Labeling for Bristol-Myers Squibb's Tequin discusses the in vitro efficacy of the quinolone antibiotic against penicillin-resistant Streptococcus pneumoniae.

FDA approved Tequin (gatifloxacin) tablets and injection Dec. 17 for treatment of acute bacterial sinusitis, community acquired pneumonia, acute bacterial exacerbation of chronic bronchitis, complicated and uncomplicated urinary tract infections, pyelonephritis and uncomplicated gonorrhea.

Tequin exhibits in vitro minimum inhibitory concentrations of

"However the safety and effectiveness of gatifloxacin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials," labeling adds.

Ortho-McNeil's quinolone Levaquin (levofloxacin) may soon gain an indication for penicillin-resistant strains. An FDA advisory committee has recommended approval of a penicillin-resistant CAP indication ("The Pink Sheet" Oct. 25, 1999, p. 5).

Bristol's original NDA also sought an indication for uncomplicated skin and skin structure infections. The skin indication "is approvable pending submission of post-marketing data confirming the safety of gatifloxacin and therefore demonstrating an acceptable risk/benefit profile," FDA's approval letter states.

Bayer's quinolone Avelox (moxifloxacin) was also deemed "approvable" for uncomplicated skin and skin structure infection when approved for other indications earlier in December ("The Pink Sheet" Dec. 20, 1999, p. 3).

The main safety concern with Tequin, as with some other quinolones, is the potential for QT interval prolongation. However, the QT warning language for Tequin is not as strong as the Avelox warning.

Tequin labeling warns that "gatifloxacin may have the potential to prolong the QTc interval," while the Avelox warning says the product "has been shown" to prolong the QT interval.

Tequin labeling notes that, in volunteer studies, "there were no subjects with abnormal QTc intervals (>450 msec); the mean +/- SD change in QTc interval was 2.9 +/- 16.5 msec." No cardiovascular adverse events attributable to QTc prolongation occurred with gatifloxacin in over 4,000 patients, including 118 patients concurrently receiving drugs known to prolong the QTc interval and 139 with uncorrected hypokalemia.

Although labeling does not discuss any clinical evidence of QTc prolongation, FDA indicated that the warning reflects information derived from both preclinical and clinical data.

Bristol will further study cardiac AEs in Phase IV. The company will submit results from seven Phase IV studies by Dec. 31, 2000. Many of the commitments are the same as those required for Avelox.

Bristol must review post-marketing AE data following at least 1 mil. patient exposures worldwide; conduct an active surveillance program of at least 15,000 patients; study the effect of gatifloxacin on the QTc interval in patients receiving the drug in ongoing studies; conduct a single oral dose escalation study of the effects of QTc at Cmax; study the effects of gatifloxacin on QTc at Cmax compared to ciprofloxacin, clarithromycin and sparfloxacin; assess pharmacokinetics in the studies on an "equal number of men and women over a broad range of ages"; and repeat its rat oral and I.V. teratology studies using "adequately high dose levels."

The dose of Tequin for all indications is 400 mg once daily (uncomplicated UTIs may also be treated with 200 mg daily), with duration of therapy ranging from one day for gonorrhea to up to 14 days for CAP. A dosage reduction to 200 mg daily after the initial 400 mg dose is recommended for patients with creatinine clearance <40>

Tequin will be available in 200 mg and 400 mg tablets and in single-use 20 mL or 40 mL (10 mg/mL) vials. Oral and I.V. doses are interchangeable and patients may be switched from Tequin I.V. injection to tablets with no dose adjustment necessary, labeling states.

Tequin is being shipped to pharmacies at a list price of $291 for a 50-count bottle of 400 mg tablets, or $583 for a 100-count blister pack. The 40 mL I.V. vial has a list price of $31.70.

The Tequin NDAs (21-161, 21-062) were submitted in December 1998 and had a Dec. 28 user fee date.

Tequin Labeling Notes In Vitro Activity Vs. Penicillin-Resistant S. Pneumoniae

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