hydrocodone and Pain

Awareness of drug interactions involving opioids is critical for patient treatment as they are common therapeutics used in numerous care settings, including both chronic and disease-related pain. Not only do opioids have narrow therapeutic indexes and are extensively used, but they have the potential to cause severe toxicity. Opioids are the classical pain treatment for patients who suffer from moderate to severe pain. More importantly, opioids are often prescribed in combination with multiple other drugs, especially in patient populations who typically are prescribed a large drug regimen. This review focuses on the current knowledge of common opioid drug-drug interactions (DDIs), focusing specifically on hydrocodone, oxycodone, and morphine DDIs. The DDIs covered in this review include pharmacokinetic DDI arising from enzyme inhibition or induction, primarily due to inhibition of cytochrome p450 enzymes (CYPs). However, opioids such as morphine are metabolized by uridine-5'-diphosphoglucuronosyltransferases (UGTs), principally UGT2B7, and glucuronidation is another important pathway for opioid-drug interactions. This review also covers several pharmacodynamic DDI studies as well as the basics of CYP and UGT metabolism, including detailed opioid metabolism and the potential involvement of metabolizing enzyme gene variation in DDI. Based upon the current literature, further studies are needed to fully investigate and describe the DDI potential with opioids in pain and related disease settings to improve clinical outcomes for patients. SIGNIFICANCE STATEMENT: A review of the literature focusing on drug-drug interactions involving opioids is important because they can be toxic and potentially lethal, occurring through pharmacodynamic interactions as well as pharmacokinetic interactions occurring through inhibition or induction of drug metabolism.

Topics: Analgesics, Opioid; Cytochrome P-450 Enzyme System; Drug Interactions; Humans; Hydrocodone; Morphine; Oxycodone; Pain

Topics: Acetaminophen; Analgesics, Non-Narcotic; Analgesics, Opioid; Drug Combinations; Humans; Hydrocodone; Opioid-Related Disorders; Pain

Recently, the U.S. Food and Drug Administration (FDA) approved Zohydro(®), an extended release formulation of the opioid analgesic hydrocodone that contains no acetaminophen. This approval was against the recommendation of the FDA's Expert Panel. Subsequently, both chronic pain advocates and anti-drug abuse advocates have steadfastly expressed their support of, or astonishment at this decision. Here, we review the pharmacokinetics, pharmacodynamics, safety and abuse liability of this hydrocodone formulation and how it relates to the Expert Panel's opinion and the FDA decision. We discuss the important issues, risk mitigation, potential use of abuse deterrents, and how the different viewpoints of the Expert Panel and FDA decision makers resulted in the approval and subsequent controversy.

Topics: Analgesics, Opioid; Delayed-Action Preparations; Humans; Hydrocodone; Pain; Substance-Related Disorders

Hysingla ER, the second single-ingredient extended-release hydrocodone product to become available in the US, is formulated for once-daily use. Zohydro ER is dosed twice daily and costs more. Both Hysingla ER and the new formulation of Zohydro ER have abuse-deterrent properties, but they will still be subject to misuse.

Topics: Analgesics, Opioid; Animals; Delayed-Action Preparations; Humans; Hydrocodone; Pain; Randomized Controlled Trials as Topic

This forum presents a clinical vignette of orofacial pain and expounds on ethical issues related to opioid therapy in the context of multidisciplinary treatment. The purpose of this forum is to assist health care providers from different disciplines in identifying ethical issues and conflicts regarding opioid therapy encountered in multidisciplinary clinical pain practices.. We use the case vignette and opioid therapy as a backdrop for a discussion of 1) an overview of ethics terminology; 2) a presentation of key ethics principles; 3) our conceptualization of ethical obligations of patients regarding opioid therapy; and 4) the process of developing an appropriate treatment plan within the context of the discussed ethical principles.

Topics: Analgesics, Opioid; Chickenpox; Cholecystectomy; Chronic Disease; Diazepam; Facial Pain; Female; Herpes Zoster; Humans; Hydrocodone; Hypnotics and Sedatives; Hysterectomy; Opioid-Related Disorders; Pain; Pain Clinics; Uterine Neoplasms

Opioids are important, if not essential, agents in treating certain types of chronic pain. However, the prevalence of drug misuse, abuse, and addiction has fostered considerable consternation among physicians, who may hesitate to prescribe these medications both due to concern for patients (misuse, abuse, and addiction), and fears of prosecution and/or professional sanction. Such practice may reflect 1) inadequate knowledge about patients' susceptibility to, or current drug misuse or abuse; 2) lack of familiarity with extant assessments and/or regulations, and/or 3) an unanticipated reaction to existing guidelines, policies or laws. We posit that assessing patients' predisposition to, and patterns of, drug misuse/abuse is a vital first step toward establishing and maintaining the safe and effective use of opioid analgesics in the treatment of chronic pain. Adherence monitoring is critical to identify patients' prior and current drug use, establish treatment basis, and evaluate compliance, so as to avoid misuse and abuse, and ensure sound and proper pain management. This paper provides a review of the numerous monitoring approaches that have been described in the literature and addresses the benefits and limitations of these techniques and tools. The complex nature of the problem of drug misuse and abuse is discussed, and while no single monitoring technique can fully address this complex issue, we describe how multiple approaches to adherence monitoring may be employed to sustain the prudent use of opioids for the treatment of chronic pain.

Topics: Analgesics, Opioid; Chronic Disease; Codeine; Drug Monitoring; Heroin; Humans; Hydrocodone; Pain; Patient Compliance

Careful selection of an effective analgesic regimen based on the amount and type of pain the patient is expected to have can prevent the stress and anxiety associated with breakthrough pain. When analgesics fail, it is not unusual for patients to go to desperate lengths to seek relief. The clinician can and should develop a variety of effective, safe analgesic regimens based on estimates of anticipated pain intensity that apply sound pharmacologic principles.

Topics: Acetaminophen; Analgesics; Analgesics, Non-Narcotic; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Anxiety; Clinical Protocols; Codeine; Contraindications; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dental Care; Dose-Response Relationship, Drug; Drug Combinations; Humans; Hydrocodone; Isoenzymes; Membrane Proteins; Oxycodone; Pain; Prostaglandin-Endoperoxide Synthases; Stress, Physiological; Tramadol

Painful infectious mouth conditions such as herpangina, hand-foot-and-mouth disease, and herpetic gingivostomatitis can cause pain, dehydration, and hospitalization in young children. Treatment for these conditions is generally supportive and directed toward pain relief from ulcerative lesions, thus facilitating oral intake, and preventing dehydration. Attempts at oral therapy at home and in the emergency department are often refused and immediately spit back out. This study evaluated the efficacy of intranasal fentanyl (INF) compared with a commonly used oral (PO) acetaminophen/hydrocodone formulation for the treatment of children with painful infectious mouth conditions.. This study was a prospective, nonblinded, randomized controlled noninferiority trial conducted in an academic tertiary care pediatric emergency department. The study enrolled children between the ages of 6 months and 18 years with painful infectious mouth lesions and poor oral intake. Patients were randomized to receive either INF (1.5 μg/kg, intervention) or PO acetaminophen/hydrocodone (0.15 mg/kg, control) based on the dose of hydrocodone. The primary outcome was volume of fluid intake per body weight (in milliliters per kilogram) 60 minutes after analgesic administration. Secondary outcomes included pain scores using a validated visual assessment scale (VAS; 1, no pain; 10, worst pain), hydration score (VAS; 1, well hydrated; 4, very dehydrated), admission rate and overall satisfaction score (VAS; 1, worst; 7, best). A priori power analysis indicated that 34 patients would achieve an 81% power with an α value of 0.05.. Of the 34 patients enrolled, 17 were randomized to INF and 17 to PO. The demographics between both groups were similar in age, weight, sex, and race. There were no significant differences in parental perception of pain ( P = 0.69) or hydration status ( P = 0.78). Oral fluid intake at 60 minutes was 20 mL/kg for INF versus 18 mL/kg for PO ( P = 0.53). Pain scores at 15 and 30 minutes were 1.7 versus 2.9 ( P = 0.09) and 0.6 versus 1.6 ( P = 0.59). Parental perceptions of pain and hydration status at 60 minutes were 2.2 versus 2.4 ( P = 0.77) and 1.7 versus 1.5 ( P = 0.37). Overall parental satisfaction was 6.4 for INF versus 6.5 for PO ( P = 0.71), and admission rate was 0 vs 12% ( P = 0.49). There were no adverse events such as respiratory, cardiac, or central nervous system depression in either group.. Intranasal fentanyl seems to be a safe and effective alternative to acetaminophen with hydrocodone in reducing pain and improving hydration status in children with painful infectious mouth lesions and poor oral intake.

Topics: Acetaminophen; Administration, Intranasal; Analgesics, Opioid; Child; Child, Preschool; Communicable Diseases; Dehydration; Double-Blind Method; Fentanyl; Humans; Hydrocodone; Infant; Pain; Pain Management; Pain Measurement; Prospective Studies

Distracted and drug-influenced driving presents a major risk for traffic safety morbidity and mortality. As part of an ongoing research program, we examined the effects of a commonly prescribed combination of medications for pain relief: alprazolam, a benzodiazepine, and a hydrocodone preparation, a combination opiate and acetaminophen, on a simulated driving protocol.. Utilizing a within-subjects design, we recruited 8 healthy experienced drivers without major physical and psychological histories. Using a double-blind, placebo-controlled crossover design, we administered placebo, alprazolam alone, hydrocodone/acetaminophen, and the combination of the 2 drugs in a standardized simulated driving protocol. Measures of lateral and longitudinal control were collected and the data were reduced and statically analyzed.. The study observed clear detrimental effects of alprazolam on driving measures of lateral control and longitudinal control. Driving appeared to more aberrant at higher speeds and in rural scenarios. There were no statistical differences between hydrocodone and placebo. A measure of sedation showed that subjects rated alprazolam as more sedating than both hydrocodone and placebo.. The findings suggest that impairing effects of this commonly prescribed combination of pharmacologic agents impact simulated driving performance. Negative changes in driving performance included measures of lateral and longitudinal control, although the deleterious effects on lateral control measures such as standard deviation of lane position (SDLP) were larger and more robust. Although the number of subjects was small, thus making it more difficult to draw conclusions on the narcotic effects, these results suggest that in this combination of central nervous system (CNS)-active drugs the benzodiazepine alprazolam accounted for the majority of impairing drug effects. The effect sizes associated with the hydrocodone preparation ranged from very small to medium. These results have potential implications for prescribing physicians and dispensing pharmacists, traffic safety experts, law enforcement officers, and patients themselves.

Topics: Acetaminophen; Adult; Alprazolam; Anxiety; Cross-Over Studies; Double-Blind Method; Driving Under the Influence; Drug Combinations; Female; Humans; Hydrocodone; Male; Pain; Psychomotor Performance; Young Adult

(1) To quantify hydrocodone (HC) and hydromorphone (HM) metabolite pharmacokinetics with pharmacogenetics in CYP2D6 ultra-rapid metabolizer (UM), extensive metabolizer (EM), and poor metabolizer (PM) metabolizer phenotypes. (2) To develop an HC phenotype-specific dosing strategy for HC that accounts for HM production using clinical pharmacokinetics integrated with pharmacogenetics for patient safety.. In silico clinical trial simulation.. Healthy white men and women without comorbidities or history of opioid, or any other drug or nutraceutical use, age 26.3±5.7 years (mean±SD; range, 19 to 36 y) and weight 71.9±16.8 kg (range, 50 to 108 kg).. CYP2D6 phenotype-specific HC clinical pharmacokinetic parameter estimates and phenotype-specific percentages of HM formed from HC.. PMs had lower indices of HC disposition compared with UMs and EMs. Clearance was reduced by nearly 60% and the t1/2 was increased by about 68% compared with EMs. The canonical order for HC clearance was UM>EM>PM. HC elimination mainly by the liver, represented by ke, was reduced about 70% in PM. However, HC's apparent Vd was not significantly different among UMs, EMs, and PM. The canonical order of predicted plasma HM concentrations was UM>EM>PM. For each of the CYP2D6 phenotypes, the mean predicted HM levels were within HM's therapeutic range, which indicates HC has significant phenotype-dependent pro-drug effects.. Our results demonstrate that pharmacogenetics afford clinicians an opportunity to individualize HC dosing, while adding enhanced opportunity to account for its conversion to HM in the body.

Topics: Adult; Analgesics, Opioid; Asthma; Biological Availability; Child, Preschool; Cross-Over Studies; Cytochrome P-450 CYP2D6; Female; Genotype; Healthy Volunteers; Humans; Hydrocodone; Male; Meta-Analysis as Topic; Pain; Pharmacogenetics; Phenotype; Time Factors; Young Adult

The use of opioid analgesics in the United States has significantly increased in recent years. However, there is minimal consensus on what discharge counseling should accompany these high-risk prescriptions and large variations in what is done in practice. The objective of this study was to evaluate the effect of a dual-modality (written and spoken) literacy-appropriate educational strategy on patients' knowledge of and safe use of opioid analgesics.. This was a prospective, randomized controlled trial. Consecutive discharged patients at an urban academic ED (>88,000 visits) with new prescriptions for hydrocodone-acetaminophen were enrolled. Patients were randomized to receive either usual care or the educational intervention. The educational intervention was a one-page information sheet about hydrocodone-acetaminophen, which was both given to the patients and read aloud by the research assistant (nonblinded). Follow-up phone calls were conducted 4 to 7 days after the visit to assess patient knowledge about the medication and self-report of activities associated with safety of use (e.g., double-dipping with acetaminophen, storage, use with alcohol or while driving).. A total of 274 patients were enrolled; 210 completed follow-up (110 usual care and 100 intervention). No significant differences in baseline characteristics emerged between the study arms; 42% were male, and 51% were white, with a median age of 43 years. Half of patients had non-back pain orthopedic injuries (49.5%). On follow-up, overall knowledge was poor, with only 28% able to name both active ingredients in the medication. The intervention group had better knowledge of precautions related to taking additional acetaminophen (usual care 18.2%, 95% confidence interval [CI] = 10.9% to 25.5% vs. intervention 38%, 95% CI = 28.3% to 47.7%; difference = 27.6, 95% CI of difference = 21.5 to 33.7) and knowledge of side effects (usual care median = 1, interquartile range [IQR] 0 to 2 vs. intervention median = 2, IQR = 1 to 2; p < 0.0001). Additionally, those who received the intervention were less likely to have reported driving within 6 hours after taking hydrocodone (usual care 13.6%, 95% CI = 7.2% to 20% vs. intervention 3%, 95% CI = -0.3% to 6.3%; difference = 10.6, 95% CI of difference = 3.4 to 17.9). There was no difference between groups related to knowledge about drinking alcohol while taking hydrocodone (overall 18.1%) or knowledge that the opioid could be addictive (overall 72.4%).. This simple strategy improved several, but not all, aspects of patient knowledge and resulted in fewer patients in the intervention arm driving while taking hydrocodone. Integration of a patient education document into conversations about opioids holds promise for improving patient knowledge about these high-risk medications.

Topics: Academic Medical Centers; Acetaminophen; Adolescent; Adult; Analgesics, Opioid; Double-Blind Method; Drug Combinations; Emergency Service, Hospital; Female; Health Knowledge, Attitudes, Practice; Health Literacy; Humans; Hydrocodone; Male; Middle Aged; Pain; Patient Discharge; Patient Education as Topic; Prospective Studies; United States; Young Adult

The objective was to test the hypothesis that hydrocodone/acetaminophen (Vicodin [5/500]) provides more efficacious analgesia than codeine/acetaminophen (Tylenol #3 [30/300]) in patients discharged from the emergency department (ED). Both are currently Drug Enforcement Administration (DEA) Schedule III narcotics.. This was a prospective, randomized, double-blind, clinical trial of patients with acute extremity pain who were discharged home from the ED, comparing a 3-day supply of oral hydrocodone/acetaminophen (5 mg/500 mg) to oral codeine/acetaminophen (30 mg/300 mg). Pain was measured on a valid and reproducible verbal numeric rating scale (NRS) ranging from 0 to 10, and patients were contacted by telephone approximately 24 hours after being discharged. The primary outcome was the between-group difference in improvement in pain at 2 hours following the most recent ingestion of the study drug, relative to the time of phone contact after ED discharge. Secondary outcomes compared side-effect profiles and patient satisfaction.. The median time from ED discharge to follow-up was 26 hours (interquartile range [IQR] = 24 to 39 hours). The mean NRS pain score before the most recent dose of pain medication after ED discharge was 7.6 NRS units for both groups. The mean decrease in pain scores 2 hours after pain medications were taken were 3.9 NRS units in the hydrocodone/acetaminophen group versus 3.5 NRS units in the codeine/acetaminophen group, for a difference of 0.4 NRS units (95% confidence interval [CI] = -0.3 to 1.2 NRS units). No differences were found in side effects or patient satisfaction.. Both medications decreased NRS pain scores by approximately 50%. However, the oral hydrocodone/acetaminophen failed to provide clinically or statistically superior pain relief compared to oral codeine/acetaminophen when prescribed to patients discharged from the ED with acute extremity pain. Similarly, there were no clinically or statistically important differences in side-effect profiles or patient satisfaction. If the DEA reclassifies hydrocodone as a Schedule II narcotic, as recently recommended by its advisory board, our data suggest that the codeine/acetaminophen may be a clinically reasonable Schedule III substitute for hydrocodone/acetaminophen at ED discharge. These findings should be regarded as tentative and require independent validation in similar and other acute pain models.

Topics: Acetaminophen; Acute Pain; Adolescent; Adult; Analgesics, Opioid; Codeine; Double-Blind Method; Drug Combinations; Emergency Service, Hospital; Extremities; Female; Humans; Hydrocodone; Male; Pain; Pain Measurement; Patient Discharge; Patient Satisfaction; Prospective Studies; Young Adult

For pain management, opioid therapy is a mainstay for treating acute pain and relieving moderate to severe chronic pain. Quantitative measurement of opioids and their metabolites in urine is used mainly for confirmation of screened results obtained for clinical and forensic purposes. Due to limitations in interpretation of urine results for pain management testing purposes, the use of blood or serum to assess opioids and their metabolites may be of benefit. This report describes a sensitive liquid chromatography-tandem mass spectrometry method for the detection of hydrocodone and its metabolites hydromorphone, norhydrocodone, and dihydrocodeine, and other common opiates that patients may be taking, including morphine, codeine, oxycodone, and oxymorphone in a single extraction. The method uses solid-phase extraction of 500 µL of sample with quantitation by liquid chromatography-tandem mass spectrometry. The assay is linear from 1.0 to 100 ng/mL and has a between-day coefficient of variation of <10%. The major advantage of this method is that a single extraction can detect hydrocodone and its metabolites and other opiates or opioids that patients frequently use simultaneously with hydrocodone.

Topics: Adolescent; Adult; Analgesics, Opioid; Chromatography, Liquid; Drug Monitoring; Female; Humans; Hydrocodone; Middle Aged; Pain; Solid Phase Extraction; Tandem Mass Spectrometry; Young Adult

The objectives for presenting these medico-legal forensic case reports are the following: 1) detail three cases where chronic opioid analgesic therapy (COAT) was alleged to cause iatrogenic addiction and/or re-addiction; 2) detail the plaintiff's and defendant's medical experts' opinions on these allegations; and 3) through analyzing these cases, develop some recommendations for future prevention of such allegations during COAT.. Case Reports.. Medico-legal issues surrounding the allegation of iatrogenic addiction were identified in each case.. Before starting COAT, physicians should obtain and document patient informed consent for the risk of addiction/re-addiction with COAT treatment. Patients with a history of addictions pre-COAT should be placed on adherence monitoring immediately on beginning COAT.

Topics: Adult; Analgesics, Opioid; Back Injuries; Expert Testimony; Female; Forensic Medicine; Humans; Hydrocodone; Iatrogenic Disease; Informed Consent; Low Back Pain; Male; Malpractice; Middle Aged; Morphine; Opioid-Related Disorders; Pain; Patient Compliance; Physical Examination; Shoulder Pain; Terminology as Topic

Abuse liability is thought to possibly be lower in long- than in short-acting opioids because lower peak serum levels may be less likely to induce psychoactive effects.. We compared patient responses to extended-release morphine, hydrocodone plus acetaminophen, and placebo in a randomized, double-blind crossover study using markers of abuse liability. Patients indicated their craving for drugs on 5 visual analog scales (VASs), completed the Addiction Research Center Inventory, and underwent cue reactivity testing. To perform the latter, subjects watched a video intended to produce a positive or a negative affect, after which a vial of medication was or was not presented (the cue) and then indicated their craving for drugs on 5 different VASs (the reactivity).. Differences in Addiction Research Inventory scores were statistically significant but clinically unimportant. Neuropsychological test results were mixed and unrelated to the medications studied. Cue reactivity did not differ among conditions but was uniformly high.. Using several markers of abuse liability, long-acting opioids do not have lower abuse potential than do short-acting opioids or placebo. Although cue reactivity did not differ among the conditions, uniformly high results in these patients suggest that it may have some value as a component of abuse liability testing.

Topics: Adult; Analgesics, Opioid; Behavior, Addictive; Chronic Disease; Conscious Sedation; Cross-Over Studies; Cues; Double-Blind Method; Female; Humans; Hydrocodone; Male; Middle Aged; Morphine; Opioid-Related Disorders; Pain; Self Administration; Stress, Physiological; Substance Abuse Detection; Surveys and Questionnaires; Time Factors

The objective was to compare subjects' change in perceived acute pain from an identical painful stimulus after receiving three separate, commonly used pain medications and placebo.. This was an institutional review board-approved, randomized, double-blind crossover study of healthy human volunteers. Subjects received 1000 mg of acetaminophen, 800 mg of ibuprofen, the combination of 650 mg of acetaminophen with 10 mg of hydrocodone, or placebo (800 mg of lactose) in a randomized order over four separate occasions each 1 week apart. Prior to receiving the drug on each study day, subjects placed their nondominant hand in a bath of 0 degrees C water for 45 seconds. The bath was divided into two sections; the larger was the reservoir of cooled water monitored at 0 degrees C, and the other half was filled from constant overflow. Water drained from the overflow section into the cooling unit and was then pumped up into the base of the reservoir through a diffusion grid. Subjects completed a 100-mm visual analog scale (VAS) representing perceived pain during the exposure. The cold water exposure and VAS were repeated 1 hour after receiving the study drug, and then subjects were observed for side effects for 4 hours. Data were compared using descriptive statistics, 95% confidence intervals (CIs), and repeated-measures analysis of variance (ANOVA).. Twenty-five subjects were enrolled. The mean VAS preexposure was 56.9 mm (+/-15.1 mm; range = 5 to 92 mm). The mean decrease in VAS after receiving the study drug for acetaminophen was 10.2% (95% CI = -1.4 to 20.4), for ibuprofen was -6.6% (95% CI = -16.5 to 3.20), for acetaminophen/hydrocodone was 9.5% (95% CI = 1.4 to 20.4), and for placebo was -6.9% (95% CI = -15.2 to 1.4). The range in change in pain scores for all agents was -91.3% to 57.6%. Mild side effects (nausea, dizziness, or somnolence) were reported in 11 subjects (44%) after receiving acetaminophen/hydrocodone; no other side effects were reported.. There was a wide range of changes in pain scores from this identical painful stimulus after receiving the study medications. Acetaminophen and acetaminophen/hydrocodone resulted in a similar decrease in pain (10.2 and 9.5%), while ibuprofen and placebo had a similar lack of effect (-6.6 and -6.9%). Forty-four percent of subjects receiving acetaminophen/hydrocodone reported mild side effects; no other side effects were seen. In this noninflammatory pain model, the VAS is not able to distinguish differences in pain relief between acetaminophen and acetaminophen/hydrocodone or ibuprofen and placebo.

Topics: Acetaminophen; Acute Disease; Analgesics; Cross-Over Studies; Double-Blind Method; Drug Combinations; Female; Human Experimentation; Humans; Hydrocodone; Ibuprofen; Male; Pain; Pain Measurement; Placebos

With the objective of comparing incidence of adverse events of the opioids codeine, hydrocodone, and tramadol in the relief of cancer pain, we conducted a randomized controlled trial in which patients with cancer were randomly assigned according to a computer-generated schedule to receive one of the three opioids. Of the 177 patients who participated, 62 patients received hydrocodone, 59 patients received codeine, and 56 patients received tramadol. The pain experienced by the participants originated most frequently from the stomach, breast, or prostate gland and was classified as either somatic (33%), visceral (52%), mixed (6%), or neuropathic (9%). At the first visit, 60% of the patients described their pain intensity as moderate (4-6/10), with the remaining 40% of the patients describing their pain as severe (7-10/10). The symptoms most associated with pain were weakness, insomnia. and anorexia. In 77% of the total number of cases, the patient was aware of his/her diagnosis prior to admittance to the palliative care unit. Of the total number of cases, 57% fell in the age range of 60-89 years old and 50% of the participants were female. No significant statistical difference in the analgesic efficacy of the three opioids was found (p: 0.69; chi(2): 0.73). Use of tramadol produced higher rates of adverse events than codeine and hydrocodone: vomiting, dizziness, loss of appetite, and weakness (p < 0.05).

Topics: Aged; Aged, 80 and over; Analgesics, Opioid; Codeine; Double-Blind Method; Female; Humans; Hydrocodone; Incidence; Male; Middle Aged; Neoplasms; Pain; Pain Measurement; Palliative Care; Quality of Life; Tramadol; Treatment Outcome

Concern about abuse/dependence in chronic pain patients taking opioid analgesics may lead to undertreatment of pain, yet little is known about the prevalence of abuse/dependence in these patients and how it differs among analgesic agents. The objective of this study was to assess the prevalence of tramadol abuse compared to nonsteroidal anti-inflammatory drugs (NSAIDs) and hydrocodone-containing analgesics in patients with chronic noncancer pain (CNP). The study had three arms. The first arm consisted of subjects prescribed tramadol alone; the second of subjects randomized to either NSAIDs or tramadol; and the third of subjects randomized to hydrocodone or tramadol. Each investigator received two boxes of prescriptions randomized so that one in every four prescriptions was for tramadol. Upon deciding on the therapeutically appropriate arm, the physician selected the appropriate box, opened the next envelope and completed the enclosed prescription. After the initial randomization, physicians could prescribe whatever medication was therapeutically appropriate. A total of 11,352 subjects were enrolled. Up to nine interviews using a structured questionnaire were conducted over a 12-month period. An algorithm called the "Abuse Index" was developed to identify subjects who were abusing the drug. The primary components of the index were increasing dose without physician approval, use for purposes other than intended, inability to stop its use, and withdrawal. The percent of subjects who scored positive for abuse at least once during the 12-month follow-up were 2.5% for NSAIDs, 2.7% for tramadol, and 4.9% for hydrocodone. When more than one hit on the algorithm was used as a measure of persistence, abuse rates were 0.5% for NSAIDs, 0.7% for tramadol, and 1.2% for hydrocodone. Thus, the results of this study suggest that the prevalence of abuse/dependence over a 12-month period in a CNP population that was primarily female was equivalent for tramadol and NSAIDs, with both significantly less than the rate for hydrocodone.

Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Female; Humans; Hydrocodone; Male; Middle Aged; Pain; Prevalence; Substance-Related Disorders; Tramadol

Previous studies have demonstrated the efficacy of oxycodone and hydrocodone for the treatment of acute pain. However, to the best of the authors' knowledge, no previous reports have compared the efficacies of these commonly prescribed agents.. To compare the efficacies of oxycodone and hydrocodone for the treatment of acute pain associated with fractures in emergency department (ED) patients.. This prospective, double-blind, randomized, controlled trial was conducted at an urban trauma center with an annual census of 65,000. Eligible participants included ED patients over the age of 12 years with fractures who consented to participate. Subjects were randomized to receive either oxycodone (5 mg orally [po]) with acetaminophen, or hydrocodone (5 mg po) with acetaminophen. Measurements included demographic information; pain scores on a verbal numeric rating scale at baseline and at 30 and 60 minutes; vital signs at baseline and at 30 and 60 minutes; and adverse effects. Ninety-five-percent confidence intervals (95% CIs) constructed about means and proportions were used to assess differences between the oxycodone and hydrocodone groups in analgesic efficacy and side effects.. Seventy-three subjects were randomized to receive oxycodone or hydrocodone. Sixty-seven subjects completed the ED study period (n = 35, oxycodone; n = 32, hydrocodone). There was no difference between the two groups in age, weight, gender, ethnicity, diagnoses, baseline pain scores, or vital signs. Patients in both groups had pain relief from baseline to 30 minutes (oxycodone mean change 3.7, 95% CI = 2.9 to 4.6; hydrocodone mean change 2.5, 95% CI = 1.7 to 3.3), and from baseline to 60 minutes (oxycodone mean change 4.4, 95% CI = 3.2 to 5.6; hydrocodone mean change 3.0, 95% CI = 2.1 to 3.9). There was no difference in pain between the patients treated with oxycodone and hydrocodone at 30 minutes (mean difference between groups -0.6, 95% CI = -1.8 to 0.5) or at 60 minutes (mean difference -0.5, 95% CI = -2.0 to 1.0). There was no difference between the groups in nausea, vomiting, itching, or drowsiness; however, the hydrocodone patients had a higher incidence of constipation (oxycodone 0%, hydrocodone 21%, difference in proportions 21%, 95% CI = 3% to 39% more with hydrocodone).. Treatment with acetaminophen and either oxycodone, 5 mg po, or hydrocodone, 5 mg po, resulted in pain relief among ED patients with acute fractures, and there was no difference between the two agents at 30 and 60 minutes. Adverse effect profiles were similar, with the exception of a higher incidence of subsequent constipation with the use of hydrocodone. These results suggest that oxycodone and hydrocodone have similarly potent analgesic effects in the first hour of treatment for ED patients with acute fractures.

Topics: Adult; Analgesics, Opioid; Double-Blind Method; Female; Fractures, Bone; Humans; Hydrocodone; Male; Middle Aged; Oxycodone; Pain; Pain Measurement; Prospective Studies

The objective of this study was to compare the effectiveness of combination hydrocodone 7.5 mg and ibuprofen 200 mg with that of combination codeine 30 mg and acetaminophen 300 mg for the treatment of chronic pain.. Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved fixed-dose combination analgesic containing an opioid and ibuprofen.. In this randomized, parallel-group, double-blind, repeated-dose, active-comparator, 4-week, multicenter study, 469 patients were randomly assigned to receive a 1-tablet (n = 156) or 2-tablet (n = 153) dose of combination hydrocodone 7.5 mg and ibuprofen 200 mg (HI1 and HI2, respectively) or a 2-tablet dose of combination codeine 30 mg and acetaminophen 300 mg (CA, n = 160), the active comparator, every 6 to 8 hours as needed for pain. Efficacy was measured through pain relief scores, number of daily doses of study medication, number of daily doses of supplemental analgesics, number of patients who discontinued therapy due to an unsatisfactory analgesic response, and global assessment scores.. Of the 469 patients, 255 (54.4%) were female and 214 (45.6%) were male. The mean age was 51.1 years. Types of chronic pain included back (214; 45.6%), arthritic (145; 30.9%), other musculoskeletal (65; 13.9%), cancer (6; 1.3%), diabetic neuropathic (3; 0.6%), postherpetic neuralgic (5; 1.1%), other neurologic (21; 4.5%), and other unclassified chronic pain (10; 2.1%). During the 48 hours prior to the study, 351 (74.8%) patients had been treated with opioid or opioid-nonopioid combination analgesics. The overall mean daily pain relief score was significantly greater in the HI2 group (2.25+/-0.89) than in the HI1 group (1.98+/-0.87) (P = 0.003) or the CA group (1.85+/-0.96) (P < 0.001). The overall mean number of daily doses of study medication was significantly less in the HI2 group (2.94+/-0.99) than in the HI1 group (3.23+/-0.76) (P = 0.036) or the CA group (3.26+/-0.75) (P = 0.014). The overall mean number of daily doses of supplemental analgesics was significantly less in the HI2 group (0.24+/-0.49) than in the HI1 group (0.34+/-0.58) (P = 0.021) or CA group (0.49+/-0.85) (P = 0.010). The number of patients who discontinued treatment due to an unsatisfactory analgesic response was significantly less in the HI2 group (2; 1.3%) than in the CA group (12; 7.5%) (P = 0.008). HI2 was more effective than HI1 and CA as measured by pain relief scores for week 1 (P < 0.001 vs HI1 and CA), week 2 (P < 0.001 vs HI1 and CA), and week 3 (P = 0.008 vs HI1 and P < 0.001 vs CA); daily doses of study medication for week 1 (P = 0.019 vs HI1 and P = 0.011 vs CA); daily doses of supplemental analgesics for week 1 (P = 0.010 vs HI1 and CA); and global assessment scores for week 1 (P = 0.018 vs HI1 and P < 0.001 vs CA), week 2 (P = 0.005 vs HI1 and P < 0.001 vs CA), and week 4 (P = 0.013 vs HI1 and P = 0.023 vs CA). There were no significant differences between HI1 and CA in any efficacy variable. There were no significant differences in the number of patients experiencing adverse events in the HI2 (127; 83%), HI1 (124; 79.5%), and CA (129; 80.6%) groups. However, the mean number of patients who discontinued treatment due to adverse events was significantly greater in the HI2 group (40; 26.1%) than in the HI1 group (23; 14.7%) (P = 0.013).. The results of this study suggest that 2-tablet doses of combination hydrocodone 7.5 mg and ibuprofen 200 mg may be more effective than either 1-tablet doses of this combination or 2-tablet doses of combination codeine 30 mg and acetaminophen 300 mg. Moreover, 1-tablet doses of combination hydrocodone 7.5 mg and ibuprofen 200 mg may be as effective as 2-tablet doses of combination codeine 30 mg and acetaminophen 300 mg.

Topics: Acetaminophen; Adult; Aged; Analgesics; Chronic Disease; Codeine; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hydrocodone; Ibuprofen; Male; Middle Aged; Pain; Pain Measurement; Placebos

To evaluate the efficacy of an oral tramadol preparation versus that of an oral hydrocodone-acetaminophen preparation in acute musculoskeletal pain.. A randomized, prospective, double-blind clinical trial was conducted in an urban teaching emergency department with an annual census of 41,000. Participants comprised a convenience sample of 68 adult ED patients with acute musculoskeletal pain caused by minor trauma. Thirty-three patients received tramadol (100 mg), and 35 patients received hydrocodone-acetaminophen (5 mg hydrocodone with 500 mg acetaminophen). The drugs were prepared in identical-appearing capsules. Pain was evaluated by a 100-mm visual analog scale (VAS) at baseline and at 30, 60, 90, 120, and 180 minutes after dosing. VAS scores were analyzed by 2-way repeated-measures ANOVA, and nominal data were analyzed by Fisher's exact test.. Mean pain scores did not differ at baseline (tramadol, 68.3+/-21.8; hydrocodone-acetaminophen, 69.1+/-17.8; P=NS) but were significantly lower in the hydrocodone-acetaminophen group beginning at 30 minutes through 180 minutes. There were 6 dropouts as a result of reported inadequate analgesia, 3 in each group (P=NS). The discharge diagnoses and prevalence of side effects did not differ significantly between groups.. Tramadol provides inferior analgesia to hydrocodone-acetaminophen in ED patients with acute musculoskeletal pain.

Topics: Acetaminophen; Acute Disease; Administration, Oral; Adolescent; Adult; Aged; Analgesics, Non-Narcotic; Analgesics, Opioid; Analysis of Variance; Double-Blind Method; Drug Combinations; Emergency Service, Hospital; Follow-Up Studies; Hospitals, Teaching; Humans; Hydrocodone; Middle Aged; Musculoskeletal System; Pain; Pain Measurement; Patient Discharge; Patient Dropouts; Prevalence; Prospective Studies; Tramadol

To evaluate the efficacy and prevalence of side effects of hydrocodone versus codeine in acute pain syndromes. TYPE OF PARTICIPANTS/SETTING: Sixty-two consecutive adult emergency department patients 18 to 70 years old with acute musculoskeletal pain. Patients using other analgesics or having any contraindication to opioid therapy were excluded. In addition, 12 patients were excluded because of insufficient data or study dropout.. In a randomized, double-blind prospective manner, patients received either 5 mg hydrocodone with 500 mg acetaminophen or 30 mg codeine with 500 mg acetaminophen to take on discharge from the ED and every four hours thereafter as needed for pain.. Pain intensity was evaluated by a visual analog scale at zero, one, two, four, eight, 24, and 48 hours. Specific side effects were sought, along with the number of patients reporting inadequate analgesia.. Data were obtained on 50 subjects (25 per group). Mean and median pain scores did not differ significantly at time zero (x vs y, 6.03 vs 5.99 and 6.8 vs 6.1, respectively) or subsequent intervals. Side effects were noted in eight hydrocodone/acetaminophen and 18 codeine/acetaminophen patients (P = .005). No significant differences in gastrointestinal side effects were reported; however, less nausea or vomiting was reported in the hydrocodone group (P = .23). Central nervous system side effects (sedation or lightheadedness) were reported in six hydrocodone/acetaminophen patients compared with 16 codeine/acetaminophen patients (P less than .005). In addition, no hydrocodone/acetaminophen patients reported inadequate analgesia compared with six codeine/acetaminophen patients (P less than .05).. Although pain scores were not significantly different, hydrocodone may be a more effective analgesic than codeine in acute musculoskeletal pain, as demonstrated by significantly fewer treatment failures. Central nervous system side effects are less common with hydrocodone than with codeine.

Topics: Acetaminophen; Acute Disease; Adolescent; Adult; Aged; Codeine; Double-Blind Method; Drug Combinations; Emergencies; Humans; Hydrocodone; Middle Aged; Musculoskeletal Diseases; Pain; Pain Measurement; Prospective Studies

1 In a double-blind study, 108 postpartum patients received single oral doses of either placebo, acetaminophen (paracetamol) 1000 mg, hydrocodone 10 mg, the combination of acetaminophen plus hydrocodone, or codeine 60 mg. 2 In the 2X2 factorial analysis, both the acetaminophen and hydrocodone effects were statistically significant, whereas the interaction contrast was not. This indicates that the analgesic effect of the combination represents the additive effect of its constituents and is consistent with the assumption that these constituents are producing analgesia by different mechanisms. 3 Although significantly superior to placebo, codeine seemed to be inferior to the other treatments. 4 Compared with placebo, both codeine and hydrocodone (centrally acting narcotics) seemed relatively more effective in uterine cramp than episiotomy pain; the reverse seemed true with acetaminophen (a peripherally acting analgesic). 5 Some methodological implications for the evaluation of analgesic combinations are discussed.

Topics: Acetaminophen; Clinical Trials as Topic; Codeine; Double-Blind Method; Drug Combinations; Female; Humans; Hydrocodone; Pain; Placebos; Postpartum Period; Pregnancy; Time Factors

Three hundred and twelve patients suffering from painful conditions were admitted to a multicentre, double-blind controlled trial, conducted in general practice in which five analgesics--floctafenine (Idarac), paracetamol, aspirin, dihydrocodeine and pentazocine--were compared. Overall ratings of analgesic effect placed floctafenine first in rank order. Floctafenine was statistically significantly superior in effect to pentazocine but not to the other three agents as far as doctor ratings were concerned; and superior to both pentazocine and dihydrocodeine in the opinion of patients. Fewer patients experienced side-effects on floctafenine than on the other four analgesics and this difference between floctafenine and pentazocine, and floctafenine and dihydrocodeine was statistically significant.

Topics: Acetaminophen; Analgesics; Aspirin; Clinical Trials as Topic; Female; Humans; Hydrocodone; Male; ortho-Aminobenzoates; Pain; Pentazocine; Quinolines

Topics: Cerebral Palsy; Female; Humans; Hydrocodone; Middle Aged; Pain; Serotonin Syndrome

Topics: Analgesics, Opioid; Celecoxib; Humans; Hydrocodone; Oxycodone; Pain; Pain, Postoperative; Tramadol

Prescription opioids are often used during pregnancy even though they are associated with neonatal opioid withdrawal syndrome (NOWS). Most studies of adverse outcomes of opioid use for pain have assessed only the class-wide outcome despite the pharmacodynamic and pharmacokinetic heterogeneity across opioid medications.. To compare the risk of NOWS across common types of opioids when prescribed as monotherapy during the last 3 months of pregnancy.. This cohort study analyzed administrative claims data of Medicaid-insured mothers and newborns in 46 states and Washington DC from January 1, 2000, through December 31, 2014. Participants were mothers with 2 or more dispensed opioid prescriptions within 90 days before delivery and their eligible live-born neonates. Data were analyzed from February 2020 to March 2021.. Different types of opioid medications were compared by agonist strength (strong vs weak) and half-life (medium vs short and long vs short) of the opioid active ingredient.. The primary outcome was NOWS, which was identified using an International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic code in the 30 days after delivery. Relative risks (RRs) were adjusted for an exposure propensity score, including demographic characteristics, comorbidities, other medication use, and opioid treatment characteristics (including morphine milligram equivalents), using fine stratification.. The cohort comprised 48 202 opioid-exposed pregnancies with live newborns. A total of 1069 neonates (2.2%) had NOWS and 559 (1.2%) had severe NOWS. Opioid exposure during pregnancy included 16 202 pregnancies exposed to codeine, 4540 to oxycodone, 1244 to tramadol, 260 to methadone (dispensed for pain), 90 to hydromorphone, and 63 to morphine compared with 25 710 exposed to hydrocodone. Demographic characteristics varied across opioids, with tramadol, oxycodone, methadone, hydromorphone, and morphine being more commonly dispensed at older maternal age (≥35 years). Compared with hydrocodone, codeine had a lower adjusted RR of NOWS (0.57; 95% CI, 0.46-0.70), with a similar adjusted RR for tramadol (RR, 1.06; 95% CI, 0.73-1.56), and 2- to 3-fold higher adjusted RRs for oxycodone (1.87; 95% CI, 1.66-2.11), morphine (2.84; 95% CI, 1.30-6.22), methadone (3.02; 95% CI, 2.45-3.73), and hydromorphone (2.03; 95% CI, 1.09-3.78). Strong agonists were associated with a higher risk of NOWS than weak agonists (RR, 1.97; 95% CI, 1.78-2.17), and long half-life opioids were associated with an increased risk compared with short half-life products (RR, 1.33; 95% CI, 1.12-1.56). Findings were consistent across sensitivity and subgroup analyses.. Results of this study show higher risk of NOWS and severe NOWS among neonates with in utero exposure to strong agonists and long half-life prescription opioids. Information on the opioid-specific risk of NOWS may help prescribers select opioids for pain management in late stages of pregnancy.

Topics: Adult; Analgesics, Opioid; Codeine; Cohort Studies; Female; Humans; Hydrocodone; Hydromorphone; Infant, Newborn; Infant, Newborn, Diseases; Methadone; Morphine; Neonatal Abstinence Syndrome; Oxycodone; Pain; Pregnancy; Prescriptions; Substance Withdrawal Syndrome; Tramadol; United States

Cytochrome P450 2D (CYP2D) metabolises many centrally-acting substrates including opioids. Hydrocodone, an opioid and CYP2D substrate, is metabolised to hydromorphone, an active metabolite. CYP2D in the brain is active in vivo and can alter drug response however, it is unknown whether metabolism by CYP2D in the brain alters oral hydrocodone induced analgesia. Propranolol, a selective CYP2D mechanism-based inhibitor, or vehicle, was administered into the right cerebral ventricle of male rats, (HAN Wistars, Envigo), 24 h before testing for analgesia from oral hydrocodone (or hydromorphone, a non-CYP2D substrate). Hydrocodone and its CYP2D-mediated metabolites were simultaneously quantified using a novel LC-MS/MS assay. After propranolol vs vehicle pretreatment, there was significantly higher analgesia from oral hydrocodone, and a significantly lower brain CYP2D metabolic ratio (an in vivo phenotype of brain CYP2D activity that was derived from the molar sum of hydromorphone and its metabolites divided by hydrocodone). The brain CYP2D metabolic ratio correlated significantly with analgesia. There was no pretreatment effect on plasma hydrocodone concentrations, elimination rates, or metabolic ratio (an in vivo phenotype for hepatic CYP2D activity). The liver CYP2D metabolic ratio did not correlate with analgesia. Propranolol pretreatment had no impact on analgesia from oral hydromorphone. These data suggest that inhibited CYP2D activity in brain, causing reduced metabolism of brain hydrocodone, resulted in higher analgesia from oral hydrocodone, despite hydrocodone having a lower μ-opioid receptor affinity than hydromorphone. Thus, variation in CYP2D in the brain may be an important source of interindividual differences in response to CYP2D substrates, including oral hydrocodone.

Topics: Analgesia; Analgesics, Opioid; Animals; Brain; Chromatography, Liquid; Cytochrome P-450 Enzyme System; Hydrocodone; Hydromorphone; Male; Pain; Propranolol; Rats; Rats, Wistar; Tandem Mass Spectrometry

Social environment influences the trajectory of developing opioid use disorder (OUD). Thus, the present study tested the hypothesis that sociability levels will affect the responses to opioids. Mice were tested for their baseline sociability, anxiety levels, pain sensitivities, and their acute locomotor response to 5 mg/kg opioids. Then, they were administered repeatedly with saline, hydrocodone, or morphine (20 mg/kg for 5 days, and then 40 mg/kg for 5 days). Subsequently, they were examined for the expression of locomotor sensitization and retested for the effects of opioids on their sociability, anxiety levels, and pain sensitivity. On the basis of their baseline sociability level, mice were divided into socially avoiding and socially exploring. Socially avoiding and socially exploring mice did not differ in their baseline weight and anxiety sensitivities. Socially avoiding mice had slightly higher baseline heat sensitivity than those in socially exploring mice. Repeated administration of opioids had differential effects in socially avoiding and socially exploring mice. In both social groups, repeated morphine administration had overall stronger effects compared with hydrocodone. Morphine-treated socially exploring mice developed greater locomotor sensitization than those in morphine-treated socially avoiding mice. Morphine-treated socially avoiding mice, but not socially exploring mice, spent more time in the center zone of the open-field test and in the light zone of light/dark boxes, and developed heat hyperalgesia. This study suggests that socially exploring animals are more sensitive to the sensitizing effects of opioids. In contrast, opioids have greater effects on the stress and pain systems of socially avoiding animals. Thus, the underlying mechanisms for developing OUD might differ in individuals with various sociability levels.

Topics: Analgesics, Opioid; Animals; Anxiety; Dose-Response Relationship, Drug; Hydrocodone; Hyperalgesia; Male; Mice; Mice, Inbred C57BL; Morphine; Opioid-Related Disorders; Pain; Pain Threshold; Social Environment

We examined the results of 1.3 million drug tests performed on patients being monitored for compliance with pain medications and substance abuse rehabilitation to determine if the 2016 CDC prescribing guidelines had any impact on opiate benzodiazepine use. We observed that the combination of the opiate drugs morphine, oxycodone, and hydrocodone with the benzodiazepine metabolites oxazepam, alphahydroxyalprazolam, and 7-aminoclonazepam showed many patients were on a combination of these drugs. This ranged from approximately 9 to 16%. There was considerable variability between opiate drug pairs, but there was a general trend to fewer patients on the combination of opiate-benzodiazepine over the 2016 to 2019 time frame.

Topics: Benzodiazepines; Centers for Disease Control and Prevention, U.S.; Drug Interactions; Drug Therapy, Combination; Guideline Adherence; Humans; Hydrocodone; Morphine; Opiate Alkaloids; Opioid-Related Disorders; Oxycodone; Pain; Pharmaceutical Preparations; United States

Our objective was to identify patterns of opioid use among pregnant women enrolled in RI Medicaid.. This study used linked RI Medicaid and RI Birth Certificate data from 01/01/2006 to 12/31/2016. We examined temporal trends of prescription opioid dispensings and identified risk factors associated with opioids use during pregnancy.. Among 25,500 RI Medicaid enrolled pregnant women who delivered a live baby from 2008 to 2016, 1,914 (7.5%) received at least one prescription for an opioid medication during pregnancy, 810 (3.2%) were during the first trimester, 633 (2.5%) during the second trimester, and 866 (3.4%) during the third trimester. Of these, 213 (0.8%) women received 3 or more opioids during pregnancy. The prevalence of prescription opioids dispensed in pregnant women increased from 4.9% in 2008 to 9.6% in 2015 (β±SD: 0.66±0.28, P=0.05).. Prescription opioid use during pregnancy has increased among women enrolled in RI Medicaid.

Topics: Adolescent; Adult; Analgesics, Opioid; Drug Prescriptions; Female; Humans; Hydrocodone; Logistic Models; Medicaid; Multivariate Analysis; Oxycodone; Pain; Pregnancy; Pregnancy Trimesters; Retrospective Studies; Rhode Island; United States; Young Adult

Opioid prescriptions have the potential for misuse. In October 2014, the federal schedule II prescribing mandate reclassified hydrocodone combination products from schedule III to schedule II drugs that required a written prescription. The aim of this study was to evaluate the opioid-prescribing practices in a graduate endodontic clinic (GEC) before and after the mandate.. Electronic health records from all patients treated in the GEC from 2010 to 2018 were reviewed retrospectively for opioid prescribing, the date of prescription, and the Current Dental Terminology code. Where opioid prescribing was documented in the electronic health record, additional data were extracted about pulpal and periapical diagnosis, pain level, opioid type, and prescription details. Prescribing rates were calculated and analyzed by using chi-square, analysis of variance, logistic regression, and multivariable analysis. Significance was set at P < .05.. Overall, 4851 patients underwent 7841 procedures; 92.2% of patients were never prescribed opioids. The remaining 380 patients underwent 420 procedures, and 509 prescriptions were provided. Prescribing rates were 7.5% (228/3021) before versus 4.0% (192/4820) after the mandate (P < .001). Hydrocodone combinations were the most prescribed opioid (77%, 392/509). Tramadol prescribing increased after the mandate (P = .023). Multivariable analysis showed significantly higher prescribing for apicoectomy procedures (P < .001). Preoperative pulpal and periapical diagnosis and pain level were not significantly associated with opioid prescribing.. An overall reduction in opioid-prescribing rates occurred coincidentally with the 2014 federal mandate. The lack of correlation between prescribing and pain level highlighted the need for evidence-based rather than habitual prescribing protocols in the GEC.

Topics: Analgesics, Opioid; Controlled Substances; Drug and Narcotic Control; Endodontics; Humans; Hydrocodone; Pain; Practice Patterns, Physicians'; Retrospective Studies

Topics: Acetaminophen; Analgesics, Opioid; Brain Injuries, Traumatic; Chromatography, High Pressure Liquid; Codeine; Female; Humans; Hydrocodone; Immunoassay; Mass Spectrometry; Medical Marijuana; Middle Aged; Pain

The impact of hydrocodone reclassification on analgesic prescribing in the Veterans Health Administration (VHA) was quantified.. In this retrospective observational study, the volume of opioid medication dispensed was calculated quarterly from October 2011 to September 2015 using national VHA administrative data. Four volume measures were examined (prescription count, tablets dispensed, days' supply dispensed, and unique patients) for 4 opioid groups: hydrocodone combination products (HCPs), other opioid combination products, tramadol, and single-agent Schedule II opioids. HCP prescription count was further tabulated within longitudinal course of receipt groups: short-term, intermediate-term, and long-term. The initiation frequency of alternative analgesic pharmacotherapy, including opioid and nonopioid medications, was assessed among patients who discontinued long-term HCP receipt at reclassification.. HCP prescriptions declined by 172,535 (19.4%) in the quarter after reclassification, whereas other opioid categories remained unchanged. The number of HCP prescriptions decreased by 10.7% among patients with short-term opioid receipt, and by 23.3% and 19.4% for intermediate- and long-term receipt groups, respectively. Among 13,416 individuals who discontinued receipt of long-term HCPs, replacement analgesics were not identified in 8,055 (60.0%) patients, whereas prescriptions for alternative opioids were observed in 3,557 (26.5%) and nonopioids in 2,753 (20.5%).. HCP dispensing in VHA declined by 19.4% in the quarter after reclassification, which was driven largely by patients receiving long-term therapy. More than 13,000 veterans discontinued receipt of long-term HCP therapy after reclassification and the majority did not receive a replacement analgesic through VHA.

Topics: Adult; Analgesics, Opioid; Controlled Substances; Drug and Narcotic Control; Drug Prescriptions; Drug Substitution; Female; Humans; Hydrocodone; Middle Aged; Pain; Practice Patterns, Physicians'; Retrospective Studies; Time Factors; United States; United States Department of Veterans Affairs

Black older adults often experience disparities in pain treatment that results in unmet pain needs. The aims of this study were to assess the pain management experiences of a group of community dwelling Black older adults and identify gaps in clinical practice. A qualitative, descriptive design was employed using the methodology of ethnography. The setting was an urban, low-income, community elderly housing high-rise facility. Participants included facility residents (n = 106); of these, 20 completed structured qualitative interviews. The Brief Pain Inventory and qualitative interviews were used to determine pain prevalence, treatment practices, and barriers. Eighty-six percent of the participants had severe pain with a mean worst pain rating of 7 on a 0 to 10 scale. Pain interfered moderately with general activity (5.59), walking (5.73) and normal work (5.70), also measured on 0 to 10 scales. Participants preferred non-opioid analgesics, topical over-the-counter treatments, and nonpharmacological interventions such as prayer/meditation, and exercise for treatment. Medications most commonly used by participants for pain management included, hydrocodone with acetaminophen (28.6%), nonsteroidal anti-inflammatory drugs (13.2%), acetaminophen with codeine (12%), and tramadol (9.9). Qualitative interviews revealed that pain management barriers were centered around communication concerns about side effects, fears of addiction, and provider mistrust. A communication gap exists between patients and providers. Discussing patient treatment preferences, providing balanced treatment information, and following-up with patients on treatment plan effectiveness by phone can improve how pain is managed for Black older adults.

Topics: Aged; Anthropology, Cultural; Black or African American; Codeine; Exercise Therapy; Faith Healing; Female; Healthcare Disparities; Housing for the Elderly; Humans; Hydrocodone; Ibuprofen; Male; Medicine, Traditional; Middle Aged; Naproxen; Pain; Pain Management; Pain Measurement; Psychometrics; Qualitative Research; Surveys and Questionnaires; Tramadol

To examine differences in opioid prescribing by patient characteristics and variation in hydrocodone combination product (HCP) prescribing attributed to states, before and after the 2014 Drug Enforcement Administration's reclassification of HCP from schedule III to the more restrictive schedule II.. We used 2013 to 2015 data for 9 202 958 patients aged 18 to 64 from a large nationally representative commercial health insurance program to assess the temporal trends in the monthly rate of opioid prescribing.. HCP prescribing decreased by 26% from June 2013 to June 2015; the rate of prescriptions for any opioid decreased by 11%. Prescribing of non-hydrocodone schedule III opioids increased slightly while prescribing of non-hydrocodone schedule II opioids and tramadol was stable. Absolute decreases in HCP prescribing rates were larger in patients being treated for cancer (-2.26% vs -0.7% for non-cancer patients, P < 0.0001) and in those with high comorbidities (-2.13% vs -0.55% for those with no comorbidity, P < 0.0001). Differences in the absolute and relative changes in HCP prescribing rates among states were large; for example, a relative decrease of 46.7% in Texas and a 12.7% increase in South Dakota. The variation in HCP prescribing attributable to the state of residence increased from 6.6% in 2013 to 8.7% in 2015.. The 2014 federal policy was associated with a decrease in rates of HCP and total opioid prescribing. The large decrease in the rates of HCP prescribing for patients with actively treated cancer may represent an unintended consequence.

Topics: Adult; Analgesics, Opioid; Controlled Substances; Drug and Narcotic Control; Drug Combinations; Drug Prescriptions; Female; Humans; Hydrocodone; Male; Middle Aged; Opioid-Related Disorders; Pain; Practice Patterns, Physicians'; United States; Young Adult

Pain is the most frequent complaint of burn-injured patients. Opioids are commonly used in the course of treatment. However, there is a lack of rodent studies that examine the differential effects of various opioids on burn pain.. This study compared the ability of morphine, oxycodone, and hydrocodone to suppress the development of burn-induced mechanical allodynia and reduce pain sensitivity.. Mice were examined for their baseline pain sensitivity thresholds using the von Frey Filaments test. Then, they were subjected to burn or sham injury and treated orally with morphine, oxycodone, hydrocodone (20 or 40 mg/kg), or saline twice daily throughout the study. They were retested on days 4, 7, 11, 14, 21, and 28 postburn.. In the sham animals, morphine produced significant opioid-induced hyperalgesia (OIH). Development of OIH was minimal for hydrocodone and was not observed for oxycodone. Secondary mechanical allodynia was observed beginning four days after the burn injury and intensified with time. All opioids produced comparable antinociceptive effects. Hydrocodone was effective in suppressing the development of burn-induced mechanical allodynia and fully treated the burn-induced increase in pain sensitivity. In contrast, morphine and oxycodone had only minimal effects on the development of burn-induced mechanical allodynia and only partially treated the burn-induced increase in pain sensitivity.. This study demonstrated that hydrocodone is effective in suppressing the development of burn-induced mechanical allodynia, while both morphine and oxycodone had minimal effects. These findings underscore the need for additional studies on the differences among various opioids using clinically relevant pain models.

Topics: Analgesics, Opioid; Animals; Burns; Dose-Response Relationship, Drug; Hydrocodone; Hyperalgesia; Male; Mice, Inbred C57BL; Morphine; Oxycodone; Pain; Pain Measurement; Pain Threshold

This study compared the development of tolerance to two orally bioavailable prescription opioids, oxycodone and hydrocodone, to that of morphine, and the reversal of this tolerance by ethanol. Oxycodone (s.c.) was significantly more potent in the mouse tail-withdrawal assay than either morphine or hydrocodone. Oxycodone was also significantly more potent in this assay than hydrocodone when administered orally. Tolerance was seen following chronic subcutaneous administration of each of the three drugs and by the chronic administration of oral oxycodone, but not following the chronic oral administration of hydrocodone. Ethanol (1 g/kg i.p.) significantly reversed the tolerance to the subcutaneous administration of each of the three opioids that developed when given 30 minutes prior to challenge doses. It took twice as much ethanol, when given orally, to reverse the tolerance to oxycodone. We investigated whether the observed tolerance to oxycodone and its reversal by ethanol were due to biodispositional changes or reflected a true neuronal tolerance. As expected, a relationship between brain oxycodone concentrations and activity in the tail-immersion test existed following administration of acute oral oxycodone. Following chronic treatment, brain oxycodone concentrations were significantly lower than acute concentrations. Oral ethanol (2 g/kg) reversed the tolerance to chronic oxycodone, but did not alter brain concentrations of either acute or chronic oxycodone. These studies show that there is a metabolic component of tolerance to oxycodone; however, the reversal of that tolerance by ethanol is not due to an alteration of the biodisposition of oxycodone, but rather is neuronal in nature.

Topics: Analgesics, Opioid; Animals; Behavior, Animal; Brain; Central Nervous System Depressants; Dose-Response Relationship, Drug; Drug Tolerance; Ethanol; Hydrocodone; Male; Mice; Oxycodone; Pain; Pain Measurement

The Drug Enforcement Administration (DEA) changed hydrocodone-containing products (HCPs) from Schedule III to II status on October 6, 2014, making codeine-containing products (CCPs) the only non-Schedule II oral opioid agents.. We sought to describe prescribing patterns of oral opioid agents in the pediatric emergency department before and after the 2014 DEA rescheduling of HCPs.. We performed a cross-sectional study evaluating prescribing patterns in the pediatric emergency department at an urban, academic, quaternary care children's hospital system for 6 months before and 6 months after the DEA rescheduling of HCPs. Differences in patient demographics, provider type, and diagnoses were assessed during the two time periods using Pearson's chi-squared test. The Breslow-Day statistic was used to assess differences in prescribing patterns by provider type.. There were 1256 prescriptions for HCPs and CCPs in our pediatric emergency department during the study period, and only 36 prescriptions for alternate oral opioid medications. Prescriptions of all opioid pain medications decreased by 55% after rescheduling. The odds of prescribing HCPs were reduced by 60% after the DEA rescheduling (odds ratio 0.40 [95% confidence interval {CI} 0.30-0.54]; p < 0.001). There was no difference between monthly ordering frequencies for CCPs before or after the DEA rescheduling (p = 0.75).. The period after rescheduling of HCPs was associated with a lower odds of HCP prescriptions in our emergency department without an increase in the prescription of CCPs.

Topics: Analgesics, Opioid; Cross-Sectional Studies; Drug Prescriptions; Emergency Service, Hospital; Female; Humans; Hydrocodone; Male; Pain; Pediatrics; Practice Patterns, Physicians'; Workforce

Burn victim patients are frequently prescribed opioids at doses that are significantly higher than standard analgesic dosing guidelines, and, even despite an escalation in opioid dosing, many continue to experience pain. Thus, the aim of this study was to determine the effect of burn injury on opioid antinociception. Mice were examined for their baseline pain sensitivity thresholds using the von Frey filaments test. Then, they were subjected to burn or sham injury to the dorsal surface of the hindpaw and treated orally with morphine, oxycodone, hydrocodone (20 or 40 mg/kg), or saline twice daily throughout the study. They were retested on days 4, 7, 11, 14, 21, and 28 following the burn injury. The antinociceptive effects of the various drugs were analyzed by computing the daily difference between pain sensitivity threshold scores (in g) before and after treatment. This study showed that burn injury decreases opioid antinociception potency. A marked reduction was observed in the antinociceptive effectiveness of all opioids, and for both doses, in the burn-injured versus the sham animals. These results suggest that burn trauma limits the ability of opioids to be effective in reducing pain.

Topics: Administration, Oral; Analgesics, Opioid; Animals; Burns; Disease Models, Animal; Dose-Response Relationship, Drug; Hydrocodone; Male; Mice; Mice, Inbred C57BL; Morphine; Oxycodone; Pain; Pain Threshold; Time Factors

Conventional pain management approaches have limitations such as gastrointestinal side effects, frequent dosing, and difficulties in swallowing medications. Hence, to overcome these limitations, we developed a transdermal analgesic patch.. This study was designed to formulate a drug in adhesive transdermal patch with codeine (CDB) and acetaminophen (APAP) that may potentially treat moderate pain in children.. Three analgesic drugs hydrocodone bitartrate, CDB and APAP were screened by a slide crystallization study using polarized light microscope and their permeation profiles were studied using vertical Franz diffusion cells across porcine ear skin, dermatomed human skin and epidermis for 24 h, and the samples were quantified by high performance liquid chromatography. Patches used for permeation studies were prepared by dissolving sub-saturation concentration of the drug(s) in adhesive (with/without 5% w/w oleic acid [OA]), cast with a film casting knife.. Among the three drugs screened, CDB demonstrated the best permeation profile (660.21 µg/cm(2)), and shortest lag time (4.35 ± 0.01 h), and hence was chosen for patch studies. The highest concentration of CDB in the patch at which drug does not crystallize was determined as 40% of its saturation solubility (Cs) and that of APAP was determined as 200% of its Cs. CDB standalone patch delivered 105.48 µg/cm(2) of CDB, while the CDB-APAP combination patch with 5% w/w OA delivered 151.40 µg/cm(2) CDB and 58.12 µg/cm(2) APAP in 24 h.. Drug-in-adhesive patches using CDB and APAP were developed for infants and children. Addition of OA enhanced solubility and permeation of drugs.

Topics: Acetaminophen; Adhesives; Administration, Cutaneous; Analgesics; Animals; Chemistry, Pharmaceutical; Codeine; Crystallization; Epidermis; Excipients; Humans; Hydrocodone; Pain; Permeability; Skin; Skin Absorption; Swine; Transdermal Patch

Topics: Analgesics, Opioid; Animals; Cytochrome P-450 CYP2D6; Humans; Hydrocodone; Pain; Pharmacogenetics; Phenotype; Precision Medicine

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.

Topics: Adult; Analgesics, Opioid; Delayed-Action Preparations; Drug Liberation; Female; Follow-Up Studies; Humans; Hydrocodone; Male; Middle Aged; Pain; Practice Patterns, Physicians'; Retrospective Studies; Time Factors; United States

The purpose of the study was to measure national prescribing patterns for hydrocodone/acetaminophen among veterans seeking emergency medical care, and to see if patterns have changed since this medication became a Schedule II controlled substance.. We conducted a retrospective cohort study of emergency department (ED) visits within the Veterans Health Administration (VA) between January 2009 and June 2015. We looked at demographics, comorbidities, utilization measures, diagnoses, and prescriptions.. During the study period, 1,709,545 individuals participated in 6,270,742 ED visits and received 471,221 prescriptions for hydrocodone/acetaminophen (7.5% of all visits). The most common diagnosis associated with a prescription was back pain. Prescriptions peaked at 80,776 in 2011 (8.7% of visits), and declined to 35,031 (5.6%) during the first half of 2015 (r=-0.99, p<0.001). The percentage of hydrocodone/acetaminophen prescriptions limited to 12 pills increased from 22% (13,949) in 2009 to 31% (11,026) in the first half of 2015. A prescription was more likely written for patients with a pain score≥7 (OR 3.199, CI [3.192-3.205]), a musculoskeletal (OR 1.622, CI [1.615-1.630]) or soft tissue (OR 1.656, CI [1.649-1.664]) diagnosis, and those below the first quartile for total ED visits (OR 1.282, CI [1.271-1.293]) and total outpatient ICD 9 codes (OR 1.843, CI [1.833-1.853]).. Hydrocodone/acetaminophen is the most frequently prescribed ED medication in the VA. The rate of prescribing has decreased since 2011, with the rate of decline remaining unchanged after it was classified as a Schedule II controlled substance. The proportion of prescriptions falling within designated guidelines has increased but is not at goal.

Topics: Acetaminophen; Adult; Aged; Analgesics, Opioid; Drug Combinations; Drug Prescriptions; Emergency Service, Hospital; Female; Humans; Hydrocodone; Male; Middle Aged; Pain; Pain Measurement; Practice Patterns, Physicians'; Retrospective Studies; United States; Veterans Health

The objective was to examine the effect of hydrocodone-containing product (HCP) rescheduling on the proportion of prescriptions for HCPs given to patients discharged from the emergency department (ED).. Electronic queries of ED records were used to identify patients aged 15 years and older discharged with a pain-related prescription in the 12 months before and after HCP rescheduling. Prescriptions were classified as HCPs; other Schedule II medications (eg, oxycodone products); other Schedule III medications (eg, codeine products); and non-Schedule II/III products (eg, nonsteroidal anti-inflammatory drugs). We compared the proportions of patients receiving each type of prescription before and after rescheduling using χ. Before rescheduling, 58.1% (95% confidence interval [CI], 57.4-58.7) of patients receiving a pain-related prescription received an HCP; after rescheduling, 13.2% (95% CI, 12.7-13.7) received an HCP (P < .001). Concurrently, other Schedule III prescriptions increased (pre: 11.7% [CI, 11.3-12.2] vs post: 44.9% [CI, 44.2-45.6], P < .001)), as did non-Schedule II/III prescriptions (pre: 51.8% [CI, 51.2-52.5] vs post: 59.3% [CI, 58.6-60.0], P < .001). When controlling for demographic characteristics, patients remained less likely to receive an HCP after rescheduling (adjusted odds ratio [AOR], 0.11; CI, 0.10-0.11) and more likely to receive other Schedule III (AOR, 6.1; CI, 5.8-6.5) and non-Schedule II/III (AOR, 1.4; CI, 1.3-1.4) products.. Rescheduling HCPs from Schedule III to Schedule II led to a substantial decrease in HCP prescriptions in our ED and an increase in prescriptions for other Schedule III and non-Schedule II/III products.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Controlled Substances; Drug and Narcotic Control; Drug Prescriptions; Emergency Service, Hospital; Female; Humans; Hydrocodone; Logistic Models; Male; Middle Aged; Pain; Patient Discharge; Practice Patterns, Physicians'; Retrospective Studies; Young Adult

Topics: Analgesics, Opioid; Dose-Response Relationship, Drug; Humans; Hydrocodone; Pain; Pharmacogenetics; Phenotype

A 44-year-old woman, chronic smoker with Graves' disease was treated with radioactive iodine ablation (RAI). One week after the treatment, she presented with severe pain in the anterior neck with radiation to the angle of the jaw associated with fatigue, tremor and odynophagia. Physical examination demonstrated an asymmetric and exquisitely tender thyroid gland. There was no laboratory evidence of thyrotoxicosis. Acute radiation thyroiditis was diagnosed. Non-steroidal anti-inflammatory drugs and hydrocodone-acetaminophen started initially were ineffective for pain control. Prednisone provided relief and was continued for 1 month with a tapering dose. Symptoms completely resolved after 1 month at which time the thyroid remained diffusely enlarged and non-tender. Three months following RAI ablation she developed hypothyroid symptoms. Levothyroxine was initiated. The patient has remained asymptomatic on continued follow-up care.

Topics: Acetaminophen; Adult; Analgesics, Opioid; Anti-Inflammatory Agents; Drug Combinations; Female; Graves Disease; Humans; Hydrocodone; Iodine Radioisotopes; Pain; Prednisone; Radiation Injuries; Thyroiditis

Oxycodone and hydrocodone are opioids which are widely used for pain management and are also commonly misused and abused. The exposure to opioid analgesics has been associated with altered responses of D2-like dopamine receptors (D2DRs). Our recent results suggest that various opioids will differentially modulate the responses of D2DRs. The D2DRs are known to be involved in the pathology of addiction and other mental illnesses, indicating the need to improve our understanding of the effects of opioid analgesics on the responses of the D2DRs. Thus, in this study, we first established equianalgesic oral doses of oxycodone, hydrocodone, and morphine using the tail withdrawal assay. Then, mice were orally administered (gavage) with the various opioids or saline once daily for 6 days. Twenty-four hours later, the mice were tested for their locomotor response to quinpirole, a D2/D3 dopamine receptor agonist. Mice pretreated with oxycodone showed significantly greater locomotor supersensitivity to quinpirole than did morphine-pretreated mice, while hydrocodone-pretreated mice showed sensitivity in between that of mice treated with morphine and oxycodone. This finding suggests that various opioids differentially modulate the responses of D2DRs. It provides further evidence supporting of the notion that various opioids carry differential risks to the dopamine reward system.

Topics: Akathisia, Drug-Induced; Analgesics, Opioid; Animals; Dopamine Agonists; Hot Temperature; Hydrocodone; Male; Mice, Inbred C57BL; Morphine; Oxycodone; Pain; Pain Measurement; Quinpirole; Receptors, Dopamine D2; Receptors, Dopamine D3

Topics: Analgesics, Opioid; Attitude of Health Personnel; Behavior, Addictive; Drug Administration Schedule; Government Regulation; Humans; Hydrocodone; Opioid-Related Disorders; Pain; Practice Patterns, Physicians'; Prescription Drug Diversion; Prescription Drugs; Texas

Topics: Acetaminophen; Analgesics; Analgesics, Opioid; Attitude to Health; Drug and Narcotic Control; Drug Combinations; Humans; Hydrocodone; Medical Marijuana; Opioid-Related Disorders; Pain; Pain Management; United States

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.. Although 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.

Topics: Acetaminophen; Adolescent; Adult; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Cohort Studies; Drug Combinations; Drug Delivery Systems; Female; Humans; Hydrocodone; Insurance, Physician Services; Male; Middle Aged; Pain; Pain Measurement; Time Factors; United States; United States Food and Drug Administration; Young Adult

This retrospective data analysis explored the relationship between codeine and its metabolites morphine, hydrocodone and hydromorphone. The objectives were: (i) to determine urine concentrations and mole fractions of codeine and metabolites and (ii) to examine the effect of cytochrome P450 (CYP) 2D6 inhibition on metabolite mole fractions. De-identified urine specimens were collected between September 2010 and July 2011 and analyzed using LC-MS-MS to determine codeine, morphine, hydrocodone and hydromorphone concentrations. Geometric mean urine concentrations were 0.833, 0.085 and 0.055 for morphine, hydrocodone and hydromorphone, respectively. Mole fractions were 0.23, 0.025 and 0.014 for morphine, hydrocodone and hydromorphone, respectively. The fraction of excreted codeine in the urine increased (slope = 0.06 ± .01, R² = 0.02) with total moles. As the total amount of codeine and metabolites increased, the fraction of codeine increased, while the fraction of active metabolites decreased. CYP2D6 inhibition with paroxetine, fluoxetine, bupropion and methadone significantly decreased the fraction of morphine excreted. The prevalence of codeine metabolism to morphine was considerably higher than codeine to hydrocodone. The urine concentration of codeine excreted was the greatest, followed by morphine and hydrocodone. Subjects should be monitored during concomitant use of codeine and CYP2D6 inhibitors as this affects the amount of morphine metabolite formation.

Topics: Analgesics, Opioid; Biotransformation; Codeine; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP2D6 Inhibitors; Drug Interactions; Drug Monitoring; Enzyme Inhibitors; Humans; Hydrocodone; Hydromorphone; Pain; Retrospective Studies; Risk Assessment; Risk Factors; Urinalysis

The purpose of this case series was to describe patients with aberrant drug-related behaviors and similar patterns of dose escalation in whom interdisciplinary assessment revealed different bases for their dose increases.. During the period from December 26 to December 30, 2011, the medical records of two patients with opioid-related aberrant behaviors were reviewed.. We described two patients with a significant cancer history and different comorbidities who presented with different aberrant drug-related behaviors and opioid requirements.. Opioid-related aberrant behaviors can be interpreted in different ways, and two of the more common syndromes in cancer patients are chemical coping and pseudoaddiction. In advanced cancer patients, the boundaries between these conditions are not as clear, and diagnosis is often made retrospectively. Furthermore, there have been relatively limited studies describing these two syndromes. Thus, they continue to pose a diagnostic and treatment challenge that requires different approaches for effective management of symptoms. The key characteristic between the two syndromes is that the behaviors displayed in chemical coping are motivated by obtaining opioids to relieve psychosocial distress, while in pseudoaddiction these behaviors are motivated by uncontrolled nociceptive input. Close monitoring of the pain syndromes, aberrant behaviors, and opioid requirements over several visits is usually necessary to distinguish the two syndromes.

Topics: Adaptation, Psychological; Adult; Analgesics, Opioid; Comorbidity; Head and Neck Neoplasms; Humans; Hydrocodone; Hydromorphone; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Opioid-Related Disorders; Pain

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

The objective was to describe trends in opioid and nonopioid analgesia prescribing for adults in U.S. emergency departments (EDs) over the past decade.. Data from the National Hospital Ambulatory Medical Care Survey (NHAMCS) 2001 through 2010 were analyzed. ED visits for adult patients (≥18 years of age) during which an analgesic was prescribed were included. Trends in the use of six commonly prescribed opioids, stratified by Drug Enforcement Agency (DEA) schedule, as well as nonopioid analgesics were explored, along with the frequency of pain-related ED visits. For 2005 through 2010, data were further divided by whether the opioid was administered in the ED versus prescribed at discharge.. Between 2001 and 2010, the percentage of overall ED visits (pain-related and non-pain-related) where any opioid analgesic was prescribed increased from 20.8% to 31.0%, an absolute increase of 10.2% (95% confidence interval [CI] = 7.0% to 13.4%) and a relative increase of 49.0%. Use of DEA schedule II analgesics increased from 7.6% in 2001 to 14.5% in 2010, an absolute increase of 6.9% (95% CI = 5.2% to 8.5%) and a relative increase of 90.8%. Use of schedule III through V agents increased from 12.6% in 2001 to 15.6% in 2010, an absolute increase of 3.0% (95% CI = 2.0% to 5.7%) and a relative increase of 23.8%. Prescribing of hydrocodone, hydromorphone, morphine, and oxycodone all increased significantly, while codeine and meperidine use declined. Prescribing of nonopioid analgesics was unchanged, 26.2% in 2001 and 27.3% in 2010 (95% CI = -1.0% to 3.4%). Hydromorphone and oxycodone had the greatest increase in ED administration between 2005 and 2010, while oxycodone and hydrocodone had the greatest increases in discharge prescriptions. There was no difference in discharge prescriptions for nonopioid analgesics. The percentage of visits for painful conditions during the period increased from 47.1% in 2001 to 51.1% in 2010, an absolute increase of 4.0% (95% CI = 2.3% to 5.8%).. There has been a dramatic increase in prescribing of opioid analgesics in U.S. EDs in the past decade, coupled with a modest increase in pain-related complaints. Prescribing of nonopioid analgesics did not significantly change.

Topics: Adolescent; Adult; Analgesics, Non-Narcotic; Analgesics, Opioid; Emergency Service, Hospital; Female; Health Care Surveys; Humans; Hydrocodone; Hydromorphone; Male; Middle Aged; Morphine; Oxycodone; Pain; Pain Measurement; Patient Discharge; Practice Patterns, Physicians'; United States

To report the prevalence of prescription opioid use and evaluate the trends in a large cohort of Medicaid-enrolled pregnant women.. A cohort of pregnancies was identified using data from the Medicaid Analytical eXtract for the period of 2000-2007. Dispensing of opioids, as a class and separately for individual agents, was evaluated using claims from filled prescriptions. Variations in patterns of prescription opioid fills were examined by demographic characteristics, by geographic region, and over time. Median number of opioid prescriptions dispensed and cumulative days of availability for prescription opioids during pregnancy were reported.. The study population consisted of more than 1.1 million women with completed pregnancies from 46 U.S. states and Washington, DC. One of five women from our cohort (21.6%) filled a prescription for an opioid during pregnancy; this proportion increased from 18.5% in 2000 to 22.8% in 2007. Substantial regional variation was seen with the proportion of women who filled a prescription during pregnancy, ranging between 9.5% and 41.6% across the states. Codeine and hydrocodone were the most commonly prescribed opioids. Among women filling at least one opioid prescription, the median (interquartile range) number of prescriptions filled was 1 (1-2) and the median (interquartile range) cumulative days of opioid availability during pregnancy were 5 (3-13) days.. We observed high and increasing number of filled prescriptions for opioids during pregnancy among Medicaid-enrolled women. These findings call for further safety evaluations of these drugs and their effects on the developing fetus to inform clinical practice.. II.

Topics: Adolescent; Adult; Analgesics, Opioid; Codeine; Drug Prescriptions; Female; Humans; Hydrocodone; Medicaid; Pain; Pregnancy; United States; Young Adult

Hydrocodone combined with acetaminophen is commonly used for moderate pain. Hydrocodone is metabolized by cytochrome P450 (CYP) 2D6 into hydromorphone and by CYP3A4 into norhydrocodone. This was a retrospective study evaluating hydrocodone, hydromorphone and norhydrocodone distributions in urine. Urine specimens (n = 76,924) were obtained from patients on chronic opioid therapy during their first or single visit and were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS-MS). The patients were at least 16 years of age and had documented hydrocodone use via a medication list. There were 48,710 specimens that were positive for all three analytes. Mean hydrocodone, hydromorphone and norhydrocodone mole fractions (95% confidence interval) were 0.39 (0.38-0.39), 0.12 (0.11-0.12) and 0.49 (0.48-0.49), respectively. Hydromorphone fractions were lower in women compared with men (0.11 versus 0.13; P < 0.0001). Hydrocodone mole fractions were higher in the 65-year and older age group compared with the 16- to 39-year age group (0.4 versus 0.36; P ≤ 0.005). Concurrent use of a CYP2D6 and/or CYP3A4 inhibitor altered hydromorphone and norhydrocodone mole fractions, compared with the control group. Patient factors affect hydrocodone and metabolite mole fractions and suggest increased awareness of their contribution when attempting to interpret urine drug testing results.

Topics: Adolescent; Adult; Age Factors; Aged; Analgesics, Opioid; Chromatography, Liquid; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Female; Humans; Hydrocodone; Hydrogen-Ion Concentration; Male; Middle Aged; Pain; Retrospective Studies; Sex Factors; Tandem Mass Spectrometry; Tissue Distribution; Urine; Young Adult

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

The hepatic cytochrome 2D6 (CYP2D6) is a saturable enzyme responsible for metabolism of approximately 25% of known pharmaceuticals. CYP interactions can alter the efficacy of prescribed medications. Hydrocodone is largely dependent on CYP2D6 metabolism for analgesia, ondansetron is inactivated by CYP2D6, and oxycodone analgesia is largely independent of CYP2D6. The objective was to determine if CYP2D6 medication coingestion decreases the effectiveness of hydrocodone.. This was a prospective observational study conducted in an academic U.S. emergency department (ED). Subjects were included if they had self-reported pain or nausea and were excluded if they were unable to speak English, were less than 18 years of age, had liver or renal failure, or carried diagnoses of chronic pain or cyclic vomiting. Detailed drug ingestion histories for the preceding 48 hours prior to the ED visit were obtained. The patient's pain and nausea were quantified using a 100-mm visual analog scale (VAS) at baseline prior to drug administration and following doses of hydrocodone, oxycodone, or ondansetron. We used a mixed model with random subject effect to determine the interaction between CYP2D6 drug ingestion and study drug effectiveness. Odds ratios (ORs) were calculated to compare clinically significant VAS changes between CYP2D6 users and nonusers.. A total of 250 (49.8%) of the 502 subjects enrolled had taken at least one CYP2D6 substrate, inhibitor, or inducing pharmaceutical, supplement, or illicit drug in the 48 hours prior to ED presentation. CYP2D6 drug users were one-third as likely to respond to hydrocodone (OR = 0.33, 95% confidence interval [CI] = 0.1 to 0.8) and more than three times as likely as nonusers to respond to ondansetron (OR = 3.4, 95% CI = 1.3 to 9.1). There was no significant difference in oxycodone effectiveness between CYP2D6 users and nonusers (OR = 0.53, 95% CI = 0.3 to 1.1).. CYP2D6 drug-drug interactions appear to change effectiveness of commonly prescribed drugs in the ED. Drug-drug interaction should be considered prior to prescribing CYP2D6 drugs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Cytochrome P-450 CYP2D6; Drug Interactions; Emergency Service, Hospital; Female; Humans; Hydrocodone; Male; Middle Aged; Nausea; Odds Ratio; Ondansetron; Oxycodone; Pain; Pain Measurement; Prospective Studies; Self Report; Treatment Outcome; Young Adult

Topics: Acetaminophen; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Codeine; Controlled Substances; Drug and Narcotic Control; Drug Therapy, Combination; Humans; Hydrocodone; Ibuprofen; Pain; Tramadol

Prescription opioid-acetaminophen products account for the majority of cases of acetaminophen-related acute liver failure in the United States. We sought to examine the frequency of opioid-acetaminophen overuse at the Providence VA Medical Center and improve the quality and safety of opioid-acetaminophen prescription practices in a system employing electronic health records and e-prescribing.. During fiscal year 2011, the Providence VA pharmacy dispensed a total of 19,841 acetaminophen prescriptions to a total of 4455 different patients. There were only 15 acetaminophen prescriptions dispensed in excess of 4g/day, and there were only 14 patients exposed to a potential maximum daily dose of acetaminophen greater than 4g.. The Providence VAMC appears to have a low rate of prescription acetaminophen misuse, in contrast to rates seen in previous studies. The VHA electronic health record, accessible to all healthcare providers, appears to offer considerable benefit in reducing the overuse of acetaminophen containing opioid products.

Topics: Acetaminophen; Analgesics, Non-Narcotic; Analgesics, Opioid; Dose-Response Relationship, Drug; Drug Combinations; Electronic Health Records; Electronic Prescribing; Hospitals, Veterans; Humans; Hydrocodone; Inappropriate Prescribing; Oxycodone; Pain; Pharmaceutical Services; Practice Patterns, Physicians'; Rhode Island

Hydrocodone is primarily metabolized to hydromorphone and norhydrocodone. Although hydromorphone is a known active metabolite of hydrocodone, the in vivo activity of norhydrocodone is not well documented. In the current study, the pharmacodynamics of norhydrocodone were evaluated and compared with hydrocodone and hydromorphone. Binding studies established that norhydrocodone, similar to hydrocodone and hydromorphone, is a μ-selective opioid ligand. In vivo analgesia studies (tail flick) demonstrated that, following subcutaneous, intrathecal, and intracerebroventricular administration, norhydrocodone produced analgesia. Following subcutaneous administration, norhydrocodone was ∼70-fold less potent, and hydromorphone was ∼5.4-fold more potent than hydrocodone in producing analgesia. Following intrathecal administration, norhydrocodone produced a shallow analgesia dose-response curve and maximal effect of 15-45%, whereas hydrocodone and hydromorphone produced dose-dependent analgesia. Intrathecal hydromorphone was ∼174-fold more potent than intrathecal hydrocodone. Following intracerebroventricular administration, norhydrocodone had similar potency to hydrocodone in producing analgesia, while hydromorphone was ∼96-fold more potent than hydrocodone. Analgesia induced by the three drugs following subcutaneous, intrathecal, and intracerebroventricular administration was antagonized by subcutaneous naltrexone, confirming that it is opioid receptor-mediated. Subcutaneous norhydrocodone-induced analgesia was completely blocked by intracerebroventricular naltrexone, indicating that norhydrocodone-induced analgesia is likely a supraspinal effect. Seizure activity was observed following intrathecal administration of all three drugs. Norhydrocodone and hydromorphone were ∼3.7 to 4.6-fold more potent than hydrocodone in inducing seizure activity. Naltrexone did not antagonize opioid-induced seizure activity, suggesting that seizures were not opioid receptor-mediated. Taken together, norhydrocodone is an active metabolite of hydrocodone and may contribute to therapeutic and toxic effects following hydrocodone administration.

Topics: Analgesics, Opioid; Animals; Binding, Competitive; Hydrocodone; Hydromorphone; Injections, Intraventricular; Injections, Spinal; Injections, Subcutaneous; Ligands; Male; Mice; Mice, Inbred Strains; Pain; Protein Binding; Receptors, Opioid, mu; Seizures

Abuse of prescription opioids for non-medical use has been on the rise over the past decade. The most commonly abused opioid is hydrocodone, a frequently prescribed pain medication metabolized by the body to hydromorphone, norhydrocodone and other minor metabolites. This study describes the excretion profile of hydrocodone, hydromorphone and norhydrocodone in urine following a single dose (10 mg) administration of hydrocodone to human subjects (n = 7) and presents a validated liquid chromatography-tandem mass spectrometry method for analysis of the drug and its metabolites. Limit of quantitation was 5 ng/mL for all analytes; limit of detection was 2.5 ng/mL for hydrocodone and norhydrocodone and 5 ng/mL for hydromorphone. Peak concentrations of hydrocodone were found at 3:30-7:00 hours post-dose and were in the range of 612-2,190 ng/mL. Hydromorphone peak concentrations were found at 6:15-26:45 hours post-dose and ranged from 102 to 342 ng/mL. For norhydrocodone, peak concentrations were found at 4:20-13:00 hours post-dose and ranged from 811 to 3,460 ng/mL. Although hydromorphone was found at lower levels than hydrocodone, in six of seven subjects, it persisted for as long as hydrocodone was detected. Norhydrocodone was found at higher levels and lasted for a longer period of time than hydrocodone, thus making the nor-metabolite a valuable tool in evaluating hydrocodone use and/or misuse.

Topics: Administration, Oral; Analgesics, Opioid; Chromatography, Liquid; Dose-Response Relationship, Drug; Female; Humans; Hydrocodone; Hydromorphone; Limit of Detection; Male; Pain; Solid Phase Extraction; Substance Abuse Detection; Tandem Mass Spectrometry

Urine drug monitoring is used by physicians treating chronic pain patients with opioid therapy. Patients are tested in part to insure that they are not taking other drugs. Therefore, the finding of hydrocodone in a patient who is only prescribed oxycodone has clinical implications. Oxycodone preparations are known to have small amounts of hydrocodone as an impurity estimated to be < 0.1%. We established the concentration of unexpected hydrocodone in patients taking oxycodone.. Urine drug testing specimens from a population of 30,000 pain patients prescribed oxycodone in various formulations were quantitatively measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The frequency and concentration of hydrocodone as a function of oxycodone concentration were determined.. There were 187 specimens with > 100,000 ng/ml of oxycodone. Of these, 72% were positive for hydrocodone. Of the 311 specimens with oxycodone concentrations > 50,000-100,000 ng/ml, 33% were positive for hydrocodone. Of the 1067 specimens with oxycodone > 20,000-50,000 ng/ml, 16% were positive for hydrocodone. Of the 8508 specimens with oxycodone > 1000-20,000 ng/ml, 16% were positive for hydrocodone.. The high frequency of hydrocodone in samples containing high concentrations of oxycodone was ascribed to the manufacturing process of the oxycodone medications. However, a significant number of patients also took hydrocodone that was not listed on their prescribed medications. When oxycodone is > 100,000 ng/ml, hydrocodone should be <1500 ng/ml. When oxycodone is < 100,000 ng/ml then hydrocodone should be <500 ng/ml. Values greater than these indicate non-prescribed hydrocodone use. Clinicians and laboratories testing urine for drugs should be aware of the possibility of low concentrations of hydrocodone in the urine of patients taking high doses of oxycodone.

Topics: Chemistry, Pharmaceutical; Drug Prescriptions; Humans; Hydrocodone; Oxycodone; Pain; Retrospective Studies

To estimate the extent of passage of hydrocodone and its active metabolite, hydromorphone, into breast milk.. This is a pharmacokinetic study of 30 postpartum women receiving hydrocodone bitartrate for postpartum pain in the inpatient setting. Mothers donated timed breast milk samples for the analysis of hydrocodone and hydromorphone.. Fully breastfed neonates received 1.6% (range 0.2%-9%) of the maternal weight-adjusted hydrocodone bitartrate dosage. When combined with hydromorphone, the total median opiate dosage from breast milk is 0.7% of a therapeutic dosage for older infants. Most mothers excreted little to no hydromorphone into breast milk.. Standard postpartum dosages of hydrocodone bitartrate appear to be acceptable to use in women nursing newborns. Prolonged use of high dosages is not advisable.

Topics: Acetaminophen; Adolescent; Adult; Analgesics, Non-Narcotic; Analgesics, Opioid; Female; Humans; Hydrocodone; Hydromorphone; Milk, Human; Pain; Postpartum Period; Pregnancy; Young Adult

Codeine has become a controversial choice for analgesia in children compared with other commonly available drugs.. To evaluate whether an educational campaign shifted resident prescribing patterns away from codeine toward more appropriate analgesics.. Our intervention consisted of a pocket-sized reference card given to all trainees and key staff in an inpatient pediatric acute care unit; pediatrics residents also had the option to attend a one-hour lecture. The pocket card recommended against codeine (including rationale) and gave prescription guidance for our institution's preferred formulary alternative analgesics, which include tramadol and hydrocodone. We used inpatient prescribing data to track the prescribing of codeine and alternative medications over time.. Following the interventions, there was a significant decrease in the percentage of patients receiving codeine (13.5% of patients received the drug in the year before, 5.4% in the year after, P < 0.0001). Use of hydrocodone-containing analgesics increased overall during the same period (7.4%-16%, P < 0.0001) as did tramadol use (0.2%-2.6%, P < 0.0001). There were no changes in pain management satisfaction scores.. A simple low-cost educational campaign consisting primarily of a pocket guide to analgesics markedly improved analgesic prescribing patterns, and that improvement extended to services not targeted by the didactic component of our educational campaign. Point-of-care decision support by means of a pocket card may be sufficient for effecting change in medication prescribing patterns of trainees.

Topics: Adolescent; Analgesics, Opioid; Child; Child, Preschool; Codeine; Decision Support Techniques; Drug Prescriptions; Female; Humans; Hydrocodone; Infant; Infant, Newborn; Male; Pain; Pain Management; Pain Measurement; Practice Patterns, Physicians'; Tramadol

Topics: Analgesics, Opioid; Female; Humans; Hydrocodone; Hydromorphone; Infant, Newborn; Milk, Human; Pain; Postpartum Period

Urine drug testing of pain patients provides objective information to health specialists regarding patient compliance, diversion, and concurrent illicit drug use. Interpretation of urine test results for semi-synthetic opiates can be difficult because of complex biotransformations of parent drug to metabolites that are also available commercially and may be abused. Normetabolites such as norcodeine, norhydrocodone and noroxycodone are unique metabolites that are not available commercially. Consequently, detection of normetabolite in specimens not containing parent drug, provides conclusive evidence that the parent drug was consumed. The goal of this study was to evaluate the prevalence and patterns of the three normetabolites, norcodeine, norhydrocodone and noroxycodone, in urine specimens of pain patients treated with opiates. Urine specimens were hydrolyzed with beta-glucuronidase and analyzed by a validated liquid chromatography tandem mass spectrometry (LC/MS/MS) assay for the presence of codeine, norcodeine, morphine, hydrocodone, norhydrocodone, hydromorphone, dihydrocodeine, oxycodone, noroxycodone, and oxymorphone. The limit of quantitation (LOQ) for these analytes was 50ng/mL. The study was approved by an Institutional Review Board. Of the total specimens (N=2654) tested, 71.4% (N=1895) were positive (>or=LOQ) for one or more of the analytes. The prevalence (%) of positive results for codeine, hydrocodone and oxycodone was 1.2%, 26.1%, and 36.2%, respectively, and the prevalence of norcodeine, norhydrocodone and noroxycodone was 0.5%, 22.1%, and 31.3%, respectively. For specimens containing normetabolite, the prevalence of norcodeine, norhydrocodone and noroxycodone in the absence of parent drug was 8.6%, 7.8% and 9.4%, respectively. From one-third to two-thirds of these specimens also did not contain other metabolites that could have originated from the parent drug. Consequently, the authors conclude that inclusion of norcodeine, norhydrocodone and noroxycodone is useful in interpretation of opiate drug source and reduces potential false negatives that would occur without tests for these unique metabolites.

Topics: Analgesics, Opioid; Chromatography, Liquid; Codeine; False Negative Reactions; Forensic Toxicology; Humans; Hydrocodone; Medication Adherence; Morphinans; Oxycodone; Oxymorphone; Pain; Tandem Mass Spectrometry

Gastrointestinal (GI) adverse effects are common with oral opioid treatment.. To estimate the costs associated with GI events after oral short-acting opioid treatment, from the payer perspective.. Medical and pharmacy claims from the PharMetrics' Patient-Centric Database were used to identify opioid-naïve patients who received a new prescription for oxycodone- or hydrocodone-containing immediate-release oral products between 2002 and 2006. Health-care resource use and costs were determined for patients with claims associated with ICD-9 CM (International Classification of Diseases-9th Clinical Modification) codes for nausea/vomiting (787.0x), constipation (564.0x), bowel obstruction (560, 560.1, 560.3, 560.39, 564.81), or antiemetic and laxative prescriptions during the 3 months after opioid index prescription and compared with patients without these GI event medical or prescription claims. Resource use data were compared using negative binomial regression and cost data were compared using ordinary least squares confirmed by generalized gamma regression analysis while controlling for demographics, treatment duration, and comorbidities.. Data from 237,447 patients were analyzed. Patients with GI event claims had significantly more hospitalizations (adjusted mean 0.20 to 0.97 vs 0.17, respectively, p < 0.001), days in the hospital (1.12 to 12.05 vs 1.00 days, p < 0.001), emergency department visits (0.36 to 1.44 vs 0.25 visits, p < 0.001), outpatient office visits (5.68 to 11.81 vs 4.11 visits, p < 0.001), and prescription claims (7.46 to 8.21 vs 6.06 claims, p < 0.001) than did patients without any GI event claims in the 3 months after index opioid prescription. Compared with patients without any GI event claims, incremental adjusted mean total health-care costs for patients with any of the GI event claims ranged from $4,880 to $36,152 and were significant (p < 0.001).. The economic burden of GI events coincident with opioid treatment is significant for patients with a GI event recorded in claims. Reducing GI adverse effects has potential cost savings for the health-care system.

Topics: Adult; Aged; Ambulatory Care; Analgesics, Opioid; Cohort Studies; Constipation; Databases, Factual; Drug Prescriptions; Drug Utilization; Emergency Medical Services; Female; Gastrointestinal Diseases; Humans; Hydrocodone; Insurance, Health, Reimbursement; Intestinal Obstruction; Male; Middle Aged; Nausea; Oxycodone; Pain; Retrospective Studies; Socioeconomic Factors; United States; Vomiting

Topics: Analgesics, Opioid; Dose-Response Relationship, Drug; Humans; Hydrocodone; Pain

This study determined the risk of serious hepatotoxicity resulting in hospitalizations among patients prescribed opioid/acetaminophen combinations.. A retrospective cohort study using an insurance claims database was conducted. Adult patients with ≥1 claim for oxycodone/acetaminophen or hydrocodone/acetaminophen combinations were included (N = 1,228,356). A pre-post design was employed to compare serious hepatotoxicity risk before versus after initiation of opioid/acetaminophen combination. Serious hepatotoxicity risk between the opioid/acetaminophen group and a control group of opioid-alone users (N = 11,809) was also examined. Within the opioid/acetaminophen group, risk of hepatotoxicity-related hospitalizations pre- versus post-opioid/acetaminophen treatment was compared using the normal approximation with the binomial distribution. The incidence rate of hepatotoxicity-related hospitalizations for the opioid/acetaminophen group was compared with the opioid-alone group using multivariate Poisson regression adjusting for baseline differences between groups.. Of the opioid/acetaminophen cohort, hepatotoxicity-related hospitalization risk in the 6-month post-opioid/acetaminophen period was lower than that in the pre-period with a risk reduction of 1.2 per 10,000 (pre-period = 0.12%; 95% confidence interval [CI], 0.12 to 0.13; post-period = 0.11%; 95% CI, 0.11 to 0.12). In the 12-month period, risk increased in the post-period by 2.4 per 10,000 (pre-period = 0.14%; 95% CI, 0.14 to 0.15; post-period = 0.17%; 95% CI, 0.16 to 0.18). After adjusting for confounders, the opioid-alone group did not demonstrate a lower rate of hepatotoxicity-related hospitalizations than the opioid/acetaminophen group (incidence rate ratio of opioid-alone over opioid/acetaminophen = 2.9; 95% CI, 1.8 to 4.7).. There is no population data-based evidence supporting elevated risk of hepatotoxicity-related hospitalization associated with opioid/acetaminophen combinations.

Topics: Acetaminophen; Adult; Aged; Analgesics, Opioid; Chemical and Drug Induced Liver Injury; Drug Combinations; Female; Hospitalization; Humans; Hydrocodone; Male; Middle Aged; Oxycodone; Pain; Risk Factors

Topics: Adult; Analgesics, Opioid; Chronic Disease; Female; Humans; Hydrocodone; Male; Middle Aged; Oxycodone; Pain

Severe nonmalignant pain affects a large proportion of adults. Optimal treatment is not clear, and opioids are an important option for analgesia. However, there is relatively little information about the comparative safety of opioids. Therefore, we sought to compare the safety of opioids commonly used for nonmalignant pain.. We devised a propensity-matched cohort analysis that used health care utilization data collected from January 1, 1996, through December 31, 2005. Study participants were Medicare beneficiaries from 2 US states who were new initiators of opioid therapy for nonmalignant pain, including codeine phosphate, hydrocodone bitartrate, oxycodone hydrochloride, propoxyphene hydrochloride, and tramadol hydrochloride; none had a cancer diagnosis, and none were using hospice or nursing home care. Our main outcome measures were incidence rates and rate ratios (RRs) with 95% confidence intervals (CIs) for cardiovascular events, fractures, gastrointestinal events, and several composite end points.. We matched 6275 subjects in each of the 5 opioid groups. The groups were well matched on baseline characteristics. The risk of cardiovascular events was similar across opioid groups 30 days after the start of opioid therapy, but it was elevated for codeine (RR, 1.62; 95% CI, 1.27-2.06) after 180 days. Compared with hydrocodone, after 30 days of opioid exposure the risk of fracture was significantly reduced for tramadol (RR, 0.21; 95% CI, 0.16-0.28) and propoxyphene (0.54; 0.44-0.66) users. The risk of gastrointestinal safety events did not differ across opioid groups. All-cause mortality was elevated after 30 days for oxycodone (RR, 2.43; 95% CI, 1.47-4.00) and codeine (2.05; 1.22-3.45) users compared with hydrocodone users.. The rates of safety events among older adults using opioids for nonmalignant pain vary significantly by agent. Causal inference requires experimental designs, but these results should prompt caution and further study.

Topics: Aged; Aged, 80 and over; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Diseases; Codeine; Cohort Studies; Cyclooxygenase 2 Inhibitors; Dextropropoxyphene; Female; Fractures, Bone; Gastrointestinal Hemorrhage; Hospitalization; Humans; Hydrocodone; Incidence; Male; Medicare; Odds Ratio; Oxycodone; Pain; Pain Measurement; Tramadol; United States

The objectives of this medicolegal case report are the following: 1) to present details of a chronic pain patient (CPP) who was placed on chronic opioid analgesic therapy (COAT), and subsequently overdosed on multiple drugs, some of which were not prescribed by his COAT physician; 2) to present both the plaintiff's and defendant's (the COAT prescriber) expert witnesses' opinions as to the allegation that COAT prescribing was the cause of death; and 3) based on these opinions, to develop some recommendations on how pain physicians can utilize the use of Controlled Substances Model Guidelines in order to protect the patient and themselves from such an occurrence.. This is a case report of a CPP treated by a pain physician.. Differences between the plaintiff's and defendant's expert's opinions are explained utilizing the Controlled Substances Model Guidelines.. Some CPPs may withhold information critical to their COAT treatment. Application of the Controlled Substances Model Guidelines and the newer Federation of State Medical Boards' policy on opioid prescribing can be helpful in improving patient care and may be helpful in protecting the physician medicolegally.

Topics: Adult; Analgesics, Opioid; Anti-Anxiety Agents; Antidepressive Agents, Tricyclic; Diazepam; Doxepin; Drug Overdose; Female; Heroin Dependence; Humans; Hydrocodone; Malpractice; Methadone; Nordazepam; Pain; Pain Measurement; Practice Guidelines as Topic; Shoulder; Shoulder Injuries; Temazepam

A monthly extended-release formulation of the opioid antagonist naltrexone (XR-NTX) is approved for treatment of alcohol dependence. There is little research regarding overriding chronic (>21 days) competitive opioid receptor blockade with opioids for acute pain. Using the hot plate test after XR-NTX or placebo microsphere administration, rats were treated with an opioid analgesic to determine the dose required to produce the maximum response latency (MRL; 60 s). Rats were later treated with the same opioid to determine any potential effects on respiration rate or locomotor activity. In naïve rats, 15 mg/kg morphine, 0.1 mg/kg fentanyl and 8 mg/kg hydrocodone produced MRL. In XR-NTX treated rats, morphine produced 36% and 46% MRL at 90 mg/kg on days 4 and 19 and 96% MRL at 45 mg/kg on day 39. Fentanyl produced 100% MRL at 2.0 mg/kg on days 4 and 19 and at 0.5 mg/kg on day 39. Hydrocodone (80 mg/kg) produced 69%, 80% and 100% MRL on days 4, 19 and 39. Compared to placebo, these doses did not further depress respiration or alter locomotor activity. Thus, opioid receptor blockade with XR-NTX can be overcome in rats with higher doses of opioids without further affecting respiration or locomotor activity.

Topics: Alcoholism; Analgesics, Opioid; Animals; Delayed-Action Preparations; Drug Interactions; Fentanyl; Humans; Hydrocodone; Male; Morphine; Motor Activity; Naltrexone; Narcotic Antagonists; Pain; Pain Measurement; Plethysmography, Whole Body; Rats; Rats, Sprague-Dawley; Respiration

Although studies have documented hospital and surgical service geographic variability, prescription use geographic variability is largely unknown. Opiate pain medications are widely used, particularly because the promulgation of clinical guidelines promoting aggressive pain treatment. This study describes temporal and interstate variability in aggregate prescription opiate medication use within U.S. Medicaid programs.. A dataset of 49 states' fee-for-service (FFS) Medicaid prescription drug dispensing records from 1996 to 2002 was compiled and used to quantify medication dispensing examining all opiates, controlled release oxycodone, and methadone. The defined daily dose (DDD) per 1000 FFS Medicaid adult enrollees per day was calculated for all opiate medication categories. A market basket of nonpain prescription medications was constructed for comparison. Rates, trends, and the coefficient of variation were determined overall, by year and for each state.. From 1996 to 2002, overall use of opiate pain medications increased 309%. The market basket use increased 170%. Total opiate dispensing varied widely from state to state, with a range of 6.9 to 44.1 DDD/1000/d in 1996, and 7.1 to 165.0 DDD/1000/d (a 23-fold difference) in 2002. The coefficient of variation was 49.6 in 2002. Controlled release oxycodone and methadone had a greater rate of increase compared with all opiates.. The dispensing of opiate medications in Medicaid programs increased at almost twice the rate of nonpain-related medications during the 7-year study period. Large, unexplained geographic variation in aggregate use exists. The impact of Medicaid cost-containment strategies on utilization and outcomes should be investigated.

Topics: Analgesics, Opioid; Data Interpretation, Statistical; Drug Prescriptions; Drug Utilization; Fee-for-Service Plans; Humans; Hydrocodone; Medicaid; Methadone; Models, Theoretical; Morphine; Oxycodone; Pain; Practice Patterns, Physicians'; United States

To prevent patient pain, the clinician may chose from opioid and nonopioid analgesics. It is rational for the practitioner to combine drugs from these classes when managing moderate to severe pain. To select combination regimens wisely, it is necessary to understand the significant pharmacological features of each category alone. Careful selection of an effective analgesic regimen based on the type and amount of pain the patient is expected to have can prevent the stress and anxiety associated with breakthrough pain. The clinician can and should develop a variety of effective, safe analgesic regimens, based on estimates of anticipated pain intensity that use sound pharmacological principles.

Topics: Acetaminophen; Analgesics, Non-Narcotic; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Anxiety; Clinical Protocols; Contraindications; Dental Care; Dextropropoxyphene; Drug Therapy; Humans; Hydrocodone; Meperidine; Oxycodone; Pain; Pentazocine; Safety; Stress, Psychological; Tramadol

This study set out to examine whether gender or race influences physicians' pain management decisions in a national sample of 712 (414 men, 272 women) practicing physicians. Medical vignettes were used to vary patient gender and race experimentally while holding symptom presentation constant. Treatment decisions were assessed by calculating maximum permitted doses of narcotic analgesic (hydrocodone) prescribed for initial pain treatment and for follow-up care. No overall differences by patient gender or race were found in decisions to treat or in maximum permitted doses. However, for persistent back pain, female physicians prescribed lower doses of hydrocodone, especially to male patients. For renal colic, lower doses were prescribed to black versus white patients when the patient was female, whereas the reverse was true when patients were male. These findings challenge a fairly extensive literature suggesting that physicians treat women and minorities less aggressively for their pain, and results offer further evidence that pain treatment decisions are influenced physician gender.

Topics: Adult; Analgesics; Analgesics, Opioid; Anti-Bacterial Agents; Back Pain; Data Collection; Decision Making; Drug Prescriptions; Ethnicity; Female; Humans; Hydrocodone; Kidney Calculi; Male; Middle Aged; Pain; Pain Management; Physicians; Sex Factors; Sinusitis; United States

Topics: Acetaminophen; Analgesics; Drug Combinations; Humans; Hydrocodone; Pain; Substance-Related Disorders; United States

To determine if patient gender and race affect decisions about pain management.. Experimental design using medical vignettes to evaluate treatment decisions. A convenience sample of 111 primary care physicians (61 men, 50 women) in the Northeast was asked to treat 3 hypothetical patients with pain (kidney stone, back pain) or a control condition (sinusitis). Symptom presentation and severity were held constant, but patient gender and race were varied.. The maximum permitted doses of narcotic analgesics (hydrocodone) prescribed at initial and return visits were calculated by multiplying mg per pill x number of pills per day x number of days x number of refills. No overall differences with respect to patient gender or race were found in decisions to treat or in the maximum permitted doses. However, for renal colic, male physicians prescribed higher doses of hydrocodone to white patients versus black patients (426 mg vs 238 mg), while female physicians prescribed higher doses to blacks (335 mg vs 161 mg, F1,85 = 9.65, P =.003). This pattern was repeated for persistent kidney stone pain. For persistent back pain, male physicians prescribed higher doses of hydrocodone to males than to females (406 mg vs 201 mg), but female physicians prescribed higher doses to females (327 mg v. 163 mg, F1,28 = 5.50, P =.03).. When treating pain, gender and racial differences were evident only when the role of physician gender was examined, suggesting that male and female physicians may react differently to gender and/or racial cues.

Topics: Adult; Aged; Analgesics, Opioid; Back Pain; Black People; Decision Support Techniques; Female; Humans; Hydrocodone; Kidney Calculi; Male; Middle Aged; Pain; Practice Patterns, Physicians'; Sex Distribution; Sex Factors; Sinusitis; White People

To describe profound hearing loss associated with hydrocodone overuse and the successful rehabilitation of these patients with cochlear implantation.. Retrospective review.. A tertiary otologic referral center.. Twelve patients with rapidly progressive hearing loss and a concurrent history of hydrocodone overuse.. Comprehensive medical histories, physical findings, audiometric tests, and, in those patients undergoing cochlear implantation, postimplantation performance data were reviewed.. Clinical characteristics of hydrocodone-related hearing loss and open set word and sentence performance in those patients undergoing cochlear implantation.. Hydrocodone overuse was associated with rapidly progressive sensorineural hearing loss in 12 patients. In four patients the initial presentation was unilateral, and two of the patients experienced vestibular symptoms. None of the 12 patients experienced improved thresholds after high-dose prednisone. Seven of the eight patients undergoing cochlear implantation have demonstrated early success with their devices.. Hydrocodone is frequently prescribed in combination with acetaminophen for the relief of pain and has a side effects profile similar to other medications in its class. Although not described previously, overuse or abuse can be associated with a rapidly progressive sensorineural hearing loss. These patients can be successfully rehabilitated with cochlear implantation.

Topics: Acetaminophen; Adult; Analgesics; Cochlear Implantation; Disease Progression; Drug Combinations; Female; Hearing Loss, Sensorineural; Humans; Hydrocodone; Male; Middle Aged; Pain; Retrospective Studies; Severity of Illness Index; Substance-Related Disorders

Topics: Acetaminophen; Acute Disease; Adolescent; Adult; Aged; Analgesics, Opioid; Double-Blind Method; Drug Combinations; Humans; Hydrocodone; Middle Aged; Musculoskeletal System; Pain; Prospective Studies; Randomized Controlled Trials as Topic; Reproducibility of Results; Tramadol; Treatment Outcome

A visual analogue scale (VAS) and a 4-point scale (FPS) have been compared in patients suffering from prolonged constant pain due to chronic inflammatory or degenerative arthropathy. Each patient was treated with a constant low or high dose of paracetamol or dihydrocodeine throughout a four week period. The VAS was accurate, as reliable and more sensitive than the FPS in registering the intensity of chronic pain. Separate records of each estimate, sealed immediately on completion by the patient, resulted in omission of significantly more pain recordings on the FPS, whereas retention by the patients of their previous records did not systematically influence subsequent judgments. In this study, the VAS appeared to be more satisfactory than the FPS for patient self-rating of pain intensity.

Topics: Acetaminophen; Chronic Disease; Dose-Response Relationship, Drug; Female; Humans; Hydrocodone; Male; Pain