Sanofi Issues Warning Letter. This week, drug maker Sanofi-Aventis sent a letter to healthcare professionals outlining the various warning and prescription changes related to their antibiotic Ketek.
The changes, mandated last month by the U.S. Food and Drug Administration (FDA), include a revision of approved indications for usage along with a variety of health-risk warnings.
According to the company, “The prescribing information has been revised to add a boxed warning and contraindication for myasthenia gravis patients. In addition, the indications for the treatment of acute exacerbation of chronic bronchitis (AECB) and acute bacterial sinusitis (ABS) have been removed from the labeling.
These revisions follow discussions with the Food and Drug Administration (FDA) regarding its decision to follow recommendations of a December 2006 Advisory Committee that the balance of the benefits and risks no longer support continued marketing of Ketek for these two indications.
It is important to note that Ketek continues to be indicated only for the treatment of community-acquired pneumonia (CAP) of mild to moderate severity.”
Sanofi adds, “Safety information regarding visual disturbances and loss of consciousness, previously in the precautions section, has been added to the warnings section. In prescribing Ketek, it is important for healthcare professionals to inform and discuss with patients the four highlighted toxicities: exacerbation of myasthenia gravis, hepatotoxicity, visual disturbances, and loss of consciousness.”
The company notes that “Ketek may cause visual disturbances
The company notes that “Ketek may cause visual disturbances particularly in slowing the ability to accommodate and the ability to release accommodation. Visual disturbances included blurred vision, difficulty focusing, and diplopia. Most events were mild to moderate; however, severe cases have been reported.”
They also point to “post-marketing adverse event reports of transient loss of consciousness including some cases associated with vagal syndrome. Because of potential visual difficulties or loss of consciousness, patients should attempt to minimize activities such as driving a motor vehicle, operating heavy machinery, or engaging in other hazardous activities during treatment with Ketek.”
The company also reiterated its warnings related to hepatotoxicity (liver damage), first issued in June of last year. “Acute hepatic failure and severe liver injury, in some cases fatal, have been reported in patients treated with Ketek,” they note.
“These hepatic reactions included fulminant hepatitis and hepatic necrosis leading to liver transplant, and were observed during or immediately after treatment. In some of these cases, liver injury progressed rapidly and occurred after administration of a few doses of Ketek.
Physicians and patients should monitor for the appearance of signs or symptoms of hepatitis, such as fatigue, malaise, anorexia, nausea, jaundice, bilirubinuria, acholic stools, liver tenderness, or hepatomegaly.”
“In addition,” they report, “less severe hepatic dysfunction associated with increased liver enzymes, hepatitis, and in some cases jaundice was reported with the use of Ketek.”
The FDA announced the most recent changes in February
The FDA announced the most recent changes in February. At the time, the FDA said, “The joint advisory committee, which met on December 14 and 15, 2006, advised that the available data including data acquired since the initial approval of Ketek support a conclusion that the benefits of Ketek outweigh the risks in patients with community acquired pneumonia, but not for patients with acute bacterial sinusitis or acute bacterial exacerbation of chronic bronchitis.”
Ketek was originally approved by the FDA in 2004, but the approval process for the controversial drug has come under scrutiny by both houses of Congress as the issue of prescription drug safety has gained momentum in recent months.
The FDA originally rejected Ketek in 2001, citing risks including liver damage and blurred vision. In response, Sanofi-Aventis commissioned a rather dubious study of the drug that suffered from falsified data, inappropriate subjects, criminal doctors, and significant violations of the study’s guidelines.
Though that study was rejected and a subsequent clinical trial was rife with inaccuracies, an FDA advisory panel pushed for Ketek’s approval in 2003. Although the full FDA declined approval that year, they reversed their decision the following year.
The controversy has ignited calls from medical professionals and congressmen for more stringent standards in the FDA’s approval of pharmaceuticals.