EFFICACY & SAFETY

 

UTEBZI achieved noninferiority* to IV imipenem-cilastatin in the treatment of adults with complicated UTI (cUTI) in the PIVOT-PO clinical trial1

Primary endpoint: composite response (combined clinical cure + microbiological response) at test-of-cure (TOC; day 17±2) in the micro-ITT population1†

Bar chart comparing composite response rates at TOC of Oral UTEBZI and IV imipenem-cilastatin in the PIVOT-PO clinical trial.
  • *

    The Z statistic was used to determine noninferiority. Noninferiority Z statistic: 2.773; efficacy boundary: >2.384. Noninferiority margin: 10% for UTEBZI - imipenem-cilastatin. Noninferiority P value (1-sided): 0.003; efficacy boundary: <0.009.2

  • †

    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

  • ‡

    Adjusted treatment difference (UTEBZI - imipenem-cilastatin) calculated using Miettinen-Nurminen score method, stratified by age at informed consent (≥18 to <65 years vs ≥65 years), baseline diagnosis (pyelonephritis vs cUTI), and presence or absence of urinary tract instrumentation at baseline.1

CI=confidence interval; cUTI=complicated urinary tract infection; micro-ITT=microbiological intent-to-treat.

Composite response in the clinical trial required both significant sign/symptom improvement and uropathogen reduction1

The UTEBZI trial was designed in accordance with current FDA guidance for cUTI trials, which includes stringent criteria for clinical trial design. The primary endpoint was composite response.1,3

Infographic illustrating the definition of a composite response, which requires both a clinical cure and a microbiological response.

CLINICAL CURE: Complete resolution or significant improvement of baseline signs and symptoms of cUTI or pyelonephritis, with no new symptoms and with no additional antimicrobial therapy required.1

 

MICROBIOLOGICAL RESPONSE: Reduction of baseline uropathogens to <103 CFU/mL with negative repeat blood culture if blood culture was positive at baseline.1

 

Patients were considered failures if they were nonresponders (achieved clinical cure only, microbiological response only, or neither at TOC) or if they had indeterminate outcomes (including those with missing data and those lost to follow-up) at TOC.4

CFU=colony forming units; TOC=test-of-cure.

SEE UTEBZI CLINICAL TRIAL DESIGN

The safety of UTEBZI was assessed in the clinical trial.

Learn about the safety profile of UTEBZI in the PIVOT-PO trial.

SEE THE SAFETY PROFILE

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. US Department of Health and Human Services. Food and Drug Administration. Complicated Urinary Tract Infections: Developing Drugs for Treatment. Guidance for Industry. Published 2018. Accessed August 17, 2026. https://www.fda.gov/media/71313/download.

  4. Data on file, GSK.