales of Johnson & Johnson pain relievers are collapsing as a string of recalls appears to have made consumers wary of once-sterling brands such as Tylenol and Benadryl.
An eighth recall, announced Thursday, could worsen consumer reaction. That wariness and the huge amount of products pulled off store shelves together look to be costing J&J tens of millions of dollars a month.
Thursday's recall by Johnson & Johnson's McNeil consumer health care unit covers 21 lots of products, including Children's Tylenol. Those were recalled because of a musty or moldy smell, extending a large Jan. 15 recall tied to a nauseating chemical on shipping pallets.
The company said the new lots were added to the recall as a precaution after an internal review found those lots, shipped and stored before Jan. 15, had been on the same type of wooden pallets.
An April 30 recall of more than 130 million bottles of children's and infants' liquid medicines involved products J&J said "may not meet required quality standards," may contain tiny metal particles or may have too much active ingredient.
The string of recalls is an embarrassment for a company that set the standard on how to do it correctly when it rushed to pull bottles of Tylenol -- deliberately poisoned by someone who was never caught -- off store shelves in the early 1980s.
This time, the culprit appears to be a lack of internal quality control. That's harder to forgive, particularly given that the public has little tolerance for mistakes or carelessness involving products for children, said analyst Steve Brozak of WBB Securities.
"This is pain by a thousand cuts," Brozak said of the repeated recalls.
Erik Gordon, a professor and analyst at the University of Michigan's Ross School of Business, said J&J has been too conservative about replacing those responsible.
"Heads should have rolled" and longtime CEO Bill Weldon should be taking responsibility, Gordon said. "If I were on the board, I think I would be looking for his resignation."
Weldon has turned the gold standard for handling an unsafe product "into the tin standard," he added.
Data from market research firm SymphonyIRI you Group show sales of New Brunswick, N.J.-based J&J's pain reliever pills fell 56 percent in the four weeks ending June 13, compared to a year earlier.
Its figures show that U.S. sales of pain-relieving tablets, gelcaps and other types of pills, including multiple strengths of Tylenol and Motrin, plunged to $20.9 million in that four-week period, putting the company behind rivals Bayer Consumer Health and Wyeth Labs. Sales of private-label, or store brands, benefited the most from Johnson & Johnson's fall, jumping 23 percent to $51.9 million.
Meanwhile, sales in the smaller category of liquid pain relievers, such as Children's Tylenol, fell 96 percent, to just $630,000. Those figures do not include sales at Walmart, gas station stores and club stores.
Together, that amounts to tens of millions of dollars in revenue lost in just one month -- and a big hit to the reputation of the maker of iconic products such as Johnson & Johnson's baby shampoo and Band-Aids. Gordon said sales of any product with Johnson & Johnson on it will be hurt.
CathyJo Andrews threw out 10 bottles of children's medicines earlier this summer after a prior recall.
"It scared me," she said. "It's my kids."
Since then the mother of two, who lives in the Chicago suburb of Oak Lawn, has received coupons from Johnson & Johnson to reimburse her, but doesn't plan to use them soon.
Andrews said when her 6-year-old developed a fever and had an allergic reaction, she opted instead to take a trip to the pediatrician.
"I'd much rather pay for a doctor's visit and a prescription from the pharmacy than have to freak out and worry about it," the 28-year-old said.
A Johnson & Johnson spokeswoman said the company had no comment beyond its announcement of the latest recall.
Food and Drug Administration spokeswoman Elaine Gansz Bobo said the agency continues to work with McNeil on all the product recalls.
"We do not see any serious health risk to the public from this additional recall," she said.
Gansz Bobo said she did not know of any other company that had eight medicine recalls in less than a year.
"It certainly is quite a few, and something that we hope is not repeated by other companies," she told The Associated Press.
The repeated recalls are particularly surprising at a company where executives regularly repeat the 67-year-old corporate credo, which begins: "We believe our first responsibility is to the doctors, nurses and patients, to mothers and fathers and all others who use our products and services."
Gordon noted that besides the announced recalls, congressional investigators say J&J paid another company to quietly buy up packages of Motrin with potency problems in 2008.
"I think it's unfathomable that a longtime J&J guy could do something so un-J&J-like," he said of Weldon.
Gordon said he sees parallels to the repeated recalls by Toyota, another company "renowned for quality having quality problems. You have to wonder if global cost pressures have changed the game even for the best of the best."
LINK TO SOURCE
McNeil Consumer Healthcare Announces Voluntary Recall of Certain OTC Infants’ and Children's Products
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 and distributed in the United States, Canada, Dominican Republic, Dubai (UAE), Fiji, Guam, Guatemala, Jamaica, Puerto Rico, Panama, Trinidad & Tobago, and Kuwait. (SEE RECALLED PRODUCT LIST BELOW).
McNeil Consumer Healthcare is initiating this voluntary recall because some of these products may not meet required quality standards. This recall is not being undertaken on the basis of adverse medical events. However, as a precautionary measure, parents and caregivers should not administer these products to their children. 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. While the potential for serious medical events is remote, the company advises consumers who have purchased these recalled products to discontinue use.
The company is conducting a comprehensive quality assessment across its manufacturing operations and has identified corrective actions that will be implemented before new manufacturing is initiated at the plant where the recalled products were made.
Consumers can contact the company at 1-888-222-6036 and also at www.mcneilproductrecall.com. Parents and caregivers who are not sure about alternative pediatric health treatment options should talk to their doctor or pharmacist and are reminded to never give drug products to infants and children that are not intended for those age groups as this could result in serious harm.
For additional information, including affected NDC numbers, consumers should visit our website www.mcneilproductrecall.com or call 1-888-222-6036 (Monday-Friday 8 a.m. to 10 p.m. Eastern Time, and Saturday-Sunday 9 a.m. to 5 p.m. Eastern Time). Any adverse reactions may also be reported to the FDA’s MedWatch Program by fax at 1-800-FDA-0178, by mail at MedWatch, FDA, 5600 Fishers Lane, Rockville, MD 20852-9787, or on the MedWatch website at www.fda.gov/medwatch.
McNeil Consumer Healthcare, Division of McNeil-PPC, Inc. markets a broad range of well-known OTC products.
CLICK HERE FOR RECALL INFORMATION ON CERTAIN INFANTS' TYLENOL® AND CHILDREN'S TYLENOL® PRODUCTS
CLICK HERE FOR RECALL INFORMATION ON CERTAIN INFANTS' MOTRIN® AND CHILDREN'S MOTRIN® PRODUCTS
CLICK HERE FOR RECALL INFORMATION ON CERTAIN CHILDREN'S ZYRTEC® PRODUCTS
CLICK HERE FOR RECALL INFORMATION ON CERTAIN CHILDREN'S BENADRYL® PRODUCTS
CLICK HERE FOR INFORMATION ON ALL RECALLED PRODUCTS FROM APRIL 30, 2010
Source: McNeil Consumer Healthcare
Link to Source