Patient harm

The use of effervescent or soluble tablets to deliver ‘part tablet doses’ of medication has been associated with patient harm. The inherent risk of inaccurate dosing related to this practice may lead to suboptimal therapy or symptomatic toxicity.

Known examples of harm include administration of a ‘whole tablet dose’ rather than the intended ‘part tablet dose’.  These have been known to result in overdoses of up to 16 times the intended dose, leading to seizures and the need for admission to hospital.

There are inconsistencies in key clinical reference sources, local formularies/clinical guidelines/protocols and practice related to the use of effervescent tablets when ‘part tablet doses’ are required, which is thought to contribute to the risk.

High risk scenarios

The small therapeutic dose range and impact of dose inaccuracy on the under 1 age group has led to a greater prevalence of harm in this age group however, all age groups are at risk of harm.

Transfer of care has the potential for inaccuracies in dosing to continue across the system.  Delays in identifying inaccuracies in those on long term therapy increases the risk of harm.

The medications most implicated with this risk are calcium and phosphate.  The use of calcium and phosphate effervescent tablets in the neonatal and paediatric population for enteral supplementation is common.

Clinical use

Licensed formulations of medicines may not be able to deliver the very small doses required in children and neonates either in liquid form or as a whole tablet.

Where a medication has no licensed oral liquid formulation available in the UK, but effervescent or soluble tablets are available, it is common practice for these to be used in children and neonates.  Healthcare professionals, caregivers and children are required to prepare and administer “part tablet doses” of the available effervescent/soluble tablets, which is an off-label use of a licensed product.

Calcium and phosphate supplementation

There are no licensed oral liquid calcium or phosphate products currently available in the UK. The use of effervescent tablets for enteral supplementation of calcium and phosphate in children and neonates is common.

Supplementation may be required short term for acute deficiency, or long-term to treat chronic conditions. Treatment may occur in any setting and therapy continued across the system.

With long term therapy children/neonates require frequent monitoring of their calcium or phosphate plasma levels to inform dosage adjustments.  Children and neonates on long term therapy may require frequent dosage adjustments.

The Neonatal and Paediatric Pharmacy Group (NPPG) have issued a position statement on Enteral Calcium and Phosphate Supplementation in Neonates and Children. 

Risk

There are inconsistencies in clinical reference sources, local formularies and clinical guidelines/protocols and practice regarding the appropriate product choice and use of effervescent tablets when ‘part tablet doses’ are required.  When ‘part tablet doses’ are required this may lead to confusion and unsafe practice among healthcare professionals and children/caregivers.

Dosage adjustment may be frequent, and a lack of documentation and communication may lead to inaccurate dosing.  Failure to perform adequate medicines reconciliation at transfers of care may amplify this risk.

Failure to undertake and act on therapeutic monitoring may lead to a delay in recognising inaccurate dosing.

Preparation and administration

Where it is necessary to use an effervescent/soluble tablet to prepare and administer a “part tablet dose” several steps and techniques are required to ensure accurate preparation and administration of the intended dose.

Steps required

Steps may include:

• Measurement of a specified proportion of the appropriately selected tablet formulation
• Dissolution of this part/whole tablet in a specified volume of diluent
• Withdrawal of a specific volume of the dissolved medication for administration

Key clinical reference sources, local formularies and clinical guidelines/protocols may omit or be inconsistent in the recommended method or measurements required for accurate dosing.

Displacement

Effervescent tablets can displace significant volumes of water on dissolution which varies between products.  Formulation specific guidance on preparation of doses is required to prevent dose preparation inaccuracy.

Preparation technique

Lack of uniformity of drug distribution in tablet fragments and prepared solutions where inaccurate tablet splitting, inadequate mixing or settling occur may lead to variable dosing.

The Neonatal and Paediatric Pharmacists Group state that when using effervescent tablets to administer “part tablet” doses, tablets dispersed into a smaller volume and then further diluted to the final volume once effervescence and dissolution are completed may result in a higher degree of dosing accuracy.  However, introducing a two step process may introduce error or not be practical for busy caregivers.

Risk

Failure to consider displacement when calculating the preparation volumes required for a “part dose” of an effervescent tablet or when switching between preparations, may lead to dosing inaccuracy.

Failure to document and communicate comprehensive and accurate information and directions could result in inadvertent over or under dosing due to incorrect preparation or, omission of therapy due to lack of clarity.

Dispersing part of a tablet into a solution may lead to dosing inaccuracy.

Known examples of harm include:

• Administration of a whole tablet dose instead of the intended ‘part tablet dose’ due to lack of information/clarity of intended dose
• Inaccurate dosing due to errors in the calculation of volume to be used for dissolution or administration
• Inaccurate dosing due to inaccurate preparation directions on prescription chart / dispensing label

Units of measurement

There is known variability in the nomenclature and description of products within the same medicinal class.  Effervescent/soluble tablets within the same medicinal class may contain differing amounts of the active ingredient.

The active component of the product may be expressed in terms of mass (e.g. gram or milligram) or mmol. Variability within calcium effervescent products also includes expression of the product as calcium salt or elemental calcium.

There are inconsistencies in the units used to describe both the product and clinically appropriate dose in key clinical references, local formularies and clinical guidelines/protocols.

Risk

There is potential confusion around the unit of measurement used for prescribing, supply, preparation and administration

Known examples of harm include:

• Errors when calculating mmol / mL from grams and milligrams
• Confusion between mmol and micromole
• Transcription errors from mmol to mL and vice versa

Supply

Quantity

The nature of effervescent and soluble tablets makes them unsuitable for ‘packing down’ to supply the exact quantity required for acute therapy courses.  Original packs are often supplied regardless of duration of therapy.

Preparation equipment

The equipment required by children or caregivers to accurately measure volumes for dissolution and volumes for administration should be provided at the supply stage.  Equipment required to accurately prepare and administer a ‘part dose of a whole tablet’ is likely to include a larger oral/enteral syringe for measurement of the initial volume of water required to disperse the tablet, a reusable plastic medicine pot in which the tablet can be dispersed, and a smaller oral/enteral syringe for measurement and administration of the required dose.

There may be a range of syringe sizes required to ensure accurate dosing and a stockholding review may be required to ensure access to suitable equipment at the supply stage.

Risk

Where a supply of medication exceeds the intended duration of therapy and this is not clearly documented or communicated, there is the potential for therapy to continue longer than intended.

Where more than one syringe size is required for the preparation and administration process, or an unsuitable volume size of syringe is provided, there is a risk of confusion and inaccurate measurement.

Failure to adequately communicate information to support accurate preparation may lead to confusion and inaccurate dosing.

Mitigation

There are opportunities to minimise potential harm where a part dose from a whole tablet of an effervescent or soluble tablet is required.

In context of the known harms, particular consideration should be given to calcium and phosphate supplementation.

Standardise practice

Standardise practice for “part tablet doses”:

• Rationalise products used in local/regional clinical guidelines/protocols and formularies to limit the risk of confusion between products.
• Ensure local clinical guidelines/protocols, prescribing systems, formularies and dispensing systems are consistent in the units used to express products and dosing guidance.
• Preparation guidance should be comprehensive, consistent and readily available to all healthcare professionals responsible for prescribing, validating or administering.

The NPPG position statement on Enteral Calcium and Phosphate Supplementation in Neonates and Children. includes suggested standardised preparation instructions for each brand of calcium and phosphate effervescent tablet currently available.  Consideration should be given to adopting the NPPG recommended preparation guidance to promote consistency across the system.

Awareness and knowledge

Ensure healthcare professionals responsible for the prescribing, supply and administration of medicines to children and neonates are aware of the risks associated with using effervescent/soluble tablets to deliver ‘part tablet doses’.

Ensure healthcare professionals involved in the practice of preparing and administering ‘part tablet doses’ have the adequate knowledge and skills required to undertake the task safely. Local training and competency requirements should meet standards outlined in any neonatal or paediatric medication administration policy.

Prescribing and validation

Ensure clear documentation and communication of the intended dose, formulation of product, units of measurement, method of preparation and duration of therapy or review date at the point of prescribing and at all transfers of care.  Prudent use of electronic prescribing functionality may support assurance that sufficient information on dosing and preparation is documented and communicated.

Ensure clarity in local policies and clinical guidelines/protocols regarding the intended number of tablets required to prepare the part dose, the volume of diluent required and the volume of the dissolved medicine for administration.  The responsibility for determining this information and documentation on the prescription where appropriate, should be unambiguous.

When the prescription is not clear, the intention of instruction with respect to the dose, units of measurement and duration should be ascertained.

Ensure dose increase/decreases are documented and communicated, including at transfers of care.

Supply

Ensure dispensing systems are set up to support users in clearly labelling the product with sufficient information to accurately prepare the dose.  This should include as a minimum:

• Number of tablet(s) required to prepare the dose
• Volume of diluent to be used
• Volume of resultant solution to be drawn up and administered

Ensure medication supply policies, dispensing systems and processes include provision of all syringes and equipment required for safe preparation.  It should be clear which syringe is required for each process and guidance should be provided on how to use all equipment provided.

Where original packs are used for dispensing ensure the intended duration of therapy, review date or stop date is documented and communicated to ensure therapy isn’t continued longer than intended.

Ensure caregivers/children are provided with comprehensive and easy to understand guidance on how to accurately prepare and administer.  Consideration should be given to include in dispensing standards the requirement for providing the Medicines for Children: How to give phosphate or calcium from effervescent tablets guide where appropriate.

Ensure caregivers/children are aware of the formulation that they are supplied with and that a switch in formulation or dose may require a change in the method of preparation.

Preparation and administration

Where prescription directions are not clear, the intention of instruction with respect to the dose, units of measurement and method of preparation should be ascertained in a timely fashion to ensure dose accuracy and avoid delays or omissions.

Ensure techniques and methodology regarding the dose preparation is communicated to the child/caregiver and that this has been adequately comprehended.  Consideration should be given to supply of standardised patient information leaflets.

Monitoring

Ensure adequate frequency of monitoring.  Clear documentation and communication of a clinically appropriate monitoring frequency may support early recognition of toxicity or suboptimal therapy.

Ensure healthcare professionals caring for, and caregivers/children of children and neonates using ‘part tablet doses’ are aware of the symptoms of toxicity to ensure early recognition and subsequent treatment.

Considerations

Standardisation of practice should not remove the need for individualised patient care.

When putting any mitigation strategies into practice there are considerations which may be locally unique which will require local assessment of the impact.

Product choice

A number of factors will influence product choice; including dosage required, availability of product, patient preference and the relative properties of the available agents.

Excipients

Effervescent tablets may contain significant quantities of sodium. Unlicensed oral liquid preparations may also contain sodium.

Consideration may also be given to potassium and/or sugar content.

The NPPG position statement on Enteral Calcium and Phosphate Supplementation in Neonates and Children notes a consideration related to carbonate which may limit the suitability of effervescent tablets in some children and neonates.

Acknowledgments

Information on prevalent risks associated with using effervescent and soluble tablets to deliver part doses of a whole tablet in paediatrics and neonates was provided by the Patient Safety Team at NHS England.

Thanks to the Neonatal and Paediatric Pharmacists Group (NPPG), Medicines for Children and the Patient Safety team at NHS England for their contributions.

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