The blood thinners included in this announcement include Arixtra (fondaparinux sodium) Solution for subcutaneous injection; Fragmin (dalteparin sodium injection) for Subcutaneous Use; Innohep (tinzaparin sodium) injection; and Lovenox (enoxaparin sodium) injection for subcutaneous and intravenous use.

The new warning states that epidural or spinal hematomas may occur in patients who are anticoagulated with low molecular weight heparins (LMWH) or heparinoids and are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Health care professionals are asked to consider these risks when scheduling patients for spinal procedures.

Factors that can increase the risk of developing epidural or spinal hematomas in these patients include:

• Use of indwelling epidural catheters
• Concomitant use of other drugs that affect hemostasis, such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants.
• A history of traumatic or repeated epidural or spinal punctures
• A history of spinal deformity or spinal surgery

Health care providers are encouraged to monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary. Benefits and risks should be weighed before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis.

SOURCE: Heparin Recall › Revised boxed warning placed on blood thinners

Anticoagulants are often administered to patients before undergoing some surgeries and medical procedures to reduce the risk of life-threatening blood clots. Lovenox has been touted as an effective replacement for the blood thinner heparin in patients undergoing abdominal surgery.

Heparin carries a laundry list of side effects such as nausea, vomiting, abdominal pain, diarrhea and low blood pressure. Concerns about heparin flooded the media last year with cases of accidental overdoes and shipments of tainted batches of the blood thinner imported from China. Both incidences caused patients serious injury or death.

The contaminated heparin scandal in particular created an urgency among consumers, the medical community and pharmaceutical companies to find safer alternatives to the commonly used blood thinner.

Momenta chief executive officer Craig A. Wheeler said in the conference call that the FDA continues to review its Abbreviated New Drug Application (ANDA) process for M-Enoxaprin. ANDA is the FDA’s Center for Drug Evaluation and Research Office of Generic Drugs review and ultimate approval process of a generic drug.

Once approved, an applicant may manufacture and market the generic drug product to provide a safe, effective, low cost alternative to the American public. “We are in regular communication with the agency and responding to their questions as they arise,” Wheeler said.

Wheeler referred to the “global contamination issue” with the heparin supply and the FDA’s plant inspections of Chinese suppliers of heparin, adding that the companies who supply heparin to Momenta’s partner distributor Sandoz for the manufacture of M-Enoxaprin have all been inspected by the FDA.

While the company has no indication that the inspections raised concerns with the FDA, Wheeler said “Any disruption in the heparin supply has the potential to impact our supply chain.” As a result, the company will diversify its sources of heparin and closely monitor the supply chain.

Momenta hopes to launch M-Enoxaparin in 2009 provided the ANDA is readily approved by the FDA.

Source:
Seeking Alpha

SOURCE: Heparin Recall › FDA approval for marketing generic Lovenox expected

Blood tends to pool in the atrial chamber of individuals with atrial fibrillation, which can lead to clotting and an increased risk for strokes. Patients with atrial fibrillation are generally treated with blood thinners to help prevent blood clots from forming.

However, blood thinners like heparin can cause serious bleeding episodes and allergic reactions. Alternatives to long-term use of blood thinners has many cardiologists taking notice.

“The findings from this clinical trial are very impressive,” said Dr. Gregg C. Fonarow, professor of cardiology at the University of California, Los Angeles. “Treatment with this novel device will be very attractive and provide patients with atrial fibrillation effective, long-term protection from stroke and systemic embolization without the bleeding risks associated with (blood thinners).”

The PROTECT-AF Trial, which involved 707 patients with a type of atrial fibrillation, showed that patients who had the device had a 32 percent lower risk of stroke and cardiovascular death compared with those on blood thinners. The study also found fewer complications with the implanted device compared to the use of blood thinners.

A Food and Drug Administration (FDA) advisory panel will meet in April to consider the sale of the device in the United States.

Source:
Eflux Media News

SOURCE: Heparin Recall › Heart device may eliminate need for heparin, warfarin

Rivaroxaban, a pill marketed in Europe as Xarelto, showed to be more effective than the anticoagulant heparin, while presenting no more side effects than heparin. Side effects of heparin and rivaroxaban include the risk of internal bleeding. Another benefit of rivaroxaban is that it does not need constant monitoring like another popular blood thinner, warfarin. Heparin is administered intravenously while warfarin is a pill taken orally.

Pharmaceutical companies have long been working on safer and easier alternatives to heparin and warfarin, especially since the tainted heparin scandal last year where more than 80 Americans died and hundreds more were made sick after receiving injections of batches of heparin that had been laced with oversulfated chondroitin sulfate (OSCS), a contaminant that mimics heparin but can cause serious allergic reactions in humans.

The FDA is expected to make a decision whether to approve rivaroxaban by May 28. If approved, rivaroxaban would be the first oral blood thinner approved since the FDA approved warfarin in 1954, according to Forbes.

“We appreciate the thoroughness of the advisory committee’s review, and we will continue to work with the FDA as they finalize their review,” Dr. Peter DiBattiste, vice president of Johnson & Johnson Pharmaceutical Research and Development, said in a prepared statement.

SOURCE: Heparin Recall › FDA panel recommends agency approval of heparin alternative

Heparin is routinely given to patients before certain types of surgery and prior to treatments such as kidney dialysis to prevent blood clots from forming. Clots that do not naturally dissolve can travel through the blood stream and end up in the brain, causing stroke or in the lungs resulting in a pulmonary embolism.

Heparin is produced naturally by most animals, including humans, but most heparin used today is derived from pig intestines. China has become a popular location for manufacturing heparin because it has a much larger pig population. It is somewhat inexpensive to produce, however, ensuring the safety of drugs manufactured overseas has been a challenge for the Food and Drug Administration (FDA). Just last year, more than 80 Americans died and hundreds more were sickened after they received injections of specific batches of heparin that were manufactured in China. That heparin was later found to have been contained with oversulfated chrondroitin sulfate (OSCS). As a result, researchers have been working to find safer alternatives to heparin.

Liu, whose Recomparin research was published online in the Proceedings of the National Academy of Sciences journal last November, says he is also looking into customizing heparin for other uses, such as a treatment for small-cell lung cancer.

SOURCE: Heparin Recall › Researcher awarded NIH grant for development of synthetic heparin

Heparin is a blood thinner used to prevent blood clots. It is often given before surgery and during treatments such as kidney dialysis to prevent clotting. In appropriate use or overdosing can be fatal.

This week, Zelenka – known to some as the “heparin murderer” – was sentenced to life for the murder of seven people, according to Czech media outlet Noviny. Police have pinned another three murders on him as well as one attempted murder.

Police are looking into 14 other cases in which they suspect murder or attempted murder. Another ten cases were closed after police couldn’t find proof that a crime was committed. Even if authorities link more murders and attempted murders to Zelenka, he will not be prosecuted as he currently will serve the highest sentence for the crimes he already has been found guilty of.

Zelenka admitted to all crimes but during the trial said he only remembers administering heparin to five patients. He says police coerced him into admitting to additional crimes.

SOURCE: Heparin Recall › Czech ‘heparin murderer’ gets life in prison

In early December, the FDA announced that it had received information about the Innohep in Renal Insufficiency Study (IRIS) that was stopped in February because of an interim finding of increased mortality in elderly patients.

As a result, in July, the company revised the prescribing information to restrict the use of Innohep in patients 90 years of age and older. However, preliminary data from IRIS suggests that the increased risk of mortality is not only limited to patients in that age range. Study results suggest that compared to unfractionated heparin, Innohep increases the risk of death for patients 70 years and older with renal insufficiency and deep vein thrombosis (DVT), pulmonary embolism (PE), or both. The FDA suggested health care professionals consider the use of alternative treatments for patients older than 70 years of age with those conditions.

The FDA says it anticipates submission of the final IRIS study report sometime in January and will complete its review soon thereafter. Additional regulatory actions as appropriate will be considered after thorough review of all applicable data from the manufacturer of Innohep.

SOURCE: Heparin Recall › Celgene issues letter warning of limited use of heparin drug

Researchers at Beaumont Hospital in Royal Oak, Michigan, have developed a treatment protocol to quickly and effectively diagnose brain bleeds in patients who are on blood thinners and bump their heads. The study treated 105 patients under the new protocol. As a result, diagnosis of brain bleeds occurred in half the time and treatments were started faster. Under this new system, death rate also was reduced from 40 percent to 11 percent.

The protocol includes rapid initial evaluation by a doctor or nurse, a CT scan performed on a priority basis, a blood transfusion and administration of vitamin K to help the blood clot, according to the report.

“These seem like relatively simple steps, but when combined they become a powerful force that helps save lives,” Emax Health quoted Greg Howells, M.D., director of Trauma Surgery. When the head bumps occur, many people can appear fine even if the injury is causing the brain to bleed. Previous studies have shown that people on blood thinners are four times more likely to die from a blow to the head than those not on blood thinners.

As a result of the study, more than 40 other hospitals across the country have asked about Beaumont’s treatment protocol for people on blood thinners who bump their heads.

SOURCE: Heparin Recall › Head injury protocol reduces death rate for patients on blood thinners

The findings come from research published this week in the Journal of the American Medical Association and funded by the National Institutes of Health and University of Chicago. The study is based on interviews of 3,000 people aged 57 to 85. The research shows that more than half of the older population is taking at least five different medications including prescriptions and over-the-counter drugs or supplements. Men are particularly at risk, according to the report. As many as one in 10 older men were taking drug combinations that could be harmful.

One alarming drug combination occurs when a patient is on a blood thinner. Combined with common over-the-counter medicines such as NSAIDS like ibuprofen, naproxen or aspirin, this can lead to excessive and uncontrolled bleeding. Cigarette smoking also decreases blood levels.

Heparin, one of the more common blood thinners administered intravenously at hospitals before some surgeries and treatments such as kidney dialysis to prevent blood clots, carries the same warnings. Patients – whether at home or in the hospital – should be forthcoming about all medications – prescription and over-the-counter – and supplements they are taking to avoid any potential risk.

Patients also should not take new over-the-counter medication or supplements or stop taking a medication without first checking with their doctors.

SOURCE: Heparin Recall › Older Americans may be taking hazardous drug combinations

Blood thinners are routinely given to patients before certain types of surgery and treatments such as kidney dialysis to prevent blood clots from forming. Clots that do not naturally dissolve can travel through the blood stream and end up in the brain, causing a stroke, or in the lungs, causing a pulmonary embolism. Blood clots, also known as thrombosis, is a serious problem affecting nearly a million Americans each year and killing nearly 300,000 annually.

Two more common types of blood thinners are heparin and warfarin. Heparin is administered intravenously, requiring medical supervision, whereas warfarin is given orally. Both drugs have been used medically for decades. Both have side effects that doctors and patients find bothersome, including easy bruising, excessive bleeding, lower back pain, weakness or light-headedness, and flu-like symptoms. Thus physicians are eager to find safer alternatives.

Furthermore, heparin has been in the spotlight continuously over the past several months for confusing labeling that has resulted from overdoses that have sickened and killed patients, as well as batches of contaminated heparin that made its way into hospitals, causing more illnesses and deaths in patients who received the bad lots.

SOURCE: Heparin Recall › Drug makers rush to produce new blood thinners

Thromboembolism is a blood clot in the blood vessel that breaks loose and is carried by the blood stream to plug another vessel. The clot may plug a vessel in the lungs, causing pulmonary embolism; brain, causing a stroke; gastrointestinal track, kidneys or leg. Thromboembolism is a common complication of cancer and cancer treatments, and is usually treated with blood thinners, such as heparin.

Though a relatively new therapy for the prevention of thromboembolism, low-molecular-weight heparins, such as nadroparin, are as effective as high-molecular-weight heparins. One benefit to low-molecular-weight heparins is that treatment can be started and completed in an outpatient setting, as opposed to high-molecular-weight treatments, which require in-hospital monitoring.

The study involved 1,166 patients with metastatic cancer receiving chemotherapy for cancers involving the lungs, breasts, head and neck, stomach, colon, rectum and pancreas. The incidence of blood clots in patients who received nadroparin was 2.1 percent compared to 3.9 in patients who received a placebo. Higher rates of thrombembolism was present in patients with lung and pancreatic caners. The study also showed a slight (0.7 percent) incidence of major bleeding in patients who received nadroparin compared to 0 percent in the placebo group.

SOURCE: Heparin Recall › Low-molecular-weight heparin good therapy for cancer patients

At the time the study was stopped, 350 patients had completed a 90 days of follow-up. Twenty-three out of 176 patients who received tinzaparin died, compared to nine out of 174 who received unfractionated heparin. The FDA says it sees no clear pattern as to the cause of death nor do the deaths appear to be related to either over-dosing or under-dosing of an anti-coagulant.

In July, the company revised the prescribing information to restrict the use of Innohep in patients 90 years of age and older. However, preliminary data from IRIS suggests that the increased risk of mortality is not only limited to patients in that age range. Study results suggest that compared to unfractionated heparin, Innohep increases the risk of death for patients 70 years and older with renal insufficiency and deep vein thrombosis (DVT), pulmonary embolism (PE), or both. The FDA suggests health care professionals consider the use of alternative treatments for patients older than 70 years of age with those conditions.

The FDA has requested that the labeling for Innohep be revised to better describe the overall results of IRIS. The agency anticipates final IRIS results in January 2009, and will complete its review at that time.

SOURCE: Heparin Recall › FDA requests better labeling of low molecular weight heparin

Baxter International makes heparin, the blood thinner that is routinely used before treatment for kidney dialysis to prevent blood clots as well as during many surgeries. Several lots of heparin manufactured in Baxter International’s China plant were recalled by the FDA earlier this year after they were found to have been contaminated during manufacturing. The tainted heparin ultimately killed more than 80 Americans and sickened hundreds more before an investigation led them to Baxter International’s China plant.

The company also lobbied on bills to improve the safety of drugs imported from foreign countries, and stood up against an effort in Congress to reform the U.S. patent system. According to the story, high-tech companies support that bill, claiming that it would cut down on “frivolous patent-infringement lawsuits.” Baxter International and the pharmaceutical industry argued that doing so would weaken patent protections on drugs by reducing infringement penalties. The bill passed the House but is not expected to pass the Senate this year.

Baxter International also lobbied to give the FDA authority to approve generic versions of biotech drugs, which have never faced generic competition because the FDA does not have the authority to approve the less expensive versions.

SOURCE: Heparin Recall › Baxter International spent thousands on lobbying efforts

“Previously it was nearly impossible to change the nature of the heparin generated by the enzyme,” said Jian Liu, Ph.D., associate professor at the UNC Eshelman School of Pharmacy medicinal chemistry and natural products division. “The degree of difficulty was 10-plus. Now it’s more like a two or three, which opens the door to the possibility of improving on the natural product.”

The method involves modifying the enzyme heparan sulfate 2-O-sulfotransferase, which produces heparin in the human body in addition to other heparin-like molecules. By modifying 2-O-sulfotransferase, researchers will be able to create customized forms of synthetic heparin with different properties, according to the report.

Heparin is typically administered to most patients during surgery and before some treatments such as kidney dialysis to prevent blood clots from forming. Heparin is produced naturally by most animals, including humans, but most heparin available today is derived from pig intestines. China has become a popular location for manufacturing heparin because it has a much larger pig population.

However, heparin manufactured in China raised concerns earlier this year after batches from Baxter International’s China plant were found to have been contaminated. The investigation into heparin resulted after more than 80 Americans died and hundreds more were sickened after receiving doses of the tainted heparin. As a result, researchers have been working to find safer alternatives to heparin, including developing synthetic versions.

“The pig stuff has served us well for 50 years and is very inexpensive, but if we cannot control the supply chain, we cannot ensure the safety of the drug,” Liu said. “I am working for the day when synthetic heparin can be brewed in large laboratories at a low cost.”

Liu and her colleagues also are looking into customizing heparin for other uses, such as a treatment for small-cell lung cancer.

Liu’s research recently was published online in the journal Proceedings of the National Academy of Sciences.

SOURCE: Heparin Recall › Scientists on road to modifying, customizing human heparin

Septic shock is a serious condition that can cause multiple organ failure and death. It is the main cause of mortality in intensive care units (ICU), with a mortality rate of up to 40 percent.

There is only one drug other than antibiotics approved to treat septic shock, and that drug costs about $10,000 per patient. But two Canadian intensive care physicians, Dr. Ryan Zarychanski and Dr. Anand Kumar, who studied the effect of the blood thinner heparin on ICU patients between 1989 and 2005, found that patients with severe sepsis who were given heparin lowered their risk of death by 30 percent. Heparin, a generic drug, costs less than $10.

The research involved nearly 1,400 Winnipeg ICU patients with septic shock. Six hundred and ninety-five of the patients received heparin for suspected heart attacks or blood clots. Another 695 did not. The study found that there were 15 percent fewer deaths among patients who had received heparin.

Heparin for the treatment of septic shock is controversial, says Zarychanski, because it refutes the belief that expensive pharmaceuticals are the best treatment option. Thus, companies are unlikely to invest in researching it for other benefits as there is little or no profit in it.

But the safety of drugs, like heparin that is imported into the U.S. from countries like China, still hangs in the balance. It is just as important to find new treatments for less expensive drugs as it is to ensure the safety of all drugs.

SOURCE: Heparin Recall › Heparin found to reduce septic shock death rate

The active ingredient in heparin is derived from pig intestines and the demand for the drug has become so great that the domestic pig population cannot meet the demand. To meet the immediate need, pharmaceutical companies have turned to China, which has three times the pig population.

But importing drugs from China has raised some serious concerns. Earlier this year, 81 people died and hundreds more were sickened after receiving doses of heparin, which was later found to have been contaminated in a Chinese manufacturing plant.

As a result, scientists are eagerly working to develop a synthetic version of heparin that could be made in U.S. labs, thus preventing future scares. In August, we told you about Rensselaer Polytechnic Institute’s Robert Linhardt, who had just announced that after years of work his research team appeared to have successfully devised a synthetic heparin.

Linhardt and his team continue to forge ahead with the synthetic drug, according to the Scientific American. The challenge, however, is that it is hard to mass produce. It took a year for Linhardt and his team to produce 100 milligrams of the synthetic version, which pales in comparison to the more than 100 metric tons of heparin needed to meet the world’s demand for just one year.

Linhardt hopes to have a gram of synthetic heparin – or enough to give 100 doses to mice to start animal trials – within a year. Far more of the synthetic drug would be needed for clinical testing on patients, presenting a further challenge. Cost could become another issue, as heparin made from pig intestines costs only about 20 cents per dose and making the synthetic version a feasible business would take years and a huge investment.

However, Linhardt says mass production of the synthetic heparin would have benefits that far outweigh the negatives: “The future is one that will be short continuously of heparin,” he was quoted in Scientific American. “Which means any adulterations of the heparin (imported by the U.S.), we’re going to have to live with—or catch.”

SOURCE: Heparin Recall › Scientists work to overcome obstacles in synthetic heparin

The blood thinner heparin made news recently when the FDA recalled batches of heparin after more than 80 people died and several others became ill after receiving heparin. It was later determined that heparin made by Baxter International was contaminated in the company’s Chinese manufacturing facility.

While heparin is considered an effective treatment for preventing blood clots and is widely used, it must be injected, which makes long-term therapy difficult. The new drugs would be taken by mouth, which would make dosing easier and eliminate the need for laboratory monitoring.

Heparins garner about $700 million in annual sales, with Sanofi-Aventis’ Lovenox making up nearly two-thirds of the world’s share of the drug. Pfizer’s Fragmin and GlaxoSmithKline’s Fraxiparine account for 6.3 and 5.9 of sales, respectively. Vitamin K Antagonists are responsible for more than $6 billion in sales worldwide, with Bristol-Myers Squibb’s Coumadin, Barr’s Warfarin and Eisai’s Warfarin owning slightly more than half the market’s share.

Three of the five companies are in the late phases of clinical testing, two of which already have been approved in Canada and are awaiting approval in the United States. Two other companies’ drugs have been approved for short-term use in Europe.

SOURCE: Heparin Recall › Pharmaceutical companies developing drugs to fight blood clots

The U.S. Food and Drug Administration announced today that Baxter Healthcare Corporation has temporarily stopped manufacturing multiple-dose vials of the injectable blood-thinning drug heparin due to reports of serious allergic reactions and hypotension (low blood pressure) in patients who receive high “bolus” doses of the drug.

Serious reactions to the drug have included difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that can lead to life-threatening shock. Four people have died after receiving heparin, although the relationship to the drug is unclear.

Heparin sodium is derived from pig intestines and has been marketed in the United States since the 1930s. Millions of patients benefit from the intravenous administration of this drug every year to avoid potentially life-threatening blood clots in the veins, arteries, and lungs.

“FDA concurs with Baxter’s decision to halt manufacture of heparin sodium in multiple-dose vials,” said Janet Woodcock, M.D., FDA’s deputy commissioner for scientific and medical programs, chief medical officer, and acting director of its Center for Drug Evaluation and Research. “FDA is vigorously investigating to determine the root cause of these serious reactions associated with the use of heparin made by Baxter. In the meantime, patients and health care professionals who cannot obtain alternative sources of heparin should use caution in administering any Baxter multiple-dose vials that remain.”

Heparin is commonly used before certain types of surgery, including coronary artery bypass graft surgery, and in kidney patients before they undergo dialysis. In some situations, heparin treatment is initiated using a high bolus dose given directly into the bloodstream (intravenously) over a short period of time, usually less than one hour. The reported adverse events occurred in patients who were given heparin in this form of administration. There are many other uses of heparin involving lower doses or administration over a longer period of time; adverse events have not been seen with those uses.

About 350 adverse events associated with the Baxter product have been reported since the end of last year compared to less than 100 reports in 2007. Most of the events have taken place at hemodialysis centers, almost exclusively involving patients receiving a bolus dose – which is a high dose administered over a short time. While most of the reports involve multiple-dose vials, several cases include patients who received a bolus dose after their health care professional combined heparin from single-dose vials.

The Missouri Department of Health and Senior Services first notified the Centers for Disease Control and Prevention (CDC) in January of several severe allergic-type reactions to heparin that occurred at a single pediatric hospital beginning in November. The CDC in turn alerted FDA and Baxter, prompting the company’s voluntary recall of nine lots of heparin on Jan. 17.

Since then, FDA has learned of adverse events that extend beyond the recalled lots and involve patients receiving heparin for other purposes besides hemodialysis. Recent cases have included patients undergoing cardiac surgery and a specialized blood cell treatment known as photopheresis.

Over one million multiple-dose vials of heparin are sold per month in the United States; half of the vials are manufactured by Baxter of Deerfield, Ill. FDA is currently investigating whether similar events have been seen with other heparin manufacturers.

Physicians, dialysis center staff and health care providers are advised to use an alternate source of heparin or another blood-thinning drug when possible. When only Baxter product is available:

• Administer the heparin as an infusion (not a bolus) whenever possible.
• Use the lowest dose necessary at the slowest infusion rate acceptable to obtain the desired clinical effect.
• Closely monitor the patient for adverse events, particularly hypotension and signs and symptoms of hypersensitivity and ensure that resuscitation equipment is available.
• Consider pretreatment with corticosteroids (cortisone type medicines) or antihistamines (drugs that relieve the symptoms of allergic reactions) although it is not known if such pretreatment is effective.

Any allergic-type reaction to heparin infusion should be reported to FDA’s MedWatch Program by phone at 800-FDA-1088, by fax at 800-FDA-0178, by mail at MedWatch, HF-2, FDA, 5600 Fishers Lane, Rockville, M.D. 20852-9787, or on the MedWatch Web site at www.fda.gov/medwatch.

SOURCE: http://www.fda.gov/bbs/topics/NEWS/2008/NEW01797.html

SOURCE: Heparin Recall › Heparin Linked to Severe Allergic Reactions