Back

Tebipenem pivoxil

Drug Cards 5 min 17

Font Size

Created On: 30/10/2026

See All

Introduction

Tebipenem pivoxil is an orally administered prodrug of tebipenem. It is a carbapenem antibacterial that kills bacteria by binding essential penicillin-binding proteins (PBPs) and disrupting cell wall biosynthesis. This drug is Food and Drug Administration (FDA) approved for adults battling complicated urinary tract infection (cUTI), including pyelonephritis, triggered by susceptible Enterobacterales and Enterococcus faecalis. It is indicated for those who have restricted or no other oral therapeutic options.[1,2]

Pharmacological class: β-lactam antibacterial[3]

Indications

It is indicated for cUTI caused by susceptible:

Escherichia coli
Klebsiella pneumoniae
Enterobacter cloacae species complex
Klebsiella oxytoca
Enterococcus faecalis[2]

Pharmachologic action

Tebipenem is an antibacterial agent with in vitro activity against selected Gram-negative and Gram-positive bacteria.
It exerts bactericidal powers by binding to essential PBPs, thereby suppressing bacterial cell wall production.
In Escherichia coli and Klebsiella pneumoniae, the drug binds to PBPs 1a, 1b, 2, 3, 4, and 5/6, demonstrating a greater binding preference for PBP 2. This suppression disrupts cell wall biosynthesis, leading to bacterial cell death.[2]

Dosage

Recommended dosage: In adults with an estimated glomerular filtration rate (eGFR) of 60–150 mL/min, administer 600 mg of tebipenem (two 300 mg tablets) orally at 6-hour intervals for 7–10 days.

The recommended dosage for adults across different levels of renal function is presented below in Table 1.

Pharmacokinetics

The key pharmacokinetic characteristics of tebipenem following oral administration are summarized below in Table 2, including its absorption, distribution, metabolism, elimination, and the effects of renal impairment.

Contraindications

It is contraindicated in those with:

Known hypersensitivity or other beta-lactam antibacterial agents.
Primary or secondary carnitine deficiency or inborn metabolic disorders that may cause substantial carnitine deficiency.[2]

Drug interaction

1. Organic anion transporter 1/3 (OAT1/OAT3) inhibitors: Tebipenem is a substrate of OAT1 and OAT3. Co-administration with inhibitors such as probenecid may increase its plasma concentrations. Combined use is generally not recommended; if necessary, increase monitoring for treatment-associated adverse reactions.

2. Valproic acid and divalproex sodium: Carbapenem co-administration may decrease valproic acid concentrations below the therapeutic range, potentially precipitating breakthrough seizures. Avoid the combination where possible. If co-administration is necessary, monitor serum concentrations and consider supplemental anticonvulsant treatment.

3. Other pivalate-generating agents: Combined administration may enhance carnitine depletion through urinary pivaloylcarnitine excretion. Concomitant use is generally not recommended. If required, counsel patients about potential manifestations of carnitine depletion, including hypoglycemia, myalgia, fatigue, and confusion.

4. Interference with newborn screening: Tebipenem use during pregnancy, particularly before delivery, may lead to a false-positive result for isovaleric acidemia in newborn screening tests. Prompt evaluation of positive results is recommended.[2]

Side effects

Commonly reported

Diarrhea
Abdominal pain
Headache
Nausea
Elevated liver enzymes
Clostridioides difficile infection (CDI)

Serious adverse reactions

Hypersensitivity reactions: Potentially severe or fatal allergic reactions.
Central nervous system (CNS) effects: Tremors, confusion, dizziness, seizures, and lightheadedness.
Carnitine depletion: Fatigue, muscle aches, muscle weakness, fainting, confusion, seizures, and hypoglycemia.
Severe antibiotic-associated diarrhea: Persistent or watery diarrhea, abdominal cramps, fever, and bloody stools associated with possible CDI.[2]

Precautions

Hypersensitivity: Assess for previous hypersensitivity to carbapenems, penicillins, cephalosporins, and other beta-lactam antibiotics prior to initiating therapy. Discontinue tebipenem pivoxil if an allergic reaction occurs and institute appropriate treatment.
CNS effects: Exercise caution in those with pre-existing CNS disorders, seizure history, or impaired renal function. Monitor susceptible patients for seizures and other neurological adverse reactions.
Drug interactions: Avoid concurrent use with valproic acid or divalproex sodium due to the potential reduction in valproate concentrations and increased likelihood of breakthrough seizures.
Carnitine depletion: Tebipenem pivoxil may cause reversible reductions in serum carnitine. Adhere to the recommended treatment duration and consider alternative therapy in those at increased risk, particularly those with significant renal impairment or reduced muscle mass. Concomitant use with valproate or other pivalate-generating agents is generally not recommended.
C. difficile–associated diarrhea: Consider CDI in patients developing diarrhea during or after treatment, including delayed presentations. If suspected or confirmed, reassess ongoing antibacterial therapy and initiate appropriate management.
Newborn screening: Administration during pregnancy before delivery may induce a false-positive newborn screening result for isovaleric acidemia; prompt follow-up is advised.
Antimicrobial resistance: Use tebipenem pivoxil only for proven or strongly suspected bacterial infections or an appropriate prophylactic indication.[2]

Clinical evidence

The PIVOT-PO trial assessed oral tebipenem pivoxil hydrobromide (TBP-PI-HBr) against intravenous (IV) imipenem-cilastatin in hospitalized adults with cUTIs or acute pyelonephritis (AP). This global, randomized, double-blind, non-inferiority study used a prespecified 10-percentage-point margin.

Primary endpoint: The proportion of patients in the microbiological intent-to-treat (micro-ITT) population achieving an overall response at the test-of-cure visit, based on both clinical cure and microbiological eradication.

Key findings: Oral TBP-PI-HBr met the prespecified criterion for non-inferiority to IV imipenem-cilastatin (Table 3).

Treatment effects were also comparable among participants with extended-spectrum β-lactamase (ESBL) + Enterobacterales infections. The overall safety profiles were similar, with diarrhea and headache among the most frequently reported treatment-emergent adverse events; no new safety signals were identified.

Clinical significance: The findings supported the potential of oral TBP-PI-HBr as an oral treatment option for cUTI and AP, including infections caused by ESBL-positive Enterobacterales.[4]

References

1. Tebipenem pivoxil. DrugBank. Available from: https://go.drugbank.com/drugs/DB16840
2. Tebipenem pivoxil tablets. FDA Label. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/215960Origs000lbl.pdf
3. Jain A, Utley L, Parr TR, Zabawa T, Pucci MJ. Tebipenem, the first oral carbapenem antibiotic. Expert Rev Anti Infect Ther. 2018 Jul;16(7):513-522.
4. Hong DK, Ascioglu S, Bhatt N, Critchley IA, Gaber M, Gasink LB, et al. Oral Tebipenem Pivoxil Hydrobromide versus Intravenous Imipenem-Cilastatin in Patients with Complicated Urinary Tract Infections or Acute Pyelonephritis: Efficacy and Safety Results from the Phase 3 PIVOT-PO study. Open Forum Infect Dis. 2026 Jan 11;13(Suppl 1):ofaf695.003.

Next
Icotrokinra