Immediate-release Hydrocodone Research Articles

Evaluating the Impact of Auto-Calculation Settings on Opioid Prescribing at an Academic Medical Center

Overprescribing of opioids is a key contributor to the opioid epidemic, which has led to a substantial increase in overdose deaths. The purpose of this study was to evaluate the discontinuation of a dispense quantity automatic calculation function on prescribing of as needed (PRN) opioids. During the implementation of a new electronic health record (EHR), Vanderbilt University Medical Center discontinued functionality that autocalculated the maximum needed dispense quantity for PRN outpatient prescription opioids. This study analyzed prescribing trends for immediate-release hydrocodone- and oxycodone-containing prescriptions 90 days before and after implementation of the new EHR. A total of 21,323 prescriptions were analyzed in the preintervention group and 22,730 prescriptions in the postintervention group. Discontinuing the autocalculation functionality resulted in a mean decrease of 1.4 dispense units per prescription (58.5 vs. 57.1; p = 0.006) across all patient care areas. The most significant finding was a 10.5% relative decrease in dispense units from inpatient discharge prescriptions (37.2 vs. 33.3; p < 0.001). In the new EHR, PRN oxycodone products defaulted to a dispense quantity of 30, which resulted in a 142.0% (10.0% vs. 24.2%; p < 0.001) increase in oxycodone prescriptions ordered for 30 dispense units but was a net reduction in the doses dispensed per oxycodone prescription. This study suggests that removing the autocalculation functionality reduced the number of opioid units ordered. In addition, using a default dispense quantity for PRN opioid prescriptions may decrease the number of opioid dispense units per prescription.

Characterizing Abuse Progression of Immediate-Release Hydrocodone Combination Products

This study examined patterns of hydrocodone combination product (HCP) abuse and their potential role in abuse progression of prescription opioids and other drugs. An Internet survey was administered to 472 adult opioid users in the United States who used HCPs nonmedically. Alternate routes (33%) and concomitant drug use (45%) were indicated more frequently during respondent’s most recent HCP nonmedical use compared with their initial use (20% and 24%, respectively). Those initiating HCP nonmedical use during adolescence used alternate routes (e.g., chewing, snorting) throughout their lifetime more frequently (69.5%) compared with those older when initiating HCP nonmedical use (51.0%). A different abuse pattern was observed from first to most recent HCP use, starting with oral administration of intact tablets followed by use of alternate routes and concomitant use of illicit drugs, sometimes use of heroin. These data may inform future public health interventions, including the potential development of abuse-deterrent immediate-release opioids.

Pharmacokinetics and Abuse Potential of Benzhydrocodone, a Novel Prodrug of Hydrocodone, After Intranasal Administration in Recreational Drug Users.

ObjectiveDeveloping an acetaminophen-free, immediate-release hydrocodone product remains an unmet medical need; however, new opioid analgesics should not introduce new abuse risks. Benzhydrocodone is a prodrug of hydrocodone that must be metabolized into hydrocodone by enzymes in the intestinal tract to optimally deliver its pharmacologic effects. This study evaluated the intranasal pharmacokinetics and abuse potential of benzhydrocodone active pharmaceutical ingredient (API) compared with hydrocodone bitartrate (HB) API.DesignSingle-center, randomized, double-blind, crossover study.SettingClinical research site.SubjectsHealthy adult, nondependent, recreational opioid users.MethodsSubjects (N = 51 Completers) were randomized to receive 13.34 mg of intranasal benzhydrocodone API and 15.0 mg of intranasal HB API (molar-equivalent doses of hydrocodone). Blood samples were taken, and Drug Liking scores (assessed on a bipolar visual analog scale) were obtained throughout each dosing interval. Nasal irritation and safety were assessed.ResultsPeak hydrocodone plasma concentration (Cmax) was 36.0% lower, and total hydrocodone exposures (AUClast and AUCinf) were 20.3% and 19.5% lower, respectively, for benzhydrocodone API compared with HB API (P < 0.0001). All partial AUC values were lower for benzhydrocodone API, with a ≥ 75% reduction in hydrocodone exposure at all time intervals up to one hour postdose (P < 0.0001). Median Tmax of hydrocodone following benzhydrocodone API was delayed by more than one hour compared with HB. Drug Liking score, as assessed by maximal liking (Emax), was significantly lower for benzhydrocodone API vs HB API (P = 0.004), with 45% of subjects showing a ≥ 30% reduction in Drug Liking Emax.ConclusionReductions in hydrocodone exposure and associated decreases in Drug Liking relative to HB suggest that the prodrug benzhydrocodone may deter intranasal abuse.

Patterns of abuse and routes of administration for immediate-release hydrocodone combination products.

PurposePrescriptions for hydrocodone immediate‐release (IR) combination products have recently decreased, yet they represent the majority of opioid prescriptions dispensed and are commonly abused analgesics among both adults and adolescents. Little data exist to understand the contribution of IR products to the problem of prescription opioid abuse. This study aimed to better understand abuse patterns for hydrocodone IR combination products among adult and adolescent substance abusers.MethodsThis cross‐sectional study examines abuse prevalence (including abuse adjusted for prescription volume and morphine milligram equivalents) and abuse characteristics for hydrocodone IR combination products and other prescription opioids among separate samples of adults and adolescents assessed for substance abuse problems or entering treatment from January 2012 through June 2015.ResultsResults indicate higher abuse for hydrocodone IR combination products than other opioid categories per 100 assessments but lower per prescriptions dispensed. Hydrocodone IR combination products had similar abuse prevalence to all extended‐release and long‐acting opioids when considering abuse measured per morphine milligram equivalents dispensed. An upward trend in hydrocodone IR combination product abuse was observed among adult substance abusers comparing the period prior to and after Drug Enforcement Administration rescheduling of these products in October 2014. Most individuals reported oral abuse of hydrocodone IR combination products, but snorting, reported by 23% of hydrocodone IR combination product abusers, also appears to be a route of abuse that may have public health relevance.ConclusionsGiven their high prescription volume, hydrocodone IR combination products, even at a relatively low prevalence of abuse, may contribute substantially to the overall problem of prescription opioid abuse. Additional public health interventions, including development of abuse‐deterrent formulations for these types of opioid products may aid in reducing their abuse.

Opioid Treatment Patterns Following Prescription of Immediate-Release Hydrocodone.

Immediate-release (IR) hydrocodone is the most widely prescribed opioid in the United States; however, little is known about the utilization patterns and duration of opioid use among patients prescribed IR hydrocodone. A better understanding of the use of IR hydrocodone would result in more appropriate prescribing patterns of extended-release opioids. To assess downstream length of opioid therapy and utilization patterns of extended-release/long-acting (ER/LA) opioids among patients on IR hydrocodone to provide a better understanding of how IR and ER/LA opioids are used to manage pain. Retrospective analysis using health care claims from the Truven MarketScan Commercial, Medicare Supplemental, and Medicaid databases was performed. Patients prescribed IR hydrocodone during the 6-month baseline period (July 2011-December 2011) and with continuous enrollment for a 12-month follow-up period (2012) post-index date (January 1, 2012) were selected. Downstream length of therapy, defined as number of days supplied with opioids, and downstream use of ER/LA opioids during follow-up were examined by average pills per month (≤ 60 vs. > 60 pills per month) and days supply (< 60 vs. ≥ 60 days supply) of IR hydrocodone during baseline to mimic intermittent and consistent IR users. At baseline, 1,743,933 commercial, 277,096 Medicare, and 157,922 Medicaid IR hydrocodone patients were identified. During follow-up, 1.7%, 2.9%, and 2.8% of patients initiated (i.e., converted to or newly started) ER/LA opioids for commercial, Medicare, and Medicaid groups, respectively. Approximately 90% of patients were prescribed IR hydrocodone for less than 2 months in the following year, while 10% were high utilizers, averaging nearly 8 months of prescribed opioid use during follow-up. Downstream initiation of ER/LA opioids was significantly higher among commercial patients prescribed IR hydrocodone for > 60 pills per month than with ≤ 60 pills per month (7.8% vs. 1.2%, respectively, P < 0.05) at baseline. For commercial patients initiating ER/LA opioids, length of ER/LA therapy during follow-up was significantly longer among patients with baseline IR hydrocodone > 60 pills per month than with ≤ 60 pills per month. All results were consistent when examined by levels of days supply. A majority of the population prescribed IR hydrocodone was not prescribed opioid therapy beyond 2 months on average in the 1-year follow-up period. Only a small subset of patients with increased pills per month or days supply of IR hydrocodone in the baseline period continued to be high utilizers in the following year, averaging nearly 8 months of prescribed opioid use. A limited proportion of patients prescribed IR hydrocodone converted to ER/LA opioids. This knowledge can assist policymakers and physicians, providing an opportunity to identify small subsets of patients to improve ER/LA opioid prescribing. Funding and support for this study was provided by Purdue Pharma L.P. Consulting fees were paid to Evidera by Purdue Pharma L.P. for this study. Kansal, Chitnis, and Paramore are employees of Evidera and were paid consultants to Purdue Pharma for this research. Holly is an employee for Purdue Pharma, and Bell and Ben-Joseph were full-time employees of Purdue Pharma during the design, planning, and execution of the studies and during the preparation of this manuscript. Burgoyne and Brixner were consultants on this project. Study design was created by Ben-Joseph, Brixner, Paramore, and Burgoyne. Data were collected by Kansal, Chitnis, Bell, Ben-Joseph, and Holly and interpreted by Ben-Joseph, Bell, Kansal, and Holly, with assistance from Brixner, Paramore, Burgoyne, and Chitnis. The manuscript was written by Ben-Joseph, Bell, Paramore, Chitnis, and Holly, with assistance from Kansal, and revised by Bell and Holly, along with Ben-Joseph, Brixner, Kansal, Paramore, Burgoyne, and Chitnis.

Pharmacokinetic Profile and Sustained 24-hour Analgesia of a Once-daily Hydrocodone Bitartrate Extended-release Tablet with Abuse-deterrent Properties

PurposeThe purpose of this study was to evaluate the pharmacokinetics (PK) and 24-hour analgesic effectiveness of once-daily, single-entity, extended-release hydrocodone (HYD) with abuse-deterrent properties. MethodsFour studies were included. Three open-label PK studies had the following designs: single-dose, 5-treatment, 4-period, crossover, dose-proportionality study; HYD 120 mg for 5 days (steady-state study 1); 2-treatment, 2-period, multiple-dose crossover study assessing the relative bioavailability of HYD 30 mg and hydrocodone 7.5 mg/ibuprofen 200 mg administered every 6 hours (steady-state study 2). A long-term, open-label study assessed the safety and effectiveness of HYD 20 to 120 mg in patients during a 52-week maintenance period. FindingsThirty-one, 25, and 22 healthy subjects completed the dose-proportionality study, steady-state study 1, and steady-state study 2, respectively, while 410 patients with moderate to severe chronic nonmalignant and non-neuropathic pain completed the long-term effectiveness study. Mean systemic exposure and peak plasma concentration were dose proportional after administration of single doses of HYD 20 to 120 mg. Pharmacokinetic profiles were comparable at day 1 and day 5 after administration of HYD 120 mg once daily. Once-daily HYD 30 mg was associated with lower-fluctuating plasma hydrocodone concentrations compared with immediate-release hydrocodone 7.5 mg/ibuprofen 200 mg administered every 6 hours. In the long-term study, pain control was consistent over the 24-hour dosing interval. ImplicationsOnce-daily HYD exhibits linear, dose-proportional PK properties and is associated with a lower variability in plasma hydrocodone concentrations when compared with an immediate-release hydrocodone combination product. Notably, analgesia provided by HYD is sustained during the 24-hour dosing interval. ClinicalTrials.gov identifier: NCT01400139 (Study 4).

Characterizing downstream healthcare resource utilization and costs based on prior utilization patterns of immediate-release hydrocodone

Objective:To assess downstream healthcare resource utilization (HRU) and costs among immediate release (IR) hydrocodone patients by days’ supply and average doses/month in the prior 6 months.Methods:Retrospective analysis using healthcare claims from Truven MarketScan commercial, Medicare supplemental, and Medicaid multistate databases was performed. Patients prescribed IR hydrocodone during the 6-month baseline (July–December 2011), and with continuous enrollment during baseline and the 12-month follow-up (2012) were selected. HRU and per-patient-per-month (PPPM) costs (2014 US dollars) were assessed at follow-up. Descriptive analyses and multivariate regressions were conducted to compare HRU and costs at follow-up by days’ supply (<60 vs ≥60 days) and average doses per month (≤60 vs >60 doses/month) of IR hydrocodone at baseline.Results:In total, 1,698,845 commercial, 264,038 Medicare, and 151,063 Medicaid IR hydrocodone patients were identified. During follow-up, commercial patients with prior ≥60 days’ supply were more likely to have an inpatient admission (13.2% vs 7.5%), outpatient hospital visit (69.1% vs 57.0%), office visit (97.6% vs 91.0%), emergency room (ER) visit (28.1% vs 21.4%), and had higher PPPM total costs ($1494 vs $842) than the <60 days’ supply sub-group (all p < 0.05). Among commercial patients the adjusted odds ratio for prior ≥60 days’ supply of IR hydrocodone vs prior <60 days’ supply was 1.62 (inpatient), 1.33 (outpatient), 2.58 (office visit) and 1.48 (ER) (all p-values <0.05). Adjusted all-cause total costs were higher ($1245 vs $851, p <0.05) among commercial patients with longer days’ supply than those with shorter days’ supply. Trends were similar with ≤60 vs >60 doses per month sub-groups and across all plan types.Conclusion:Increased days’ supply and higher doses/month of IR hydrocodone in the prior 6 months may help to predict levels of HRU and costs in the following year, providing an opportunity to identify patients in order to implement interventions to improve their quality of care.

Non-oral abuse of immediate-release hydrocodone

83% to 100%, and none of the participants missed more than one counseling session. There was a significant decrease in opioid (heroin) use, 68% of the participants reported using heroin at 1 month, 13% at 2 months and none after 3 months of treatment. Fifty-one (35.2%)wereHIV-positive,with fournotpreviously known to be positive. All 51 HIV-positive participants received HIV treatment. Eighty-nine (68.0%)were HCV-positive, 42 (46.7%)were newlydiagnosed.Only2participants (2.4%)had receivedHCVtreatment. Conclusions: At 6-month, the findings showed the added value of an integrated treatment programondrug use, HIV detection, and access to HIV care. Long-term follow-up is needed to confirm the impact of this program. Financial support: NIDA R01-DA033671-01.

Single- and multiple-dose pharmacokinetics of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen (MNK-155) compared with immediate-release hydrocodone bitartrate/ibuprofen and immediate-release tramadol HCl/acetaminophen.

ObjectiveTo characterize the single-dose and steady-state pharmacokinetics (PK) of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen (IR/ER HB/APAP), IR HB/ibuprofen, and IR tramadol HCl/APAP.MethodsIn this single-center, open-label, randomized, four-period crossover study, healthy participants received four treatments under fasted conditions: 1) a single dose of two IR/ER HB/APAP 7.5/325 mg tablets (15/650 mg total dose) on day 1, followed by two tablets every 12 hours (q12h) beginning on day 3; 2) a single dose of IR HB/ibuprofen 15/400 mg (divided as one 7.5/200 mg tablet at hour 0 and 6), followed by one tablet every 6 hours (q6h) beginning on day 3; 3) a single dose of IR tramadol HCl/APAP 75/650 mg (divided as one 37.5/325 mg tablet at hour 0 and 6), followed by one tablet q6h beginning on day 3; and 4) a single dose of three IR/ER HB/APAP 7.5/325 mg tablets (22.5/975 mg total dose) on day 1, a three-tablet initial dose at 48 hours followed by two-tablet doses q12h beginning on day 3. Hydrocodone and APAP single-dose and steady-state PK were assessed. Adverse events were monitored.ResultsThe PK analysis was carried out on 29 of 48 enrolled participants who completed all treatment periods. Single-dose hydrocodone exposure was similar for IR/ER HB/APAP 22.5/975 mg and IR HB/ibuprofen 15/400 mg; time to maximum observed plasma concentration was shorter and half-life was longer for IR/ER HB/APAP (22.5/975 mg and 15/650 mg) vs IR HB/ibuprofen. Single-dose APAP exposure was similar for IR/ER HB/APAP 15/650 mg and IR tramadol HCl/APAP 75/650 mg. Steady-state hydrocodone and APAP exposures were similar between treatments. Adverse events were similar for each treatment and typical of low-dose combination opioid analgesics. With dosing q12h, IR/ER HB/APAP had half as many concentration peaks and troughs as the comparators treated q6h.ConclusionWith dosing q12h, IR/ER HB/APAP provided similar peak and total steady-state hydrocodone and APAP exposure vs IR comparators.

A Retrospective Cohort Study of Long-Term Immediate-Release Hydrocodone/Acetaminophen Use and Acetaminophen Dosing Above the Food and Drug Administration Recommended Maximum Daily Limit Among Commercially Insured Individuals in the United States (2008–2013)

Immediate-release (IR) hydrocodone/acetaminophen is the most prescribed opioid in the United States; however, patterns of use, including long-term treatment and dose, are not well described. Duration of use, including the percentage of patients on long-term treatment (>90 days of continuous use), was assessed for patients newly prescribed IR hydrocodone/acetaminophen compared to other opioid analgesics in a national commercial insurance database (January 2008–September 2013). Though only a small percentage of IR hydrocodone/acetaminophen patients continued treatment long-term (1.7%), the number was large (104,839) and was nearly 5 times the number receiving extended-release (ER) morphine (n = 22,338) and nearly 4 times the number receiving ER oxycodone (n = 26,946) long-term. Using a less conservative allowable gap in treatment increased the number of patients meeting the criteria for long-term use (approximately 160,000 for IR hydrocodone/acetaminophen vs <30,000 for ER morphine and ER oxycodone). Most patients meeting these criteria received IR hydrocodone doses between >20 and ≤60 mg/d (n = 56,220, 53.6%) in month 4; 5.5% (n = 5,743) received doses >60 mg/d. Moreover, approximately 15% of IR hydrocodone/acetaminophen patients (n > 900,000) were prescribed total daily acetaminophen doses exceeding 4 g (the limit recommended by the U.S. Food and Drug Administration) at their initial IR hydrocodone/acetaminophen prescription or any time during therapy. PerspectiveAlthough most patients were prescribed IR hydrocodone/acetaminophen for acute pain, the number of patients prescribed long-term therapy exceeds the number of patients prescribed ER opioids. It is important to consider the benefits and risks inherent with long-term opioid therapy, whether with IR or ER opioids, to ensure safe use of these products.

Human abuse potential of immediate-release/extended-release versus immediate-release hydrocodone bitartrate/acetaminophen: a randomized controlled trial in recreational users of prescription opioids

Background. The abuse potential of prescription opioids is well established. This study compared positive, subjective drug effects of single, equal doses of biphasic immediate release (IR)/extended release (ER) hydrocodone bitartrate (HB)/acetaminophen (acetyl-p-aminophenol [APAP]) 7.5/325 mg tablets versus IR HB/APAP 7.5/325-mg tablets and placebo. Methods: Healthy adult recreational users of prescription opioids entered this randomized, double-blind, double-dummy, active- and placebo-controlled, seven-way crossover study. Participants received single, total doses of IR/ER HB/APAP 22.5/975 mg (intact; three active tablets) and 45/1950 mg (intact and crushed [encapsulated]; six active tablets), IR HB/APAP 22.5/975 mg (intact; three active tablets) and 45/1950 mg (intact and crushed [encapsulated]; six active tablets), and placebo. Peak subjective effects (Emax); time to peak effects (TEmax); and area under the drug–effect curves for drug liking, high, and good drug effects were measured using visual analog scales. Median values with 95% confidence interval (CI) were compared using analysis of variance. Results: Among completers (n = 52), IR/ER HB/APAP produced delayed and lower peak effects compared to equal doses of IR HB/APAP. Comparing intact tablets, the drug liking Emax (median [95% CI]) was significantly lower for IR/ER HB/APAP 45/1950 mg (78.0 [73.0, 81.0]) than an equal dose of IR HB/APAP (89.5 [85.0, 93.0]; difference, –8.5 [–12.0, –6.0]; P < 0.001). Similar results were observed for intact IR/ER HB/APAP and IR HB/APAP 22.5/975 mg. Crushing IR/ER HB/APAP 45/1950 mg delayed these effects compared with an equal dose of crushed IR HB/APAP and intact IR/ER HB/APAP. Conclusion. IR/ER HB/APAP resulted in lower subjective positive drug effects than an equal dose of IR HB/APAP. Crushing IR/ER HB/APAP also delayed the onset of subjective effects compared with intact IR/ER HB/APAP. These findings suggest that biphasic IR/ER HB/APAP has lower abuse potential than IR HB/APAP in single equal doses. Registration: This Phase I clinical trial conducted in the USA was not registered.

A long-term, open-label safety study of single-entity hydrocodone bitartrate extended release for the treatment of moderate to severe chronic pain.

ObjectiveTo evaluate the long-term safety, tolerability, and effectiveness of single-entity extended-release hydrocodone in opioid-experienced subjects with moderate to severe chronic pain not receiving adequate pain relief or experiencing intolerable side effects from their current opioid.MethodsThis multicenter, open-label study started with a conversion/titration phase (≤6 weeks) where subjects (n=638) were converted to individualized doses (range 20–300 mg) of extended-release hydrocodone dosed every 12 hours, followed by a 48-week maintenance phase (n=424). The primary objective (safety and tolerability) and the secondary objective (long-term efficacy as measured by change in average pain score; 0= no pain, 10= worst imaginable pain) were monitored throughout the study.ResultsSubjects were treated for a range of chronic pain etiologies, including osteoarthritis, low back pain, and neuropathic and musculoskeletal conditions. The mean hydrocodone equivalent dose at screening was 68.9±62.2 mg/day and increased to 139.5±81.7 mg/day at the start of the maintenance phase. Unlimited dose adjustments were permitted at the investigator’s discretion during the maintenance phase, reflecting typical clinical practice. No unexpected safety issues were reported. Common adverse events during the conversion/titration and maintenance phases, respectively, were constipation (11.3% and 12.5%), nausea (10.7% and 9.9%), vomiting (4.1% and 9.7%), and somnolence (7.7% and 4.2%). Four deaths occurred during the study; all were considered unrelated to treatment. One subject died 13 months after the study ended. From the start to end of the conversion/titration phase, 84% of subjects had a clinically meaningful improvement in average pain score (≥30% improvement), and the mean average pain scores remained stable through the maintenance phase.ConclusionThis single-entity, extended-release formulation of hydrocodone was generally safe, well tolerated, and effective in reducing chronic pain for 48 weeks. This formulation provides a new option for patients experiencing chronic pain, especially those who are taking immediate-release hydrocodone and have concerns about liver toxicity due to acetaminophen.

(430) Single- and multiple-dose pharmacokinetics of 1 and 2 tablets of extended-release hydrocodone bitartrate/acetaminophen tablets (MNK-155) compared with immediate-release hydrocodone bitartrate/acetaminophen

(430) Single- and multiple-dose pharmacokinetics of 1 and 2 tablets of extended-release hydrocodone bitartrate/acetaminophen tablets (MNK-155) compared with immediate-release hydrocodone bitartrate/acetaminophen

(421) Comparison of subjective drug effects of orally administered MNK-155 extended-release hydrocodone bitartrate/acetaminophen (HB/APAP ER) tablets versus immediate-release hydrocodone bitartrate/acetaminophen tablets in recreational users of prescription opioids

(421) Comparison of subjective drug effects of orally administered MNK-155 extended-release hydrocodone bitartrate/acetaminophen (HB/APAP ER) tablets versus immediate-release hydrocodone bitartrate/acetaminophen tablets in recreational users of prescription opioids

(428) Single- and multiple-dose pharmacokinetics of extended-release hydrocodone bitartrate/acetaminophen tablets (MNK-155) with a loading dose of 3 tablets followed by 2 tablets administered q12h compared with immediate-release hydrocodone bitartrate and acetaminophen tablets

(428) Single- and multiple-dose pharmacokinetics of extended-release hydrocodone bitartrate/acetaminophen tablets (MNK-155) with a loading dose of 3 tablets followed by 2 tablets administered q12h compared with immediate-release hydrocodone bitartrate and acetaminophen tablets

(431) Single- and multiple-dose pharmacokinetics of extended-release hydrocodone bitartrate/acetaminophen tablets (MNK-155) with and without loading dose compared with marketed immediate-release hydrocodone bitartrate/acetaminophen tablets

(431) Single- and multiple-dose pharmacokinetics of extended-release hydrocodone bitartrate/acetaminophen tablets (MNK-155) with and without loading dose compared with marketed immediate-release hydrocodone bitartrate/acetaminophen tablets

Evaluation of the abuse potential of an extended release hydrocodone bitartrate tablet formulated with OraGuard™ technology in non-dependent, recreational opioid users

This study examined the relative abuse potential of crushed and intact extended-release (ER) hydrocodone bitartrate tablets formulated with OraGuard™ technology as compared to immediate-release (IR) hydrocodone. Healthy adult subjects with a history of recreational opioid use who were not dependent on opioids were enrolled. After confirming that eligible subjects were able to tolerate a 45 mg dose of IR hydrocodone and differentiate the effects of hydrocodone from placebo, subjects were randomized to the double-blind crossover portion of the study in which abuse potential was assessed.

Effects of low-dose naltrexone on analgesia produced by hydrocodone

Purpose To assess the impact of oral naltrexone (NTX) on the analgesic effects of oral immediate-release hydrocodone (HYIR) in healthy subjects with thermally induced hyperalgesia. Methods Subjects first received a thermal discomfort test to determine hyperalgesic response and their responsiveness to opioid analgesic effects. Subjects who qualified then entered a 4-way crossover, double blind phase in which they received HYIR + NTX placebo, or HYIR + NTX 0.25, 0.5, or 1.0 mg. Results No significant differences occurred between HYIR + NTX placebo and HYIR + NTX 0.25, 0.5, or 1.0 mg in thermal discomfort scores, pain latency, or other measures of hyperalgesia. There were no significant differences among treatments or consistent dose-related trends in the subjective opioid agonist effects of HYIR measured in this study. No safety concerns were associated with any HYIR and/or NTX dose. No adverse events commonly associated with opioid use occurred with the NTX 1.0 mg dose. Conclusion No dose of NTX studied resulted in a significant decrease in HYIR-induced analgesia. There was no consistent, dose-related NTX effect on the subjective opioid agonist effects of HYIR measured in this study. Clinical Pharmacology & Therapeutics (2004) 75, P71–P71; doi: 10.1016/j.clpt.2003.11.267