Actinomycosis (off-label use):
Note: For initial therapy of mild infection or step-down therapy following parenteral treatment of severe infection.
Oral: 500 mg to 1 g every 6 hours (Brook 2020; Hsieh 1993; Smego 1998). Optimal duration is uncertain; some experts suggest total durations of 2 to 6 months for mild infection and 6 to 12 months for severe or extensive infection (Brook 2020).
Anthrax (alternative agent for penicillin-susceptible strains) (off-label use):
Note: Consult public health officials for event-specific recommendations. A high index of suspicion for emergent beta-lactam resistance during therapy is warranted (CDC [Hendricks 2014]).
Inhalational exposure (postexposure prophylaxis): Oral: 500 mg every 6 hours (CDC [Hendricks 2014]); duration depends on anthrax vaccine status and series completion, age, immune status, and pregnancy/breastfeeding status; for those who have not previously received anthrax vaccine, duration ranges from 42 to 60 days (CDC [Bower 2019). Note: Anthrax vaccine should also be administered to exposed individuals (CDC [Bower 2019]; CDC [Hendricks 2014]).
Cutaneous, without systemic involvement, treatment: Oral: 500 mg every 6 hours; duration is 7 to 10 days after naturally acquired infection and 60 days following biological weapon–related event. Note: Patients with extensive edema or cutaneous lesions of the head or neck should be treated with a parenteral regimen recommended for systemic infection (CDC [Hendricks 2014]).
Asplenia, prophylaxis against bacterial infection in select high-risk patients (off-label use):
Oral: 250 mg twice daily. Duration varies based on patient-specific factors (Pasternack 2020; Spelman 2008).
Bite wound infection, prophylaxis of high-risk bite or treatment (animal or human bite) (alternative agent) (off-label use):
Oral: 500 mg 4 times daily as part of an appropriate combination regimen. For prophylaxis, duration is 3 to 5 days; for treatment of established infection, duration is typically 5 to 14 days and varies based on clinical response and patient-specific factors (Baddour 2021a; Baddour 2021b; IDSA [Stevens 2014]).
Diphtheria (adjunctive therapy with antitoxin) (off-label use):
Oral: 250 mg 4 times daily following parenteral treatment, to complete a total treatment course of 14 days (CDC 2015).
Gingivitis, acute simple, plaque-associated:
Note: Reserve systemic therapy for patients with rapidly progressive disease, severe pain, or immunocompromising conditions (Chow 2022).
Oral: 500 mg every 6 to 8 hours in combination with metronidazole for 5 to 7 days (Chow 2022; manufacturer's labeling).
Meningococcal prophylaxis in patients with complement deficiency (eg, due to C5 inhibitor therapy) (off-label use): Limited data:
Oral: 500 mg twice daily in addition to meningococcal vaccination; for those taking a C5 inhibitor, administer meningococcal vaccination 2 weeks prior to initiation of C5 inhibitor therapy and give penicillin V potassium for the duration of C5 inhibitor therapy (Apicella 2020; Hawkins 2017; Liszewski 2020; McNamara 2017).
Pneumococcal prophylaxis in allogeneic hematopoietic cell transplant (off-label use):
Note: For select patients post-engraftment (eg, those with chronic graft-vs-host disease or hypogammaglobulinemia); use only in areas where incidence of penicillin-resistant Streptococcus pneumoniae is low.
Oral: 250 to 500 mg twice daily (ASBMT [Tomblyn 2009]).
Prosthetic joint infection, chronic suppression (off-label use):
Note: For infection caused by beta-hemolytic streptococci, penicillin-susceptible Enterococcus spp., or Cutibacterium spp. (following pathogen-specific IV therapy in patients undergoing 1-stage exchange or debridement with retention of prosthesis) (Berbari 2022; IDSA [Osmon 2013]).
Oral: 500 mg 2 to 4 times daily (IDSA [Osmon 2013]); duration depends on patient-specific factors (Berbari 2022).
Rat bite fever, uncomplicated infection (off-label use):
Oral: 500 mg every 6 hours following parenteral therapy to complete a total treatment course of 14 days (King 2022; Washburn 2015).
Skin and soft tissue infection:
Cellulitis, long-term suppression of recurrent infection (off-label use): Note: For patients with ≥3 episodes/year of known or presumed beta-hemolytic streptococcal cellulitis when predisposing factors cannot be controlled (IDSA [Stevens 2014]).
Oral: 250 to 500 mg twice daily after completion of treatment (IDSA [Stevens 2014]; Spelman 2022; Thomas 2013).
Erysipelas, treatment of mild infection or step-down therapy after initial parenteral therapy: Oral: 500 mg every 6 hours; total duration is 5 days, with extension to 14 days for slow response, severe infection, or immunosuppression (IDSA [Stevens 2014]; Spelman 2022).
Erysipeloid (localized cutaneous Erysipelothrix rhusiopathiae infection), treatment (off-label use): Oral: 500 mg every 6 hours for 5 to 10 days (IDSA [Stevens 2014]; Reboli 2020).
Streptococcus, group A:
Pharyngitis: Oral: 500 mg 2 to 3 times daily for 10 days (AHA [Gerber 2009]; IDSA [Shulman 2012]).
Secondary prophylaxis in patients with rheumatic fever (prevention of recurrent attacks) (alternative agent): Note: IM benzathine penicillin G is preferred, except in patients who are at elevated risk of death from cardiovascular compromise with IM penicillin (eg, severe valvular disease, ventricular ejection fraction <50%, NYHA class III/IV symptoms) (AHA [Sanyahumbi 2022]).
Oral: 250 mg twice daily. Duration depends on risk factors, age, and presence of valvular disease (AHA [Gerber 2009]).
Chronic carriage (off-label use): Note: Most individuals with chronic carriage do not require antimicrobial treatment (IDSA [Shulman 2012]).
Oral: 500 mg 4 times daily for 10 days; add rifampin for the last 4 days of therapy (Chaudhary 1985; IDSA [Shulman 2012]).
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 manufacturer’s labeling. Use with caution; excretion is prolonged in patients with renal impairment.
There are no dosage adjustments provided in manufacturer’s labeling.
(For additional information see "Penicillin V potassium (oral): Pediatric drug information")
General dosing: Infants, Children, and Adolescents:
Mild to moderate infection: Oral: 25 to 50 mg/kg/day in divided doses every 6 hours; maximum daily dose: 2,000 mg/day (Bradley 2019; Red Book [AAP 2018]).
Anthrax (penicillin-susceptible strains) (alternative agent) (AAP [Bradley 2014]): Infants, Children, and Adolescents:
Postexposure prophylaxis, exposure to aerosolized spores: Oral: 50 to 75 mg/kg/day in divided doses every 6 to 8 hours for 60 days.
Cutaneous, without systemic involvement: Oral: 50 to 75 mg/kg/day in divided doses every 6 to 8 hours. Duration: 7 to 10 days for naturally acquired infection, up to 60 days for biological weapon-related event/exposure to aerosolized spore.
Systemic, oral step-down therapy: Oral: 50 to 75 mg/kg/day in divided doses every 6 to 8 hours to complete 60-day course; should be used as a component of combination therapy.
Fusospirochetosis (Vincent infection), mild to moderately severe infections: Children ≥12 years and Adolescents: Oral: 250 to 500 mg every 6 to 8 hours.
Pneumonia, community-acquired; Group A Streptococcus , mild infection or step-down therapy:
Infants, Children, and Adolescents: Oral: 50 to 75 mg/kg/day in divided doses 4 times daily (Bradley 2019; Red Book [AAP 2018]); Note: Usual adult maximum daily dose is 2,000 mg/day.
Pneumococcal infection prophylaxis, anatomic or functional asplenia (eg, sickle cell disease [SCD]) (AAP 2000; Gaston 1986; NHLBI 2014):
Infants (as soon as SCD diagnosed or asplenic) and Children <3 years: Oral: 125 mg twice daily.
Children ≥3 years: Oral: 250 mg twice daily.
Note: Current guidelines recommend discontinuation of prophylaxis at 5 years of age unless the patient has experienced invasive pneumococcal infection or splenectomy; data regarding when to discontinue are limited and practice varies; decision should be made on a case-by-case basis (McCavit 2013; Red Book [AAP 2018]).
Pneumococcal infection prophylaxis, patients post-hematopoietic cell transplant with chronic graft-versus-host disease or low IgG levels (Tomblyn 2009): Note: Use only in areas where incidence of penicillin-resistant Streptococcus pneumoniae is low.
Infants ≥2 months and Children ≤3 years: Oral: 125 mg twice daily.
Children >3 years: Oral: 250 mg twice daily.
Adolescents: Oral: 250 to 500 mg twice daily or 500 to 1,000 mg once daily.
Streptococcus, group A:
Pharyngitis/tonsillitis: Limited data available in <12 years of age:
Children ≤27 kg: Oral: 250 mg every 8 to 12 hours for 10 days (AHA [Gerber 2009]; IDSA [Shulman 2012]).
Children >27 kg and Adolescents: Oral: 500 mg every 8 to 12 hours for 10 days (AHA [Gerber 2009]; IDSA [Shulman 2012]).
Rheumatic fever, secondary prevention: Limited data available in <12 years of age: Note: IM benzathine penicillin G is preferred, except in patients who are at elevated risk of death from cardiovascular compromise with IM penicillin (eg, severe valvular disease, ventricular ejection fraction <50%, NYHA class III/IV symptoms) (AHA [Sanyahumbi 2022]).
Children and Adolescents: Oral: 250 mg twice daily. Duration depends on risk factors including number of previous attacks, risk of exposure to Group A streptococcal infections, age, and presence of valvular disease (AHA [Gerber 2009]).
Chronic carriage: Limited data available: Note: Most individuals with chronic carriage do not require antibiotic treatment (IDSA [Shulman 2012]).
Children and Adolescents: Oral: 50 mg/kg/day in 4 divided doses for 10 days; maximum dose: 500 mg/dose; give in combination with oral rifampin for the last 4 days of therapy (IDSA [Shulman 2012]).
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. Use with caution; excretion is prolonged in patients with kidney impairment.
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Oral:
Generic: 125 mg/5 mL (100 mL, 200 mL); 250 mg/5 mL (100 mL, 200 mL)
Tablet, Oral:
Generic: 250 mg, 500 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Generic: 300 mg
Oral: Administer around-the-clock to promote less variation in peak and trough serum levels. Take on an empty stomach 1 hour before or 2 hours after meals, to enhance absorption.
Oral: To enhance absorption, administer with water on an empty stomach.
Erysipelas: Treatment of mild infection or step-down therapy after initial parenteral therapy.
Gingivitis, acute simple, plaque-associated: Treatment of odontogenic infection, in conjunction with dental care for infections involving gum tissue.
Odontogenic infection (acute simple gingivitis): Treatment of odontogenic infection, in conjunction with dental care for infections involving gum tissue.
Pneumococcal infections: Treatment of mild to moderately severe pneumococcal respiratory tract infections, including otitis media.
Streptococcus, group A: Secondary prophylaxis for rheumatic fever (prevention of secondary attacks).
Streptococcus, group A pharyngitis: Initial treatment of pharyngitis caused by group A Streptococcus.
Actinomycosis; Anthrax; Asplenia, prophylaxis against bacterial infection in select high-risk patients; Bite wound infection, prophylaxis of high-risk bite or treatment (animal or human bite); Cellulitis, long-term suppression of recurrent infection; Diphtheria (adjunctive therapy with antitoxin); Erysipeloid (localized cutaneous Erysipelothrix rhusiopathiae infection); Meningococcal prophylaxis in patients with complement deficiency (eg, due to C5 inhibitor therapy); Pneumococcal prophylaxis in allogeneic hematopoietic cell transplant; Prosthetic joint infection, chronic suppression; Rat bite fever, uncomplicated infection; Streptococcus, group A chronic carriage
Penicillin may be confused with penicillamine
Penicillin V potassium may be confused with penicillin G potassium
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Gastrointestinal: Melanoglossia, mild diarrhea, nausea, oral candidiasis, vomiting
<1%: Acute interstitial nephritis, anaphylaxis, convulsions, exfoliative dermatitis, fever, hemolytic anemia, hypersensitivity reaction, positive direct Coombs test, serum-sickness like reaction
Hypersensitivity to penicillin or any component of the formulation.
Documentation of allergenic cross-reactivity for beta-lactams (eg, penicillins and cephalosporins) is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Concerns related to adverse effects:
• Anaphylactic/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity or history of sensitivity to multiple allergens.). Use with caution in asthmatic patients. If a serious reaction occurs, treatment with supportive care measures and airway protection should be instituted immediately.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Renal impairment: Use with caution in patients with severe renal impairment.
• Seizure disorders: Use with caution in patients with a history of seizure disorder; high levels, particularly in the presence of renal impairment, may increase risk of seizures.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.
Other warnings/precautions:
• Prolonged use: Extended duration of therapy or use associated with high serum concentrations (eg, in renal insufficiency) may be associated with an increased risk for some adverse reactions (neutropenia, hemolytic anemia, serum sickness).
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
Guar Gum (Partially Hydrolyzed): May decrease the serum concentration of Penicillin V Potassium. Risk C: Monitor therapy
Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. 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
Vitamin K Antagonists (eg, warfarin): Penicillins may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Food decreases drug absorption rate; decreases drug serum concentration. Management: Take on an empty stomach 1 hour before or 2 hours after meals around-the-clock to promote less variation in peak and trough serum levels.
Penicillin crosses the placenta (Heikkilä 1994).
Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of penicillin V may be altered in the second and third trimester (Heikkilä 1993).
Penicillin is widely used in pregnant patients. Based on available data, penicillin is generally considered compatible for use during pregnancy (Ailes 2016; Bookstaver 2015; Crider 2009; Damkier 2019; Dencker 2002; Heikkilä 1994; Heinonen 1977; Lamont 2014; Muanda 2017a; Muanda 2017b).
Penicillin is recommended for the management of syphilis during pregnancy. Penicillin V is not recommended for treatment; however, it may be used in the desensitization protocol so that the appropriate penicillin formulation may then be used (CDC [Workowski 2021]; Dallé 2018).
If treatment for the management of Bacillus anthracis is needed in pregnant patients, other agents are preferred (Meaney-Delman 2014).
Penicillin V is present in breast milk (Matheson 1988).
Information related to the presence of penicillin V in breast milk is available from a study that evaluated lactating women with unilateral mastitis (n = 9) or bilateral mastitis (n = 1) in comparison to healthy controls (n = 4). All women in the treatment group received penicillin V for 7 days; an initial dose of 1,320 mg was given followed by daily administration of 3 doses at 8-hour intervals of 660 mg, 660 mg, and 1,320 mg, respectively. Women in the control group received 1 dose of penicillin V 1,320 mg. In both groups, milk samples were obtained prior to and at various intervals for 8 hours after a 1,320 mg dose. Penicillin V was detected in the breast milk of all subjects. Peak concentrations were higher in women with mastitis than the controls. Peak penicillin V milk concentrations ranged from 0.21 to 1.55 mg/L when collected from breasts with mastitis and from 0.30 to 1.25 mg/L in the same women when collected from the unaffected breast. The time to peak milk concentrations was 2.6 hours in mastitic milk and 5.4 hours in the healthy control milk. The authors calculated the average dose of penicillin V to a breastfeeding infant would be 0.23 mg/kg or 0.5% of the weight-adjusted maternal dose (2,640 mg per 60 kg); assuming a maternal weight of 70 kg, the calculated relative infant dose (RID) is 0.6% of the weight-adjusted maternal dose (Matheson 1988). In general, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016; Ito 2000).
Penicillin V may be detected in the urine of some breastfeeding infants (Matheson 1988).
Loose stools and rash have been reported in breastfeeding infants exposed to penicillin V (Matheson 1988). In general, antibiotics that are present in breast milk may cause nondose-related modification of bowel flora. Monitor infants for GI disturbances (WHO 2002).
Penicillin V is considered compatible with breastfeeding when used in usual recommended doses (WHO 2002).
Periodic renal and hematologic function tests during prolonged therapy; monitor for signs of anaphylaxis during first dose
Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs); which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
Protein binding, plasma: 80%.
Bioavailability: Oral: 60% to 73% (Nathwani 1993).
Half-life elimination: Terminal: Oral: 30 minutes (Nathwani 1993); 62 ± 14 minutes (Lindberg 1987); 112 ± 47 minutes (Heikkilä 1993).
Excretion: Urine (as unchanged drug and metabolites).
Altered kidney function: Excretion is considerably delayed.
Pediatric: In neonates and young infants, excretion is considerably delayed.
Anti-infective considerations:
Parameters associated with efficacy:
Time dependent, associated with time free drug concentration (fT) > minimum inhibitory concentration (MIC), goal: ≥50% fT > MIC (bactericidal) (Craig 1996; Craig 1998).
Expected drug exposure in adults with normal renal function:
Cmax (peak):
500 mg every 6 hours, steady state: 4.9 to 6.3 mg/L (MacGregor 1997).
Postantibiotic effect: Minimal bacterial killing continues after penicillin concentration falls below the MIC of targeted pathogen and varies based on the organism:
Gram-positive cocci: 1.5 to 3.5 hours (Craig 1991; Garcia 1995; Zhanel 1991).
Gram-negative bacilli: 0 to 1.5 hours (Craig 1991; Zhanel 1991).
Solution (reconstituted) (Penicillin V Potassium Oral)
125 mg/5 mL (per mL): $0.10
250 mg/5 mL (per mL): $0.11
Tablets (Penicillin V Potassium Oral)
250 mg (per each): $0.46 - $1.19
500 mg (per each): $0.78 - $2.02
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