Technology

The abuse-deterrent technology of EMBEDA

Specifically designed with sequestered naltrexone HCl

EMBEDA is the first approved agonist/antagonist abuse-deterrent opioid with properties expected to reduce abuse via the oral and intranasal routes
ABUSE OF EMBEDA IS STILL POSSIBLE THROUGH ORAL, INTRANASAL, AND INTRAVENOUS ROUTES. DATA FROM LABORATORY AND CLINICAL STUDIES MAY NOT FULLY PREDICT ABUSE POTENTIAL.
REFERENCES

1. Embeda [prescribing information]. New York, NY: Pfizer Inc; December 2016. 2. Stauffer J, Setnik B, Sokolowska M, Romach M, Johnson F, Sellers E. Subjective effects and safety of whole and tampered morphine sulfate and naltrexone hydrochloride (ALO-01) extended-release capsules versus morphine solution and placebo in experienced non-dependent opioid users: a randomized, double-blind, placebo-controlled, crossover study. Clin Drug Investig. 2009;29(12):777-790. 3. Webster LR, Brewer R, Wang C, et al. Long-term safety and efficacy of morphine sulfate and naltrexone hydrochloride extended release capsules, a novel formulation containing morphine and sequestered naltrexone, in patients with chronic, moderate to severe pain. J Pain Symptom Manage. 2010;40(5):734-746. 4. Bryson PD. Narcotic antagonists. In: Bryson PD. Comprehensive Review in Toxicology for Emergency Clinicians. 3rd ed. Washington, DC: Taylor & Francis; 1996:449-458.

EMBEDA is specifically designed with sequestered naltrexone HCl, which is released with manipulation by crushing 1,2

EMBEDA capsules contain pellets of ER morphine sulfate and sequestered naltrexone HCl

The role of sequestered naltrexone HCl in EMBEDA

When taken as directed, the sequestered naltrexone is intended to have no clinical effect

The morphine, a full opioid agonist, binds primarily with the μ-opioid receptor.

If the capsules are crushed or chewed, the sequestered naltrexone releases

  • Up to 100% of the sequestered naltrexone could be released, bioequivalent to an IR naltrexone oral solution of the same dose and competitively bind with the μ-opioid receptors. Naltrexone is a μ-opioid antagonist that reverses the subjective and analgesic effects of μ-opioid receptor agonists, such as morphine.
    • In opioid-tolerant patients, the absorption of naltrexone may increase the risk of precipitating withdrawal
  • 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
ABUSE OF EMBEDA IS STILL POSSIBLE THROUGH ORAL, INTRANASAL, AND INTRAVENOUS ROUTES. DATA FROM LABORATORY AND CLINICAL STUDIES MAY NOT FULLY PREDICT ABUSE POTENTIAL.
 

Naltrexone HCl data

Naltrexone concentrations were measured in a separate, phase 3, long-term, open-label, safety study where an average dose of EMBEDA was up to 860 mg of morphine administered twice daily for 12 months (N=465) 1,3

  • The primary purpose of this study was to evaluate the long-term safety of EMBEDA administered for up to 12 months.3
  • Efficacy was measured in patients with chronic, moderate to severe, nonmalignant pain, using subjects’ pain intensity, as measured with the BPI Short Form questionnaire.4
  • Naltrexone concentrations were measured as a secondary end point.3
    • 11% of blood samples at predose time-points at steady-state had detectable plasma naltrexone concentrations ranging from 4 to 145 pg/mL, which is significantly below the 2000 pg/mL of naltrexone required to be clinically effective.1,4
  • In opioid-dependent individuals, consuming EMBEDA that has been altered by crushing, chewing, or dissolving the pellets can release sufficient naltrexone to precipitate withdrawal.1
    • Symptoms of withdrawal usually appear within 5 minutes of ingestion of naltrexone and can last for up to 48 hours.1

Study description

Phase 3, long-term, open-label safety study of an extended-release formulation of morphine sulfate plus naltrexone in subjects with chronic moderate to severe nonmalignant pain (N=465)3

  • The primary purpose of this study was to evaluate the long-term safety of EMBEDA administered for up to 12 months. Safety was measured using treatment-emergent adverse events (TEAEs), clinical laboratory data, vital signs, physical examinations, electrocardiograms (ECGs), and measures of opioid withdrawal, using the Clinical Opiate Withdrawal Scale (COWS). Efficacy was evaluated based on the subjects’ pain intensity, using the BPI Short Form questionnaire. Additional evaluations of efficacy included the results of the Global Assessment of Study Drug and the use of rescue medication (acetaminophen). One secondary end point was the evaluation of naltrexone concentrations. One hundred twenty-four subjects completed the 12-month treatment phase. Subjects were required to return for a follow-up visit approximately 1 month after the final dose of study drug to assure that the appropriate tapering from study drug and transition to standard of care had been accomplished.3
 
REFERENCES

1. Embeda [prescribing information]. New York, NY: Pfizer Inc; December 2016. 2. Stauffer J, Setnik B, Sokolowska M, Romach M, Johnson F, Sellers E. Subjective effects and safety of whole and tampered morphine sulfate and naltrexone hydrochloride (ALO-01) extended-release capsules versus morphine solution and placebo in experienced non-dependent opioid users: a randomized, double-blind, placebo-controlled, crossover study. Clin Drug Investig. 2009;29(12):777-790. 3. Webster LR, Brewer R, Wang C, et al. Long-term safety and efficacy of morphine sulfate and naltrexone hydrochloride extended release capsules, a novel formulation containing morphine and sequestered naltrexone, in patients with chronic, moderate to severe pain. J Pain Symptom Manage. 2010;40(5):734-746. 4. Bryson PD. Narcotic antagonists. In: Bryson PD. Comprehensive Review in Toxicology for Emergency Clinicians. 3rd ed. Washington, DC: Taylor & Francis; 1996:449-458.