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Pivmecillinam (Pivya)

Picture of pivmecillinam (Pivya) pending

The FDA-approved product’s package insert (Pivya) is pending release

KEY POINTS

  • Pivmecillinam (Pivya, Selexid) is a penicillin class (and beta-lactam) antibiotic pro-drug that is hydrolyzed by non-specific esterases to mecillinam (the active antibacterial agent)
    • Mecillinam interferes with bacterial cell wall synthesis via interacting with penicillin binding protein 2 (PBP-2)
    • Considered narrow-spectrum
      • Generally considered to have activity against Citrobacter species, Enterobacter species, E. coli, Klebsiella species, Proteus mirabilis, Salmonella species, Shigella species, and Yersenia species
        • Has been shown to be effective versus ESBL-producing E. coli
        • Expected to have low levels of cross-resistance with other beta-lactams (i.e., penicillins, cephalosporins)
        • Resistance may develop by beta-lactamases or modifications to PBPs
      • Has shown clinical benefit against Staphylococcus saprophyticus, attributed to high concentrations in the urinary tract
      • Lacks activity against Pseudomonas aeruginosa, Enterococcus faecalis, and Staphylococcus aureus
  • FDA approved 24 April 2024 for treatment of female adults with uncomplicated urinary tract infections (UTIs) caused by susceptible isolates of Escherichia coli, Proteus mirabilis and Staphylococcus saprophyticus.
    • Uncomplicated UTIs are bacterial infections of the bladder in females with no structural abnormalities of their urinary tract. Approximately one-half of all women experience at least one UTI in their lifetime.
    • Has been used outside the United States prior to the FDA approval
  • FDA approval is with UTILITY therapeutics Ltd.
  • Has been placed next to nitrofurantoin by many experts as a go-to drug for consideration when treating uncomplicated cystitis, due to good efficacy and tolerability
  • Dose is 185 mg oral TID for 3 to 7 days as clinically indicated
    • May be given with or without food
    • Generally give at least 3 days, for 48 hours after symptoms resolve, and for up to 7 days
    • Each film coated tablet includes 185 mg of pivmecillinam which is equivalent to 200 mg of pivmecillinam hydrochloride
      • Table contains simethicone
  • Pivmecillinam achieves very high urinary concentration of mecillinam >200 mg/L after intake of one 400 mg tablet
    • Primary elimination pathway is urine, where 80% is excreted as mecillinam
  • Contraindicated in:
    • Serious hypersensitivity reaction
      • Not recommended for use in patients who have had severe hypersensitivity to other beta-lactams
    • Primary or secondary carnitine deficiency resulting from inherited disorders of mitochondrial fatty acid oxidation and carnitine metabolism, and other inborn errors of metabolism (e.g., methylmalonic aciduria, or propionic acidemia)
    • Acute porphyria
  • Holds a precaution for:
    • Hypersensitivity reactions
    • Severe cutaneous adverse reactions
    • Carnitine depletion (not recommended to use if primary or secondary carnitine deficiency)
    • Clostridioides difficile-associated diarrhea
    • Interference with a newborn screening test for isovaleric acidemia, a rare metabolic disorder
  • Most common side effects are nausea and diarrhea
  • May reduce clearance of methotrexate

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