NATIONAL HARBOR, MD. – Pharmaceutical companies are stepping up to address increasing opioid abuse and misuse by developing innovative abuse-deterrent formulations and drug delivery systems, Dr. Lynn R. Webster said at the annual meeting of the American Academy of Pain Medicine.
Dr. Webster discussed several new opioid formulations that are currently available and some promising technologies in the pipeline. Dr. Webster is board certified in anesthesiology and pain medicine and is certified in addiction medicine. He is also the medical director and founder of the Lifetree Clinical Research and Pain Clinic in Salt Lake City.
New Opioids. In January 2011, the Food and Drug Administration approved Abstral (Prostrakan), a fentanyl transmucosal tablet indicated for the management of breakthrough cancer pain in adults. As an alternative to oral tablets or injections of fentanyl pain medications, the quick-dissolving tablet is placed under the tongue, providing very fast relief for cancer-related pain in patients already receiving opioids for pain treatment.
Approved in 2010, Exalgo is an extended-release formulation of hydromorphone indicated for once-daily administration for the management of moderate to severe pain in opioid-tolerant patients who require continuous, around-the-clock opioid analgesia for an extended period. Exalgo (Mallinckrodt) is not intended for use as an as-needed analgesic. The formulation utilizes a new osmotic, controlled-release oral delivery system in which osmosis attracts water in the body to the inside of the capsule to trigger release of hydromorphone. It takes about 6 hours for effective levels of hydromorphone to be released and 4-5 days for drug levels to reach a steady state in the body, Dr. Webster said.
There has been a resurgence of interest in buprenorphine. This drug has been around for several decades, but is now being used to treat chronic pain. Buprenorphine is a partial mu-opioid agonist, an antagonist at the kappa-opioid receptor, and a partial agonist at the ORL1/nociceptin and delta-opioid receptors. "There is a little bit of complexity with how the pharmacology of this drug works. We probably don’t understand clinically what all of that means yet," Dr. Webster said. Buprenorphine is the only opioid classified as a schedule III drug, making it an attractive choice for pain management. Buprenorphine also is associated with fewer of the side effects typical of opioids, such as respiratory depression.
In 2010, the FDA approved Butrans, an extended-release buprenorphine patch (Purdue Pharma), in 5-, 10- and 20-mcg/hour doses. The drug is indicated for the management of moderate to severe chronic pain in patients requiring continuous, around-the-clock opioid treatment for an extended period.
Notably, Subutex (buprenorphine monotherapy) and Suboxone (a buprenorphine/naloxone combination product) are approved for use in opioid addiction treatment, though other forms of the drug are not. However, other forms of buprenorphine are commonly used off-label for the management of addiction disorders, Dr. Webster said. Because buprenorphine is an opioid partial agonist, its maximal effects are less than those of full agonists (like heroin and methadone). At low doses, buprenorphine is thought to produce enough of an agonist effect to enable opioid-addicted individuals to discontinue the misuse of opioids without experiencing withdrawal symptoms. Buprenorphine has poor oral bioavailability and only moderate sublingual bioavailability.
In the Pipeline. Acurox (Acura Pharmaceuticals and King Pharmaceuticals [now part of Pfizer]) is an oral immediate-release oxycodone tablet with a proposed indication for the relief of moderate to severe pain. Acurox is formulated so that if the tablets are dissolved in an attempt to extract the opioid for intravenous injection, the tablets turn into a viscous gel mixture with the active drug trapped in the gel. The Aversion technology used also causes burning and irritation of the nasal passages if the drug is crushed and snorted.
Last year, the FDA rejected an application for a version of the drug containing niacin, which was formulated so that the uncomfortable "niacin flush" would deter overuse of the drug. In February 2011, the FDA accepted a new drug application for Acurox (oxycodone) tablets without niacin.
MoxDuo (QRxPharma) is an immediate-release dual opioid intended for the acute management of moderate to severe pain. The drug is a combination of morphine and oxycodone that has been clinically shown to have a synergistic effect on pain with a significant reduction of total opioid dose and side effects.
"This formulation is built upon that thought that there are different receptor selectivities to an opioid," Dr. Webster said. Because opioid receptors differ, "you can get enhanced analgesia with using overall less morphine equivalents, or you could get fewer side effects with the same level of analgesia, when you combine two different opioids."