NEW YORK--(BUSINESS WIRE)-- Pfizer Inc. (NYSE: PFE) announced today results from three Phase 4 studies of EMBEDA® (morphine sulfate and naltrexone hydrochloride) Extended Release Capsules CII designed to assess the effect of the drug when crushed and taken either orally or intranasally.
Studies ALO-01-10-4005 and ALO-01-10-4004 were double-blind cross-over designed studies in non-dependent, recreational opioid users that compared subjective measures relating to abuse potential of crushed EMBEDA to crushed extended-release morphine sulfate and placebo following oral (study 4005) and intranasal (study 4004) administration. In both studies, the use of EMBEDA was associated with significantly (p<0.01)lower scores on the primary endpoints of “drug liking” and “high,” as well as the secondary endpoints including “good effects,” “overall drug liking” and “take drug again” as compared with extended-release morphine sulfate. Both medications had significantly higher scores on all measures as compared with placebo. Common adverse events observed following oral administration of crushed EMBEDA in study ALO-01-10-4005 included somnolence, nausea, pruritis and dizziness, and in study ALO-01-10-4004 following intranasal administration of crushed EMBEDA included euphoric mood, somnolence and headache.
The third study, ALO-01-09-111, was a double-blind cross-over study in opioid-dependent patients with moderate-to-severe non-cancer chronic pain stabilized on EMBEDA therapy. This study used an opioid withdrawal scale to assess the ability of a single dose of crushed EMBEDA to induce withdrawal symptoms compared with intact EMBEDA swallowed whole, as crushing releases the sequestered naltrexone. The trial was not fully enrolled as the study was discontinued early due to the voluntary recall of EMBEDA. Only six patients completed the study, compared with a target of 12 to 16 patients. Ingestion of crushed EMBEDA induced signs and symptoms of withdrawal of at least moderate intensity in three of the six patients. The most common adverse events reported in the trial following administration of crushed EMBEDA were anxiety, tremor, yawning, nausea, restlessness, diarrhea and flushing.
EMBEDA is approved by the U.S. Food and Drug Administration for the management of moderate-to-severe pain when a continuous, around-the-clock opioid analgesic is needed for an extended period of time. EMBEDA is NOT intended for use as a prn analgesic. EMBEDA contains pellets of an extended-release oral formulation of morphine sulphate, an opioid receptor agonist, with a sequestered core of naltrexone hydrochloride, an opioid receptor antagonist. Proper use requires EMBEDA to be swallowed whole or the contents of the capsules to be sprinkled on apple sauce. The pellets in the capsules are not to be crushed, dissolved, or chewed before swallowing. Misuse or abuse of EMBEDA by tampering with the formulation by crushing or chewing the pellets causes the rapid release and absorption of both morphine and naltrexone. The resulting morphine dose may be fatal, particularly in opioid-naïve individuals. In opioid-tolerant individuals, the absorption of naltrexone may increase the risk of precipitating withdrawal. There is no evidence that the naltrexone in EMBEDA reduces the abuse liability of EMBEDA.
In March 2011, Pfizer voluntarily recalled from U.S. wholesalers and retailers all dosage forms of EMBEDA because a pre-specified stability requirement was not met during routine testing. Pfizer has been continuing its efforts to address the stability requirement and reintroduce EMBEDA to the U.S. market as quickly as possible. There are several key decision points during 2012 that will determine the necessary corrective action and associated timing.
Important Safety Information
WARNING: EMBEDA® (morphine sulfate and naltrexone hydrochloride) Extended Release Capsules contain morphine, an opioid agonist and a Schedule II controlled substance with an abuse liability similar to other opioid agonists. EMBEDA® can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing EMBEDA® in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion.
EMBEDA® contains pellets of an extended-release oral formulation of morphine sulfate, an opioid receptor agonist, surrounding an inner core of naltrexone hydrochloride, an opioid receptor antagonist indicated for the management of moderate to severe pain when a continuous, around-the-clock opioid analgesic is needed for an extended period of time.
EMBEDA® is NOT intended for use as a prn analgesic.
EMBEDA® 100 mg/4 mg IS FOR USE IN OPIOID-TOLERANT PATIENTS ONLY. Ingestion of these capsules or the pellets within the capsules may cause fatal respiratory depression when administered to patients not already tolerant to high doses of opioids.
Patients should not consume alcoholic beverages while on EMBEDA® therapy. Additionally, patients must not use prescription or non-prescription medications containing alcohol while on EMBEDA® therapy. The co-ingestion of alcohol with EMBEDA® may result in an increase of plasma levels and potentially fatal overdose of morphine. EMBEDA® is to be swallowed whole or the contents of the capsules sprinkled on apple sauce. The pellets in the capsules are not to be crushed, dissolved, or chewed due to the risk of rapid release and absorption of a potentially fatal dose of morphine.
Crushing, chewing, or dissolving EMBEDA® will also result in the release of naltrexone which may precipitate withdrawal in opioid-tolerant individuals.
The common adverse events seen on initiation of therapy with EMBEDA® are dose dependent, and their frequency depends on the clinical setting, the patient’s level of opioid tolerance, and host factors specific to the individual. They should be expected and managed as part of opioid analgesia. The most frequent of these include drowsiness, dizziness, constipation, and nausea.
Additional common adverse events reported during clinical studies include constipation, nausea, and somnolence.
Indications and Usage
EMBEDA® is an extended-release oral formulation of morphine sulfate and naltrexone hydrochloride indicated for the management of moderate to severe pain when a continuous, around-the-clock opioid analgesic is needed for an extended period of time.
EMBEDA® is NOT intended for use as a prn analgesic.
EMBEDA® is not indicated for acute/postoperative pain or if the pain is mild or not expected to persist for an extended period of time. EMBEDA® is only indicated for postoperative use if the patient is already receiving chronic opioid therapy prior to surgery or if the postoperative pain is expected to be moderate to severe and persist for an extended period of time.
For EMBEDA Full Prescribing Information please visit www.embeda.com
Pfizer Inc.: Working together for a healthier world®
At Pfizer, we apply science and our global resources to improve health and well-being at every stage of life. We strive to set the standard for quality, safety and value in the discovery, development and manufacturing of medicines for people and animals. Our diversified global health care portfolio includes human and animal biologic and small molecule medicines and vaccines, as well as nutritional products and many of the world’s best-known consumer products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as the world’s leading biopharmaceutical company, we also collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, Pfizer has worked to make a difference for all who rely on us. To learn more about our commitments, please visit us at www.pfizer.com.
DISCLOSURE NOTICE: The information contained in this release is as of December 22, 2011. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.
This release contains forward-looking information that involves substantial risks and uncertainties regarding the reintroduction of EMBEDA in the U.S. market as quickly as possible. Such risks and uncertainties include, among other things, the Company’s ability to address the stability requirement and the timing of the necessary corrective action. A further list and description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2010 and in its reports on Form 10-Q and Form 8-K.
MacKay Jimeson, 212-733-2324
Suzanne Harnett, 212-733-8009
KEYWORDS: United States North America New York
INDUSTRY KEYWORDS: Health Clinical Trials Pharmaceutical FDA