Australia to adopt INNs

The Therapeutic Goods Administration (TGA) has announced that it will proceed with international harmonisation of drug names used in Australia from April 2016. For the past decade or so, since the United Kingdom moved to the World Health Organization’s International Nonproprietary Names (INNs), we’ve been in the anomalous situation of using former British Approved Names despite these no longer being used in the UK (nor listed in the British Pharmacopoeia). The TGA website has a list of affected drugs.

Some changes are trivial:

  • Substitution of “ph” with “f” (e.g. cefalexin, guaifenesin)
  • Substitution of “y” with “i” (e.g. amoxicillin, ciclosporin)
  • Substitution of “th” with “t” (e.g. indometacin)

Others are more significant (and will require dual-labelling for 3 years), for example:

  • Dosulepin (dothiepin)
  • Formoterol (eformoterol)
  • Furosemide (frusemide)
  • Glycopyrronium bromide (glycopyrrolate)
  • Hydroxycarbamide (hydroxyurea)
  • Lidocaine (lignocaine)

On the contentious subject of adrenaline vs epinephrine, the TGA has followed the UK practice where dual-labelling “adrenaline (epinephrine)” will be used indefinitely.

eGFR vs CrCl

Estimated glomerular filtration rate (eGFR) and creatinine clearance (CrCl) are often, incorrectly, used interchangeably when discussing renal function and drug dose adjustment.

Creatinine clearance, usually estimated using the 1976 Cockcroft-Gault formula rather than actually measured by (notoriously unreliable) 24-hour urine collection, has traditionally been used for drug dosing as it is relatively standardised despite overestimating renal function due to tubular secretion of creatinine. In addition to the usual caveats associated with basing renal function estimates on serum creatinine (acute illness, muscle mass, diet, etc), accuracy of the formula is limited by changes to serum creatinine assays and the rise in obesity since 1976.

Renal function is assessed nowadays using formula-derived eGFR (actual GFR is impracticable to measure routintely). Until recently this was usually calculated using the MDRD formula (1999), which has been well validated but has limited accuracy above 60 mL/min. Laboratories in Australia now report eGFR calculated using the superior CKD-EPI formula (2009). Although both of these formulae give better estimates of true renal function (GFR) than CrCl, they are both still based on serum creatinine with its associated caveats above.

Some studies have shown a reasonable concordance between CrCl (Cockcroft-Gault) and eGFR (MDRD) with respect to drug dosing,1 whereas others have noted significant differences.2–3 At the end of the day, CrCl and eGFR are not the same thing and prescribers should remain vigilant as to which measurement has been used to formulate dosage adjustment recommendations.

1. Stevens LA, et al. Am J Kidney Dis 2009;54:3342
2. Wargo KA, et al. Ann Pharmacother 2006;40:124853
3. Park EJ, et al. Ann Pharmacother 2012;46:117487

Biotechnology descriptors

Whilst giving a presentation at grand rounds recently, I noted that approved names for biological medications in Australia are suffixed with a three-letter abbreviation – the “biotechnology descriptor” – to indicate the biotechnology production system used, e.g. insulin lispro (rbe).

The most common biotechnology descriptors are:

  • ghu – gene-activated human cell line
  • rbe – recombinant bacteria Escherichia coli
  • rch – recombinant Chinese Hamster ovary cell line
  • rmc – recombinant mouse cell line
  • rys – recombinant yeast Saccharomyces cerevisiae

Incidentally, I cringe whenever someone refers to this group of medications as “biologics” – an Americanism that has crept into the Australian medical lexicon. Australian English still retains the “-ical” ending (rather than shortening to “-ic” in American English), therefore we should continue to refer to these medications as “biologicals”.

Pregnancy category mnemonic

It seems that most of us in the Sydney Medical School have become suckers for mnemonics… Recently, after the Problem 4.05 theme session on drugs in pregnancy, I came up with a mnemonic to help people remember the Australian Drug Evaluation Committee (ADEC) pregnancy categories used for medications in Australia.

Category A = A-OK – generally considered safe
Drugs which have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the fetus having been observed. (ADEC, 2007)
Category C = Careful – may be harmful
Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details. (ADEC, 2007)
Categories B = Buggered if I know – limited data available
Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. (The allocation of a B category does NOT imply greater safety than the C category.) (ADEC, 2007)
Category D = Danger – risk of irreversible harm
Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details. (ADEC, 2007)
Category X = X-men – high-risk teratogens
Drugs which have such a high risk of causing permanent damage to the fetus that they should not be used in pregnancy or when there is a possibility of pregnancy. (ADEC, 2007)

Of course the use of drugs in pregnancy requires more than simply looking-up the ADEC pregnancy category, but the categorisation does prove quite useful as a quick reference in clinical practice.