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Although a black box warning for tardive dyskinesia was announced by the FDA in February 2009, lawsuits filed against the makers of Reglan (metoclopramide) allege the drug companies knew for decades that the risk of movement disorders was much greater than acknowledged in previous labels.
According to an expert witness report filed in a Georgia lawsuit by Dr Robert Nelson, a former 20-year employee of the FDA and National Institute of Health, "the 1/500 EPS labeling was inaccurate and misleading from the moment the oral dosage form was approved."
In citing a 2008 study on the causes of TD at a university-based movement disorder clinic, Nelson reports that from 2000-2006, metoclopramide induced TD "was more common than any other cause, accounting for 34.5%" of all cases, or 87 out of 250.
Reglan is approved only for the short term treatment (12 weeks max) of gastroesophageal reflux disease (GERD), in adults who have not responded to other therapies, and for diabetic gastroparesis, for two to 8 weeks.
In the February 2009, letters notifying the drug makers of a need for a black box, the FDA stated, "we have become aware of continued spontaneous reports to the FDA of tardive dyskinesia associated with metoclopramide use. Exposure greater than 12 weeks was evident in a majority of these reports."
In fact, a telephone survey conducted, by then Reglan maker (AH Robins), back in 1985, "found that 38% of Reglan users took the drug for between one and two years and another 46% of Reglan users took the drug for three to six months," Dr Bob West, a pharmacologist and toxicoligist, says in a report filed in a Louisiana lawsuit.
Tardive dyskinesia is one of the most devastating of all drug-induced movement disorders, according to Dr Peter Breggin, author of about twenty books, including "Medication Madness."
"The abnormal movements or spasms can strike any of the muscles that are under voluntary control, including muscles of the face, eyes, mouth, tongue, neck, shoulders, arms, legs, hands, and feet," he says. "Breathing, speaking, and swallowing can also be impaired."
"Tardive dyskinesia often looks so "strange" or "bizarre" that it is mistaken for a mental illness rather than a neurological disorder," he notes.
Reglan can also cause uncontrolled muscle spasms (dystonia), Neuroleptic Malignant Syndrome, Parkinsonism, depression, thoughts of suicide, and suicide. Common side effects include feeling restless, sleepy, tired, dizzy, or exhausted, headache, confusion, and trouble sleeping, according to a June 9, 2009, FDA approved medication guide.
Pregnant Women Targeted
Four months after the black box for TD was announced, a New England Journal of Medicine study claimed that Reglan was safe for pregnant women with morning sickness.
The news of the study was sent out to all the media outlets and a massive off-label marketing campaign followed to promote the sale of Reglan to pregnant women, with journalists publishing almost identical talking points.
Reporter, Linda Johnson, put out articles through the Associated Press newswire which resulted in headlines such as, "Study Suggests Drug Is Safe For Morning Sickness," popping up all over the internet and for major media stories for a couple weeks.
For instance, in a June 10, 2009, article that appeared in USA Today, on Fox and ABC news Websites, and even in the UK’s Guardian on June 12, 2009, Johnson wrote: "For the first time, a large study shows that pregnant women who suffer morning sickness are not risking harm to their babies if they take a certain anti-nausea drug."
"The result may lead more doctors to prescribe the drug metoclopramide and women to feel less guilty about using it during their baby’s crucial first few months of development, experts said," she reported. Johnson never mentioned the black box for TD in her articles.
The June 10, headline for the same article on the MSNBC Website read: "Morning sickness drug shown safe for babies." On June 11, a Johnson article appeared in the Boston Globe and the same story was in the Durango Herald News as late as June 22.
To begin with, running headlines claiming that Reglan is safe based on the NEJM study was misleading and irresponsible because the majority of women, 2,502 out of 3,458, only took Reglan for 7 days, or less, in the first trimester. The average duration of fetal exposure was about a week. Only 164 took the drug for 22 days or more. Plus, the study only looked at harm at birth with no later follow-up on the babies.
There was no mention in the actual study of the black box for TD, or any other adverse effects, that could harm the mom or the fetus. Yet, the Los Angeles Times ran a June 10, story with claims that the "first study of the anti-nausea drug metoclopramide in pregnant women has found that it is safe for both fetuses and mothers." The Times failed to mention any side effects but included the main talking point that as "many as 80% of pregnant women suffer morning sickness in the first trimester."
Huge Customer Base
Over four million women give birth each year in the US, according to the CDC. The study reported that between 50% and 80% of pregnant women get morning sickness. Those numbers translate into between 2 and 3.2 million new Relgan customers in the US alone, year in and year out.
The women in the NEJM study took three 10mg tablets per day. The current price of Reglan at DrugStore.com is $182 for 100 tablets. Each pregnant woman could buy 2 or 3 months of Reglan for the first trimester, plus the study notes that nausea and vomiting "can continue beyond the first trimester." Two months of the drug at a cost of $364, times 2.5 million women, could potentially ring up $910 million each year.
It sounds like the study’s kick-off will definitely boost sales. "I think that women will be comforted by this," Dr Keith Eddleman, director of obstetrics at Mount Sinai Medical Center in New York, told Johnson in an AP article. "Most women are reluctant (to take anti-nausea medicine) just because of the stories they’ve heard and the perception that taking something in the first trimester can cause harm."
"There are very few drugs approved for use in the first trimester of pregnancy," Dr Jennifer Niebyl, a professor of obstetrics and gynecology at the University of Iowa, told Time Magazine on June 10, 2009.
"But this study could lead to metoclopramide getting approved to treat morning sickness because this is good data with big numbers," she said. "These findings may change practice and help people to be less hesitant to use the drug."
Dr Laura Riley, a Massachusetts General Hospital obstetrician and spokeswoman for the Society for Maternal Fetal Medicine, told Johnson women are far more cautious than doctors about medication. "For some who are on the fence, it’ll allow them to take it."
The chairman of obstetrics and gynecology at St John’s Health Center in Santa Monica, Dr James Moran, told the LA Times that he thinks the findings should be replicated but that he "wouldn’t hesitate to use Reglan at all."
Infants heavily dosed
Reglan is also marketed off-label to nursing mothers to stimulate breast milk even though the medication guide warns women that the drug "can pass into breast milk and may harm your baby."
Reglan is also used to treat GERD in newborns, especially premature babies. Any use with infants is off-label. Yet a study in the June 2006, Pediatrics journal titled, "Reported Medication Use in the Neonatal Intensive Care Unit: Data From a Large National Data Set," found Reglan was one of the 10 drugs reported most commonly for the NICU.
A Medline abstract for a paper in the January 2005, Movement Disorders Journal, reported the "first documented case of tardive dyskinesia in an infant," developed at 2 months "after a 17-day treatment with metoclopramide for gastroesophageal reflux."
The "Pediatric Gastroesophageal Reflux Clinical Practice Guidelines," in the October 2009, Journal of Pediatric Gastroenterology and Nutrition, warn that "Metoclopramide commonly produces adverse side effects in infants and children, particularly lethargy, irritability, gynecomastia, galacctorhea, and extrapyramidal reactions and has caused permanent tardive dyskinesia."
An infant treated for GERD, born to a mother who took Reglan for morning sickness and to increase breast milk, would undergo triple exposure.
Women Need Warnings
"Women need to be aware of the potential risk Reglan poses to themselves and their children," according to Roger Drake, the lead Reglan attorney at the California-based Baum, Hedlund, Aristei & Goldman law firm, in cases of persons who developed TD.
Concerns about tardive dyskinesia extend to children and infants, especially babies born prematurely, who may have been treated with Reglan to stimulate their digestive system, Drake reports.
He points out that no studies have been conducted to examine the risk of tardive dyskinesia in babies whose mothers take Reglan, even though the drug makers know that Reglan is used in such circumstances.
The adverse effects for babies are the same as for adults, he says, but infants are more at risk because there are no FDA approved dosing requirements established for the safe use of Reglan with children of any age, much less infants.
Baum Hedlund has two decades of experience representing thousands of injured clients against drug companies.
(This article is part of the Reglan Litigation Update Series and is sponsored by the Baum, Hedlund, Aristei & Goldman law firm)
EVELYN PRINGLE is an investigative journalist focused on exposing corruption in government and corporate America.