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Neonatal Network : NN Apr 1996
Review
Topics: Analgesics, Opioid; Drug Monitoring; Humans; Infant, Newborn; Morphine; Neonatal Nursing
PubMed: 8715655
DOI: No ID Found -
Pain Physician 2011Morphine sulfate and naltrexone hydrochloride extended-release capsules (EMBEDA, King Pharmaceuticals, Inc., Bristol, TN), indicated for management of chronic,... (Review)
Review
BACKGROUND
Morphine sulfate and naltrexone hydrochloride extended-release capsules (EMBEDA, King Pharmaceuticals, Inc., Bristol, TN), indicated for management of chronic, moderate-to-severe pain, contain pellets of extended-release morphine sulfate with a sequestered naltrexone core (MS-sNT). Taken as directed, morphine provides analgesia while naltrexone remains sequestered; if tampered with by crushing, naltrexone is released to mitigate morphine-induced euphoric effects. While it is necessary to establish that formulations intended to reduce attractiveness for abuse are successful in doing so, it is also necessary to demonstrate that product therapeutic integrity is maintained for patients.
OBJECTIVES
Data were reviewed from 3 studies to determine: 1) the quantity of naltrexone released when MS-sNT pellets are crushed (MS-sNTC) for at least 2 minutes with mortar and pestle); 2) the extent to which the naltrexone released upon crushing mitigated morphine-induced subjective effects; and 3) whether sequestered naltrexone precipitates opioid withdrawal when MS-sNT is taken as directed.
METHODS
The naltrexone bioavailability study compared naltrexone release from MS-sNTC with that from whole intact MS-sNT capsules (MS-sNTW) and an equal naltrexone solution (NS) dose. Equivalent bioavailability was established if 90% confidence intervals (CIs) for geometric mean ratios (maximum plasma naltrexone concentration [Cmax] and area under the concentration-time curve extrapolated to infinity [AUC∞]) fell between 80% and 125%. The oral pharmacodynamic study assessed drug liking and euphoria and pharmacokinetic properties of MS-sNTC and MS-sNTW compared with morphine sulfate solution (MSS) and placebo. The 12-month, open-label (OL) safety study evaluated safety of MS-sNT administered orally as directed in patients with chronic, moderate-to-severe pain. Safety assessments included withdrawal symptoms based on the Clinical Opiate Withdrawal Scale (COWS).
RESULTS
Naltrexone from MS-sNTC met criteria for equivalent bioavailability to NS. Although morphine relative bioavailability was similar for MS-sNTC and MSS, mean peak (Emax) visual analog scale (VAS) scores for drug liking and Cole/Addiction Research Center Inventory Stimulation-Euphoria were significantly reduced for MS-sNTC vs MSS (p < 0.001). In these 2 studies, a total of 6 participants had one measurement of plasma naltrexone after MS-sNTW that was above the lower limit of quantification. In the OL safety study, 72/93 participants (77%) had no quantifiable naltrexone concentrations. There was neither evidence of naltrexone accumulation for any participant nor any significant correlation with MS-sNT dose, age, or sex. Of 4 participants with the highest naltrexone concentrations, none had COWS scores consistent with moderate opioid withdrawal symptoms. Only 5 participants had COWS scores consistent with moderate opioid withdrawal; all 5 had not taken MS-sNT as directed.
LIMITATIONS
Study populations may not be fully representative of patients receiving opioid therapy for the management of chronic, moderate-to-severe pain and of opioid abusers.
CONCLUSIONS
When MS-sNT capsules are crushed, all of the sequestered naltrexone (relative to oral NS) is released and immediately available to mitigate morphine-induced effects. When MS-sNT was crushed, the naltrexone released abated drug liking and euphoria relative to that from an equal dose of immediate-release morphine from MSS administration in a majority of participants. Naltrexone concentrations were low over a period of 12 months without evidence of accumulation, and there were no observable opioid withdrawal symptoms when MS-sNT was taken as directed.
Topics: Area Under Curve; Biological Availability; Capsules; Drug Combinations; Humans; Morphine; Naltrexone; ROC Curve
PubMed: 21785483
DOI: No ID Found -
The American Journal of Emergency... Aug 2021Renal colic emerging from renal stone is virtually the most severe pain which is experienced. Intravenous infusion of morphine sulfate is known as a usual treatment for... (Comparative Study)
Comparative Study Randomized Controlled Trial
OBJECTIVE
Renal colic emerging from renal stone is virtually the most severe pain which is experienced. Intravenous infusion of morphine sulfate is known as a usual treatment for the disease. This study was designed to compare the efficacy of magnesium sulfate vs morphine sulfate in renal colic relief as for analgesic effect as well as lack of morphine sulfate side effects when using magnesium sulfate.
METHODS
We conducted a double-blind randomized clinical trial in renal colic patients who had referred to the emergency department of Shahid Sadoughi Hospital in Yazd, Iran. A total of 80 eligible patients were selected and randomly assigned into two groups; patients in the case group received 50 mg/kg intravenous magnesium sulfate, and those in the control group 0.1 mg/kg intravenous morphine. The primary outcome was the pain score measured on a numerical rating scale at 0, 10 and 20 minutes after infusion. Data were analyzed using SPSS.
RESULTS
The two groups were similar in terms of demographic features and pain intensity at the time of referral (P <.0001). Ten minutes after drug administration, the pain mean score in the morphine group leveled at 4.88, and in the magnesium group 5.70, which proved to be greater in the morphine group (P- = 0.06). However, the pain mean score turned out to be 3.65 in the morphine group and 3.20 in the magnesium group thus significantly indifferent (P = .48).
CONCLUSIONS
In this study, we concluded that administration of intravenous 50 mg/kg magnesium sulfate could be as effective as morphine in reducing renal colic without any further complications.
Topics: Adult; Analgesics; Analgesics, Opioid; Female; Humans; Infusions, Intravenous; Iran; Magnesium Sulfate; Male; Middle Aged; Morphine; Pain Management; Pain Measurement; Renal Colic
PubMed: 33071088
DOI: 10.1016/j.ajem.2020.07.035 -
Expert Opinion on Pharmacotherapy Jun 2008Morphine sulfate extended-release capsules (KADIAN) contain polymer-coated morphine sulfate pellets that are formulated to deliver sustained plasma morphine levels with...
BACKGROUND
Morphine sulfate extended-release capsules (KADIAN) contain polymer-coated morphine sulfate pellets that are formulated to deliver sustained plasma morphine levels with minimal fluctuation. Morphine sulfate extended-release capsules, the only opioid formulation indicated in the US for both once- and twice-daily (every 12 and every 24 h) dosing, is approved in eight dosage strengths and is effective against pain from diverse sources in a variety of patient types. The formulation of morphine sulfate extended-release capsules allows flexible dosing options: capsules can be taken whole or the contents can be sprinkled on apple sauce or delivered via a gastrostomy tube. Morphine sulfate extended-release capsules have no immediate-release component and no components that would limit high doses.
RESULTS/CONCLUSION
The bioavailability of morphine sulfate extended-release capsules is not compromised when taken with food and dose dumping (immediate elevations in dose) does not occur when morphine sulfate extended-release capsules are taken concomitantly with alcohol. Nearly all patients taking morphine sulfate extended-release capsules for pain relief adhere to the recommended dosing frequency. The flexibility available with morphine sulfate extended-release capsules may offer clinical advantages for pain management.
Topics: Analgesics, Opioid; Capsules; Chronic Disease; Delayed-Action Preparations; Humans; Morphine; Pain; Randomized Controlled Trials as Topic; Trauma Severity Indices; Treatment Outcome
PubMed: 18518787
DOI: 10.1517/14656566.9.9.1585 -
Pharmaceutical Development and... Sep 2022This study aimed to use an intelligent formulation design for the development of mini-tablets for the modified release of morphine sulfate. A formulation (F1) was...
This study aimed to use an intelligent formulation design for the development of mini-tablets for the modified release of morphine sulfate. A formulation (F1) was proposed using the Hiperstart® software. Based on the suggested formulation, two other formulations (F2 and F3) were prepared: one for modified and another for immediate drug release. The powders were characterized as bulk and tapped density, Hausner's factor, and compressibility index analyses. Mini-tablets were directly compressed and characterized by hardness, friability, size, and weight variation. The drug release profile was carried out according to apparatus 1 of USP. Formulations showed good flow properties, and the mini-tablets displayed characteristics according to the specified. In comparison to F3 (immediate release), F1 and F2 displayed slower drug release time, showing the efficiency of the matrix formed. F3 displayed 90% of drug released up to 10 min, while F1 and F2 required 240 min. The results highlight the importance to use intelligent formulation design for the development of improved mini-tablet matrices. Formulation F1 was found to be suitable for modified morphine sulfate release. Further studies with more formulations are necessary for the production of optimized mini-tablets with suitable prolonged morphine sulfate release.
Topics: Delayed-Action Preparations; Drug Compounding; Drug Liberation; Morphine; Powders; Tablets
PubMed: 36017971
DOI: 10.1080/10837450.2022.2118769 -
Expert Opinion on Pharmacotherapy May 2011Public concern over the increased incidence of prescription opioid abuse has prompted the development of products designed to be less attractive for abuse. This article... (Review)
Review
Morphine sulfate and naltrexone hydrochloride extended release capsules for the management of chronic, moderate-to-severe pain, while reducing morphine-induced subjective effects upon tampering by crushing.
INTRODUCTION
Public concern over the increased incidence of prescription opioid abuse has prompted the development of products designed to be less attractive for abuse. This article characterizes morphine sulfate and naltrexone hydrochloride extended release capsules (MS-sNT), the first long-acting opioid approved in the USA for the management of chronic, moderate-to-severe pain that is also designed to reduce drug liking and euphoria if tampered with by crushing.
AREAS COVERED
This article reviews the pharmacokinetics, pharmacodynamics, efficacy and safety of MS-sNT when taken as directed by patients with chronic, moderate-to-severe pain and when tampered with by crushing. A literature search was conducted using Medline, Embase and Biosis for the years from 1995 to January 2011, limited to humans and the English language. Search terms varied with the structure of the databases, and included 'naltrexone' and 'morphine', 'delayed-action preparations', 'drug combinations', 'extended-', 'slow-' or 'controlled-release', 'combinations' and 'EMBEDA'. Also included were congress presentations available from the manufacturer.
EXPERT OPINION
Although no product is likely to be abuse-proof in the hands of clever and determined abusers, new opioid products, such as MS-sNT, may potentially help physicians provide analgesia while at the same time providing a potential way to address the risk of misuse, abuse and diversion. Epidemiological studies are required to determine the impact of such products on real-world abuse.
Topics: Analgesics, Opioid; Delayed-Action Preparations; Drug Combinations; Euphoria; Female; Humans; Male; Morphine; Naltrexone; Pain
PubMed: 21470065
DOI: 10.1517/14656566.2011.571205 -
International Journal of Clinical... Mar 2008Chronic pain, one of the most common reasons for which patients seek medical attention, is defined as pain that persists beyond the normal healing time, usually about 3... (Review)
Review
Chronic pain, one of the most common reasons for which patients seek medical attention, is defined as pain that persists beyond the normal healing time, usually about 3 months. Chronic pain can be malignant or nonmalignant in origin, or can appear in the absence of identifiable pathology. Pharmacological treatment options include non-opioid and opioid analgesics, as well as adjuvant medications. Opioids, the most potent analgesics, are typically reserved for the treatment of chronic, moderate-to-severe pain that has not responded to non-opioid therapy. Morphine remains the gold standard among commonly used opioids. Long-acting opioids are formulated to offer continuous delivery of analgesia around the clock. These agents are formulated to maintain therapeutic blood levels of morphine, with minimal fluctuations. KADIAN Capsules, which contain polymer-coated extended-release morphine sulfate pellets, is one such formulation available for the treatment of moderate-to-severe pain for which an analgesic is indicated for more than a few days. This article reviews KADIAN and identifies unique features from early pharmacokinetic and pharmacodynamic studies, recent data on pharmacokinetic interactions with alcohol and results from recent trials in treating nonmalignant pain.
Topics: Adult; Aged; Alcohol Drinking; Analgesics, Opioid; Capsules; Chronic Disease; Delayed-Action Preparations; Dose-Response Relationship, Drug; Humans; Middle Aged; Morphine; Neoplasms; Pain; Pain Measurement; Severity of Illness Index; Treatment Outcome
PubMed: 18261077
DOI: 10.1111/j.1742-1241.2007.01688.x -
The American Journal of Emergency... Jul 2022
Randomized Controlled Trial
Topics: Administration, Intravenous; Analgesics, Opioid; Double-Blind Method; Humans; Infusions, Intravenous; Magnesium Sulfate; Morphine; Renal Colic
PubMed: 34949475
DOI: 10.1016/j.ajem.2021.12.018 -
American Journal of Perinatology Jan 2014To determine the incidence of admission in labor after morphine sleep (therapeutic rest), patient characteristics associated with labor, and adverse outcomes associated...
OBJECTIVES
To determine the incidence of admission in labor after morphine sleep (therapeutic rest), patient characteristics associated with labor, and adverse outcomes associated with treatment.
METHODS
We reviewed medical records of women treated with morphine sleep from December 2005 to December 2009. Variables evaluated included medications used for treatment, cervical examination, maternal demographic characteristics and obstetric history, fetal heart rate patterns, and maternal/neonatal outcomes. These characteristics were compared between those admitted in labor after morphine sleep versus those discharged.
RESULTS
Fifty-eight women received morphine sleep: 36 (62%) were admitted in labor, 17 (29%) were discharged, and 5 (9%) were admitted secondary to category II fetal heart rate tracings. All fetuses had category I fetal heart rate tracings prior to treatment. Median dose of morphine sulfate was 20 mg. Those with effacement > 50% (p < 0.01) and carrying term gestations (p < 0.01) were more likely to be admitted in labor after treatment. There were no adverse maternal outcomes. There were no significant differences in neonatal outcomes.
CONCLUSION
Sixty-two percent of women were admitted in labor after morphine sleep. Admission effacement > 50% and term gestational age were associated with admission in labor. There were no significant differences in maternal or neonatal morbidity in those admitted versus discharged home after treatment with morphine sleep.
Topics: Abdominal Pain; Analgesics, Opioid; Cervix Uteri; Female; Gestational Age; Heart Rate, Fetal; Hospitalization; Humans; Labor, Obstetric; Morphine; Pregnancy; Uterine Contraction
PubMed: 23471604
DOI: 10.1055/s-0033-1334448 -
The American Review of Respiratory... Sep 1984To determine whether morphine sulfate alters the bronchoconstrictive response to inhalation of distilled water, we gave 13 subjects with mild asthma 0.15 mg/kg morphine... (Clinical Trial)
Clinical Trial Comparative Study
To determine whether morphine sulfate alters the bronchoconstrictive response to inhalation of distilled water, we gave 13 subjects with mild asthma 0.15 mg/kg morphine sulfate or normal saline intravenously, after which they inhaled increasing volumes of nebulized distilled water from an ultrasonic nebulizer. We constructed stimulus-response curves, and by interpolation determined the provocative output of the nebulizer that resulted in a 50% increase in SRaw from baseline (PO50). On a separate day the subjects inhaled 2.0 mg of atropine sulfate 30 min before they inhaled distilled water. We compared the bronchoconstrictive response after morphine and after atropine with the bronchoconstrictive response after saline by determining the ratio of the PO50 values. Atropine was considered effective in inhibiting bronchoconstriction in 7 of the 13 subjects in whom the ratio of PO50 after atropine to the PO50 after saline was greater than 2.0. By similar criteria, morphine was also considered effective in 5 of these 7 subjects. Neither atropine nor morphine was effective in the remaining 6 subjects. By chi-square analysis, we found a positive correlation between the inhibitory effects of morphine and those of atropine (p less than 0.05). In the 5 subjects in whom morphine was effective, naloxone reversed the inhibitory effect of morphine. Atropine caused significant baseline bronchodilation when compared with placebo (normal saline), whereas morphine did not. We conclude that opiate receptor stimulation by morphine causes inhibition of the vagally mediated component of water-induced bronchoconstriction.
Topics: Adult; Airway Resistance; Asthma; Atropine; Bronchi; Female; Humans; Lung Volume Measurements; Male; Morphine; Naloxone; Vagus Nerve; Water
PubMed: 6476586
DOI: 10.1164/arrd.1984.130.3.363