Benzylpenicillin: Indication, Dosage, Side Effect, Precaution

This information is not country-specific. Please refer to the Indonesia prescribing information.

Generic Medicine Info

Indications and Dosage

Intramuscular, Intravenous
Brain abscess, Gas gangrene, Leptospirosis, Listeriosis, Osteomyelitis, Pasteurella infection, Respiratory tract infections, Septicaemia, Skin infections

Adult: Benzylpenicillin 600 mg is equivalent to approx 1 million international units. Dosage: 600-3,600 mg (1-6 million units) daily in 4-6 divided doses via IV inj, IV infusion, or IM inj. Higher doses (up to 14,400 mg [24 million units] daily) may be needed for more serious infections and are given via IV, often by infusion. Rate of not more than 300 mg/min is recommended for IV doses exceeding 1,200 mg (2 million units). Dosage and treatment duration depend on the pathogen type and susceptibility, severity of infection, and patient condition. Treatment recommendations may vary among countries and individual products (refer to specific product guidelines).
Child: 1 month to 12 years 18-60 mg/kg (30,000-100,000 units/kg) daily in 4-6 divided doses via IV inj, IV infusion, or IM inj. High doses of 60-300 mg/kg (100,000-500,000 units/kg) daily in 4-6 divided doses may be given via IV. Dosage and treatment duration depend on the pathogen type and susceptibility, severity of infection, and patient condition. Treatment recommendations may vary among countries and individual products (refer to specific product guidelines).

Intramuscular, Intravenous
Diphtheria

Adult: Benzylpenicillin 600 mg is equivalent to approx 1 million international units. As adjunctive treatment after antitoxin administration and for prevention of carrier state: 1,200-1,800 mg (2-3 million units) daily in divided doses 4-6 hourly. Doses may be given via IV infusion or IM inj; IV administration is advisable when large doses are needed. Treatment duration: 10-12 days. Dosage recommendations may vary among countries and individual products (refer to specific product guidelines).
Child: As adjunctive treatment after antitoxin administration and for prevention of carrier state: 90-150 mg/kg (150,000-250,000 units/kg) daily in divided doses 6 hourly. Doses may be given via IV infusion or IM inj. Treatment duration: 7-10 days. Dosage recommendations may vary among countries and individual products (refer to specific product guidelines).

Intramuscular, Intravenous
Actinomycosis

Adult: Benzylpenicillin 600 mg is equivalent to approx 1 million international units. For cervicofacial disease: 600-3,600 mg (1-6 million units) daily in divided doses 4-6 hourly. For thoracic and abdominal disease: 6,000-12,000 mg (10-20 million units) daily in divided doses 4-6 hourly. Doses may be given via IV infusion or IM inj; IV administration is advisable when large doses are needed. Treatment recommendations may vary among countries and individual products (refer to specific product guidelines).

Intramuscular, Intravenous
Suspected meningococcal disease

Adult: Benzylpenicillin 600 mg is equivalent to approx 1 million international units. Dosage: 1,200 mg (2 million units) as a single dose via IV or IM inj prior to transfer to hospital.
Child: 1-11 months 300 mg (500,000 units); 1-9 years 600 mg (1 million units); 10-17 years 1,200 mg (2 million units). All doses are given as a single dose via IV or IM inj prior to transfer to hospital.

Intramuscular, Intravenous
Botulism

Adult: Benzylpenicillin 600 mg is equivalent to approx 1 million international units. As adjunctive therapy to antitoxin: 12,000 mg (20 million units) daily in divided doses 4-6 hourly. Doses may be given via IV infusion or IM inj; IV administration is advisable when large doses are needed. Dosage recommendations may vary among countries and individual products (refer to specific product guidelines).

Intramuscular, Intravenous
Rat bite fever

Adult: Benzylpenicillin 600 mg is equivalent to approx 1 million international units. For cases caused by susceptible Spirillum minus or Streptobacillus moniliformis: 7,200-12,000 mg (12-20 million units) daily in divided doses 4-6 hourly for 3-4 weeks. Doses may be given via IV infusion or IM inj; IV administration is advisable when large doses are needed. Dosage recommendations may vary among countries and individual products (refer to specific product guidelines).

Intramuscular, Intravenous
Tetanus

Adult: Benzylpenicillin 600 mg is equivalent to approx 1 million international units. As an alternative adjunctive treatment to tetanus Ig: 12,000 mg (20 million units) daily in divided doses 4-6 hourly for 7-10 days. Doses may be given via IV infusion or IM inj; IV administration is advisable when large doses are needed. Dosage recommendations may vary among countries and individual products (refer to specific product guidelines).

Intravenous
Bacterial endocarditis

Adult: Benzylpenicillin 600 mg is equivalent to approx 1 million international units. Dosage: 7,200-14,400 mg (12-24 million units) daily in divided doses 4-6 hourly via IV infusion. Dosage and treatment duration depend on the pathogen type and susceptibility. Recommendations may vary among countries and individual products (refer to specific product guidelines).
Child: 120-180 mg/kg (200,000-300,000 units/kg) daily in divided doses 4 hourly via IV infusion for at least 4 weeks. Max: 14,400 mg (24 million units) daily. For some resistant organisms, may use in combination with gentamicin. Dosage recommendations may vary among countries and individual products (refer to specific product guidelines).

Intravenous
Intrapartum prophylaxis against group B streptococcal infection in neonates

Adult: Benzylpenicillin 600 mg is equivalent to approx 1 million international units. Initially, 3,000 mg (5 million units) as a single loading dose given to the mother, followed by 1,500 mg (2.5 million units) 4 hourly until delivery. Doses are given via IV inj or infusion.

Intravenous
Bacterial meningitis

Adult: Benzylpenicillin 600 mg is equivalent to approx 1 million international units. Dosage: 2,400 mg (4 million units) 4 hourly via IV inj or infusion. Treatment duration may vary depending on the causative pathogen and clinical response. Dosage or treatment recommendations may vary among countries and individual products (refer to specific product guidelines).
Child: 180-240 mg/kg (300,000-400,000 units/kg) daily in divided doses 4-6 hourly. Max: 2,400 mg (4 million units) per dose; 14,400 mg (24 million units) daily. Doses are given via IV infusion. Dosage or treatment recommendations may vary among countries and individual products (refer to specific product guidelines).

Intravenous
Anthrax

Adult: Benzylpenicillin 600 mg is equivalent to approx 1 million international units. Dosage: 4,800 mg (8 million units) daily in divided doses 6 hourly via IV infusion. Higher doses may be needed depending on pathogen susceptibility. Concomitant use with other antibacterials may also be indicated. Dosage recommendations may vary among countries and individual products (refer to specific product guidelines).
Child: As part of appropriate combination regimen: 240 mg/kg (400,000 units/kg) daily in divided doses 4 hourly. Max: 2,400 mg (4 million units) per dose. Doses are given via IV infusion. Treatment duration: At least 14 days if meningitis is excluded or at least 14-21 days if meningitis cannot be excluded, and until the patient is clinically stable. Recommendations may vary among countries (refer to local guidelines).

Intravenous
Neurosyphilis

Adult: Benzylpenicillin 600 mg is equivalent to approx 1 million international units. Dosage: 1,200-2,400 mg (2-4 million units) 4 hourly via IV infusion for 10-14 days.
Child: ≥1 month 30 mg/kg (50,000 units/kg) 4-6 hourly for 10-14 days. Max: 14,400 mg (24 million units) daily. Doses are given via IV infusion.

Intravenous
Lyme disease

Adult: Benzylpenicillin 600 mg is equivalent to approx 1 million international units. As an alternative agent: 10,800-14,400 mg (18-24 million units) daily in divided doses 4 hourly. Treatment duration: 10-28 days (early stage); 14-28 days (late stage). Alternatively, 12,000-18,000 mg (20-30 million units) daily in 2-3 divided doses for 14 days. Doses are given via IV infusion. Dosage recommendations may vary among countries and individual products (refer to specific product guidelines).
Child: As an alternative agent: 120-240 mg/kg (200,000-400,000 units/kg) daily in divided doses 4 hourly. Max: 14,400 mg (24 million units) daily. Alternatively, 300 mg/kg (500,000 units/kg) daily in 2-3 divided doses. Doses are given via IV infusion. Treatment duration depends on the clinical syndrome. Dosage recommendations may vary among countries and individual products (refer to specific product guidelines).

Renal Impairment

For doses of 600-1,200 mg (1-2 million units), dosing intervals must be no more frequent than 8-10 hourly.

For high-dose regimen:
Anuric patients: 300 mg (500,000 units) 6 hourly or 600 mg (1 million units) 8 hourly.

CrCl (mL/min)	Dosage
10	600 mg (1 million units) 6 hourly.
20	600 mg (1 million units) 4 hourly.
40	900 mg (1.5 million units) 4 hourly.
60	1,200 mg (2 million units) 4 hourly.

Patients on haemodialysis: Additional dose of 300 mg (500,000 units) 6 hourly during dialysis run.

Alternative dosing:
CrCl <10 mL/min/1.73 m²: Administer usual dose as a loading dose, followed by 50% of the usual dose given 8-10 hourly. Uraemic patients with CrCl ≥10 mL/min/1.73 m²: Administer usual dose as a loading dose, followed by 50% of the usual dose given 4-5 hourly. Dosage recommendations may vary among countries and individual products. Refer to specific product guidelines.

Hepatic Impairment

Patients with advanced liver disease associated with severe renal failure: 300 mg (500,000 units) 8 hourly. Dosage recommendations may vary among countries and individual products. Refer to specific product guidelines.

Reconstitution

Powder for solution for inj or infusion: Reconstitute to the desired concentrations with the appropriate volume of diluent (e.g. sterile water for inj, NaCl 0.9%) specified in the product guideline. Hold the vial horizontally and rotate it while adding the diluent slowly, directing the stream against the wall of the vial. Shake the vial vigorously. Recommendations on reconstitution may vary among individual products (refer to specific product guidelines).

Incompatibility

Incompatible with metal ions, amphotericin B, cimetidine, cytarabine, hydroxyzine, flucloxacillin, promethazine, methylprednisolone, some cephalosporins, aminoglycosides, vancomycin. May be inactivated by oxidising and reducing agents, alcohol, macrogols, glycerol, and other hydroxylated compounds.

Contraindications

Hypersensitivity to penicillin. History of severe immediate hypersensitivity reaction (e.g. anaphylaxis) to other β-lactam agents (e.g. cephalosporin, carbapenem).

Special Precautions

Patient with history of significant allergies and/or asthma; severe heart condition, severe electrolyte disturbances of any other origin, diabetes mellitus, seizure disorder, mononucleosis, acute lymphatic leukaemia. Avoid accidental intra-arterial inj into or near major peripheral nerves or blood vessels. Avoid skin contact with benzylpenicillin. Renal impairment; hepatic impairment associated with severe renal failure. Neonates and children. Pregnancy and lactation.

Adverse Reactions

Significant: Jarisch-Herxheimer reaction (particularly in patients with syphilis or other spirochetal infections); fungal or bacterial superinfection (prolonged use).
Blood and lymphatic system disorders: Neutropenia; bleeding diathesis secondary to platelet dysfunction (high doses).
Gastrointestinal disorders: Nausea, vomiting, stomatitis, glossitis, black or hairy tongue.
General disorders and administration site conditions: Pain at inj site.
Immune system disorders: Hypersensitivity reactions (e.g. urticaria, pruritus, fever, serum sickness-like reaction).
Nervous system disorders: Rarely, CNS toxicity (e.g. convulsions).
Renal and urinary disorders: Rarely, interstitial nephritis with renal tubular necrosis.
Skin and subcutaneous tissue disorders: Contact dermatitis (during preparation of solutions).
Vascular disorders: Thrombophlebitis, phlebitis (IV).
Potentially Fatal: Anaphylactic reactions, severe cutaneous adverse reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, acute generalised exanthematous pustulosis); Clostridioides difficile-associated diarrhoea, pseudomembranous colitis (particularly during prolonged use); severe electrolyte disturbances (particularly with high IV doses).

Pregnancy Category (US FDA)

IM/IV/Parenteral: B

Monitoring Parameters

Perform culture and susceptibility tests; consult local institutional recommendations before treatment initiation due to antibiotic resistance risks. Monitor for hypersensitivity reactions 30 minutes after administration; seizures or other neurologic activity (particularly in patients with history of seizures). Monitor electrolyte balance, hepatic, renal, and haematologic functions, and cardiac and vascular status periodically during prolonged or high-dose treatment.

Overdosage

Symptoms: Agitation, convulsion, confusion, asterixis, hallucinations, multifocal myoclonus, stupor, encephalopathy, electrolyte disturbances (e.g. hyperkalaemia, hypernatraemia) and coma. Management: Symptomatic and supportive treatment.

Drug Interactions

Increased serum concentration and prolonged elimination half-life with probenecid. Antipyretics, antirheumatics, and anti-inflammatories (e.g. indometacin, phenylbutazone, and high doses of salicylates) may compete for renal tubular secretion and prolong the serum half-life of benzylpenicillin. Concurrent use of bacteriostatic antibiotics (e.g. chloramphenicol, tetracycline, erythromycin) may antagonise the bactericidal effect of benzylpenicillin. May reduce the efficacy of oral contraceptives. May reduce the excretion of methotrexate and increase the risk of methotrexate toxicity. May enhance the effect of oral anticoagulants (e.g. warfarin).

Lab Interference

May lead to positive Coombs' test, false-positive reaction for urinary glucose test using copper sulfate, and false-positive results for urinary and/or serum proteins using certain test methods. May interfere with tests which use bacteria (e.g. Guthrie test).

Action

Description:
Mechanism of Action: Benzylpenicillin, a β-lactam antibiotic, inhibits bacterial cell wall synthesis during the stage of active multiplication leading to bacterial cell wall death and consequent bactericidal activity.
Synonym(s): Penicillin G.
Pharmacokinetics:
Absorption: Rapidly absorbed after IM inj. Time to peak plasma concentration: 15-30 minutes (IM).
Distribution: Widely distributed throughout the body (including lungs, liver, kidneys, muscle, bone; pericardial, pleural, peritoneal, and synovial fluids); penetrates poorly in CSF except when meninges are inflamed. Crosses the placenta; enters breast milk (small amounts). Volume of distribution: 0.53-0.67 L/kg. Plasma protein binding: Approx 60%, mainly to albumin.
Metabolism: Metabolised to a limited extent into penicilloic acid derivative (inactive).
Excretion: Via urine (58-85% as unchanged drug); bile (small amounts). Elimination half-life: 31-50 minutes.

Chemical Structure

Storage

Benzylpenicillin sodium powder for inj: Store intact vials between 20-25°C. Reconstituted solution: May store between 2-8°C for up to 3 days. Benzylpenicillin potassium powder for inj: Store intact vials below 30°C. Reconstituted solution: May store between 2-8°C for up to 7 days. Storage recommendations may vary among individual products. Refer to specific product guidelines.

MIMS Class

Penicillins

ATC Classification

J01CE01 - benzylpenicillin ; Belongs to the class of beta-lactamase sensitive penicillins. Used in the systemic treatment of infections.

References

Puopolo KM, Lynfield R, Cummings JJ, AAP Committee on Fetus and Newborn, AAP Committee on Infectious Diseases. Management of Infants at Risk for Group B Streptococcal Disease. Pediatrics. 2019;144(2):e20191881. https://doi.org/10.1542/peds.2019-1881. Accessed 14/04/2023

Committee on Infectious Diseases, American Academy of Pediatrics, Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH. "Tables of Antibacterial Drug Dosages", Red Book: 2021-2024 Report of the Committee on Infectious Diseases. American Academy of Pediatrics [online]. Accessed 14/06/2023.

Anon. Benzylpenicillin [Penicillin G] (Parenteral/Aqueous). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 14/04/2023.

Anon. Penicillin G (Parenteral/Aqueous) (Pediatric and Neonatal Lexi-Drugs). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 14/04/2023.

Anon. Penicillin G. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 11/07/2023.

Benzylpenicillin Sodium 1,200 mg Powder for Injection (Genus Pharmaceuticals). MHRA. https://products.mhra.gov.uk. Accessed 14/04/2023.

Benzylpenicillin Sodium 600 mg Powder for Solution for Injection/Infusion (Sandoz Limited). MHRA. https://products.mhra.gov.uk. Accessed 11/07/2023.

Bepen Injection (Averroes Pharmaceutical Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 14/04/2023.

Buckingham R (ed). Benzylpenicillin. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 14/04/2023.

Joint Formulary Committee. Benzylpenicillin Sodium. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 14/04/2023.

Novartis New Zealand Limited. Penicillin G Sodium (Benzylpenicillin Sodium) Injection data sheet 15 July 2020. Medsafe. http://www.medsafe.govt.nz. Accessed 14/04/2023.

Paediatric Formulary Committee. Benzylpenicillin Sodium. BNF for Children [online]. London. BMJ Group, Pharmaceutical Press, and RCPCH Publications. https://www.medicinescomplete.com. Accessed 14/04/2023.

Penicillin G Sodium Injection, Powder, for Solution (Sandoz Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 11/07/2023.

Penicillin G. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 11/07/2023.

Pfizerpen Powder, for Solution (Roerig). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 14/04/2023.

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