July 8, 2008
Antibiotics can harm tendons, FDA warns
Certain antibiotic drugs such as Bayer AG's Cipro need stronger "black box" warnings about the risk of tendonitis and ruptured tendons, U.S. health regulators said on Tuesday.
The warnings also would apply to Bayer's Avelox, Oscient Pharmaceuticals Corp's Factive and Depomed Inc's Proquin XR. They would also affect Johnson & Johnson's Levaquin and Floxin and Merck & Co Inc's Noroxin. The drugs are members of a family known as fluoroquinolones.
Cipro is sold by various generic makers as ciprofloxacin and Floxin is sold generically as ofloxacin.
Labels for the antibiotics already include cautions about the tendon problems. Despite those warnings, "the FDA continues to receive a considerable number of reports of tendon-related adverse events," Edward Cox, director of the agency's antimicrobial products office, told reporters. "The FDA believes that these new labeling changes will better inform health-care providers and patients about the risk," Cox said.
The risk is greater in patients ages 60 and older, those who have had certain organ transplants and those using steroid therapy, the agency said. It added that doctors should restrict use of the drugs to conditions clearly caused by bacteria.
Patients with tendon pain should immediately stop taking the drug, halt any exercise and call a doctor, the FDA said. The estimated risk of tendon ruptures is about three to four times higher with fluoroquinolones, said Dr. Renata Albrecht, head of the FDA's division of special pathogen and transplant products. The rate in the general population is about 1 in 100,000, Albrecht said.
Most cases involve the Achilles tendon, which attaches the calf muscle to the heel. Less frequent ruptures affected tendons in the shoulders, biceps, hands and elsewhere.
Patients may recover if they act before a rupture, while others need surgery to repair a torn tendon. Even with surgery some patients may not return to normal, Albrecht said.
The FDA was sued earlier this year by consumer group Public Citizen, which had petitioned for the boxed warnings in 2006. At the time, the group said government data showed 262 reported tendon ruptures, 258 cases of tendonitis and 274 other tendon disorders through the end of 2005. Since then, roughly 100 more cases have been reported, Sidney Wolfe, head of Public Citizen's Health Research Group, told Reuters on Tuesday.
The FDA's Albrecht said several hundred cases of tendon- related problems had been reported.
Public Citizen, which was calling for tendon warnings as far back as 1996, also sued the FDA to require companies to notify doctors directly about the risk, something the FDA did not order on Tuesday. "If the doctor is left out of the loop, it just doesn't make any sense," Wolfe said.
Companies will be required to provide guides for patients about possible side effects, the FDA said.
Johnson & Johnson will add the new warning to Levaquin and Floxin, said Amy Firsching, a spokeswoman for the company's Ortho-McNeil unit. Merck also will comply with the FDA request for its drug Noroxin, company spokeswoman Amy Rose said.
Oscient said in a statement it would review the matter. Representatives for other companies did not respond or had no immediate comment. By Susan Heavey
see also: FDA Sued Over Antibiotics Warnings
Daily Mail, 7th February 2012
Taking antibiotics ruptured my tendon
The hidden dangers of everyday drugs we assume are harmless
When Judy Thomas was prescribed a strong antibiotic to shift her chest infection, she didnt think twice about it.
It was a few days before Christmas and I was just relieved to get something before the holidays, says Judy, 59, a housewife from Ferndown, Dorset.
It was a high dose of 500mg of ciprofloxacin twice a day for five days. My GP didnt mention any possible side-effects.
Three days later, Judy woke up with an all-pervading tight feeling in the backs of both calves.
I could barely walk; I thought the tendon was going to snap, she recalls.
Ten days later, when I was standing making tea in the kitchen, something did seem to snap in the back of my left calf.
'The pain was so sharp I felt like Id been shot or kicked, and I blacked out for a few seconds. Afterwards, I was in excruciating pain.
Next day, she went to A&E with her husband, Geoff, 64, and her left leg was put in plaster because doctors suspected a ruptured Achilles tendon.
I was baffled because I hadnt been doing any exercise and its something I thought you only got with running or sport, says Judy.
It was my sister Sally, a retired nurse, who Googled it later that evening and discovered tendon rupture can be a side-effect of taking ciprofloxacin.
'Imagine my horror when this was confirmed by my GP the next day.
It can take six months on average to get back to normal activities after an Achilles tendon rupture, but in some cases much longer. A month after taking ciprofloxican Judy is still incapacitated.
Ive been left unable to walk properly, she says. I cant bear weight on it and have been confined to the house.
'Now Im terrified the tendon in my right leg will rupture, too, as the doctor I saw in A&E said it was showing signs of severe damage.
Ive got pins and needles in my left arm and shoulder, too, which started at the same time. Im worried this is also connected to the antibiotics, and might be permanent.
One in six of all prescriptions in the UK is for antibiotics, with the drugs given for everything from ear infections to sore throats.
But what many patients dont realise is that like all drugs, antibiotics can cause side-effects.
Amoxicillin, the most commonly prescribed antibiotic in the UK, can cause rashes and diarrhoea, but also nausea, wheezing, itching and a swollen tongue.
Another antibiotic, Flucloxacillin, can cause diarrhoea and nausea, and in rarer cases breathing difficulties, jaundice, bruising and abdominal pain.
And erythromycin, used to treat middle ear and throat infections, cannot only cause nausea, vomiting and diarrhoea and a rash, but less commonly temporary deafness, skin blisters, jaundice and fever.
Theres been a perception that antibiotics are a bit like vitamins in that it wont do the patient any harm to take them, even if its not absolutely certain they do have an infection, says Dr Kieran Hand, consultant pharmacist at Southampton General Hospital and a spokesman for the Royal Pharmaceutical Society.
We are realising antibiotics are not completely harmless, and prescribing them is not a decision to be taken lightly.
This is particularly true for a class of powerful broad spectrum antibiotics called fluoroquinolones, which include ciprofloxacin (the drug Judy was prescribed), levofloxacin, moxifloxacin, ofloxacin and norfloxacin.
Just under a million prescriptions for these drugs were given out in the UK in 2010 for conditions such as chest infections and urinary tract and gastro-intestinal infections.
Some of the alarming side-effects listed for fluoroquinolines include inflamed or ruptured tendon, chest pain, rapid heart beat, black outs, swelling, hot flushes, sweating, pancreatitis (inflamed pancreas) and tinnitus.
Its only the fluoroquinolone group of antibiotics that have been linked with tendon problems and other muscolo-skeletal issues.
These may start immediately after taking the drugs, or months later.
As a result, doctors and patients often fail to make the link with the antibiotics.
The Medicines and Healthcare Products Regulatory Agency, the UKs drug safety watchdog, received reports of 2,269 suspected adverse reactions associated with fluoroquinolone antibiotics, including 67 deaths, since January 2000.
Four years ago, concern about the potential side-effects led to the U.S. Food and Drug Administration telling manufacturers to add a black box warning to fluoroquinolones.
This is the most serious warning, short of pulling a drug from the market, and indicates that it carries a significant risk of serious or life-threatening adverse events.
In the UK, the British National Formulary, a prescribing guide for doctors and pharmacists, added a specific warning about fluoroquinolones in 2009, stating they should be used with caution in patients over 60, those taking corticosteroids, and patients with a history of epilepsy or tendon disorders.
But Judy says she had none of these risk factors.
Nor did Rebecca Robinson, a 44-year-old self-employed hairdresser from Bristol, who was prescribed five courses of ciprofloxacin over a 12-month period after developing cystitis and then a kidney infection in 2006.
Five years later, she is still suffering persistent lower leg pain and other unexplained symptoms, including pain and burning in her lower legs, cervical dystonia (neck spasms), tinnitus and muscle twitching some of which are recognised side-effects of ciprofloxacin.
The reaction started immediately after the first dose: I felt giddiness, back pain and needed to pass urine frequently, she says.
But it felt just like the kidney infection coming back, so I was prescribed more of the drugs.
Id never felt right since I took those antibiotics but doctors told me there was no connection.
'After three years of tests and no answers, I went online and discovered there were thousands of other people who had taken ciprofloxacin and had similar side-effects to me.
'I have lost half my customers as I have balance problems and find it difficult to stand for long periods.
'Ive never claimed any disability benefits and always worked to support myself, but what happens if I get worse?
Doctors stress that we must finish a course of antibiotics and dont mention adverse reactions, so people continue taking the drugs, not realising they are causing them damage.
Philip Howard, consultant pharmacist and a specialist in antibiotics, says although ciprofloxacin has been around for 25 years, its only in the past ten years that more side-effects have emerged.
When ciprofloxacin was first introduced, it was one of the first broad spectrum antibiotics which could be given as a tablet, so patients didnt need to stay in hospital.
'That was a major advantage but also came to be one of its major failings, because it then was over-prescribed.
As with all drugs, the rarer side-effects sometimes dont become apparent until large numbers of people have been treated with them.
He says there are few reasons why ciprofloxacin should still be prescribed by a GP except where there is no alternative, such as where the patient has an allergy to penicillin or where other antibiotics havent worked.
There is this assumption that antibiotics have no side-effects, but all drugs carry risks. Id say that unless you need treatment, dont take them.
Neal Patel, pharmacist with the Royal Pharmaceutical Society, says serious side-effects from antibiotics are rare, but patients should be aware of the risks.
If patients notice anything untoward while taking antibiotics they should seek advice from their GP or pharmacist as soon as possible.
A spokesman for Bayer, manufacturer of ciprofloxacin, said the drug has been used in millions of patients worldwide and has a well-established safety profile.
It added: The product information includes information about tendinitis and tendon rupture, which are recognised but very rare adverse drug reactions.
Judy Thomas, though, remains convinced ciprofloxacin is the most likely explanation for her ruptured Achilles tendon and pins and needles.
I feel very strongly that there should be more prominent warnings on patient information leaflets, she says.
Antibiotics are something that all of us take without thinking, but we all need to be aware that they have risks as well as benefits. By Jo Waters