Penicillin V (Monograph)

Drug class: Natural Penicillins
VA class: AM110
Chemical name: [2S-(2α,5α,6β)]-3,3-Dimethyl-7-oxo-6-[(phenoxyacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid monopotassium salt
CAS number: 132-98-9

Medically reviewed by Drugs.com on Aug 31, 2023. Written by ASHP.

Introduction

Antibacterial; β-lactam antibiotic; natural penicillin.^{10 61}

Uses for Penicillin V

Pharyngitis and Tonsillitis

Treatment of pharyngitis and tonsillitis caused by susceptible Streptococcus pyogenes (group A β-hemolytic streptococci; GAS) and prevention of initial attacks (primary prevention) of rheumatic fever.^{292 375 580}

AAP, IDSA, and AHA recommend a penicillin regimen (i.e., 10 days of oral penicillin V or oral amoxicillin or single dose of IM penicillin G benzathine) as treatment of choice for S. pyogenes pharyngitis and tonsillitis;^{292 375 580} other anti-infectives (narrow-spectrum oral cephalosporins, oral macrolides, oral clindamycin) recommended as alternatives in penicillin-allergic patients.^{292 375 580}

If signs and symptoms of pharyngitis recur shortly after initial treatment and presence of S. pyogenes documented, retreatment with original or alternative anti-infective recommended.^{292 375 580} Alternative regimens recommended for retreatment include a narrow-spectrum oral cephalosporin, oral clindamycin, oral fixed combination of amoxicillin and clavulanate, oral macrolide, or IM penicillin G benzathine.^{292 375 580}

Consider that multiple, recurrent episodes of symptomatic pharyngitis within a period of several months to years may indicate the patient is a long-term pharyngeal carrier of S. pyogenes experiencing repeated episodes of nonstreptococcal (e.g., viral) pharyngitis.^{292 375 580}

Treatment not usually recommended for asymptomatic chronic pharyngeal carriers of S. pyogenes.^{292 375 580} Eradication of the carrier state may be desirable in certain situations (e.g., community outbreak of acute rheumatic fever, acute poststreptococcal glomerulonephritis, or invasive S. pyogenes infections; outbreak of S. pyogenes pharyngitis in a closed or partially closed community; multiple episodes of documented symptomatic S. pyogenes pharyngitis occurring within a family for many weeks despite appropriate treatment; personal or family history of acute rheumatic fever).^{292 580} In such situations, recommended regimens include oral clindamycin, oral fixed combination of amoxicillin and clavulanate, or oral rifampin used in conjunction with either IM penicillin G benzathine or oral penicillin V.^{292 580}

Streptococcal Infections

Treatment of mild to moderate infections (without bacteremia) caused by susceptible streptococci.^{2 3 4 5 10 197} Usually active against S. pyogenes (group A β-hemolytic streptococci; GAS) and streptococci groups C, G, H, L, and M.^{2 3 4 5 10}

Respiratory Tract Infections

Treatment of mild community-acquired pneumoniae (CAP) caused by susceptible S. pyogenes or for step-down treatment of CAP caused by S. pyogenes after an initial parenteral regimen.⁵¹³

Treatment of mild to moderately severe respiratory tract infections caused by susceptible S. pneumoniae or other susceptible streptococci.^{2 3 4 5 10 61 197 292} Consider that other penicillins (penicillin G, amoxicillin, fixed combination of amoxicillin and clavulanate, ampicillin, fixed combination of ampicillin and sulbactam) usually recommended when a penicillin used for treatment of respiratory tract infections.^{61 292 512 513}

Consult current IDSA clinical practice guidelines available at [Web] for additional information on treatment of CAP.^{512 513 514}

Skin or Skin Structure Infections

Treatment of mild skin or skin structure infections caused by susceptible streptococci (e.g., nonpurulent cellulitis, erysipelas).^{2 3 4 5 10 61 543}

Treatment of mild skin or skin structure infections caused by susceptible non-penicillinase-producing staphylococci.^{2 3 4 5} Because of high incidence of penicillinase-producing staphylococci, confirm susceptibility with in vitro testing.^{2 3 4 5}

Consult current IDSA clinical practice guidelines available at [Web] for additional information on treatment of skin and skin structure infections.^{514 543}

Necrotizing Ulcerative Gingivitis

Has been used for treatment of mild to moderate infections of the oropharynx caused by Fusobacterium, including acute necrotizing ulcerative gingivitis (Vincent’s infection, trench mouth, Fusobacterium gingivitis or pharyngitis).^{2 3 4 5}

Prevention of Rheumatic Fever Recurrence

Alternative for prevention of recurrent attacks of rheumatic fever (secondary prophylaxis) in individuals who have had a previous attack of rheumatic fever.^{2 3 4 5 10 61 292 375}

IM penicillin G benzathine generally considered drug of choice for secondary prophylaxis of rheumatic fever because it ensures compliance;^{292 375} alternatives include oral penicillin V or oral sulfadiazine.^{292 375}

AHA and AAP recommend long-term (continuous) secondary prophylaxis following treatment of documented acute rheumatic fever (even if manifested solely by Sydenham chorea) and in those with evidence of rheumatic heart disease (even after prosthetic valve replacement).^{292 375}

Initiate prophylaxis as soon as rheumatic fever or rheumatic heart disease diagnosed,^{292 375} although patients with acute rheumatic fever should first receive usually recommended anti-infective treatment for S. pyogenes pharyngitis and tonsillitis (see Pharyngitis and Tonsillitis under Uses).³⁷⁵

Prevention of Invasive Pneumococcal Disease in Asplenic Individuals

Prevention of invasive S. pneumoniae disease in children with anatomic or functional asplenia^{† [off-label]} (e.g., congenital asplenia or polysplenia, splenectomy, sickle cell disease, thalassemia).^{55 56 57 58 59 61 292} AAP recommends such prophylaxis be continued until at least 5 years of age in those with sickle cell disease and for at least 1 year after splenectomy in all age groups.²⁹²

Prevention of invasive S. pneumoniae disease in certain asplenic adults^{† [off-label]};^{55 57 61} some clinicians recommend that such prophylaxis be continued for at least 1–2 years after splenectomy in adults.^{55 57}

Asplenic infants, children, adolescents, and adults are at increased risk of fulminant septicemia, most commonly caused by S. pneumoniae.^{55 61 292} Age-appropriate vaccination against pneumococcal disease with pneumococcal 13-valent conjugate vaccine (PCV13) and pneumococcal 23-valent polysaccharide vaccine (PPSV23) recommended in all asplenic individuals.^{55 199 292} Anti-infective prophylaxis recommended by AAP for young children with anatomic or functional asplenia, regardless of vaccination status.²⁹²

Penicillin V usually considered drug of choice for prophylaxis of pneumococcal disease in asplenic children;²⁹² some experts recommend amoxicillin.²⁹²

Prevention of Bacterial Endocarditis

Has been recommended in the past for prevention of bacterial endocarditis in patients with certain cardiac risk factors undergoing certain dental or upper respiratory tract procedures.^{2 3 4 5}

Not included in current AHA guidelines for prevention of bacterial endocarditis; oral amoxicillin is drug of choice when prevention of bacterial endocarditis indicated in patients with certain cardiac conditions undergoing certain dental or upper respiratory tract procedures.⁴⁵¹

Consult most recent AHA recommendations for specific information on which cardiac conditions are associated with highest risk of adverse outcomes from endocarditis and specific recommendations regarding use of prophylaxis to prevent endocarditis in these patients.⁴⁵¹

Anthrax

Alternative for postexposure prophylaxis of anthrax^{† [off-label]} following exposure to Bacillus anthracis spores (inhalational anthrax).^{671 672 673 686} Ciprofloxacin or doxycycline are initial drugs of choice for prophylaxis following suspected or confirmed exposure to aerosolized anthrax spores, including exposures that occur in the context of biologic warfare or bioterrorism.^{663 668 671 672 682 683 686} If penicillin susceptibility confirmed, consideration can be given to changing prophylaxis to a penicillin (oral amoxicillin or penicillin V) in infants and children, pregnant or lactating women, or when drugs of choice not tolerated or not available;^{663 668 671 672 673 681 683} oral amoxicillin may be preferred,^{663 668 671 681 682 683} especially in infants and children.⁶⁷¹

Treatment of mild, uncomplicated cutaneous anthrax^{† [off-label]} caused by susceptible B. anthracis that occurs as the result of naturally occurring or endemic exposure to anthrax.^{543 668 670 680} If cutaneous anthrax occurs in the context of biologic warfare or bioterrorism, initial drugs of choice are ciprofloxacin or doxycycline.^{668 671 672 673 683 686} If penicillin susceptibility confirmed, consideration can be given to changing treatment to a penicillin (oral amoxicillin or penicillin V) in infants and children, pregnant or lactating women, or when drugs of choice not tolerated or not available;^{668 671 672 683 686} oral amoxicillin may be preferred,^{668 671 683 686} especially in infants and children.⁶⁷¹

Actinomycosis

Treatment of actinomycosis^{† [off-label]} after initial response obtained with IV penicillin G or ampicillin.^{10 27 28 29 32 292}

Treatment of mild cervicofacial actinomycosis^†;³² oral amoxicillin may be preferred.²⁷

Rat-bite Fever

Has been used for treatment of rat-bite fever^† caused by susceptible Streptobacillus moniliformis in patients who responded to initial treatment with IV penicillin G.^{10 30 31 292}

Penicillin V Dosage and Administration

Administration

Oral Administration

Administer orally.^{2 3 4 5}

Although manufacturers state oral penicillin V may be given with meals,^{2 3 4 5} administration in fasting state (preferably 1 hour before meals) generally recommended.⁶¹ Maximum oral absorption achieved when given at least 1 hour before or 2 hours after meals.^{321 343}

Do not use for initial treatment of severe infections.^{2 3 4 5 292} Should not be relied on in patients with nausea, vomiting, gastric dilatation, cardiospasm, or intestinal hypermotility.^{2 3 4 5}

Reconstitution

Reconstitute powder for oral solution at time of dispensing by adding the amount of water specified on the bottle to provide a solution containing 125 or 250 mg of penicillin V per 5 mL.^{2 3} Add the water in 2 portions;^{2 3} shake vigorously after each addition.^{2 3}

Dosage

Available as the potassium salt.^{2 3 4 5} Dosage usually expressed as mg of penicillin V,^{2 3 4 5} but may be expressed in terms of penicillin V units.^{2 3 4 5}

Potency of penicillin V potassium preparations containing 125, 250, or 500 mg of penicillin V is approximately equivalent to 200,000, 400,000, or 800,000 penicillin V units, respectively.^{2 3 4 5}

Pediatric Patients

General Dosage in Children Beyond the Neonatal Period

Mild to Moderate Infections

Oral

AAP recommends 25–75 mg/kg daily given in 3 or 4 divided doses.²⁹²

Some clinicians recommend 125 mg 4 times daily in children <5 years of age and 250–500 mg every 6 hours in those >5 years of age.⁶¹

Manufacturers state pediatric patients ≥12 years of age may receive usual adult dosage;^{2 3 4 5} some clinicians state that those >5 years of age may receive usual adult dosage.⁶¹

Pharyngitis and Tonsillitis

Oral

Children: 250 mg 2 or 3 times daily for 10 days recommended by AAP, AHA, and IDSA.^{292 375 580} Some experts recommend 500 mg 2 or 3 times daily in those weighing >27 kg.³⁷⁵

Adolescents: 500 mg 2 or 3 times daily for 10 days^{292 580} or 250 mg 4 times daily for 10 days.⁵⁸⁰

Eradication of chronic pharyngeal carriage of S. pyogenes in certain circumstances (see Pharyngitis and Tonsillitis under Uses): IDSA states 50 mg/kg daily (up to 2 g daily) in 4 divided doses for 10 days in conjunction with oral rifampin (20 mg/kg daily as a single dose [up to 600 mg daily] given during last 4 days of penicillin V treatment) is an option.⁵⁸⁰

Respiratory Tract Infections

Oral

Children ≥3 months of age: 50–75 mg/kg daily in 3 or 4 divided doses recommended for treatment of mild CAP caused by S. pyogenes or as step-down after initial parenteral treatment.⁵¹³

Adolescents ≥12 years of age: 125–250 mg every 6–8 hours for 10 days recommended by manufacturers for treatment of mild to moderate infections (including scarlet fever) caused by susceptible streptococci.^{2 3 4 5}

Adolescents ≥12 years of age: 250–500 mg every 6 hours recommended by manufacturers for treatment of mild to moderately severe infections (including otitis media) caused by susceptible S. pneumoniae;^{2 3 4 5} continue until afebrile for at least 2 days.^{2 3 4 5}

Skin and Skin Structure Infections

Oral

Adolescents ≥12 years of age: 125–250 mg every 6–8 hours for 10 days recommended by manufacturers for treatment of mild to moderate erysipelas caused by susceptible streptococci.^{2 3 4 5}

Adolescents ≥12 years of age: 250–500 mg every 6–8 hours recommended by manufacturers for mild infections caused by susceptible non-penicillinase-producing staphylococci.^{2 3 4 5} Because of high incidence of resistant strains, perform in vitro culture and susceptibility testing when treating suspected staphylococcal infections.^{2 3 4 5}

Necrotizing Ulcerative Gingivitis

Oral

Adolescents ≥12 years of age: 250–500 mg every 6–8 hours for mild to moderate infections.^{2 3 4 5}

Prevention of Rheumatic Fever Recurrence

Oral

Children: AAP and AHA recommend 250 mg twice daily.^{292 375}

Adolescents ≥12 years of age: Manufacturers recommend 125–250 mg twice daily.^{2 3 4 5}

Long-term, continuous prophylaxis required.^{292 375} (See Table 1.) Some clinicians use IM penicillin G benzathine initially and change to oral prophylaxis (usually penicillin V) when patient reaches late adolescence or young adulthood and has remained free of rheumatic attacks for ≥5 years.³⁷⁵

Prevention of Invasive Pneumococcal Disease in Asplenic Individuals†

Oral

Children <3 years of age: 125 mg twice daily recommended by AAP.²⁹²

Children ≥3 years of age: 250 mg twice daily recommended by AAP.²⁹²

Infants with sickle cell anemia: Initiate prophylaxis as soon as diagnosis established (preferably by 2 months of age).²⁹² AAP states discontinuance of prophylaxis may be considered at 5 years of age if child receives regular medical attention, is fully immunized against pneumococcal disease, and has not had a severe pneumococcal infection or surgical splenectomy.²⁹²

Children with asplenia from causes other than sickle cell anemia: Appropriate duration of prophylaxis unknown;²⁹² some experts recommend such children receive prophylaxis throughout childhood and into adulthood.²⁹² AAP recommends continuing prophylaxis for at least 1 year after splenectomy.²⁹²

Anthrax†

Postexposure Prophylaxis of Anthrax†

Oral

Full-term neonates exposed to aerosolized B. anthracis spores in the context of biologic warfare or bioterrorism: AAP recommends 75 mg/kg daily given in divided doses every 6–8 hours in those ≤1 week of age and 75 mg/kg daily given in divided doses every 8 hours in those 1–4 weeks of age.⁶⁷¹

Preterm neonates (gestational age 32–37 weeks) exposed to aerosolized B. anthracis spores in the context of biologic warfare or bioterrorism: AAP recommends 50 mg/kg daily given in divided doses every 12 hours in those ≤1 week of age and 75 mg/kg daily given in divided doses every 8 hours in those 1–4 weeks of age.⁶⁷¹

Infants and children ≥1 month of age exposed to aerosolized B. anthracis spores in the context of biologic warfare or bioterrorism: AAP recommends 50–75 mg/kg daily given in divided doses every 6–8 hours.⁶⁷¹

Use only if penicillin-susceptible B. anthracis involved.⁶⁷¹

Total duration of anti-infective prophylaxis should be ≥60 days.^{663 668 671 681 682 683 686}

Treatment of Cutaneous Anthrax†

Oral

Full-term neonates with cutaneous anthrax without systemic involvement that occurred in the context of biologic warfare or bioterrorism: AAP recommends 75 mg/kg daily given in divided doses every 6–8 hours in those ≤1 week of age and 75 mg/kg daily given in divided doses every 8 hours in those 1–4 weeks of age.⁶⁷¹

Preterm neonates (gestational age 32–37 weeks) with cutaneous anthrax without systemic involvement that occurred in the context of biologic warfare or bioterrorism: AAP recommends 50 mg/kg daily given in divided doses every 12 hours in those ≤1 week of age and 75 mg/kg daily given in divided doses every 8 hours in those 1–4 weeks of age.⁶⁷¹

Infants and children ≥1 month of age with cutaneous anthrax without systemic involvement that occurred in the context of biologic warfare or bioterrorism: AAP recommends 50–75 mg/kg daily given in divided doses every 6–8 hours.⁶⁷¹

Children with mild, uncomplicated cutaneous anthrax resulting from naturally occurring or endemic exposure: 25–50 mg/kg daily given in 2 or 4 divided doses.^{670 680}

Use only if infection known to be caused by penicillin-susceptible B. anthracis.⁶⁷¹

Although 3–10 days of treatment may be adequate if cutaneous anthrax occurred as the result of natural or endemic exposures,^{543 668 680 683} some experts recommend duration of 7–14 days.⁶⁸⁰ CDC, AAP, and others recommend 60 days of anti-infective treatment if cutaneous anthrax occurred as the result of exposure to aerosolized anthrax spores (e.g., in context of biologic warfare or bioterrorism).^{668 671 680 683 686}

Rat-bite Fever

Oral

Children: 25–50 mg/kg daily (up to 3 g daily) given in 4 divided doses after initial treatment with IV penicillin G.³⁰

Adults

Pharyngitis and Tonsillitis

Oral

500 mg 2 or 3 times daily for 10 days^{375 580} or 250 mg 4 times daily for 10 days.⁵⁸⁰

Eradication of chronic pharyngeal carriage of S. pyogenes in certain circumstances (see Pharyngitis and Tonsillitis under Uses): IDSA states 50 mg/kg daily (up to 2 g daily) in 4 divided doses for 10 days in conjunction with oral rifampin (20 mg/kg daily as a single dose [up to 600 mg daily] given during last 4 days of penicillin V treatment) is an option.⁵⁸⁰

Respiratory Tract Infections

Oral

125–250 mg every 6–8 hours for 10 days recommended by manufacturers for mild to moderately severe infections (including scarlet fever) caused by susceptible streptococci.^{2 3 4 5}

250–500 mg every 6 hours recommended by manufacturers for mild to moderately severe infections (including otitis media) caused by susceptible S. pneumoniae;^{3 4 5} continue until afebrile for at least 2 days.^{2 3 4 5}

Skin and Skin Structure Infections

Oral

125–250 mg every 6–8 hours for 10 days recommended by manufacturers for mild to moderate erysipelas caused by susceptible streptococci.^{2 3 4 5}

250–500 mg every 6–8 hours recommended by IDSA for nonpurulent skin and skin structure infections (e.g., cellulitis) caused by susceptible streptococci.⁵⁴³

250–500 mg every 6–8 hours recommended by manufacturers for mild infections caused by susceptible non-penicillinase-producing staphylococci.^{2 3 4 5} Because of high incidence of resistant strains, perform in vitro culture and susceptibility testing when treating suspected staphylococcal infections.^{2 3 4 5}

Necrotizing Ulcerative Gingivitis

Oral

250–500 mg every 6–8 hours for mild to moderate infections.^{2 3 4 5}

Prevention of Rheumatic Fever Recurrence

Oral

AHA recommends 250 mg twice daily.³⁷⁵

Manufacturers recommend 125–250 mg twice daily.^{2 3 4 5}

Long-term, continuous prophylaxis required.^{292 375} (See Table 2.)

Anthrax†

Postexposure Prophylaxis of Anthrax†

Oral

500 mg every 6 hours in adults (including pregnant and postpartum women) exposed to aerosolized B. anthracis spores in the context of biologic warfare or bioterrorism.^{672 673}

Use only if penicillin-susceptible B. anthracis involved.^{672 673}

Total duration of anti-infective prophylaxis should be ≥60 days.^{663 668 672 673 681 682 683 686}

Treatment of Cutaneous Anthrax†

Oral

Mild, uncomplicated cutaneous anthrax resulting from naturally occurring or endemic exposure: 500 mg 4 times daily;^{543 680} some clinicians recommend 200–500 mg 4 times daily.⁶⁷⁰

Cutaneous anthrax without systemic involvement that occurred in the context of biologic warfare or bioterrorism: 500 mg 4 times daily in adults (including pregnant and postpartum women).^{672 673}

Use only if infection known to be caused by penicillin-susceptible B. anthracis.^{672 673}

Although 3–10 days of treatment may be adequate if cutaneous anthrax occurred as the result of natural or endemic exposures,^{543 668 680 683} some experts recommend duration of 7–14 days.^{673 680} CDC and others recommend 60 days of anti-infective treatment if cutaneous anthrax occurred as the result of exposure to aerosolized anthrax spores (e.g., in context of biologic warfare or bioterrorism).^{668 672 673 680 683 686}

Actinomycosis†

Oral

2–4 g daily given in divided doses every 6 hours for 6–12 months after initial 2–6 weeks of treatment with IV penicillin G.^{28 32}

Mild cervicofacial actinomycosis: 2-month regimen of penicillin V may be adequate.³²

Rat-bite Fever†

Oral

500 mg every 6 hours recommended after initial response obtained with IV penicillin G.¹⁰

Special Populations

Renal Impairment

Dosage adjustments not usually needed.⁶¹

Cl_cr <10 mL/minute: Some clinicians suggest increasing dosing interval to every 8 hours.²⁴

Cautions for Penicillin V

Contraindications

• Known hypersensitivity to any penicillin.^{2 3 4 5}

Warnings/Precautions

Warnings

Superinfection/Clostridium difficile-associated Diarrhea and Colitis

Possible emergence and overgrowth of nonsusceptible organisms, including fungi.^{2 3 4 5} Institute appropriate therapy if superinfection occurs.^{2 3 4 5}

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.^{2 3 4 5 303 304} C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) reported with nearly all anti-infectives, including penicillin V, and may range in severity from mild diarrhea to fatal colitis.^{2 3 4 5 302 303 304} C. difficile produces toxins A and B which contribute to development of CDAD;^{2 3 4 5 302} hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.^{2 3 4 5}

Consider CDAD if diarrhea develops during or after therapy and manage accordingly.^{2 3 4 5 302 303 304} Obtain careful medical history since CDAD may occur as late as ≥2 months after anti-infective therapy discontinued.^{2 3 4 5}

If CDAD suspected or confirmed, discontinue anti-infectives not directed against C. difficile as soon as possible.^{2 3 4 5 302} Initiate appropriate anti-infective therapy directed against C. difficile (e.g., vancomycin, fidaxomicin, metronidazole), appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), and surgical evaluation as clinically indicated.^{2 3 4 5 302 303 304}

Sensitivity Reactions

Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, reported with penicillins.^{2 3 4 5 61 710 713 715}

Rash (maculopapular), exfoliative dermatitis, urticaria and other serum sickness-like reactions, laryngeal edema, and anaphylaxis reported with oral penicillins.^{2 3 4 5} Fever and eosinophilia may frequently be the only reaction observed.^{2 3 4 5}

Prior to initiation of therapy, make careful inquiry concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens.^{2 3 4 5} Partial cross-allergenicity occurs among penicillins and other β-lactam antibiotics, including cephalosporins and cephamycins.^{2 3 4 5 61 611 615 770 779}

Hypersensitivity reactions more likely to occur in individuals with history of penicillin hypersensitivity and/or history of sensitivity to multiple allergens.^{2 3 4 5} Use with caution in individuals with history of clinically important allergies and/or asthma.^{2 3 4 5}

If hypersensitivity reaction occurs, discontinue immediately and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway and oxygen).^{2 3 4 5}

General Precautions

Severe Infections

Use only for mild to moderate infections caused by susceptible bacteria.^{2 3 4 5}

Do not use for initial treatment of severe infections, including pneumonia, empyema, bacteremia, pericarditis, meningitis, or arthritis.^{2 3 4 5}

Phenylketonuria

Some penicillin V oral solutions contain aspartame,³ which is metabolized in the GI tract to phenylalanine.^{43 44 45} These oral solutions containing 125 or 250 mg of penicillin V per 5 mL contain 4.5 mg of phenylalanine per 5 mL.³

Consider the aspartame content in individuals with phenylketonuria (i.e., homozygous genetic deficiency of phenylalanine hydroxylase) and others who must restrict their intake of phenylalanine.^{43 44 45}

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of penicillin V and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.^{2 3 4 5}

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.^{2 3 4 5} In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.^{2 3 4 5}

Specific Populations

Pregnancy

Available data regarding use of penicillin V in pregnant women, including first-trimester exposures, have not revealed evidence of an association between the drug and congenital defects.²⁵

Some clinicians state penicillin V considered low risk²⁵ and safe for use during pregnancy.⁶¹

Lactation

Distributed into milk.^{40 61 355 373} Some clinicians state penicillin V usually considered compatible with breast-feeding;^{25 40 61} others state use with caution in nursing women.²⁴

Pediatric Use

Renal clearance of penicillin V is delayed in neonates and young infants.^{2 3 4 5 10 64}

Renal Impairment

Substantially eliminated by kidneys; renal clearance delayed in renal impairment.^{2 3 4 5 10 64}

Common Adverse Effects

Adverse GI effects (e.g., nausea, vomiting, epigastric distress, diarrhea, black hairy tongue), hypersensitivity reactions (e.g., fever, eosinophilia, rash, urticaria, serum sickness-like reactions).^{2 3 4 5}

Penicillin V Pharmacokinetics

Absorption

Bioavailability

Approximately 60–73% of an oral dose of penicillin V (no longer commercially available in US) or penicillin V potassium is absorbed from GI tract in healthy, fasting adults.^{63 88 320} Considerable interindividual variation in extent of oral absorption;⁶¹ some patients may not absorb therapeutic concentrations of oral penicillins.^{2 3 4 5}

Peak serum concentrations attained within 30–60 minutes.^{61 67 70 71 356 357 370 420}

Food

Variable results obtained in studies evaluating effect of food on GI absorption of penicillin V potassium.^{61 70 320 321 343} Food may result in lower and delayed peak serum concentrations.^{2 3 4 5 61 70 343 363}

If administered 1 hour before a meal, peak serum concentrations may be threefold higher and total amount absorbed may be twofold higher compared with administration with food.⁶¹

Distribution

Extent

Widely distributed into body tissues.^{2 3 4 5 61} Highest concentrations in kidneys;^{2 3 4 5} also distributed into liver,^{2 3 4 5} skin,^{2 3 4 5} intestines,^{2 3 4 5} bile,⁶¹ tonsils,³³⁰ maxillary sinus secretions,^{61 599} saliva,³²¹ and ascitic,⁶¹ synovial,⁶¹ pleural,⁶¹ and pericardial fluids.⁶¹

Only minimal amounts distributed into CSF.^{2 3 4 5 10 61 64}

Crosses human placenta.^{40 61 70}

Distributed into human milk.^{40 61 355 373}

Plasma Protein Binding

Approximately 75–89%.^{2 3 4 5 61 63 320 336 337 420}

Elimination

Metabolism

Metabolized in the liver.³⁶⁶

Approximately 35–70% of an oral dose metabolized to penicilloic acid which is microbiologically inactive.^{88 320 366 370 420}

Elimination Route

Penicillin V and metabolites principally excreted in urine by tubular secretion.^{71 370}

Approximately 20–65% of an oral dose excreted in urine as unchanged drug and metabolites within 6–8 hours;^{61 71 370 420} small amounts excreted in feces³⁷⁰ and bile.^{61 64 70 81}

Half-life

Serum half-life is 0.5 hours in adults with normal renal function.⁸¹

Special Populations

Neonates and young infants: Delayed renal clearance.^{2 3 4 5 64}

Renal impairment: Delayed renal clearance.^{2 3 4 5 10 64}

Pregnant women: Increased renal clearance during second and third trimesters.^{25 40}

Stability

Storage

Oral

Tablets

20–25°C.^{2 3 4 5} Keep container tightly closed;^{2 3 4 5} protect from moisture.³

For Solution

20–25°C.^{2 3} Keep container tightly closed;^{2 3} protect from moisture.³

Following reconstitution, refrigerate and discard after 14 days.^{2 3}

Actions and Spectrum

• Penicillin V is a β-lactam antibacterial classified as a natural penicillin.^{10 61} The phenoxymethyl analog of penicillin G.^{2 3 4 5}

• Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.^{2 3 4 5 10} Usually bactericidal.^{2 3 4 5}

• Spectrum of activity similar to that of penicillin G, but penicillin V is less potent than penicillin G against susceptible bacteria.⁶¹

• Gram-positive aerobes: Active in vitro and in clinical infections against Staphylococcus (non-penicillinase-producing strains only),^{2 3 4 5 61} Streptococcus pneumoniae,^{2 3 4 5 61} S. pyogenes (group A β-hemolytic streptococci; GAS),^{2 3 4 5 61} viridans streptococci,⁶¹ and other streptococci (groups C, G, H, L, M).^{2 3 4 5}

• Also active in vitro against Bacillus anthracis,^{2 3 4 5 61} Corynebacterium diphtheriae,^{2 3 4 5 61} and Listeria monocytogenes.^{2 3 4 5}

• Other organisms: Active in vitro against some Actinomyces,^{2 3 4 5} Clostridium (C. perfringens, C. tetani),^{2 3 4 5 61} Leptospira,^{2 3 4 5} and Streptobacillus moniliformis.^{2 3 4 5}

• Penicillinase-producing bacteria, including penicillinase-producing staphylococci^{2 3 4 5 10} are resistant. Enterococci are resistant.^{2 3 4 5 10}

Advice to Patients

• Advise patients that antibacterials (including penicillin V) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).^{2 3 4 5}

• Importance of completing full course of therapy, even if feeling better after a few days.^{2 3 4 5}

• Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with penicillin V or other antibacterials in the future.^{2 3 4 5}

• Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued.^{2 3 4 5} Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after last dose.^{2 3 4 5}

• Advise individuals with phenylketonuria and other individuals who must restrict their intake of phenylalanine that some penicillin V oral solutions contain aspartame,³ which is metabolized in the GI tract to phenylalanine.^{43 44 45}

• Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, and any concomitant illnesses.^{2 3 4 5}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{2 3 4 5}

• Importance of advising patients of other important precautionary information.^{2 3 4 5} (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Medical Disclaimer