Benzylpenicillin Sodium

These indications are based on manufacturer information for both originator and generic products. For product specific registered indications, please refer to product specific manufacturer information

Registered South African indications: 

• Infections caused by benzylpenicillin-sensitive microorganisms when rapid and high penicillinemia is required
• Prevention of recurrence of rheumatic fever
• Prophylaxis of infective endocarditis in patients with valvular heart disease undergoing surgical procedures

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
  - Penicillin allergy
• Hypersensitivity (or cross-allergy) to other beta-lactams, such as cephalosporins

Cautions

• Breastfeeding
• Renal impairment 
• Hepatic impairment
• Elderly
• Massive doses or high-dose treatment for more than 5 days
• Skin sensitisation (when handling the medicine)
• History of allergy, especially to medicines
• IM depot injection (in diabetics)
• Prolonged use
• Syphilis or neurosyphilis
• Sodium-controlled diet

Forms avail. in SA and covered in this monograph: inj

Dosages below include:

• South African Standard Treatment Guidelines indications and dosages
• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

Infections caused by: Some aerobic Gram-positive microorganisms, such as Bacillus anthracis, Corynebacterium diphtheriae, Haemolytic streptococci (including Streptococcus pyogenes), Listeria monocytogenes, Streptococcus pneumoniae, Streptococcus viridans, Aerobic Gram-negative microorganisms, such as Neisseria gonorrhoeae, Neisseria meningitidis, Pasteurella multocida, Some anaerobic microorganisms, such as Actinomyces israelii, Fusobacterium nucleatum and Fusobacterium necrophorum, Gram-positive sporing bacilli (including Clostridium tetani and Clostridium perfringens (welchii)), Gram-positive cocci (including peptostreptococcus), Borrelia bugdorferi, Capnocytophaga canimorosus, Leptospirae, Streptobacillus moniliformis and spirrillum minus, Treponema pallidum 

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Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

South African Standard Treatment Guidelines indications and dosages

Infective endocarditis
- Empiric therapy (native valve) (Additional agent required)
- Directed therapy (native valve) for streptococcal fully susceptible to penicillin (MIC: <0.2mg/l)
- Directed therapy (native valve) for streptococcal moderately susceptible to penicillin (MIC: 0.12-0.5mg/l) (Additional agent required)
- Directed therapy (native valve) for streptococcal moderately resistant to penicillin (MIC: 0.5-4mg/l) Enterococci and Abiotrophia spp. (nutritionally variant streptococci) (Additional agent required)
- Directed therapy (native valve) for enterococcal fully susceptible to penicillin (MIC: <4mg/l)
- Directed therapy (native valve) for enterococcal moderately resistant to penicillin (MIC: 0.5-4mg/l) Enterococci and Abiotrophia spp. (nutritionally variant streptococci) (Additional agent required)

• IV: 5 000 000U (five million units), 6hrly; Treatment duration: 4 weeks
  (STG, Adult 2019)

Meningococcal meningitis
- For confirmed meningococcal disease only 

• IV: 20 000 000 - 24 000 000U (twenty million to twenty four million units), dly in 4-6 divided doses; Treatment duration: 7 days 
  (STG, Adult 2019)

Pneumococcal meningitis
- If sensitive to penicillin

• IV: 20 000 000 - 24 000 000U (twenty million to twenty four million units), dly in 4-6 divided doses; Treatment duration: 10 days 
  (STG, Adult 2019)

Meningovascular syphilis (neurosyphilis)

• IV: 20 000 000U (twenty million units), dly in 4-6 divided doses; Treatment duration: 10 days
  (STG, Adult 2019)

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See additional prescribing points for administration directions

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South African registered indications and dosages

Prevention of recurrence of rheumatic fever

• IM: 200 000 U (two hundred thousand units), 12hrly

Patients with valvular heart disease undergoing surgery

• IV/IM: 2 000 000 U (2 million units) 30-60mins pre-operatively; Then: 1 000 000 U (1 million units), 6 hours after pre-operative dose

Infections caused by benzylpenicillin-sensitive microorganisms 

• IV/IM: 500 000-20 000 000 U (five hundred thousand to twenty million units), dly, in divided doses

Severe infections caused by benzylpenicillin-sensitive microorganisms 
- Meningitis
- Endocarditis
- Peritonitis  

• IV/IM: 20 000 000 U (twenty million units), dly

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In the treatment of beta-haemolytic streptococcal infections a therapeutic dose must be administered for ≥10 days

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Where doses of 2 million units or more are required, these should be administered by slow IV infusion at a rate of less than 500 000 units per minute, or by intermittent piggy-back infusion

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Indications and dosages registered in other jurisdictions

Wound infections
Pyogenic infections of the skin
Soft tissue infections
Infections of the nose, throat, nasal sinuses, respiratory tract and middle ear
Generalised infections
Septicaemia and pyaemia from susceptible bacteria
Acute and chronic osteomyelitis
Sub-acute bacterial endocarditis
Suspected meningococcal disease
Gas gangrene
Tetanus
Actinomycosis
Anthrax
Leptospirosis
Rat-bite fever
Listeriosis
Severe Lyme disease
Complications secondary to gonorrhoea and syphilis
- Gonococcal arthritis or endocarditis
- Neurosyphilis
Diptheria
Brain abscesses
Pasteurellosis

• IV/IM: 600-3600mg, divided into 4-6 doses, dly

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Higher doses (up to 14.4 g/day (24 mega units) in divided doses) may be given in serious infections such as adult meningitis by the IV route

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Bacterial endocarditis

• IV: 7.2-12g, dly in divided doses, administered as an infusion

Rapidly spreading gas gangrene

• IV: Max: 43.2g/24hrs

Meningococcal disease

• IV: 2.4g, 4hrly

Suspected meningococcal disease

• IV/IM: 1200mg, as a single dose

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If meningococcal disease is suspected general practitioners should give a single dose of benzylpenicillin sodium, before transferring the patient to hospital

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Prevention of Group B Streptococcal disease of the newborn

• IV/IM: Loading dose: 3g; Then: 1.5g, 4hrly until delivery

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Alternate sites should be used for repeated injections

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High doses should be administered by IV injection or infusion, with IV doses in excess of 1.2g (2 mega units) being given slowly, taking at least one minute for each 300 mg (0.5 mega unit) to avoid high levels causing irritation of the central nervous system and/or electrolyte imbalance

Paed. forms avail. in SA and covered in this monograph: inj

Paed. dosages below include:

• South African Standard Treatment Guidelines indications and dosages
• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

Infections caused by: Some aerobic Gram-positive microorganisms, such as Bacillus anthracis, Corynebacterium diphtheriae, Haemolytic streptococci (including Streptococcus pyogenes), Listeria monocytogenes, Streptococcus pneumoniae, Streptococcus viridans, Aerobic Gram-negative
microorganisms, such as Neisseria gonorrhoeae, Neisseria meningitidis, Pasteurella multocida, Some anaerobic microorganisms, such as Actinomyces israelii, Fusobacterium nucleatum and Fusobacterium necrophorum, Gram-positive sporing bacilli (including Clostridium tetani and Clostridium perfringens (welchii)), Gram-positive cocci (including peptostreptococcus), Borrelia bugdorferi, Capnocytophaga canimorosus, Leptospirae, Streptobacillus moniliformis and spirrillum minus, Treponema pallidum 

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

South African Standard Treatment Guidelines indications and dosages

Infective endocarditis
- Empiric treatment (Additional agent required)

• IV: 50 000U/kg (fifty thousand units per kilogram), 6hrly; Treatment duration: 4-6 weeks, the longer duration of therapy is used for patients with complications or prosthetic valves 
  (STG, Paed. 2017)

Diphtheria
- Parenteral treatment for patients unable to swallow: switch to oral as soon as patient able to swallow

• IV: 50 000U/kg (fifty thousand units per kilogram), 6hrly; Treatment duration: 14 days 
  (STG, Paed. 2017)

Prophylactic treatment for diphtheria contacts

• <6 years: IM: 600 000U (six hundred thousand units), as a single dose
•  >6 years: IM: 1 200 000U (one million two hundred thousand units), as a single dose
  (STG, Paed. 2017)

Confirmed meningococcal septicaemia

• IV: 100 000U/kg (one hundred thousand units per kilogram), immediately THEN 4hrly; Treatment duration: 7 days 
  (STG, Paed. 2017)

Early congenital syphilis
- Symptomatic baby

• IV: 50 000U/kg (fifty thousand units per kilogram), 12hrly; Treatment duration: 10 days
  (STG, Paed. 2017

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South African registered indications and dosages

Patients with valvular heart disease undergoing surgery

• IV: 50 000 U/kg (fifty thousand units per kilogram) administered 30-60mins pre-operatively; Then: 25 000 U/kg (twenty five thousand units per kilogram) administered 6 hours after pre-operative dose

Infections caused by benzylpenicillin-sensitive microorganisms 

Neonates

• IV: 50 000 U/kg/day (fifty thousand units per kilogram per day), in divided doses

Children

• IV: 10 000 - 50 000 U/kg/day (ten thousand to fifty thousand units per kilogram per day), in 4 divided doses

Severe infections caused by benzylpenicillin-sensitive microorganisms 

Neonates

• IV: 50 000 - 200 000 U/kg/day (fifty thousand to two hundred thousand units per kilogram per day)

Children

• IV: 300 000 - 400 000 U/kg/day (three hundred thousand to four hundred thousand units per kilogram per day)

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In the treatment of beta-haemolytic streptococcal infections a therapeutic dose must be administered for ≥10 days

---

Where doses of 2 million units or more are required, these should be administered by slow IV infusion at a rate of less than 500 000 units per minute, or by intermittent piggy-back infusion

---

Indications and dosages registered in other jurisdictions

Wound infections
Pyogenic infections of the skin
Soft tissue infections
Infections of the nose, throat, nasal sinuses, respiratory tract and middle ear
Generalised infections
Septicaemia and pyaemia from susceptible bacteria
Acute and chronic osteomyelitis
Sub-acute bacterial endocarditis
Suspected meningococcal disease
Gas gangrene
Tetanus
Actinomycosis
Anthrax
Leptospirosis
Rat-bite fever
Listeriosis
Severe Lyme disease
Complications secondary to gonorrhoea and syphilis
- Gonococcal arthritis or endocarditis
- Neurosyphilis
Diptheria
Brain abscesses
Pasteurellosis

Newborn Infants

• IV: 50mg/kg/day, in 2 divided doses

Between 1-4 weeks

• IV: 75mg/kg/day, in 3 divided doses

Between 1 month - 12 years

• IV/IM: 100mg/kg/day, in 4 divided doses; Max: 4g/24hrs

Older than 12 years

• See adult dosage

Meningococcal disease

Newborn infants

• IV: 100mg/kg/day, in 2 divided doses

Between 1-4 weeks

• IV: 150mg/kg/day, in 3 divided doses

Between 1 month - 12 years

• IV: 180-300mg/kg/day, in 4-6 divided doses; Max: 12g/24hrs

Older than 12 years

• See adult dosage

Suspected meningococcal disease

Younger than 1 year

• IV/IM: <1 year: 300mg, as a single dose

Between 1-9 years

• IV/IM: 600mg, as a single dose

Older than 10 years

• See adult dosage  

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If meningococcal disease is suspected general practitioners should give a single dose of benzylpenicillin sodium, before transferring the patient to hospital

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Dosing should not be more frequent than every 8 or 12 hours in premature babies and neonates, since renal clearance is reduced at this age and the mean half-life of benzylpenicillin may be as long as 3 hours

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Since infants have been found to develop severe local reactions to IM injections, IV treatment should preferably be used

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Alternate sites should be used for repeated injections

Pregnancy

• Safe
• Benzylpenicillin sodium has been taken by a large number of pregnant women and women of childbearing age without an increase in malformations or other direct or indirect harmful effects on the foetus having been observed

Breastfeeding

• Caution
• Although it is not known if benzylpenicillin sodium may be excreted into the breast milk of breastfeeding mothers, it is actively transported from the blood to milk in animals and trace amounts of other penicillins in human milk have been detected

Renal Impairment

• Caution; dose adjustment recommended
  - For doses of 0.6-1.2g (1-2 mega units) the dosing interval should be no more frequent than every 8-10 hours
  - For high doses, e.g. 14.4g (24 mega units) required for the treatment of serious infections such as meningitis, the
  dosage and dose interval of benzylpenicillin sodium should be adjusted in accordance with the following schedule:

CrCl (ml/min)	Dose (g)	Dose (mega units)	Dose interval (hrs)
125	1.2 or 1.8	2 or 3	2 or 3
60	1.2	2	4
40	0.9	1.5	4
20	0.6	1.0	4
10	0.6	1.0	6
Nil	0.3 or 0.6	0.5 or 1.0	6 or 8
The dose in the above table should be further reduced to 300mg (0.5 mega units) 8 hourly if advanced hepatic disease is associated with severe renal failure If haemodialysis is required, an additional dose of 300mg (0.5 mega units) should be given 6 hourly during the procedure

- Sodium overload and/or heart failure may occur if benzylpenicillin sodium is administered in sodium-containing solvents to patients who suffer from renal failure and/or heart failure. Therefore, for such patients, benzylpenicillin sodium should not be reconstituted in sodium-containing liquids such as sodium chloride injection or Ringer's solution

Hepatic Impairment

• Caution; no dose adjustment recommended
  Further dose adjustments are recommended when hepatic impairment is associated with renal impairment

Elderly

• Caution; no dose adjustment recommended
  Elimination may be delayed in elderly patients and dose reduction may be necessary

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Central nervous system toxicity
• Seizures

Genitourinary Disorders

• Interstitial nephritis

Immune, Blood and Lymphatic System Disorders

• Haemolytic anaemia
• Granulocytopenia (neutropenia)
• Agranulocytosis
• Leucopenia  
• Thrombocytopenia
• Jarisch-Herxheimer reaction
• Hypersensitivity
  - Rashes
  - Fever
  - Serum sickness
• Anaphylactic reactions

• Oral contraceptives
• Methotrexate
• Probenecid

Other

• Laboratory tests
  - Urinary glucose test
  - Coomb's tests
  - Tests for urinary or serum proteins
  - Tests which use bacteria e.g. Guthrie test

None routine. Specific cases may require

• Electrolytes
• Renal function
• Hepatic function
• Full blood count (high dose therapy)
• Cardiac function (high dose therapy)

Additional observations

• Signs and symptoms of anaphylaxis (during first dose)
• Seizure activity

Administration directions

Concentration Using 600mg Vial	Addition of Sterile Water
200 000 U/ml	4.6ml
500 000 U/ml	3.6ml
1 000 000 U/2ml	1.6ml
1 000 000 U/5ml	4.6ml

 

Concentration Using 3g vial	Addition of Sterile Water
250 000 U/ml	17.8ml
500 000 U/ml	7.8ml
2 000 000 U/5ml	10.4ml
5 000 000 U/10ml	7.8ml

 

Benzylpenicillin sodium is a beta-lactam antibiotic. It is bacteriocidal by inhibiting bacterial cell wall biosynthesis.

Spectrum of activity: Some aerobic Gram-positive microorganisms, such as Bacillus anthracis, Corynebacterium diphtheriae, Haemolytic streptococci (including Streptococcus pyogenes), Listeria monocytogenes, Streptococcus pneumoniae, Streptococcus viridans, Aerobic Gram-negative
microorganisms, such as Neisseria gonorrhoeae, Neisseria meningitidis, Pasteurella multocida, Some anaerobic microorganisms, such as Actinomyces israelii, Fusobacterium nucleatum and Fusobacterium necrophorum, Gram-positive sporing bacilli (including Clostridium tetani and Clostridium perfringens (welchii)), Gram-positive cocci (including peptostreptococcus), Borrelia bugdorferi, Capnocytophaga canimorosus, Leptospirae, Streptobacillus moniliformis and spirrillum minus, Treponema pallidum

Injection (per vial) 600mg (1 million units)

• Bio-Pen 1 MU (Biotech Lab) (Discontinued)
• Benzyl penicillin Fresenius (Fresenius) originator (Discontinued)

Injection (per vial) 3g (5 million units)

• Bio-Pen 5 MU (Biotech Lab) (Discontinued)
• Benzyl penicillin Fresenius (Fresenius) originator (Discontinued)