Extended-Release Hydrocodone: The Devil in Disguise or Just Misunderstood?

Opioid abuse in the United States increased significantly over the past decade, leading to opioid-related deaths. Approval of Zohydro ER, a product that lacks an abuse-deterrent formulation, has provoked media controversy and aggressive legislative action from multiple stakeholders. Only the American Academy of Pain Management has released a position statement on this medication, and individual opinion varies. Additional single-entity extended-release hydrocodone formulations are in the pipeline, and Zohydro ER\u27s limited clinical utility may make the controversy associated with its approval a moot point. As with other opioids, providers will need to assess individual patient risk versus benefit when prescribing Zohydro ER

A Systematic Review of the Evidence Behind Use of Reduced Doses of Acetaminophen in Chronic Liver Disease

Acetaminophen is among the most commonly used nonopioid analgesics, but significant variation exists in its prescribing practices for cirrhosis patients. Our primary objective was to describe the quality of evidence supporting or refuting the use of acetaminophen in patients with hepatic dysfunction. A comprehensive literature review of PubMed, Cochrane Library, Web of Science, and International Pharmaceutical Abstracts using the search terms “acetaminophen,” “paracetamol,” “chronic liver disease,” “cirrhosis,” and “hepatic disease” for studies describing changes in acetaminophen metabolism in patients with hepatic dysfunction was conducted. Twelve studies and four abstracts were included. Ten studies and three abstracts were pharmacokinetic studies. Two studies and one abstract evaluated the association of acetaminophen use and decompensation in the cirrhotic patient. The level of certainty for dosing recommendations obtainable from reviewing the evidence is low due to a small number of studies meeting search criteria, small samples sizes, inadequate information regarding cirrhosis etiology and compensated versus uncompensated liver disease, and lack of information on patient centered health outcomes. High-quality trials are not available to support the use of decreased acetaminophen doses in compensated cirrhosis patients. Acetaminophen can be a safe analgesic in patients with compensated hepatic dysfunction after careful analysis of patient-specific factors

Methadone and Corrected QT Prolongation in Pain and Palliative Care Patients: A Case–Control Study

Background: Methadone (ME) is commonly used in pain and palliative care (PPC) patients with refractory pain or intolerable opioid adverse effects (AEs). A unique ME AE is its corrected QT (QTc) interval prolongation risk, but most evidence exists in methadone maintenance therapy patients. Objective: Our goal was to identify QTc interval prolongation risk factors in PPC patients receiving ME and other medications known to prolong the QTc interval and develop a risk stratification tool. Design: We performed a case–control study of adult inpatients receiving ME for pain management. Settings/Subjects: Adult inpatients receiving ME with a QTc \u3e470 msec (males) and \u3e480 msec (females) were matched 1:2 according to age, history of QTc prolongation, and gender with ME patients who did not have a prolonged QTc interval. QTc prolongation risk factors were collected for both groups. Covariates were analyzed using conditional logistic regression. Classification and regression tree analysis was used to identify the ME dose associated with QTc prolongation. Results: Predictors of QTc prolongation included congestive heart failure (CHF) (OR: 11.9; 95% CI: 3.7–38.2; p \u3c 0.00), peptic ulcer disease (PUD) (odds ratio [OR]: 8.3; 95% confidence interval [95% CI]: 2.4–28.9; p \u3c 0.00), hypokalemia (OR: 6.5; 95% CI: 1.5–28.2; p \u3c 0.01), rheumatologic diseases (OR: 4.7; 95% CI: 1.6–13.9; p \u3c 0.00), taking medications with a known torsades de pointes (TdP) risk (OR: 4.4; 95% CI: 1.8–10.7; p \u3c 0.01), malignancy (OR: 3.3; 95% CI: 1.2–9.3; p \u3c 0.03), hypocalcemia (OR: 2.1; 95% CI: 0.9–4.8; p \u3c 0.07), and ME doses \u3e45 mg per day (OR: 1.9; 95% CI: 0.8–4.8; p \u3c 0.16). Mild liver disease was protective against QTc prolongation (OR: 0.05; 95% CI: 0.0–0.46; p \u3c 0.01). Conclusions: Predictors of QTc prolongation in our multivariate conditional logistic regression model included CHF, PUD, hypokalemia, rheumatologic disorders, use of medications with a known TdP risk, malignancy, hypocalcemia, and ME doses \u3e45 mg per day

Design of a Problem-Based Learning Pain and Palliative Care Elective Course

Objective To implement and evaluate a problem-based learning (PBL) pain and palliative care elective course to develop studentsʼ pain and symptom management pharmacotherapy knowledge, clinical reasoning process, and self-directed learning skills. Methods Each week students received a patient case to independently develop an assessment and plan for each pain and symptom management problem. During class the students discussed their findings within small groups in preparation for a large-group discussion with the instructor. Studentsʼ course grades were based on weekly pre-class case preparation, individual case studies, and self-reflection questions. To assess knowledge gained over the semester a free-response pre- and post-course test was given. Results Twenty-five students enrolled in this course. A t-test comparison of the pre- and post-tests yielded a significant difference between the pre- and post-test scores (p \u3c 0.001), with the mean score for the tests increasing from 9.6 (out of 20 points) on the pre-test to 14.1 on the post-test. Pearsonʼs correlation coefficient between the pre- and post-test was 0.45, indicating increased scores were not a result of improvement only among the strong students. The normalized gain \u3cg\u3e was 0.43. The average score for each individual case study was slightly more than 80%. Four themes were noted in the studentsʼ self-reflections including patient/family goals of care, individualization of patient care and contrast to curative treatment, improved comfort with “gray therapeutic areas,” and advantages and disadvantages of problem-based learning. Conclusions Students demonstrated improved pain and symptom management pharmacotherapy knowledge, clinical reasoning process, and self-directed learning skills after course completion. The skills developed by students will benefit them in future clinical practice. Additional studies are needed to assess the long-term impact of the skills developed in this course

Formulation and Stability of an Extemporaneously Compounded Oral Solution of Chlorpromazine HCl

Chlorpromazine is a phenothiazine antipsychotic which is often used in hospice and palliative care to treat hiccups, delirium, and nausea. With the discontinuation of the commercial oral solution concentrate, there is a need to prepare this product by extemporaneous compounding. This study was initiated to identify an easy-to-prepare formulation for the compounding pharmacist. A stability study was also conducted to select the proper storage conditions and establish the beyond-use date. Chlorpromazine HCl powder and the Ora-Sweet® syrup vehicle were used to prepare the 100 mg/mL solution. Once the feasibility was established, a batch of the solution was prepared and packaged in amber plastic prescription bottles for a stability study. These samples were stored at refrigeration (2–8°C) or room temperature (20–25°C) for up to 3 months. At each monthly time point, the samples were evaluated by visual inspection, pH measurement, and high performance liquid chromatography (HPLC). A separate forced stability study was conducted to confirm that the HPLC method was stability indicating. A clear and colorless solution of 100 mg/mL chlorpromazine HCl was obtained by dissolving the drug powder in Ora-Sweet® with moderate agitation. The stability study results indicated that this solution product remained unchanged in visual appearance or pH at both refrigeration and room temperature for up to 3 months. The HPLC results also confirmed that all stability samples retained 93.6–101.4% of initial drug concentration. Chlorpromazine HCl solution 100 mg/mL can be compounded extemporaneously by dissolving chlorpromazine HCl drug powder in Ora-Sweet®. The resulting product is stable for at least three months in amber plastic prescription bottles stored at either refrigeration or room temperature

A Review of the Food and Drug Administration Adverse Event Reporting System for Tramadol-Related Hypoglycemia

Background: Hypoglycemia is a rare adverse effect of tramadol that is described in the medical literature and package insert. Objective: The purpose of this study was to review reports of tramadol and hypoglycemia in the Food and Drug Administration Adverse Event Reporting System (FAERS) database to determine a potential association. Methods: Disproportionality analysis with Bayesian correction was used to compare tramadol and hypoglycemia with other medications in FAERS. The results were considered significant if the fifth percentile of the Empirical Bayesian geometric mean distribution (EB05) \u3e2. Logistic regression odds ratios was used to determine if age, diabetes medications, and renal insufficiency masked the disproportionality of hypoglycemia, with the fifth percentile of the logistic regression odds ratio (LR05) \u3e2 indicating a potential signal. The Interaction Signal Score (INTSS) was computed to determine the influence of predisposing risk factors on the signal. Results: A total of 605 cases of tramadol-associated hypoglycemia were reported, but our results were not significant (EB05: 1.590). Tramadol-associated hypoglycemia was significant in patients who did not take diabetes medications (EB05: 2.256; LR05: 2.2104). Renal insufficiency was not found to increase the risk of tramadol-associated hypoglycemia (INTSS: 0.865). There was a significant signal for tramadol-associated hypoglycemia in patients aged 0 to 1 year (LR05: 3.0240) and 2 to 4 years (LR05: 2.6853). Conclusion and Relevance: Results of our analysis suggest a potential signal between hypoglycemia and tramadol use in patients not taking diabetes medications. Our results do not support a predisposition for tramadol-associated hypoglycemia in patients with renal insufficiency, increasing age, and/or diabetes as noted in the tramadol package insert

Morphine and Hydromorphone-Induced Hyperalgesia in a Hospice Patient

Opioids including morphine and hydromorphone are widely used for control of moderate to severe pain and dyspnea in hospice and palliative care patients. Accumulation of the active morphine-3-glucuronide (M3G) and hydromorphone-3-glucuronide (H3G) metabolites is one proposed mechanism for the development of neuroexcitatory effects including allodynia and opioid-induced hyperalgesia (OIH). We report the case of a 43-year-old female hospice patient with metastatic non-small cell lung cancer who initially developed allodynia following morphine administration and again following administration of hydromorphone. The allodynia resolved both times following the discontinuation of the opioid and rotation to a different opioid regimen. Potential opioid-induced neuroexcitatory treatment options include opioid rotation to an agent with inactive metabolites, use of adjuvant pain medications for opioid-sparing effects, management of undesired symptoms (e.g., myoclonus), or increasing opioid clearance with intravenous (IV) fluids. Although the incidence is not well defined in the literature, hospice and palliative care clinicians should suspect OIH in patients with allodynia and/or hyperalgesia, especially when repeated dose escalations do not improve analgesia or pain escalates following opioid dose titration

A Pilot Chemical and Physical Stability Study of Extemporaneously Compounded Levetiracetam Intravenous Solution

Levetiracetam is a commonly used antiepileptic medication for tumor-related epilepsy. However, the 100 mL intravenous (IV) infusion volume can be burdensome to imminently dying hospice patients. A reduced infusion volume would improve patient tolerability. The purpose of this study was to evaluate the stability of 1000 mg/25 mL (40 mg/mL) levetiracetam IV solution in sodium chloride 0.9%. We prepared levetiracetam 40 mg/mL IV solution and added it to polyvinyl chloride (PVC) bags, polyolefin bags, and polypropylene syringes. Triplicate samples of each product were stored at refrigeration (2–8°C) and analyzed on days 0, 1, 4, 7, and 14. Samples were subjected to visual inspection, pH measurement, and stability-indicating high-performance liquid chromatography (HPLC) analysis. Over the 2-week storage period, there was no significant change in visual appearance or pH for any of the stability samples. The HPLC results confirmed that all stability samples retained 94.2–101.3% of initial drug concentration and no degradation products or leachable material from the packaging materials were observed. We conclude that levetiracetam 1000 mg/25 mL IV solution in sodium chloride 0.9% is physically and chemically stable for up to 14 days under refrigeration in polypropylene syringes, PVC bags, and polyolefin bags

Dose Ratios between High Dose Oral Morphine or Equivalents and Oral Methadone

Background: Methadone is a commonly used opioid in hospice and palliative care for patients with refractory pain. Various methadone dose conversion methods utilize progressively higher morphine equivalent dose (MED) to methadone dose ratios to compensate for increased methadone potency with escalating opioid doses. Objective: The purpose of this study was to determine the dose ratio between equianalgesic doses of high dose oral morphine (daily doses \u3e1200 mg morphine or MED) and oral methadone. Methods: This study was a retrospective chart review of 324 patients who received methadone at Strong Memorial Hospital or the associated outpatient clinic during a nine-month period in 2011. Ten patients met the study inclusion and exclusion criteria. A Wilcoxon signed-rank test was used to compare the pain scale scores. The Spearman correlation coefficient was used to assess level of correlation between morphine dose and methadone dose. Results: Patients rotated to methadone from high opioid doses had a two-point improvement in median pain scale scores after conversion (p=0.039). However, there was no correlation identified for patients taking daily doses \u3e1200 mg oral morphine or MED prior to methadone rotation (p=0.19). There were no reported methadone adverse effects during the study. Conclusions: No correlation was identified between high MED doses and methadone at dose stabilization after opioid rotation. A fixed maximum methadone dose of 30 mg/day produced clinically meaningful improvements in pain scores without adverse drug effects. Caution should be exercised before considering rotation to methadone doses higher than 30 mg/day in a patient receiving \u3e1200 mg oral MED/day

The Crossroads of Interprofessionalism: Four Avenues of Collaboration at the Wegmans School of Pharmacy

Objective: The utilization of interprofessional education and collaborative practice delivers optimal health services and improves patient outcomes. Training future healthcare providers in an integrated environment promotes a “collaborative practice-ready” workforce. The aim of this study was to identify ongoing specific interprofessional collaborative projects and promote their awareness among faculty at the St. John Fisher College Wegmans School of Pharmacy. Methods: Faculty members were surveyed to identify the ongoing interprofessional collaborative initiatives among pharmacy faculty. Results: A total of four collaborative practices were identified among faculty: ambulatory care, assisted-living, didactic, and assessment. The ambulatory care setting at an osteoporosis clinic provides patient-centered care with a clinical component. Each patient with a new diagnosis or change in medication therapy receives education/counseling from a pharmacist, a registered nurse for medication administration and a physician for a physical exam. In the assisted-living setting, pharmacy and nursing students are paired to conduct a high-level health assessment in their respective disciplines. Didactic interprofessional efforts are being conducted to create a flexible and comprehensive pain education curriculum. Physicians, dentists, nurses, pharmacists, psychologists, chiropractors, and oriental medicine practitioners will develop the curriculum. The pain module will be adaptable for interprofessional education activities. Finally, recognizing the similarities in accreditation standards for communication and professionalism, the School of Pharmacy and the NY Chiropractic School are sharing strategies and rubrics for assessing these outcomes. Implications: The survey revealed a broader range of interprofessional collaborations than was originally suspected. The school will continue to foster and support interprofessional education and collaborative practice