Co-administering diclofenac with intravenous paracetamol or Hartmann's solution

Abstract

Since the withdrawal of Dyloject™ (Therabel Pharma UK Ltd, Maidenhead, Berkshire, UK) in May 2010, Novartis Pharmaceuticals have been the sole supplier of intravenous diclofenac in the UK, and advise that the drug is administered intravenously after dilution into 100-500 ml glucose 5% or sodium chloride 0.9%, with the addition of 1 ml sodium bicarbonate 4.2% or 0.5 ml sodium bicarbonate 8.4% 1. Owingto the complexity of this preparation, some anaesthetists have adopted the practice of either diluting diclofenac into a 100-ml vial of paracetamol, or adding it to an infusion of Hartmann's solution without pH adjustment. To my knowledge, there have been no instances of adverse events' being attributed to these practices, and there appears to be no known interaction between paracetamol and diclofenac (personal communication, Novartis Pharmaceuticals Ltd Medical Information, 08/03/2013). In correspondence to gain further information about the reasons for the manufacturer's dilution requirements, Novartis Pharmaceuticals advised that diclofenac is “practically insoluble in water and the overall solubility depends exponentially on pH”, recommending alkalinisation to a pH of 6.8–8.3 for preventing supersaturation and crystallisation (personal communication, Novartis, as above). Intravenous preparations of paracetamol maintain a pH of approximately 5.5 (personal communication, Bristol-Myers Squibb Pharmaceutical Ltd Medical Information, 19/03/2013), thus increasing the risk of precipitation with diclofenac admixture. Hartmann's solution has a pH between 5.0 and 7.0 2. Clearly, adding diclofenac to either solution risks supersaturation or crystallisation, with the potential for harm to the patient. Furthermore, Novartis re-iterated that “diluting the (diclofenac) ampoules with any solution other than that recommended in the Summary of Product Characteristics would be outside of licence and use would be the responsibility of the prescribing physician” (personal communication, Novartis, as above). Based on this information, the practice of mixing diclofenac with either paracetamol or Hartmann's solution for intravenous injection cannot be recommended, for possible risk of causing patient harm.