Pivmecillinam

1. INDICATIONS AND USAGE PIVYA is a penicillin class antibacterial indicated for the treatment of female patients 18 years of age and older with uncomplicated urinary tract infections (uUTI) caused by susceptible isolates of Escherichia coli, Proteus mirabilis and Staphylococcus saprophyticus. To reduce the development of drug-resistant bacteria and maintain the effectiveness of PIVYA and other antibacterial drugs, PIVYA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

PIVYA is an antibacterial drug.

2. DOSAGE AND ADMINISTRATION The recommended dosage of PIVYA is one 185 mg tablet orally 3 times a day for 3 to 7 days as clinically indicated. Administer PIVYA with or without food.

4. CONTRAINDICATIONS Serious hypersensitivity reactions (e.g., anaphylaxis or Stevens-Johnson syndrome) to PIVYA or to other beta-lactam antibacterial drugs (e.g., penicillins and cephalosporins). 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.

5. WARNINGS AND PRECAUTIONS Hypersensitivity Reactions: Serious hypersensitivity reactions including anaphylaxis have been reported in patients treated with PIVYA. If hypersensitivity reactions occur, discontinue treatment with PIVYA and institute appropriate therapy. Severe Cutaneous Adverse Reactions (SCAR): Acute Generalized Exanthematous Pustulosis (AGEP), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), Steven-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) have been reported with PIVYA. Monitor patients closely and discontinue PIVYA at the first signs or symptoms of SCAR or other signs of hypersensitivity. Carnitine Depletion: Clinically significant hypocarnitinemia has been observed in patients at risk for reductions in serum carnitine.

6. ADVERSE REACTIONS The following clinically significant adverse reactions are described in greater detail in the Warnings and Precautions section of labeling: Hypersensitivity Reactions Severe Cutaneous Adverse Reactions Carnitine Depletion Acute Porphyria Clostridioides difficile -Associated Diarrhea The most common adverse reactions observed in ≥2% of the patients receiving PIVYA in clinical trials are nausea and diarrhea.

7. DRUG INTERACTIONS Other Pivalate-Generating Drugs Avoid concurrent treatment with valproic acid, valproate, or other pivalate-generating drugs. If concomitant use with PIVYA is necessary, counsel patients to monitor adverse reactions associated with carnitine depletion (e.g., hypoglycemia, muscle aches, fatigue, and confusion). Pivmecillinam is a pivalate-generating prodrug. Pivalate can be activated to a coenzyme-A thioester in cells which is further converted to pivaloylcarnitine and excreted in urine. Pivalate elimination associated with concomitant use of pivmecillinam with other pivalate-generating drugs decreases carnitine concentrations in plasma which may increase the risk of carnitine depletion-associated adverse reactions.

Store PIVYA tablets at 20 o C to 25 o C (68 o F to 77 o F), excursions permitted between 15°C to 30°C (59°F to 86°F). Store and dispense tablets in the unit-dose blisters.