Efficacy and safety of long-term, once-daily morphine sulfate extended-release capsules in cancer patients with chronic, moderate-to-severe pain

EMBEDA® (morphine sulfate and naltrexone hydrochloride) Extended Release Capsules for oral use, indicated for the management of chronic moderate to severe pain, contain extended-release pellets of morphine sulfate with a sequestered core of naltrexone, an opioid antagonist. When EMBEDA is taken orally as directed, it is bioequivalent with regard to rate and extent of plasma morphine absorption to KADIAN® (morphine sulfate extended-release) Capsules, a similar formulation without naltrexone. EMBEDA has been shown to be significantly superior to placebo in maintaining pain relief over 12 weeks and, in one of the longest durability studies, to reduce pain intensity for up to 12 months. Upon tampering by crushing EMBEDA, naltrexone is released to mitigate morphine-induced euphoria. Euphoria and drug-liking measures after oral administration of intact or crushed EMBEDA were similar, and were reduced compared with morphine sulfate solution; crushing EMBEDA did not yield more euphoria and desirability for abuse than the intact product. The most common adverse events after long-term use were constipation, nausea, and vomiting, which are typical of opioids. Over long-term use as directed, there was no evidence of naltrexone accumulation or opioid withdrawal. The impact of formulations such as EMBEDA on the abuse rate among real-world abusers requires long-term epidemiologic studies.

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Short- and Long-Term Cardiovascular Effects of Mixed Amphetamine Salts Extended-Release in Adolescents With ADHD

CNS Spectrums ◽

10.1017/s1092852900014115 ◽

2005 ◽

Vol 10 (S15) ◽

pp. 22-30 ◽

Cited By ~ 15

Author(s):

Timothy E. Wilens ◽

Thomas J. Spencer ◽

Joseph Biederman

Keyword(s):

Extended Release ◽

Cardiovascular Effects ◽

Dose Titration ◽

Open Label ◽

Double Blind ◽

Once Daily ◽

Open Label Extension ◽

Short And Long Term ◽

Clinically Significant

AbstractObjectiveAssess cardiovascular effects of once-daily mixed amphetamine salts extended release (MAS XR) in adolescents (13–17 years of age) with attention-deficit/hyperactivity disorder (ADHD).MethodsBlood pressure (BP), pulse, and electrocardiograms were assessed in 327 healthy subjects during a 4-week, randomized, double-blind, placebo-controlled, forced dose-titration study. Placebo (n=69) or once-daily MAS XR(10, 20, 30, or 40 mg) was administered to subjects ≤75 kg (n=233); 50- and 60-mg MAS XR was administered to subjects >75 kg (n=25). One hundred thirty-eight subjects participated in a 6-month, open-label extension study.FindingsChanges in BP and QTcB (Bazett's formula) intervals at 4 weeks with MAS XR were not significantly different from the placebo group. Pulse increased by 5.0 and 8.5 bpm after 3 weeks with MAS XR 20 and 50 mg/day, respectively (P≤.002). After 6 months of open-label MAS XR treatment, mean increases in systolic BP (1.7 mm Hg; P=.0252) and pulse (4.4 bpm; P<.0001) were statistically, but not clinically, significant diastolic BP was not significantly changed (0.6 mm Hg) A decrease in QTcB interval (-4.6±19.9 msec) was statistically (P=.009), but not clinically, significant. There were no serious cardiovascular adverse events.ConclusionCardiovascular effects of short- and long-term MAS XR treatment (≤60 mg/day) were minimal in otherwise healthy adolescents with ADHD.

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