Orlynvah From Iterum Therapeutics

The FDA has approved sulopenem etzadroxil and probenecid oral tablets (Orlynvah; Iterum Therapeutics) for the treatment of uncomplicated urinary tract infections (uUTIs) caused by Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis in women who have limited or no alternative oral antibacterial treatment options.¹ An estimated 60% of women will have a uUTI during their lifetime, and approximately 40% will experience a recurrence. Each year, 40 million uUTI prescriptions are filled in the United States, with approximately 1% caused by resistant pathogens.²

Image credit: Andreas Nägeli | stock.adobe.com

Treatment with sulopenem etzadroxil and probenecid is not indicated for the treatment of complicated UTIs (cUTIs), as step-down treatment after intravenous antibacterial treatment for cUTI, for the treatment of complicated intra-abdominal infections (cIAIs), or as step-down treatment after intravenous antibacterial treatment of cIAI. The FDA approval states that to reduce the development of drug-resistant bacteria and maintain the effectiveness of antibacterial drugs, the medication should be used only to treat uUTIs that are proven or strongly suspected to be caused by susceptible bacteria.¹

PHARMACOLOGY AND PHARMACOKINETICS

Sulopenem etzadroxil is a penem antibacterial agent that is hydrolyzed to the active drug sulopenem after oral administration. Sulopenem has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria by the inhibition of cell wall synthesis. When taken with food, it reaches maximum plasma concentrations 2 hours after administration and has an elimination half-life of approximately 1.28 hours.¹

Probenecid is a renal tubular transport inhibitor that inhibits OAT3-mediated renal clearance of sulopenem to increase sulopenem concentrations. When taken with food, it reaches maximum plasma concentrations 2 hours after administration and has an elimination half-life of approximately 3.83 hours.¹

DOSAGE AND ADMINISTRATION

The recommended dose is 1 tablet (sulopenem etzadroxil 500 mg and probenecid 500 mg) orally twice daily with food for 5 days. If a dose is missed, it should be taken as soon as possible. The dose should not be doubled to compensate for the missed dose.¹

CLINICAL TRIALS

The efficacy of sulopenem etzadroxil and probenecid for the treatment of uUTI was evaluated in 2 double-blind, randomized clinical trials. REASSURE (NCT05584657) randomly assigned 2214 women with uUTI to receive either sulopenem etzadroxil and probenecid twice daily for 5 days or amoxicillin 875 mg/clavulanate 125 mg twice daily for 5 days. The trial results found sulopenem etzadroxil and probenecid to be noninferior and statistically superior to amoxicillin/clavulanate in the amoxicillin/clavulanate-susceptible population.^1,2

In SURE 1 (NCT03354598), 1660 women with uUTI received either sulopenem etzadroxil and probenecid twice daily for 5 days or oral ciprofloxacin 250 mg twice daily for 3 days. Treatment with sulopenem etzadroxil and probenecid was found to be superior to ciprofloxacin in fluoroquinolone-resistant infections.^1,2

CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS

Treatment with sulopenem etzadroxil and probenecid is contraindicated in patients with hypersensitivity to any component of the medication or other β-lactam antibacterial agents, known blood dyscrasias, or known uric acid kidney stones and during concomitant treatment with ketorolac tromethamine. The most common adverse reactions are diarrhea, headache, nausea, vomiting, and vulvovaginal mycotic infection.¹

Hypersensitivity reactions have been reported during treatment with sulopenem etzadroxil and probenecid. Before beginning treatment, patients should be asked about previous hypersensitivity reactions to other β-lactams, carbapenems, cephalosporins, or penicillins. If an allergic reaction occurs, the medication should be discontinued and appropriate supportive treatment initiated. Clostridioides difficile–associated diarrhea has been reported with almost all systemic antibacterial agents and should be considered in patients who present with diarrhea after antibacterial use. Treatment with sulopenem etzadroxil and probenecid may exacerbate gout. It should not be used concomitantly with ketoprofen. Sulopenem etzadroxil and probenecid should not be used in patients with creatinine clearance less than 15 mL/min or in patients undergoing hemodialysis.

REFERENCES

1. Orlynvah. Prescribing information. Iterum Therapeutics; 2024. Accessed February 28, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/213972s000lbl.pdf

2. Iterum Therapeutics receives U.S. FDA approval of Orlynvah (oral sulopenem) for the treatment of uncomplicated urinary tract infections. News release. Iterum Therapeutics. October 25, 2024. Accessed February 28, 2025. https://www.iterumtx.com/news/press-releases/detail/136/iterum-therapeutics-receives-u-s-fda-approval-of