• Beatrice Setnik, Carl L Roland, Veeraindar Goli, Kenneth Sommerville, and Lynn Webster.
• Pfizer Inc, Cary, NC, USA.
• J Opioid Manag. 2013 Mar 1;9(2):139-50.

ObjectiveTo evaluate whether intact or crushed doses of an extended-release formulation of morphine sulfate surrounding an inner core of sequestered naltrexone (MSN) induces signs and symptoms of withdrawal in opioid-dependent patients.DesignRandomized, double-blind, two-way crossover study.SettingSingle center.PatientsFourteen patients with chronic moderate-to-severe noncancer pain receiving opioids were enrolled into the study; six completed the maintenance and treatment phases prior to early study discontinuation for issues with manufacturing; eight discontinued: adverse effects (4), noncompliance (1), patient decision (1), study termination (2).InterventionsPatients were titrated to a stable dose of MSN (ranging from 30/1.2 to 100/4.0 mg of morphine/naltrexone) that was used in the single-dose crossover evaluation of crushed and intact MSN.Main Outcome MeasuresClinical Opiate Withdrawal Scale (COWS).ResultsClinically significant withdrawal (COWS ≥ 13) was observed with rapid onset (≤0.8 hours postdose) in three patients (50 percent) following treatment with crushed MSN at the highest doses administered of ≥60/2.4 mg. Although naltrexone exposure was negligible following exposure to intact MSN, increasing plasma levels of naltrexone and 6-β-naltrexol were associated with COWS score ≥13 in patients who received crushed MSN. COWS ≥ 13 was observed in one patient receiving intact MSN without quantifiable naltrexone concentrations.ConclusionCrushing the MSN capsule may precipitate moderate-to-severe signs and symptoms of opioid withdrawal in opioid-dependent individuals. The negligible exposure to naltrexone following exposure to intact MSN supports that intact capsules may be taken safely without precipitating withdrawal in opioid-dependent individuals.

51 keywords...

hide…