Sulopenem etzadroxil and Probenecid (Orlynvah) photo pending
KEY POINTS
- Similar to a carbapenem, but structurally a bit differentSolupenem is a penem and beta-lactam antibiotic administered as the pro-drug solupenem etzadroxil, which is hydrolyzed upon oral administration to the active drug solupenem. Solupenem interferes with bacterial cell wall synthesis by binding with penicillin binding proteins (PBP), with affinity for PBP2 > PBP1A > PBP1B > PBP4 > PBP3 > PBP5/6.
- Probenicid is a renal tubular inhibitor, which inhibits OAT1/3, which increases solupenem concentrations. This may also increase the concentration of other drugs that are dependent on OAT1/3 for elimination (e.g., rifampin, naproxen, methotrexate, lorazepam)
- FDA-approved 25 October 2024 for 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.
- Label specifically says is not indicated for treatment of complicated UTI or complicated intra-abdominal infection
- Failed to meet clinical efficacy goal in a RCT evaluating it for complicated UTI
- Failed to meet clinical efficacy goal in a RCT evaluating it for complicated intra-abdominal infection
- Label specifically says is not indicated for treatment of complicated UTI or complicated intra-abdominal infection
- Routine dosing is one tablet twice daily x5 days
- Each tablet contains 500 mg of solupenem and 500 mg of probenecid, which are film-coated fixed doses
- Store at room temperature (66-77 F)
- Use not recommended for CrCl below 15 mL/min or hemodialysis as per label, due to lack of data
- Effect of hepatic impairment unknown, no dose adjustment listed in label
- 40% excreted in urine (3% unchanged) and 44% excreted in feces (27% unchanged)
- Contraindications include known blood dycrasias, known uric acid kidney stones, or concomitant ketorolac tromethamine
- Has a warning for exacerbation of gout in patients with a history of gout
- Like all antibiotics, can cause C. difficile associated diarrhea
- In a study of 1932 patients, the most common adverse reaction was diarrhea, which occurred in 10% of patients who got solupenem
- Can cause a false-positive glycosuria test due to interference with coppers sulfate urine glucose tests
- Does NOT have an interaction with valproic acid (which interacts with carbapenems)
- Does not appear to have interactions with P-gp inhibitors or gastric-acid reducing agents
- Active against some resistant gram negative bacteria, including those harboring CTX-M, TEM, SHV, and AmpC
- Has activity versus various gram-positive and gram-negative bacteria, but only recommended for use against those listed on the FDA approval
- Clinically compared to amox/clav, with both arms having clinical cure rate of about 77%
- Clinically compared to ciprofloxacin, for which solupenem had a 84% clinical cure rate compared to 46% for ciprofloxacin
- Registered to Iterum Therapeutics
- The cost of solupenem is not yet available, but is expected to be expensive
- Considerable concern exists in the infectious diseases community on how the use of solupenem may impact the rate of carbapenem resistance in gram-negative bacteria
- It is notable that solupenem may be an oral option for a patient who would otherwise require intravenous treatment. Avoiding IV medications is usually clinically and economically preferable.
RESOURCES
- Solupenem Package Insert
- FDA Release for Solupenem Approval
- Iterum Therapeutics FDA-Approval Press Release
- Sulopenem for the Treatment of Complicated Urinary Tract Infections Including Pyelonephritis: A Phase 3, Randomized Trial
- Sulopenem or Ciprofloxacin for the Treatment of Uncomplicated Urinary Tract Infections in Women: A Phase 3, Randomized Trial
- Sulopenem: An Intravenous and Oral Penem for the Treatment of Urinary Tract Infections Due to Multidrug-Resistant Bacteria
RECOMMENDED TO YOU