Commentary: Is Polyethylene Glycol Toxicity From Intravenous Methocarbamol Fact or Fiction?

Methocarbamol is an antispasmodic muscle relaxant and was the fourth most-prescribed muscle relaxant by volume in the United States in 2021. Intravenous (IV) methocarbamol contains the excipient, polyethylene glycol (PEG), which has been implicated in metabolic acidosis and nephrotoxicity. Intravenous methocarbamol was first approved by the US Food and Drug Administration in 1959 and at that time the IV methocarbamol prescribing information warned of PEG-associated adverse drug events in patients living with renal impairment; however, the manufacturer acknowledged data were lacking to objectively support this claim. Clinicians prescribing and dispensing IV methocarbamol may encounter the warning for PEG-associated metabolic acidosis and nephrotoxicity without knowing the potential risks, or lack thereof, supporting or disavowing this phenomenon. This commentary debates the merits supporting and arguments refuting PEG-associated metabolic acidosis and nephrotoxicity in patients treated with IV methocarbamol.

Opioid-Free Discharge After Pancreatic Resection Through a Learning Health System Paradigm.

Importance: Postoperative opioid overprescribing leads to persistent opioid use and excess pills at risk for misuse and diversion. A learning health system paradigm using risk-stratified pancreatectomy clinical pathways (RSPCPs) may lead to reduction in inpatient and discharge opioid volume. Objective: To analyze the outcomes of 2 iterative RSPCP updates on inpatient and discharge opioid volumes. Design, Setting, and Participants: This cohort study included 832 consecutive adult patients at an urban comprehensive cancer center who underwent pancreatic resection between October 2016 and April 2022, comprising 3 sequential pathway cohorts (version [V] 1, October 1, 2016, to January 31, 2019 [n = 363]; V2, February 1, 2019, to October 31, 2020 [n = 229]; V3, November 1, 2020, to April 30, 2022 [n = 240]). Exposures: After V1 of the pathway established a baseline and reduced length of stay (n = 363), V2 (n = 229) updated patient and surgeon education handouts, limited intravenous opioids, suggested a 3-drug (acetaminophen, celecoxib, methocarbamol) nonopioid bundle, and implemented the 5×-multiplier (last 24-hour oral morphine equivalents [OME] multiplied by 5) to calculate discharge volume. Pathway version 3 (n = 240) required the nonopioid bundle as default in the recovery room and scheduled conversion to oral medications on postoperative day 1. Main Outcomes and Measures: Inpatient and discharge opioid volume in OME across the 3 RSPCPs were compared using nonparametric testing and trend analyses. Results: A total of 832 consecutive patients (median [IQR] age, 65 [56-72] years; 410 female [49.3%] and 422 male [50.7%]) underwent 541 pancreatoduodenectomies, 285 distal pancreatectomies, and 6 other pancreatectomies. Early nonopioid bundle administration increased from V1 (acetaminophen, 320 patients [88.2%]; celecoxib or anti-inflammatory, 98 patients [27.0%]; methocarbamol, 267 patients [73.6%]) to V3 (236 patients [98.3%], 163 patients [67.9%], and 238 patients [99.2%], respectively; P < .001). Total inpatient OME decreased from a median 290 mg (IQR, 157-468 mg) in V1 to 184 mg (IQR, 103-311 mg) in V2 to 129 mg (IQR, 75-206 mg) in V3 (P < .001). Discharge OME decreased from a median 150 mg (IQR, 100-225 mg) in V1 to 25 mg (IQR, 0-100 mg) in V2 to 0 mg (IQR, 0-50 mg) in V3 (P < .001). The percentage of patients discharged opioid free increased from 7.2% (26 of 363) in V1 to 52.5% (126 of 240) in V3 (P < .001), with 187 of 240 (77.9%) in V3 discharged with 50 mg OME or less. Median pain scores remained 3 or lower in all cohorts, with no differences in postdischarge refill requests. A subgroup analysis separating open and minimally invasive surgical cases showed similar results in both groups. Conclusions and Relevance: In this cohort study, the median total inpatient OME was halved and median discharge OME reduced to zero in association with a learning health system model of iterative opioid reduction that is freely adaptable by other hospitals. These findings suggest that opioid-free discharge after pancreatectomy and other major cancer operations is realistic and feasible with this no-cost blueprint.

Impact of methocarbamol on opioid use after ventral incisional hernia repair.

BACKGROUND: Alternatives to opioid analgesia are needed to reduce the risk of abuse, misuse, and diversion. Musculoskeletal pain is a significant contributor to postoperative pain after ventral hernia repair (VHR). We report the impact of methocarbamol on opioid prescribing after VHR. METHODS: Review of all robotic and open VHR, Jan 2020-July 2022. Data was collected in the Abdominal Core Health Quality Collaborative (ACHQC) with additional chart review to assess for opioid refills. A 2:1 propensity score match was performed comparing opioid prescribing in patients prescribed vs not prescribed methocarbamol. RESULTS: 101 patients received methocarbamol compared with 202 without. Similar number of patients received an opioid prescription (87.1 vs 86.6%; p = 0.904). Study patients received significantly lower MME prescription at discharge (60 v 75; p = 0.021) with no difference in refills (12.5 vs 16.6%; p = 0.386). CONCLUSION: Addition of methocarbamol to a multimodal analgesic regimen after VHR facilitates reduction in prescribed opioid with no increase in refills.

Impact of methocarbamol on opioid use after primary ventral and inguinal hernia repair.

BACKGROUND: Multimodal analgesia is now a mainstay of perioperative care. Our aim is to assess the impact of adding methocarbamol on opioid use for patients undergoing primary ventral (umbilical and epigastric) hernia repair (PVHR) and inguinal hernia repair (IHR). METHODS: Retrospective review of patients undergoing PVHR and IHR who received methocarbamol, propensity score matched in a 2:1 fashion to patients not receiving methocarbamol. RESULTS: Fifty-two PVHR patients receiving methocarbamol were matched to 104 control patients. Study patients were prescribed fewer opioids (55.8 vs 90.4%; p < 0.001) and received lower MME (20 vs 50; p < 0.001), with no difference in refills or rescue opioids. For IHR, study patients received fewer prescriptions (67.3 vs 87.5%; p < 0.001) and received lower MME (25 vs 40; p < 0.001), with no difference in rescue opioid (5.9 vs 0%; p = 0.374). CONCLUSIONS: Methocarbamol significantly reduced opioid prescribing in patients undergoing PVHR and IHR without increasing the risk of refill or rescue opioid.

Association Between Postoperative Methocarbamol and Postoperative Pain Opioid Dose Requirements: A Retrospective Cohort Study.

OBJECTIVES: We tested the hypothesis that patients who received methocarbamol postoperatively experience less severe pain and require smaller doses of opioids than those who did not receive methocarbamol. MATERIALS AND METHODS: This is a retrospective cohort study of patients undergoing surgery involving the musculoskeletal system. Of 9089 patients, 704 received methocarbamol during 48 hours postoperatively, while 8385 did not receive methocarbamol. The patients who received methocarbamol postoperatively and the patients who did not receive methocarbamol were compared on the time-weighted average (TWA) pain score and opioid dose requirements in morphine milligram equivalents (MME) during the first 48 hours postoperatively, using propensity score-weighted regression models to adjusting for preoperative and intraoperative covariates. RESULTS: Postoperative 48-hour TWA pain scores were 5.5±1.7 (mean±SD), and 4.3±2.1 for methocarbamol and non-methocarbamol patients. Postoperative 48-hour opioid dose requirements in MME were 276 [170-347] (median [interquartile range (IQR)]) mg, and 190 [60-248] mg for methocarbamol and non-methocarbamol patients. In propensity score-weighted regression models, receiving methocarbamol postoperatively was associated with 0.97-point higher postoperative TWA pain score (95% CI, 0.83-1.11; P <0.001), and 93.6-MME higher postoperative opioid dose requirements (95% CI, 79.9 to 107.4; P <0.001), compared with not receiving methocarbamol postoperatively. DISCUSSION: Postoperative methocarbamol was associated with significantly higher acute postoperative pain burden and opioid dose requirements. Although the results of the study are influenced by residual confounding, they suggest a limited-if any-benefit of methocarbamol as an adjunct of postoperative pain management.

Methocarbamol versus diazepam in acute low back pain in the emergency department: a randomised double-blind clinical trial.

BACKGROUND: Acute low back pain (LBP) is a common complaint in the emergency department and achieving effective analgesia can be challenging. METHODS: In this multicentre randomised double-blind clinical trial conducted at three EDs in Iran from August to November 2020, we assessed the efficacy and adverse effects of two muscle relaxants in patients aged 18 years or older who suffered LBP in the last 6 weeks. Group 1 received intravenous methocarbamol and group 2 received intravenous diazepam followed by a weight-based dose of intravenous morphine in both groups. Exclusion criteria mainly included non-spine aetiologies, cord compression, acute gastrointestinal bleeding, renal/hepatic insufficiency, pregnancy, breast feeding and unstable vital signs. Pain scores and adverse events were measured by a Numeric Rating Scale (NRS) at baseline and after 30 and 60 min by one of the researchers who was not involved with patient visits and was blinded to the intervention. We used t-test to assess the mean difference of NRS at 30 and 60 min. RESULTS: Out of 101 enrolled patients, 50 participants received methocarbamol and 51 diazepam. The baseline mean pain scores and demographic characteristics were not different between the study groups. Pain scores were reduced by both agents after 60 min, with slightly greater pain reductions in the diazepam group in comparison with methocarbamol (mean difference -6.1, 95% CI -6.5 to -5.7 vs mean difference -5.2, 95% CI -5.7 to -4.7, respectively, p<0.001). ED length of stay of patients did not differ between the groups (methocarbamol 5.9 vs diazepam 4.8 hours, p=0.365). Patients receiving diazepam were more likely to report drowsiness (2 (4.0%) vs 15 (29.4%), p=0.001). CONCLUSIONS: In patients with LBP, the pain was relieved in the methocarbamol and diazepam groups after 60 min. Although diazepam was more effective, its use was associated with a slightly higher risk of drowsiness. TRIAL REGISTRATION NUMBER: The protocol of this clinical trial was prospectively registered in the irct.ir (IRCTID: IRCT20151113025025N4; https://irct.ir/trial/50148) .

Effective spectrophotometric methods for resolving the superimposed spectra of Diclofenac Potassium and Methocarbamol.

The UV spectra of Diclofenac Potassium DIC and Methocarbamol MET are superimposed making their analysis using direct or derivative spectrophotometric methods quite complicated. This study presents four effective spectrophotometric methods that enable simultaneous determination of both drugs without interference. The first method is based on application of simultaneous equation method on their zero order spectra where DIC has shown absorbance maxima at 276 nm and MET displays two absorbances maxima at 273 nm and 222 nm in distilled water. The second method relies on dual wavelength method, the two wavelengths (232 and 285 nm) were chosen for determination of DIC where the absorbance differences at these wavelengths are proportional to DIC concentration while the absorbance differences of MET are equal to zero. For the determination of MET, the two wavelengths (212 and 228 nm) were selected. The third method of first-derivative ratio has been applied where the derivative ratio absorbances of DIC and MET were measured at 286.1 and 282.4 nm, respectively. The fourth method utilizing ratio difference spectrophotometric (RD) method was eventually performed on the binary mixture. The amplitude difference between the two wavelengths (291and 305 nm) was calculated for DIC estimation while the amplitude difference between the two wavelengths (227and 273 nm) for MET determination. All methods show linearity range from 2.0-25 µg. mL-1 and 6.0-40 µg. mL-1 for DIC and MET respectively. The developed methods have been statistically compared with a reported method based on first derivative method and the results of statistical comparison confirm the accuracy and precision of the proposed methods therefore they can be effectively applied for determination of MET and DIC in pharmaceutical dosage form.

Insights into tablet sticking: a quantitative case study with an ibuprofen and methocarbamol-based formulation.

OBJECTIVES AND METHODS: Tablet sticking is a continuous accumulation of pharmaceutical powder onto tooling surfaces during compression. Its occurrence greatly impacts tablet productivity, quality attributes, and tooling age. In a previous study, the authors proposed a multivariate data analysis approach to gain insights into tablet sticking directly on the industrial stage. The objective was to determine the combination of factors that could help distinguish between batches affected and unaffected by sticking. The present study aims to generalize this approach by extending it to quantitative predictions of punch sticking intensity. A total of 345 variables was gathered on 28 industrial batches of an ibuprofen and methocarbamol-based formulation. RESULT AND CONCLUSION: Using PLS regression models, it was shown that the association of granulation duration and compression force allows to significantly explain ∼60% of sticking variations of studied formulation. In addition, unlike the classification models developed in the earlier work, the validation residues in the present study were found to be normally distributed (Shapiro-Wilks p value = 0.96) and independent from the target variable (R2 = 9.5%).

Gamma irradiation-induced degradation and mineralization of methocarbamol in aqueous solution.

Gamma irradiation degradation of the extensively used muscle relaxant in the world methocarbamol (MET) was studied. MET aqueous solutions were irradiated by gamma rays emitted by a Cobalt 60 source at doses of 1-4 kGy. Our findings demonstrated that gamma irradiation degraded more than 98.5% of MET. Absorption spectra analysis revealed that when increased irradiation dose, the absorption bands declined with complete disappearance at 4 kGy dose. Additionally, the most radiolytic degradation rate was recorded at neutral pH, marked by Total Organic Carbon (TOC) removal rate of 98% reflecting the total mineralization of MET at 4 kGy. In-depth spectrophotometric analyses advocated a pseudo-first-order type of MET degradation kinetics. The obtained apparent rate constant value was kapp, MET = (0.02167 ± 0.0006) min-1. Gas chromatography-mass spectrometry (GC-MS) allowed the detection of 3-(o-methoxyphenoxy)-1,2 propanediol,2-methoxyphenol, 1,2,3 propanetriol, 1,2-dihydroxybenzene and 1,2,4 benzentriol identified as by-products generated during radiolytic degradation. Finally, an outline of the degradation mechanism was suggested according to the obtained by-products.

Development and application of a membrane assisted solvent extraction-molecularly imprinted polymer based passive sampler for monitoring of selected pharmaceuticals in surface water.

In this work, we demonstrate the development, evaluation and pre-liminary application of a novel passive sampler for monitoring of selected pharmaceuticals in environmental waters. The samplers were calibrated in laboratory-based experiments to obtain sampling rates (Rs) for carbamazepine, methocarbamol, etilefrine, venlafaxine and nevirapine. Passive sampling was based on the diffusion of the target pharmaceuticals from surface water through a membrane bag which housed an ionic liquid as a green receiving solvent and a molecularly imprinted polymer. Effects of biofouling, deployment time and solvent type for the receiver phase were optimized for selective uptake of analytes in surface water. Notably, there was a decrease in the uptake of selected pharmaceuticals and consequently a decrease in their sampling rates in the presence of biofouling. The optimum matrix-matched sampling rates ranged from 0.0007 - 0.0018 L d-1 whilst the method detection and quantification limits ranged from 2.45 - 3.26 ng L-1 and 8.06 - 10.81 ng L-1, respectively. The optimized passive sampler was deployed in a dam situated in the heart of a typical highly populated township in the Gauteng Province of South Africa. Only etilefrine and methocarbamol were detected and quantified at maximum time weighted average concentrations of 12.88 and 72.29 ng L-1, respectively.

Identifying Clinically Relevant Drug-Drug Interactions With Methadone and Buprenorphine: A Translational Approach to Signal Detection.

Methadone and buprenorphine have pharmacologic properties that are concerning for a high risk of drug-drug interactions (DDIs). We performed high-throughput screening for clinically relevant DDIs with methadone or buprenorphine by combining pharmacoepidemiologic and pharmacokinetic approaches. We conducted pharmacoepidemiologic screening via a series of self-controlled case series studies (SCCS) in Optum claims data from 2000 to 2019. We included persons 18 years or older who experienced an outcome of interest during target drug treatment. Exposures were all overlapping medications (i.e., the candidate precipitants) during target drug treatment. Outcomes were opioid overdose, non-overdose adverse effects, and cardiac arrest. We used conditional Poisson regression to calculate rate ratios, accounting for multiple comparisons with semi-Bayes shrinkage. We explored the impact of key study design choices in analyses that varied the exposure definitions of the target drugs and the candidate precipitant drugs. Pharmacokinetic screening was conducted by incorporating published data on CYP enzyme metabolism into an equation-based static model. In SCCS analysis, 1,432 events were included from 248,069 new users of methadone or buprenorphine. In the primary analysis, statistically significant DDIs included gabapentinoids with either methadone or buprenorphine; baclofen with methadone; and benzodiazepines with methadone. In sensitivity analysis, additional statistically significant DDIs included methocarbamol, quetiapine, or simvastatin with methadone. Pharmacokinetic screening identified two moderate-to-strong potential DDIs (clonidine and fluconazole with buprenorphine). The combination of clonidine and buprenorphine was also associated with a significantly increased risk of opioid overdose in pharmacoepidemiologic screening. These DDI signals may be the most important targets for future confirmation studies.

Comparative Risk of Opioid Overdose With Concomitant Use of Prescription Opioids and Skeletal Muscle Relaxants.

BACKGROUND AND OBJECTIVES: The concomitant use of prescription opioids and skeletal muscle relaxants has been associated with opioid overdose, but little data exist on the head-to-head safety of these drug combinations. The objective of this study was to compare the risk of opioid overdose among patients on long-term opioid therapy who concurrently initiate skeletal muscle relaxants. METHODS: We conducted an active comparator cohort study spanning 2000 to 2019 using healthcare utilization data from 4 US commercial and public insurance databases. Individuals were required to have at least 180 days of continuous enrollment and at least 90 days of continuous prescription opioid use immediately before and on the date of skeletal muscle relaxant initiation. Exposures were the concomitant use of prescription opioids and skeletal muscle relaxants, and the main outcome was the hazard ratio (HR) and bootstrapped 95% CI of opioid overdose resulting in an emergency department visit or hospitalization. The primary analysis quantified opioid overdose risk across 7 prescription opioid-skeletal muscle relaxant therapies and a negative control outcome (sepsis) to assess potential confounding by unmeasured illicit opioid use. Secondary analyses evaluated two-group and five-group comparisons in patients with similar baseline characteristics; individuals without previous recorded substance abuse; and subgroups stratified by baseline opioid dosage, benzodiazepine codispensing, and oxycodone or hydrocodone use. RESULTS: Weighted HR of opioid overdose relative to cyclobenzaprine was 2.52 (95% CI 1.29-4.90) for baclofen; 1.64 (95% CI 0.81-3.34) for carisoprodol; 1.14 (95% CI 0.53-2.46) for chlorzoxazone/orphenadrine; 0.46 (95% CI 0.17-1.24) for metaxalone; 1.00 (95% CI 0.45-2.20) for methocarbamol; and 1.07 (95% CI 0.49-2.33) for tizanidine in the 30-day intention-to-treat analysis. Findings were similar in the as-treated analysis, 2-group and 5-group comparisons, and patients without previous recorded substance abuse. None of the therapies relative to cyclobenzaprine were associated with sepsis, and no subgroups indicated an increased risk of opioid overdose. DISCUSSION: Concomitant use of prescription opioids and baclofen relative to cyclobenzaprine is associated with opioid overdose. Clinical interventions may focus on prescribing alternatives in the same drug class or providing access to opioid antagonists if treatment with both medications is necessary for pain management.

The effect of methocarbamol and mexiletine on murine muscle spindle function.

INTRODUCTION/AIMS: The muscle relaxant methocarbamol and the antimyotonic drug mexiletine are widely used for the treatment of muscle spasms, myotonia, and pain syndromes. To determine whether these drugs affect muscle spindle function, we studied their effect on the resting discharge and on stretch-induced action potential frequencies of proprioceptive afferent neurons. METHODS: Single unit action potential frequencies of proprioceptive afferents from muscle spindles in the murine extensor digitorum longus muscle of adult C57BL/6J mice were recorded under resting conditions and during ramp-and-hold stretches. Maximal tetanic force of the same muscle after direct stimulation was determined. High-resolution confocal microscopy analysis was performed to determine the distribution of Nav 1.4 channels, a potential target for both drugs. RESULTS: Methocarbamol and mexiletine inhibited the muscle spindle resting discharge in a dose-dependent manner with IC50 values around 300 µM and 6 µM, respectively. With increasing concentrations of both drugs, the response to stretch was also affected, with the static sensitivity first followed by the dynamic sensitivity. At high concentrations, both drugs completely blocked muscle spindle afferent output. Both drugs also reversibly reduced the specific force of the extensor digitorum longus muscle after tetanic stimulation. Finally, we present evidence for the presence and specific localization of the voltage-gated sodium channel Nav 1.4 in intrafusal fibers. DISCUSSION: In this study we demonstrate that both muscle relaxants affect muscle spindle function, suggesting impaired proprioception as a potential side effect of both drugs. Moreover, our results provide additional evidence of a peripheral activity of methocarbamol and mexiletine.

The Relative Efficacy of Seven Skeletal Muscle Relaxants. An Analysis of Data From Randomized Studies.

BACKGROUND: Low back pain (LBP) causes 2.6 million visits to U.S. emergency departments (EDs) annually. These patients are often treated with skeletal muscle relaxants (SMRs). OBJECTIVES: The goal of this study was to determine whether efficacy of SMRs is associated with age, sex, or baseline LBP severity. METHODS: This was a planned analysis of data from 4 randomized studies of patients with acute nonradicular LBP. Patients were enrolled during an ED visit and followed-up 1 week later. The primary outcome was improvement in the Roland-Morris Disability Questionnaire (RMDQ) between ED discharge and the 1-week follow-up. We compared the change in RMDQ among 8 groups: placebo, baclofen, metaxalone, tizanidine, diazepam, orphenadrine, methocarbamol, and cyclobenzaprine. All patients also received a nonsteroidal anti-inflammatory drug. We performed analysis of variance to determine statistically significant differences between medications and linear regression to determine the association of age, sex, and baseline severity with the primary outcome. RESULTS: The mean improvement in RMDQ per group was placebo 10.5 (95% confidence interval [CI] 9.5-11.5), baclofen 10.6 (95% CI 8.6-12.7), metaxalone 10.3 (95% CI 8.1-12.4), tizanidine 11.5 (95% CI 9.5-13.4), diazepam 11.1 (95% CI 9-13.2), orphenadrine 9.5 (95% CI 7.4-11.5), methocarbamol 8.1 (95% CI 6.1-10.1), and cyclobenzaprine 10.1 (95% CI 8.3-12). The between-group differences were not statistically significantly different. Results were similar regardless of age, sex, and baseline severity. Higher baseline RMDQ was associated with greater clinical improvement (B coefficient 5.7, p < 0.01). Adverse medication effects were more common with cyclobenzaprine than with placebo (p < 0.01). CONCLUSIONS: Among patients in the ED with acute LBP treated with a nonsteroidal anti-inflammatory drug, SMRs do not improve outcomes more than placebo. Neither age, sex, nor baseline impairment impacts these results.

The medication violations in racehorses at Louisiana racetracks from 2016 to 2020.

INTRODUCTION/BACKGROUND: The number of publications for most common drug violations in racehorses is limited. This study reports the most common medication violations in racehorses at four major racetracks in Louisiana between 2016 and 2020. METHODS: During this 5-year period, 27,237 blood samples and 25,672 urine samples collected during the course of normal race meeting activities were analysed by initial screening procedure utilizing Liquid Chromatography Mass Spectrometry (LC-MS/MS). Following initial screening, suspect samples were subject to quantitative or semi- quantitative confirmation analysis by LC-MS/MS. RESULTS: The total number of violations reported was 534 (1.01% of the total number of specimens analysed). The total number of violations reported in Thoroughbred horses was 210 while the total number of violations reported in Quarter Horses was 324. The percentage of total violations was %0.59 for all the specimens analysed in Thoroughbred horses while this percentage was %1.9 for all the specimens analysed in Quarter Horses during this 5-year period. The most frequent violations included the overages (concentrations of permitted medications equal to or exceeding the set threshold) of clenbuterol (165 violations), non-steroidal anti-inflammatory drugs (NSAIDs) such as phenylbutazone (73 violations), combination of phenylbutazone with flunixin (45 violations) and muscle relaxant methocarbamol (40 violations). DISCUSSION/CONCLUSIONS: The total number of violations were relatively low during 5-year period, but wide varieties of medications with different pharmacological actions were confirmed in performance horses in Louisiana. The most frequently reported violations in Louisiana were for permitted therapeutic medications (clenbuterol, phenylbutazone, flunixin methocarbamol) with established threshold and/or withdrawal guidelines in racehorses.

A New Approach on the pain management of intramuscular injection: A Triple-Blind Randomized Clinical Trial.

BACKGROUND: Pain management is an important part of care provided by nurses. AIMS: The present study aimed to investigate the effect of an innovative method named the skin traction, pressure, and rapid muscle release (TPR) on reducing IM injection pain compared with the Z-track injection method DESIGN: This triple-blind clinical trial investigated 63 patients who required Methocarbamol injection. METHODS: Two, 5-cc methocarbamol injections were given to each patient by the two techniques in two of his/her muscles. In the TPR technique, after applying skin traction and imposing deep pressure on the muscle, the needle was inserted at a 90° angle near the skin and the muscle was released rapidly towards the needle. Hence, the needle was embedded in the muscle. However, muscle release was not applied in the Z-track method. The visual analog scale (VAS) was used to measure pain intensity. For data analysis, T-independent and χ2 tests were used. RESULTS: The findings showed that the mean pain score in TPR and Z-track methods was 1.68 ± 1.20 and 3.76 ± 1.42, respectively. The difference was statistically significant. CONCLUSION: The results of this study showed that the innovative method (TPR) can be used as a substitute for the Z-track method to reduce IM injection pain.

COMET - effectiveness and tolerability of methocarbamol versus oral opioid-analgesics as add-on measure in patients with non-specific low back pain refractory to recommended 1st line treatments. A retrospective analysis of depersonalized propensity score matched open-label real-world 4-week data from the German Pain e-Registry.

BACKGROUND: To compare the 4-week effectiveness and tolerability of an add-on treatment with oral high dose methocarbamol (MET) vs long-acting oral opioid analgesics (LAO) in patients with non-specific low back pain (nsLBP) poorly responsive to recommended 1st line treatments. METHODS: Analysis of anonymized, propensity score-matched real-world data from the German Pain e-Registry, using a sequential non-inferiority superiority approach, for adult outpatients with nsLBP who had initiated treatment with MET or LAO between 1st January 2018 and 31st December 2019 (EUPAS identifier: 38484). The primary effectiveness variable was the absolute change of the average 24-h. pain intensity index (PIX). Safety was assessed by incidence of physician-confirmed drug-related adverse events (DRAEs), and DRAEs leading to discontinuation. RESULTS: Propensity score-matched data were analyzed for 374 patients treated with MET and 374 patients treated with LAO. Mean ± SD (median) MET dose over the 4-week evaluation period was 2390.4 ± 1980 (3000) mg and 69.6 ± 25.9 (60) mg morphine equivalent for LAO. With 25.8 ± 11.4 (median 26, 95%CI: 24.5-27.1) vs. 11.4 ± 6.8 (median 11; 95%CI: 10.6-12.2) mm VAS, absolute 4-week improvement vs. baseline was superior for MET vs. LAO [p < .001; effect size 1.6; least square mean difference 14.4 (95%CI: 13.4-15.3)]. Percentages of patients with a PIX improvement ≥ MCID was 81.8 vs. 24.6% [p < .001; OR: 13.8 (9.7-19.6), RR: 4.0 (3.2-5.0), NNT: 1.7]. A significantly lower number of patients treated with MET vs. LAO reported DRAEs in response to study medication: 36 (9.6%) vs. 139 (37.2%; p < .001; NNT 4), and 9 patients treated with MET (2.4%) vs. 86 (23.0%) treated with LAO discontinued treatment in response to these DRAEs (p < .001; NNT: 5). CONCLUSION: 4-week add-on treatment with MET in patients with nsLBP who showed an inadequate response to recommended 1st line treatments is superior effective to LAO and significantly better tolerated.KEY MESSAGESLow back pain is the most common musculoskeletal problem worldwide.In the majority of patients, LBP does not have a specific cause and the most prevalently coded form is mechanical, non-specific (ns) LBP associated with muscular tension, restrictions in mobility, and static malposition.Current treatment recommendations for nsLBP are largely "non-specific" as well, limited to symptomatic pain-relieving measures.In our propensity score-matched two cohort analyses of depersonalized real-world data from the German Pain e-Registry, a 4-week treatment with the muscle relaxant methocarbamol proved superior effective and significantly better tolerated than treatment with oral long-acting opioid analgesics in patients who poorly responded to recommended 1st line treatments.

A New Application of PARAFAC Model to UPLC Dataset for the Quantitative Resolution of a Tri-Component Drug Mixture.

In the presented work, a three-way analysis of ultra-performance liquid chromatography-photodiode array (UPLC-PDA) dataset was performed by parallel factor analysis (PARAFAC) for quantitatively resolving a ternary mixture containing paracetamol and methocarbamol with indapamide selected as an internal standard in their co-eluted chromatographic conditions. Paracetamol and methocarbamol were quantified in the working range between 3-24 and 5-50 µg/mL by applying PARAFAC decomposition to UPLC-PDA data array obtained under unresolved chromatographic peak conditions. To compare the experimental results provided by co-eluted UPLC-PARAFAC method, an ordinary UPLC method was developed ensuring proper separation of the peaks. The performance of both PARAFAC and ordinary UPLC methods were assessed by quantifying independent test samples, intra- and inter-day samples and spiked samples of pharmaceutical preparations. Then, both methods were applied for quantitative estimation of the related drugs in a commercial pharmaceutical preparation. In this study, PARAFAC method was proved to be a very powerful alternative for the quality control of pharmaceutical preparations containing paracetamol and methocarbamol even in their co-eluted chromatograms with high precision and accuracy in a short chromatographic runtime of 1.2 min.

Development and Validation of a Stability-Indicating High-Performance Liquid Chromatographic Method for the Quantification of Methocarbamol and Its Impurities in Pharmaceutical Dosage Forms.

A novel, delicate, stability-indicating, gradient, reversed-phase high-performance liquid chromatographic method has been established for the quantitative estimation of methocarbamol (MTC) and its impurities present in a pharmaceutical oral suspension. XBridge C18, 5 µm, 250 mm × 4.6 mm column was used to accomplish chromatographic separation with a buffered mobile phase consisting of a mixture of 0.01 M of sodium dihydrogen phosphate (pH 7.0 buffer) and methanol in the ratio of 95:05 (v/v), respectively, were used as solvent A and a mixture of methanol and Milli-Q water in the ratio 90:10 (v/v), respectively, was used as solvent B. Analysis was carried out at 0.8 mL/min flow rate and the detection wavelength at 225 nm. The compartment temperature of the column is put at 25°C. The resolution of MTC and its four impurities has been attained >2.0 for all pairs of compounds. Significant degradation of MTC was photolytic, thermal and oxidative stress conditions. Validation of the developed method was performed as stated by the International Conference on Harmonization guidelines with regard to all validation parameters like specificity, accuracy, linearity, precision, limit of detection, limit of quantitation and robustness.