Prescription Painkillers: Companies Attempt Abuse-Proof Opioids


Niacin, which can induce a chemical flush, was added as an extra disincentive, but critics said the flushing, could be easily defeated by taking an aspirin or even just food with the drug. Also there was concern that niacin could cause flush even among people who took the medicine as directed.

Yet the addition of niacin has been one of few means of addressing abusers who take handfuls of pills, which is particularly a problem with short-acting opioids like hydrocodone (Vicodin).

Cawkwell says the company is exploring other alternatives, and last December it submitted a new drug application (NDA) for a niacin-free version of Acurox. The FDA has fast-tracked this version and the company anticipates a final decision in June.

Pfizer has another abuse-resistant drug -- Remoxy, a gelatinous form of long-acting oxycodone -- also under FDA review.

In this case the formulation -- think molasses -- makes it impossible to crush or chew. Likewise it is too viscous to be drawn into a syringe and Cawkwell said that mixing it with alcohol to release the full potency of the opioid -- a popular technique used by abusers -- doesn't work.

She said that FDA is expected to rule on the Remoxy NDA later this year.

In Development

Other companies have pursued the agonist-antagonist route -- including Elite Pharmaceuticals with OxyNal and Pain Therapeutics with Oxytrex -- but the status of these products remains unclear. That may be related to troubles with Embeda, the other agonist-antagonist combination; it could also have to do with the fact that more companies are pursuing molecular-based solutions instead.

Collegium Pharmaceuticals has received FDA fast-track status to develop two long-acting opioids incorporating its DETERx technology, which involves a "multi-particulate matrix formation in a capsule."

Essentially, that's beads of gelatin oxycodone that are hard to crush and won't release a punch if pulverization is attempted, according to Dr. Lynn Webster, of Lifetree Pain Clinic in Salt Lake City, who is a consultant to various companies developing tamper-resistant drugs.

The bead-filled capsule is also intended to prevent overdose in patients who can't swallow pills and need to mix the contents with food or water.

Other companies are targeting the chemistry of opioids themselves and hoping to alter chemical structure to short circuit abuse.

Nektar Therapeutics said it has modified an opiate with a permanently bound polymer that slows the rate at which the drug can cross the blood-brain barrier. Dr. Lorianne Masuoka, chief medical officer for Nektar, told MedPage Today, "there's nothing you can do to make it enter the brain more quickly."

"This feature is inherent to the molecule," Masuoka added. "There's no coating, no polymer matrix. It's part of the chemistry itself."

The compound, NKTR-181, has just entered a phase-I trial that will enroll 75 patients.

Taking a similar path, PharmacoFore is using an amino acid to mask opioid molecules. Once the compound PF329 hits the small intestine, the amino acid is cleaved off by the digestive enzyme trypsin, activating controlled release of the drug.

No crushing or dissolving can sever the bonds of the molecule, according to PharmacoFore chief financial officer Greg Sturmer.

And because the key "unlocking" enzyme isn't in the blood, injecting or snorting the drug won't do the user any good.

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