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At least 19 recordsLinked to original sources
PubMed1995

Steady-state pharmacokinetics of hydromorphone and hydromorphone-3-glucuronide in cancer patients after immediate and controlled-release hydromorphone.

Although the pharmacokinetics of oral hydromorphone has been evaluated in healthy volunteers after small single oral doses, data are not available regarding the disposition of hydromorphone and its principal metabolite, hydromorphone-3-glucuronide (H3G), at steady-state and after large oral doses. The authors studied the pharmacokinetics of hydromorphone and H3G after oral administration of an immediate-release (IR) and controlled-release (CR) formulation of hydromorphone at a daily dose of 48 +/- 11 mg (range 6-216 mg) in a randomized, double-blind, steady-state, two-way crossover evaluation in 18 patients with chronic cancer pain. Controlled-release hydromorphone demonstrated equivalent bioavailability and acceptable CR characteristics, when compared with IR hydromorphone (CR vs. IR: AUC0-12 123.10 +/- 20.38 vs. 118.98 +/- 20.92 ng.hr.mL-1, P = NS, Cmax 17.76 +/- 3.07 vs. 19.70 +/- 4.04 ng.mL-1, P = NS, Cmin 6.04 +/- 1.01 vs. 5.28 +/- 1.000 ng.mL-1, P = NS, and Tmax 4.78 +/- 0.78 vs. 1.47 +/- 0.22 hr, P = 0.0008). A significant linear relationship existed between hydromorphone dose and hydromorphone AUC (r = 0.8315, P = 0.0001) and between hydromorphone AUC and H3G AUC (r = 0.8048, P = 0.0001) over a wide dose range. The steady-state molar ratio of H3G to hydromorphone was 27:1. The authors conclude that CR hydromorphone provides a pharmacokinetic profile consistent with 12 hourly dosing and that at steady state, oral hydromorphone is extensively metabolized to H3G, although the pharmacologic activity of this metabolite remains unknown.

Administration, Oral↗
PubMed2002

LC-MS-MS analysis of hydromorphone and hydromorphone metabolites with application to a pharmacokinetic study in the male Sprague-Dawley rat.

1. A high performance liquid chromatography-mass spectrometry-mass spectrometry (LC-MS-MS) assay was developed for the analysis of hydromorphone and its metabolites, namely dihydromorphine, dihydroisomorphine, hydromorphone-3-glucuronide, dihydromorphine-3-glucuronide and dihydroisomorphine-3-glucuronide, in rat plasma samples. 2. Analytes were extracted by solid-phase extraction using C2 cartridges. The extraction recoveries were > 76% for all analytes. Both intra- and interassay variabilities were < or = 12%. Using a plasma sample size of 100 microl, the limits of detection were 7.0 nmol(-1) (2.0 ng ml(-1)) for hydromorphone, dihydromorphine and dihydroisomorphine and 11 nmol l(-1) (5.0 ng ml l(-1)) for hydrormorphone-3-glucuronide, dihydromorphine-3-glucuronide and dihydroisomorhine-3-glucuronide at a signal-to-noise ratio = 3. 3. The present assay was applied to a pharmacokinetic study in rat after intraperitoneal administration of hydromorphone.

Analgesics, Opioid↗
PubMed2005

Comparative efficacy of oral extended-release hydromorphone and immediate-release hydromorphone in patients with persistent moderate to severe pain: two randomized controlled trials.

Two multicenter, randomized, double-blind, crossover studies with identical designs evaluated the efficacy of oral extended-release hydromorphone (HHER) administered q24h compared with immediate-release hydromorphone (HHIR) dosed four times daily in patients with persistent moderate to severe pain. Patients titrated to a stable HHER dose were randomized to individualized doses of HHER or HHIR for 3 to 7 days before crossover to the second treatment. Primary efficacy end point was the mean of average pain intensity (API) scores, rated on a 0- to 10-point numeric scale, over the last 2 days before the pharmacokinetics/pharmacodynamics day of each double-blind period. Difference between treatments (HHER - HHIR) in study 1 was 0.17 with a 90% confidence interval (CI) (-0.01, 0.34); in study 2, difference was 0.07 with a 90% CI (-0.12, 0.26). There were no significant differences between treatments in API scores or amount of rescue medication used at any time interval within the 24-hour dosing period. No reduction in pain control occurred in patients administered HHER at the end of the 24-hour dosing period. Most treatment-emergent adverse events were opioid-related. In these studies, HHER administered q24h and HHIR dosed four times daily provided comparable analgesia at an equivalent total daily dose.

Administration, Oral↗
PubMed1996

A randomized, double-blind, double-dummy, crossover trial comparing the safety and efficacy of oral sustained-release hydromorphone with immediate-release hydromorphone in patients with cancer pain. Canadian Palliative Care Clinical Trials Group.

PURPOSE: To evaluate the safety and efficacy of a new slow-release preparation of hydromorphone (SRH) in the treatment of cancer pain. PATIENTS AND METHODS: Ninety-five adult patients from three Canadian Palliative Care Centers with no evidence of mental impairment received treatment for cancer pain with an oral opioid analgesic. After informed consent was obtained, patients underwent titration to a stable dose of immediate-release hydromorphone (IRH) for 48 hours, and were then randomized to receive IRH or SRH for 5 days in a double-blind basis. During day 6, a crossover took place, and patients received the alternate drug for 5 days. Pain intensity was assessed using a visual analog scale (VAS) and ordinal scale (OS). Side effects were assessed using VAS. Patients and investigators made a blinded global rating of efficacy a blinded final choice between SRH and IRH. RESULTS: In 75 assessable patients, pain intensity of the VAS and OS were (mean +/- SD) 27 +/- 21 and 1.3 +/- 0.6 on IRH, versus 29 +/- 21 (P = .13) and 1.3 +/- 0.6 (P = .19) on SRH, respectively. The total number of extra doses of opioids, global rating, and final blinded choice by both patients and investigators were not significantly different between IRH and SRH. Differences in side effects were not significant. CONCLUSION: Our findings suggest that SRH is as safe and effective as IRH in the treatment of cancer pain.

Adult↗
PubMed1994

Comparative clinical efficacy and safety of immediate release and controlled release hydromorphone for chronic severe cancer pain.

BACKGROUND: The short elimination half-life of hydromorphone necessitates 4-hourly dosing to maintain optimal levels of analgesia in patients with chronic cancer pain. The purpose of this study was to compare the clinical efficacy and safety of controlled release hydromorphone administered every 12 hours and immediate release hydromorphone administered every 4 hours in patients with chronic severe cancer pain. METHODS: Forty-eight patients with stable chronic severe cancer pain were randomized, in a double-masked crossover study, to controlled release hydromorphone every 12 hours or immediate release hydromorphone every 4 hours for 7 days each. Pain intensity was assessed using a visual analog scale (VAS) and the Present Pain Intensity Index of the McGill Pain Questionnaire. Nausea and sedation were also assessed using a VAS. Assessments were made by the patient four times a day at 7:00 a.m., 11:00 a.m., 3:00 p.m., and 7:00 p.m. Use of rescue hydromorphone also was recorded by the patient. RESULTS: Forty-five patients completed the study (26 women, 19 men; mean age, 57.1 +/- 13.6 years) and received a mean daily dose of 76 +/- 133 mg (range, 6-768 mg). There were no significant differences between controlled release hydromorphone and immediate release hydromorphone in overall VAS pain intensity scores (19 +/- 14 vs. 20 +/- 14 mm), ordinal pain intensity scores (1.2 +/- 0.8 vs. 1.2 +/- 0.8) and pain scores by day of treatment or time of day. The daily rescue analgesic consumption during controlled release hydromorphone and immediate release hydromorphone did not differ significantly overall (1.1 +/- 1.1 vs. 1.0 +/- 1.1 doses per day) or with respect to time of day. There were no significant differences in overall VAS sedation scores (18 +/- 18 mm vs. 19 +/- 18 mm) and in overall mean VAS nausea scores (12 +/- 15 mm vs. 11 +/- 14 mm) between controlled release hydromorphone and immediate release hydromorphone. CONCLUSIONS: Controlled release hydromorphone administered every 12 hours is as effective as immediate release hydromorphone administered every 4 hours in the management of patients with chronic severe cancer pain. The benefits of controlled release hydromorphone lie in the convenience of its capsule formulation, which can be sprinkled on soft food, and its 12-hour duration of action, which allows patients uninterrupted sleep and improved compliance.

Chronic Disease↗
PubMed2002

Hydromorphone for acute and chronic pain.

BACKGROUND: While morphine is the gold standard for the management of severe cancer pain, some patients either do not achieve adequate analgesia, or suffer intolerable morphine-related toxicity. For these patients alternatives such as hydromorphone are recommended. However, there appear to be gaps in our understanding of the efficacy and potency of hydromorphone. OBJECTIVES: This review explores and assesses the evidence for the efficacy of hydromorphone in the management of pain. SEARCH STRATEGY: Randomised trials which included hydromorphone were sought using electronic databases and by handsearching relevant journals. Date of the most recent search: February 2000. SELECTION CRITERIA: RCTs which involved the administration of hydromorphone, for both acute and chronic pain conditions, in adults and children, were included. DATA COLLECTION AND ANALYSIS: A data extraction form was designed for the purpose of the review. The validity of each trial for inclusion was assessed using criteria described in the Cochrane Handbook. A grade was allocated to each study on the basis of allocation concealment. A checklist was used to assess blinding. MAIN RESULTS: Forty three studies (2725 subjects) were included in the review. Approximately half of these studies received a low quality score. In addition, the heterogeneity of the studies precluded combination of data and results. A meta-analysis was therefore not possible. Of the 43 included studies, 11 (645 subjects) involved chronic pain conditions (all cancer) and 32 (2080 subjects) acute pain. Three studies were placebo-controlled. Of the remainder, hydromorphone was compared with other opioids (morphine, fentanyl, sufentanyl, meperidine, oxycodone, diamorphine), bupivicaine and with itself, using different formulations. The routes of administration included intravenous, oral, spinal, intramuscular and subcutaneous. Overall, hydromorphone appears to be a potent analgesic. The limited number of studies available suggest that there is little difference between morphine and hydromorphone in terms of analgesic efficacy, adverse effect profile and patient preference. However, as most studies involved small numbers of patients, it is difficult to determine real differences between both drugs. In the context of both acute and chronic pain, the issue of equi-analgesic ratios between morphine and hydromorphone was not resolved. REVIEWER'S CONCLUSIONS: The studies included in this review were varied in terms of quality and methodology. However, the majority demonstrated that hydromorphone is a potent analgesic, that the clinical effects of hydromorphone appear to be dose-related, and that the adverse effect profile of hydromorphone is similar to that of other mu opioid receptor agonists.

Acute Disease↗
PubMed2006

Multicenter, open-label, prospective evaluation of the conversion from previous opioid analgesics to extended-release hydromorphone hydrochloride administered every 24 hours to patients with persistent moderate to severe pain.

BACKGROUND: Hydromorphone hydrochloride is a mu-opioid agonist with dose-dependent analgesic properties. Extended-release hydromorphone hydrochloride (ER hydromorphone HCl) capsules have been developed for administration every 24 hours. OBJECTIVES: This prospective evaluation focused on the first (ie, conversion) phase of 2 identically designed, randomized, controlled studies that compared the safety and efficacy of once-daily ER hydromorphone HCl capsules with immediate-release hydromorphone hydrochloride (IR hydromorphone HCl) tablets administered 4 times daily in the treatment of persistent moderate to severe cancer- and noncancer-related pain. METHODS: Patients being treated with opioid analgesics for persistent moderate to severe pain were converted to ER hydromorphone HCl using an 8:1 conversion ratio. The dose was titrated to attain an average pain intensity (API) score < or = 4 on a 0- to 10-point numeric rating scale. Supplemental oral IR hydromorphone HCl tablets were used as rescue medication at a dose of one eighth to one sixth of the daily ER hydromorphone HCl dose. RESULTS: A total of 343 patients (272 [79%] with cancer pain; mean age, 57.8 years) were enrolled and converted to ER hydromorphone HCl from their previous opioids. About half (51%) were women. At baseline, the mean (SD) API score was 5.3 (2.1). Mean (SD) API scores were 4.7 (2.0) after the first 48 hours and 3.4 (2.1) by the end of titration. After 4 to 21 days of titration, 239 (70%) patients reached stabilization defined as a > or = 48-hour period with an API score of < or =4, unchanged ER hydromorphone HCl dose, and < or = 2 rescue doses per day. The stabilized patients had mean (SD) API scores of 2.7 (1.1) at the end of titration. At stabilization, 102 (43%) of 239 patients remained at their initial conversion dose, 129 (54%) had a dose increase, and 8 (3%) had a dose decrease. Frequent (> or =10% of patients) adverse events that occurred within the first 48 hours after conversion and during the entire titration phase were nausea, somnolence, headache, constipation, vomiting, and dizziness. CONCLUSION: In this prospective evaluation of the conversion and titration phase of 2 randomized, controlled studies, a conversion ratio of 8:1 mg of oral morphine to oral ER hydromorphone HCl was found to be clinically useful in patients with persistent moderate to severe cancer-related or noncancer-related pain.

Administration, Oral↗
PubMed2002

Dose conversion and titration with a novel, once-daily, OROS osmotic technology, extended-release hydromorphone formulation in the treatment of chronic malignant or nonmalignant pain.

The objective of this open-label, repeated-dose, single-treatment, multicenter study was to evaluate the outcomes associated with a standardized conversion from prior opioid therapy to a novel, once-daily, OROS osmotic technology, extended-release (ER) hydromorphone formulation in an outpatient population with chronic malignant or nonmalignant pain. The study period was divided into 3 phases: the prior opioid stabilization phase (> or =3 days), the conversion and titration phase (3-21 days), and the maintenance phase (14 days). Patients were evaluated at 5 visits during the study period. Analgesic efficacy was measured using the Brief Pain Inventory (BPI). At baseline, patients were required to have daily oral morphine equivalent requirements of > or =45 mg. Prior oral or transdermal opioid therapy was converted to single daily doses of ER hydromorphone (8, 16, 32, and 64 mg tablets) at a 5:1 (morphine equivalent to hydromorphone) ratio. Immediate-release (IR) hydromorphone was given as rescue medication for breakthrough pain. Among the 445 patients who enrolled, 404 received the study medication. Of these, 73 (18.1%) had chronic malignant pain and 331 (81.9%) had chronic nonmalignant pain. Dose stabilization (defined as a 3-day period during which the total daily dose of ER hydromorphone remained unchanged and < or =3 doses of IR hydromorphone per day were required) was attained by 73.8% of patients (298/404), of whom 70.1% (209/298) were stabilized with < or =2 titration steps. The mean +/- standard deviation (SD) time to dose stabilization was 12.1 +/- 5.7 days (range of 3 to 33 days). The mean +/- SD final daily dose of ER hydromorphone was 63.4 +/- 129.2 mg. The mean +/- SD final daily dose of IR hydromorphone was 11.5 +/- 36.4 mg, and the mean +/- SD final number of daily doses of IR hydromorphone was 1.7 +/- 1.3. Intent-to-treat and completer analysis demonstrated significant improvements in BPI ratings from prior opioid therapy to the end of ER hydromorphone therapy (P < 0.01 for all pairwise comparisons). Adverse events were consistent with those expected of an opioid agonist in such a patient group, affecting primarily the gastrointestinal and central nervous systems. This uncontrolled study delineates a regimen by which patients with chronic malignant or nonmalignant pain can be readily converted from prior opioid therapy and titrated to an appropriate maintenance dose of ER hydromorphone. Controlled longitudinal studies are required to further evaluate the use of ER hydromorphone in patients with discrete chronic malignant or nonmalignant pain conditions.

Adult↗
PubMed1998

[Hydromorphone--review of pharmacological properties and therapeutic efficacy with special regard to a controlled release preparation].

UNLABELLED: Hydromorphone is a micro receptor agonist opioid. According to WHO recommendations, hydromorphone is to be classified in step III of pain therapy. An oral formulation with a prolonged duration of action of 12 hours has been evaluated only recently. The controlled release capsule is especially suited for the regular twice a day administration in cases of severe and persistent pain. The oral formulation of hydromorphone increases the number of opioid analgesics available for pain therapy in step III. Hydromorphone is recommended when morphine fails to produce sufficient pain relief (despite increase of doses) or causes intolerable side effects (despite treatment of symptoms). In principle, no differences in efficacy of morphine and hydromorphone are to be expected. However, clinical experience shows that changing one opioid analgesic to another one can improve the treatment of patients so that hydromorphone may replace another opioid analgesic to which a patient fails to respond well or develops side effects. The dose of hydromorphone equivalent to 2 times 30 mg controlled release morphine is about 2 times 4 mg. The values for the absorption, bioavailability and maximum plasma concentration after the administration of controlled release hydromorphone every 12 hours -of three times the dose- are equivalent to those of an immediate release tablet given every 4 hours. In several open label and controlled studies, hydromorphone proved to be of good efficacy in the treatment of acute and persistent pain, especially in patients with severe cancer pain. With regard to the incidence of side effects, no significant differences between morphine and hydromorphone could be established. In general, the side effects of hydromorphone are typical for opioid analgesics. DISCUSSION: In conclusion, controlled release hydromorphone seems to be well suited for the control of severe chronic pain when given twice daily.

English Abstract↗
PubMed2000

Comparing the subjective, psychomotor, and physiological effects of intravenous hydromorphone and morphine in healthy volunteers.

RATIONALE: The psychopharmacological profile of hydromorphone, an opioid that has been used extensively for many years for post-operative pain management, has not been adequately characterized in non-drug abusers. OBJECTIVES: To characterize the subjective, psychomotor, and physiological effects of a range of single doses of hydromorphone in non-drug-abusing volunteers and to compare the effects of hydromorphone with that of morphine, a benchmark mu opioid agonist. METHODS: Subjects in a six-session study were injected in an upper extremity vein with 0, 0.33, 0.65, 1.3 mg/70 kg hydromorphone, and 5 and 10 mg/70 kg morphine, using a randomized, double-blind, crossover design. RESULTS: Hydromorphone increased scores on the pentobarbital-chlorpromazine-alcohol group and lysergic acid diethylamide scales and decreased scores on the benzedrine group scale of the Addiction Research Center Inventory, increased adjective checklist ratings of ("dry mouth", "flushing", and "nodding", and increased visual analog scale ratings indicative of both pleasant (e.g., drug liking) and unpleasant (e.g., "feel bad") effects. The subjective effects of morphine at putatively equianalgesic doses to those of hydromorphone were similar to those of hydromorphone, but in some cases of lesser magnitude. Psychomotor impairment was modest with hydromorphone and absent with morphine. Both opioids produced dose-dependent decreases in pupil size. A relative potency analysis indicated that hydromorphone was 10 times as potent as morphine (1 mg hydromorphone=10 mg morphine). CONCLUSIONS: The results of this study demonstrate that 0.33-1.3 mg hydromorphone had orderly, dose-related effects on subjective, psychomotor, and physiological variables, and similar effects to those of a benchmark mu opioid agonist, morphine.

Adult↗
PubMedDate not supplied

In vitro and in vivo studies of subcutaneous hydromorphone implants designed for the treatment of cancer pain.

Unrelieved cancer pain remains a significant problem worldwide. Patients receive inadequate analgesia for a variety of complex and multifactorial reasons. Limited availability of opioids secondary to concerns about potential diversion of these medications for illicit use and poor compliance with oral regimens are significant factors in many countries. This study was designed to develop and test an implantable opioid delivery device capable of releasing a potent opioid subcutaneously at a continuous rate for 4 weeks. A low temperature solvent casting technique was used to formulate ethylene vinyl acetate (EVA) copolymer disks containing 50% hydromorphone by weight. The release characteristics of disks of different height and diameter, coated and uncoated, and with and without a central uncoated channel were studied. The effect of temperature and pH were also evaluated. In vitro assessments were conducted in phosphate buffer using UV spectrophotometry. In vivo studies employed New Zealand White Rabbits and a radioimmunoassay. Plasma levels following hydromorphone delivery by polymer, osmotic pump, and intravenous administration were compared. In vitro, uncoated EVA polymer disks measuring 1.05 cm in diameter and 0.27 cm in height released an initial large burst of hydromorphone. Coating the disks with 100-200 microM of poly(methyl-methacrylate) prevented drug egress from the polymer. A central uncoated channel measuring 1.25 mm in diameter in an otherwise coated polymer virtually eliminated the initial burst of drug release and provided near zero-order hydromorphone release at an average rate of 164 micrograms per hour for 4 weeks. Doubling the height of the polymer approximately doubled the release rate while doubling the diameter of the polymer extended the duration of drug release to over 8 weeks. In rabbits, stable plasma hydromorphone concentrations (23-37 ng/ml) were sustained for 4 weeks following implantation of 2 polymers with an uncoated central channel. No initial burst of hydromorphone release was noted. Increasing the number of polymers produced sustained and predictable increases in plasma hydromorphone concentrations. Plasma levels were similar with subcutaneous hydromorphone delivered by polymer and osmotic pump and much less variable than with intravenous bolus hydromorphone. A uniquely configured implantable drug delivery device has been developed using materials which are approved for human use. It safely and reproducibly releases hydromorphone for weeks in vitro and in vivo without an initial burst of drug release. Varying the thickness, diameter, and number of implants provides flexibility in the release rate and duration of release. This implantable opioid delivery device could provide a sustained subcutaneous infusion of hydromorphone to patient with cancer pain in developed and developing nations without pumps, catheters, or extensive outpatient support services. In addition, it should improve compliance and reduce concern regarding illicit diversion of opioids.

Analgesics, Opioid↗
PubMedDate not supplied

Evidence of morphine metabolism to hydromorphone in pain patients chronically treated with morphine.

Minor metabolic pathways in human subjects have been shown to exist for the conversion of codeine to hydrocodone but have not been reported for the metabolic conversion of morphine to hydromorphone. In this study, urine specimens were collected in an out-patient setting from 13 pain patients who were chronically treated with morphine and other opioids (methadone, oxycodone, and fentanyl). The chronic pain patients were chosen for study because they were treated with high-dose morphine and had no personal or family history of addiction. Results of the initial evaluation and follow up of these patients with random urine tests did not indicate opioid misuse. The specimens were analyzed by GC-MS for the presence of hydromorphone. The reporting limit for hydromorphone was 100 ng/mL. Ten of the 13 morphine-treated patients excreted hydromorphone in minor amounts ranging 120 to 1400 ng/mL. Concurrent morphine concentrations were exceedingly high in these 10 patients and frequently exceeded the upper limit of linearity (> 10,000 ng/mL) of the assay. The ratio of hydromorphone to morphine ranged from 0.015 to 0.024. Morphine concentrations in the three patients in which hydromorphone was not detected tended to be lower than those observed in other patients. For comparison, one additional patient was included in the study, who was prescribed both morphine and hydromorphone. Concentrations of hydromorphone in this patient were in the range of 3400-13,000 ng/mL, while concurrent morphine concentrations were in the range of 3200-6600 ng/mL. These data are highly suggestive that hydromorphone can be produced as a minor metabolite of morphine in humans. Although additional studies in more restricted settings are needed, it is recommended that interpretation of low urinary concentrations of hydromorphone in combination with high concentrations of morphine in morphine-treated pain patients should not be considered as conclusive evidence of hydromorphone misuse.

Adult↗
PubMed2001

Pharmacodynamics of orally administered sustained- release hydromorphone in humans.

BACKGROUND: The disposition kinetics of hydromorphone generally necessitates oral administration every 4 h of the conventional immediate-release tablet to provide sustained pain relief. This trial examined time course and magnitude of analgesia to experimental pain after administration of sustained-release hydromorphone as compared with that after immediate-release hydromorphone or placebo. METHODS: Using a 4 x 4 Latin square double-blind design, 12 subjects were randomized to receive a single dose of 8, 16, and 32 mg sustained-release hydromorphone and placebo. The same subjects had received 8 mg immediate-release hydromorphone before this study. Using an electrical experimental pain paradigm, analgesic effects were assessed for up to 30 h after administration, and venous hydromorphone plasma concentrations were measured at corresponding times. RESULTS: The hydromorphone plasma concentration peaked significantly later (12.0 h [12.0--18.0] vs. 0.8 h [0.8--1.0]; median and interquartile range) but was maintained significantly longer at greater than 50% of peak concentration (22.7 +/- 8.2 h vs. 1.1 +/- 0.7 h; mean +/- SD) after sustained-release than after immediate-release hydromorphone. Similarly, sustained-release hydromorphone produced analgesic effects that peaked significantly later (9.0 h [9.0--12.0] vs. 1.5 h [1.0--2.0]) but were maintained significantly longer at greater than 50% of peak analgesic effect (13.3 +/- 6.3 h vs. 3.6 +/- 1.7 h). A statistically significant linear relation between the hydromorphone plasma concentration and the analgesic effect on painful stimuli existed. CONCLUSION: A single oral dose of a new sustained-release formulation of hydromorphone provided analgesia to experimental pain beyond 24 h of its administration.

Administration, Oral↗
PubMed2001

[Postoperative pain therapy with hydromorphone and metamizole. A prospective randomized study in intravenous patient-controlled analgesia (PCA)].

Most potent opioid analgesics available in Germany have been investigated for use in postoperative patient-controlled analgesia (PCA). To conclude an older comparative series, it was the aim of the present study to define analgesic potency, side effects and patient acceptance of hydromorphone and its interaction with the non-opioid analgesic metamizole. A total of 120 patients recovering from elective abdominal or orthopaedic surgery, performed under standardised general anaesthesia, were randomised into 3 double-blind treatment groups to receive intravenous PCA demand doses of hydromorphone 283 micrograms (low dose, LD), 566 micrograms (high dose, HD) or a combination of hydromorphone 283 micrograms and metamizole 50 mg (low dose hydromorphone + metamizole, LM). Demand-independent low-dose background infusions were added to deliver hydromorphone at 67.9 micrograms/h in all groups, with additional metamizole at 12 mg/h in group LM. Lockout times were set to 2 min. After an average observation time of 24.5 +/- 2.6 h (mean, SD) since start of PCA, cumulative PCA hydromorphone doses in groups LD, HD and LM were 7.8 +/- 3.3, 12.1 +/- 4.8 and 7.5 +/- 2.0 mg, respectively, with the well known large inter-individual variability in all groups. Although hydromorphone consumption was significantly higher in group HD, self-reported pain intensities (VAS, retrospective pain scores) were quite comparable between the groups. Low dose, PCA bolus-linked metamizole did not significantly reduce hydromorphone consumption nor improve patient acceptance. Side-effects were typical for potent postoperative opioids, but never required special treatment; haemodynamic or respiratory complications were not observed in any patient. It can be concluded by comparison with other PCA opioid investigations performed under the same study protocol that hydromorphone is about 3-4 times as potent an analgesic as morphine under the conditions of intravenous postoperative PCA. Due to a favourable patient acceptance, hydromorphone can be recommended as a suitable alternative to other opioids for the treatment of postoperative pain.

Adolescent↗
PubMed2006

A myoclonic reaction with low-dose hydromorphone.

OBJECTIVE: To report a case of myoclonus associated with the use of a low dose of the opioid analgesic hydromorphone. CASE SUMMARY: A 55-year-old white man with a history of nonobstructive hypertrophic cardiomyopathy was hospitalized for treatment of severe chest pain. On hospital day 1, intravenous hydromorphone (6 doses, total dose of 4 mg) was administered. The pain continued and, on day 2, the dose was increased, with a total of 6 mg administered on day 2. The patient developed uncontrollable jerking movements of the head, neck, arms, and legs after he received the hydromorphone. The myoclonic movements stopped within a few hours following discontinuation of hydromorphone and did not recur. DISCUSSION: Myoclonus is a neuroexcitatory symptom that has been reported with chronic, high-dose administration of hydromorphone in patients with impaired renal function. The hydromorphone-3-glucuronide metabolite is devoid of analgesic activity and has been shown to cause neuroexcitatory effects. This patient's symptoms appeared soon after hydromorphone was initiated and resolved in a timely manner after the medication was discontinued. Based on the patient's presentation and course of therapy, it is probable, as indicated by the Naranjo probability scale, that the myoclonic symptoms were induced by hydromorphone. This case was unique, however, in that the patient received hydromorphone for only a short duration and did not have impaired renal function. CONCLUSIONS: Neuroexcitatory effects of hydromorphone may occur at relatively low doses in patients without renal dysfunction. Early recognition and intervention are required to achieve resolution of these symptoms and prevent further sequelae to the patient.

Drug Administration Schedule↗
PubMedDate not supplied

Antinociceptive effects of hydromorphone, butorphanol, or the combination in cats.

The goal of this study was to assess the antinociceptive activity of a single dose of hydromorphone or butorphanol and to examine the effect of their coadministration on thermal thresholds in cats. Thermal thresholds were measured after IM administration of hydromorphone (0.1 mg/kg), butorphanol (0.4 mg/kg), a combination of butorphanol and hydromorphone (0.4 and 0.1 mg/kg), or saline to each of 6 cats in a randomized, blinded, crossover study design. There were at least 12 days between treatments. Thermal thresholds were measured by a thorax-mounted thermal threshold-testing device specifically developed for cats. Thermal thresholds were measured before treatment, at varying intervals to 12 hours, and at 24 hours after treatments. Data were analyzed by an analysis of variance with a repeat factor of time. Dysphoria was associated with butorphanol administration but not with hydromorphone or hydromorphone-butorphanol combined administration. Vomiting was seen with hydromorphone but not with butorphanol or hydromorphone-butorphanol combined. The control treatment group was stable over time (P = .22; mean threshold, 40.1 degrees C). Thresholds were significantly (P < .05) higher than the control treatment between 15 and 165 minutes for butorphanol, between 15 and 345 minutes for hydromorphone, and between 15 and 540 minutes for hydromorphone-butorphanol combined. The addition of butorphanol to hydromorphone decreased the intensity of antinociception during the 1st 2 hours but extended the duration of observable antinociception from 5.75 to 9 hours. The present study suggests that the combination of butorphanol and a pure OP3 (mu) receptor agonist clinically does not produce increased analgesia and indeed may result in decreased analgesia.

Analgesics↗