FDA Approves New Indication for Wyeth’s TYGACIL (tigecycline) for the Treatment of Adult Patients with Community-Acquired Bacterial Pneumonia

Indication Offers New Option for Adult Patients Suffering From Community-Acquired Bacterial Pneumonia


Collegeville, Pa.– Wyeth Pharmaceuticals, a division of Wyeth (NYSE: WYE), announced today that the U.S. Food and Drug Administration (FDA) approved TYGACIL® (tigecycline), for the treatment of adult patients with community-acquired bacterial pneumonia (CABP) caused by susceptible strains of indicated pathogens. TYGACIL was first approved by the FDA in 2005 for the treatment of complicated intra-abdominal infections (cIAI) and complicated skin and skin structure infections (cSSSI) caused by susceptible strains of indicated pathogens in adults.

“The approval of this new indication is timely. Antibiotic resistance continues to grow and new antimicrobials are needed,” says Joseph Camardo, M.D., Senior Vice President, Global Medical Affairs, Wyeth Pharmaceuticals. “The approval of TYGACIL for CABP is an important milestone in Wyeth’s commitment to exploring new treatment options in the anti-infective therapeutic area.”

Thomas File, M.D., Chief of Infectious Disease Services for Summa Health System in Akron, Ohio, says, “CABP is a serious and potentially fatal respiratory disease that affects millions of Americans each year. The approval of TYGACIL for CABP means that physicians will have an additional option available to treat patients suffering from the disease.”

CABP accounts for an estimated 4.5 million visits to physician offices, emergency departments, and outpatient clinics each year.

About the CABP Clinical Trials

The approval was based on results of two randomized, double-blind, active-controlled, multinational studies (Studies 308 and 313) that evaluated TYGACIL for the treatment of CABP in adults. The two studies (N=859) were conducted at 116 sites in 28 countries and evaluated the efficacy and safety of TYGACIL compared with levofloxacin in subjects hospitalized with CABP. Results showed that clinical cure rates of patients hospitalized with CABP were comparable for both TYGACIL and levofloxacin. Clinical cure rates in clinically evaluable patients were 90.6 percent for TYGACIL and 87.2 percent for levofloxacin in Study 308 and 88.9 percent for TYGACIL and 85.3 percent for levofloxacin in Study 313.

About Community-Acquired Bacterial Pneumonia

Community-acquired bacterial pneumonia, or CABP, is commonly defined as an acute infection of the pulmonary parenchyma (the functional part of the lungs) that is generally associated with at least some symptoms of acute infection, in a patient who has not been hospitalized or resided in a long-term care facility within 14 days of symptom onset. Symptoms of CABP include cough, fever, chills, fatigue, shortness of breath, and chest pain.

Indications

TYGACIL is indicated for the treatment of adults with:

Complicated skin and skin structure infections (cSSSI) caused by Escherichia coli, Enterococcus faecalis (vancomycin-susceptible isolates), Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus agalactiae, Streptococcus anginosus group (includes S. anginosus, S. intermedius, and S. constellatus), Streptococcus pyogenes, Enterobacter cloacae, Klebsiella pneumoniae, and Bacteroides fragilis.

Complicated intra-abdominal infections (cIAI) caused by Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Enterococcus faecalis (vancomycin-susceptible isolates), Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus anginosus group (includes S. anginosus, S. intermedius, and S. constellatus), Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Clostridium perfringens, and Peptostreptococcus micros.

Community-acquired bacterial pneumonia (CABP) caused by Streptococcus pneumoniae (penicillin-susceptible isolates), including cases with concurrent bacteremia, Haemophilus influenzae (beta-lactamase negative isolates), and Legionella pneumophila.

In vitro activity of TYGACIL

TYGACIL, the first glycylcycline IV antibiotic has an expanded broad spectrum of in vitro activity against many gram positives, gram negatives, anaerobes, methicillin-resistant and -susceptible Staphylococcus aureus (MRSA and MSSA), and vancomycin-resistant enterococci (VRE). TYGACIL is unaffected by extended-spectrum beta-lactamases (ESBLs).

With this approval, the in vitro profile of TYGACIL has now been expanded to include: Haemophilus influenzae (ampicillin-resistant) and Haemophilus parainfluenzae. The clinical significance of in vitro activity is unknown.

Empiric monotherapy

TYGACIL can be used as an empiric monotherapy to treat a variety of cIAI and cSSSI, both hospital- and community-acquired, including complicated appendicitis, intra-abdominal abscesses, infected burns, deep soft-tissue infections, and infected ulcers.

TYGACIL provides clinicians with an expanded broad-spectrum antibiotic option that can be used at the onset of treatment when the specific bacteria present are not yet known. When culture and susceptibility information are available, they should be considered in modifying antibacterial therapy. In addition, TYGACIL does not require dosage adjustment in patients with impaired renal function, and is conveniently dosed every 12 hours.

Important Safety Information

• To reduce the development of drug-resistant bacteria and maintain the effectiveness of TYGACIL and other antibacterial drugs, TYGACIL should be used only to treat infections proven or strongly suspected to be caused by susceptible bacteria
• Anaphylaxis/anaphylactoid reactions have been reported with nearly all antibacterial agents, including tigecycline, and may be life-threatening
• TYGACIL is contraindicated in patients with known hypersensitivity to tigecycline
• TYGACIL should be administered with caution in patients with known hypersensitivity to tetracycline class antibiotics
• TYGACIL is structurally similar to tetracycline-class antibiotics and may have similar adverse effects. Such effects may include: photosensitivity, pseudotumor cerebri, and anti-anabolic action (which has led to increased BUN, azotemia, acidosis, and hyperphosphatemia). As with tetracyclines, pancreatitis has been reported with the use of TYGACIL
• The safety and efficacy of TYGACIL in patients with hospital-acquired pneumonia have not been established
• In clinical trials, the most common treatment-emergent adverse events in patients treated with TYGACIL were nausea (26%) and vomiting (18%)
• TYGACIL may cause fetal harm when administered to a pregnant woman
• The safety and effectiveness of TYGACIL in patients below age 18 and lactating women have not been established
• Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including TYGACIL, and may range in severity from mild diarrhea to fatal colitis
• Concurrent use of antibacterial drugs with oral contraceptives may render oral contraceptives less effective
• The use of TYGACIL during tooth development may cause permanent discoloration of the teeth. TYGACIL should not be used during tooth development unless other drugs are not likely to be effective or are contraindicated
• Prothrombin time or other suitable anticoagulant test should be monitored if TYGACIL is administered with warfarin
• Monotherapy should be used with caution in patients with clinically apparent intestinal perforation
• Isolated cases of significant hepatic dysfunction and hepatic failure have been reported in patients being treated with tigecycline. Some of these patients were receiving multiple concomitant medications. Patients who develop abnormal liver function tests during tigecycline therapy should be monitored for evidence of worsening hepatic function. Adverse events may occur after the drug has been discontinued
• In patients with severe hepatic impairment (Child Pugh C), the initial dose of TYGACIL should be 100 mg followed by 25 mg every 12 hours. Patients should be treated with caution and monitored for treatment response
• The following drugs should not be administered simultaneously through the same Y-site as TYGACIL: amphotericin B and diazepam