When I use a word . . . Naming medicines—mixtures and co-names

Naming things

In Chapter VIII in Through the Looking Glass and What Alice Found There (1871) Alice, playing the part of a white pawn, and travelling across the looking-glass chess board in search of queendom, is rescued from the clutches of a red knight by a white knight. Lewis Carroll describes how Alice furthers her trip in the company of the White Knight, who is generally regarded as a self-portrait of the author. The knight tells her that he has written a song, and he describes its four different names:

“The name of the song is called ‘Haddocks' Eyes.’”

“Oh, that's the name of the song, is it?” Alice said, trying to feel interested.

“No, you don't understand,” the Knight said, looking a little vexed. “That's what the name is called. The name really is ‘The Aged Aged Man.’”

“Then I ought to have said ‘That's what the song is called’?” Alice corrected herself.

“No, you oughtn't: that's quite another thing! The song is called ‘Ways and Means’: but that's only what it's called, you know!”

“Well, what is the song, then?” said Alice, who was by this time completely bewildered.

“I was coming to that,” the Knight said. “The song really is ‘A-sitting on a Gate’: and the tune's my own invention.”

Give a drug a good name

Like the White Knight’s song, medicines can have four different types of names: what the medicine is, what the medicine’s name is, what the medicine’s name is called, and what the medicine itself is called:

● Name 1—what the medicine is, as indicated by its full chemical name, as determined by the International Union of Pure and Applied Chemistry (IUPAC; https://iupac.org).

● Name 2—what the medicine’s name is, i.e. its generic name, such as the International Nonproprietary Name (INN), assigned by the World Health Organization; other generic names include the British Approved Name (BAN) and the United Sates Adopted name (USAN).

● Name 3—what the medicine’s name is called, i.e. any brand name assigned by a pharmaceutical company.

● Name 4—what the medicine itself is called, i.e. what people call it, i.e. colloquial names given to it by the general public.

Here are examples.

Some medicines have only two names. For example, acetylsalicylic acid is the chemical name (Name 1) of a compound that has no generic name; it is commonly called “aspirin,” which was initially a brand name (Name 3) but which has become the name by which it is commonly known (Name 4).1

Most medicines have three names. Take, for example, the chemical name 2-(4-isobutylphenyl)propionic acid (Name 1), the INN of which is ibuprofen (Name 2); it has been marketed under many different brand names (Name 3 variants), including Actifen, Brufen, and Caldolor¸ ..., Tefin, Upfen, and Zydol.2

Now consider the chemical that is called (R)-1-(3,4-dihydroxyphenyl)-2-methylaminoethanol (Name 1), which is better known by its INN, epinephrine (Name 2). It is marketed in various branded formulations with different routes of administration, including Asthmanefrin, Epipen, Micronefrin, and Nephron (Name 3 variants). However, epinephrine has a variant Name 2, adrenaline. In the UK the generic names of medicines, their British Approved Names (BANs) are almost always the same as the INNs. However, as a rare exception, the BAN for epinephrine is adrenaline.3

Indeed, it is not uncommon for local generic names to differ from INNs. For example, paracetamol (INN and BAN) is known as acetaminophen in the USA. Several other United States Adopted Names (USANs) differ from INNs and BANs, including albuterol (INN and BAN salbutamol), inamrinone (INN and BAN amrinone), glyburide (INN and BAN glibenclamide), meperidine (INN and BAN pethidine), and rifampin (INN and BAN rifampicin).

Finally, some drugs, typically recreational drugs and drugs of abuse, have four names. For example, N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]propanamide (Name 1) is better known by its INN, fentanyl (Name 2), and is sold under various brand names (Name 3 variants), such as Actiq, Duragesic, Fentora, Lazanda, and Sublimaze. However, since it became a drug of abuse it has also acquired many colloquial names (Name 4 variants), also known as street names.4 These include Breath, Crazy One, Dance Fever, Dragon Fire, Fenty, Friend, Goodfella, Great Bear, He-Man, Jackpot, King Ivory, and Lollipop.

Mixtures and co-names

In the 1960s a nomenclatural problem arose when the combination of trimethoprim with a sulfonamide, sulfamethoxazole, turned out to be at least as effective, sometimes more so, in treating a range of infections than either drug alone or than other antibacterial drugs.56789101112 Two companies marketed formulations containing the combination; Burroughs Wellcome marketed it as Septrin and Roche as Bactrim. Before long a BAN had been invented to describe the combination, by using co- as a prefix and adding syllables from each of the compounds in the mixture—trim from trimethoprim and oxazole from sulfamethoxazole. Thus: co-trimoxazole.

Since then another 25 mixtures have been given co-names. Here is the complete list of 26, with the date on which the co-name is first to be found and the contents of each mixture:

● co-trimoxazole (1971) sulfamethoxazole+trimethoprim

● co-trifamole (1978) trimethoprim+sulfamoxole

● co-trimazine (1979) trimethoprim+sulfadiazine

● co-dergocrine (1979) dihydroergocornine+dihydroergocristine+

dihydroergocryptines

● co-codamol (1985) codeine+paracetamol

● co-codaprin (1985) codeine+aspirin

● co-danthramer (1985) danthron+poloxamer

● co-danthrusate (1985) danthron+doctyl sodium sulfosuccinate

● co-dydramol (1985) dihydrocodeine+paracetamol

● co-proxamol (1985) dextropropoxyphene+paracetamol

● co-amilofruse (1989) amiloride+furosemide

● co-amilozide (1989) amiloride+hydrochlorothiazide

● co-amoxiclav (1989) amoxicillin+clavulanic acid

● co-beneldopa (1989) benserazide+levodopa

● co-careldopa (1989) carbidopa+levodopa

● co-fluampicil (1989) flucloxacillin+ampicillin

● co-flumactone (1990) hydroflumethiazide+spironolactone

● co-phenotrope (1990) diphenoxylate+atropine

● co-prenozide (1990) oxprenolol+cyclopenthiazide

● co-simalcite (1990) simethicone+hydrotalcite

● co-tenidone (1990) atenolol+chlortalidone

● co-magaldrox (1992) magnesium hydroxide+aluminium hydroxide

● co-triamterzide (1992) triamterene+hydrochlorothiazide

● co-methiamol (1996) methionine+paracetamol

● co-zidocapt (1999) hydrochlorothiazide+captopril

● co-cyprindiol (2000) cyproterone+ethinylestradiol

Some of these mixtures are no longer available (e.g. co-trifamole and co-trimazine), while others are still listed in the British National Formulary.

However, there is a problem with these names. The WHO's document Guidance on the Use of International Nonproprietary Names (INNs) for Pharmaceutical Substances gives instructions on the naming of mixtures, as follows13: “INNs are selected in principle only for single, well-defined substances that can be unequivocally characterized by a chemical name (or formula). It is the policy of the INN Programme not to select names for mixtures of substances ....”

In other words, co-names are not INNs.

There are good reasons for this restriction. The main purpose of the INN programme is to provide a unique name for a medicine, a name that is publicly available and can be used globally. Patient safety is a major concern in the choice of names, and giving a single name to a mixture of compounds hides the identity of each of the components of the mixture, making room for prescribing errors.

As an example of the problems that can occur, in a study of 330 reports of adverse incidents related to prescriptions the drugs most commonly involved were insulin (10% of incidents), gentamicin (7%), co-amoxiclav (5%), and amoxicillin (5%). In 15 cases co-amoxiclav was given to people with penicillin allergy (4.5% of the total).14 If you don’t know that co-amoxiclav contains amoxicillin, this is an error that you can easily make, with potentially fatal consequences.

It is now becoming increasingly common, partly because of an anomaly in the financial reimbursement system in place in the UK, for manufacturers, when issuing products that contain mixtures, to print the names of the individual components on the package but not the co-name. This too can lead to problems, through lack of recognition that the mixture is the same as the mixture that was previously available under a co-name.

When using a formulation that is labelled with a co-name, prescribers should ensure that they know what the contents of the mixture are. Conversely, when the label on a package specifies the ingredients of a mixture by listing each name, without specifying the co-name, it is important that prescribers know what the corresponding co-name is.