Posted by Phillipa on October 23, 2009, at 21:39:46
Embreda combo morphine-naltrexone for preventing opiod abuse. Phillipa
From Medscape Medical News
Morphine-Naltrexone Formulation Maintains Efficacy in Bioavailability Studies
Nancy A. Melville
A novel formulation of the opioid morphine sulfate with a naltrexone hydrochloride core (Embeda, King Pharmaceuticals Inc.) maintains efficacy while offering a delivery system that is designed to deter abuse, according to a review of 2 studies presented here at the American Association of Pain Management 20th annual clinical meeting.With the abuse of opioids such as morphine representing a significant problem in the prescription of pain medication, drug developers are working on formulations that make drugs less desirable, thus lowering the potential for abuse without compromising therapeutic integrity.
Embeda represents the first long-acting opioid to receive approval from the US Food and Drug Administration (FDA) along those lines, The drug, which received FDA approval in August and was commercially launched in September, is formulated with extended-release morphine pellets, each with an inner core of the opioid receptor antagonist naltrexone hydrochloride, according to King Pharmaceuticals. Euphoria, or a drug "high," is less likely to occur if the drug is tampered with by crushing or chewing.
The sequestered naltrexone hydrochloride passes through the body with no intended clinical effect when the drug is taken as directed. If the capsules are crushed or chewed, however, the naltrexone is released and absorbed with the morphine, reversing the morphine's analgesic and other subjective effects.
The first of the 2 studies looked at Embeda's bioavailability over the course of 72 hours. It was an open-label randomized single-dose study of 36 patients comparing concentrations of Embeda with another extended-release morphine sulfate formulation (Kadian) that does not contain naltrexone.
The results showed serum morphine concentration ratios of 102.2% and 93.8% for the Embeda and Kadian groups, respectively, falling within the boundaries required for bioequivalence.
The second study was a randomized multicenter trial of 113 patients treated with Embeda or Kadian over a 14-day period. The results showed steady-state plasma morphine exposure to be statistically similar, with plasma naltrexone and 6-β-naltrexol concentrations to be either not quantifiable or not clinically meaningful.
Pain scores were significantly reduced to similar levels in both groups; adverse events were also similar and typical of those commonly associated with opioids.
There have been 2 previous clinical trials that supported the pharmacodynamic effect of naltrexone in combination with Embeda. One was a comparison of Embeda, whole or crushed, with immediate-release morphine and placebo. In that study, 87.5% of subjects had some reduction in drug craving after receiving crushed Embeda, and 69% of subjects showed some decrease in euphoria with crushed Embeda, compared with immediate-release morphine.
A second randomized double-blind study was a comparison of intravenous (IV) morphine 30 mg alone and IV morphine 30 mg plus IV naltrexone 1.2 mg with simulated parenteral use of crushed Embeda. The combination of morphine with naltrexone resulted in 71% of subjects reporting a reduction in euphoria, compared with morphine alone.
Beatrice Setnik, PhD, a coauthor of the 2 studies evaluating bioavailability, noted that, despite the research behind Embeda, only time will tell how much of an impact the formulation will have as an abuse deterrent.
"The clinical significance of the degree of reduction in drug-liking and euphoria reported in these studies has not yet been established," said Dr. Setnik, who is a member of King Pharmaceuticals' medical team.
"No head-to-head studies have compared the antagonist core technology to other technologies in development designed to resist extraction/defeat of controlled-release mechanisms or produce some type of temporary unpleasant effect when excess quantities are consumed," Dr. Setnik told Medscape Neurology. No other similar drugs are in development.
"The ability of these technologies to reduce abuse, misuse, or diversion can be established only when epidemiologic data on their impact confirming such effects are available," she added.
Through different mechanisms, drug makers have attempted to find formulations that deter opioid abuse, but a broader approach might be key to having a true impact, said Douglas Gourlay, MD, director of the Pain and Chemical Dependency Division, Wasser Pain Centre, Mount Sinai Hospital in Toronto, Ontario.
"The pharmacological idea of modifying abuse risk by punishing the end user isn't new and it certainly isn't bullet-proof," he said. "The reality is people abuse drugs in a variety of ways and, as such, the net result is that no one system is essentially going to eliminate the abuse liability of any member of a class of drug."
"At the end of the day, the molecule carries risk, the patient carries risk, and the situation the drug is used in carries risk. So really, the strategy toward managing that risk has to be more of a composite approach, with more of a focus on education," Dr. Gourlay observed.
The study received funding from King Pharmaceuticals Inc. Dr. Setnik is a member of King Pharmaceuticals' medical team. Dr. Gourlay has disclosed no relevant financial relationships.
American Academy of Pain Management (AAPM) 2009 annual meeting; Poster abstract 45. Presented October 10, 2009
buse of opiods.
poster:Phillipa
thread:922174
URL: http://www.dr-bob.org/babble/20091021/msgs/922174.html