hydrocodone and Chronic-Pain

Topics: Analgesics, Opioid; Chemistry, Pharmaceutical; Chronic Pain; Delayed-Action Preparations; Humans; Hydrocodone; Pain Measurement

Hydrocodone bitartrate is the most commonly used drug for acute and chronic pain in the U.S. with over 135 million prescriptions in 2012. The U.S. is the primary consumer of hydrocodone, using 99% of the global supply for 4.4% of the global population. With its easy availability and abuse patterns, hydrocodone has been touted as a primary driver of opioid-related abuse and misuse. There are no clinical efficacy studies of hydrocodone in short-acting form in combination with acetaminophen or ibuprofen in chronic pain. Hydrocodone has been approved with two long-term formulations since 2014. The FDA has rescheduled hydrocodone from Schedule III to Schedule II which went into effect on October 6, 2014, along with a limit on added acetaminophen of 325 mg for each dose of hydrocodone. This review examines the evolution of hydrocodone into a common and yet controversial drug in the U.S. with its pharmacokinetics, pharmacodynamics, safety and efficacy.

Topics: Analgesics, Opioid; Chronic Pain; Drug Interactions; Humans; Hydrocodone

While a collaborative relationship is optimal for pain management, there may be times when saying No is the best treatment. This review--and easy-to-use "decision tree"--can help with both.

Topics: Acetaminophen; Analgesics, Non-Narcotic; Analgesics, Opioid; Chronic Pain; Decision Support Techniques; Decision Trees; Drug Therapy, Combination; Humans; Hydrocodone; Low Back Pain; Male; Middle Aged; Morphine; Pain Management; Pain Measurement; Physician-Patient Relations; Risk Assessment

This phase 3 study evaluated quality of life, functioning, and productivity after treatment with extended-release (ER) hydrocodone formulated with CIMA. Patients with chronic pain were rolled over from a 12-week placebo-controlled hydrocodone ER study or were newly enrolled. Hydrocodone ER doses were titrated (15 to 90 mg every 12 hours) to an analgesic dose, and patients received up to 52 weeks of open-label treatment. Assessments included Clinician Assessment of Patient Function (CAPF), Patient Assessment of Function (PAF), Brief Pain Inventory-Short Form (BPI-SF), 36-item Short-Form Health Survey (SF-36), Sheehan Disability Scale (SDS), and World Health Organization Health and Work Performance Questionnaire-Short Form (HPQ-SF).. Of 330 enrolled patients, 291 composed the full analysis population. By week 4, ≥ 50% of patients showed improvement from baseline in all 5 CAPF domains (general activities, walking, work/daily living, relationships, and enjoyment of life) and 6 of 7 PAF domains (work attendance, work performance, walking, exercise, socializing, and enjoying life). Mean decreases from baseline of 2 to 3 points were noted for BPI-SF pain interference questions from week 4 through endpoint. Mean improvements from baseline to endpoint in SF-36 subscales ranged from 3.3 to 22.3, and SDS scores improved from moderate (4.8 to 5.1) to mild (2.5 to 2.8) disruptions in work/school, social life, and family life. At endpoint, mean HPQ-SF absolute absenteeism scores decreased from 13.6 to 10.0 hours lost/month and absolute presenteeism scores improved from 67.0 to 77.1.. Patients receiving hydrocodone ER showed early numeric improvements in functioning that continued throughout this 12-month study.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Chronic Pain; Delayed-Action Preparations; Disability Evaluation; Drug Compounding; Educational Status; Efficiency; Female; Humans; Hydrocodone; Male; Middle Aged; Opioid-Related Disorders; Pain Measurement; Quality of Life; Social Behavior; Tablets; Work; Young Adult

This post hoc analysis examined the effectiveness and safety of hydrocodone bitartrate (HYD) in patients with moderate-to-severe chronic pain who were previously taking extended-release morphine (morphine ER) for pain management.. The primary analysis was an open-label, 12-month study.. The study was conducted in 88 sites in the United States.. The study was approved by an institutional review board. Eligible patients were enrolled and titrated to a once-daily dose of HYD 20, 40, 60, 80, or 120 mg for a 45-day period. The subgroup of patients in this report was using morphine ER prior to study entry. After achieving a stable HYD daily dose, patients entered a 12-month maintenance period during which additional dose adjustment could be made and nonopioid or short-acting opioid medications could be received. Average pain over the last 24 hours was recorded daily (on a scale of 0 to 10) Patients completed the Brief Pain Inventory (BPI) short form, which assessed pain severity and the interference of pain in daily life, every 4 weeks during the maintenance period. Safety was assessed routinely.. Of the 26 patients who switched from morphine ER to HYD, 19 entered the maintenance period. At study entry, mean "average pain over the last 24 hours" was scored as 5.21. This was reduced to 3.90 by the time patients entered the maintenance phase; this level of pain control was maintained over the 12-month period, with 16 patients requiring no further HYD dose adjustment. BPI scores decreased for both pain severity and pain interference during the maintenance period. HYD was well tolerated.. The results of this subgroup analysis suggest that rotation from morphine ER to once-daily HYD in patients with moderate-to-severe chronic pain maintains or improves pain relief and does not increase safety concerns.

Topics: Adult; Aged; Analgesics, Opioid; Chronic Pain; Delayed-Action Preparations; Female; Humans; Hydrocodone; Male; Middle Aged; Morphine; Pain Management; Pain Measurement; Treatment Outcome; United States

To evaluate long-term use of Hysingla(®) ER (HYD), a single-entity, extended-release, once-daily hydrocodone bitartrate tablet with abuse-deterrent properties in patients with moderate-to-severe chronic noncancer and nonneuropathic pain.. This open-label study consisted of a dose-titration period (up to 45 days), a 52-week maintenance period and a 24-week extension period. Opioid-naïve or opioid-experienced patients with controlled or uncontrolled chronic pain conditions were treated with HYD 20-120 mg daily. Supplemental nonopioid and short-acting opioid analgesics were permitted. This paper presents the results of 106 patients who continued HYD treatment for up to 76 weeks. Primary safety measures included the incidence of adverse events, as well as audiologic, clinical laboratory and electrocardiogram measurements. Effectiveness was measured by the change between baseline and the overall 76-week treatment period in "average pain over the last 24 h" (0 = no pain, 10 = pain as bad as you can imagine), Brief Pain Inventory-Short Form survey, Medical Outcomes Study 36-Item Short Form Health Survey, Medical Outcomes Study Sleep Scale-Revised and concomitant nonstudy opioid analgesic use.. Among 410 patients who completed the maintenance period, 106 continued into the extension. Of these, 83 (78%) completed the entire 76-week treatment period. Treatment-emergent adverse events were typical of those observed with μ-opioid agonists. No study drug abuse or diversion was reported. Clinically important analgesia and functional improvement were achieved during the dose-titration period and were maintained in most patients throughout 76 weeks without the need for continued HYD dose increases or changes in concomitant nonstudy opioid analgesics. The mean pain score was 6.1 at baseline, 3.8 at the end of the dose titration period and 3.8 through 76 weeks.. HYD was generally well tolerated. No unexpected safety concerns emerged. Pain control was sustained throughout 76 weeks of treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Chronic Pain; Delayed-Action Preparations; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Hydrocodone; Male; Middle Aged; Pain Measurement; Treatment Outcome; Young Adult

The 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.. Four 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.. Thirty-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.. Once-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).

Topics: Adult; Aged; Aged, 80 and over; Analgesia; Chronic Pain; Cross-Over Studies; Delayed-Action Preparations; Drug Administration Schedule; Female; Humans; Hydrocodone; Longitudinal Studies; Male; Middle Aged; Substance-Related Disorders; Tablets; Young Adult

Hydrocodone/acetaminophen combination analgesics are frequently prescribed for chronic pain management; however, acetaminophen presents potential hepatotoxicity to patients and thus dose limitations. These opioid medications are also widely abused. Once-daily, single-entity hydrocodone (Hysingla™ ER tablets [HYD]) is a novel formulation with abuse-deterrent properties for the management of chronic pain and represents a suitable option for those patients receiving analgesics containing the same opioid analgesic, hydrocodone. This post-hoc analysis evaluated the efficacy and safety of HYD in patients whose primary pre-study analgesic was hydrocodone/acetaminophen analgesics (23-31% of the study populations).. Data were analyzed from two Phase III trials, a 12-week randomized, placebo-controlled trial (RCT) and an open-label, 52-week trial. In both trials, a dose-titration period with HYD was followed by respective periods of fixed-dose double-blind (randomized controlled trial [RCT]) or open-label, flexible-dose maintenance treatment. Pain intensity was assessed using a numerical rating scale (0-10, 0 = no pain). For the RCT, primary and sensitivity analyses of pain scores used different approaches to handle missing data. Safety data for both studies were summarized.. In the RCT, the mean baseline pain score was 7.3. Pain relief was greater with HYD than placebo during double-blind treatment. In the open-label, flexible-dose trial, the majority of patients were maintained on their titrated dose. Mean baseline pain score was 6.3, about 57% of patients completed the 1-year maintenance period, and mean pain scores were between 3.6 and 4.1 during the maintenance period. Use of supplemental pain medication decreased or was maintained during the maintenance treatment with HYD. Adverse events in both trials were typical of those associated with opioid analgesics.. In patients whose primary pretrial analgesic was hydrocodone/acetaminophen combination tablets, single-entity HYD was effective in reducing pain intensity and in maintaining analgesia over time without need for continued dose increase. HYD's safety and tolerability profiles were similar to other opioid analgesics.

Topics: Acetaminophen; Adult; Aged; Analgesics, Non-Narcotic; Analgesics, Opioid; Chronic Pain; Double-Blind Method; Drug Combinations; Female; Humans; Hydrocodone; Male; Middle Aged; Pain Measurement; Treatment Outcome; United States; Young Adult

This study aimed to assess the tolerability of the extended use (≤35 days) of MNK-155, a biphasic (immediate-release/extended-release) hydrocodone bitartrate/N-acetyl-p-aminophenol (acetaminophen) (IR/ER HB/APAP) 7.5/325-mg fixed-dose combination analgesic agent, in patients with chronic noncancer pain (CNCP) caused by osteoarthritis or chronic low back pain. IR/ER HB/APAP tablets deliver 25% of the HB dose and 50% of the APAP dose by IR and the remainder by ER over a 12-hour dosing interval. Although IR/ER HB/APAP is being developed for the management of moderate to severe acute pain, this model of CNCP was used for assessing tolerability over a term longer than would be possible in a model of acute pain.. This Phase III, multicenter, open-label study enrolled patients with moderate to severe OA (knee or hip) pain despite the use of nonopioid or opioid analgesic agents, or with moderate to severe CLBP present for several hours per day for ≥3 months. Patients received a 3-tablet initial dose of IR/ER HB/APAP (total dose, 22.5/975 mg) on day 1, followed by 2 tablets of IR/ER HB/APAP (total dose, 15/650 mg) q12h for up to 35 days. Tolerability, the primary end point, was assessed using time to treatment discontinuation, the prevalence of treatment-emergent adverse events (TEAEs), vital sign measurements, pulse oximetry, clinical laboratory tests, and compliance. Secondary outcomes included the modified Brief Pain Inventory-Short Form, the Western Ontario and McMaster Universities Arthritis Index, and The Roland-Morris Low Back Pain and Disability Questionnaire.. Of the 153 patients enrolled (95 women [62.1%]; mean age, 53.9 [14.5] years; OA, n = 73; CLBP, n = 80), 37 (24.2%) discontinued the study early (mean time to discontinuation, 21.3 days). Thirteen patients (8.5%) discontinued because of TEAEs. A total of 88 patients (57.5%) reported ≥1 TEAE, 65 (42.5%) of whom experienced AEs considered by the investigator as treatment related. The most frequent TEAEs were nausea (16.3%), somnolence (14.4%), and constipation (11.1%). Eight severe TEAEs were experienced by 6 (3.9%) patients and included single occurrences of nausea, fatigue, nasopharyngitis, elevated liver enzymes, headache, nightmare, and ejaculation delay. No serious treatment-related AEs were reported. Clinically significant changes in laboratory values were reported in 13 patients, 6 of whom had abnormal liver function test results that did not meet Hy's law criteria for acute liver failure. Most laboratory abnormalities were mild and transient. Measures of pain intensity, function, and quality of life improved from baseline but in an open-label study these changes cannot be attributed to treatment.. The safety profile of IR/ER HB/APAP during extended use was consistent with those of other low-dose opioid/APAP combination products. IR/ER HB/APAP is intended for acute pain; its efficacy for relief of CNCP would require further evaluation in an active- or placebo-controlled study. ClinicalTrials.gov Identifier: NCT01722864.

Topics: Acetaminophen; Adult; Aged; Analgesics, Non-Narcotic; Analgesics, Opioid; Chronic Pain; Delayed-Action Preparations; Drug Combinations; Female; Humans; Hydrocodone; Low Back Pain; Male; Middle Aged; Osteoarthritis, Hip; Osteoarthritis, Knee; Pain Measurement; Quality of Life; Tablets

To evaluate the durability of pain relief provided by a new formulation of single-entity, hydrocodone extended-release (ER) (Zohydro(®) ER) throughout the 12-hour dosing interval by examining patterns of rescue medication use.. Phase 3, enriched enrollment, randomized withdrawal study with an open-label, conversion/titration phase (≤6 weeks) followed by a placebo-controlled, double-blind treatment phase (12 weeks).. Fifty-seven study sites in the United States enrolled patients.. One hundred and fifty-one opioid-experienced subjects with moderate to severe chronic low back pain who were treated with hydrocodone ER once every 12 hours.. Post hoc analysis of rescue medication use by frequency and distribution of use following the morning and evening dose of hydrocodone ER.. No rescue medication was used following the morning or evening dose of hydrocodone ER during 36.0% and 76.7% of the dosing days, respectively. Time distribution of rescue medication use showed that 79.3% of all rescue medication doses were administered following the morning dose, with the highest rate of usage (46.2%) occurring 4-8 hours postdose, followed by 18.7% and 14.4% usage 0-4 and 8-12 hours postdose, respectively. Examination of the three 4-hour intervals following the evening dose of hydrocodone ER revealed similar minimal rescue medication use (5.6-8.2%).. End-of-dose failure was not observed based on the use of rescue medication after administration of single-entity, twice daily, hydrocodone ER capsules (Zohydro ER).

Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Chronic Pain; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hydrocodone; Longitudinal Studies; Low Back Pain; Male; Middle Aged; Pain Measurement; Placebo Effect; Treatment Outcome; United States; Young Adult

A single-agent, extended-release formulation of hydrocodone (HC) has been developed for treatment of chronic moderate-to-severe pain. This study was designed to examine the safety and efficacy of HC extended release in opioid-experienced adults with moderate-to-severe chronic low back pain (CLBP).. This multicenter, enriched enrollment, randomized withdrawal study comprised an open-label conversion/titration phase (≤6 weeks) followed by placebo-controlled, double-blind treatment (12 weeks). During the conversion/titration phase, subjects (N = 510) converted from their current opioid and were titrated to a stabilized dose of HC extended release (20-100 mg every 12 hours). During treatment, subjects (N = 151 per group) received HC extended release or placebo; rescue medication was permitted. The primary efficacy end point was mean change in average pain intensity from baseline to day 85. Response rates (30% pain improvement) and satisfaction (Subject Global Assessment of Medication) were assessed.. Demographic and baseline characteristics were similar between groups. Mean ± SD change in average pain intensity score from baseline to day 85 was significantly lower in the HC extended-release treatment group vs placebo (0.48 ± 1.56 vs 0.96 ± 1.55; P = 0.008). Significantly more responders were in the treatment group (68% vs 31%; P < 0.001). Mean Subject Global Assessment of Medication scores increased significantly (0.8 ± 1.3 vs 0.0 ± 1.4; P < 0.0001), indicating greater satisfaction with HC extended release. The adverse event profile was consistent with other opioids.. Extended-release HC is well tolerated and effective, without acetaminophen-associated risks of liver toxicity, for treatment of CLBP.

Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Chronic Pain; Delayed-Action Preparations; Double-Blind Method; Drug Tolerance; Female; Humans; Hydrocodone; Low Back Pain; Male; Middle Aged; Pain Measurement; Severity of Illness Index; Young Adult

Patients with chronic noncancer pain frequently report symptoms of depression and anxiety (negative affect), which are associated with higher ratings of pain intensity and a greater likelihood of being prescribed chronic opioid therapy. The purpose of this secondary analysis was to test the hypothesis that initial levels of negative affect can predict treatment-related outcomes in a double-blind, placebo-controlled study of extended-release (ER) hydromorphone among opioid-tolerant patients with chronic low back pain.. Four hundred fifty-nine (N = 459) patients participated in the titration/conversion phase of a multicenter study, of which 268 were randomized to receive once-daily hydromorphone or placebo. All patients completed the Hospital Anxiety and Depression Scale (HADS) at baseline and were divided evenly into Low (N = 157), Moderate (N = 155), and High (N = 147) negative affect groups based on their scores. Group differences in numerical pain intensity measures at home and in the clinic, Roland-Morris Disability ratings, and measures of symptoms from the Subjective Opiate Withdrawal Scale (SOWS) throughout the trial were analyzed.. Two hundred sixty-eight of the initial 459 subjects who entered the 2 to 4-week titration/conversion phase (pretreatment) were successfully randomized to either placebo or ER hydromorphone; a total of 110 patients then completed this double-blind phase of the study. Those in the Moderate and High negative affect groups tended to drop out more often during the titration/conversion phase because of the adverse effects or lack of efficacy of their prescribed opioid than those in the Low negative mood group (P < 0.05). Overall, those patients in the Moderate and High groups reported significantly higher pain intensity scores in at-home and in-clinic pain intensity ratings (P < 0.05), greater disability on the Roland-Morris Scale (P < 0.01), and more withdrawal symptoms on the SOWS (P < 0.05) than those in the Low group. Higher negative affect scores also predicted less favorable ratings of the study drug during the titration phase (P < 0.05). Interestingly, the High negative affect group showed the most improvement in pain in the placebo condition (P < 0.05).. Negative affect is associated with diminished benefit during a trial of opioid therapy and is predictive of dropout in a controlled clinical trial.

Topics: Affective Symptoms; Analgesics, Opioid; Anxiety; Chronic Pain; Depression; Double-Blind Method; Female; Humans; Hydrocodone; Low Back Pain; Male; Middle Aged; Treatment Outcome

Hydrocodone is frequently prescribed for moderate to severe pain. Nicotine has analgesic properties and it is hypothesized that cigarette smoking might decrease the dosage of hydrocodone needed for the relief of chronic pain. This would be a topic of importance to clinicians as it relates to individualized medicine and pharmacotherapy for chronic pain management. Smokers and nonsmokers were assigned randomly to one of two groups to receive hydrocodone daily for 30 days. This study concluded that the dose of hydrocodone consumed did not statistically differ between the two Groups. Smokers however, had significantly less pain relief than nonsmokers.

Topics: Adolescent; Adult; Analgesics, Opioid; Chronic Pain; Drug Synergism; Female; Humans; Hydrocodone; Low Back Pain; Male; Middle Aged; Nicotine; Nicotinic Agonists; Smoking; Young Adult

The use of opioid medications for treating chronic noncancer pain is growing; however, there is a lack of good evidence regarding their long-term effectiveness, association with substance abuse, and proper prescribing guidelines. The current study directly compares for the first time in a randomized trial the effectiveness of a conservative, hold the line (Stable Dose) prescribing strategy for opioid medications with a more liberal dose escalation (Escalating Dose) approach. This 2-arm, parallel, randomized pragmatic clinical trial followed 135 patients referred to a specialty pain clinic at a Veterans Affairs Hospital for 12 months (94% male and 74% with musculoskeletal pain). Primary outcomes included monthly or quarterly evaluations of pain severity, pain relief from medications, pain-related functional disability, and opioid misuse behaviors. All subjects received identical pain treatment except for the application of treatment group specific strategies for opioid prescriptions. No group differences were found for primary outcomes of usual pain or functional disability although the Escalating Dose group did show a small but significantly larger increase in self-rated pain relief from medications. About 27% of patients were discharged over the course of the study due to opioid misuse/noncompliance, but there were no group differences in rate of opioid misuse.. The results of this study demonstrate that even in carefully selected patients there is a significant risk of problematic opioid misuse. Although in general there were no statistically significant differences in the primary outcomes between groups, the escalating dose strategy did lead to small improvements in self-reported acute relief from medications without an increase in opioid misuse, compared to the stable dose strategy.

Topics: Aged; Analgesia; Analgesics, Opioid; Chronic Pain; Codeine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Hydrocodone; Male; Middle Aged; Morphine; Musculoskeletal Diseases; Oxycodone; Pain Measurement

To compare the safety profiles of low and high-dose tramadol, short-acting hydrocodone, and short-acting oxycodone therapies among chronic noncancer pain individuals.. A retrospective cohort study of individuals with back/neck pain/osteoarthritis with an initial opioid prescription for tramadol, hydrocodone, or oxycodone was conducted using IQVIA PharMetrics Plus claims for Academics database (2006 to 2020). Two cohorts were created for separately studying opioid-related adverse events (overdoses, accidents, self-inflicted injuries, and violence-related injuries) and substance use disorders (opioid and nonopioid). Patients were followed from the index date until an outcome event, end of enrollment, or data end. Time-varying exposure groups were constructed and Cox regression models were estimated.. A total of 1,062,167 (tramadol [16.5%], hydrocodone [61.1%], and oxycodone [22.4%]) and 986,809 (tramadol [16.5%], hydrocodone [61.3%], and oxycodone [22.2%]) individuals were in the adverse event and substance use disorder cohorts. All high-dose groups had elevated risk of nearly all outcomes, compared with low-dose hydrocodone. Compared with low-dose hydrocodone, low-dose oxycodone was associated with a higher risk of opioid overdose (hazard ratio: 1.79 [1.37 to 2.33]). No difference in risk was observed between low-dose tramadol and low-dose hydrocodone (hazard ratio: 0.85 [0.64 to 1.13]). Low-dose oxycodone had higher risks of an opioid use disorder, and low-dose tramadol had a lower risk of accidents, self-inflicted injuries, and opioid use disorder compared with low-dose hydrocodone.. Low-dose oxycodone had a higher risk of opioid-related adverse outcomes compared with low-dose tramadol and hydrocodone. This should be interpreted in conjunction with the benefits of pain control and functioning associated with oxycodone use in future research.

Topics: Analgesics, Opioid; Chronic Pain; Humans; Hydrocodone; Opioid-Related Disorders; Oxycodone; Retrospective Studies; Tramadol

Opioids relieve acute pain, but there is little evidence to support the stability of the benefit over long-term treatment of chronic noncancer pain. Previous systematic reviews consider only group level published data which did not provide adequate detail. Our goal was to use patient-level data to explore the stability of pain, opioid dose, and either physical function or pain interference in patients treated for 12 months with abuse deterrent formulations of oxycodone and hydrocodone. All available studies in the Food and Drug Administration Document Archiving, Reporting, and Regulatory Tracking System were included. Patient-level demographics, baseline data, exposure, and outcomes were harmonized. Individual patient slopes were calculated from a linear model of pain, physical function, and pain interference to determine response over time. Opioid dose was summarized by change between baseline and the final month of observation. Patients with stable or less pain, stable or lower opioid dose, and stable or better physical function (where available) met our prespecified criteria for maintaining long-term benefit from chronic opioids. Of the complete data set of 3192 patients, 1422 (44.5%) maintained their pain level and opioid dose. In a secondary analysis of 985 patients with a measured physical function, 338 (34.3%) maintained their physical function in addition to pain and opioid dose. Of 2040 patients with pain interference measured, 788 (38.6%) met criteria in addition. In a carefully controlled environment, about one-third of patients successfully titrated on opioids to treat chronic noncancer pain demonstrated continued benefit for up to 12 months.

Topics: Analgesics, Opioid; Chronic Pain; Delayed-Action Preparations; Humans; Hydrocodone; Oxycodone; Pharmaceutical Preparations; United States; United States Food and Drug Administration

We describe the case of a 75-year-old female with chronic low back pain (CLBP), on opioids for more than 15 years. She presented with an acute episode of nausea, vomiting, abdominal pain, and shortness of breath. After a complete work-up, it was concluded that her presenting symptoms were likely due to her high levels of CLBP and high dose opioids. At the time of intervention, her opioid dosage was between 50-90 MME (Morphine milligram equivalent) (Norco 8 × 7.5 mg/day + Fentanyl 12 mcg patch). She was subsequently seen by the physician for seven outpatient internal medicine appointments over nine months and received Pain Neuroscience Education (PNE) in conjunction with monitored tapering of opioids and other medication associated with her CLBP. This case report demonstrates how a physician might deliver PNE as a viable nonpharmacological treatment option for the tapering of long-term opioids for chronic pain.

Topics: Acetaminophen; Aged; Analgesics, Opioid; Chronic Pain; Female; Fentanyl; Humans; Hydrocodone; Low Back Pain; Patient Education as Topic; Physicians

In October 2014, the US Drug Enforcement Agency moved hydrocodone combination products (HCPs) from schedule III to II of the Controlled Substances Act, further restricting their access. The aim of the study is to quantify the effect of hydrocodone's "upscheduling" on the use of opioid and nonopioid analgesics among chronic users.. Using IQVIA LRx LifeLink anonymized pharmacy data 2013 to 2015, we performed interrupted time series analysis and group-based trajectory modeling to characterize the effect of rescheduling on 316 731 long-term hydrocodone users. Main measures were the number of prescriptions, patients, tablets, and morphine milligram equivalents of opioids and nonopioid analgesics pre and post the policy change. We used logistic regression to assess the relationship between sociodemographic characteristics and these measures.. The schedule change was associated with significant declines in opioid prescriptions (20.9%, from 421 798 to 333 627) and the number of patients using opioids (11.4%, from 307 974 to 272 804). Majority of hydrocodone users filled prescriptions for nonopioid analgesics with some declines in the number of users after the schedule change (5.2%, from 181 085 to 171 758). Based on group-based trajectory models, majority of patients continued to fill HCP prescriptions consistently after the policy change, while 15.4% showed large declines in HCP use, accounting for two-thirds of the decrease in opioid volume. There was no evidence that the policy change was associated with significant increases in the use of alternative analgesics.. The upscheduling of hydrocodone led to reductions in opioid use, which were concentrated among a small subset of chronic hydrocodone users, without evidence of commensurate increases in the use of alternative pharmacologic pain treatments.

Topics: Adult; Aged; Analgesics, Non-Narcotic; Chronic Pain; Cohort Studies; Controlled Substances; Drug and Narcotic Control; Drug Combinations; Drug Prescriptions; Drug Utilization; Female; Humans; Hydrocodone; Interrupted Time Series Analysis; Male; Middle Aged; Opioid-Related Disorders; Policy; Practice Patterns, Physicians'; Program Evaluation; United States; United States Office of National Drug Control Policy

This study evaluated the safety and effectiveness of a once-daily, single-entity, extended-release hydrocodone bitartrate (HYD) among patients with chronic noncancer and non-neuropathic pain who required opioid rotation from a previous analgesic regimen that primarily consisted of immediate-release (IR) oxycodone.. Post hoc analyses of a primary study that assessed HYD 20 to 120 mg over a 52-week period are presented. The primary study included a dose titration period (up to 45 days), a 52-week maintenance period, and an optional taper period (up to 14 days).. Relative to baseline, mean "average pain over the last 24 hours" declined by 1.9 points at the end of the titration period and by 2.6 points at the end of the maintenance period. Additionally, interference and severity of pain as measured by the Brief Pain Inventory-Short Form decreased by 2.3 and 1.9 points, respectively, during the maintenance period. The use of supplemental opioid analgesics decreased. Most patients remained on a stable HYD dose throughout the maintenance period. Most patients indicated satisfaction with HYD and considered it convenient and easy to use. HYD demonstrated a safety profile typical of µ opioids; nausea, constipation, vomiting, and dizziness were the most frequently reported opioid-related adverse events during the study.. In patients with chronic pain who received HYD over a 52-week period, treatment was generally well tolerated and provided effective analgesia among those who rotated from a pain regimen primarily consisting of IR oxycodone.

Topics: Adult; Aged; Analgesia; Analgesics, Opioid; Chronic Pain; Delayed-Action Preparations; Drug Administration Schedule; Female; Humans; Hydrocodone; Male; Middle Aged; Oxycodone; Pain Management

Long-term safety and effectiveness of a once-daily, single-entity, extended-release formulation of hydrocodone bitartrate (HYD) for the treatment of moderate to severe noncancer and nonneuropathic pain among patients with and without concurrent depression/anxiety at baseline.. Post hoc analysis.. HYD demonstrated a safety profile consistent with μ-opioid agonists: Serious adverse events in 12% patients with depression/anxiety including four deaths; 6% without depression/anxiety including one death. All pain scores declined by ≥2 points and mean daily HYD dose remained stable in both subgroups.. More serious adverse events occurred among patients with comorbid depression/anxiety at baseline than among those without. HYD provided stable and effective analgesia for 52 weeks among chronic pain patients with and without comorbid depression/anxiety at baseline.

Topics: Analgesics, Opioid; Anxiety; Chronic Pain; Delayed-Action Preparations; Depression; Female; Humans; Hydrocodone; Male; Middle Aged; Pain Management; Tablets; Treatment Outcome

Topics: Analgesics, Opioid; Chronic Pain; Cocaine; Cocaine-Related Disorders; Drug Monitoring; Female; Humans; Hydrocodone; Immunoassay; Low Back Pain; Middle Aged; Opioid-Related Disorders; Sensitivity and Specificity; Substance Abuse Detection

To characterize cancer-related breakthrough pain (BTcP) among community-dwelling patients with cancer.. Data from the National Breakthrough Pain Study, a cross-sectional observational survey describing breakthrough pain (BTP) in the community, were analyzed for a subset of patients with BTcP. Eligible patients were community-dwelling adults with commercial insurance and insurance claims consistent with cancer and chronic pain who consented to a structured telephone interview. Assessments included the Brief Pain Inventory-Short Form (BPI), the Short Form 12 Health Survey, the Sheehan Disability Scale, the Work Performance Questionnaire, Generalized Anxiety Disorder-7 Screener, and Patient Health Questionnaire-2.. In total, 112 patients with cancer pain also experienced BTcP; 83.3% were in remission. Most patients reported experiencing ≥2 BTcP episodes per day, a median time to BTcP peak of 15 minutes, and a median duration of BTcP of 30 minutes. Mild pain at onset that gradually worsened was reported by 54.5% of patients, and incidental pain triggered by physical activity was reported by 58.0%. Most patients who reported using a medication to manage BTcP received an oral immediate-release opioid, such as oxycodone or hydrocodone, and only 1 received a rapid-onset opioid; few (24.1%) reported that pharmacologic treatment for BTcP worked every time. Patients reported mean (standard deviation) BPI scores of 4.2 (1.75) and 5.7 (1.98) for average and worst pain intensity during the preceding 24 hours, respectively, and high interference with activity, mood, ability to walk and work, social relations, sleep, and enjoyment of life.. Results indicate that BTcP among community-dwelling patients with cancer continues to be a health burden and reveals opportunities to improve its management.

Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Breakthrough Pain; Chronic Pain; Cross-Sectional Studies; Female; Health Surveys; Humans; Hydrocodone; Independent Living; Male; Middle Aged; Neoplasms; Oxycodone; Pain Measurement; Quality of Life; Surveys and Questionnaires; United States

Osteoarthritis (OA)-related chronic pain is associated with physical and psychosocial impairment as well as poorer quality of life. There is limited literature on long-term opioid therapy in OA patients. This post hoc analysis of OA patients assessed the long-term safety and effectiveness of a once-daily, single-entity, extended-release formulation of hydrocodone (HYD) with abuse-deterrent properties for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which other treatment options are inadequate.. This is a post hoc analysis of the 307 patients with OA pain from a primary open-label study. Following screening and dose titration, patients who achieved a stable HYD dose continued into a 52-week maintenance period. Supplemental non-opioid or short-acting opioid analgesics were allowed throughout the study. Safety was monitored. Effectiveness evaluations included "average pain over the last 24 hours" scores, "pain right now" scores, Brief Pain Inventory-Short Form and treatment satisfaction questionnaire.. No new or unexpected safety concerns emerged during treatment with HYD. HYD demonstrated a safety profile consistent with other µ-opioid agonists with 22% discontinuations of treatment due to adverse events, a majority of which were related to the study drug. Clinically meaningful analgesia was achieved as mean "average pain over the last 24 hours"; scores decreased by 2.9 points from baseline to the end of maintenance. During the maintenance period, pain severity declined 2.7 points and interference by 2.5 points from baseline. Mean "pain right now" scores were similar at dosing and 12 hours later. A majority of patients reported satisfaction with HYD.. In OA patients, long-term HYD treatment was generally well tolerated and provided clinically important analgesia.

Topics: Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Chemistry, Pharmaceutical; Chronic Pain; Delayed-Action Preparations; Female; Humans; Hydrocodone; Male; Middle Aged; Osteoarthritis; Prescription Drug Misuse; United States; Young Adult

To conduct an Internet patient survey through the National Fibromyalgia & Chronic Pain Association on reactions to the first 100 days following the rescheduling of hydrocodone.. Face-valid survey questions were created with expert consensus along with repurposed questions used on previous NFMCPA surveys covering domains such as demographics and symptoms. The questionnaire was designed to be administered over the Internet.. 6,420 responders met screening criteria and completed the survey. Most (5,181, or 82.5%) had been prescribed hydrocodone for more than 1 year. 2,296, (39.0%) reported no changes in access to hydrocodone, while the majority experienced some barriers. Of those who could no longer get hydrocodone, 1,067 (18.1%) borrowed pain medications, 1,007 (17.1%) turned to marijuana, 773 (13.1%) used alcohol, and 135 (2.3%) used illicit drugs. Most respondents had to visit their healthcare providers more often (N = 3,699, 64.2%) and 1,735 (30.3%) reported some type of issue interacting with their pharmacy. Most felt that the rescheduling was neither a fair nor appropriate solution to the abuse of hydrocodone (N = 4,938, 88.3%). For those still working, 801 (46.2%) reported that they had missed work because of the stricter regulations. 1,462 (27.2%) reported having thoughts of suicide since the rescheduling.. The unintended consequences for people with chronic pain that have been caused by the rescheduling effort to impede hydrocodone abuse are negatively impacting thousands. These consequences include suffering from being placed on less effective drugs, increased cost, inconvenience, and negative influence on physician-patient and pharmacist-patient relationships.

Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Chronic Pain; Female; Humans; Hydrocodone; Male; Middle Aged; Online Systems; Surveys and Questionnaires; Young Adult

Topics: Analgesics, Opioid; Chronic Pain; Drug Tolerance; Female; Humans; Hydrocodone; Low Back Pain; Male; Severity of Illness Index

Topics: Analgesics, Opioid; Chronic Pain; Drug Tolerance; Female; Humans; Hydrocodone; Low Back Pain; Male; Severity of Illness Index

Topics: Analgesics, Opioid; Canada; Chronic Pain; Drug Administration Routes; Drug Approval; Humans; Hydrocodone; Opioid-Related Disorders; Risk Assessment; United States; United States Food and Drug Administration

Topics: Analgesics, Opioid; Capsules; Chronic Pain; Delayed-Action Preparations; Drug Approval; Drug Packaging; Humans; Hydrocodone; Opioid-Related Disorders; United States; United States Food and Drug Administration

Topics: Analgesics, Opioid; Chronic Pain; Delayed-Action Preparations; Drug Approval; Humans; Hydrocodone; United States; United States Food and Drug Administration

In the past decade, more and more behavioral health providers have begun consultation practices in primary-care settings. Their availability makes multidisciplinary care a reality and the possibility of improved outcomes for patients with chronic pain more feasible. However, behavioral health providers encounter new ethical quandaries in providing services to patients with chronic pain and to the primary-care providers who plan their treatment. This article presents two cases to illustrate the questions that arise in delivery of primary-care behavioral health services to patients with chronic pain. Relevant professional ethical guidelines for psychologists, social workers, and physicians are examined and recommendations for addressing the gaps in extant guides are offered.

Topics: Acetaminophen; Back Pain; Behavioral Medicine; Chronic Pain; Clinical Competence; Codes of Ethics; Drug Combinations; Female; Humans; Hydrocodone; Interdisciplinary Communication; Male; Middle Aged; Narcotic Antagonists; Negotiating; Pain Management; Primary Health Care; Professional-Patient Relations; Quality of Life; Recurrence; Referral and Consultation; Substance-Related Disorders; Workforce

Topics: Chronic Pain; Dentists; Drug and Narcotic Control; Education, Dental; Government Regulation; Humans; Hydrocodone; Narcotics; Opioid-Related Disorders; Pharmacology, Clinical; Prescription Drug Diversion; United States; United States Food and Drug Administration

Hydrocodone in combination with acetaminophen is commonly used to control moderate pain and is metabolized by cytochrome P4502D6 to form the active metabolite, hydromorphone. The purpose of this study was to determine the metabolic relationship and variability between hydrocodone and its conversion to hydromorphone using urinary excretion data from chronic pain patients. Liquid chromatography-tandem mass spectrometry was used to quantitate hydrocodone and hydromorphone concentrations in urine specimens. The first visits of 25,200 subjects who took hydrocodone and not hydromorphone and had measurable concentrations were included in this study. The geometric mean (95% confidence index) of hydrocodone and hydromorphone urine concentrations were 1.39 (1.37-1.41) mg per gram of creatinine and 0.224 (0.221-0.227) mg per gram of creatinine, respectively. The log of creatinine-corrected hydromorphone versus the log of creatinine-corrected hydrocodone showed a positive relationship (R(2) = 0.20), with 60-fold variability between subjects. The plot of the log of the metabolic ratio ([hydromorphone] divided by [hydrocodone]) versus the log of creatinine-corrected hydrocodone had a coefficient of determination of R(2) = 0.42, with 125-fold variability between subjects. Ultra-rapid metabolizers represented 0.6% of the population, whereas 4% were poor metabolizers. Within-subject variability for the excretion of hydrocodone in urine was 23-fold, whereas between-subject variability was 134-fold. Hydrocodone and hydromorphone urine concentrations showed great variability within and between subjects.

Topics: Analgesics, Opioid; Chromatography, High Pressure Liquid; Chronic Pain; Drug Monitoring; Humans; Hydrocodone; Hydromorphone; Reference Values; Reproducibility of Results; Retrospective Studies; Tandem Mass Spectrometry; Time Factors