Probenecid and Sulopenem etzadroxil

ORLYNVAH, a combination of sulopenem etzadroxil, a penem antibacterial, and probenecid, a renal tubular transport inhibitor, is indicated for the treatment of uncomplicated urinary tract infections (uUTI) caused by the designated microorganisms Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis in adult women who have limited or no alternative oral antibacterial treatment options. Limitations of Use ORLYNVAH is not indicated for the treatment of: Complicated urinary tract infections (cUTI) or as step-down treatment after intravenous antibacterial treatment of cUTI. Complicated intra-abdominal infections (cIAI) or as step-down treatment after intravenous antibacterial treatment of cIAI.

ORLYNVAH is a combination of sulopenem etzadroxil, a penem antibacterial drug and probenecid, a renal tubular transport inhibitor. Probenecid inhibits OAT3-mediated renal clearance of sulopenem, resulting in increased plasma concentrations of sulopenem.

The recommended dosage of ORLYNVAH is one tablet orally twice daily for 5 days. Administration of ORLYNVAH with food is recommended. Recommended Dosage The recommended dosage of ORLYNVAH is one tablet (sulopenem etzadroxil 500 mg and probenecid 500 mg) orally twice daily for 5 days. Recommended Dosage in Patients with Renal Impairment Administration of ORLYNVAH is not recommended in patients with creatinine clearance (CrCL) less than 15 mL/min or patients on hemodialysis. No dosage adjustment is required for ORLYNVAH in patients with CrCL greater than or equal to15 mL/min. Recommendations Regarding Missed Dose(s) If a dose of ORLYNVAH is missed, instruct patients to take the dose as soon as possible. Do not double the dose to make up for the missed dose.

ORLYNVAH is contraindicated in patients with: • A history of hypersensitivity to the components of ORLYNVAH (sulopenem etzadroxil and probenecid) or other beta-lactam antibacterial drugs • Known uric acid kidney stones Concomitant use of ORLYNVAH and ketorolac tromethamine is contraindicated Patients with a history of hypersensitivity to the components of ORLYNVAH (sulopenem etzadroxil and probenecid) or other beta- lactam antibacterial drugs. Patients with known uric acid kidney stones. Concomitant use of ORLYNVAH and ketorolac tromethamine is contraindicated.

Hypersensitivity Reactions: Hypersensitivity reactions have been reported in patients treated with ORLYNVAH. Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, have been reported with beta-lactam antibacterial drugs. Severe allergic reactions and anaphylaxis have been reported with the use of probenecid (a component of ORLYNVAH). If an allergic reaction to ORLYNVAH occurs, discontinue the drug and institute appropriate therapy. Clostridioides difficile -Associated Diarrhea (CDAD): This has been reported with nearly all systemic antibacterial agents. Evaluate if diarrhea occurs. Exacerbation of Gout: When prescribing ORLYNVAH to patients with a known history of gout, ensure appropriate therapy of gout is instituted.

The following adverse reactions are described in greater detail in the Warnings and Precautions section. Hypersensitivity Reactions Clostridioides difficile -Associated Diarrhea Risk of Uric Acid Kidney Stone Development Exacerbation of Gout The most common adverse reactions (≥2%) in patients treated with ORLYNVAH were diarrhea, nausea, vulvovaginal mycotic infection, headache, and vomiting.

Ketoprofen: Concomitant use is not recommended. See full prescribing information for additional clinically significant drug interactions with ORLYNVAH

Store ORLYNVAH tablets at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F).