Adverse effects of fixed-dose combination medicines

Identifying the active ingredient causing adverse effects

Some adverse effects of fixed-dose combination medicines (FDCs) are common to many active ingredients so it may be difficult to identify which medicine is responsible. Watch for signs and symptoms specific to individual components.

Adverse effects are often overlooked in older people because associated signs and symptoms may be confused with the underlying disease or normal ageing.1 Sometimes the only way to know whether a symptom is a side effect is to temporarily stop the medicine and see if the symptoms improve.2

Make sure patients are aware that if they develop adverse effects to the fixed-dose combination medicine (which requires them to stop it) they will most likely need to restart one of its components.

Patients taking fixed-dose combination medicines may be eligible for a Home Medicines Review if they are taking more than 12 doses of medicine a day, have had a significant change to their medicine regimen in the past 3 months or have symptoms of an adverse drug reaction.3

Start with the individual medicines first

In some situations it is best to start and stabilise patients on individual tablets before starting the corresponding fixed-dose combination medicine.4 If patients start treatment using fixed-dose combination medicines, ensure that the relatively inflexible dosing of fixed-dose combination medicines is compatible with their requirements.

Dose adjustment of individual active ingredients is required in some situations:

  • Older patients: for example, the metformin–glibenclamide fixed-dose combination medicine may cause hypoglycaemia if patients taking it have not previously been stabilised on a longer-acting sulfonylurea.4
  • Patients with kidney impairment: for example, the sitagliptin–simvastatin fixed-dose combination medicine does not provide an option for dose adjustment of the sitagliptin component (lower doses are required in this population).5

For more information

  1. Rambhade S, Chakarborty A, Shrivastava A, et al. A survey on polypharmacy and use of inappropriate medications. Toxicol Int 2012;19:68–73. [PubMed]
  2. Bain KT, Holmes HM, Beers MH, et al. Discontinuing medications: a novel approach for revising the prescribing stage of the medication-use process. J Am Geriatr Soc 2008;56:1946–52. [PubMed]
  3. Australian Government Department of Health and Ageing. Home Medicines Review (HMR). 20 August 2013. [Online] (accessed 9 October 2013).
  4. Alphapharm Pty Limited. Glucovance. 2010. [Online] (accessed 9 October 2013).
  5. Merck Sharp & Dohme (Australia) Pty Limited. Juvicor Product Information. 2012. [Online] (accessed 28 February 2013).