VA Class:AM110

AHFS Class:

• Natural Penicillins 8:12.16.04

Generic Name(s):

• Penicillin V Potassium

Chemical Name:

• [2 S -(2α,5α,6β)]-3,3-Dimethyl-7-oxo-6-[(phenoxyacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid monopotassium salt

Associated Monographs

• Natural Penicillins General Statement

Penicillin V, a natural penicillin, is a β-lactam antibiotic.10,61

Penicillin V potassium is used for the treatment of mild to moderately severe upper respiratory tract infections caused by susceptible streptococci or mild skin and skin structure infections caused by susceptible streptococci or staphylococci2,3,4,5,10,61,197,543 and for prophylaxis of certain streptococcal infections.2,3,4,5,10,61

For some infections, oral penicillin V is used after an initial response is obtained with parenteral penicillin G.10,26,28,30,31,32,61,292,513 Penicillin V should not be used for initial treatment of severe infections, including pneumonia, empyema, bacteremia, pericarditis, meningitis, or arthritis.2,3,4,5 In addition, the high incidence of staphylococci resistant to the drug should be considered.2,3,4,5

For additional information on the uses of penicillin V potassium, see Uses in the Natural Penicillins General Statement 8:12.16.04.

Pharyngitis and Tonsillitis

Penicillin V is a drug of choice for the treatment of pharyngitis and tonsillitis caused by Streptococcus pyogenes (group A β-hemolytic streptococci; GAS) and prevention of initial attacks (primary prevention) of rheumatic fever.292,375,580

Selection of an anti-infective for the treatment of S. pyogenes pharyngitis and tonsillitis should be based on the drug's spectrum of activity, bacteriologic and clinical efficacy, potential adverse effects, ease of administration, patient compliance, and cost.292,375,580 No regimen has been found to date that effectively eradicates group A β-hemolytic streptococci in 100% of patients.375

Because the drugs have a narrow spectrum of activity, are inexpensive, and generally are effective with a low frequency of adverse effects, the American Academy of Pediatrics (AAP),292 Infectious Diseases Society of America (IDSA),580 and American Heart Association (AHA)375 recommend a penicillin regimen (i.e., 10 days of oral penicillin V or oral amoxicillin or a single dose of IM penicillin G benzathine) as the treatment of choice for S. pyogenes pharyngitis and tonsillitis.292,375,580 Other anti-infectives (narrow-spectrum oral cephalosporins, oral macrolides, oral clindamycin) are 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 is documented, retreatment with the original or an alternative anti-infective is recommended.292,375,580 Initial treatment failures may occur more frequently with oral penicillins than with IM penicillin G benzathine because of poor adherence to the oral regimen.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

If there are multiple, recurrent episodes of symptomatic pharyngitis within a period of several months to years, it may be difficult to determine whether these are true episodes of S. pyogenes infection or whether the patient is a long-term pharyngeal carrier of S. pyogenes who is experiencing repeated episodes of nonstreptococcal (e.g., viral) pharyngitis.292,375,580

Treatment of asymptomatic chronic pharyngeal carriers of S. pyogenes is not usually indicated and these individuals should not receive repeated courses of anti-infective therapy.292,375,580 However, eradication of the carrier state may be desirable in certain situations (e.g., during a community outbreak of acute rheumatic fever, acute poststreptococcal glomerulonephritis, or invasive S. pyogenes infections; during an outbreak of S. pyogenes pharyngitis in a closed or partially closed community; when multiple episodes of documented symptomatic S. pyogenes pharyngitis are occurring within a family for many weeks despite appropriate treatment; when there is a 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

Prevention of Rheumatic Fever Recurrence

Penicillin V is used as an 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 is considered the 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 Sulfadiazine is recommended when hypersensitivity precludes the use of a penicillin; however, a macrolide (azithromycin, clarithromycin, erythromycin) should be used in patients allergic to penicillins and sulfonamides.375 Even with optimal patient adherence, the risk of recurrence of rheumatic fever is higher in individuals receiving an oral prophylaxis regimen than in those receiving IM penicillin G benzathine.375

AHA and AAP recommend long-term (continuous) secondary prophylaxis in patients who have been treated for 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

Prophylaxis should be initiated as soon as the diagnosis of rheumatic fever or rheumatic heart disease is made,292,375 although patients with acute rheumatic fever should first receive the usually recommended anti-infective treatment for S. pyogenes pharyngitis and tonsillitis (see Uses: Pharyngitis and Tonsillitis).375

Prevention of Invasive Pneumococcal Disease in Asplenic Individuals

Penicillin V is used for prevention of invasive S. pneumoniae disease in children with anatomic or functional asplenia† (e.g., congenital asplenia or polysplenia, splenectomy, sickle cell disease, thalassemia).55,56,57,58,59,61,292 AAP recommends that such prophylaxis be continued until at least 5 years of age in those with sickle cell disease and continued for at least 1 year after splenectomy in all age groups.292

Penicillin V also is used for prevention of invasive S. pneumoniae disease in certain asplenic adults†.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) is recommended in all asplenic individuals.55,199,292 AAP states that anti-infective prophylaxis for prevention of invasive pneumococcal disease is recommended for young children with anatomic or functional asplenia, regardless of vaccination status.292

Although penicillin V usually is considered a drug of choice for prevention of pneumococcal infections in asplenic children,292 some experts recommend amoxicillin.292

Anthrax

Penicillin V has been recommended as an alternative for postexposure prophylaxis of anthrax† following exposure to Bacillus anthracis spores (inhalational anthrax).671,672,673,686 Ciprofloxacin or doxycycline are the 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.663,668,671,672,673,682,683,686 If penicillin susceptibility is 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 the drugs of choice are 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

Penicillin V is used for the treatment of mild, uncomplicated cutaneous anthrax† 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, the initial drugs of choice are ciprofloxacin or doxycycline.668,671,672,673,683,686 If penicillin susceptibility is 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 the drugs of choice are not tolerated or not available;668,671,672,673,680,683,686 oral amoxicillin may be preferred,668,671,683,686 especially in infants and children.671

For additional information on recommendations for postexposure prophylaxis following exposure to anthrax spores and treatment of anthrax, see Uses: Anthrax, in Ciprofloxacin 8:12.18.

Reconstitution and Administration

Penicillin V potassium is administered orally.2,3,4,5

Although the manufacturers state that penicillin V potassium may be given with meals,2,3,4,5 the drug generally should be administered in the fasting state (preferably 1 hour before meals).61 Maximum oral absorption is achieved when the drug is administered at least 1 hour before or 2 hours after meals.321,343

Oral penicillin V potassium should not be used for initial treatment of severe infections and should not be relied on in patients with nausea, vomiting, gastric dilatation, cardiospasm, or intestinal hypermotility.2,3,4,5

Penicillin V potassium powder for oral solution should be reconstituted at the 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 The water should be added to the powder for oral solution in 2 portions and the solution agitated vigorously immediately after each addition.2,3

Dosage

Dosage of penicillin V potassium is expressed in terms of penicillin V.2,3,4,5 Although dosage of the drug is usually expressed as mg of penicillin V, it 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 Dosage

General Pediatric Dosage

The American Academy of Pediatrics (AAP) states that the usual dosage of oral penicillin V for the treatment of mild to moderate infections in pediatric patients beyond the neonatal period is 25-75 mg/kg daily given in 3 or 4 divided doses.292

Some clinicians recommend that children younger than 5 years of age receive oral penicillin V in a dosage of 125 mg 4 times daily and that those older than 5 years of age receive a dosage of 250-500 mg every 6 hours.61

The manufacturers state that pediatric patients 12 years of age or older may receive the usual adult dosage of penicillin V.2,3,4,5 Some clinicians state that children older than 5 years of age may receive the usual adult dosage of the drug.61

Pharyngitis and Tonsillitis

For the treatment of Streptococcus pyogenes (group A β-hemolytic streptococci; GAS) pharyngitis and tonsillitis and prevention of initial attacks (primary prevention) of rheumatic fever in children, AAP, American Heart Association (AHA), and Infectious Diseases Society of America (IDSA) recommend that oral penicillin V be given in a dosage of 250 mg 2 or 3 times daily for 10 days.292,375,580 Some experts recommend a dosage of 500 mg 2 or 3 times daily in children weighing more than 27 kg.375

When used for the treatment of S. pyogenes pharyngitis and tonsillitis and prevention of initial attacks (primary prevention) of rheumatic fever in adolescents, oral penicillin V should be given in a dosage of 500 mg 2 or 3 times daily for 10 days375,580 or 250 mg 4 times daily for 10 days.580

Although anti-infective treatment is not recommended for most individuals identified as chronic pharyngeal carriers of S. pyogenes (see Uses: Pharyngitis and Tonsillitis), IDSA states that a regimen of oral penicillin V given in a dosage of 50 mg/kg daily (up to 2 g daily) in 4 divided doses for 10 days used in conjunction with oral rifampin (20 mg/kg daily as a single dose [up to 600 mg daily] given during the last 4 days of penicillin V treatment) is an option when eradication of the carrier state is desirable.580

Respiratory Tract Infections

If oral penicillin V is used for the treatment of mild community-acquired pneumonia (CAP) caused by susceptible S. pyogenes or for step-down treatment of CAP caused by S. pyogenes after initial parenteral treatment, IDSA recommends that children 3 months of age or older receive 50-75 mg/kg daily in 3 or 4 divided doses.513

For the treatment of mild to moderate upper respiratory tract infections (including scarlet fever) caused by susceptible streptococci in adolescents 12 years of age or older, the manufacturers recommend that oral penicillin V be given in a dosage of 125-250 mg every 6-8 hours for 10 days.2,3,4,5

For the treatment of mild to moderately severe respiratory tract infections (including otitis media) caused by susceptible Streptococcus pneumoniae in adolescents 12 years of age or older, the manufacturers recommend that oral penicillin V be given in a dosage of 250-500 mg every 6 hours until the patient has been afebrile for at least 2 days.2,3,4,5

Skin and Skin Structure Infections

For the treatment of mild to moderate erysipelas caused by susceptible streptococci in adolescents 12 years of age or older, the manufacturers recommend that oral penicillin V be given in a dosage of 125-250 mg every 6-8 hours for 10 days.2,3,4,5

If oral penicillin V is used for the treatment of mild skin or skin structure infections caused by susceptible non-penicillinase-producing staphylococci in adolescents 12 years of age or older, the manufacturers recommend a dosage of 250-500 mg every 6-8 hours.2,3,4,5 Because of the high incidence of resistant strains, in vitro culture and susceptibility testing should be performed when treating suspected staphylococcal infections.2,3,4,5

Necrotizing Ulcerative Gingivitis

If oral penicillin V is used for the 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), in adolescents 12 years of age or older, the manufacturers recommend a dosage of 250-500 mg every 6-8 hours.2,3,4,5

Prevention of Rheumatic Fever Recurrence

For prevention of recurrent rheumatic fever (secondary prophylaxis), AAP and AHA recommend that children receive oral penicillin V in a dosage of 250 mg twice daily.292,375 The manufacturers recommend that adolescents 12 years of age or older receive oral penicillin V in a dosage of 125-250 mg twice daily for such prophylaxis.2,3,4,5

Prevention of recurrent rheumatic fever requires long-term, continuous prophylaxis.292,375 (See Table 1.) Some clinicians use IM penicillin G benzathine initially and change to oral prophylaxis (usually with oral penicillin V) when the patient reaches late adolescence or young adulthood and has remained free of rheumatic attacks for at least 5 years.375

Prevention of Invasive Pneumococcal Disease in Asplenic Individuals

If oral penicillin V is used for prevention of invasive pneumococcal disease† in children with anatomic or functional asplenia, AAP recommends a dosage of 125 mg twice daily in those younger than 3 years of age and 250 mg twice daily in those 3 years of age or older.292

In infants with sickle cell anemia, AAP recommends that penicillin V prophylaxis be initiated as soon as the diagnosis is established (preferably by 2 months of age).292 At 5 years of age, discontinuance of prophylaxis can be considered if the child is receiving regular medical attention, is fully immunized against pneumococcal disease, and has not had a severe pneumococcal infection or surgical splenectomy.292

In children with asplenia from causes other than sickle cell anemia, the appropriate duration of prophylaxis is unknown.292 Some experts recommend that such children receive prophylaxis throughout childhood and into adulthood.292 AAP recommends that prophylaxis be continued for at least 1 year after splenectomy.292

Anthrax

If oral penicillin V is used as an alternative for postexposure prophylaxis of anthrax† following exposure to aerosolized Bacillus anthracis spores in the context of biologic warfare or bioterrorism when penicillin-susceptible strains are involved, AAP recommends that infants and children 1 month of age or older receive 50-75 mg/kg daily given in divided doses every 6-8 hours.671 Because of the possible persistence of anthrax spores in lung tissue following an aerosol exposure, the US Centers for Disease Control and Prevention (CDC), AAP, and other experts recommend that the total duration of anti-infective prophylaxis should be at least 60 days.663,668,671,681,682,683,686

If oral penicillin V is used for the treatment of mild, uncomplicated cutaneous anthrax† caused by penicillin-susceptible B. anthracis that occurs as the result of naturally occurring or endemic exposure to anthrax and when IV therapy is not considered necessary, the recommended dosage in children is 25-50 mg/kg daily given in 2 or 4 divided doses.670,680 For the treatment of cutaneous anthrax without systemic involvement† caused by penicillin-susceptible strains that occurs in the context of biologic warfare or bioterrorism, AAP recommends that infants and children 1 month of age or older receive oral penicillin V in a dosage of 50-75 mg/kg daily given in divided doses every 6-8 hours.671

If oral penicillin V is used in full-term neonates as an alternative for postexposure prophylaxis† following exposure to aerosolized B. anthracis spores in the context of biologic warfare or bioterrorism when penicillin-susceptible strains are involved or for the treatment of cutaneous anthrax† without systemic involvement caused by penicillin-susceptible strains that occurred in the context of biologic warfare or bioterrorism, AAP recommends a dosage of 75 mg/kg daily given in divided doses every 6-8 hours in those up to 1 week of age and 75 mg/kg daily given in divided doses every 8 hours in those 1-4 weeks of age.671 In preterm neonates (gestational age 32-37 weeks), AAP recommends a dosage of 50 mg/kg daily given in divided doses every 12 hours in those up to 1 week of age and 75 mg/kg daily given in divided doses every 8 hours in those 1-4 weeks of age.671

Although 3-10 days of anti-infective therapy may be adequate for the treatment of mild, uncomplicated cutaneous anthrax that occurs as the result of naturally occurring or endemic exposures to anthrax,668,680,683 some experts recommend a duration of 7-14 days.680 CDC and other experts recommend that anti-infectives be continued for 60 days if cutaneous anthrax occurred as the result of exposure to aerosolized B. anthracis spores since the possibility of inhalational anthrax would also exist.668,671,680,683,686 Although anti-infective therapy may limit the size of the cutaneous anthrax lesion and it usually becomes sterile within the first 24 hours of treatment, the lesion will still progress through the black eschar stage despite effective treatment.670,680,703 It is not known whether infants and young children are at increased risk of disseminated, systemic disease and/or meningoencephalitis after focal anthrax infection.671 CDC has recommended that initial treatment of cutaneous anthrax in young children (i.e., younger than 2 years of age) in the context of biologic warfare or bioterrorism should be IV (not oral) and combination anti-infective therapy should be considered.703

Rat-bite Fever

If oral penicillin V is used in children for the treatment of rat-bite fever† caused by Streptobacillus moniliformis after an initial response is obtained with IV penicillin G, a dosage of 25-50 mg/kg daily (up to 3 g daily) in 4 divided doses has been recommended.30

Adult Dosage

Pharyngitis and Tonsillitis

When used for the treatment of S. pyogenes (group A β-hemolytic streptococci; GAS) pharyngitis and tonsillitis and prevention of initial attacks (primary prevention) of rheumatic fever in adults, AHA and IDSA recommend that oral penicillin V be given in a dosage of 500 mg 2 or 3 times daily for 10 days375,580 or 250 mg 4 times daily for 10 days.580

Although anti-infective treatment is not recommended for most individuals identified as chronic pharyngeal carriers of S. pyogenes (see Uses: Pharyngitis and Tonsillitis), IDSA states that a regimen of oral penicillin V given in a dosage of 50 mg/kg daily (up to 2 g daily) in 4 divided doses for 10 days used in conjunction with oral rifampin (20 mg/kg daily as a single dose [up to 600 mg daily] given during the last 4 days of penicillin V treatment) is an option when eradication of the carrier state is desirable.580

Respiratory Tract Infections

For the treatment of mild to moderate upper respiratory tract infections (including scarlet fever) caused by susceptible streptococci in adults, the manufacturers recommend that oral penicillin V be given in a dosage of 125-250 mg every 6-8 hours for 10 days.2,3,4,5

For the treatment of mild to moderately severe respiratory tract infections (including otitis media) caused by susceptible S. pneumoniae in adults, the manufacturers recommend that oral penicillin V be given in a dosage of 250-500 mg every 6 hours until the patient has been afebrile for at least 2 days.2,3,4,5

Skin and Skin Structure Infections

For the treatment of mild to moderate erysipelas caused by susceptible streptococci in adults, the manufacturers recommend that oral penicillin V be given in a dosage of 125-250 mg every 6-8 hours for 10 days.2,3,4,5

For the treatment of nonpurulent skin and skin structure infections (e.g., cellulitis) caused by susceptible streptococci in adults, IDSA recommends that oral penicillin V be given in a dosage of 250-500 mg every 6 hours.543

If oral penicillin V is used for the treatment of mild skin or skin structure infections caused by susceptible non-penicillinase-producing staphylococci in adults, the manufacturers recommend a dosage of 250-500 mg every 6-8 hours.2,3,4,5 Because of the high incidence of resistant strains, in vitro culture and susceptibility tests should be performed when treating suspected staphylococcal infections.2,3,4,5

Necrotizing Ulcerative Gingivitis

If oral penicillin V is used in adults for the 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), the manufacturers recommend a dosage of 250-500 mg every 6-8 hours.2,3,4,5

Prevention of Rheumatic Fever Recurrence

For prevention of recurrent rheumatic fever (secondary prophylaxis), AHA recommends that oral penicillin V be given in a dosage of 250 mg twice daily.375 The manufacturers recommend a dosage of 125-250 mg twice daily for such prophylaxis.2,3,4,5

Prevention of recurrent rheumatic fever requires long-term, continuous prophylaxis.292,375 (See Table 2.)

Anthrax

If oral penicillin V is used as an alternative for postexposure prophylaxis of anthrax† following exposure to aerosolized B. anthracis spores in the context of biologic warfare or bioterrorism when penicillin-susceptible strains are involved, CDC recommends that adults (including pregnant and postpartum women) receive a dosage of 500 mg every 6 hours.672,673 Because of the possible persistence of anthrax spores in lung tissue following an aerosol exposure, CDC and other experts recommend that the total duration of anti-infective prophylaxis should be at least 60 days.663,668,672,673,681,682,683,686

If oral penicillin V is used for the treatment of mild, uncomplicated cutaneous anthrax† caused by penicillin-susceptible B. anthracis that occurs as the result of naturally occurring or endemic exposure to anthrax and when IV therapy is not considered necessary, the recommended dosage in adults is 500 mg 4 times daily,543,680 although some clinicians recommend 200-500 mg 4 times daily.670 For the treatment of cutaneous anthrax without systemic involvement† that occurs in the context of biologic warfare or bioterrorism, CDC recommends that adults (including pregnant and postpartum women) receive oral penicillin V in a dosage of 500 mg 4 times daily.672,673

Although 3-10 days of anti-infective therapy may be adequate for the treatment of mild, uncomplicated cutaneous anthrax that occurs as the result of naturally occurring or endemic exposures to anthrax,668,673,680,683 some experts recommend a duration of 7-14 days.680 CDC and other experts recommend that anti-infectives be continued for 60 days if cutaneous anthrax occurred as the result of exposure to aerosolized B. anthracis spores since the possibility of inhalational anthrax would also exist.668,672,673,680,683,686 Although anti-infective therapy may limit the size of the cutaneous anthrax lesion and it usually becomes sterile within the first 24 hours of treatment, the lesion will still progress through the black eschar stage despite effective treatment.670,680

Actinomycosis

If oral penicillin V is used for the treatment of actinomycosis† in adults after at least 2-6 weeks of initial treatment with IV penicillin G, a dosage of 2-4 g daily given in divided doses every 6 hours for 6-12 months is recommended.28,32

If oral penicillin V is used for the treatment of mild cervicofacial actinomycosis†, a 2-month regimen of the drug may be adequate.32

Rat-bite Fever

If oral penicillin V is used for the treatment of rat-bite fever† caused by S. moniliformis in adults after an initial response is obtained with IV penicillin G, a dosage of 500 mg every 6 hours has been recommended.10

Dosage in Renal Impairment

Dosage adjustments are not usually necessary in patients with renal impairment.61 Some clinicians suggest increasing the dosing interval to every 8 hours in patients with creatinine clearance less than 10 mL/minute.24

Adverse Effects

Adverse effects reported with oral penicillin V potassium are similar to those reported with penicillin G.61

The most common adverse effects reported in patients receiving oral penicillins are GI effects (e.g., nausea, vomiting, epigastric distress, diarrhea, black hairy tongue).2,3,4,5

Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, have been reported with penicillins.2,3,4,5,61,710,713,715 Hypersensitivity reactions that have been reported with oral penicillins include rash (maculopapular), exfoliative dermatitis, urticaria and other serum sickness-like reactions, laryngeal edema, and anaphylaxis.2,3,4,5 Fever and eosinophilia may frequently be the only reaction observed.2,3,4,5

For additional information on adverse effects reported with penicillin V potassium, see Cautions in the Natural Penicillins General Statement 8:12.16.04.

Precautions and Contraindications

Penicillin V potassium is contraindicated in individuals with known hypersensitivity to any penicillin.2,3,4,5

Oral penicillin V potassium shares the toxic potentials of the penicillins, including the risk of hypersensitivity reactions, and the usual precautions of penicillin therapy should be observed.2,3,4,5

Prior to initiation of therapy with penicillin V potassium, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens.2,3,4,5 There is clinical and laboratory evidence of partial cross-allergenicity among penicillins and other β-lactam antibiotics including cephalosporins and cephamycins.2,3,4,5,61,611,770,779

Hypersensitivity reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens.2,3,4,5 Penicillins should be used with caution in individuals with a history of clinically important allergies and/or asthma.2,3,4,5

If a hypersensitivity reaction occurs, penicillin V potassium should be discontinued immediately and appropriate therapy instituted as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway and oxygen).2,3,4,5

Some penicillin V potassium oral solutions contain aspartame,3 which is metabolized in the GI tract to phenylalanine following oral administration.43,44,45 These penicillin V potassium oral solutions containing 125 or 250 mg of penicillin V per 5 mL contain 4.5 mg of phenylalanine per 5 mL.3 The aspartame content should be considered in individuals with phenylketonuria (i.e., homozygous genetic deficiency of phenylalanine hydroxylase) and other individuals who must restrict their intake of phenylalanine.43,44,45

For additional information on precautions associated with the use of penicillin V potassium, see Cautions: Precautions and Contraindications, in the Natural Penicillins General Statement 8:12.16.04.

Pregnancy, Fertility, and Lactation

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 that penicillin V is considered low risk25 and safe for use during pregnancy.61

Lactation

Penicillin V is distributed into milk.40,61,355,373 Some clinicians state that oral penicillin V usually is considered compatible with breast-feeding;25,40,61 others state that the drug should be used with caution in nursing women.24

Spectrum

Based on its spectrum of activity, penicillin V is classified as a natural penicillin.10,61 For information on the classification of penicillins based on spectra of activity, see the Preface to the General Statements on Penicillins 8:12.16.

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

For specific information on the spectrum of activity of penicillin V and resistance to the drug, see the sections on Spectrum and on Resistance in the Natural Penicillins General Statement 8:12.16.04.

Pharmacokinetics

For additional information on the absorption, distribution, and elimination of penicillin V, see Pharmacokinetics in the Natural Penicillins General Statement 8:12.16.04.

Absorption

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

Following oral administration of a single dose of penicillin V61,67,70,71,420 or penicillin V potassium67,75,76,356,357,370,420 in fasting children or adults, peak serum concentrations of penicillin V are generally attained within 30-60 minutes. Peak serum penicillin V concentrations are attained sooner and are slightly higher following administration of the potassium salt than the free acid.62,70,81

Following oral administration of a single 125-mg tablet of penicillin V potassium in healthy, fasting adults in one study, serum penicillin V concentrations averaged 1.2, 1.2, 0.5, and 0.1 mcg/mL at 30 minutes, 1 hour, 2 hours, and 4 hours, respectively, after the dose.76 Oral administration of a single 250-mg tablet of penicillin V potassium in healthy, fasting adults results in serum penicillin V concentrations averaging 2.1-2.8, 2.3-2.7, 0.8-0.9, and 0.1-0.2 mcg/mL at 30 minutes, 1 hour, 2 hours, and 4 hours, respectively, after the dose.75,76 Following oral administration of a single 500-mg tablet of penicillin V potassium in healthy, fasting adults, serum penicillin V concentrations average 4.7-5, 4.9-6.3, 2.3-3, and 0.04-0.1 mcg/mL at 30 minutes, 1 hour, 2 hours, and 6 hours, respectively, after the dose.73,76

Variable results have been obtained in studies evaluating the effect of food on GI absorption of penicillin V and penicillin V potassium.61,70,320,321,343 In most studies, presence of food in the GI tract resulted in lower and delayed peak serum concentrations of penicillin V.2,3,4,5,61,70,343,363 If penicillin V is administered 1 hour before a meal, peak serum concentrations may be threefold higher and the total amount absorbed may be twofold higher compared with administration with food.61

Distribution

Penicillin V is widely distributed into body tissues with highest concentrations attained in the kidneys and lower amounts in the liver, skin, and intestine.2,3,4,5 Penicillin V also is distributed into bile,61 tonsils,330 maxillary sinus secretions,61,599 saliva,321 and ascitic,61 synovial,61 pleural,61 and pericardial fluids.61

Minimal concentrations of penicillin V generally distribute into CSF.2,3,4,5,61,64

Penicillin V is approximately 75-89% bound to serum proteins.2,3,4,5,61,63,320,336,337,420

Penicillin V readily crosses the placenta40,61,70 and is distributed into milk.40,61,355,373

Elimination

The serum half-life of penicillin V in adults with normal renal function is reportedly 0.5 hours.81

Approximately 35-70% of an oral dose of penicillin V or penicillin V potassium is metabolized to penicilloic acid which is microbiologically inactive.88,320,366,370,420 Small amounts of 6-aminopenicillanic acid (6-APA) have also been found in urine of patients receiving penicillin V.366 In addition, the drug appears to be hydroxylated to a small extent to one or more microbiologically active metabolites which are also excreted in urine.61,370,420

Penicillin V and its metabolites are excreted in urine mainly by tubular secretion.71,370 Small amounts of the drug are also excreted in feces370 and bile.61,64,70,81

Following oral administration of a single dose of penicillin V or penicillin V potassium in adults with normal renal function, 20-65% of the dose is excreted in urine as unchanged drug and metabolites within 6-8 hours;61,70,71,81,370,420 approximately 32% of the dose is excreted in feces.370

Renal clearance of penicillin V is delayed in neonates and young infants and in individuals with impaired renal function.2,3,4,5,64

Renal clearance of penicillin V may be increased in pregnant women during the second and third trimesters.25,40

Chemistry and Stability

Chemistry

Penicillin V is a natural penicillin produced by fermentation of Penicillium chrysogenum in a medium containing phenoxyacetic acid.61,64 Penicillin V is the phenoxymethyl analog of penicillin G and is commercially available as the potassium salt.2,3,4,5

Although potency of penicillin V potassium generally is expressed in terms of mg of penicillin V, potency of the drug 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 equivalent to 200,000, 400,000, or 800,000 penicillin V units, respectively.2,3,4,5

Each tablet containing 250 mg of penicillin V as the potassium salt contains approximately 0.7 mEq (approximately 28 mg) of potassium;2,3 each tablet containing 500 mg of penicillin V as the potassium salt contains approximately 1.4 mEq (approximately 56 mg) of potassium.2,3 When reconstituted as directed, oral solutions of penicillin V potassium have a pH of 5-7.5.1

Stability

Commercially available penicillin V potassium tablets should be stored in a tight container at 20-25°C2,3,4,5 and protected from moisture.3

Penicillin V powder for oral solution should be stored in a tight container at 20-25°C2,3 and protected from moisture.3 Following reconstitution, penicillin V potassium oral solutions should be refrigerated and any unused solution should be discarded after 14 days.2,3

Additional Information

For further information on chemistry and stability, mechanism of action, spectrum, resistance, pharmacokinetics, uses, cautions, drug interactions, laboratory test interferences, and dosage and administration of penicillin V, see the Natural Penicillins General Statement 8:12.16.04.

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