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Penicillin G Benzathine

Medically reviewed by Last updated on Aug 16, 2020.


(pen i SIL in jee BENZ a theen)

Index Terms

  • Benzathine Benzylpenicillin
  • Benzathine Penicillin G
  • Benzylpenicillin Benzathine

Dosage Forms

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

Suspension, Intramuscular:

Bicillin L-A: 600,000 units/mL (1 mL); 1,200,000 units/2 mL (2 mL); 2,400,000 units/4 mL (4 mL) [contains methylparaben, propylparaben]

Brand Names: U.S.

  • Bicillin L-A

Pharmacologic Category

  • Antibiotic, Penicillin


Interferes with bacterial cell wall synthesis during active multiplication, causing cell wall death and resultant bactericidal activity against susceptible bacteria


IM: Slow


Minimal concentrations attained in CSF with inflamed or uninflamed meninges; highest levels in the kidney; lesser amounts in liver, skin, intestines


Excreted by renal tubular excretion; penicillin G is detected in urine for up to 12 weeks after a single IM injection; renal clearance is delayed in neonates, young infants, and patients with impaired renal function

Time to Peak

Serum: Within 12 to 24 hours; serum levels are usually detectable for 1 to 4 weeks depending on the dose; larger doses result in more sustained levels rather than higher levels

Duration of Action

Dose dependent: 1 to 4 weeks; larger doses result in more sustained levels

Protein Binding


Use: Labeled Indications

Acute glomerulonephritis: Prophylaxis (secondary) in patients with a history of acute glomerulonephritis

Respiratory tract infections: Treatment of mild to moderate upper respiratory tract infections (including pharyngitis) caused by streptococci susceptible to low, prolonged serum concentrations of penicillin G

Rheumatic fever and chorea: Prophylaxis (secondary) of rheumatic fever and/or chorea

Rheumatic heart disease: Prophylaxis (secondary) in patients with rheumatic heart disease

Syphilis and other venereal diseases: Treatment of syphilis, yaws, bejel, and pinta

Off Label Uses

Streptococcal (group A) chronic carriage

Based on the IDSA guidelines for diagnosis and management of group A streptococcal pharyngitis, penicillin G benzathine, in combination with rifampin, is an effective and recommended agent for the treatment of chronic group A streptococcus carriage.


Hypersensitivity to penicillin(s) or any component of the formulation

Dosing: Adult

Usual dosage range: IM: 1.2 to 2.4 million units as a single dose

Streptococcus (group A):

Pharyngitis, acute treatment: IM: 1.2 million units as a single dose (AHA [Gerber 2009]; IDSA [Shulman 2012])

Secondary prophylaxis for rheumatic fever (prevention of recurrent attacks): IM: 1.2 million units once every 21 to 28 days. Duration depends on risk factors and presence of valvular heart disease (AHA [Gerber 2009]).

Manufacturer's labeling: Dosing in the prescribing information may not reflect current clinical practice. IM: 600,000 units every 2 weeks

Secondary prophylaxis of glomerulonephritis: IM: 1.2 million units every 4 weeks or 600,000 units twice monthly

Chronic carriage (off-label use): IM: 1.2 million units as a single dose in combination with oral rifampin. Note: Most individuals with chronic carriage do not require antibiotics (IDSA [Shulman 2012]).

Syphilis (CDC [Workowski 2015]):

Primary, Secondary, Early Latent (<1 year duration): IM: 2.4 million units as a single dose

Late Latent, Latent with unknown duration, or Tertiary Syphilis (with normal CSF examination): IM: 2.4 million units once weekly for 3 doses

Neurosyphilis (including Ocular Syphilis): Not indicated for initial treatment; aqueous penicillin G IV is preferred initial therapy (refer to Penicillin G Parenteral/Aqueous monograph for dosing). Following penicillin G IV initial treatment, may consider administration of penicillin G benzathine 2.4 million units IM once weekly for 3 weeks to provide a comparable total duration of therapy as for latent syphilis.

Yaws, bejel, and pinta: IM: 1.2 million units as a single dose

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Group A streptococcal (Streptococcus pyogenes) infection:

Pharyngitis, treatment (primary prevention of rheumatic fever): Note: Empiric treatment is generally not recommended; treatment should be prescribed only when testing confirms presence of Group A Streptococcus (AHA [Gerber 2009]; IDSA [Shulman 2012]; Red Book [AAP 2018]).

Infants, Children, and Adolescents: IM:

≤27 kg: 600,000 units as a single dose.

>27 kg: 1.2 million units as a single dose.

Rheumatic fever, secondary prevention: Note: Duration varies based on risk factors and presence of residual heart disease; see guidelines for details (AHA [Gerber 2009]).

Infants, Children, and Adolescents: IM:

≤27 kg: 600,000 units every 3 to 4 weeks.

>27 kg: 1.2 million units every 3 to 4 weeks.

Note: Every-4-week administration is recommended in the US where rheumatic fever incidence is low; every 3 weeks should be used to maintain desirable serum drug concentrations in patients who have had a breakthrough episode despite every-4-week dosing and in areas where incidence of acute rheumatic fever remains high (AHA [Gerber 2009]; Lue 1994; Red Book [AAP 2018]).

Chronic carriers of Group A Streptococcus, treatment: Limited data available: Note: Antibiotic therapy is generally not recommended for chronic S. pyogenes carriage; however, it may be considered in certain cases (IDSA [Shulman 2012]; Red Book [AAP 2018]).

Infants, Children, and Adolescents: IM:

≤27 kg: 600,000 units as a single dose in combination with oral rifampin for 4 days.

>27 kg: 1.2 million units as a single dose in combination with oral rifampin for 4 days.

Syphilis: Note: Not recommended for the initial treatment of neurosyphilis (CDC [Workowski 2015]; Red Book [AAP 2018]).

Congenital; patients with no clinical manifestations and normal cerebrospinal fluid (CSF): Limited data available: Infants and Children: IM: 50,000 units/kg/dose once weekly for up to 3 weeks; maximum dose: 2.4 million units/dose (Bradley 2019; CDC [Workowski 2015]; Red Book [AAP 2018]). Note: See guidelines for treatment of congenital syphilis in patients with clinical manifestations and/or abnormal CSF; aqueous penicillin G is the preferred treatment (Bradley 2019; CDC [Workowski 2015]; Red Book [AAP 2018]).

Primary, secondary, or early latent (<1 year duration): Infants, Children, and Adolescents: IM: 50,000 units/kg once; maximum dose: 2.4 million units/dose (CDC [Workowski 2015]; Red Book [AAP 2018]).

Re-treatment of primary, secondary, or early latent disease after failure of previous therapy: Infants, Children, and Adolescents: 50,000 units/kg/dose once weekly for 3 weeks; maximum dose: 2.4 million units/dose (CDC [Workowski 2015]; Red Book [AAP 2018]). Note: If CSF examination positive, treat as neurosyphilis (CDC [Workowski 2015]; Red Book [AAP 2018]).

Late latent (>1 year or unknown duration): Infants, Children, and Adolescents: IM: 50,000 units/kg/dose once weekly for 3 weeks; maximum dose: 2.4 million units/dose (CDC [Workowski 2015]; Red Book [AAP 2018]).


IM: Warm to room temperature before administration to lessen the pain associated with injection. Administer by deep IM injection at a slow, steady rate in the dorsogluteal region (upper outer quadrant of the buttock) or the ventrogluteal region. Do not inject near an artery or a nerve; permanent neurological damage or gangrene may result. When doses are repeated, rotate the injection site. Do not administer IV, intra-arterially, or SubQ.


Store at 2°C to 8°C (36°F to 46°F); do not freeze. Extended storage information at room temperature may be available; contact product manufacturer to obtain current recommendations.

Drug Interactions

Acemetacin: May increase the serum concentration of Penicillins. Monitor therapy

Aminoglycosides: Penicillins may decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. 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

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. 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; false-positive or negative urinary glucose using Clinitest®

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Frequency not defined:

Cardiovascular: Cerebrovascular accident, hypersensitivity angiitis, hypotension, palpitations, pulmonary embolism, syncope, tachycardia, vasodilation, vasospasm, vasodepressor syncope

Central nervous system: Anxiety, coma, confusion, dizziness, drowsiness, euphoria, fatigue, headache, localized warm feeling, nervousness, neurologic abnormality (neurogenic bladder), numbness of extremities, pain, seizure, transverse myelitis

Dermatologic: Diaphoresis, gangrene of skin and/or other subcutaneous tissues, pallor, pruritus, skin mottling, skin or other tissue necrosis (Nicolau syndrome), skin ulceration at injection site

Gastrointestinal: Blood in stool, Clostridioides difficile associated diarrhea, intestinal necrosis, nausea, vomiting

Genitourinary: Hematuria, impotence, priapism, proteinuria

Hematologic & oncologic: Lymphadenopathy

Hepatic: Increased serum aspartate aminotransferase

Hypersensitivity: Anaphylaxis, hypersensitivity reaction

Immunologic: Jarisch-Herxheimer reaction

Local: Abscess at injection site, atrophy at injection site, bleeding at injection site, bruising at injection site, cellulitis at injection site, localized edema (at injection site), inflammation at injection site, injection site reaction (neurovascular damage), pain at injection site, residual mass at injection site, tissue necrosis at injection site

Neuromuscular & skeletal: Arthropathy, asthenia, exacerbation of arthritis, periosteal disease, rhabdomyolysis, tremor

Ophthalmic: Blindness, blurred vision

Renal: Increased blood urea nitrogen, increased serum creatinine, myoglobinuria, renal failure syndrome

Respiratory: Apnea, cyanotic extremities, dyspnea, hypoxia, pulmonary hypertension

ALERT: U.S. Boxed Warning

Appropriate administration:

Not for IV use. Do not inject IV or admix with other IV solutions. There have been reports of inadvertent IV administration of penicillin G benzathine that has been associated with cardiorespiratory arrest and death. Prior to administration of this drug, carefully read the Warnings, Adverse Reactions, Dosage, and Administration sections of the labeling.


Concerns related to adverse effects:

• 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 (including cephalosporins), history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Serious anaphylactic reactions require immediate emergency treatment with epinephrine, oxygen, intravenous steroids and airway management (including intubation) as indicated.

• Severe cutaneous adverse reactions: Severe cutaneous adverse reactions (SCAR) (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis) have been reported; discontinue immediately if SCAR is suspected.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including Clostridioides (formerly Clostridium) 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 renal impairment.

• 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.

• Syphilis/neurosyphilis use: CDC and AAP do not currently recommend the use of penicillin G benzathine for the initial treatment regimen for congenital syphilis or neurosyphilis due to reported treatment failures and lack of published clinical data on its efficacy (CDC [Workowski 2015]).

Other warnings/precautions:

• Appropriate administration: [US Boxed Warning]: Not for IV use; cardiopulmonary arrest and death have occurred from inadvertent IV administration. Administer by deep IM injection only. Quadriceps femoris fibrosis and atrophy have been reported after repeated IM injections of penicillin preparations into the anterolateral thigh. Injection into or near an artery or nerve could result in severe neurovascular damage or permanent neurological damage.

• Appropriate use: Use only for treatment of infections due to penicillin G sensitive gram positive organisms, few gram-negative organisms such as Neisseria gonorrhoeae, and some anaerobes and spirochetes. Use only for infections susceptible to the low and very prolonged serum concentrations of benzathine penicillin G.

• 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

Observe for signs and symptoms of anaphylaxis during first dose

Pregnancy Considerations

Penicillin G benzathine crosses the placenta (Nathan 1993; Weeks 1997).

Penicillin is widely used in pregnant women. Based on available data, penicillin is generally considered compatible for use during pregnancy (Ailes 2016; Bookstaver 2015; Crider 2009; Damkier 2019; Galvao 2013; Heinonen 1977; Lamont 2014; Muanda 2017a; Muanda 2017b).

Penicillin G is the drug of choice for treatment of syphilis during pregnancy (CDC [Workowski 2015]). Untreated maternal syphilis can cause congenital syphilis which is associated with bone deformities, neurologic impairment, stillbirth, or neonatal death (USPSTF [Curry 2018]). Symptoms of congenital syphilis may include hepatosplenomegaly, jaundice, nonimmune hydrops, pseudoparalysis of an extremity, rhinitis, or skin rash. The Centers for Disease Control and Prevention (CDC) Sexually Transmitted Diseases Treatment Guidelines provide recommendations for the treatment of syphilis in pregnant patients. The penicillin regimen (dose, duration, and preparation) for the treatment of pregnant patients is the same as for a nonpregnant patient and depends on the stage of syphilis. However, parenteral penicillin G is the only agent with documented efficacy in pregnancy. Patients who are allergic to penicillin should be desensitized and treated with penicillin. Pregnant women being treated for latent syphilis must repeat the full course of therapy if any doses are missed. A Jarisch-Herxheimer reaction may occur in any patient within the first 24 hours of therapy, including pregnant women. This reaction may induce early labor or fetal distress; however, it is not a reason to prevent or delay maternal therapy (CDC [Workowski 2015]).

Use of penicillin G benzathine should be continued for the secondary prophylaxis of rheumatic fever/heart disease during pregnancy when indicated (Russell 2018).

Patient Education

What is this drug used for?

• It is used to treat or prevent bacterial infections.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Diarrhea

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain

• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes

• Chills

• Sore throat

• Swelling

• Joint pain

• Severe dizziness

• Passing out

• Severe loss of strength and energy

• Bruising

• Bleeding

• Injection site irritation, hardness, lump, or dark scab

• Numbness

• Tingling

• Weakness

Clostridioides (formerly Clostridium) difficile-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.