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Home  »  E-Library  »  Health Management  »  Patient Safety  »  Improving the Safety and Cost of an Important Paediatric Medication

Improving the Safety and Cost of an Important Paediatric Medication

The Children's Hospital at Westmead

Abstract

In 2007, the Pharmacy Department at The Children's Hospital at Westmead (CHW) was manufacturing large volumes of Tacrolimus 0.5mg/mL suspension with a two month shelf-life. Our aim was to improve the extemporaneous formulation of Tacrolimus, as well as simplifying manufacturing, promoting safe administration in children and ensure cost effectiveness.

A literature review and a survey of compounding chemists and hospitals was conducted to review the various processes for the manufacture of Tacrolimus formulations. In September 2007, the Pharmacy started manufacturing a 1mg/mL Tacrolimus suspension, formulated to provide extended stability, good bioavailability, and improved patient adherence. The manufacturing of a 1mg/mL suspension ($4.65/1mg dose) is more cost effective than an equivalent amount of the 0.5mg/mL ($5.22/1mg dose). Cost savings over a six month period from January to June 2008 were $10,000.

Aim

To develop, over a six month period, an improved extemporaneous formulation of Tacrolimus that simplifies the manufacturing process, promotes ease and safety of use in paediatrics and is cost effective.

Nature of the Problem

Tacrolimus 0.5mg/mL suspension is one of the most frequently dispensed extemporaneous medications in the pharmacy at CHW, with annual use of approximately 60 000mLs, at an estimated cost of $156,600 for 2007. The existing 0.5mg/mL suspension has a two month expiry date, requiring frequent manufacture, which resulted in significant waste of unused suspension.

At the existing concentration, large volumes are required to provide doses and the 0.5mg/mL strength caused confusion in the milligrams and millilitres dosing. In addition, there were no funds to support expensive stability studies required to extend the shelf-life of the existing Tacrolimus formulations.

Extent of the Problem

Tacrolimus suspension is used in most paediatric hospitals. Many compounding chemists were using the Tacrolimus powder to manufacture the suspension because of the cost advantage and to avoid excipients which could make stability studies difficult to perform. However, there are reports in the literature of differences in the bioavailability of Tacrolimus products prepared using the powder versus the capsules, and the use of the capsules attracts S100 reimbursement, which may affect the overall cost. 

A literature survey indicated that a 1mg/mL suspension with a four month expiry could be prepared from the capsules (Elefante, 2006). It was decided to explore the possibility of using this formulation after consultation with the main prescribers of Tacrolimus suspension, due to the advantages of longer expiry and convenient dosing.

Extemporaneously manufactured medicines like the Tacrolimus suspension do not have a consumer medicine information leaflet, so this had to be developed to ensure appropriate counselling and compliance.

Strategic Importance

The problem of administering solid oral dosage forms to young children and patients with swallowing difficulties is a universal issue, especially when there are no commercially available liquid preparations. Furthermore, with the escalating cost of healthcare, our goal was to manufacture a cost-effective Tacrolimus suspension with an improved stability profile and a counselling leaflet that could be produced using existing resources. This is consistent with the NSW Health Plan of delivering high quality medicines and information to children and their carers within the existing boundaries of finite resources with safe and cost-effective quality use of medicine.

Planning and Implementing Solutions

  • Prior to October 2007, the Pharmacy Department at CHW was manufacturing a 0.5mg/mL Tacrolimus suspension and varying concentrations of topical formulations.
  • A literature review and survey of compounding chemists, paediatric hospitals and Paedpharm network were conducted to review the Tacrolimus formulations currently being used elsewhere, with a view to improving our formulation.
  • The survey questions were aimed at providing information on:
    • the types of extemporaneous Tacrolimus formulations in use
    • the most commonly used Tacrolimus preparations
    • the stability and bioavailability of the products and supporting data
    • the source of the active ingredient
  • Results from the surveys were used to re-assess and improve the current CHW formulation of Tacrolimus suspension.
  • A literature survey indicated that a 1mg/mL suspension with a four month expiry could be prepared from the capsules.
  • After consultation with the relevant prescribers of Tacrolimus suspension, it was decided to trial this formulation at our paediatric hospital because of the associated advantages of longer expiry and convenience in dosing.
  • A patient information sheet on Tacrolimus suspension was developed after a comprehensive literature search.
  • Prescribers, nurse educators, pharmacists and parents were informed of the date of the change to the new 1mg/mL Tacrolimus suspension.
  • After a month’s trial on patients using the 1mg/mL oral Tacrolimus suspension, a survey was conducted among health professionals and parents of patients taking the new Tacrolimus suspension to evaluate the new formulation and the usefulness of the parent information leaflet.
  • A cost analysis to manufacture the 1mg/mL Tacrolimus suspension versus the 0.5mg/mL suspension was done and the cost saving over a six month period from January to June 2008 was calculated.
  • Post study survey on hospitals using the new formulation was conducted in 2008.

Outcomes and Evaluation

  • None of the 17 compounding chemists or eight paediatric hospitals surveyed were manufacturing a Tacrolimus 1mg/mL oral suspension with an extended shelf life of four months.
  • The Parent Information leaflet was compiled and given to parents.
  • Feedback from 15 Pharmacists and two clinical nurse consultants indicated that the extended expiry of the new formulation was advantageous, dose calculation was easier and the Tacrolimus information sheet was useful, informative and easy to read and understand.
  • The carers’ feedback on the new 1mg/mL Tacrolimus formulation is shown in table one.

Table 1. Patient benefits of the 1mg/mL Tacrolimus suspension
  • Convenient to administer a smaller volume
  • Easier to calculate the doses for administration
  • Prevents dosing errors
  • Advantage of a longer expiry date
  • Decreased wastage of unused suspension
  • Has a parent information sheet which was very useful and informative

  • A smaller volume of Tacrolimus is being currently manufactured, even though the usage has increased. 17 500mLs of the 1mg/mL suspension was manufactured from January to June 2008, compared to 30 000 mLs of the 0.5mg/mL manufactured over the same period in 2007 (Figures 1 and 2).

Figure 1. Tacromilus Suspension 0.5mg in 1mL Manufactured from January to June 2007

tacrolimus_suspension

Figure 2. Tacromilus 1mg in 1mL Suspension Manufactured from January to June 2008

tacromilus_2008

  • The manufacture of a 1mg/mL suspension ($4.65/1mg dose) is more cost effective than an equivalent amount of the 0.5mg/mL ($5.22/1mg dose) with a current cost saving of approximately $1663 per month (Table 2). This supports the NSW initiative of smart choices in effectively managing finite resources that has evidence of cost benefits in delivering quality healthcare.

Table 2. Cost Analysis of Tacrolimus 1mg/mL manufactured vs. equivalent Tacrolimus 0.5mg/mL over a six month period (January to June 2008)
  Tacrolimus 1mg/ml Tacrolimus 0.5mg/ml
Volume required 17 500 mLs 35 000mLs (17 500mLs x 2)
Cost to manufacture $81 375 ($4.65/mL) $91 350 ($2.61/mL)

Sustaining Change

  • The 1mg/mL Tacrolimus suspension with a four month expiry has replaced the 0.5mg/mL suspension on the Hospital drug formulary.
  • The new formulation had an alert of change in strength stickers and parents were informed of this change.
  • Currently, all patients commencing treatment of Tacrolimus for the first time are supplied with the Tacrolimus information sheet.
  • Cost analysis indicates that the 1mg/mL suspension is more cost effective, with the potential to produce significant savings in reducing product wastage and staff preparation time.  The cost saving over a six month period from January to June 2008 was $10,000.

Future Scope

The new 1mg/mL Tacrolimus suspension formula has been shared with other paediatric hospitals within NSW and nationally. This study was presented at the Society of Hospital Pharmacists of Australia (SHPA) Federal conference in Sydney in 2007. The information has also been disseminated by the Paedpharm Network, which includes paediatric hospital pharmacists from Australia, New Zealand and internationally. A post-study survey indicates that many other paediatric hospitals have started manufacturing the 1mg/mL suspension with the clear evidence of improved stability, bioavailability and cost-effectiveness. An article is now being compiled for submission to the SHPA Journal of Pharmacy Practice and Research.

Reference

  • Elefante, A, et al 2006, ‘Long-term stability of a patient-convenient 1mg/mL suspension of Tacrolimus for accurate maintenance of stable therapeutic levels’, Bone Marrow transplantation, 37:781-784.

Contact


Co-ordinator, Service Improvement Unit
The Children's Hospital at Westmead
Phone: 02 9845 2093
 
 
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