Version July 2025
Dosage guidance:
Dosing: Doses are expressed as the amount of pivmecillinam, consistent with US labeling; in Canada and some other countries, dosing is expressed as pivmecillinam hydrochloride.
Urinary tract infection:
Note: Pivmecillinam 185 mg is equivalent to pivmecillinam hydrochloride 200 mg.
Children and Adolescents: Limited data available: Oral: 18.5 to 37 mg pivmecillinam/kg/day in divided doses every 6 to 12 hours for 3 to 7 days; maximum dose: 370 mg pivmecillinam/dose (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no specific dosage adjustments provided in the manufacturer's labeling; manufacturer recommends reducing dose in proportion to degree of loss of kidney function. In patients with severe kidney impairment, use with caution and consider plasma concentration monitoring (Ref).
Children >6 years and Adolescents, weighing ≥40 kg: No dosage adjustments necessary (Ref).
(For additional information see "Pivmecillinam: Drug information")
Dosage guidance:
Dosing: Doses are expressed as the amount of pivmecillinam consistent with US labeling; in some other countries, dosing may be expressed as pivmecillinam hydrochloride. Pivmecillinam 185 mg is equivalent to pivmecillinam hydrochloride 200 mg.
Cystitis, acute uncomplicated or acute simple cystitis (infection limited to the bladder without signs/symptoms of upper tract, prostate, or systemic infection): Note: Limited evidence suggests decreased efficacy compared with other agents; avoid if early pyelonephritis is suspected (Ref).
Females: Oral: 185 mg 3 times daily for 3 to 7 days (Ref). Note: Limited data suggest a higher dose (ie, 370 mg 3 times daily) may be needed for extended-spectrum beta-lactamase-producing organisms (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; safety data suggest no dosage adjustment necessary despite reduction in systemic elimination and urinary excretion of mecillinam with decreased kidney function.
No dosage adjustment necessary.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
1% to 10%:
Dermatologic: Skin rash (≤1%)
Gastrointestinal: Abdominal pain (≤1%), diarrhea (2%), dyspepsia (≤1%), nausea (4%), vomiting (≤1%)
Genitourinary: Genital pruritus (2%), vulvovaginal candidiasis (2%)
Nervous system: Headache (1%)
Postmarketing:
Dermatologic: Acute generalized exanthematous pustulosis, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria
Endocrine & metabolic: Decreased plasma carnitine concentrations
Gastrointestinal: Clostridioides difficile-associated diarrhea, esophageal ulcer, esophagitis, oral mucosa ulcer
Hematologic & oncologic: Thrombocytopenia
Hepatic: Abnormal hepatic function tests
Hypersensitivity: Anaphylaxis, angioedema, drug reaction with eosinophilia and systemic symptoms
Nervous system: Dizziness, vertigo
Hypersensitivity (eg, anaphylaxis, Stevens-Johnson syndrome) to pivmecillinam, other beta-lactam antibacterials (eg, penicillins, cephalosporins), or any component of the formulation; primary or secondary carnitine deficiency resulting from inherited disorders of mitochondrial fatty acid oxidation and carnitine metabolism, and other inborn errors of metabolism (eg, methylmalonic aciduria, propionic acidemia); porphyria.
Concerns related to adverse effects:
• Anaphylactic/Hypersensitivity reactions: Serious hypersensitivity reactions, including anaphylaxis, were observed in patients treated with pivmecillinam. Patients with a history of hypersensitivity to beta-lactams (ie, penicillins, cephalosporins, carbapenems) or multiple allergens may be at increased risk. If an allergic reaction occurs, discontinue therapy and institute appropriate supportive measures.
• Carnitine depletion: May cause carnitine depletion with long-term or frequently repeated use. Symptoms may include hypoglycemia, muscle aches, fatigue, and confusion. Pivmecillinam is not recommended when prolonged treatment is necessary. Patients with significant renal impairment or decreased muscle mass may be at increased risk; consider alternative therapy.
• Severe cutaneous adverse reactions: Severe cutaneous adverse reactions (SCARs) (eg, acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported; discontinue immediately if a SCAR is suspected.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including Clostridioides difficile infection and pseudomembranous colitis; increased risk of C. difficile infection may persist up to 3 months post antibiotic treatment (Hensgens 2012).
Pivya tablets: FDA approved April 2024; anticipated availability currently unknown. Information pertaining to this product within the monograph is pending revision. Pivya is indicated for the treatment of uncomplicated urinary tract infections caused by susceptible strains of Escherichia coli, Proteus mirabilis, and Staphylococcus saprophyticus in females ≥ 18 years of age. Consult the prescribing information for additional information.
Oral: Administer with plenty of fluids to avoid esophageal ulceration. May administer without regard to meals (Ref).
Oral: Administer without regard to meals.
Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). Store and dispense tablets in the unit dose blisters.
Treatment of uncomplicated urinary tract infection caused by susceptible isolates of Escherichia coli, Proteus mirabilis, or Staphylococcus saprophyticus (FDA approved in females ages ≥18 years and adults).
Canadian labeling: Treatment of uncomplicated urinary tract infection caused by susceptible strains of E. coli, Klebsiella spp., Enterobacteria spp., or Proteus spp. in ages >6 years weighing >40 kg and adults.
Selexid brand name for pivmecillinam [multiple international markets] may be confused with Celexa brand name for citalopram [United States, Canada]; Selectin brand name for pravastatin [Italy]; Selexa brand name for celecoxib [Portugal].
Substrate of OAT1/3;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Acemetacin: May increase serum concentration of Penicillins. Risk C: Monitor
Aminoglycosides: Penicillins may decrease serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Risk C: Monitor
Bacillus clausii: Antibiotics may decrease therapeutic effects of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider Therapy Modification
BCG (Intravesical): Antibiotics may decrease therapeutic effects of BCG (Intravesical). Risk X: Avoid
BCG Vaccine (Immunization): Antibiotics may decrease therapeutic effects of BCG Vaccine (Immunization). Risk C: Monitor
Cholera Vaccine: Antibiotics may decrease therapeutic effects of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid
Dichlorphenamide: Penicillins may increase hypokalemic effects of Dichlorphenamide. Risk C: Monitor
Erythromycin (Systemic): May decrease therapeutic effects of Pivmecillinam. Risk C: Monitor
Fecal Microbiota (Live) (Oral): May decrease therapeutic effects of Antibiotics. Risk X: Avoid
Fecal Microbiota (Live) (Rectal): Antibiotics may decrease therapeutic effects of Fecal Microbiota (Live) (Rectal). Risk X: Avoid
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor
Lactobacillus and Estriol: Antibiotics may decrease therapeutic effects of Lactobacillus and Estriol. Risk C: Monitor
Methotrexate: Penicillins may increase serum concentration of Methotrexate. Risk C: Monitor
Mycophenolate: Antibiotics may decrease active metabolite exposure of Mycophenolate. Specifically, concentrations of mycophenolic acid (MPA) may be reduced. Risk C: Monitor
Pivalate-Conjugated Medications: May increase adverse/toxic effects of Pivmecillinam. Specifically, the risk for carnitine deficiency may be increased. Management: Use of pivmecillinam with other pivalate-conjugated medications should be avoided due to the risk of carnitine depletion. If use of the combination cannot be avoided, monitor closely for adverse reactions that could be evidence of carnitine depletion. Risk D: Consider Therapy Modification
Probenecid: May increase serum concentration of Penicillins. Risk C: Monitor
Sodium Benzoate: Penicillins may decrease therapeutic effects of Sodium Benzoate. Risk C: Monitor
Sodium Picosulfate: Antibiotics may decrease therapeutic effects of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider Therapy Modification
Tetracyclines: May decrease therapeutic effects of Penicillins. Risk C: Monitor
Typhoid Vaccine: Antibiotics may decrease therapeutic effects of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider Therapy Modification
Valproic Acid and Derivatives: May increase adverse/toxic effects of Pivmecillinam. Specifically, the risk for carnitine deficiency may be increased. Management: Concurrent use of pivmecillinam with valproate products should be avoided due to the risk of carnitine depletion. If use of the combination cannot be avoided, monitor closely for adverse reactions that could be evidence of carnitine depletion. Risk D: Consider Therapy Modification
Vitamin K Antagonists: Penicillins may increase anticoagulant effects of Vitamin K Antagonists. Risk C: Monitor
Mecillinam, the active metabolite of pivmecillinam, crosses the placenta. Low concentrations can be detected in the fetus and amniotic fluid (Heikkilä 1992).
As a class, penicillin antibiotics are widely used in pregnant patients. Based on available data, penicillin antibiotics are generally considered compatible for use during pregnancy (Ailes 2016; Bookstaver 2015; Crider 2009; Damkier 2019; Lamont 2014; Larsen 2001; Muanda 2017a; Muanda 2017b; Nørgaard 2008; Vinther Skriver 2004). Maternal use of pivmecillinam may cause a false-positive test for isovaleric acidemia during newborn screening if administered shortly before delivery.
Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of pivmecillinam may be altered; however, dose adjustments are not needed (Heikkilä 1992; Kjer 1986).
Untreated urinary tract infections (UTIs) during pregnancy are associated with adverse pregnancy outcomes, including preterm birth and delivery of low-birth-weight infants. Treatment with a targeted antibiotic is recommended to minimize these untoward effects and reduce the incidence of pyelonephritis (ACOG 2023). Maternal adverse events may be increased with pivmecillinam compared to other antibiotics used for UTIs during pregnancy (Guinto 2010).
Pivmecillinam is a prodrug containing the pivaloyloxymethylester of the amidinopenicillanic acid that is metabolized to the active form of the drug mecillinam. Mecillinam, a beta-lactam antibacterial, interferes with the bacterial cell wall and has a mode of action different from other penicillins by exerting high specificity against penicillin-binding protein 2 (PBP-2) in the gram-negative cell wall.
Distribution: Vd: 51 L.
Protein binding: <25%.
Metabolism: Converted to mecillinam (active antibacterial moiety) and pivalic acid by nonspecific esterases; mecillinam undergoes minimal metabolism.
Bioavailability: 25% to 35%.
Half-life elimination: 61 ± 32 minutes.
Time to peak, serum: 90 ± 33 minutes.
Excretion: Urine (80% as mecillinam).
Altered kidney function: Elimination and urinary excretion of mecillinam decreases with degree of renal function.
Anti-infective considerations:
Parameters associated with efficacy: No data are available for pivmecillinam. Given the beta-lactam structure, likely associated with time free drug concentration (fT) > minimum inhibitory concentration (MIC) (Craig 1996; Craig 1998).
Expected drug exposure in normal renal function:
Adults: Oral:
Cmax (peak): Single dose:
185 mg: 1.7 ± 1.1 mg/L (Heikkilä 1992; manufacturer's labeling).
370 mg: 2.5 mg/L (Andrews 1976).
AUC0–8 hours: Single dose:
185 mg: 3.6 mg•hour/L (Heikkilä 1992; manufacturer's labeling).
