GlaxoSmithKline PLC, Sanofi-Aventis, and the Medicines Company are a few companies manufacturing other blood thinners which could be substituted for Heparin, but only in limited circumstances, according to doctors, drug makers, and the federal government. The U.S. Food and Drug Administration (FDA) cautioned about alternatives to Heparin on its Website saying, "There is no experience with the other anticoagulants to achieve the immediate anticoagulation needed for" dialysis and certain cardiac procedures. The FDA said it's working with APP Pharmaceuticals Inc. and others to increase production of Heparin sodium. Hospira Inc. and B. Braun Medical Inc. also supply some Heparin sodium for injection.
Still, doctors may have to seek alternatives and one is another form of Heparin known as "low-molecular-weight Heparin." A popular version is Lovenox from Sanofi-Aventis and is approved to prevent a type of blood clot known as deep-vein thrombosis in surgeries and to prevent heart attacks in some situations. The drug "could be used interchangeably for the vast majority of patients" with those diagnoses, said Charles Francis, hematologist and professor of medicine at University of Rochester School of Medicine in Rochester, N.Y. "The place where others would have trouble is cardiac bypass surgery," where Heparin is used in high doses, Francis said.
Arixtra from the U.K.'s GlaxoSmithKline, is approved to prevent blood clots in some surgeries and treat clots in certain situations. "It has some advantages and would be an alternative for many indications," Francis said. Spokeswoman Mary Anne Rhyne said there is some overlap between approved uses for the drugs, but "Heparin is approved for a wide range of uses." Direct thrombin inhibitors such as Angiomax from Medicines Co., Refludan from Bayer AG, and Argotroban from GlaxoSmithKline could be used in some situations. Angiomax, is approved to help prevent clots when stents are inserted to prop open arteries and can treat a Heparin side effect called thrombocytopenia.
Other factors could limit alternatives. "They're very expensive," said Patrick McCarthy, head of cardiothoracic surgery at Northwestern Memorial Hospital in Chicago. "We try not to use them. I don't honestly even know if they'd be made in the kind of quantities we'd need if there was a shortage of Heparin."
The FDA said it received reports of four deaths and about 350 other health problems associated with Baxter's Heparin since late 2007; 40 percent were deemed serious. Reactions included difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that—in some—led to life-threatening shock and, in others, led to death.
If Americans "knew how little the FDA did to assure the food and drug supply, if the truth ever came out...people would be marching in the street," Stupak told The Wall Street Journal recently. "That's (Accutane) just one drug. There are many like that," Stupak says. Now, as the FDA is under fire for mistakes over international inspections and other issues, Stupak—an eight-term Democratic congressman and chairman of the Subcommittee on Oversight and Investigations of the House's powerful Energy and Commerce panel, which has jurisdiction over the FDA—is at the center of an aggressive effort by congressional Democrats to spotlight what they say are problems with the Bush administration's position on consumer-safety issues.
Stupak's subcommittee is probing the FDA's handling of Baxter International Inc.’s Heparin, the blood-thinning drug that has been potentially linked to hundreds of patient reactions and four deaths. The subcommittee is also examining Pfizer Inc.'s Lipitor, Vytorin from Schering-Plough Corporation and Merck & Company, and anemia drugs sold by Amgen Inc. and Johnson & Johnson. Ketek, an antibiotic from Sanofi-Aventis SA, has been under review for over a year. Stupak is holding hearings on the safety of imported food, medicines, and medical devices and says he has a bigger agenda adding, that "It's a broken agency."
Stupak called for the resignation of FDA commissioner, Andrew von Eschenbach and other top officials and says that step has nothing to with partisan politics, adding that Republican Senator Tom Coburn of Oklahoma—a medical doctor—would be a good replacement. Coburn's opposition to abortion rights would make him unacceptable to many Democrats.
Democratic lawmakers are expected to pass only limited legislation this year, with the Senate divided and President Bush resisting some Democratic initiatives. Republicans complain that some of the Democrats' moves seem aimed at getting attention, such as Representative Michael Burgess, a Texas Republican and a member of Stupak's subcommittee. Burgess says he wants the FDA examined, but "sometimes it just seems like we want to call names and point fingers, not pursue solutions."
von Eschenbach, who was confirmed to lead the FDA in late 2006, says they introduced a new food-safety plan, hired a chief information officer to manage information technology issues, and are working to install inspectors in countries including China and India. The Bush administration's budget included a proposed increase for the FDA.
Stupak and Representative John Dingell, the Michigan Democrat who is chairman of the full Energy and Commerce panel, say the investigations are building a case for broader efforts to overhaul the FDA. Dingell says he plans far more ambitious FDA legislation, "The import bill is a good beginning, but it isn't far enough." Stupak says he'd like to look at granting the FDA subpoena power, regulating drug-industry consumer ads, and increasing the agency's funding.
Heparin is a blood thinner administered in surgery and other critical care areas to prevent clots, is crucial in dialysis and heart surgery, and is used for the bedridden. Heparin, which has been manufactured since 1930, is administered to millions of patients yearly and Baxter manufactures about half of all multiple-dose Heparin vials sold in the U.S. The FDA reported that, since the end of 2007, it received about 350 reports of health problems associated with Baxter's multiple-dose injectable Heparin; 40 percent were deemed serious. Reactions included difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that—in some—led to life-threatening shock and, in four cases, death. Baxter stopped selling multiple-dose Heparin vials earlier this month and the FDA has advised doctors to prescribe alternatives.
Joseph Famulare, deputy director for compliance at the FDA's center for drug evaluation and research, said that when the company that makes the active ingredient for Heparin applied for FDA approval, the FDA believed the application came from another company with a similar name that had been inspected. "To date, this is an isolated situation, but the wrong firm was put into the database," he said. Famulare would not name the Chinese company approved in error. FDA officials said that although federal law does not require inspections of foreign drug makers, the agency will generally inspect before a new foreign drug, or foreign active drug ingredient, is allowed in an FDA-approved prescription medication. That inspection need not include an on-site visit if the foreign company passed previous inspections for other drugs.
The Government Accountability Office and some members of Congress have concluded that the FDA lacks the resources to inspect thousands of imported drugs and drug ingredients, particularly those from India and China. Representative John D. Dingell (D-Michigan), chairman of the House Energy and Commerce Committee, said to the FDA in a letter that the Heparin situation illustrates the "disastrous state of your agency's foreign inspection program related to pharmaceuticals manufactured abroad." Dingell noted the FDA seems unclear about the actual number of foreign drug makers: One database states 7,000, another 3,000. In response, FDA Commissioner Andrew C. von Eschenbach proposed basing FDA inspectors and technical advisers in China, India, the Middle East, and three other regions and requested the State Department approve a permanent FDA presence at the U.S. Embassy in Beijing and two American consulates in China.
Michael Rogers, director of field investigations for the FDA’s Office of Regulatory Affairs, said that the Heparin investigation is "one of the agency's top priorities" and that inspectors will remain in China until they determine whether health problems associated with Heparin originated there. He said the FDA is unsure about the "root cause" of the adverse reactions.
Heparin is a blood thinner administered in surgery and other critical care areas to prevent blood clots, is crucial in dialysis and heart surgery, and is used for the bedridden. Other drugs thin blood, but their effects are not considered as effective. Heparin is administered to millions of patients yearly, and Baxter manufactures about half of all multiple-dose Heparin vials sold in the U.S. The FDA reported that, since the end of 2007, it received about 350 reports of health problems associated with Baxter's multiple-dose injectable Heparin; 40 percent were deemed serious. Reactions included difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that—in some—led to life-threatening shock.
In December, American and Chinese regulators signed an agreement under which China promised to begin registering its thousands of companies selling drug ingredients, some of which are the source of counterfeit or diluted drugs. The revelations regarding the Baxter Heparin supplier are frightening, given that China provides a growing number of the active pharmaceutical ingredients used in drugs sold in the US. Chinese regulators claim all producers are required to obtain certification by the State Food and Drug Administration; however, some active ingredients in Chinese exports are manufactured by chemical companies not falling under jurisdiction of their drug agency.
Scientific Protein said its Chinese plant had no license from the Chinese agency, but its raw ingredients come from a licensed supplier and that an “independent private U.S. validation company” found the plant to be in compliance with good manufacturing practices. Eric S. Langer, managing partner of BioPlan Associates, which prepares and publishes reports on the biopharmaceutical and biotechnology industry said, “Being able to produce a pharmaceutical or a biologic in the U.S. or anywhere without having regulatory oversight really doesn’t happen. I find it surprising from a regulatory perspective and I find it surprising from a business perspective.”
Karen Riley, spokeswoman for the FDA, said inspectors would be visiting the Changzhou plant soon, but could not be more specific. Erin Gardiner, a Baxter spokeswoman, said while the cause of the adverse reactions is unknown, tests performed by Baxter detected unspecified differences between some lots. She did not say whether the lots came from China or Wisconsin.
Congress criticized the FDA’s oversight of bulk pharmaceutical ingredients made by foreign manufacturers and sold in the US. A growing number of those ingredients now come from China and of 700 approved Chinese drug plants, yet the FDA inspects no more than 20 annually. Two Congressional committees have asked the FDA for more information about inspections of plants making the active ingredient of Heparin.
Samples of Baxter Heparin have turned up “irregularities” in the blood thinner that might be responsible for hundreds of allergic reactions in the US. Some of the irregularities found in the Baxter Heparin where found in batches in which the active ingredient came from a supplier's plant in China. Yesterday, it was learned that the Food & Drug Administration (FDA) had never inspected the overseas plant that supplied active ingredients for Baxter Heparin. However, Baxter Healthcare has said that it conducted its own inspection of the facility just six months ago.
Baxter recalled 9 lots of its tainted Heparin vials last month, after they were linked to dozens of serious and potentially life-threatening reactions at hospitals and dialysis clinics around the country. Then, earlier this week, Baxter announced its decision to suspend Heparin production until it can resolve the safety issue. The same day, the FDA warned doctors not to use Baxter Heparin. According to the FDA, it has received 350 reports in 2008 of side effects linked to Baxter Heparin. Four people died while taking the drug, though the agency said it wasn’t clear if the drug was to blame. In all of 2007, the agency received 100 reports of problems with the drug.
A Baxter spokesperson told the LA Times that testing had revealed”differences between lots [of the active ingredient] but it's unclear what the impact of these differences is”. Some of the Heparin samples where irregularities were found contained active ingredients supplied by Scientific Protein Laboratories of Waunakee, Wis. The firm's website says it maintains manufacturing facilities for the drug in Waunakee and Changzhou, China. Baxter maintains that the defective Heparin was tested before it was shipped to hospitals and dialysis centers, and that those test fully complied with industry and regulatory requirements. But the previous tests were not as sophisticated as the tests Baxter is running now and failed to detect any possible problems with the Heparin.
Yesterday’s revelation that the FDA had never inspected Baxter’s Chinese supplier has renewed criticism over the agency’s oversight of overseas manufacturers that import products to the US. According to a report released last month by the Government Accountability Office (GAO), the FDA has not been able to keep up with its inspections of overseas plants that produce foods, drugs and medical devices sold in the US. The GAO said that the FDA is so understaffed, it would take the agency at least 27 years to inspect every foreign medical device plant that exports to the US, 13 years to check every foreign drug plant and 1,900 years to examine every foreign food plant.
Several members of Congress are again criticizing the FDA, asserting that its inability to police foreign drug makers is to blame for the Baxter Heparin problems. "How do you allow these drugs into this country when you don't even inspect?" asked Rep. Bart Stupak (D-Mich.), a leading FDA critic. "Where is the enforcement to make sure you are doing things right?"
The FDA did not say why the Chinese plant that makes the Baxter Heparin was not inspected, but plans to correct the oversight. "Preparations are being made to perform an inspection as soon as possible," according to FDA spokeswoman Karen Riley. Meanwhile, Baxter claims it inspected the facility within the last six months and plans another inspection in the near future.
Heparin is a blood thinner that is administered in surgery and other critical care areas to prevent blood clots. Heparin is crucial in dialysis and heart surgery, and is used for the bedridden. Other drugs thin blood, but their effects are not considered to be as quick or as easily reversed. Heparin, which has been manufactured since 1930, is administered to millions of patients yearly and Baxter manufactures about half of all multiple-dose Heparin vials sold in the U.S.
On Tuesday, the FDA reported that, since the end of 2007, it received about 350 reports of health problems associated with Baxter's multiple-dose injectable Heparin; 40 percent were deemed serious. Reactions included difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that—in some—led to life-threatening shock.
Baxter initially recalled nine Heparin lots, but problems continued and Baxter was forced to suspend manufacturing the multi-dose vials. Baxter continues to make Heparin single-dose vials and says it is not recalling additional lots because to do so might cause a shortage and create more of a risk to patients requiring Heparin therapy than the increased potential for an adverse reaction.
U.S. regulators have advised doctors to consider alternatives to Baxter’s Heparin as shortages are expected. While alternatives exist, doctors warned there could be serious consequences if Heparin becomes scarce. “Inadequate Heparin would cause a health care crisis in this country,” said Dr. Daniel Coyne, a professor of medicine at Washington University in St. Louis. Dr. John Jenkins, director of the FDA’s office of new drugs, said the FDA allowed Baxter to continue distributing the multi-dose vials it had made because a full recall “would result in an immediate and severe shortage of this medically necessary drug.” Jenkins added, “There is going to be a shortage problem in the immediate and long-term future with the suspension of Baxter’s manufacturing. Facilities and physicians will have to decide immediately what they do with the Heparin on hand, and they’ll have to start looking for Heparin for the long term.”
Doctors said they would face difficult choices if Heparin supplies ran low. “It’s an essential part of dialysis treatment,” said Dr. Jay Wish, professor of medicine at Case Western Reserve. Without Heparin, many more patients would likely experience significant blood loss, worsening their chronic anemia, Wish warned. “Trying to operate without Heparin would be a scary proposition for the dialysis industry,” Wish said.
The FDA said it received reports of four deaths and about 350 other health problems associated with Baxter's Heparin since late 2007; 40 percent were deemed serious. Nearly all adverse reactions were seen in those receiving a "bolus"—or high—doses over short periods. Reactions included difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that—in some—led to life-threatening shock. The link to Baxter’s Heparin is unclear, according to the FDA, which is investigating if similar problems occurred with Heparin made by other manufacturers. Adverse events were not seen in patients receiving lower doses or those who received higher doses over longer periods.
Baxter initially recalled nine Heparin lots, but problems continued. Baxter suspended manufacturing the multi-dose vials but continues to make single-dose vials. Baxter says it is not recalling additional lots because to do so might cause a shortage and create more of a risk to patients requiring Heparin therapy than the increased potential for an adverse reaction.
Meanwhile, U.S. regulators advised doctors to consider alternatives to Baxter’s Heparin as shortages are expected. While alternatives exist, doctors warned there could be serious consequences if Heparin becomes scarce. “Inadequate Heparin would cause a health care crisis in this country,” said Dr. Daniel Coyne, a professor of medicine at Washington University in St. Louis. Dr. John Jenkins, director of the FDA’s office of new drugs, said the FDA allowed Baxter to continue distributing the multi-dose vials it had made because a full recall “would result in an immediate and severe shortage of this medically necessary drug.” Jenkins said doctors who must use Baxter’s Heparin should use the lowest possible dose, infuse it slowly, monitor patients closely, and consider administering steroids or antihistamines before Heparin. “There is going to be a shortage problem in the immediate and long-term future with the suspension of Baxter’s manufacturing,” Dr. Jenkins said. “Facilities and physicians will have to decide immediately what they do with the Heparin on hand, and they’ll have to start looking for Heparin for the long term.”
Doctors said they would face difficult choices if Heparin supplies ran low. “It’s an essential part of dialysis treatment,” said Dr. Jay Wish, professor of medicine at Case Western Reserve. Without Heparin, many more patients would likely experience significant blood loss, worsening their chronic anemia, Wish warned. “Trying to operate without Heparin would be a scary proposition for the dialysis industry,” Wish said.
Baxter recalled 9 lots of its tainted Heparin vials last month, after they were linked to dozens of serious reactions at hospitals and dialysis clinics around the country. Generally, the reactions to the Baxter Heparin have occurred within minutes of the drug being administered. According to the Centers for Disease Control (CDC) symptoms experienced by victims of the defective Heparin included facial swelling, nausea, rapid heart beat and decreased blood pressure. Now it appears that the problems related to Baxter Heparin are not confined to the nine recalled lots.
According to the FDA, it has received 350 reports in 2008 of side effects linked to Baxter Heparin. Four people died while taking the drug, though the agency said it wasn't clear if the drug was to blame. In all of 2007, the agency received 100 reports of problems with the drug. The FDA is now inspecting Baxter's manufacturing sites to locate the source of the Heparin problems.
The FDA said nearly all the reported problems have been in dialysis patients who received high doses of Heparin over a short time. The FDA is cautioning that doctors who continue to use Baxter Heparin should use the lowest doses possible and administer it slowly. Kidney-failure patients receive Heparin to prevent clotting of blood during the dialysis process. The drug is also used in certain types of heart surgery.
Baxter has had problems with its Heparin in the past. Last year, the FDA, in collaboration with Baxter, issued a two-page safety alert in February 2007 warning of the fatal dangers of mistaking high 10,000 unit and low 10 unit dose vials of Heparin. The memo advised hospitals to double-check their inventory to ensure dispensing errors do not occur. The 2007 alert was issued after three infants died in Indiana after they were mistakenly given adult doses. In December, actor Dennis Quaid and his wife named Baxter in a lawsuit after their newborn twins were mistakenly given potentially fatal overdoses of Heparin because of a vial mix up. In addition to the Quaid twins, at least six newborns and two other patients are known to have received an overdose of Heparin since 2001.
Kidney patients receive Heparin to prevent clotting of blood during the dialysis process. Generally, the reactions to the Baxter Heparin have occurred within minutes of the drug being administered. According to the Centers for Disease Control (CDC) symptoms experienced by victims of the defective Heparin included facial swelling, nausea, rapid heart beat and decreased blood pressure. Some of these reactions may be severe or life threatening, Baxter officials said when announcing last week's recall. So far, these Baxter Heparin side effects have been reported at 19 dialysis facilities in California, Florida, Minnesota, Missouri, New Jersey, New York, North Carolina, North Dakota, Ohio, Pennsylvania, West Virginia and Wisconsin.
CDC officials are also looking into allergic-type reactions to the Baxter Heparin in seven cardiac patients in North Carolina who got Baxter-made Heparin. They're also looking into four cardiac cases in Florida, including one patient who died. The Florida death occurred at HealthPark Medical Center in Fort Myers, Florida. Lee Memorial Health System, which runs HealthPark, was among the first health care agencies to notify authorities and Baxter about suspicions that Heparin could be causing serious - and in one case possibly fatal — reactions ins some patients. All of the Florida patients experienced shock and low blood pressure after receiving Baxter Heparin to prevent blood clots.
So far, Baxter’s tainted Heparin has been linked to 53 allergy type reactions, and the CDC is investigating 35 others. The Heparin has been tested for bacteria and endotoxin, but neither was found. According to the CDC, the Baxter Heparin cases are the largest national outbreak of treatment-related allergic reactions ever seen in dialysis patients.
Baxter has had problems with its Heparin in the past. Last year, the Food and Drug Administration, in collaboration with Baxter, issued a two-page safety alert in February 2007 warning of the fatal dangers of mistaking high 10,000 unit and low 10 unit dose vials of Heparin. The memo advised hospitals to double-check their inventory to ensure dispensing errors do not occur. The 2007 alert was issued after three infants died in Indiana after they were mistakenly given adult doses. In December, actor Dennis Quaid and his wife named Baxter in a lawsuit after their newborn twins were mistakenly given potentially fatal overdoses of Heparin because of a vial mix up. In addition to the Quaid twins, at least six newborns and two other patients are known to have received an overdose of Heparin since 2001.
According to naplesnews.com, Lee Memorial Health System, which runs HealthPark, was among the first health care agencies to notifiy authorities and Baxter International about suspicions that Heparin could be causing serious - and in one case possibly fatal -- reactions ins some patients. All of the Florida patients experienced shock and low blood pressure after receiving Baxter Heparin to prevent blood clots. Reports from HealthPark and other hospitals prompted Baxter to issue the Heparin recall on January 17. Officials from Baxter have arrived at HealthPark to investigate the incidents. In the meantime, Lee Memorial Health System has disposed of the Heparin batches involved, and there have been no other incidents.
According to the Baxter Heparin recall notice, a variety of reactions have been reported in relation to the recalled Heparin, including abdominal pain, abdominal pain (upper), decreased blood pressure, burning sensation, chest pain, diarrhea, dizziness, drug ineffectiveness, dyspepsia, dyspnea, erythema, flushing, headache, hyperhidrosis, hypoesthesia, hypotension, lacrimation increased, loss of consciousness, malaise, nausea, pallor, palpitations, paresthesia, paresthesia (oral), pharyngeal edema, restlessness, vomiting/retching, stomach discomfort, tachycardia, thirst, trismus, and unresponsiveness to stimuli.
At the time it issued the Heparin recall, Baxter had received 100 reports of such reactions, and by Tuesday morning there had been another 50. Allergic reactions to Heparin are not unusual, however so many cases of varying symptoms in a short time is cause for alarm. In addition to Baxter’s probe, the Food & Drug Administration (FDA) is also conducting its own investigation into the defective Heparin.
Baxter has had problems with its Heparin in the past. Last year, the FDA, in collaboration with Baxter, issued a two-page safety alert in February 2007 warning of the fatal dangers of mistaking high 10,000 unit and low 10 unit dose vials of Heparin. The memo advised hospitals to double-check their inventory to ensure dispensing errors do not occur. The 2007 alert was issued after three infants died in Indiana after they were mistakenly given adult doses. In December, actor Dennis Quaid and his wife named Baxter in a lawsuit after their newborn twins were mistakenly given potentially fatal overdoses of Heparin because of a vial mix up. In addition to the Quaid twins, at least six newborns and two other patients are known to have received an overdose of Heparin since 2001.
According to the Baxter Heparin recall notice, a variety of reactions have been reported in relation to the recalled Heparin, including abdominal pain, abdominal pain (upper), decreased blood pressure, burning sensation, chest pain, diarrhea, dizziness, drug ineffectiveness, dyspepsia, dyspnea, erythema, flushing, headache, hyperhidrosis, hypoesthesia, hypotension, lacrimation increased, loss of consciousness, malaise, nausea, pallor, palpitations, paresthesia, paresthesia (oral), pharyngeal edema, restlessness, vomiting/retching, stomach discomfort, tachycardia, thirst, trismus, and unresponsiveness to stimuli.
Involved in the Baxter Heparin recall are nine lots of Heparin Sodium 1000 unit/mL for injection. They include:
• NDC# 0641244045, Lot #107054, Heparin 1000units/mL 10mLvial, expiration date 10/2009
• NDC# 0641244045, Lot #117085, Heparin 1000units/mL 10mLvial, expiration date 11/2009
• NDC# 0641245045, Lot #047056, Heparin 1000units/mL30mL vial, expiration date 10/2008
• NDC# 0641245045, Lot #097081, Heparin 1000units/mL30mL vial, expiration date 09/2009
• NDC# 0641245045, Lot #107024, Heparin 1000units/mL30mL vial, expiration date 10/2009
• NDC# 0641245045, Lot #107064, Heparin 1000units/mL30mL vial, expiration date 10/2009
• NDC# 0641245045, Lot #107066, Heparin 1000units/mL30mL vial, expiration date 10/2009
• NDC# 0641245045, Lot #107074, Heparin 1000units/mL30mL vial, expiration date 10/2009
• NDC# 0641245045, Lot #107111, Heparin 1000units/mL30mL vial, expiration date 10/2009
This is not the first time that Baxter’s Heparin vials have caused problems. The Food & Drug Administration (FDA), in collaboration with Baxter, issued a two-page safety alert in February 2007 warning of the fatal dangers of mistaking high 10,000 unit and low 10 unit dose vials of Heparin. The memo advised hospitals to double-check their inventory to ensure dispensing errors do not occur. The 2007 alert was issued after three infants died in Indiana after they were mistakenly given adult doses. In December, actor Dennis Quaid and his wife named Baxter in a lawsuit after their newborn twins were mistakenly given potentially fatal overdoses of Heparin because of a vial mix up. In addition to the Quaid twins, at least six newborns and two other patients are known to have received an overdose of Heparin since 2001.
According to the Baxter recall notice, no deaths have been reported in connection with the recalled Heparin vials. However, on Friday, a Florida TV station reported that one patient had died, and four others had suffered reactions that could be linked to the recalled Baxter Heparin. An official at HealthPark Medical Center in Lee County Florida told nbc2.com that they had removed all of the Baxter Heparin from the facility. State and Federal authorities are investigating the incident, and according to the report, Baxter is expected to visit the facility this week to see if the patient’s death and the other reactions were linked to the recalled Heparin.
Heparin comes in 10 unit vials for babies and vials up to 10,000 units for adults. The twins were dosed from 10,000 unit vials with one dose given on Sunday morning and another Sunday evening; both infants were each given two over-dosages. The babies began to bleed out just before midnight and were transferred to neo-natal intensive care and given protamine sulfate to reverse Heparin’s effects. Pharmacy technicians stock the drug Heparin for use in preventing clots and for flushing IVs. Hospital protocol is to keep the different units separated, but a technician accidentally put the 10,000 unit vials in the drawer where the 10 unit vials were stored. The Quaids have sued Baxter Healthcare Corp., the Illinois-based makers of Heparin, accusing them of negligence in packaging different doses in similar vials with blue backgrounds.
The Food & Drug Administration (FDA), in collaboration with Baxter Healthcare Corporation, issued a two-page safety alert last February warning of the fatal dangers of mistaking the high 10,000 unit and low 10 unit dose vials of Heparin and advised hospitals to double-check their inventory to ensure dispensing errors do not occur. Cedars-Sinai was among the recipients of the alert, which was issued after three infants died in Indiana after they were mistakenly given adult doses. But, six newborns received an overdose and were not among the first to be affected in this sort of mix-up, apparently also happening back in 2001 when two patients were given incorrect dosages of the drug. One parent claims her child is suffering long-term effects from a Heparin overdose and, at 15 months, is not doing everything other children his age are and should be doing.
The Quaids criticized Cedars-Sinai, saying they were particularly upset to learn from a state investigation that their babies were medicated with dosages 2,000 times stronger than what was prescribed. The report's findings released Wednesday by California’s Department of Public Health conflict with the hospital's report that the twins each received one vial containing 10,000 units per milliliter of Heparin instead of the 10 units per milliliter dosage. The report confirmed the twins, in fact, received two of the vials and faulted the hospital for deficient practices. The investigation also found the hospital did not adequately educate staff about the safe use of Heparin and nurses and pharmacy technicians did not check labels on the vials and did not keep adequate records of when it was used.
According to a statement released by the Quaids, they said, "We were told by upper Cedars-Sinai administration that our children had received only one 10,000 unit dose of Heparin when in fact they had received two 10,000 unit doses over an eight-hour period that we now know of. The hospital's lack of candor has left us with the uneasy feeling that we may never know the whole story," the statement said.
Around 40 people have been sickened in Texas and Illinois by the tainted Sierra Pre-Filled Syringes, including 20 outpatients at Rush University Medical Center in Chicago; no deaths have been reported. Of the 20 Rush outpatients who fell ill, 14 required hospitalization. Although all responded quickly to antibiotic treatment, one patient remains hospitalized as of Tuesday, said Dr. John Segreti, hospital epidemiologist.
Doctors at Rush were able to trace the infections to Heparin-filled Sierra Pre-Filled Syringes the patients used during home treatment for cancer and other ailments. Heparin is a blood thinner and the syringes are used to clear out catheters and intravenous lines. The infections were caused by bacteria found in a single batch of the Heparin-filled syringes made in North Carolina, by a company called Sierra Pre-Filled. The infections were caused by a bacterium called Serratia marcescens (pronounced Sur-AY'-she-uh mar-SUH'-sens). Syringes from that batch were also sent to Colorado, Florida, and Pennsylvania but infections—so far—have turned up only in Illinois and Texas, said Dr. Arjun Srinivasan of the CDC. The infections can cause fever and chills and can be serious but generally respond well to antibiotics.
The Sierra Pre-Filled Syringe recall includes the company’s Heparin Lock Flush Solution USP, 100 units/ml, 5ml in pre-filled syringes; lot number: 070926H; NDC number: 64054-1003-02; Catalog number: 1003-02. The CDC is working to ensure doctors are alerted about the contamination; doctors and hospitals should be aware that more cases could surface. The FDA is asking doctors are advised to trace the recalled Sierra Pre-Filled Syringes and make sure their patients stop using them at once. The contaminated Sierra Pre-Filled Syringes should be put into "quarantine" and returned to the distributor.
Heparin is the same drug linked to recent overdoses accidentally given to actor Dennis Quaid's newborn twins. In that case, the Heparin was made by Deerfield, Illinois-based Baxter Healthcare Corporation. The overdoses given to the Quaid twins were a result of the babies being dosed with medication from the 10,000 unit vials used for adults and not the 10 unit vials for babies. Also this year, an alert was issued after three infants died in Indiana after they were mistakenly given adult doses of Heparin. Six other newborns received an overdose and were not among the first to be affected in this sort of mix-up, apparently also happening back in 2001 when two patients were given incorrect dosages of the drug. Both the 10,000 unit adult vials and the 10 unit baby vials of Heparin bear similar packaging which seems to be at the root of under and overdosing errors.
Around 40 people have been sickened in Texas and Illinois, including 20 outpatients at Rush University Medical Center in Chicago. So far, no deaths have been reported, but of the 20 Rush outpatients who fell ill, 14 required hospitalization. Although all responded quickly to antibiotic treatment, one patient remains hospitalized as of Tuesday, said Dr. John Segreti, hospital epidemiologist.
Doctors at Rush were able to trace the infections to Heparin-filled syringes the patients used during home treatment for cancer and other ailments. Heparin is a blood thinner and the syringes are used to clear out catheters and intravenous lines. The infections were caused by bacteria found in a single batch of heperin-filled syringes made in North Carolina, by a company called Sierra Pre-Filled. The infections were caused by a bacterium called Serratia marcescens (pronounced Sur-AY'-she-uh mar-SUH'-sens).
Taitned Sierra Pre-Filled syringes from that batch were also sent to Colorado, Florida, and Pennsylvania but infections—so far—have turned up only in Illinois and Texas, said Dr. Arjun Srinivasan of the CDC. The infections can cause fever and chills and can be serious but generally respond well to antibiotics. The president of Sierra Pre-Filled, Dushyant Patel, said the company is working with both the CDC and the Food and Drug Administration (FDA) on the investigation and has voluntarily recalled the implicated lot. "There's nothing out there anymore," according to Patel.
The affected Sierra Pre-Filled syringes where from lot 070926H, Srinivasan said. He said the CDC is working to ensure doctors are alerted about the contamination; doctors and hospitals should be aware that more cases could surface. "Our highest priority is to ensure that all of those cases that occur are identified," he said. ”Patients who think they used affected syringes should contact their doctors,” Srinivasan said, adding, “We'll be working to perform genetic fingerprinting on the bacteria to confirm a link between bacteria in the syringes and the case patients.
Heparin is the same drug linked to recent overdoses accidentally given to actor Dennis Quaid's newborn twins. In that case, the Heparin was made by Deerfield, Illinois-based Baxter Healthcare Corporation. The twins appeared to be doing well, a lawyer for the Quaids said earlier this month. Patel said the Heparin in his company's pre-filled syringes comes from a different company. The overdoses given to the Quaid twins were a result of the babies being dosed with medication from the 10,000 unit vials used for adults and not the 10 unit vials for babies. Also this year, an alert was issued after three infants died in Indiana after they were mistakenly given adult doses of Heparin. Six other newborns received an overdose and were not among the first to be affected in this sort of mix-up, apparently also happening back in 2001 when two patients were given incorrect dosages of the drug. Both the 10,000 unit adult vials and the 10 unit baby vials of Heparin bear similar packaging which seems to be at the root of under and overdosing errors.
Heparin comes in 10 unit vials for babies and vials up to 10,000 units for adults. The babies were dosed from 10,000 unit vials twice and began to bleed out before being transferred to the Cedars Sinai neo-natal intensive care unit where they were given protamine sulfate to reverse Heparin's effects. The Cedars-Sinai hospital's protocol is to keep the different units separated, but a technician accidentally put the 10,000 unit vials in the drawer where the 10 unit vials were stored.
The Food & Drug Administration (FDA), in collaboration with Baxter Healthcare Corporation, issued a two-page safety alert last February warning of the fatal dangers of mistaking the high 10,000 unit and low 10 unit dose vials of Heparin. The memo advised hospitals to double-check their inventory to ensure dispensing errors do not occur. Cedars-Sinai Medical Center was among the recipients of the FDA alert.
The 2007 alert was issued after three infants died in Indiana after they were mistakenly given adult doses. In addition to the Quaid twins, at least six newborns and two other patients are known to have received an overdose of Heparin since 2001. The mother of one of those children has said that her child is still suffering long-term affects from a Heparin overdose and, at 15 months, is not doing everything other children his age are and should be doing. An attorney representing two families affected by previous overdoses as a result of labeling mix-ups says that these are not new problems and will likely continue, as human error is inevitable given the similar labeling on the two sizes of Heparin vials.
The Quaid suit accuses Baxter Healthcare of failing to put clear distinguishing labels on its 10-unit and 10,000-unit vials of Heparin, and failing to recall the product after the three other infants died because of a mix-up. The complaint filed in Cook County Circuit Court, Illinois, said both the small and large doses of Heparin had similar blue background labels. It also accused Baxter Healthcare of failing to recall or repackage the 10,000 unit vials "when it had actual knowledge that prior infant deaths had occurred as a result of medication errors." The Quaids are seeking at least $50,000 in damages.
Heparin comes in 10 unit vials for babies and vials up to 10,000 units for adults. The babies were dosed from 10,000 unit vials with one dose given on Sunday morning and again on Sunday. The babies began to bleed out just before midnight and were transferred to the neo-natal intensive care unit where they were given protamine sulfate to reverse Heparin’s effects.
Pharmacy technicians stock the drug Heparin, used to prevent clots and flush out IVs. The Cedas-Sinai hospital’s protocol is to keep the different units separated, but a technician accidentally put the 10,000 unit vials in the drawer where the 10 unit vials were stored.
The hospital apologized Tuesday to the families of three patients involved, saying tests indicated that there were no adverse effects on the babies. The California Department of Public Health says they are investigating the incident.
Cedars issued a statement acknowledging the mistake and calling it a highly unusual, preventable error that involved failure of their staff to follow standard Cedar-Sinai policies and procedures. The hospital claims seven patients in total were given the wrong dosages, but there have been reports that as many as 13 patients were dosed incorrectly with Heparin.
The FDA, in collaboration with Baxter Healthcare Corporation—one of the pharmaceutical companies that manufacture Heparin - issued a two-page safety alert last February warning of the fatal dangers of mistaking the high 10,000 unit and low 10 unit dose vials of Heparin. The memo advised hospitals to double-check their inventory to ensure dispensing errors do not occur. Cedars-Sinai Medical Center was among the recipients of the FDA alert.
The 2007 alert was issued after three infants died in Indiana after they were mistakenly given adult doses. But, six newborns received an overdose and were not among the first to be affected in this sort of mix-up, apparently also happening back in 2001 when two patients were given incorrect dosages of the drug. One parent claims her child is suffering long-term affects from a Heparin overdose and, at 15 months, is not doing everything other children his age are and should be doing. An attorney representing two families affected by previous overdoses as a result of labeling mix-ups says that these are not new problems, the problem is ongoing and human error is inevitable given the similar labeling.
In addition, patients who do not develop the life-threatening drug reaction called Heparin Induced Thrombocytopenia (HIT) are also at a higher risk of postoperative complications.
The study followed patients undergoing coronary bypass grafting (CABG) and/or valves surgery for a period of 2 ½ years and demonstrated that the patients who tested positive for Heparin/platelet factor 4 (HPF4) antibodies are at a demonstrably higher risk for serious postoperative adverse reactions including renal (kidney) failure requiring dialysis, prolonged mechanical ventilation, gastrointestinal complications, and acute limb ischemia.
According to Dr. David Kress, the leading study investigator and senior cardiothoracic surgeon at Aurora St. Luke's Medical Center in Milwaukee, Wisconsin: "The clinical risk associated with HPF4 antibodies in patients who don't have HIT syndrome is poorly understood in clinical practice. This study suggests that just having HPF4 antibodies, even without HIT or thrombocytopenia, confer a risk of adverse outcomes."
This study is the first to control for comprehensive preoperative risk factors and uses the Society of Thoracic Surgeons (STS) National Adult Cardiac Surgery Database to evaluate postoperative outcomes.
The results confirm prior studies that show 12.7 to 22 % of patients who test positive for HPF4 antibodies prior to cardiac surgery, independent of HIT, are at an increased risk for complications.
This suggests that optimal preoperative care for cardiac surgery patients should include screening for HPF4 antibody status to identify and minimize the development of HPF4 antibodies during cardiac surgery and to reduce the risk in the overall cardiac surgery patient population.