Patient harm

Safety concerns related to the risk of confusion between salts of benzylpenicillin are system wide and have potential to affect any patient in a care setting where any of the salts are used.

Confusion between the different salts can result in the inadvertent prescribing, supply or administration of an incorrect penicillin salt. This may lead to:

• Potential treatment failure or delayed treatment of significant infections, if the correct preparation is not administered at the intended dose, frequency and via the relevant route
• Symptomatic overdose of penicillin, including convulsions and coma
• Severe neurovascular damage, oedema, cardiorespiratory arrest and death as a result of inadvertent administration via the incorrect route

High risk scenarios

Presence of a benzylpenicillin salt not routinely used within the clinical setting.

Supply from a setting where multiple salts are stocked.

Products

There are three injectable salts of benzylpenicillin available in England.

• Benzylpenicillin sodium
• Benzathine benzylpenicillin
• Procaine benzylpenicillin

There are known inconsistencies in nomenclature used in key reference sources, local formularies and clinical guidelines/protocols.

Product Summary of Product Characteristics (SPC) and product labelling may not always reflect the International Non-proprietary Name (INN). Benzathine benzylpenicillin may use alternative nomenclature which may contribute to potential confusion.

The dictionary of medicines and devices (DM+D) entry for benzylpenicillin sodium was updated in 2024. Systems using DM+D nomenclature may require updates to reflect the change.

Clinical use

The three salts are not clinically interchangeable.

Benzylpenicillin sodium is used to treat a range of infections and is regularly stocked and used within adult, paediatric and neonatal clinical areas across acute, out of hospital care and ambulance care settings.

Benzathine benzylpenicillin and procaine benzylpenicillin are indicated for syphilis, erysipelas, yaws and pinta as well as prophylaxis of other conditions. Used predominately by specialists such as those in sexual health, these salts are not routinely initiated or prescribed in non-specialist primary care settings. Supply is usually made from hospital pharmacy or specialist services.

Dose and strength

The numerical presentation of the indicated doses and the strengths of injectable preparations available are similar and may contribute to potential confusion.

Benzylpenicillin sodium

A short acting form of benzylpenicillin injection with individual adult doses of 600mg to 3 grams dependent on indication. Doses in neonates and children are dependent on indication and age or weight.

Products strengths available include 600mg and 1.2 grams.

Benzathine benzylpenicillin

A long-acting form of benzylpenicillin injection with adult doses of 1.2 million units or 2.4 million units, dependent on indication.

Product strengths available include 600,000 units, 1.2 million units and 2.4 million units.

Procaine benzylpenicillin

A long-acting form of benzylpenicillin which is combined with the local anaesthetic procaine. Although currently unlicensed in the UK, the British Association for Sexual Health and HIV (BASHH) Guidelines for Syphilis 2024 includes doses of 600,000 units – 2.4 million units.

Product strengths available include 600,000 units, 1.2 million units and 1.5 grams.

Administration

Benzylpenicillin sodium may be administered by the intramuscular or intravenous route.

Benzathine benzylpenicillin and procaine benzylpenicillin should be administered intramuscularly.

Inadvertent administration of the incorrect salt via the intravascular route may lead to harm, including severe neurovascular damage, severe oedema, cardiorespiratory arrest and death.

Time critical nature

The use of benzylpenicillin us used to treat a range of infections where therapy may be time critical.

Benzathine benzylpenicillin and procaine penicillin are not routinely kept as stock in clinical settings or on transport services as indications may be considered less time critical.

Risk

Examples of confusion between the salts in practice include:

• Prescribing the incorrect salt from an electronic drop-down list, leading to delays in therapy or administration of the incorrect salt.
• Supply of the incorrect salt via wholesale supply, leading to the inadvertent administration of benzathine benzylpenicillin instead of the intended benzylpenicillin sodium in a patient with symptoms of potential meningitis.
• Supply of the incorrect salt form via a pharmacy wholesale supply service for inclusion in ambulance service emergency bags. The ambulance service did not identify the incorrect supply and the incorrect salt was administered to a patient with symptoms of potential meningitis.
• Benzylpenicillin sodium inadvertently being prescribed as benzathine benzylpenicillin when transcribing medication during a transfer between care setting.
• Supply of benzylpenicillin sodium as ward stock for sexual health services instead of the intended preparations of benzathine benzylpenicillin.

Product selection

Inconsistencies in the nomenclature of the different salts and the similarities in the numerical presentation of the strengths contribute to the risk of potential confusion.

Awareness

The specialist use of two of the salts may contribute to a lack of awareness of availability and risk of confusion with different salts. Being unaware that different salts exist may lead individuals into a false perception that any product with a label of ‘benzylpenicillin’ is the product intended.

Delay to therapy

Supply of an incorrect salt product to a clinical area may delay time critical therapy. The highest risk of delayed therapy is with benzylpenicillin sodium for life threatening infections.

Mitigation

Ensure local clinical guidelines/protocols, prescribing systems and formularies are consistent in the nomenclature used for benzylpenicillin salts:

• Benzylpenicillin sodium
• Benzathine benzylpenicillin
• Procaine benzylpenicillin

Utilise electronic functionality to ensure electronic prescribing, dispensing and supply systems are set up to support users in choosing the correct product.

Review and rationalise stockholding of injectable benzylpenicillin salts to minimise the potential for selecting the incorrect product. Where more than one salt is stocked, e.g. hospital pharmacy, utilise opportunities to minimise selection errors such as separate locations and visual alerts.

Promote awareness among healthcare professionals responsible for the prescribing, supply and administration of medicines of the availability of different benzylpenicillin salts and risks associated with selecting the incorrect salt.