Version May 2024
Urinary tract infection: Note: Limited evidence suggests decreased efficacy compared with other agents; avoid if early pyelonephritis is suspected (IDSA/ESCMID [Gupta 2011]; Nicolle 2002).
Cystitis, acute uncomplicated or acute simple cystitis (infection limited to the bladder without signs/symptoms of upper tract, prostate, or systemic infection):
Females: Oral: 400 mg 2 to 3 times daily for 3 to 7 days (IDSA/ESCMID [Gupta 2011]; Jansåker 2014; manufacturer's labeling [Canadian]); some experts prefer 400 mg 3 times daily, especially for resistant (eg, extended-spectrum beta-lactamase-producing) organisms (Gupta 2021; Jansåker 2014).
Urinary tract infection, recurrent: Oral: 200 to 400 mg 3 times daily; according to the manufacturer, these doses can also be given 4 times daily, but published data support 3 times daily. The duration is uncertain; the manufacturer warns against long-term use (Bresky 1982; Kalager 1978; Canadian product monograph).
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, although the manufacturer recommends reducing dose in proportion to degree of loss or renal function. Use with caution and consider plasma level monitoring in patients with severe renal impairment.
No dosage adjustments necessary.
Refer to adult dosing.
Urinary tract infection: Children and Adolescents >6 years of age and weight >40 kg: Oral: 20 to 40 mg/kg/day (maximum daily dose: 1,200 mg/day) in 3 divided doses for 3 to 7 days.
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, although the manufacturer recommends reducing dose in proportion to degree of loss or renal function. Use with caution and consider plasma level monitoring in patients with severe renal impairment.
No dosage adjustments necessary.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%:
Gastrointestinal: Diarrhea, nausea
Genitourinary: Vulvovaginal candidiasis
<1%:
Dermatologic: Pruritus, skin rash (including erythematous rash, macular eruption, maculopapular rash), urticaria
Endocrine & metabolic: Decreased plasma carnitine concentrations
Gastrointestinal: Abdominal pain, Clostridioides difficile colitis, dyspepsia, esophageal ulcer, esophagitis, oral mucosa ulcer, vomiting
Hepatic: Abnormal hepatic function tests
Hematologic & oncologic: Thrombocytopenia
Hypersensitivity: Anaphylaxis
Nervous system: Dizziness, fatigue, headache, vertigo
Frequency not defined: Dermatologic: Severe dermatological reaction
Postmarketing: Hypersensitivity: Hypersensitivity reaction (including anaphylactic shock, angioedema)
Hypersensitivity to pivmecillinam, other penicillins and/or cephalosporins, or any component of the formulation; impaired transit through esophagus; genetic metabolism anomalies causing severe carnitine deficiency (eg, carnitine transporter defect, methylmalonic aciduria, propionic acidemia)
Concerns related to adverse effects:
• Anaphylactic/hypersensitivity reactions: [Canadian Boxed Warning]: Serious and occasionally fatal hypersensitivity (including angioedema and anaphylaxis) and severe cutaneous adverse reactions (SCAR) have been reported in patients receiving therapy with beta-lactams, including pivmecillinam. Patients with a history of hypersensitivity to multiple allergens may be at increased risk. If an allergic reaction occurs, discontinue therapy and institute appropriate supportive measures.
• 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 C. difficile infection (CDI) and pseudomembranous colitis; increased risk of CDI may persist up to 3 months postantibiotic treatment (Hensgens 2012).
• Carnitine deficiency: May cause carnitine deficiency with long-term or frequently repeated use. Symptoms may include muscle aches, fatigue, and confusion.
Disease-related concerns:
• Porphyria: Use caution in patients with porphyria, may induce an acute attack.
• Renal impairment: Use caution and reduce dose in patients with renal impairment due to decreased clearance; consider monitoring plasma level in patients with severe renal impairment.
Selexid: Health Canada approved July 2016; anticipated availability is unknown.
Oral: Administer with at least one-half glass of fluid, without regards to meals.
Oral: Administer with at least one-half glass of fluid, without regards to meals.
Note: Not approved in the United States.
Urinary tract infection: Treatment of acute uncomplicated cystitis and recurrent urinary tract infection caused by susceptible strains of Escherichia coli, Klebsiella species, Enterobacter species, and Proteus species in adults and children >6 years of age and >40 kg.
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].
ALERT: Canadian Boxed Warning: Health Canada–approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling.
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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acemetacin: May increase the serum concentration of Penicillins. Risk C: Monitor therapy
Aminoglycosides: Penicillins may decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Risk C: Monitor therapy
Bacillus clausii: Antibiotics may diminish the therapeutic effect 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 diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect 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 combination
Dichlorphenamide: Penicillins may enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy
Erythromycin (Systemic): May diminish the therapeutic effect of Pivmecillinam. Risk C: Monitor therapy
Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Methotrexate: Penicillins may increase the serum concentration of Methotrexate. Risk C: Monitor therapy
Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Penicillins. Risk C: Monitor therapy
Sodium Benzoate: Penicillins may diminish the therapeutic effect of Sodium Benzoate. Risk C: Monitor therapy
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect 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 diminish the therapeutic effect of Penicillins. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect 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
Valproate Products: May enhance the adverse/toxic effect of Pivmecillinam. Specifically, the risk for carnitine deficiency may be increased. Risk X: Avoid combination
Vitamin K Antagonists (eg, warfarin): Penicillins may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Mecillinam, the active metabolite of pivmecillinam, crosses the placenta. Low concentrations can be detected in the fetus and amniotic fluid.
Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of pivmecillinam may be altered; however, dose adjustments are not needed (Heikkilä 1992; Kjer 1986).
As a class, penicillin antibiotics are widely used in pregnant women. 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).
Pivmecillinam may be used for the treatment of urinary tract infections during pregnancy when clinically indicated; other antibiotics may be preferred due to side effect profile (Guinto 2010).
Mecillinam, the active metabolite of pivmecillinam, is present in breast milk.
Adverse effects to a breastfed infant are not expected when used in therapeutic doses; the manufacturer notes that pivmecillinam may be used during breastfeeding.
Renal function periodically with prolonged therapy and consider plasma levels in patients with severe renal impairment; hepatic function tests periodically with prolonged therapy; hematologic function periodically with prolonged therapy.
Pivmecillinam is a 6-aminopenicillanic acid derivative that is metabolized to the active form of the drug, mecillinam. Mecillinam 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.
Absorption: Well absorbed
Protein binding: 5% to 10%
Metabolism: Hydrolyzed via non-specific enzymatic esterases in the blood, GI mucosa, and other tissues to its active form, mecillinam
Bioavailability: 60% to 70% (unaffected by food)
Half-life elimination: ~1 hour
Time to peak, serum: 1 to 1.5 hours (mecillinam)
Excretion: Urine (~60% to 70% as mecillinam; almost all within the first 6 hours after dose resulting in urine concentrations >200 mg/L after one 400 mg tablet) and bile
Altered kidney function: Elimination of mecillinam is reduced by ~75% in patients with severe renal impairment.
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