“How on earth did they come up with that name?”

This is a question commonly posed by patients and health professionals alike. Even a most experienced practitioner may hesitate at names such as eptifibatide, levetiracetam and bevacizumab. While the creativity of the developers plays a part, formulating a name for a medicine involves considerable forethought, particularly with regards to safety for the public. “Safe and quality use of medicines” requires clear prescribing, accurate dispensing, and unambiguous communication and exchange of information between health professionals. Misreading or misinterpreting a name can compromise any of these steps. In response to this, pharmaceutical companies must meet requirements set by regulatory bodies before the proposed names can become valid.

Three’s Company

Every medicine needs at least three names: a chemical name, a generic name and a brand name. Naturally, the chemical name describes the exact structure of the compound. The nomenclature is governed by rules of the International Union of Pure and Applied Chemistry (IUPAC). A widely used bronchodilator, for instance, has a chemical name of di[(RS)-2-(1,1-dimethylethyl)amino-1-(4-hydroxy-3-hydroxymethylphenyl)ethanol]sulfate. To improve practicality, a simpler yet equally unique name is allocated, in this case salbutamol. This is known as the generic or International Nonproprietary Name (INN). Maintained by the World Health Organisation (WHO), INNs serve as unique, globally accepted references for marketed active pharmaceutical substances. Finally, a trademarked brand name, e.g. Ventolin®, is created by the pharmaceutical company responsible for discovering and developing the medicine for marketing purposes.

Generic Engineering

While there is a literal formula to determine chemical names, the same cannot be said for generic names. As previously mentioned, the WHO INN committee manages an ever-expanding list of standard names in an effort to deliver a level of nomenclature consistency worldwide. Presently 7,000 names long and growing, the list is comprehensive but does not cover all substances or terms available in any given country. In Australia, generic medicine names are primarily regulated by the Therapeutic Goods Administration (TGA). The TGA manages lists of Australian approved terminology for medicines to ensure data accuracy and consistency. Where possible, the INN register is referenced and utilised to converge national and international listings, reducing confusion and ambiguity, particularly when medicines are exported overseas.

One of the most important features of the WHO’s INN register is the official compilation of short name fragments or ‘stems’. These stems are assigned to chemically or pharmacologically related groups to indicate similar therapeutic actions, and new names must adapt to these whenever possible. Implementing the usage of standard stems promotes consistency and allows a medicine’s general pharmacological effect to be recognised quickly by practitioners. This in turns assists with predicting interactions and rationalising medicinal therapies.

Generally, if a new medicine belongs in an existing class, it must take on the stem that has been delegated for that therapeutic class.

For example:

  • It is common industry knowledge that monoclonal antibodies have the suffix ‘mab’ at the end of their names. However, there are also codes to indicate the species on which the immunoglobulin is based. For instance:
    • ’zu’ represents a humanised origin
    • ’xi’ represents a chimeric origin
    • ‘xizu’ represents antibodies containing both chimeric and humanised chains.
      Therefore, the name bevacizumab reveals that the medicine is a humanised monoclonal antibody, and the name rituximab indicates that this medicine is a chimeric monoclonal antibody.
    • Macrolide antibiotics have names that end with ‘-mycin’ i.e. azithromycin, roxithromycin, clarithromycin and erythromycin. The suffix is derived from the name ‘Streptomyces’, a group of strains from which these antibiotics are produced.
    • Some immunomodulators contain the suffix ‘-imod’ which still retain a small resemblance to its class name. Examples include fingolimod and imiquimod.
    • Anticonvulsants which act as gabaminergics are marked by the infix ‘-gab-’, e.g. gabapentin, pregabalin, tiagabine and vigabatrin.

In an effort to reduce medicine errors, submitted names are also analysed to determine if they can be misleading in any way. The spelling, scripted appearance and even spoken pronunciation of proposed names are compared against existing terms to gauge whether they are sufficiently different, with the aid of various computational methods and public databases. In America, the
Food and Drug Administration (FDA) scrutinises different but legible handwriting samples of a submitted name’s autographic appearance in an effort to reduce handwritten medicine errors.

Despite rigorous review processes, accepted names may still cause unanticipated confusion. The sheer number of existing names and submissions, coupled with the use of common stems increases the possibility of similar names to co-exist, for example:

  • cephazolin versus cephalothin
  • moxifloxacin versus norfloxacin
  • thiamine versus thyroxine
  • dexamethasone versus dexamphetamine
  • risperidone versus ropinirole
  • cyclosporin versus cycloserine
  • valaciclovir versus valganciclovir

One technique used to combat this problem is to create more unusual letter combinations. To some extent this explains why so many eccentrically constructed names like abciximab, xylometazoline, canagliflozin, eptacog alfa and fingolimod are acceptable entries. Still, pharmaceutical companies are also obligated to consider the extent of potential difficulties in pronunciation and memorability, and to revise their entries until these requirements are sufficiently satisfied.

Furthermore, the promotional potential of a name is considered. A name which may lead someone to draw an overly positive conclusion about the medicine’s benefits is almost always rejected. In addition, terms which suggest minimised risk, or broaden product indications, risk a similar fate. This ensures submissions like “fatbeegone” and “kompletekure” are turned down.

Thinking Outside the Medicine Box

Regulatory conditions aside, creativity and whim assists with name designs. Many are inspired by unexpected sources and at times give fascinating insights into the origin of the medicine itself.

Warfarin, for example, acquired its name from the place it was discovered – the Wisconsin Alumni Research Foundation (or WARF). Additionally, its suffix ‘-arin’ was derived from the chemical compound coumarin, which acts as a precursor in the synthesis of warfarin.

The name montelukast was also inspired by the location in which it was developed: Montreal. Interestingly, its originating company initially submitted the name ‘realukast’, with the ‘real’ prefix paying homage to Montreal and ‘lukast’ to indicate its action as a leukotriene receptor antagonist. However, the name was rejected on the basis that ‘REALukast’ implies superiority as a true leukotriene receptor antagonist in comparison to others within this class. Therefore, montelukast was chosen in keeping with its native land.

Closing Thoughts

Seemingly nonsensical names may not always be greeted with immediate popularity. But understanding how they might have come about and whether or not they contain a familiar stem alluding to a particular mechanism of action can help improve familiarity and with time make them more user-friendly.

References:

  1. Asmol (salbutamol sulfate) CFC-free Inhaler Australian approved product information. Millers Point: Alphapharm Pty Limited. Approved 26 November 1998, amended 16 October 2012.
  2. Connolly A, Loftus P. Making drug names easy to swallow. Wall Street Journal – Health 2010; June 30.
  3. Division of Drug Management & Policies. Guidelines on the Use of International Nonproprietary Names (INNs) for Pharmaceutical Substances. Doc No. WHO/PHARMS/NOM 1570. Geneva: WHO; 1997.
  4. Francis CW. Warfarin: an historical perspective. Hematology Am Soc Hematol Educ Program. 2008: 251
  5. Hoffman JM., Proulx SM. Medication errors caused by confusion of drug names. Drug Saf. 2003; 26(7): 445-52.
  6. Segura-Bedmar I, Martínez P, Segura-Bedmar M. Drug name recognition and classification in biomedical texts. A case study outlining approaches underpinning automated systems. Drug Discov Today. 2008 Sep; 13(17-18): 816-23.
  7. Therapeutic Goods Administration. TGA Approved Terminology for Medicines. Woden: Department of Health and Ageing; 1999.
  8. U.S. Food and Drug Administration. How FDA Reviews Proposed Drug Names. U.S. Department of Health and Human Services.
  9. World Health Organisation (WHO). Guidance on INN. Geneva: WHO; 2014.
  10. World Health Organization (WHO). The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances 2013. Doc No. WHO/EMP/RHT/TSN/2013.1. Geneva: WHO; 2013.

Subscribe Knowledge Centre Updates

Enter your details to receive Knowledge Centre updates