The FDA has received reports of floating matter in IV bags manufactured by Claris Lifesciences Limited, in Ahmedabad, India. Foreign matter should not be present in a sterile injectable product. Potentially affected products are sold under the Claris, Sagent Pharmaceuticals, Pfizer, and West-Ward Pharmaceuticals labels.
Healthcare professionals should NOT use and should immediately remove from their pharmacy inventories any Metronidazole, Ondansetron, and Ciprofloxacin intravenous bags sold under the following labels: Claris, Sagent Pharmaceuticals, Pfizer, and West–Ward Pharmaceuticals
Patients who have received these products should be observed for signs or symptoms of illness and treated appropriately.
Metronidazole and Ciprofloxacin are antibiotics used to treat a variety of infections. Ondansetron is an antiemetic used to treat nausea and vomiting associated with chemotherapy or surgery.
The FDA said a Claris customer received a complaint of white matter in a bag of Metronidazole, and subsequent microbiological analysis identified the matter as a Cladosporium mold. Molds of this type can cause infections in susceptible patients, such as immunocompromised individuals.
Another customer complaint of white matter in a bag of Ondansetron was received, and that bag is currently under analysis. At this time, FDA is not aware of any reports of injuries due to administration of these products.
Claris is initiating a recall of all lots of these two products, as well as all lots of Ciprofloxacin. These products were all manufactured on the same manufacturing line. FDA is investigating the situation and will notify the public when new information becomes available.
Only Metronidazole, Ciprofloxacin, and Ondansetron in intravenous bags sold under the Claris, Sagent, Pfizer, and West-Ward Pharmaceuticals labels are affected.
In conducting this latest fluoroquinolone study, researchers at Casey Eye Institute at the Oregon Health and Science University in Portland analyzed all eye-related adverse event associated with the drugs that had been reported in international databases and the medical literature between 1986 and 2008. The found 171 case reports of double vision. Of those, 75 cases were linked to Cipro, 9 to Tequin, 20 to Levaquin, 16 to Avelox, 11 to Noroxin and 40 to Floxin. In the 53 reported cases in which a patient stopped taking the medication, vision returned to normal quickly. In five of those cases where the patient was then given the drug again, the problem returned.
The more frequently prescribed fluoroquinolones were more likely to be the subject of double vision reports. This suggests that the problem involves the class of drugs rather than just one or two types of fluoroquinolones, the study authors said.
The study did not reach a conclusion as to the cause of the double vision, but did speculate that the antibiotics may have had an effect on tendons involving the eyes, impacting their ability to focus.
Fluoroquinolones are very strong antibiotics that are used to treat bacterial infections of the lungs, urinary tract and skin. They have been associated with a number of serious side effects, including tendonitis. Last July, the Food & Drug Administration (FDA) asked the manufacturers of fluoroquinolones to add a Black Box warning to the drugs’ labels because of their association with tendon damage. At the time, the FDA said the risk of tendon damage was greatest for those over age 60, those on concomitant steroid therapy, and kidney, heart, and lung transplant recipients. The ruptures generally related to the use of fluoroquinolones involve the Achilles tendon as well as ruptures of the shoulder, hand, biceps, and thumbs. At the time of the warning, he FDA has received nearly 2,250 reports of tendon disorders and 775 reports of tendon ruptures among patients taking fluoroquinolones.
Other side effects associated wit fluoroquinolones have included liver damage, gastrointestinal problems, skin phototoxicity and nervous system problems. Several fluoroquinolones, including Tequin, have been withdrawn from the market because of side effect issues.
The first fluoroquinolone was introduced in 1986. Critics of these drugs allege that fluoroquinolone antibiotics were developed and put on the fast track for Food & Drug Administration (FDA) approval without the benefit of adequate premarket testing to accurately determine the probability of certain side effects within the general population. After gaining FDA approval, the new fluoroquinolone antibiotics were aggressively marketed by the manufacturers.
Cipro became widely known when it was used to treat and prevent anthrax infections in people exposed to the virus as a result of the 2001 mail attacks. While Cipro was apparently an effective weapon against anthrax, it left some victims with lingering health problems.
Last July, the FDA asked the manufacturers of Cipro and other fluoroquinolones to add a black box warning to the drugs’ labels about their association with tendon damage. The FDA said the risk of tendon damage was greatest for those over age 60, those on concomitant steroid therapy, and kidney, heart, and lung transplant recipients. The ruptures generally related to the use of fluoroquinolones involve the Achilles tendon as well as ruptures of the shoulder, hand, biceps, and thumbs. At the time of the warning, he FDA has received nearly 2,250 reports of tendon disorders and 775 reports of tendon ruptures among patients taking fluoroquinolones, though the actual numbers are likely much greater since most side effects are never reported.
According to the Atlanta Constitution-Journal, the tendon risks associated with fluoroquinolones have been known for close to 20 years. The FDA warning only came after the agency was sued by a consumer group for ignoring the drugs' safety risks.
When the FDA finally had the makers of these drugs add warnings to their labels, it stopped short of requiring that drug companies send letters to doctors alerting them of the change. Only a few, such as Bayer HealthCare Pharmaceuticals the maker of Cipro and Avelox, and Oscient Pharmaceuticals, which sells Factive, have voluntarily done so.
As a result, fluoroquinolones are still being prescribed at a high rate, despite the fact that there are safer alternatives. According to the Atlanta Constitution-Journal, in 2007, U.S. patients received more than 40 million prescriptions for fluoroquinolone antibiotics. What's worse, studies have shown that these drugs are often used to treat diseases that don't even respond to antibiotics.
The fact that few doctors and patients are aware of the risks of fluoroquinolones is a serious concerns. The tendon damage often caused by these antibiotics can be mitigated if patients are treated - and switched to another antibiotic - as soon as they start feeling pain. But without the right knowledge, most won't even know the medicine they are taking could be causing their discomfort. If they continue taking the drug, the result could be a tendon rupture, which will require even more intervention - including surgery.
"You don't want to be giving readers the impression that we shouldn't be using antibiotics (when needed)," Dr. David Relman, senior author of the study told the Canadian Press. However, his study found that digestive effects from Cipro, and the negative symptoms of those effects, were still present in healthy patients six months after cessation of antibiotic treatment.
The study, which was published this week in the journal PLoS Biology, found that at the six month mark, “good” bacteria in the digestive tract were either present at decreased levels or not at all present.
According to the Canadian Press report, Relman did agree that “we do overuse antibiotics" and that digestive disruption is “the flip side. It's the trade-off part.” Relman is an infectious diseases specialist at Stanford University and the Veteran Affairs Hospital at Palo Alto, California. He conducted the study—funded by the Doris Duke Charitable Foundation and the U.S. National Institutes of Health—with a team of colleagues, said the Canadian Press.
The study noted that because antibiotics cannot target one bacteria while ignoring others, people can develop problems such as yeast infections or the diarrheal illness, C. difficile, from taking them.
According to the Canadian Press, Relman's team worked with three volunteers and the antibiotic Ciprofloxacin, known as Cipro, which is considered the mildest of antibiotics when it comes to flora disruption. All three volunteers received one course of treatment with Cipro. The team “collected stool samples from their volunteers before they started, during treatment, and for months after,” reported The Canadian Press.
Although the study continues, actually extending out one year, and includes other volunteers, the article in PLoS Biology only refers to the first six months of study, said The Canadian Press. Over that time, the researchers found that “the diversity in bacterial types” decreased by “about one-third.” The large reduction surprised the team, according to Relman, who was also quoted by The Canadian Press as saying, "We find that Cipro was more disruptive than we had thought.... About 30 percent of all of the strains and species that we could see were disrupted. And most of them were ... either knocked out or knocked down."
Both the Infectious Diseases Society of America and the Society of Healthcare Epidemiology of America have published guidelines meant to minimize the spread of the C. diff superbug that include avoiding the overuse of antibiotics.
Coincidentally, earlier this month, the federal Centers for Disease Control and Prevention reported that cases of the C. diff diarrhea bug have been seen in all 50 states.
The findings are part of a new study on antibiotic reactions in the U.S. - the first of its kind -conducted by the Centers or Disease Control (CDC). The researchers used the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project, a sample of 63 U.S. hospitals, between 2004 and 2006. According to their survey, the hospitals recorded more than 6,600 emergency visits that were due to an adverse reaction to an antibiotics. They were able to extrapolate this to the whole country and estimated that 142,000 such emergency visits are made every year.
Systemic antibiotics (pills or injections as opposed to creams) were implicated in 19.3 percent of all emergency department visits for drug-related adverse events," they wrote in the September 15 issue of Clinical Infectious Diseases.
Penicillin and related antibiotics such as amoxicillin - among the most trusted and widely prescribed drugs - accounted for half the emergency visits. Other classes of antibiotics such as cephalosporins, fluoroquinolones - the class that includes Cipro - and newer antibiotics accounted for the rest.
The study found that 78 percent of the adverse events in the study were allergic reactions, ranging from rash to a serious reaction known as anaphylaxis, and the remaining 22 percent were caused by errors and overdoses.
The researchers said that their findings prove that overuse of antibiotics is a serious public health problem. "This number is an important reminder for physicians and patients that antibiotics can have serious side effects and should only be taken when necessary," said the CDC's Dr. Daniel Budnitz, who led the study.
Some studies have found that half of the estimated 100 million antibiotic prescriptions written for respiratory tract infections in the U.S. are unnecessary. The majority of these functions are caused by viruses, and antibiotics are useless against them.
Serious reactions to antibiotics are nothing new. Last month, the Food & Drug Administration (FDA) asked the manufacturers of Cipro and other fluorquinolones to add a black box warning to the drugs’ labels about their association with tendon damage. The FDA said the risk of tendon damage was greatest for those over age 60, those on concomitant steroid therapy, and kidney, heart, and lung transplant recipients. The ruptures generally related to the use of fluoroquinolones involve the Achilles tendon as well as ruptures of the shoulder, hand, biceps, and thumbs
Cipro belongs to the antibiotic group known as fluoroquinolones. Fluoroquinolones are known to carry a number of risks. These include liver problems and tendon damage. The first fluoroquinolone was introduced in 1986, but they are really modified quinolones, a class of antibiotics discovered in the early 1960s. Critics of these drugs allege that fluoroquinolone antibiotics were developed and put on the fast track for Food & Drug Administration (FDA) approval without the benefit of adequate premarket testing to accurately determine the probability of certain side effects within the general population. After gaining FDA approval, the new fluoroquinolone antibiotics were aggressively marketed by the manufacturers.
Cipro became widely known when it was used to treat and prevent anthrax infections in people exposed to the virus as a result of the 2001 mail attacks. While Cipro was apparently an effective weapon against anthrax, it left some victims with lingering health problems.
One of those was John Angell, who was working on Capitol Hill as staff director for Senator Max Baucus (D-Mont.) when the anthrax attacks occurred. While not diagnosed with anthrax, like hundreds of other people, Angell took a course of Cipro to prevent infection. He told The Wall Street Journal that a few days later, he felt pain in both his Achilles tendons. A week after that, the pain had grown so bad that he talked to a doctor, who switched him to another antibiotic.
Angell's Cipro injury was so bad, that he became all but immobile for a time. He had to undergo rehab, and missed a great deal of work. He had to give up his staff director position, and now holds a much less senior job. Even today, Angell still walks with a cane and can’t hike or play tennis the way he used to.
Last month, the FDA asked the manufacturers of Cipro and other fluorquinolones to add a black box warning to the drugs' labels about their association with tendon damage. The FDA said the risk of tendon damage was greatest for those over age 60, those on concomitant steroid therapy, and kidney, heart, and lung transplant recipients. The ruptures generally related to the use of fluoroquinolones involve the Achilles tendon as well as ruptures of the shoulder, hand, biceps, and thumbs
Unfortunately, the new black box warning came too late for John Angell and many others like him.
Cipro and Levaquin belong to the antibiotic group known as fluoroquinolones, which are sold by several drug makers under a variety of brand and generic names. Although the drug labels warn of the risk of tendon ruptures, none include black-box warnings. A black-box warning is in bold type, surrounded by a black box to make it stand out. Such warnings usually appear at the top of drug labels. Any advertising of products that carry black box labels must also include the black box warning information as part of the advertisement. The FDA also announced it will ask the drug companies to create a Medication Guide to be provided to patients to alert them about possible side effects.
Serious reports of tendonitis and tendon rupture are on the rise with the use of these drugs, which finally prompted the FDA to ask drug companies to add the stronger labeling. The ruptures generally related to the use of fluoroquinolones involve the Achilles tendon as well as ruptures of the shoulder, hand, biceps, and thumbs. Tendons are the areas that connect your muscles to your joints. The Achilles tendon is at the back of the ankle. The risk of tendonitis and tendon rupture linked to drugs such as Cipro and Levaquin is "especially increased" in patients older than 60, as well as those who have received kidney, heart, or lung transplants and people on “concomitant” steroid therapy.
Fluoroquinolone Antimicrobial Drugs include: CCiprofloxacin, marketed as Cipro and generic Ciprofloxacin; Ciprofloxacin extended release, marketed as Cipro XR and Proquin XR; gemifloxacin, marketed as Factive; levofloxacin, marketed as Levaquin; moxifloxacin, marketed as Avelox; norfloxacin, marketed as Noroxin; and ofloxacin, marketed as Floxin and generic ofloxacin.
The FDA believes that the addition of a black box warning and a Medication Guide would strengthen the existing warning information already included in the prescribing information for fluoroquinolone drugs.
The FDA warns that physicians “should advise patients, at the first sign of tendon pain, swelling, or inflammation—symptoms that typically precede tendon rupture and tendonitis—to stop taking the fluoroquinolone, to avoid exercise and use of the affected area, and to promptly contact their doctor about changing to a non-fluoroquinolone antimicrobial drug.” Fluoroquinolone is only suggested for the treatment or prevention of an infection proven to be caused by, or strongly suspected to be caused by, bacteria.
According to the FDA release, other side effects experienced in those taking Fluoroquinolones include “seizures, hallucinations, depression, heart rhythm changes (QTc prolongation and torsade de points), and intestine infection with diarrhea. Rarely, damage to the liver, kidneys or bone marrow, and changes to blood sugar may occur.”
Fluoroquinolones are used to treat bacterial infections in many different parts of the body. They work by killing bacteria or preventing their growth. From November 1997 through December 2005, the FDA received 262 reports of tendon ruptures, mainly of the Achilles tendon, 258 cases of tendinitis and 274 cases of other tendon disorders in patients using fluoroquinolone antibiotics. An additional 74 tendon ruptures have subsequently been reported to the FDA for a total of 336. But Public Citizen contends that only a small fraction of cases are typically reported to the FDA, so the actual number of ruptures and other tendon injuries attributable to the antibiotic is probably much higher.
Public Citizen announced yesterday that it had sued the FDA in the U.S. District Court for the District of Columbia over the issue of floroquinolone antibiotics and tendon damage. Public Citizen wants the court to force the FDA to act upon a petition the consumer group filed with the agency 16 months ago. So far, the FDA has failed to respond to the petition, which asked the agency to put a “black box” warning on fluoroquinolone antibiotics to make doctors and patients are more aware of the risk of serious tendon injury before tendons actually rupture.
The Public Citizen petition also urged the FDA to send a warning letter to physicians, as well as require an FDA-approved medication guide to be dispensed when prescriptions are filled. In a press release announcing the antibiotic lawsuit, Public Citizen asserted that stronger warnings could lead to earlier intervention and prevent needless injuries by allowing doctors to switch patients to other antibiotics. “While the FDA sits idly by and ignores the problem, more people will suffer serious tendon ruptures that could have been prevented,” said Dr. Sidney Wolfe, director of Public Citizen’s Health Research Group. “The current warning is buried in a long list of possible adverse reactions and is far too easy to miss.”
Public Citizen said in its complaint that by failing to act upon its fluoroquinolone petition, the FDA is violating the Administrative Procedure Act.