New Drug
Lauren Howell, PharmD
In October 2024, FDA approved Orlynvah (sulopenem etzadroxil and probenecid—Iterum Therapeutics) for the treatment of uncomplicated UTIs caused by E. coli, Klebsiella pneumoniae, or Proteus mirabilis in adult women who have limited or no alternative antibiotic options. Uncomplicated UTIs, bacterial infections of the bladder in women with no structural abnormalities of their urinary tract, affect approximately one-half of all women at least once in their lifetime.
Dosage and administration
Orlynvah is a combination of sulopenem etzadroxil, a penem antibacterial, and probenecid, a renal tubular transport inhibitor. It is not indicated for the primary treatment of complicated UTIs or as step-down treatment after I.V. antibacterial treatment of complicated UTIs.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of antibacterial drugs, Orlynvah should only be used to treat uncomplicated UTIs that are proven or strongly suspected to be caused by susceptible bacteria. Culture and susceptibility information should be carefully considered and utilized when selecting or modifying antibacterial therapy.
The recommended dosage of Orlynvah is one tablet orally twice daily for 5 days.
Each tablet contains 500 mg of sulopenem etzadroxil and 500 mg of probenecid. Administration of Orlynvah with food is recommended.
Adverse effects and safety
The most common adverse reactions in patients treated with Orlynvah are diarrhea, nausea, vulvovaginal mycotic infection, headache, and vomiting. Hypersensitivity reactions have been reported in some patients. Serious and occasionally fatal hypersensitivity reactions have been reported with b-lactam antibiotics. Severe allergic reactions have also been reported with the use of probenecid. If an allergic reaction to Orlynvah does occur, discontinue the drug and institute appropriate therapy.
Clostridioides difficile–Clostridioides difficile–associated diarrhea has been reported with nearly all systemic antibacterial agents. Evaluate patients if diarrhea occurs. When prescribing or dispensing Orlynvah to patients with a known history of gout, ensure appropriate therapy of gout is in place. Concomitant use of Orlynvah with ketoprofen is not recommended.
Orlynvah is contraindicated in patients with a history of hypersensitivity to the components of Orlynvah or other b-lactam antibiotics, known blood dyscrasias, and known uric acid kidney stones. Concomitant use with ketorolac tromethamine is also contraindicated.
Clinical trials and efficacy
The efficacy of Orlynvah is based on two clinical trials. A total of 3,861 women were enrolled in the trials, with most being from the United States and 700 patients enrolled in Russia and Ukraine. The average age of patients from the United States was 48 years, and 78.3% were white, 17.3% were Black, and 4.4% were other races.
Participants were randomized to either receive Orylnvah or a comparator antibiotic (one trial used amoxicillin/clavulanate while the other used ciprofloxacin). Orlynvah benefit was determined by comparing the percentage of patients treated with Orlynvah versus the comparator antibiotic who experienced cure of UTI symptoms and had a negative urine culture after treatment.
In the first trial, among patients who had growth of bacteria in their urine culture that was sensitive to amoxicillin/clavulanate, 61.7% of patients treated with Orlynvah achieved overall success compared to 55.0% of patients treated with amoxicillin/clavulanate. In the second trial, among patients who had growth of a bacteria in their urine culture that was sensitive to ciprofloxacin, Orlynvah was not as effective as ciprofloxacin. However, among patients who had growth of bacteria in their urine culture that was not sensitive to ciprofloxacin, Orlynvah was effective with 48.1% of patients experiencing overall success compared with 32.9% of patients treated with ciprofloxacin. The incidence of adverse reactions was similar between the white and Black participants and older and younger participants. ■