Penicillin G Procaine

Medical Editor: John P. Cunha, DO, FACOEP Last updated on RxList: 7/21/2022
Drug Description

What is Penicillin G Procaine and how is it used?

Penicillin G Procaine is a prescription medicine used to treat the symptoms of Moderately Severe Infections. Penicillin G Procaine may be used alone or with other medications.

Penicillin G Procaine belongs to a class of drugs called Penicillins, Natural.

It is not known if Penicillin G Procaine is safe and effective in children.

What are the possible side effects of Penicillin G Procaine?

Penicillin G Procaine may cause serious side effects including:

  • hives,
  • difficulty breathing,
  • swelling of your face, lips, tongue, or throat,
  • diarrhea that is watery or bloody,
  • peeling skin,
  • severe pain,
  • changes in skin color where the medicine was injected,
  • dizziness,
  • joint or muscle pain,
  • fast or pounding heartbeats,
  • numbness, tingling, pain, swelling, or redness in your arms or legs,
  • confusion,
  • agitation,
  • depression,
  • unusual thoughts or behavior,
  • chest pain,
  • problems with vision or speech,
  • lightheadedness,
  • fever,
  • chills,
  • muscle pain,
  • rapid breathing,
  • uncontrolled muscle movements,
  • problems with balance or walking,
  • pale skin,
  • easy bruising,
  • unusual bleeding,
  • weakness,
  • sore throat,
  • flu symptoms,
  • little or no urination,
  • rash,
  • itching,
  • swollen glands,
  • joint pain,
  • general ill feeling,
  • slow heart rate,
  • weak pulse,
  • fainting, and
  • slow breathing

Get medical help right away, if you have any of the symptoms listed above.

The most common side effects of Penicillin G Procaine include:

  • pain where the injection was given,
  • vaginal itching or discharge,
  • white patches in your mouth or throat,
  • nausea,
  • vomiting,
  • blurred vision,
  • ringing in your ears,
  • headache,
  • dizziness, and
  • mild skin rash

Tell the doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Penicillin G Procaine. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

1 mL and 2 mL Syringe with needle for deep IM injection only

Prior to administration of the drug, carefully read the WARNINGS, ADVERSE REACTIONS, and DOSAGE AND ADMINISTRATION sections of the labeling.


This product is designed to provide a stable aqueous suspension of penicillin G procaine, ready for immediate use. This eliminates the necessity for addition of any diluent, required for the usual dry formulation of injectable penicillin.

Penicillin G procaine is chemically designated as (2S, 5R, 6R)-3,3-Dimethyl-7-oxo-6-(2-phenylacetamido)-4-thia-1- azabicyclo[3.2.0]heptane-2-carboxylic acid compound with 2-(diethylamino)ethyl p-aminobenzoate (1:1) monohydrate.

Its molecular formula is C16H18N2O4S•C13H20N2O2•H2O with a molecular weight of 588.72. Its structural formula is as follows:

PENICILLIN G PROCAINE - Structural Formula Illustration

Each syringe, 1,200,000 units (2 mL size) or 600,000 units (1 mL size), contains penicillin G procaine in a stabilized aqueous suspension with sodium citrate buffer; and as w/v, approximately 0.5% lecithin, 0.5% carboxymethylcellulose, 0.5% povidone, 0.1% methylparaben, and 0.01% propylparaben.

Penicillin G Procaine Injectable Suspension is viscous and opaque. Read CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, and DOSAGE AND ADMINISTRATION sections prior to use.



Penicillin G procaine is indicated in the treatment of moderately severe infections in both adults and pediatric patients due to penicillin-G-susceptible microorganisms that are susceptible to the low and persistent serum levels common to this particular dosage form in the indications listed below. Therapy should be guided by bacteriological studies (including susceptibility tests) and by clinical response.

NOTE: When high, sustained serum levels are required, aqueous penicillin G, either IM or IV, should be used.

The following infections will usually respond to adequate dosages of intramuscular penicillin G procaine: Moderately severe to severe infections of the upper respiratory tract, skin and soft-tissue infections, scarlet fever, and erysipelas due to susceptible streptococci (Group A-without bacteremia).

NOTE: Streptococci in Groups A, C, G, H, L, and M are very sensitive to penicillin G. Other groups, including Group D (enterococcus), are resistant. Aqueous penicillin is recommended for streptococcal infections with bacteremia.

Moderately severe infections of the respiratory tract due to susceptible pneumococci.

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

Moderately severe infections of the skin and soft tissues due to susceptible staphylococci (penicillin G-susceptible).

NOTE: Reports indicate an increasing number of strains of staphylococci resistant to penicillin G, emphasizing the need for culture and sensitivity studies in treating suspected staphylococcal infections. Indicated surgical procedures should be performed.

Fusospirochetosis (Vincent's gingivitis and pharyngitis). Moderately severe infections of the oropharynx due to susceptible fusiform bacilli and spirochetes.

NOTE: Necessary dental care should be accomplished in infections involving the gum tissue.

Syphilis (all stages) due to susceptible Treponema pallidum.

NOTE: This drug should not be used in the treatment of beta-lactamase producing organisms which include most strains of Neisseria gonorrhea.

Yaws, Bejel, Pinta due to susceptible organisms.

Penicillin G procaine is an adjunct to antitoxin for prevention of the carrier stage of diphtheria due to susceptible C. diphtheriae.

Anthrax due to Bacillus anthracis, including inhalational anthrax (post-exposure): to reduce the incidence or progression of the disease following exposure to aerosolized Bacillus anthracis.

Rat-bite fever due to susceptible Streptobacillus moniliformis and Spirillum minus organisms.

Erysipeloid due to susceptible Erysipelothrix rhusiopathiae.

Subacute bacterial endocarditis, only in extremely sensitive infections, due to susceptible Group Astreptococci.


Fungal Skin Infections: Types, Symptoms, and Treatments See Slideshow


Do not inject into or near an artery or nerve. Injection into or near a nerve may result in permanent neurologic damage (see WARNINGS).

Penicillin G procaine (aqueous) is for intramuscular injection only.

Administer by DEEP INTRAMUSCULAR INJECTION in the upper, outer quadrant of the buttock. In neonates, infants and small children, the midlateral aspect of the thigh may be preferable. When doses are repeated, vary the injection site.

Because of the high concentration of suspended material in this product, the needle may be blocked if the injection is not made at a slow, steady rate.

Pneumonia (pneumococcal), moderately severe (uncomplicated): 600,000 to 1,000,000 units daily.

Streptococcal infections (Group A), moderately severe to severe tonsillitis, erysipelas, scarlet fever, upper respiratory tract, skin and soft tissue: 600,000 to 1,000,000 units daily for 10-day minimum.

Staphylococcal infections, moderately severe to severe: 600,000 to 1,000,000 units daily.

In pneumonia, streptococcal (Group A) and staphylococcal infections in pediatric patients under 60 pounds: 300,000 units daily.

Bacterial endocarditis (Group A streptococci) only in extremely sensitive infections: 600,000 to 1,000,000 units daily.

Penicillin G procaine is not recommended for prophylaxis against bacterial endocarditis. For prophylaxis against bacterial endocarditis in patients with congenital heart disease or rheumatic or other acquired valvular heart disease when undergoing dental procedures or surgical procedures of the upper respiratory tract, use penicillin V. For patients unable to take oral medications, aqueous penicillin G is recommended.


Primary, secondary, and latent with a negative spinal fluid in adults and pediatric patients over 12 years of age: 600,000 units daily for 8 days-total 4,800,000 units.

Late (tertiary, neurosyphilis, and latent syphilis with positive spinal-fluid examination or no spinal-fluid examination): 600,000 units daily for 10 to 15 days-total 6 to 9 million units.

Congenital syphilis under 70-lb. body weight: 50,000 units/kg/day for 10 days.

Yaws, Bejel, and Pinta: Treatment as for syphilis in corresponding stage of disease.

Diphtheria-adjunctive therapy with antitoxin: 300,000 to 600,000 units daily.

Diphtheria carrier state: 300,000 units daily for 10 days.

Anthrax-cutaneous: 600,000 to 1,000,000 units/day.

Anthrax-inhalational (post-exposure): 1,200,000 units every 12 hours in adults, 25,000 units per kilogram of body weight (maximum 1,200,000 unit) every 12 hours in children. The available safety data for penicillin G procaine at this dose would best support a duration of therapy of 2 weeks or less. Treatment for inhalational anthrax (post-exposure) must be continued for a total of 60 days. Physicians must consider the risks and benefits of continuing administration of penicillin G procaine for more than 2 weeks or switching to an effective alternative treatment.

Vincent's infection (fusospirochetosis): 600,000 to 1,000,000 units/day.

Erysipeloid: 600,000 to 1,000,000 units/day.

Streptobacillus moniliformis and Spirillum minus (rat-bite fever): 600,000 to 1,000,000 units/day.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.


Penicillin G Procaine Injectable Suspension is supplied in packages of 10 syringes as follows:

1 mL size, containing 600,000 units per syringe (21 gauge, thin-wall 1-½ inch needle), NDC 60793-130-10.

2 mL size, containing 1,200,000 units per syringe (21 gauge, thin-wall 1-½ inch needle), NDC 60793-131-10.

Store in a refrigerator, 2° to 8°C (36° to 46°F).

Keep from freezing.

Distributed by: Pfizer Inc., New York,  NY 10017. Revised: Oct 2016

Side Effects & Drug Interactions


Allergic Reactions

Penicillin is a substance of low toxicity but does possess a significant index of sensitization. The following hypersensitivity reactions associated with use of penicillin have been reported: Skin rashes, ranging from maculopapular eruptions to exfoliative dermatitis; urticaria; serum-sicknesslike reactions, including chills, fever, edema, arthralgia, and prostration. Severe and often fatal anaphylaxis has been reported (see WARNINGS). As with other treatments for syphilis, the Jarisch-Herxheimer reaction has been reported.

Procaine toxicity manifestations and hypersensitivity reactions have been reported (see WARNINGS and PRECAUTIONS).


Pseudomembranous colitis has been reported with the use of penicillin G. Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment (see WARNINGS).


Tetracycline, a bacteriostatic antibiotic, may antagonize the bactericidal effect of penicillin and concurrent use of these drugs should be avoided.

Concurrent administration of penicillin and probenecid increases and prolongs serum penicillin levels by decreasing the apparent volume of distribution and slowing the rate of excretion by competitively inhibiting renal tubular secretion of penicillin.


Bowel regularity means a bowel movement every day. See Answer


Penicillin G procaine should only be prescribed for the indications listed in this insert.

NOTE: This drug is no longer indicated in the treatment of gonorrhea.



Pseudomembranous Colitis

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including penicillin G, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.

Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridium. Studies indicate that a toxin produced by Clostridium difficile is one primary cause of “antibiotic-associated colitis.”

After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management of fluids and electrolytes, protein supplementation and treatment with an antibacterial drug clinically effective against C. difficile colitis.

Procaine Reactions

Immediate toxic reactions to procaine may occur in some individuals, particularly when a large single dose is administered (4.8 million units). These reactions may be manifested by mental disturbances, including anxiety, confusion, agitation, depression, weakness, seizures, hallucinations, combativeness, and expressed “fear of impending death.” The reactions noted in carefully controlled studies occurred in approximately one in 500 patients who received large doses of penicillin G procaine. Reactions are transient, lasting from 15 to 30 minutes.

Method Of Administration

Do not inject into or near an artery or nerve.

Injection into or near a nerve may result in permanent neurological damage.

Inadvertent intravascular administration, including inadvertent direct intra-arterial injection or injection immediately adjacent to arteries, of Penicillin G Procaine Injectable Suspension and other penicillin preparations has resulted in severe neurovascular damage, including transverse myelitis with permanent paralysis, gangrene requiring amputation of digits and more proximal portions of extremities, and necrosis and sloughing at and surrounding the injection site. Such severe effects have been reported following injections into the buttock, thigh, and deltoid areas. Other serious complications of suspected intravascular administration which have been reported include immediate pallor, mottling, or cyanosis of the extremity, both distal and proximal to the injection site, followed by bleb formation; severe edema requiring anterior and/or posterior compartment fasciotomy in the lower extremity. The above-described severe effects and complications have most often occurred in infants and small children. Prompt consultation with an appropriate specialist is indicated if any evidence of compromise of the blood supply occurs at, proximal to, or distal to the site of injection.1-9 (See PRECAUTIONS, and DOSAGE AND ADMINISTRATION.)

Quadriceps femoris fibrosis and atrophy have been reported following repeated intramuscular injections of penicillin preparations into the anterolateral thigh.




Penicillin should be used with caution in individuals with histories of significant allergies and/or asthma.

Care should be taken to avoid intravenous or intra-arterial administration, or injection into or near major peripheral nerves or blood vessels, since such injections may produce neurovascular damage. (See WARNINGS, and DOSAGE AND ADMINISTRATION.)

A small percentage of patients are sensitive to procaine. If there is a history of sensitivity, make the usual test: Inject intradermally 0.1 mL of a 1 to 2 percent procaine solution. Development of an erythema, wheal, flare, or eruption indicates procaine sensitivity. Sensitivity should be treated by the usual methods, including barbiturates, and procaine penicillin preparations should not be used. Antihistaminics appear beneficial in treatment of procaine reactions.

The use of antibiotics may result in overgrowth of nonsusceptible organisms. Constant observation of the patient is essential. If new infections due to bacteria or fungi appear during therapy, the drug should be discontinued and appropriate measures taken.

Whenever allergic reactions occur, penicillin should be withdrawn unless, in the opinion of the physician, the condition being treated is life-threatening and amenable only to penicillin therapy.

Laboratory Tests

In suspected staphylococcal infections, proper laboratory studies, including susceptibility tests, should be performed.

In prolonged therapy with penicillin, and particularly with high-dosage schedules, periodic evaluation of the renal and hematopoietic systems is recommended. In such situations, use of penicillin for more than 2 weeks may be associated with an increased risk of neutropenia and an increased incidence of serum sickness-like reactions.

When treating gonococcal infections in which primary or secondary syphilis may be suspected, proper diagnostic procedures, including dark-field examinations, should be done. In all cases in which concomitant syphilis is suspected, monthly serological tests should be made for at least four months.

Carcinogenesis, Mutagenesis, Impairment Of Fertility

No long-term animal studies have been conducted with these drugs.


Teratogenic Effects

Reproduction studies performed in the mouse, rat, and rabbit have revealed no evidence of impaired fertility or harm to the fetus due to penicillin G. Human experience with the penicillins during pregnancy has not shown any positive evidence of adverse effects on the fetus. There are, however, no adequate and well-controlled studies in pregnant women showing conclusively that harmful effects of these drugs on the fetus can be excluded. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

Penicillins are excreted in human milk. Caution should be exercised when penicillins are administered to a nursing woman.

Pediatric Use

Because of incompletely developed renal function in newborns, penicillin elimination may be delayed. Guidelines for administration of this drug to pediatric patients are presented in DOSAGE AND ADMINISTRATION.

Geriatric Use

Clinical studies of penicillin G procaine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. (See CLINICAL PHARMACOLOGY) Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.


1. SHAW, E.: Transverse myelitis from injection of penicillin. Am. J. Dis. Child., 111:548, 1966.

2. KNOWLES, J.: Accidental intra-arterial injection of penicillin. Am. J. Dis. Child., 111:552, 1966.

3. DARBY, C. et al: Ischemia following an intragluteal injection of benzathine-procaine penicillin G mixture in a one-year-old boy. Clin. Pediatrics, 12:485, 1973.

4. BROWN, L. & NELSON, A.: Postinfectious intravascular thrombosis with gangrene. Arch. Surg., 94:652, 1967.

5. BORENSTINE, J.: Transverse myelitis and penicillin (Correspondence). Am. J. Dis. Child., 112:166, 1966.

6. ATKINSON, J.: Transverse myelopathy secondary to penicillin injection. J. Pediatrics, 75:867, 1969.

7. TALBERT, J. et al: Gangrene of the foot following intramuscular injection in the lateral thigh: A case report with recommendations for prevention. J. Pediatrics, 70:110, 1967.

8. FISHER, T.: Medicolegal affairs. Canad. Med. Assoc. J., 112:395, 1975.

9. SCHANZER, H. et al: Accidental intra-arterial injection of penicillin G. JAMA, 242:1289, 1979.

Overdosage & Contraindications


No Information provided


A previous hypersensitivity reaction to any penicillin is a contraindication.

Clinical Pharmacology


Penicillin G procaine is an equimolecular compound of procaine and penicillin G, administered intramuscularly as a suspension. It dissolves slowly at the site of injection, giving a plateau type of blood level at about 4 hours which falls slowly over a period of the next 15 to 20 hours.

Approximately 60% of penicillin G is bound to serum protein. The drug is distributed throughout the body tissues in widely varying amounts. Highest levels are found in the kidneys with lesser amounts in the liver, skin, and intestines. Penicillin G penetrates into all other tissues to a lesser degree with a very small level found in the cerebrospinal fluid. With normal kidney function, the drug is excreted rapidly by tubular excretion. In neonates and young infants and in individuals with impaired kidney functions, excretion is considerably delayed. Approximately 60 to 90 percent of a dose of parenteral penicillin G is excreted in the urine within 24 to 36 hours.


Mechanism Of Action

Penicillin G exerts a bactericidal action against penicillin-susceptible microorganisms during the stage of active multiplication. It acts through the inhibition of biosynthesis of cell-wall peptidoglycan, rendering the cell wall osmotically unstable.

Mechanism Of Resistance

Penicillin is not active against penicillinase-producing bacteria, or against organisms resistant to beta-lactams because of alterations in the penicillin-binding proteins. Resistance to penicillin G has not been reported in Streptococcus pyogenes.

Antibacterial Activity

Penicillin G procaine has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.

Gram-positive Bacteria

Streptococcus pyogenes
Streptococcus pneumoniae

While in vitro studies have demonstrated the susceptibility of most strains of the following organisms, clinical efficacy for infections other than those included in the INDICATIONS AND USAGE section has not been documented. Penicillin G is also active in vitro against susceptible strains of the following organisms: Neisseria meningitidis, Corynebacterium diphtheriae, Bacillus anthracis, Clostridium species, Actinomyces species, Spirillum minus, Streptobacillus moniliformis, Listeria monocytogenes, Leptospira species and Treponema pallidum.

Susceptibility Test Methods

When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility test results for antimicrobial drug products used in resident hospitals to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting an antibacterial drug product for treatment.

Dilution Techniques

Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure (broth and/or agar).10,11 The MIC values should be interpreted according to the criteria provided in Table 1.

Diffusion Techniques

Quantitative methods that require the measurement of zone diameters can also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size provides an estimate of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized test method.11,12 This procedure uses paper discs impregnated with 10 units penicillin to test the susceptibility of microorganisms to penicillin. The disk diffusion interpretive criteria are provided in Table 1.

Table 1: Susceptibility Test Interpretive Criteria for Penicillin G Procaine

Pathogen Minimum Inhibitory Concentrations (mcg/mL) Disk Diffusion (zone diameters in mm)
Streptococcus pneumoniae (nonmeningitis)* ≤ 2 4 ≥ 8 - - -
Streptococcus pyogenes ≤ 0.12 - - ≥ 24 - -
*Disk susceptibility testing of isolates of pneumococci is performed using 1 mcg oxacillin disks. 11,12
†Susceptibility testing of penicillins for treatment of β-hemolytic streptococcal infections need not be performed routinely, because non-susceptible isolates are extremely rare in any β-hemolytic streptococcus and have not been reported in Streptococcus pyogenes. Any β-hemolytic streptococcal isolate found to be non-susceptible to penicillin should be re-identified, retested, and, if confirmed, submitted to a public health authority. 10,11

Quality Control

Standardized susceptibility test procedures require the use of laboratory control microorganisms to monitor and ensure the accuracy and precision of the supplies and reagents used in the assay, and the techniques of the individuals performing the test. Standard penicillin powder should provide the following range of MIC values noted in Table 2. For the diffusion technique using the 10 unit penicillin disk, the criteria in Table 2 should be achieved.

Table 2: Acceptable Quality Control Ranges for Penicillin

Pathogen Minimum Inhibitory Concentrations (mcg/mL) Disk Diffusion (zone diameters in mm)
Enterococcus faecalis ATCC 29212 1-4 -
Neisseria gonorrhoeae ATCC 49226 0.25-1* 26-34
Staphylococcus aureus ATCC 25923 - 26-37
Staphylococcus aureus ATCC 29213 0.25-2 -
Streptococcus pneumoniae ATCC 49619 0.25-1 24-30
*MIC by agar dilution method


10. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard - Tenth Edition. CLSI document M07-A10, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.

11. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twentyfifth Informational Supplement, CLSI document M100-S25, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.

12. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk Diffusion Susceptibility Tests; Approved Standard – Twelfth Edition. CLSI document M02- A12, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015. LAB 0587-6.0

Medication Guide


No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

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