hydrocodone and Nausea

To evaluate the prevention of opioid-induced nausea and vomiting (OINV) and the relief of moderate to severe acute pain by CL-108, a novel drug combining a low-dose antiemetic (rapid-release promethazine 12.5 mg) with hydrocodone 7.5 mg/acetaminophen 325 mg (HC/APAP) was used.. This was a multicenter, randomized, double-blind, placebo- and active-controlled multidose study. After surgical extraction of two or more impacted third molar teeth (including at least one mandibular impaction), 466 patients with moderate to severe pain (measured on a categorical pain intensity scale [PI-CAT]) were randomized to CL-108, HC/APAP, or placebo. Over the next 24 hours, patients used the PI-CAT to assess pain at regular intervals whereas nausea, vomiting, and other opioid-related side effects were also assessed prospectively. Study medications were taken every four to six hours as needed; supplemental rescue analgesic and antiemetic medications were permitted. Co-primary end points were the incidence of OINV and the time-weighted sum of pain intensity differences over 24 hours (SPID24).. Relative to HC/APAP treatment alone, CL-108 treatment reduced OINV by 64% (P < 0.001). Treatment with CL-108 significantly reduced pain intensity compared with placebo (SPID24 = 16.2 vs 3.5, P < 0.001). There were no unexpected or serious adverse events.. CL-108 is a safe and effective combination analgesic/antiemetic for the prevention of OINV during treatment of moderate to severe acute pain.

Topics: Acetaminophen; Acute Pain; Adolescent; Adult; Analgesics, Opioid; Antiemetics; Drug Combinations; Female; Humans; Hydrocodone; Male; Molar, Third; Nausea; Pain Measurement; Pain, Postoperative; Promethazine; Tooth Extraction; Tooth, Impacted; Treatment Outcome; Vomiting; Young Adult

A fixed-dose combination biphasic immediate-release (IR)/extended-release (ER) hydrocodone bitartrate (HB)/acetaminophen (APAP) tablet is being developed for the management of acute pain severe enough to require opioid treatment and for which alternative treatment options are inadequate.. This Phase III, randomized, double-blind, placebo-controlled, parallel-group study evaluated the analgesic efficacy and safety of IR/ER HB/APAP (n = 201) versus placebo (n = 202) over a period of 48 hours in patients with acute moderate to severe pain following unilateral bunionectomy. Patients received three tablets of placebo or IR/ER HB/APAP as an initial dose (hour 0) followed by two tablets every 12 hours for a total daily dose of 37.5/1625 mg HB/APAP on day 1 and 30/1300 mg HB/APAP thereafter. The primary efficacy outcome was the summed pain intensity difference (SPID) over the first 48 hours (SPID48) after the first dose.. SPID48 was significantly greater with IR/ER HB/APAP versus placebo (p < 0.001). SPID dosing interval analyses demonstrated consistent, superior pain relief with IR/ER HB/APAP for each dosing interval (all p < 0.001). Mean PID was greater with IR/ER HB/APAP versus placebo beginning 30 minutes after the first dose (p < 0.05), and IR/ER HB/APAP demonstrated faster median time to the onset of perceptible, meaningful, and confirmed pain relief (all p < 0.001). Mean total pain relief scores also indicated greater pain relief with IR/ER HB/APAP versus placebo throughout the 48-hour period (p = 0.012) for all comparisons. A greater proportion of IR/ER HB/APAP versus placebo patients was either "very satisfied" or "satisfied" with their pain relief (69.3% vs 49.4%; p < 0.001). Nausea was the most common treatment-emergent adverse event (TEAE; IR/ER HB/APAP, 25%; placebo, 7.9%). All TEAEs in IR/ER HB/APAP-treated patients were mild or moderate in severity.. IR/ER HB/APAP provided rapid, significant, and consistent analgesic efficacy over a period of 48 hours in an established model of acute pain and was tolerated with a safety profile similar to other low-dose opioids.

Topics: Acetaminophen; Acute Pain; Adult; Analgesics, Non-Narcotic; Analgesics, Opioid; Delayed-Action Preparations; Double-Blind Method; Drug Combinations; Female; Humans; Hydrocodone; Male; Middle Aged; Nausea; Orthopedic Procedures; Pain Management; Pain Measurement; Pain, Postoperative; Tablets; Treatment Outcome

Biphasic immediate-release (IR)/extended-release (ER) hydrocodone bitartrate (HB)/acetaminophen (APAP) 7.5/325-mg tablets are formulated with gastroretentive ER drug delivery technology that has been associated with clinically meaningful food effects in other approved products. Two phase 1 studies evaluated potential effects of food on single-dose pharmacokinetics of IR/ER HB/APAP tablets.. These were single-center, open-label, randomized, single-dose, 3-period crossover studies in healthy volunteers (aged 18-55 years). IR/ER HB/APAP was administered as a single 2-tablet dose (study 1) or 3-tablet dose (study 2) under fed (high- and low-fat) and fasted conditions. Area under the plasma concentration-time curve from 0 h to time t (AUC0-t) and from time 0 extrapolated to infinity (AUC0-inf) and maximum observed plasma concentration (Cmax) of hydrocodone and APAP under fed versus fasted conditions were compared using analysis of variance. A 90% confidence interval of the geometric least squares mean ratio fully contained within 80 to 125 % indicated no treatment difference. Safety and tolerability were assessed.. Forty of 48 participants in study 1 and 21 of 30 in study 2 completed all treatments. In both studies, under fed (high- or low-fat meal) versus fasted conditions, 90% CIs for AUC0-t and AUC0-inf for both hydrocodone and APAP were entirely contained within the bioequivalent range (80-125%), indicating that high- and low-fat meals did not affect the extent of exposure. In both studies, a high-fat meal did not affect the Cmax for hydrocodone. Hydrocodone Cmax was not affected by a low-fat meal in study 1 but increased by approximately 19% in study 2. A high-fat meal decreased APAP Cmax by approximately 20 % (study 1) and 13 % (study 2); a low-fat meal decreased APAP Cmax by 22% (study 1) and 21% (study 2). Approximately 50% of participants in both studies reported ≥1 treatment-emergent adverse event (TEAE), with no notable difference based on food intake. There were no serious or severe AEs. The most common TEAEs were nausea, vomiting, and dizziness.. Pharmacokinetic and safety findings were similar regardless of food intake. TEAEs were consistent with those reported with low-dose combination opioids. IR/ER HB/APAP can be administered without regard to food.. ClinicalTrials.gov NCT02561650 and NCT02561741 .

Topics: Acetaminophen; Adult; Analgesics, Non-Narcotic; Area Under Curve; Cross-Over Studies; Delayed-Action Preparations; Eating; Fasting; Female; Headache; Healthy Volunteers; Humans; Hydrocodone; Male; Metabolic Clearance Rate; Middle Aged; Narcotics; Nausea; Tablets; Young Adult

To determine the effectiveness of around-the-clock (ATC) analgesic administration, with or without nurse coaching, compared with standard care with as needed (PRN) dosing in children undergoing outpatient tonsillectomy.. Children 6 to 15 years of age were randomized to receive acetaminophen and hydrocodone (167 mg/2.5 mg/5 mL) for 3 days after surgery: Group A (N=39)-every 4 hours PRN, with standard postoperative instructions; Group B (N=34)-every 4 hours ATC, with standard postoperative instructions, without nurse coaching; and Group C (N=40)-every 4 hours ATC, with standard postoperative instructions, with coaching. Parents completed a medication log, and recorded the presence and severity of opioid-related adverse effects and children's reports of pain intensity using a 0 to 10 numeric rating scale.. No differences were found in analgesic administration or pain intensity scores between the 2 ATC groups. Therefore, they were combined for comparison with the PRN group. Children in the ATC group received more analgesic than those in the PRN group (P<0.0001). Children in the PRN group had higher pain intensity scores compared to children in the ATC group, both at rest (P=0.017) and with swallowing (P=0.017). Pain intensity scores for both groups were higher in the morning compared with the evening (P<0.0001). With the exception of constipation, scheduled analgesic dosing did not increase the frequency or severity of opioid-related adverse effects.. Scheduled dosing of acetaminophen and hydrocodone is more effective than PRN dosing in reducing pain intensity in children after tonsillectomy. Nurse coaching does not impact parent's adherence to ATC dosing.

Topics: Acetaminophen; Adolescent; Analgesics, Non-Narcotic; Analgesics, Opioid; Analysis of Variance; Child; Double-Blind Method; Dreams; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hydrocodone; Male; Nausea; Pain Measurement; Pain, Postoperative; Tonsillectomy; Treatment Outcome; Vomiting

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

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

Increasingly larger series of laparoscopic fundoplications (LF) are being reported. A well-documented advantage of the laparoscopic approach is shortened hospital stay. Most centers report typical lengths of stay (LOS) for LF of 2-3 days. Our success with LF with a LOS of 1 day led to an attempt at performing LF on an ambulatory basis.. Sixty-one consecutive patients with appropriate criteria for LF underwent surgery at our institution. Patients were counseled by the authors as to the usual postop course and progression of diet. All patients received preemptive analgesia (PEA) consisting of perioperative ketorolac and preincisional local infiltration with bupivicaine. Anesthetic management included induction with propofol, high-dose inhalational anesthetics, minimizing administration of parenteral narcotics, and avoidance of reversal of neuromuscular blockade. Immediate postop pain management included parenteral ketorolac and oral hydro- or oxycodone. All patients were given oral fluids and soft solids after transfer from the recovery room to the postoperative observation unit. Two patients were excluded from ambulatory consideration due to excessive driving distance from our hospital. Another two were hospitalized for observation after experiencing intraoperative technical problems.. Of 57 patients in whom same-day discharge was attempted, there were three failures requiring overnight hospitalization: All were due to pain and nausea; one patient also suffered transient urinary retention. There were no adverse outcomes related to early discharge, and there were no readmissions. One patient returned to the emergency room after delayed development of urinary retention. Median time from conclusion of operation to discharge was less than 5 h. No patients expressed dissatisfaction with early discharge on follow-up interview.. LF can be safely performed as an ambulatory procedure. Analgesic and anesthetic management should be tailored to minimize nausea and provide adequate pain control.

Topics: Adult; Aged; Ambulatory Surgical Procedures; Analgesics, Non-Narcotic; Analgesics, Opioid; Anesthetics, Inhalation; Anesthetics, Intravenous; Anesthetics, Local; Bupivacaine; Diet; Enteral Nutrition; Female; Fundoplication; Hospitalization; Humans; Hydrocodone; Injections, Subcutaneous; Ketorolac; Laparoscopy; Length of Stay; Male; Middle Aged; Nausea; Oxycodone; Pain, Postoperative; Patient Education as Topic; Patient Readmission; Patient Satisfaction; Postoperative Care; Premedication; Propofol; Tolmetin; Urinary Retention