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Penicillin G Procaine

Pronunciation

(pen i SIL in jee PROE kane)

Index Terms

  • APPG
  • Aqueous Procaine Penicillin G
  • Procaine Benzylpenicillin
  • Procaine Penicillin G
  • Wycillin

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension, Intramuscular:

Generic: 600,000 units/mL (1 mL, 2 mL)

Pharmacologic Category

  • Antibiotic, Penicillin

Pharmacology

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.

Absorption

IM: Slow

Distribution

High distribution in kidneys, lesser amounts in liver, skin and intestines. Very small levels found in CSF.

Excretion

Urine (60% to 90% as unchanged drug); renal clearance is delayed in neonates, young infants, and patients with impaired renal function

Time to Peak

Serum: Within 1 to 4 hours and can persist within the therapeutic range for 15 to 24 hours

Duration of Action

Therapeutic: 15 to 24 hours

Protein Binding

60%

Use: Labeled Indications

Anthrax, prophylaxis: To reduce the incidence of the disease following exposure to aerosolized Bacillus anthracis.

Anthrax, treatment: Treatment of anthrax, including post-exposure inhalational disease due to aerosolized B. anthracis.

Diphtheria: As an adjunct to antitoxin for prevention of the carrier stage of diphtheria caused by susceptible Corynebacterium diphtheriae.

Endocarditis, subacute: Treatment of subacute bacterial endocarditis, only in extremely sensitive infections, caused by susceptible group A streptococci.

Erysipeloid: Treatment of erysipeloid caused by susceptible Erysipelothrix rhusiopathiae.

Fusospirochetosis: Treatment of fusospirochetosis (Vincent gingivitis and pharyngitis) in conjunction with dental care, and moderately severe infections of the oropharynx caused by susceptible fusiform bacilli and spirochetes.

Pneumococcal infection: Treatment of moderately severe infections of the respiratory tract caused by susceptible pneumococci.

Limitations of use: Severe pneumonia, empyema, bacteremia, pericarditis, meningitis, peritonitis, and arthritis of pneumococcal etiology are better treated with aqueous penicillin G during the acute stage.

Rat bite fever: Treatment of rat bite fever caused by susceptible Streptobacillus moniliformis and Spirillum minus organisms.

Skin and soft tissue infection: Treatment of moderately severe infections of the skin and soft tissues caused by susceptible staphylococci (penicillin G-susceptible).

Streptococcal infections: Treatment of moderately severe to severe infections of the upper respiratory tract, skin and soft tissue infections, scarlet fever, and erysipelas caused by susceptible streptococci (group A, without bacteremia).

Limitations of use: Some streptococcal groups, including group D (enterococcus), are resistant. Aqueous penicillin is recommended for streptococcal infections with bacteremia.

Syphilis: Treatment of syphilis (all stages) caused by susceptible Treponema pallidum.

Yaws, bejel, and pinta: Treatment of yaws, bejel, and pinta caused by susceptible organisms.

Limitations of use: When high, sustained serum levels are required, use aqueous penicillin G, either intramuscularly (IM) or intravenously (IV). Do not use in the treatment of beta-lactamase-producing organisms, which includes most strains of Neisseria gonorrhea.

Contraindications

Hypersensitivity to any penicillin or any component of the formulation.

Dosing: Adult

Anthrax:

Inhalational (postexposure prophylaxis): IM: 1,200,000 units every 12 hours

Note: Not a preferred regimen (Hendricks 2014). Overall treatment duration should be 60 days. Available safety data suggest continued administration of penicillin G procaine for longer than 2 weeks may incur additional risk of adverse reactions. Clinicians may consider switching to effective alternative treatment for completion of therapy beyond 2 weeks (FDA 2001).

Cutaneous (treatment): IM: 600,000 to 1,000,000 units daily; Note: Not a preferred regimen (Hendricks 2014).

Diphtheria, adjunctive therapy with antitoxin: IM:

Manufacturer's labeling: 300,000 to 600,000 units daily.

Alternate regimen (patients >10 kg): 600,000 units daily for 14 days (CDC 2014).

Diphtheria, carrier state: 300,000 units once daily for 10 days; Note: Penicillin G benzathine is preferred (CDC 2014).

Neurosyphilis (including ocular syphilis): IM:

Manufacturer's recommendations: 600,000 units daily for 10 to 15 days.

Alternate regimen: 2.4 million units once daily with concomitant probenecid for 10 to 14 days; Note: Aqueous penicillin G IV monotherapy is the preferred initial treatment (CDC [Workowski 2015]).

Pneumococcal pneumonia (uncomplicated, moderately severe): IM: 600,000 to 1,000,000 units daily.

Staphylococcal infections (moderately severe to severe): IM: 600,000 to 1,000,000 units daily

Streptococcal infections (Group A; moderately severe to severe): IM: 600,000 to 1,000,000 units daily for a minimum of 10 days

Yaws: IM: 600,000 units daily. Note: Duration dependent upon the stage of disease; azithromycin is the preferred agent (Mitja 2015).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Anthrax, inhalational (postexposure prophylaxis): Infants, Children, and Adolescents: IM: 25,000 units/kg every 12 hours (maximum: 1,200,000 units/dose every 12 hours). Note: Not a preferred regimen (Bradley 2014). Overall treatment duration should be 60 days. Available safety data suggest continued administration of penicillin G procaine for longer than 2 weeks may incur additional risk for adverse reactions. Clinicians may consider switching to effective alternative treatment for completion of therapy beyond 2 weeks. (FDA 2001)

Diphtheria, adjunctive therapy with antitoxin: Infants, Children, and Adolescents: IM:

Manufacturer's labeling: 300,000 to 600,000 units daily.

Alternate regimen:

Patients ≤10 kg: 300,000 units daily for 14 days (CDC 2014)

Patients >10 kg: 600,000 units daily for 14 days (CDC 2014).

Diphtheria, carrier state: Infants, Children, and Adolescents: IM: 300,000 units once daily for 10 days; Note: Penicillin G benzathine is preferred (CDC 2014).

Syphilis (congenital): Infants and Children: IM: 50,000 units/kg/dose once daily for 10 days; if more than 1 day of therapy is missed, the entire course should be restarted (CDC [Workowski 2015])

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer's labeling, however, excretion is delayed with impaired renal function and dosage adjustments may be necessary. Use with caution.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer's labeling.

Administration

IM: Procaine suspension for deep IM injection only; do not inject in gluteal muscle in children <2 years of age; rotate the injection site; avoid IV, intravascular, or intra-arterial administration of penicillin G procaine since severe and/or permanent neurovascular damage may occur

Storage

Store at 2°C to 8°C (36°F to 46°F). Keep from freezing.

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

Teriflunomide: May increase the serum concentration of OAT3 Substrates. Monitor therapy

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

Positive Coombs' [direct], false-positive urinary and/or serum proteins

Adverse Reactions

Frequency not defined.

Cardiovascular: Cardiac conduction disturbance, cardiac insufficiency, thrombophlebitis, vasodilatation

Central nervous system: Central nervous system stimulation, confusion, drowsiness, myoclonus, seizure

Hematologic & oncologic: Hemolytic anemia, neutropenia, positive direct Coombs test

Hypersensitivity: Anaphylactoid reaction, hypersensitivity reaction, serum sickness

Immunologic: Jarisch-Herxheimer reaction

Local: Pain at injection site, sterile abscess at injection site

Renal: Interstitial nephritis

Warnings/Precautions

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, and/or history of sensitivity to multiple allergens. Use with caution in asthmatic patients. If an allergic reaction occurs, discontinue therapy and institute appropriate supportive measures.

• Fibrosis and atrophy: Quadriceps femoris fibrosis and atrophy have been reported following repeated IM injections of penicillins into the anterolateral thigh.

• Neurovascular damage: Avoid IV, intravascular, or intra-arterial administration since severe and/or permanent neurovascular damage (eg, transverse myelitis with permanent paralysis, gangrene requiring digit or proximal extremity amputation, necrosis and sloughing at and surrounding the injection site) may occur. These reactions have occurred following injection into the deltoid, thigh, or buttock areas. Other serious complications of suspected intravascular administration (eg, immediate distal and proximal pallor, mottling or cyanosis of the extremity around the injection site followed by bleb formation or severe edema requiring anterior and/or posterior compartment fasciotomy in the lower extremity) occur most often in infants and small children. If any evidence of blood supply compromise is noted, consult appropriate specialists promptly.

• Procaine neuropsychiatric reactions: Immediate toxic reactions (eg anxiety, confusion, agitation, depression, weakness, seizures, hallucinations, combativeness and expressed “fear of impending death”) have been reported. Mental disturbance reactions are more common in patients receiving a large single dose (eg 4.8 million units). Reactions are transient and last 15 to 30 minutes.

• Procaine sensitivity: If there is a history of hypersensitivity to procaine, test with 0.1 mL of 1% or 2% procaine solution. If erythema, wheal, flare, or eruption occurs, patient may be sensitive to procaine; do not use penicillin G procaine in these patients. Treat sensitivity with supportive measures, including antihistamines.

• 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; dosage adjustment may be necessary.

• 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 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.

Other warnings/precautions:

• Appropriate use: Do not use for the treatment of gonorrhea.

• Choice of preparation: Penicillin G procaine is not the same preparation as penicillin G benzathine-penicillin G procaine (eg, Bicillin C-R). Dispensing errors have occurred (CDC 2005).

• 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

Hypersensitivity reactions with first dose, injection site reactions, mental status post injection, periodic renal and hematologic function tests with prolonged therapy.

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies. Penicillin G crosses the placenta. Maternal use of penicillins has generally not resulted in an increased risk of adverse fetal effects. Penicillin G procaine may be used in the treatment of syphilis during pregnancy (consult current guidelines) (CDC [Workowski 2015]). Penicillin G procaine is also approved for the management of Bacillus anthracis, however other agents are preferred for use in pregnant women (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 diarrhea. Have patient report immediately to prescriber bruising; bleeding; injection site irritation or edema; or signs of Clostridium difficile (C. diff)-associated diarrhea (stomach pain or cramps, very loose 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.

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