A genetically engineered version of human activated protein C (a naturally occurring protein), for reducing mortality in adults with severe sepsis (sepsis associated with acute organ dysfunction) who have a high risk of death. The first biologic and the first treatment approved specifically for sepsis.

* Recommended dosage: Infused at a rate of 24 [micro]g/kg per hour over 96 hours.

* Special considerations: Serious bleeding events, the most significant concern, occurred in 3.5% of Xigris-treated patients, vs. 2% of those on placebo in a 28-day study.

* Comment: Approval was based on a 28-day study of almost 1,700 adults with severe sepsis. Among patients considered to be at a greater risk of death, 31% of those treated with Xigris died, vs. 44% of those treated with placebo, a 13% absolute reduction. (Mortality was not lower in those who were considered less severely ill--a population for whom Xigris is not indicated.)

Xigris has three potential mechanisms that counteract the body's reaction to a serious infection: It has an anti-inflammatory response and suppresses production of inflammatory mediators (at least in vitro); it inhibits certain coagulation factors to prevent clotting; and although it is not lytic itself, it enhances fibrinolysis so blood flow can be restored to tissues, said the lead investigator, Dr. Gordon Bernard.

"This is the first time in my professional lifetime that we have a new treatment for something we see commonly in critically ill patients that really works and reduces mortality" said Dr. Bernard, director of the division of allergy pulmonary and critical care medicine at Vanderbilt University, Nashville, and a consultant to Eli Lilly "It's not an absolute cure by any means, but it does mean that for every 16 patients with this problem who are treated with Xigris, you save one life you otherwise wouldn't have saved."

Paxil

(paroxetine, GlaxoSmithKline)

A selective serotonin reuptake inhibitor for posttraumatic stress disorder (PTSD), the second drug approved for this indication.

* Recommended dosage: Start at 20 mg/day If indicated, can increase by 10mg increments at intervals of at least 1 week. Doses of 20-50 mg are effective.

* Special considerations: In a study of 551 adults with chronic PTSD, the most common side effects in Paxil-treated subjects were asthenia, diarrhea, abnormal ejaculation, impotence, nausea, and somnolence.

* Comment: After 12 weeks, 62% on 20 mg and 54% on 40 mg of Paxil daily were rated as "very much" or "much improved," vs. about 35% of those on placebo, a significant difference. Paxil also reduced reexperiencing, avoidance and/or numbing, and hyperarousal, making this the first study to show a therapeutic effect on all three PTSD symptom clusters (Am. J. Psychiatry 158[12]:1982-88, 2001).

The lead author, Dr. Randall Marshall, director of trauma studies at New York State Psychiatric Institute, New York, said the study was larger than prior studies and excluded patients with treatment-refractory PTSD. It's now known that a PTSD treatment can affect all three dusters and be effective in both sexes. "Paroxetine is a particularly good medication for PTSD because it has such a calming effect, and does not create insomnia," added Dr. Marshall, who is a consultant to the manufacturer.

Tracleer

(bosentan, Actelion Pharmaceuticals US)

An endothelin receptor antagonist for patients with pulmonary arterial hypertension (PAH) and severely limited physical activity. The first approved drug in this class.

* Recommended dosage: 62.5 mg b.i.d., increasing to a 125 mg b.i.d. maintenance dose after 4 weeks.

* Special considerations: Because it is teratogenic and can cause serious liver injury, Tracleer must be obtained directly from the manufacturer, with stringent pregnancy prevention measures. Tracleer may alter metabolism of hormonal contraceptives, which should be used with other contraceptive methods.

* Comment: In studies of 245 patients, Tracleer users had improved 6-minute walking distance and delayed clinical worsening (death, hospitalization, worsening of PAH, or initiation of intravenous therapy). Tracleer blocks receptor binding of endothelin, a potent blood vessel constrictor; elevated levels of the neurohormone in PAH suggest that it plays a pathogenic role.

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