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Natural Penicillin Antibiotic Pregnancy: §4.6 verbatim and in full: '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. Although it is not known if benzylpenicillin sodium may be excreted into the breast milk of nursing mothers, it is actively transported from the blood to milk in animals and trace amounts of other penicillins in human milk have been detected.' §4.2 also gives an intrapartum regimen: 'For the prevention of Group B Streptococcal disease of the newborn, a 3 g (5 mega units) loading dose should be given to the mother initially, followed by 1.5 g (2.5 mega units) every 4 hours until delivery.'

Benzylpenicillin (Penicillin G)

Brand names: Crystapen

Benzylpenicillin (penicillin G) is a narrow-spectrum beta-lactam antibiotic given parenterally for serious streptococcal, meningococcal, pneumococcal and other susceptible infections, including suspected meningococcal disease in the community.

Adult dose

Dose: Adults, general range: 600 mg to 3,600 mg (1 to 6 mega units) daily, divided into 4 to 6 doses, depending on the indication. Serious infections such as adult meningitis: higher doses up to 14.4 g/day (24 mega units) in divided doses by the intravenous route. Meningococcal disease, adults and children over 12 years: 2.4 g every 4 hours. Suspected meningococcal disease before transfer to hospital — a single dose: adults and children over 10 years 1,200 mg IV (or IM); children 1–9 years 600 mg IV (or IM); children under 1 year 300 mg IV (or IM). Bacterial endocarditis: 7.2 to 12 g (12 to 20 mega units) or more daily in divided doses by the intravenous route, often by infusion. Rapidly spreading gas gangrene: doses up to 43.2 g (72 mega units) per day may be necessary. Prevention of Group B Streptococcal disease of the newborn: a 3 g (5 mega units) loading dose to the mother, then 1.5 g (2.5 mega units) every 4 hours until delivery.
Route: Intramuscular or intravenous — §4.2: 'Route of administration: Intramuscular, intravenous.' and 'The following dosages apply to both intramuscular and intravenous injection. Alternate sites should be used for repeated injections.' High doses must go IV: 'High doses should be administered by intravenous injection or infusion, with intravenous 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.'
Frequency: Divided into 4 to 6 doses daily for the general adult range; every 4 hours for meningococcal disease in adults and children over 12 years; every 4 hours for the intrapartum Group B Streptococcus regimen after the loading dose.
Max: No maximum is stated for adults anywhere in the fetched SPC — the words 'maximum' and 'do not exceed' do not appear against any adult regimen. The highest adult daily figure in the retrieved text belongs to one specific indication and is not a general ceiling: §4.2 verbatim — 'Doses up to 43.2 g (72 mega units) per day may be necessary for patients with rapidly spreading gas gangrene.' For serious infections such as adult meningitis the stated upper figure is 14.4 g/day (24 mega units) in divided doses, and for bacterial endocarditis it is '7.2 to 12 g (12 to 20 mega units) or more' daily. The '24 g/day' ceiling currently shown on this page does not appear anywhere in this SPC.
VERBATIM §4.2 — Adults: '600 to 3,600 mg (1 to 6 mega units) daily, divided into 4 to 6 doses, depending on the indication. 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 intravenous route. In bacterial endocarditis, 7.2 to 12 g (12 to 20 mega units) or more may be given daily in divided doses by the intravenous route, often by infusion. Doses up to 43.2 g (72 mega units) per day may be necessary for patients with rapidly spreading gas gangrene.' Meningococcal disease, 'Adults and children over 12 years: 2.4 g every 4 hours.' Suspected meningococcal disease: 'If meningococcal disease is suspected general practitioners should give a single dose of benzylpenicillin sodium, before transferring the patient to hospital, as follows: Adults and children over 10 years: 1,200 mg IV (or IM); Children 1-9 years: 600 mg IV (or IM); Children under 1 year: 300 mg IV (or IM).' Group B Streptococcus: 'For the prevention of Group B Streptococcal disease of the newborn, a 3 g (5 mega units) loading dose should be given to the mother initially, followed by 1.5 g (2.5 mega units) every 4 hours until delivery.' || RECONSTITUTION (1200 mg vials), §4.2 verbatim: 'Only freshly prepared solutions should be used. Reconstituted solutions of benzylpenicillin sodium are intended for immediate administration. Intravenous Injection: 1200 mg (2 mega units) dissolved in at least 8 ml of Sodium Chloride Injection BP or Water for Injections BP. Intravenous Infusion: It is recommended that 1200 mg (2 mega units) should be dissolved in at least 20 ml of Sodium Chloride Injection BP or Water for Injections BP.' These are MINIMUM volumes, not a fixed concentration, so no mg/mL figure can be derived from them. || SODIUM-FREE DILUENT IN RENAL OR CARDIAC FAILURE, §4.2 verbatim: '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 BP or Ringer's solution.' || ELECTROLYTES, §4.2: 'High dosage of benzylpenicillin sodium may result in hypernatraemia and hypokalaemia unless the sodium content is taken into account.' §4.4: '1200 mg benzylpenicillin contains 77.4mg (3.36 mmol) of sodium… equivalent to 3.86% of the recommended maximum daily dietary intake of sodium for an adult. 5 dosage units (6g) reflects the lowest number of dosage units for which the threshold of 17mmol (391mg) of sodium is reached.' || ELDERLY, §4.2 verbatim: 'Elimination may be delayed in elderly patients and dose reduction may be necessary.' || TRUNCATION: §4.4 was cut at the source-fetch limit as §4.5 began, so interactions were not retrieved.

Paediatric dose

Dose: 100 mg/kg/day
Route: Intravenous or intramuscular. §4.2: 'Since infants have been found to develop severe local reactions to intramuscular injections, intravenous treatment should preferably be used.'
Frequency: AGE-BANDED — this figure is the TOTAL DAILY dose for children aged 1 month to 12 years, divided into 4 doses. Neonates and infants under 1 month, and meningococcal disease at any age, use different figures (see notes).
Max: Maximum 4 g/day — §4.2 states the daily total for children aged 1 month to 12 years is 'not exceeding 4 g/day'. For meningococcal disease in the same age band the SPC gives a different ceiling, 'not exceeding 12 g/day'.
⚠️ AGE-BANDED AND INDICATION-BANDED — the 100 figure above applies ONLY to general use in children aged 1 month to 12 years. §4.2 verbatim, in full: 'Children aged 1 month to 12 years 100 mg/kg/day in 4 divided doses; not exceeding 4 g/day. Infants 1-4 weeks 75 mg/kg/day in 3 divided doses. Newborn Infants 50 mg/kg/day in 2 divided doses.' MENINGOCOCCAL DISEASE is dosed separately and much higher — §4.2 verbatim: 'Children 1 month to 12 years: 180-300 mg/kg/day in 4-6 divided doses, not exceeding 12 g/day. Infants 1-4 weeks: 150 mg/kg/day in 3 divided doses. Newborn infants: 100 mg/kg/day in 2 divided doses. Adults and children over 12 years: 2.4 g every 4 hours.' SUSPECTED MENINGOCOCCAL DISEASE, PRE-HOSPITAL, single fixed doses (not weight-based) — §4.2 verbatim: 'Adults and children over 10 years: 1,200 mg IV (or IM); Children 1-9 years: 600 mg IV (or IM); Children under 1 year: 300 mg IV (or IM).' PREMATURE BABIES AND NEONATES — §4.2 verbatim: 'Dosing should not be more frequent than every 8 or 12 hours in this age group, since renal clearance is reduced at this age and the mean half-life of benzylpenicillin may be as long as 3 hours. Since infants have been found to develop severe local reactions to intramuscular injections, intravenous treatment should preferably be used.' Note this frequency rule conflicts with a 3-divided-dose or 2-divided-dose reading at the extremes of prematurity — follow the SPC text and local neonatal guidance. CONCENTRATION: left null deliberately. The SPC gives only minimum reconstitution volumes ('at least 8 ml' for IV injection, 'at least 20 ml' for IV infusion of a 1200 mg vial), which do not define a fixed mg/mL, so no figure can be entered without inventing one. Verify every paediatric figure against a children's formulary before use.

Dose adjustments

Renal

§4.2 Patients with renal insufficiency, verbatim: 'For doses of 0.6-1.2 g (1-2 mega units) the dosing interval should be no more frequent than every 8-10 hours. For high doses e.g. 14.4 g (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:' ⚠️ CAUTION — that creatinine-clearance schedule is CORRUPTED in the fetched text: the comparator symbols and the row and column boundaries were lost, so the raw string reads 'Creatinine clearance (ml per minute) Dose (g) Dose (mega units) Dosing interval (hours) 125 1.2 or 1.8 2 or 3 2 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 8'. No creatinine-clearance threshold and no banded dose is asserted here — read the table directly from the SPC. Also verbatim: 'If haemodialysis is required, an additional dose of 300 mg (0.5 mega units) should be given 6 hourly during the procedure.' Diluent, §4.2: in renal failure and/or heart failure benzylpenicillin sodium 'should not be reconstituted in sodium-containing liquids such as Sodium Chloride Injection BP or Ringer's solution'. Safety, §4.4: 'In the presence of impaired renal function, large doses of penicillin can cause cerebral irritation, convulsions and coma.'

Hepatic

No standalone hepatic-impairment dosing statement appears in any fetched section (§4.2, §4.3, §4.4, §4.6, §4.8). The only hepatic reference sits inside the renal schedule — §4.2 verbatim: 'The dose in the above table should be further reduced to 300 mg (0.5 mega units) 8 hourly if advanced liver disease is associated with severe renal failure.'

Dose independently re-sourced from UK Summary of Product Characteristics (SPC) via the eMC — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Paediatric weight-based calculator

⚠️ AGE-BANDED AND INDICATION-BANDED — the 100 figure above applies ONLY to general use in children aged 1 month to 12 years. §4.2 verbatim, in full: 'Children aged 1 month to 12 years 100 mg/kg/day in 4 divided doses; not exceeding 4 g/day. Infants 1-4 weeks 75 mg/kg/day in 3 divided doses. Newborn Infants 50 mg/kg/day in 2 divided doses.' MENINGOCOCCAL DISEASE is dosed separately and much higher — §4.2 verbatim: 'Children 1 month to 12 years: 180-300 mg/kg/day in 4-6 divided doses, not exceeding 12 g/day. Infants 1-4 weeks: 150 mg/kg/day in 3 divided doses. Newborn infants: 100 mg/kg/day in 2 divided doses. Adults and children over 12 years: 2.4 g every 4 hours.' SUSPECTED MENINGOCOCCAL DISEASE, PRE-HOSPITAL, single fixed doses (not weight-based) — §4.2 verbatim: 'Adults and children over 10 years: 1,200 mg IV (or IM); Children 1-9 years: 600 mg IV (or IM); Children under 1 year: 300 mg IV (or IM).' PREMATURE BABIES AND NEONATES — §4.2 verbatim: 'Dosing should not be more frequent than every 8 or 12 hours in this age group, since renal clearance is reduced at this age and the mean half-life of benzylpenicillin may be as long as 3 hours. Since infants have been found to develop severe local reactions to intramuscular injections, intravenous treatment should preferably be used.' Note this frequency rule conflicts with a 3-divided-dose or 2-divided-dose reading at the extremes of prematurity — follow the SPC text and local neonatal guidance. CONCENTRATION: left null deliberately. The SPC gives only minimum reconstitution volumes ('at least 8 ml' for IV injection, 'at least 20 ml' for IV infusion of a 1200 mg vial), which do not define a fixed mg/mL, so no figure can be entered without inventing one. Verify every paediatric figure against a children's formulary before use.

Verify in a children's formulary

Contraindications

  • Allergy to penicillins — §4.3 verbatim: 'Allergy to penicillins.'
  • Hypersensitivity to any ingredient of the preparation — §4.3 verbatim: 'Hypersensitivity to any ingredient of the preparation.'
  • Cross-allergy to other beta-lactams — §4.3 verbatim: 'Cross allergy to other beta-lactams such as cephalosporins should be taken into account.'
  • Not in §4.3 but a §4.4 absolute bar: 'Benzylpenicillin should be used with caution in patients with a history of non-severe hypersensitivity reactions to any other beta-lactam antibiotics (e.g. cephalosporins or carbapenems) and not at all in patients with history of severe hypersensitivity reactions.'
  • §4.4 was truncated at the source-fetch limit as §4.5 began; the interaction section was not retrieved and must be read on the eMC.

Side effects

  • Very common (>10%): 'Patients undergoing treatment for syphilis or neurosyphilis with benzylpenicillin may develop a Jarisch-Herxheimer reaction.'
  • Common (1-10%): 'Hypersensitivity to penicillin in the form of rashes (all types), fever, and serum sickness may occur (1-10% treated patients). These may be treated with antihistamine drugs.'
  • Rare (0.01%-0.1%): anaphylactic reactions ('<0.05% treated patients')
  • Rare (0.01% - 0.1%): 'Granulocytopenia (neutropenia), agranulocytosis and leucopenia have been reported in patients receiving prolonged high doses of benzylpenicillin sodium (eg. Subacute bacterial endocarditis).' Frequency not known: anaemia, thrombocytopenia
  • Diarrhoea caused by Clostridium difficile (blood and lymphatic system disorders section, §4.8)
  • Rare: 'Central nervous system toxicity, including convulsions, has been reported with massive doses over 60 g per day and in patients with severe renal impairment.' Frequency not known: metabolic encephalopathy
  • Rare: 'Interstitial nephritis has been reported after intravenous benzylpenicillin sodium at doses of more than 12 g per day.'
  • Frequency not known: angioedema; acute generalised exanthematous pustulosis (AGEP), pruritus, maculo-papular rash, rash morbilliform, erythema
  • Severe cutaneous adverse reactions (SCARs) — Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, acute generalised exanthematous pustulosis — 'have been reported with beta-lactam antibiotics, including penicillins'
  • §4.4 adds: 'Massive doses of Benzylpenicillin Sodium can cause hypokalaemia and sometimes hypernatraemia.'

Monitoring

  • Observe after every dose — §4.4 verbatim: 'Patients should be observed for 30 minutes after administration and if an allergic reaction occurs the drug should be withdrawn and appropriate treatment given.'
  • High-dose courses — §4.4 verbatim: 'In patients undergoing high-dose treatment for more than 5 days, electrolyte balance, blood counts and renal functions should be monitored.'
  • Electrolytes with large doses — §4.2: 'High dosage of benzylpenicillin sodium may result in hypernatraemia and hypokalaemia unless the sodium content is taken into account.' §4.4: 'Massive doses of Benzylpenicillin Sodium can cause hypokalaemia and sometimes hypernatraemia. Use of a potassium-sparing diuretic may be helpful.'
  • Sodium load in patients on a low-salt diet — §4.4: '1200 mg benzylpenicillin contains 77.4mg (3.36 mmol) of sodium… equivalent to 3.86% of the recommended maximum daily dietary intake of sodium for an adult. 5 dosage units (6g) reflects the lowest number of dosage units for which the threshold of 17mmol (391mg) of sodium is reached.'
  • Superinfection — §4.4: 'Prolonged use of benzylpenicillin may occasionally result in an overgrowth of non-susceptible organisms or yeast and patients should be observed carefully for superinfections.'
  • Diarrhoea — §4.4: 'Pseudomembranous colitis should be considered in patients who develop severe and persistent diarrhoea during or after receiving benzylpenicillin. In this situation, even if Clostridium difficile is only suspected, administration of benzylpenicillin should be discontinued and appropriate treatment given.'
  • Skin — §4.4: severe cutaneous adverse reactions (SJS, TEN, DRESS, AGEP) have been reported with beta-lactams; 'If a severe allergic reaction or SCAR occurs during treatment with benzylpenicillin, treatment with the medicinal product should be discontinued and appropriate measures taken.'
  • Neurological status in renal impairment — §4.4: 'In the presence of impaired renal function, large doses of penicillin can cause cerebral irritation, convulsions and coma.'
  • Handling — §4.4: 'Skin sensitisation may occur in persons handling the antibiotic and care should be taken to avoid contact with the substance.'

Clinical monograph

How it works

It inhibits bacterial cell-wall peptidoglycan synthesis by binding penicillin-binding proteins, producing a bactericidal effect against susceptible, predominantly Gram-positive and certain Gram-negative organisms.

Prescribing in practice

  • Contraindicated in penicillin hypersensitivity and used with caution in those with a history of significant beta-lactam allergy, as cross-reactivity and anaphylaxis can occur.
  • It is acid-labile and not effective orally, so must be given by injection or infusion.
  • Most beta-lactamase-producing staphylococci are resistant, so it is not appropriate empirically for staphylococcal infection.

Monitoring

Monitor clinical response and, with high-dose or prolonged therapy or renal impairment, watch renal function, electrolytes and for neurotoxicity.

Counselling the patient

  • This penicillin is given by injection in hospital or by paramedics for serious infection.
  • Report any rash, swelling or breathing difficulty immediately.
  • Always mention previous penicillin reactions to staff.

Evidence & guidelines

Benzylpenicillin remains a guideline-recommended agent for susceptible streptococcal and meningococcal infections and for pre-hospital treatment of suspected meningococcal disease.

Reference: Meningitis Research Foundation; NICE Bacterial Meningitis NG33; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

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