There has been concern in the past three or four years about the potentially lethal side effects of the drug Ketek®. Ketek® is the trade name for telithromycin, an antibiotic, and is manufactured by Sanofi-Aventis. As stated on their Ketek® website (www.ketek.com), it is to be used for people 18 years and older, to treat the respiratory tract infections of:
- Community-acquired pneumonia (CAP), mild to moderate in severity
- Acute bacterial sinusitis (ABS)
- Acute exacerbation of chronic bronchitis (AECB)1
when these infections are caused by certain specified bacteria. It is not anti-viral. The Ketek® dose is 800 mg per day, and depending on which particular infection is being treated, the treatment period is between five and ten days.2As described by the FDA 2004 Approval Letter, the Ketek tablets are light orange, oval, film-coated tablets at 400 mg.3
The Controversy
Ketek® has been linked to temporary blindness, abnormal heart rhythms, and liver damage. The issues are whether enough safety studies have been done, and whether any of those done were flawed.
FDA Timeline
- In 2001 and 2003 the FDA refused approval of Ketek® pending further analysis and information.4
- In April 2004 the FDA approved it for treating the above three infections.4
- On January 20, 2006, the FDA stated in its Public Health Advisory:
- Today, January 20, 2006, Annals of Internal Medicinepublished an article reporting three patients who experienced serious liver toxicity following administration of Ketek (telithromycin). These cases have also been reported to FDA MedWatch. Telithromycin is marketed and used extensively in many other countries, including countries in Europe and Japan … the FDA is continuing to evaluate the issue of liver problems in association with use of telithromycin in order to determine if labeling changes or other actions are warranted.5
The outcomes in those three cases of liver toxicity were one death, one recovery, and one liver transplant.6
The FDA Advisory went on to recommend that healthcare providers and patients should watch for signs of liver problems, such as yellowing of the skin or eyes, and that the drug should be used strictly for the conditions for which it was approved, noting in particular that it is for bacterial, not viral infections (e.g. colds).
The FDA Advisory also noted that, “Based on the pre-marketing clinical data, it appeared that the risk of liver injury with telithromycin was similar to that of other marketed antibiotics.”
- On May 19, 2006, in a News Release, the FDA connected “rare cases of serious liver injury and liver failure” (including four which ended in death and one which required a liver transplant) to Ketek®.7
- On June 29, 2006, the FDA issued a report at the conclusion of its Safety Assessment of Ketek®. It advised both health practitioners and patients to “be aware of rare but potentially serious health risks.” It also instructed Sanofi-Aventis to add a warning to its Ketek® label about these safety concerns. Then it gave the green light to continued Ketek® availability:
Although it is difficult to determine the exact frequency of Ketek-associated adverse events on the basis of FDA’s mandatory and voluntary reporting systems, the agency has concluded that the drugs’ (sic) benefit to patients for the approved indications outweighs its risk, including the rare risk of liver failure, and supports its continued availability.8
- On December, 2006, an article posted athttp://www.stjosephhospital.com/webmd/display_article.phpi?id=117813
discussed the upcoming FDA panel assembled to decide whether Ketek® should be taken off the market. This article gives an overview of the medical and political situation and refers to a Senate Finance Committee report just released which “…concluded that FDA officials did not tell the advisory panel in 2003 that a Sanofi Aventis safety study, called 3014, was flawed.”
It goes on to say:
FDA officials have said they did not take that study into account when they approved Ketek. They instead relied on European safety studies attempting to measure Ketek’s safety on the market in France, Germany, and other countries.
The Liver9
The liver is the largest organ in humans (weighing three or four pounds), with many blood vessels, and is situated in the abdomen, just below the diaphragm. Foods we eat are broken down in the stomach and intestines, so that fats, proteins, and carbohydrates are extracted and absorbed into the blood. The blood carries them to the liver.
Some Functions of the Liver
- It secretes bile, a yellowish-green liquid which it sends to the intestines, to help absorb and emulsify fats
- It filters the blood sent to it, storing nutrients or changing them to be more usable by the body, and breaking down poisonous substances to less harmful ones.
- It breaks down carbohydrates into glucose, which we use for energy. Any glucose that we don’t immediately need as energy is stored in the liver as glycogen (It’s also stored in the muscles). When we need energy, the liver converts glycogen back to glucose. The brain depends on a steady supply of glucose to function properly.
- It processes old red blood cells so they can be excreted and new ones can take their place.
Jaundice
One of the early signs of liver problems is a yellowish color in the skin and/or eyes. This is known as jaundice10, and is caused by bilirubin, a byproduct of old red blood cells. We discard old blood cells every day, creating new ones, and if liver function is impaired, so that it can’t keep up with disposing of the old cells, bilirubin builds up in the body, causing jaundice.
Mild jaundice usually resolves itself and can be seen in bruises, and in many newborn babies. Pathologic jaundice is the name for health-threatening jaundice, of which one cause is liver damage or disease.
Hepatitis11, 12
Hepatitis is a gastrointestinal disease in which the liver becomes fatty and its cells become bloated and inflamed, unable to do their crucial jobs.
- Infectious hepatitis – can be caused by a virus, bacteria, fungus, or parasite
- Non–infectious hepatitis – can be caused by medications, toxins and autoimmune disorders.
Whatever the cause, hepatitis is inflammation of the liver, has many unpleasant symptoms, and can lead to death.
Side Effects of Ketek®13
According to the National Institutes of Health, the many possible side-effects of Ketek® are as follows. If you are taking Ketek® and notice any of these, report it to your doctor immediately.
Mild:
- Diarrhea
- Upset stomach
- Headache
- Dizziness
- Vomiting
- Loose stools
- Changes in ability to taste
- Blurred vision
Serious:
- Fainting
- Rapid, irregular, or pounding heartbeat
- Extreme tiredness
- Unusual bleeding or bruising
- Lack of energy
- Loss of appetite
- Pain in the upper right part of the stomach
- Yellowing of the skin or eyes
- Flu-like symptoms
- Hives
- Rash
- Itching
- Difficulty breathing or swallowing
- Swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
- Hoarseness
For more information on possible problems with Ketek®, see the FDA’s Patient Information Sheet at http://www.fda.gov/cder/drug/InfoSheets/patient/telithromycinPIS.HTM.
How Ketek® Differs from Other Antibiotics
Ketek® is marketed as “The Word’s First Ketolide”14 and it is indeed the only ketolide on the market so far. Ketolides are a fairly new family of semisynthetic antibiotics (antimicrobials). They are derived from erythromycin, and are particularly effective against some otherwise resistant bacteria because they can bind to two different sites on the bacteria, instead of just one. This means they can more effectively inhibit protein synthesis, preventing the bacteria from reproducing.
Contact the FDA
If you take Ketek® and experience any serious side effects, the FDA invites you to contact them15:
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration’s (FDA) MedWatch Adverse Event Reporting program online [at http://www.fda.gov/MedWatch/report.htm] or by phone
[1-800-332-1088].
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Sources
- www.ketek.com/professional/home.aspx
- www.ketek.com/professional/tailored_coverage.aspx
- www.fda.gov/cder/foi/label/2004/21144_ketek_lbl.pdf
- www.cooperativeresearch.org/timeline.jsp?
- timeline=us_health_care_tmln&case_studies_drugs=ketek
- www.fda.gov/cder/drug/advisory/telithromycin.htm
- www.fda.gov/cder/drug/infopage/telithromycin/qa.htm
- www.fda.gov/medwatch/safety/2006/safety06.htm#Ketek2
- www.fda.gov/bbs/topics/NEWS/2006/NEW01401.html
- www.britishlivertrust.org.uk/content/liver/diet.asp
- www.nlm.nih.gov/medlineplus/ency/article/003243.htm
- http://en.wikipedia.org/wiki/Hepatitis
- http://www.emedicine.com/emerg/topic244.htm
- www.nlm.nih.gov/medlineplus/druginfo/medmaster/a604026.html
- www.ketolide.com/
- www.nlm.nih.gov/medlineplus/druginfo/medmaster/a604026.html
