hydrocodone and Osteoarthritis--Knee

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

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

Knee osteoarthritis (OA) is a chronic pathology that is treated across multiple specialties. Opioid prescribing practices for knee OA have not been described on a national level. The purpose of this study was to (1) investigate the trends in opioid prescriptions for knee OA, (2) characterize and identify predominant opioid based medications prescribed for knee OA, and (3) identify patient- and provider-related factors influencing opioid prescribing patterns in the treatment of knee OA in the outpatient setting.. The National Ambulatory Medical Care Survey (NAMCS) was used to identify all patients in the United States who presented to an outpatient clinic for knee OA between 2007 and 2016. New opioid prescriptions were determined using a previously published algorithm. Generalized linear models were used to assess trends.. A total of 41,389,332 patients were included, of which 12.8% were prescribed an opioid-based medication. Opioid prescription rose from 2007/2008 to 2013/2014. Analysis of the opioid type demonstrated that the prescription of hydrocodone-based medication and "other" traditional opioids followed the aforementioned trends. However, tramadol prescription demonstrated a sustained increase throughout the years peaking at 2015/2016. Patient income in the lowest quartile, a worker's compensation status, and depression were independently associated with higher odds of opioid prescription for knee OA.. Opioid prescription for knee OA remains high. Decreases in traditional opioid prescription have been countered by increase in tramadol prescription. The risks and addictive potential of tramadol and patient and provider risk factors should be emphasized.

Topics: Analgesics, Opioid; Drug Prescriptions; Humans; Hydrocodone; Osteoarthritis, Knee; Practice Patterns, Physicians'; United States