Key points on fixed-dose combination medicines

Prescribers are increasingly faced with a range of fixed-dose combination medicines (FDCs) as an option in place of individual components prescribed separately. Switching patients from individual medicines to fixed-dose combination medicines must be done judiciously taking the following into consideration:

Assess patient’s need

  • Evidence for improved adherence with combination medicines is strongest when the reduction in pill burden is greatest1,2
    Assess the level of complexity involved in a patient's medicine regimen before choosing fixed-dose combination therapy.
  • A large number of factors contribute to non-adherence3
    Do not choose fixed-dose combination therapy solely on the possibility of improved adherence, convenience or cost advantages of the preparation.
  • Will the benefits outweigh the risks?

Table 1. Benefits and risks of fixed-dose combination medicines

Benefits2,4-6
Risks

Convenience

Decreased pill burden

Reduced cost

Being unable to adjust the doses of individual components in specific patients7,8

Misidentifying the causative medicine when the patient experiences side effects

Over- or under-dosing

Individualise therapy

  • It is best to start and stabilise patients on the individual components before starting the corresponding fixed-dose combination medicine9
    This facilitates adjustment of dose based on response and monitoring of adverse effects.
  • Be alert to unintended double- or under-dosing at the time of switching and discuss this with the patient
    show patients which medicines are being replaced by the combination medicine. Encourage them to use and maintain a Medicines List to keep track of the active ingredients as well as the brand names of their medicines.

Monitor response

  • Identify which component(s) in a fixed-dose combination are responsible for adverse effects if they occur
    Watch for signs and symptoms specific to individual components.
  • Patients taking fixed-dose combination medicines may be eligible for a Home Medicines Review
    Patients at risk of medicines-related problems are:
    • those taking five or more regular medicines
    • those taking more than 12 doses of medicine a day
    • those who have had a significant change to their medicine regimen in the past 3 months or who have symptoms of an adverse drug reaction.10

For more information

References
  1. Moulds RFW. Combination products – love them or loathe them? Aust Prescr 2001;24:127–9. [Full text]
  2. Llibre JM, Arribas JR, Domingo P, et al. Clinical implications of fixed-dose coformulations of antiretrovirals on the outcome of HIV-1 therapy. AIDS 2011;25:1683–90. [PubMed]
  3. Australian Government Department of Health and Ageing. Compliance Medicines Working Group Report to Pharmaceutical Benefits Advisory Committee. April 2010. [Online]  (accessed 11 December 2012).
  4. Simons LA, Ortiz M, Calcino G. Persistence with a single pill versus two pills of amlodipine and atorvastatin: the Australian experience, 2006–2010. Med J Aust 2011;195:134–7. [PubMed]
  5. Gupta AK, Arshad S, Poulter NR. Compliance, safety, and effectiveness of fixed-dose combinations of antihypertensive agents: a meta-analysis. Hypertension 2010;55:399–407. [PubMed]
  6. Bangalore S, Kamalakkannan G, Parkar S, et al. Fixed-dose combinations improve medication compliance: a meta-analysis. Am J Med 2007;120:713–9. [PubMed]
  7. Alphapharm Pty Limited. Glucovance. 2010. [Online] (accessed 9 October 2013).
  8. Merck Sharp & Dohme (Australia) Pty Limited. Juvicor Product Information. 2012. [Online] (accessed 28 February 2013).
  9. Gadzhanova S, Gillies M, Roughead E, et al. Fixed dose combination diabetes medicines - usage in the Australian veteran population. Aust Fam Physician 2011;40:811–5. [PubMed]
  10. Australian Government Department of Health and Ageing. Home Medicines Review (HMR). 20 August 2013. [Online] (accessed 9 October 2013).