Archive | October 2013

Pfizer Warning De-Claws the Tiger (Tygacil)

Tiger mugIt had a great name and memorable marketing campaign, but Tygacil suffered a serious blow with Pfizer’s warning of an “All-Cause Mortality Imbalance” related to the once-promising antibiotic.

Tygacil, colloquially referred to as ‘The Tiger’ was found to increase mortality by 0.6% compared with control antibiotics.  We’ll get into the numbers in a bit, but this was enough for Tygacil to be deemed, “…reserved for use in situations when alternative treatments are not suitable.”   In other words, use something else if at all possible.

Tygacil isn’t a common antibiotic, its intravenous only and not something one is prescribed during a routine office visit.  It has three labeled indications; complicated skin/skin structure infections, complicated intra-abdominal infections, and community acquired bacterial pneumonia.

Patients who need Tygacil are sick, with a serious soft tissue infection such as extensive cellulitis, necrotizing fasciitis, or an intra-abdominal abscess as would be seen in a number of major conditions.  It was once thought as a possible treatment for diabetic foot infections, but was found not to be adequately effective for this indication.

The TigerThe marketing materials were memorable, with tiger-striped giveaways and tigers appearing on brochures and other media.  The best image, printed in countless medical journals, featured a white-coated clinician heading down the hall accompanied by an orange-and-black striped beast standing waist high and weighing around 650 lbs.  The image implies that whatever the threatening bacteria, it is going to be done for when these two get to the room.

How bad is it?  The mailing describes the results of a meta-analysis (basically, a compliation of a number of smaller studies) showing excess mortality in patients undergoing treatment for approved indications of 0.6% compared to patients treated with comparator drugs.  2.5% of patients treated with Tygacil died compared with 1.8% of patients treated with other drugs.  Put another way, Tygacil deaths occurred in excess at a rate of six per thousand patients.  It may not sound like much, but extrapolating out into national numbers means potentially thousands of excess deaths every year.

The reason for the deaths is not clear, and this is not surprising given that these patients were likely all very ill with co-morbidities, so teasing out the cause isn’t easy.  And even with the numbers presented, it isn’t certain that the drug is to blame, but the significance level is enough to put out the warning and continue to watch things closely.

The earlier studies of effectiveness were conducted with smaller numbers of patients (under 300) so rarer events will not be picked up in the majority of cases.  With new drugs, there is always some leap of faith when a product is released for wide use.  Post-marketing (Phase IV) trials are for catching problem drugs once they are released into the wild.  And in this case, the Tiger had to be hunted down.

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