Imovane (zopiclone) vs. Lunesta (eszopiclone)

We sometimes get emails wondering about the difference between Lunesta (eszopiclone) and Imovane (zopiclone). Since both of these medications share the same original maker - Sepracor (and the same atoms apparently), it’s understandable that many are curious.

The US Food and Drug Administration (FDA) approved eszopiclone (Lunesta) as a “new” sleeping pill on December 15, 2004. We put “new” in quotes because eszopiclone is in fact derived from zopiclone (generic Imovane), a drug that has been available in 85 foreign countries (but not the US) since 1987. Zopiclone was in fact originally created by Sepracor who now market Lunesta.

The background on this is that Zopiclone has two identical atoms called isomers - one active and one inactive. One of these is eszopiclone. However, the two isomers that make up zopiclone are mirror images.

The marketing of drugs like this - by utilizing a single isomer of an existing drug that contains mirror isomers — is becoming more popular with drug manufacturers. Drug companies need a supply of patented drugs to continue monopoly pricing. However, a single isomer drug rarely offers a therapeutic advantage over the mixture of isomers from which it is derived. However, the single isomer is patentable distinct from its multiple-isomer origin. Thus, the drug company can get a monopoly.

Consequently, Lunesta is viewed by many to be more of a �?marketing’ breakthrough than a medical breakthrough since it allows Sepracor to market it under patent protection.

Since eszopiclone and zopiclone are, for all practical purposes, the same drug, it is clear that eszopiclone is nothing special compared to sleeping pills that already on the market.

Incidentally, prior to the Lunesta patents, the British National Institute for Clinical Excellence (NICE), an organization created to make sure that public money is spent wisely for drugs in the United Kingdom, reviewed zaleplon, zolpidem, and zopiclone in April 2004.

They concluded that…

“It is recommended that, because of the lack of compelling evidence to distinguish between zaleplon, zolpidem, zopiclone or the shorter-acting benzodiazepine hypnotics, the drug with the lowest purchase cost (taking into account daily required dose and product price per dose) should be prescribed.”

Getting back to Lunesta, Sepracor submitted six clinical trials to the FDA in support of the drug’s approval. In four of these trials the primary endpoint, the outcome used as the basis for the drug’s approval, was Objective Latency to Persistent Sleep, or the time it takes to fall to sleep. The FDA medical officer found that one of these four studies had “serious problems” and that it “cannot provide clinically meaningful results.”

In the remaining three trials for which time to sleep was the primary endpoint, the average time to fall asleep in patients taking 3 milligrams of eszopiclone ranged from 18.0 to 19.3 minutes. In patients given the placebo, the range was from 33.0 to 40.8 minutes. The difference in these three trials between eszopiclone and placebo ranged from 15.0 to 21.5 minutes.

One of these three trials also compared 3 milligrams of eszopiclone to a placebo and also to 10 milligrams of zolpidem. On average, patients taking eszopiclone fell asleep in 18.3 minutes. Patients on zolpidem took 16.6 minutes. This is an average difference of only 1.7 minutes, favoring zolpidem.

The editors of The Medical Letter on Drugs and Therapeutics, an independent source of drug information written for pharmacists and physicians, reviewed eszopiclone in their February 28, 2005 issue. Their conclusion was that:

The main difference between all of them [eszopiclone, zaleplon, zolpidem], except for half-life, may be that the manufacturer of Lunesta sponsored a 6-month trial and submitted the results to the FDA, while the other 2 manufacturers did not.