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)
Pharmacology
Mechanism of Action
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.
Pharmacokinetics/Pharmacodynamics
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.
Dosage and Administration
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:
Patients >10 kg: 600,000 units daily for 14 days (CDC 2014)
Manufacturer's labeling: Dosing in the prescribing information may not reflect current clinical practice. 300,000 to 600,000 units daily.
Diphtheria, carrier state: IM: 300,000 units once daily for 10 days; Note: Penicillin G benzathine is preferred (CDC 2014).
Neurosyphilis (including ocular syphilis): IM: 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
Note: Although FDA approved for some indications, dosing may not be provided if current guidelines do not recommend use (eg, streptococcal or staphylococcal pneumonia or pharyngitis [AHA (Gerber 2009); IDSA (Bradley 2011); IDSA [Shulman 2012]).
General dosing, susceptible infection (mild to moderate) (Red Book [AAP 2015]): Infants, Children, and Adolescents: IM: 50,000 units/kg/day in divided doses every 12 to 24 hours; maximum daily dose: 1.2 million units/day
Anthrax, inhalational (postexposure prophylaxis): Note: Although FDA approved, penicillin G procaine in not a preferred regimen (AAP [Bradley 2014]). Infants, Children, and Adolescents: IM: 25,000 units/kg/dose every 12 hours; maximum dose: 1.2 million units/dose. 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.
Diphtheria, adjunctive therapy with antitoxin (CDC 2015): Infants, Children, and Adolescents: IM:
Patients ≤10 kg: 300,000 units daily for 14 days
Patients >10 kg: 600,000 units daily for 14 days
Syphilis:
Congenital: Infants and Children: IM: 50,000 units/kg/day once daily for 10 days; maximum daily dose: 2.4 million units/day; if more than 1 day of therapy is missed, the entire course should be restarted (CDC [Workowski 2015]); in HIV-exposed/-positive patients, penicillin G procaine is not the preferred therapy due to poor CNS penetration (HHS [OI pediatric 2016])
Neurosyphilis (including ocular or otic syphilis): HIV-exposed/-positive: Adolescents: IM: 2.4 million units once daily for 10 to 14 days; give in combination with probenecid (HHS [OI adult 2016])
Administration
IM: Procaine suspension for deep IM injection only; rotate the injection site; do not administer IV, intravascularly, or intra-arterially 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
Acemetacin: May increase the serum concentration of Penicillins. Monitor therapy
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. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Avoid combination
Dichlorphenamide: Penicillins may enhance the hypokalemic effect of Dichlorphenamide. Monitor therapy
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
Nitisinone: May increase the serum concentration of OAT1/3 Substrates. Monitor therapy
Pretomanid: May increase the serum concentration of OAT1/3 Substrates. Monitor therapy
Probenecid: May increase the serum concentration of Penicillins. Monitor therapy
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification
Teriflunomide: May increase the serum concentration of OAT1/3 Substrates. Monitor therapy
Tetracyclines: May diminish the therapeutic effect of Penicillins. Monitor therapy
Tolvaptan: May increase the serum concentration of OAT1/3 Substrates. Management: Patients being treated with the Jynarque brand of tolvaptan should avoid concomitant use of OAT1/3 substrates. Concentrations and effects of the OAT1/3 substrate would be expected to increase with any combined use. 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.
<1%, postmarketing, and/or case reports: Anaphylaxis, central nervous system toxicity, Clostridioides difficile colitis, exfoliative dermatitis, hypersensitivity reaction, Jarisch-Herxheimer reaction, maculopapular rash, serum sickness-like reaction, skin rash, urticaria
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.
- Methemoglobinemia: Has been reported with local anesthetics, including procaine; clinically significant methemoglobinemia requires immediate treatment along with discontinuation of the anesthetic and other oxidizing agents. Onset may be immediate or delayed (hours) after anesthetic exposure. Patients with G6PD deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, exposure to oxidizing agents or their metabolites, or infants <6 months of age are more susceptible and should be closely monitored for signs and symptoms of methemoglobinemia (eg, cyanosis, headache, rapid pulse, shortness of breath, lightheadedness, fatigue).
- 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
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; chills, swelling, joint pain, severe dizziness, passing out, anxiety, confusion, agitation, depression, severe loss of strength and energy, seizures, sensing things that seem real but are not, behavioral changes numbness, tingling, weakness, or signs of Clostridioides (formerly Clostridium) difficile-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.
