Summary of Product Characteristics Updated 15-Sep-2016 | Genus Pharmaceuticals
Route of administration:Intramuscular, intravenous.
Preparation of solutions:
Pharmaceutical preparationOnly freshly prepared solutions should be used. Reconstituted solutions of benzylpenicillin sodium are intended for immediate administration.
1200 mg vialsIntravenous 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.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.
Dosage and administration:The following dosages apply to both intramuscular and intravenous injection.Alternate sites should be used for repeated injections.
Adults600 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.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.High dosage of benzylpenicillin sodium may result in hypernatraemia and hypokalaemia unless the sodium content is taken into account.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.
Children aged 1 month to 12 years100 mg/kg/day in 4 divided doses; not exceeding 4 g/day.
Infants 1-4 weeks75 mg/kg/day in 3 divided doses.
Newborn Infants50 mg/kg/day in 2 divided doses.
|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 diseaseIf 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)|
Premature babies and neonatesDosing 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.
Patients with renal insufficiencyFor 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:
|Creatinine clearance (ml per minute)||Dose (g)||Dose (mega units)||Dosing interval (hours)|
|125||1.2 or 1.8||2 or 3||2 3|
|Nil||0.3 or 0.6||0.5 or 1.0||6 8|
Elderly PatientsElimination may be delayed in elderly patients and dose reduction may be necessary.
Blood and Lymphatic System Disorders
Rare (0.01% - 0.1%)Haemolytic anaemia and granulocytopenia (neutropenia), agranulocytosis, leucopenia and thrombocytopenia, have been reported in patients receiving prolonged high doses of benzylpenicillin sodium (eg. Subacute bacterial endocarditis).
Immune System Disorders
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%)More rarely, anaphylactic reactions have been reported (<0.05% treated patients).
Nervous System Disorders
Rare (0.01%-.01%)Central nervous system toxicity, including convulsions, has been reported with massive doses over 60 g per day and in patients with severe renal impairment.
Renal and Urinary Disorders
Rare (0.01%-0.1%)Interstitial nephritis has been reported after intravenous benzylpenicillin sodium at doses of more than 12 g per day.
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
General Properties:Benzylpenicillin sodium is a beta-lactam antibiotic. It is bacteriocidal by inhibiting bacterial cell wall biosynthesis.
Breakpoints:The tentative breakpoints (British Society for Antimicrobial Chemotherapy, BSAC) for benzylpenicillin sodium are as follows:
|Organism||S ≤ (mg/L)||I (mg/L)||R ≥ (mg/L)|
|Streptococcus pneumoniae Neisseria gonorrhoeae||0.06||0.12-1.0||2.0|
|Haemolytic streptococci Staphylococci Moraxella catarrhalis Haemophilus influenzae||0.12||0.25|
|Rapidly growing anaerobes||1.0||2.0|
Susceptibility:The prevalence of resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. The following table gives only approximate guidance on probabilities whether microorganisms will be susceptible to benzylpenicillin sodium or not.
|Susceptible and intermediately susceptible microorganisms|
|Type of Microorganism||Microorganism||Range of acquired resistance|
|Aerobic Gram-positive microorganisms||• Bacillus anthracis||0%**|
|• Corynebacterium diphtheriae||0%*|
|• Haemolytic streptococci (including Streptococcus pyogenes)||0%*-3%**|
|• Listeria monocytogenes||0%**|
|• Streptococcus pneumoniae||4%*-40%**|
|• Streptococcus viridans||3-32%*|
|Aerobic Gram-negative microorganisms||• Neisseria gonorrhoeae||9-10%*|
|• Neisseria meningitidis||18%*|
|• Pasteurella multocida||0%***|
|Anaerobic microorganisms||• Actinomyces israelii||8%**|
|• Fusobacterium nucleatum and Fusobacterium necrophorum||Usually sensitive|
|• Gram-positive sporing bacilli (including Clostridium tetani and Clostridium perfringens (welchii))||14%**|
|• Gram-positive cocci (including peptostreptococcus)||7%*|
|Other microorganisms||• Borrelia bugdorferi||Usually sensitive|
|• Capnocytophaga canimorosus||Usually sensitive|
|• Leptospirae||Usually sensitive|
|• Streptobacillus moniliformis and spirrillum minus||Usually sensitive|
|• Treponema pallidum||0%***|
|Type of Microorganism||Microorganism||Range of acquired resistance|
|Aerobic Gram-positive microorganisms||• Coagulase negative Staphylococcus||71-81%*|
|• Enterococcus Spp||Resistant|
|• Staphylococcus aureus||79-87%*|
|Aerobic Gram-negative microorganisms||• Acinetobacter||Resistant|
|• Bordetella pertussis||Generally resistant|
|• Brucella spp.||Resistant|
|• Enterobacteriaceae (including Escherichia coli, Salmonella, Shigella, Enterobacter, Klebsiella, Proteus, Citrobacter).||Generally resistant|
|• Haemophilus influenzae||Resistant|
|Anaerobic microorganisms||• Bacteroides fragilis||100%***|
Known Resistance Mechanisms and Cross-resistancePenicillin resistance can be mediated by alteration of penicillin binding proteins or development of beta-lactamases.Resistance to penicillin may be associated with cross-resistance to a variety of other beta lactam antibiotics either due to a shared target site that is altered, or due to a beta-lactamase with a broad range of substrate molecules. In addition to this, cross resistance to unrelated antibiotics can develop due to more than one resistance gene being present on a mobile section of DNA (e.g. plasmid, transposon etc) resulting in two or more resistance mechanisms being transferred to a new organism at the same time.
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