First Oral Carbapenem Approved for Complicated UTIs

The FDA approved oral tebipenem pivoxil (Utebzi) as the first oral carbapenem antibiotic to treat complicated urinary tract infections (UTIs), the agency announced on Wednesday.

Tebipenem pivoxil is indicated for complicated UTIs, including pyelonephritis, caused by the susceptible microorganisms Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae species complex, Klebsiella oxytoca, and Enterococcus faecalis, in adults who have limited or no alternative oral treatment options.

FDA based its approval decision on the phase III PIVOT-PO trial, where oral tebipenem pivoxil proved noninferior to IV imipenem-cilastatin in hospitalized patients with complicated UTIs, including acute pyelonephritis. At day 17, 58.5% of patients randomized to the oral carbapenem responded compared with 60.2% of patients treated with the IV antibiotic, a finding that was enough to stop the trial early.

“For patients with complicated UTIs and their caregivers, this approval is a major milestone, as today’s standard of care places a serious burden on them and hospitals,” said Bilal Chughtai, MD, of Northwell Health in Syosset, New York, in press release from drugmaker GSK. “A new effective oral treatment offering an alternative option to intravenous care has the potential to enable more treatment in the outpatient settings with the ambition to improve their experience.”

Complicated UTIs include those that happen in male, pregnant, or immunocompromised patients, as well as infections that involve the kidneys or are linked to fevers, stones, urinary obstruction, catheters, or sepsis. Associated with significant morbidity and mortality, complicated UTIs are increasingly caused by antimicrobial-resistant bacteria, including multidrug-resistant bacteria. The infections lead to more than 620,000 hospital admissions annually in the U.S.

Tebipenem pivoxil’s recommended dosage is two 300-mg tablets taken orally every 6 hours for 7 to 10 days in adult patients who have an estimated glomerular filtration rate (eGFR) ranging from 60 to 150 mL/min. Lower doses are recommended in patients with renal impairment and an eGFR less than 60 mL/min.

Tebipenem pivoxil’s most common adverse events (at least 1%) in patients were diarrhea, headache, nausea, abdominal pain, hepatic enzyme increases, and Clostridioides difficile infection. The antibiotic’s prescribing information notes contraindications including concomitant use with valproic acid or divalproex sodium, or treatment beyond the recommended duration, which could lead to carnitine deficiency.

Tebipenem pivoxil should be available to U.S. patients by the end of 2026, GSK said.