EFFICACY & SAFETY

 

UTEBZI was studied in a phase 3, randomized, double-blind, double-dummy, active-comparator, noninferiority clinical trial1,2

PIVOT-PO trial design2,3

Flowchart of the PIVOT-PO phase 3 clinical trial design for UTEBZI including screening, treatment, TOC and LFU phases.

PRIMARY ENDPOINT:

Composite response‖ in the micro-ITT† population at test-of-cure (TOC) visit (day 17±2).1

The Z statistic was used to determine noninferiority. The Z statistic boundary for noninferiority was 2.384. Noninferiority margin was 10%.2

 

Key inclusion criteria3:

  • Hospitalized nonpregnant patients aged ≥18 years
  • Diagnosis of cUTI or pyelonephritis
  • Urine specimen within 24 hours of randomization with evidence of pyuria that included ≥1 of the following: ≥10 WBCs/HPF in urine sediment, ≥10 WBCs/mm3 in unspun urine, or positive leukocyte esterase on urinalysis

 

Key exclusion criteria3:

  • Receipt of a potentially effective antibiotic ≤72 hours before randomization or anticipated concomitant use of an antimicrobial
  • CrCl ≤30 mL/min
  • Severe hepatic impairment
  • Immunodeficient or immunocompromised patients
  • History of CDAD
  • Confirmed/suspected acute or chronic bacterial prostatitis, orchitis, or epididymitis
  • *

    Randomization stratified by age at informed consent (≥18 to <65 years vs ≥65 years), baseline diagnosis (cUTI vs pyelonephritis), and presence or absence of urinary tract instrumentation at baseline.2

  • †

    The micro-ITT population comprised randomized patients with Enterobacterales pathogens isolated from urine (≥105 CFU/mL, or concurrently in blood culture at baseline). Patients with >2 microorganisms identified in urine culture and with any baseline pathogens not susceptible to imipenem were excluded; patients could be co-infected with Enterococcus faecalis, Staphylococcus aureus, or Staphylococcus saprophyticus.1

  • ‡

    Study days = calendar days, not 24-hour days.3

  • §

    Placebo matched comparator.3

  • ‖

    Composite response: clinical cure + microbiological response. Clinical cure: complete resolution or significant improvement of signs and symptoms of cUTI/pyelonephritis present at baseline, without new symptoms or further antimicrobial therapy. Microbiological response: reduction of baseline uropathogens to <10³ CFU/mL and negative repeat blood culture if blood culture was positive at baseline.1

C. difficile=Clostridioides difficile; CDAD=C. difficile-associated diarrhea; CFU=colony-forming unit; CrCl=creatinine clearance; cUTI=complicated urinary tract infection; HPF=high-power field; ICF=informed consent form; imi-cil=imipenem-cilastatin; ITT=intent-to-treat; LFU=long-term follow-up; micro-ITT=microbiological intent-to-treat; q6h=every 6 hours; TOC=test of cure; WBC=white blood cell.

Learn about the clinical trial population.

Review patient demographics from the PIVOT-PO trial.

SEE THE TRIAL POPULATION

Indication & Important Safety Info

Indication

Important Safety Information

Indication

UTEBZI is indicated for the treatment of adults with complicated urinary tract infections (cUTI), including pyelonephritis, caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae species complex, Klebsiella oxytoca, and Enterococcus faecalis, who have limited or no alternative oral treatment options.

Usage to Reduce Development of Drug-Resistant Bacteria

To reduce the development of drug-resistant bacteria and maintain effectiveness of UTEBZI and other antibacterial drugs, UTEBZI should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.

Important Safety Information

CONTRAINDICATIONS

UTEBZI is contraindicated in patients with hypersensitivity to UTEBZI or other beta-lactam drugs.

UTEBZI is contraindicated in patients with primary or secondary carnitine deficiency or inborn errors of metabolism that may result in clinically significant carnitine deficiency.

WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions

  • Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam and carbapenem drugs. Before initiating UTEBZI, assess patients for previous hypersensitivity to carbapenems, penicillins, cephalosporins or other beta-lactams. If an allergic reaction to UTEBZI occurs, discontinue, and institute appropriate supportive measures.

Seizures and Other Central Nervous Systems (CNS) Adverse Reactions

  • Seizures and other CNS adverse reactions have been reported in patients receiving therapy with beta-lactam and carbapenem drugs, including UTEBZI. These reactions occurred most commonly in patients with CNS disorders and/or compromised renal function. Monitor patients at risk for convulsive activity. If CNS adverse reactions including seizures occur, evaluate neurologically to determine whether UTEBZI should be discontinued.

Interactions with Valproic Acid

  • Concomitant use of carbapenems, including UTEBZI, with valproic acid or divalproex sodium may reduce the plasma concentration of valproic acid, potentially increasing the risk of breakthrough seizures. Avoid concomitant use of UTEBZI with valproic acid or divalproex sodium.

Carnitine Depletion

  • Clinical manifestations of carnitine deficiency may occur with pivalate-containing compounds, including UTEBZI. UTEBZI is contraindicated in patients with primary and secondary carnitine deficiency or inborn errors of metabolism that may result in clinically significant carnitine deficiency. Do not use UTEBZI beyond the recommended treatment duration. Consider alternative antibacterial therapy in patients at risk for reductions in serum carnitine (eg, patients with significant renal impairment or decreased muscle mass). Concomitant use with valproic acid, valproate, or other pivalate-generating drugs is generally not recommended due to the increased risk of carnitine depletion.

Clostridioides difficile Infection (CDI)

  • Clostridioides difficile infection has been reported with nearly all systemic antibacterial agents, including UTEBZI and may range in severity from mild diarrhea to fatal colitis. CDI is associated with increased morbidity and mortality. Evaluate patients if diarrhea occurs. Careful medical history is necessary since CDI has been reported to occur over 2 months after the administration of antibacterials. Consider discontinuation of ongoing antibacterials if CDI is suspected or confirmed.

Interference with Newborn Screening Test

  • Treatment of a pregnant individual with UTEBZI prior to delivery may cause a false positive test for isovaleric acidemia in newborn screening. Prompt follow-up of a positive result is recommended.

Development of Drug-Resistant Bacteria

  • Prescribing UTEBZI in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit and increases the risk of the development of drug-resistant bacteria.

ADVERSE REACTIONS

  • The most common adverse reactions occurring in ≥1% of patients are diarrhea, headache, nausea, abdominal pain, hepatic enzyme increased, and Clostridioides difficile infection.

DRUG INTERACTIONS

  • Organic anion transporter 1 (OAT1) and OAT3 inhibitors: Concomitant use is generally not recommended due to increased tebipenem plasma concentrations. If concomitant use is necessary, monitor more frequently for adverse reactions associated with UTEBZI.
  • Valproic acid and divalproex sodium: Avoid concomitant use as it may reduce valproic acid plasma concentrations, increasing the risk of breakthrough seizures. If concomitant use is necessary, monitoring of valproic acid serum concentrations is recommended and consider supplemental anticonvulsant therapy.
  • Other pivalate-generating drugs: Concomitant use is generally not recommended due to decreased carnitine plasma concentrations which may increase the risk of carnitine depletion-associated adverse reactions. If concomitant use is necessary, counsel patients to monitor adverse reactions associated with carnitine depletion.
  • Treatment of a pregnant individual with UTEBZI prior to delivery may cause a false positive test for isovaleric acidemia in the newborn as part of newborn screening. Prompt follow-up of a positive result is recommended.

USE IN SPECIFIC POPULATIONS

  • Pregnancy: There are insufficient data on the use of UTEBZI in pregnant women. There is a pregnancy safety study for UTEBZI. Healthcare providers or patients may report UTEBZI exposure while pregnant by contacting GSK at 1-888-825-5249. Treatment of a pregnant individual with UTEBZI prior to delivery may cause a false positive test for isovaleric acidemia in the newborn as part of newborn screening.
  • Renal Impairment: Tebipenem plasma concentrations increase with decreasing renal function. Dosage adjustments for UTEBZI are recommended for patients with renal impairment (eGFR 15 mL/min to < 60 mL/min). Use in adults with eGFR >150 mL/min is not recommended because it is predicted to decrease tebipenem exposure, which may reduce UTEBZI efficacy. If use is necessary, monitor clinical response closely and counsel patients to promptly report lack of improvement or worsening of their condition.

Please see full Prescribing Information, including Patient Information, for UTEBZI.

To report SUSPECTED ADVERSE REACTIONS, contact GSK at gsk.public.reportum.com or 1-888-825-5249, or
FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

References

  1. UTEBZI (tebipenem pivoxil) tablets. Prescribing Information. GSK; 2026.
  2. Hong DK, Ascioglu S, Bhatt N, et al. Oral tebipenem pivoxil hydrobromide vs intravenous imipenem-cilastatin in patients with complicated urinary tract infections or acute pyelonephritis: efficacy and safety results from the phase 3 PIVOT-PO study. Presented at: IDWeek 2025; October 19-22, 2025; Atlanta, GA.
  3. Data on file, GSK.