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Penicillin V Potassium


(pen i SIL in vee poe TASS ee um)

Index Terms

  • Pen VK
  • Phenoxymethyl Penicillin

Dosage Forms

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

Pharmacologic Category

  • Antibiotic, Penicillin


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.


Urine (as unchanged drug and metabolites)

Protein Binding

Plasma: 80%

Special Populations: Renal Function Impairment

Excretion is considerably delayed.

Special Populations: Children

In neonates and young infants, excretion is considerably delayed.

Use: Labeled Indications

Fusospirochetosis (Vincent gingivitis and pharyngitis): Treatment of fusospirochetosis (Vincent gingivitis and pharyngitis), 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.

Rheumatic fever and/or chorea prophylaxis: Prophylaxis (chronic, secondary) of rheumatic fever and/or chorea.

Staphylococcal infections (penicillin G-sensitive): Treatment of mild infections of the skin and soft tissues.

Streptococcal infections (without bacteremia): Treatment of mild to moderate streptococcal infections of the upper respiratory tract, scarlet fever, and mild erysipelas.


Hypersensitivity to penicillin or any component of the formulation

Dosing: Adult

Usual dosage range: Oral: 125 to 500 mg every 6 to 8 hours

Actinomycosis (off-label use): Oral: Note: Duration is dependent upon disease location and patient-specific factors; complicated infections requiring surgical intervention usually initiate IV therapy with penicillin G until disease subsidence followed by long term oral therapy (Hsieh 1993, Sudhakar 2004):

2 to 4 g/day in divided doses every 6 hours (Smego 1998)

Bite wounds (animal) (off-label use): Oral: 500 mg 4 times daily in combination with dicloxacillin (IDSA [Stevens 2014])

Cutaneous anthrax, community-acquired (off-label use): Oral: 500 mg 4 times daily for 7 to 10 days (IDSA [Stevens 2014])

Cutaneous erysipeloid (off-label use): Oral: 500 mg 4 times daily for 7 to 10 days (IDSA [Stevens 2014])

Erysipelas: Oral:

Manufacturer’s labeling: 125 to 250 mg every 6 to 8 hours for 10 days

Alternate dosing: 500 mg 4 times daily (IDSA [Stevens 2014])

Fusospirochetosis (Vincent infection): Oral: 250 to 500 mg every 6 to 8 hours

Pharyngitis (streptococcal): Oral:

Acute treatment, group A streptococci:

Manufacturer’s labeling: Acute treatment, group A streptococci: 125 to 250 mg every 6 to 8 hours for 10 days

Alternate dosing: 500 mg 2 to 3 times daily for 10 days (Gerber 2009) or 250 mg 4 times daily or 500 mg twice daily for 10 days (Shulman 2012)

Chronic carrier treatment, group A streptococcal: 500 mg 4 times daily (maximum: 2,000 mg daily) for 10 days in combination with oral rifampin (Shulman 2012)

Prophylaxis of recurrent rheumatic fever infections: Oral: 250 mg twice daily (Gerber 2009)

Prosthetic joint infection (off-label use): Chronic oral antimicrobial suppression (Enterococcus spp [penicillin-susceptible], streptococci [beta-hemolytic], Propionibacterium spp): Oral: 500 mg 2 to 4 times daily (Osmon 2013)

Streptococcal skin infection (off-label dose): Oral: 250 to 500 mg every 6 hours (IDSA [Stevens 2014])

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

General dosing, susceptible infections:

Infants and Children <12 years: Mild to moderate infection: Oral: 25 to 75 mg/kg/day in divided doses every 6 to 8 hours (maximum daily dose: 2,000 mg/day) (Red Book [AAP 2015])

Children ≥12 years and Adolescents: Oral:

Manufacturer’s labeling (fixed dosing): 125 to 500 mg every 6 to 8 hours

Alternate dosing (weight-based): Mild to moderate infection: 25 to 75 mg/kg/day in divided doses every 6 to 8 hours (maximum daily dose: 2,000 mg/day [Red Book (AAP 2015)])

Indication-specific dosing:

Anthrax (cutaneous), community-acquired (off-label use): Infants, Children, and Adolescents: Oral: 25 to 50 mg/kg/day in divided doses 2 or 4 times daily; maximum single dose: 500 mg (Stevens 2005)

Fusospirochetosis (Vincent infection), mild to moderately severe infections: Children ≥12 years and Adolescents: Oral: Refer to adult dosing.

Tonsillopharyngitis; Group A streptococcal infection, treatment and primary prevention of rheumatic fever:

Acute treatment (Gerber 2009; Shulman 2012; WHO 2004):

Children ≤27 kg: Oral: 250 mg 2 to 3 times daily for 10 days

Children >27 kg and Adolescents: Oral: 500 mg 2 to 3 times daily for 10 days; in adolescents, 250 mg 4 times daily has also been suggested

Chronic carrier treatment (Group A streptococci) (off-label use): Children and Adolescents: 50 mg/kg/day in 4 divided doses for 10 days in combination with oral rifampin; maximum daily dose: 2,000 mg/day (Shulman 2012)

Recurrent rheumatic fever, prophylaxis (off-label): Children and Adolescents: 250 mg twice daily (Gerber 2009)

Pneumococcal infection prophylaxis for anatomic or functional asplenia (eg, sickle cell disease [SCD]) (off-label use) (AAP 2002; Kavanagh 2011; 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; the decision to discontinue penicillin prophylaxis after 5 years of age in children who have not experienced invasive pneumococcal infection and have received recommended pneumococcal immunizations is patient and clinician dependent

Pneumonia, community-acquired; Group A Streptococcus, mild infection or step-down therapy (off-label use): Infants ≥3 months, Children, and Adolescents: Oral: 50 to 75 mg/kg/day in 3 to 4 divided doses (Bradley 2011); maximum daily dose: 2,000 mg/day

Dosing: Renal Impairment

There are no dosage adjustments provided in manufacturer’s labeling. Use with caution; excretion is prolonged in patients with renal impairment.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in manufacturer’s labeling.


Reconstitute powder for oral solution with appropriate amount of water as specified in the manufacturer’s labeling. Shake vigorously until dissolved.


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.


Powder for oral solution: Store dry powder at 20°C to 25°C (68°F to 77°F). Reconstituted oral solution should be stored in refrigerator. Discard unused solution after 14 days (consult manufacturer labeling for specific recommendations).

Tablet: Store at 20°C to 25°C (68°F to 77°F).

Drug Interactions

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Avoid combination

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Methotrexate: Penicillins may increase the serum concentration of Methotrexate. 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. Monitor therapy

Probenecid: May increase the serum concentration of Penicillins. Management: Avoid the routine use of penicillins and probenecid, but this combination may be used advantageously in select cases with careful monitoring. Monitor for toxic effects of penicillins if probenecid is initiated or the dose is increased. Consider therapy modification

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. Consider therapy modification

Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

Vitamin K Antagonists (eg, warfarin): Penicillins may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Test Interactions

False-positive or negative urinary glucose determination using Clinitest®; positive Coombs' [direct]; false-positive urinary and/or serum proteins

Adverse Reactions

>10%: Gastrointestinal: Melanoglossia, mild diarrhea, nausea, oral candidiasis, vomiting

<1% (Limited to important or life-threatening): Acute interstitial nephritis, convulsions, exfoliative dermatitis, hemolytic anemia, hypersensitivity reaction, positive Coombs' reaction, serum-sickness like reactions


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.

Concurrent drug therapy related issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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).

Monitoring Parameters

Periodic renal and hematologic function tests during prolonged therapy; monitor for signs of anaphylaxis during first dose

Pregnancy Considerations

Penicillin crosses the placenta. Maternal use of penicillins has generally not resulted in an increased risk of adverse fetal effects. Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of penicillin V may be altered in the second and third trimester (Heikkilä 1993). If treatment for the management of Bacillus anthracis is needed in pregnant women, other agents are preferred (Meaney-Delman 2014)

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, vomiting, abdominal pain, tongue discoloration, or diarrhea. Have patient report immediately to prescriber signs of Clostridium difficile (C. diff)-associated diarrhea (abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.