When a sponsor chooses a portion (prefix, infix, suffix, or common letter string) of an existing or approved proprietary name to introduce a new product that does not contain the exact same active ingredient(s) or active moiety(ies), this naming strategy is referred to as a brand extension.

Name safety research focuses on the prevention of medication errors by examining proposed brand names prior to being approved by a regulatory agency. Brand extension can lead to confusion in practice when a healthcare professional makes assumptions based on the brand name and provides the patient with an product that was not intended.

In general, “FDA advises against using brand name extension to introduce a new product.” (Source: Guidance for Industry Best Practices in Developing Proprietary Names for Human Prescription Drug Products Guidance December 2020 Drug Safety, section E. Brand Name Extension page 6). However, we can share a few examples of brand name extensions that were approved by the FDA over the last decade and marketed in the U.S.

There are several approved pharmaceutical drug products identified on Drugs@FDA that were at one time in the U.S. marketplace where the brand name contained the letter string, “MET” and includes metformin as one of the active ingredients. However, there are no guidelines or recommendations to use or not use the letter string “MET” in a brand name. We wanted to explore whether this type of brand name extension could lead to confusion in practice.

Based on the brand names alone, can you identify the 5 products that DO NOT contain the active ingredient, metformin?

Brand Name (https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm)

Actoplus MET	CoMETriq	JanuMET XR
AldoMET	FortaMET	METaglip
AnzeMET	GluMETza	PrandiMET
AvandaMET	InvokaMET XR	RioMET ER
CesaMET	JanuMET	SineMET

The five products that do not contain metformin include: Aldomet (methydopa, Merck), Anzemet (dolasetron mesylate, Validus Pharms), Cesamet (nabilone, Bausch), Cometriq (cabozantinib s-maleate, Exelixis), and Sinemet (carbidopa and levodopa, Organon).

A difficult challenge but hopefully this exercise has shown that the brand extension name strategy should be carefully considered for the potential for confusion in practice.

Brand extension can reference the concept of generic percent derivation (i.e., using letters in the active ingredient sometimes referred to as the generic name in the brand name of the product) but this naming strategy also considers the concept of “combination of active ingredients”. Section III.C of the FDA Guidance (December 2020), states that the “FDA recommends against proprietary names of fixed combination drug products that include or suggest the name of one or more, but not all, of its active ingredients (as defined in § 210.3(b)(7)), because such names can mislead the end user by implying that the product contains only the ingredient or ingredients included in, or suggested by the name (see 21 CFR 201.6(b) and section 201(n) of the FD&C Act).

Here is an example of two products approved by the FDA and marketed in the U.S. called NEXLETOL and NEXLIZET.

• Based on the brand names alone, can you confirm that these two distinct products share a common active ingredient? If not, continue reading.
• Can you identify which of these two distinct products contains multiple active ingredients – where both ingredients are represented in the brand name? If not, continue reading.

It is safe to say that the brand naming strategy for “brand extension” is complex and when you add the aspect of “combination of active ingredients” into the discussion, the aspect of what is considered the extension must be present and logical but does not necessarily need to be obvious.

The letter string, “NEXL” in the prefix position of NEXLETOL and NEXLIZET helps extend the product brands and “communicates” that both products contain the same active ingredient. It is not clear that that active ingredient is “bempedoic acid” but is not a requirement to pull letters from the active ingredient and add to the brand name to satisfy a brand extension. The brand product that contains “bempedoic acid” as the only active ingredient is NEXLETOL.

The letter string “ZET” in the suffix position of NEXLIZET helps reference the second ingredient, ezetimibe, in the fixed-dose combination product and satisfies the “combination of active ingredients” guideline, to have the brand name reference all ingredients. The “ZET” suffix is also used with other ezetimibe combination products suchs as Lypqozet (atorvastatin/ezetimibe, Norvium), Liptruzet (atorvastatin/ezetimibe, Organon), and Roszet (rosuvastatin/ezetimibe, Althera). The innovator brand name for single agent ezetimibe is ZETIA® (by Organon). However, it is unclear whether the reference made to the second ingredient is to the trade name or the active ingredient or both.

It is interesting to note that in the public Proprietary Name Review dated May 21, 2019, (211617Orig1s000NameR.pdf) for NEXLIZET, that the FDA states the following:

• The Office of Prescription Drug Promotion (OPDP) determined that Nexlizet would not misbrand the proposed product.
• The Division of Medication Error Prevention and Analysis (DMEPA) and the Division of Metabolism and Endocrinology Products (DMEP) concurred with the findings of OPDP’s assessment for Nexlizet.
• We previously considered whether the proposed name, Nexlizet, adequately represents both active ingredients of this multi-ingredient product. At that time, we determined that the name, Nexlizet, is suggestive of both active ingredients and we maintain our previous conclusion that the naming approach is acceptable.
• This proprietary name is comprised of a single word that does not contain any components (i.e. a modifier, route of administration, dosage form, etc.) that are misleading or can contribute to medication error.
• The proposed proprietary name, Nexlizet, is acceptable.

Another aspect to consider in the brand extension conversation is how the brand name evaluation will consider the inherent similarity between the branded products. In the current example, NEXLIZET vs. NEXLETOL, would be categorized as a “highly similar name pair” based on the FDA POCA scores. [Combined POCA: 74%, Orthographic POCA: 78%, and Phonetic POCA: 71%. This name pair would cause additional discussion because according to the latest FDA Guidance (December 2020), the Agency states the following under “Name Attributes section:”

We note that the beginning of the drug name plays a significant role in contributing to confusion. Additionally, drug name pairs that start with the same first letter and contain a shared letter string of at least 3 letters in both names are major contributing factors in the confusion of drug names.

Overall, the letter string that is considered the “extension” in the brand extension, the product profile overlaps, and the unique letters selected for the second product that indicate the additional active ingredient(s) are all relevant data points to considered when evaluating brand names that are considered “brand extensions.”

If you are faced with a brand extension opportunity – be proactive and explore realistic options that speak to the active ingredient(s) in your brand.

If you would like to discuss naming strategy options, give us a call!