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Anaesthesia Aug 2021The aim of this systematic review was to develop recommendations for the management of postoperative pain after primary elective total hip arthroplasty, updating the...
The aim of this systematic review was to develop recommendations for the management of postoperative pain after primary elective total hip arthroplasty, updating the previous procedure-specific postoperative pain management (PROSPECT) guidelines published in 2005 and updated in July 2010. Randomised controlled trials and meta-analyses published between July 2010 and December 2019 assessing postoperative pain using analgesic, anaesthetic, surgical or other interventions were identified from MEDLINE, Embase and Cochrane databases. Five hundred and twenty studies were initially identified, of which 108 randomised trials and 21 meta-analyses met the inclusion criteria. Peri-operative interventions that improved postoperative pain include: paracetamol; cyclo-oxygenase-2-selective inhibitors; non-steroidal anti-inflammatory drugs; and intravenous dexamethasone. In addition, peripheral nerve blocks (femoral nerve block; lumbar plexus block; fascia iliaca block), single-shot local infiltration analgesia, intrathecal morphine and epidural analgesia also improved pain. Limited or inconsistent evidence was found for all other approaches evaluated. Surgical and anaesthetic techniques appear to have a minor impact on postoperative pain, and thus their choice should be based on criteria other than pain. In summary, the analgesic regimen for total hip arthroplasty should include pre-operative or intra-operative paracetamol and cyclo-oxygenase-2-selective inhibitors or non-steroidal anti-inflammatory drugs, continued postoperatively with opioids used as rescue analgesics. In addition, intra-operative intravenous dexamethasone 8-10 mg is recommended. Regional analgesic techniques such as fascia iliaca block or local infiltration analgesia are recommended, especially if there are contra-indications to basic analgesics and/or in patients with high expected postoperative pain. Epidural analgesia, femoral nerve block, lumbar plexus block and gabapentinoid administration are not recommended as the adverse effects outweigh the benefits. Although intrathecal morphine 0.1 mg can be used, the PROSPECT group emphasises the risks and side-effects associated with its use and provides evidence that adequate analgesia may be achieved with basic analgesics and regional techniques without intrathecal morphine.
Topics: Arthroplasty, Replacement, Hip; Humans; Pain Management; Pain, Postoperative; Practice Guidelines as Topic
PubMed: 34015859
DOI: 10.1111/anae.15498 -
European Journal of Anaesthesiology Sep 2021Complex spinal procedures are associated with intense pain in the postoperative period. Adequate peri-operative pain management has been shown to correlate with improved...
BACKGROUND
Complex spinal procedures are associated with intense pain in the postoperative period. Adequate peri-operative pain management has been shown to correlate with improved outcomes including early ambulation and early discharge.
OBJECTIVES
We aimed to evaluate the available literature and develop recommendations for optimal pain management after complex spine surgery.
DESIGN AND DATA SOURCES
A systematic review using the PROcedure SPECific postoperative pain managemenT methodology was undertaken. Randomised controlled trials and systematic reviews published in the English language from January 2008 to April 2020 assessing postoperative pain after complex spine surgery using analgesic, anaesthetic or surgical interventions were identified from MEDLINE, EMBASE and Cochrane Databases.
RESULTS
Out of 111 eligible studies identified, 31 randomised controlled trials and four systematic reviews met the inclusion criteria. Pre-operative and intra-operative interventions that improved postoperative pain were paracetamol, cyclo-oxygenase (COX)-2 specific-inhibitors or non-steroidal anti-inflammatory drugs (NSAIDs), intravenous ketamine infusion and regional analgesia techniques including epidural analgesia using local anaesthetics with or without opioids. Limited evidence was found for local wound infiltration, intrathecal and epidural opioids, erector spinae plane block, thoracolumbar interfascial plane block, intravenous lidocaine, dexmedetomidine and gabapentin.
CONCLUSIONS
The analgesic regimen for complex spine surgery should include pre-operative or intra-operative paracetamol and COX-2 specific inhibitors or NSAIDs, continued postoperatively with opioids used as rescue analgesics. Other recommendations are intra-operative ketamine and epidural analgesia using local anaesthetics with or without opioids. Although there is procedure-specific evidence in favour of intra-operative methadone, it is not recommended as it was compared with shorter-acting opioids and due to its limited safety profile. Furthermore, the methadone studies did not use non-opioid analgesics, which should be the primary analgesics to ultimately reduce overall opioid requirements, including methadone. Further qualitative randomised controlled trials are required to confirm the efficacy and safety of these recommended analgesics on postoperative pain relief.
Topics: Analgesia, Epidural; Analgesics, Opioid; Anesthetics, Local; Humans; Pain Management; Pain, Postoperative
PubMed: 34397527
DOI: 10.1097/EJA.0000000000001448 -
Anaesthesia Mar 2022Video-assisted thoracoscopic surgery has become increasingly popular due to faster recovery times and reduced postoperative pain compared with thoracotomy. However,...
Video-assisted thoracoscopic surgery has become increasingly popular due to faster recovery times and reduced postoperative pain compared with thoracotomy. However, analgesic regimens for video-assisted thoracoscopic surgery vary significantly. The goal of this systematic review was to evaluate the available literature and develop recommendations for optimal pain management after video-assisted thoracoscopic surgery. A systematic review was undertaken using procedure-specific postoperative pain management (PROSPECT) methodology. Randomised controlled trials published in the English language, between January 2010 and January 2021 assessing the effect of analgesic, anaesthetic or surgical interventions were identified. We retrieved 1070 studies of which 69 randomised controlled trials and two reviews met inclusion criteria. We recommend the administration of basic analgesia including paracetamol and non-steroidal anti-inflammatory drugs or cyclo-oxygenase-2-specific inhibitors pre-operatively or intra-operatively and continued postoperatively. Intra-operative intravenous dexmedetomidine infusion may be used, specifically when basic analgesia and regional analgesic techniques could not be given. In addition, a paravertebral block or erector spinae plane block is recommended as a first-choice option. A serratus anterior plane block could also be administered as a second-choice option. Opioids should be reserved as rescue analgesics in the postoperative period.
Topics: Analgesics; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Drug Therapy, Combination; Humans; Nerve Block; Pain Management; Pain, Postoperative; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Thoracic Surgery, Video-Assisted
PubMed: 34739134
DOI: 10.1111/anae.15609 -
JAMA Psychiatry Mar 2021Precise estimation of the drug metabolism capacity for individual patients is crucial for adequate dose personalization. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Precise estimation of the drug metabolism capacity for individual patients is crucial for adequate dose personalization.
OBJECTIVE
To quantify the difference in the antipsychotic and antidepressant exposure among patients with genetically associated CYP2C19 and CYP2D6 poor (PM), intermediate (IM), and normal (NM) metabolizers.
DATA SOURCES
PubMed, Clinicaltrialsregister.eu, ClinicalTrials.gov, International Clinical Trials Registry Platform, and CENTRAL databases were screened for studies from January 1, 1990, to June 30, 2020, with no language restrictions.
STUDY SELECTION
Two independent reviewers performed study screening and assessed the following inclusion criteria: (1) appropriate CYP2C19 or CYP2D6 genotyping was performed, (2) genotype-based classification into CYP2C19 or CYP2D6 NM, IM, and PM categories was possible, and (3) 3 patients per metabolizer category were available.
DATA EXTRACTION AND SYNTHESIS
The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed for extracting data and quality, validity, and risk of bias assessments. A fixed-effects model was used for pooling the effect sizes of the included studies.
MAIN OUTCOMES AND MEASURES
Drug exposure was measured as (1) dose-normalized area under the plasma level (time) curve, (2) dose-normalized steady-state plasma level, or (3) reciprocal apparent total drug clearance. The ratio of means (RoM) was calculated by dividing the mean drug exposure for PM, IM, or pooled PM plus IM categories by the mean drug exposure for the NM category.
RESULTS
Based on the data derived from 94 unique studies and 8379 unique individuals, the most profound differences were observed in the patients treated with aripiprazole (CYP2D6 PM plus IM vs NM RoM, 1.48; 95% CI, 1.41-1.57; 12 studies; 1038 patients), haloperidol lactate (CYP2D6 PM vs NM RoM, 1.68; 95% CI, 1.40-2.02; 9 studies; 423 patients), risperidone (CYP2D6 PM plus IM vs NM RoM, 1.36; 95% CI, 1.28-1.44; 23 studies; 1492 patients), escitalopram oxalate (CYP2C19 PM vs NM, RoM, 2.63; 95% CI, 2.40-2.89; 4 studies; 1262 patients), and sertraline hydrochloride (CYP2C19 IM vs NM RoM, 1.38; 95% CI, 1.27-1.51; 3 studies; 917 patients). Exposure differences were also observed for clozapine, quetiapine fumarate, amitriptyline hydrochloride, mirtazapine, nortriptyline hydrochloride, fluoxetine hydrochloride, fluvoxamine maleate, paroxetine hydrochloride, and venlafaxine hydrochloride; however, these differences were marginal, ambiguous, or based on less than 3 independent studies.
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, the association between CYP2C19/CYP2D6 genotype and drug levels of several psychiatric drugs was quantified with sufficient precision as to be useful as a scientific foundation for CYP2D6/CYP2C19 genotype-based dosing recommendations.
Topics: Antidepressive Agents; Antipsychotic Agents; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2D6; Humans; Pharmacogenomic Variants
PubMed: 33237321
DOI: 10.1001/jamapsychiatry.2020.3643 -
The Cochrane Database of Systematic... Sep 2022Oral nirmatrelvir/ritonavir (Paxlovid®) aims to avoid severe COVID-19 in asymptomatic people or those with mild symptoms, thereby decreasing hospitalization and death.... (Review)
Review
BACKGROUND
Oral nirmatrelvir/ritonavir (Paxlovid®) aims to avoid severe COVID-19 in asymptomatic people or those with mild symptoms, thereby decreasing hospitalization and death. Due to its novelty, there are currently few published study results. It remains to be evaluated for which indications and patient populations the drug is suitable. OBJECTIVES: To assess the efficacy and safety of nirmatrelvir/ritonavir (Paxlovid®) plus standard of care compared to standard of care with or without placebo, or any other intervention for treating COVID-19 and for preventing SARS-CoV-2 infection. To explore equity aspects in subgroup analyses. To keep up to date with the evolving evidence base using a living systematic review (LSR) approach and make new relevant studies available to readers in-between publication of review updates.
SEARCH METHODS
We searched the Cochrane COVID-19 Study Register, Scopus, and WHO COVID-19 Global literature on coronavirus disease database, identifying completed and ongoing studies without language restrictions and incorporating studies up to 11 July 2022. This is a LSR. We conduct monthly update searches that are being made publicly available on the open science framework (OSF) platform.
SELECTION CRITERIA
Studies were eligible if they were randomized controlled trials (RCTs) comparing nirmatrelvir/ritonavir plus standard of care with standard of care with or without placebo, or any other intervention for treatment of people with confirmed COVID-19 diagnosis, irrespective of disease severity or treatment setting, and for prevention of SARS-CoV-2 infection. We screened all studies for research integrity. Studies were ineligible if they had been retracted, or if they were not prospectively registered including appropriate ethics approval.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology and used the Cochrane risk of bias 2 tool. We rated the certainty of evidence using the GRADE approach for the following outcomes: 1. to treat outpatients with mild COVID-19; 2. to treat inpatients with moderate-to-severe COVID-19: mortality, clinical worsening or improvement, quality of life, (serious) adverse events, and viral clearance; 3. to prevent SARS-CoV-2 infection in post-exposure prophylaxis (PEP); and 4. pre-exposure prophylaxis (PrEP) scenarios: SARS-CoV-2 infection, development of COVID-19 symptoms, mortality, admission to hospital, quality of life, and (serious) adverse events. We explored inequity by subgroup analysis for elderly people, socially-disadvantaged people with comorbidities, populations from LICs and LMICs, and people from different ethnic and racial backgrounds.
MAIN RESULTS
As of 11 July 2022, we included one RCT with 2246 participants in outpatient settings with mild symptomatic COVID-19 comparing nirmatrelvir/ritonavir plus standard of care with standard of care plus placebo. Trial participants were unvaccinated, without previous confirmed SARS-CoV-2 infection, had a symptom onset of no more than five days before randomization, and were at high risk for progression to severe disease. Prohibited prior or concomitant therapies included medications highly dependent on CYP3A4 for clearance and CYP3A4 inducers. We identified eight ongoing studies. Nirmatrelvir/ritonavir for treating COVID-19 in outpatient settings with asymptomatic or mild disease For the specific population of unvaccinated, high-risk patients nirmatrelvir/ritonavir plus standard of care compared to standard of care plus placebo may reduce all-cause mortality at 28 days (risk ratio (RR) 0.04, 95% confidence interval (CI) 0.00 to 0.68; 1 study, 2224 participants; estimated absolute effect: 11 deaths per 1000 people receiving placebo compared to 0 deaths per 1000 people receiving nirmatrelvir/ritonavir; low-certainty evidence, and admission to hospital or death within 28 days (RR 0.13, 95% CI 0.07 to 0.27; 1 study, 2224 participants; estimated absolute effect: 61 admissions or deaths per 1000 people receiving placebo compared to eight admissions or deaths per 1000 people receiving nirmatrelvir/ritonavir; low-certainty evidence). Nirmatrelvir/ritonavir plus standard of care may reduce serious adverse events during the study period compared to standard of care plus placebo (RR 0.24, 95% CI 0.15 to 0.41; 1 study, 2224 participants; low-certainty evidence). Nirmatrelvir/ritonavir plus standard of care probably has little or no effect on treatment-emergent adverse events (RR 0.95, 95% CI 0.82 to 1.10; 1 study, 2224 participants; moderate-certainty evidence), and probably increases treatment-related adverse events such as dysgeusia and diarrhoea during the study period compared to standard of care plus placebo (RR 2.06, 95% CI 1.44 to 2.95; 1 study, 2224 participants; moderate-certainty evidence). Nirmatrelvir/ritonavir plus standard of care probably decreases discontinuation of study drug due to adverse events compared to standard of care plus placebo (RR 0.49, 95% CI 0.30 to 0.80; 1 study, 2224 participants; moderate-certainty evidence). No study results were identified for improvement of clinical status, quality of life, and viral clearance. Subgroup analyses for equity Most study participants were younger than 65 years (87.1% of the : modified intention to treat (mITT1) population with 2085 participants), of white ethnicity (71.5%), and were from UMICs or HICs (92.1% of study centres). Data on comorbidities were insufficient. The outcome 'admission to hospital or death' was investigated for equity: age (< 65 years versus ≥ 65 years) and ethnicity (Asian versus Black versus White versus others). There was no difference between subgroups of age. The effects favoured treatment with nirmatrelvir/ritonavir for the White ethnic group. Estimated effects in the other ethnic groups included the line of no effect (RR = 1). No subgroups were reported for comorbidity status and World Bank country classification by income level. No subgroups were reported for other outcomes. Nirmatrelvir/ritonavir for treating COVID-19 in inpatient settings with moderate to severe disease No studies available. Nirmatrelvir/ritonavir for preventing SARS-CoV-2 infection (PrEP and PEP) No studies available.
AUTHORS' CONCLUSIONS
There is low-certainty evidence that nirmatrelvir/ritonavir reduces the risk of all-cause mortality and hospital admission or death based on one trial investigating unvaccinated COVID-19 participants without previous infection that were at high risk and with symptom onset of no more than five days. There is low- to moderate-certainty evidence that nirmatrelvir/ritonavir is safe in people without prior or concomitant therapies including medications highly dependent on CYP3A4. Regarding equity aspects, except for ethnicity, no differences in effect size and direction were identified. No evidence is available on nirmatrelvir/ritonavir to treat hospitalized people with COVID-19 and to prevent a SARS-CoV-2 infection. We will continually update our search and make search results available on OSF.
Topics: Aged; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inducers; Humans; Ritonavir; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 36126225
DOI: 10.1002/14651858.CD015395.pub2 -
Clinical Pharmacology and Therapeutics Jun 2021Proton pump inhibitors (PPIs) are widely used for acid suppression in the treatment and prevention of many conditions, including gastroesophageal reflux disease, gastric...
Proton pump inhibitors (PPIs) are widely used for acid suppression in the treatment and prevention of many conditions, including gastroesophageal reflux disease, gastric and duodenal ulcers, erosive esophagitis, Helicobacter pylori infection, and pathological hypersecretory conditions. Most PPIs are metabolized primarily by cytochrome P450 2C19 (CYP2C19) into inactive metabolites, and CYP2C19 genotype has been linked to PPI exposure, efficacy, and adverse effects. We summarize the evidence from the literature and provide therapeutic recommendations for PPI prescribing based on CYP2C19 genotype (updates at www.cpicpgx.org). The potential benefits of using CYP2C19 genotype data to guide PPI therapy include (i) identifying patients with genotypes predictive of lower plasma exposure and prescribing them a higher dose that will increase the likelihood of efficacy, and (ii) identifying patients on chronic therapy with genotypes predictive of higher plasma exposure and prescribing them a decreased dose to minimize the risk of toxicity that is associated with long-term PPI use, particularly at higher plasma concentrations.
Topics: Cytochrome P-450 CYP2C19; Gastroesophageal Reflux; Genotype; Humans; Pharmacogenetics; Proton Pump Inhibitors
PubMed: 32770672
DOI: 10.1002/cpt.2015 -
Clinical Pharmacology and Therapeutics Aug 2020Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used analgesics due to their lack of addictive potential. However, NSAIDs have the potential to... (Meta-Analysis)
Meta-Analysis
Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used analgesics due to their lack of addictive potential. However, NSAIDs have the potential to cause serious gastrointestinal, renal, and cardiovascular adverse events. CYP2C9 polymorphisms influence metabolism and clearance of several drugs in this class, thereby affecting drug exposure and potentially safety. We summarize evidence from the published literature supporting these associations and provide therapeutic recommendations for NSAIDs based on CYP2C9 genotype (updates at www.cpicpgx.org).
Topics: Anti-Inflammatory Agents, Non-Steroidal; Clinical Decision-Making; Consensus; Cytochrome P-450 CYP2C9; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Genotype; Humans; Pharmacogenetics; Pharmacogenomic Testing; Pharmacogenomic Variants; Phenotype; Predictive Value of Tests; Risk Assessment; Risk Factors
PubMed: 32189324
DOI: 10.1002/cpt.1830 -
Anaesthesia Oct 2019Rotator cuff repair can be associated with significant and difficult to treat postoperative pain. We aimed to evaluate the available literature and develop...
Rotator cuff repair can be associated with significant and difficult to treat postoperative pain. We aimed to evaluate the available literature and develop recommendations for optimal pain management after rotator cuff repair. A systematic review using procedure-specific postoperative pain management (PROSPECT) methodology was undertaken. Randomised controlled trials published in English from 1 January 2006 to 15 April 2019 assessing postoperative pain after rotator cuff repair using analgesic, anaesthetic or surgical interventions were identified from MEDLINE, Embase and Cochrane Databases. Out of 322 eligible studies identified, 59 randomised controlled trials and one systematic review met the inclusion criteria. Pre-operative and intra-operative interventions that improved postoperative pain were paracetamol, cyclo-oxygenase-2 inhibitors, intravenous dexamethasone, regional analgesia techniques including interscalene block or suprascapular nerve block (with or without axillary nerve block) and arthroscopic surgical technique. Limited evidence was found for pre-operative gabapentin, perineural adjuncts (opioids, glucocorticoids, or α-2-adrenoceptor agonists added to the local anaesthetic solution) or postoperative transcutaneous electrical nerve stimulation. Inconsistent evidence was found for subacromial/intra-articular injection, and for surgical technique-linked interventions, such as platelet-rich plasma. No evidence was found for stellate ganglion block, cervical epidural block, specific postoperative rehabilitation protocols or postoperative compressive cryotherapy. The analgesic regimen for rotator cuff repair should include an arthroscopic approach, paracetamol, non-steroidal anti-inflammatory drugs, dexamethasone and a regional analgesic technique (either interscalene block or suprascapular nerve block with or without axillary nerve block), with opioids as rescue analgesics. Further randomised controlled trials are required to confirm the influence of the recommended analgesic regimen on postoperative pain relief.
Topics: Guidelines as Topic; Humans; Orthopedic Procedures; Pain Management; Pain, Postoperative; Randomized Controlled Trials as Topic; Rotator Cuff
PubMed: 31392721
DOI: 10.1111/anae.14796 -
Frontiers in Endocrinology 2023To compare the effects of five hypoxia-inducible factor-prolyl hydroxylase domain inhibitors (HIF-PHIs), two erythropoiesis-stimulating agents (ESAs), and placebo on... (Meta-Analysis)
Meta-Analysis
Effects of hypoxia-inducible factor-prolyl hydroxylase inhibitors . erythropoiesis-stimulating agents on iron metabolism in non-dialysis-dependent anemic patients with CKD: A network meta-analysis.
OBJECTIVE
To compare the effects of five hypoxia-inducible factor-prolyl hydroxylase domain inhibitors (HIF-PHIs), two erythropoiesis-stimulating agents (ESAs), and placebo on iron metabolism in renal anemia patients with non-dialysis-dependent chronic kidney disease (NDD-CKD).
METHOD
Five electronic databases were searched for studies. Randomized controlled clinical trials comparing HIF-PHIs, ESAs, and placebo in NDD-CKD patients were selected. The statistical program used for network meta-analysis was Stata/SE 15.1. The main outcomes were the change in hepcidin and hemoglobin (Hb) levels. The merits of intervention measures were predicted by the surface under the cumulative ranking curve method.
RESULTS
Of 1,589 original titles screened, data were extracted from 15 trials (3,228 participants). All HIF-PHIs and ESAs showed greater Hb level-raising ability than placebo. Among them, desidustat demonstrated the highest probability of increasing Hb (95.6%). Hepcidin [mean deviation (MD) = -43.42, 95%CI: -47.08 to -39.76], ferritin (MD= -48.56, 95%CI: -55.21 to -41.96), and transferrin saturation (MD = -4.73, 95%CI: -5.52 to -3.94) were decreased, while transferrin (MD = 0.09, 95%CI: 0.01 to 0.18) and total iron-binding capacity (MD = 6.34, 95%CI: 5.71 to 6.96) was increased in HIF-PHIs versus those in ESAs. In addition, this study observed heterogeneity in the ability of HIF-PHIs to decrease hepcidin. Compared with darbepoetin, only daprodustat (MD = -49.09, 95% CI: -98.13 to -0.05) could significantly reduce hepcidin levels. Meanwhile, daprodustat also showed the highest hepcidin-lowering efficacy (84.0%), while placebo was the lowest (8.2%).
CONCLUSION
For NDD-CKD patients, HIF-PHIs could ameliorate functional iron deficiency by promoting iron transport and utilization, which may be achieved by decreasing hepcidin levels. Interestingly, HIF-PHIs had heterogeneous effects on iron metabolism.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=242777, Identifier CRD42021242777.
Topics: Humans; Hepcidins; Hematinics; Prolyl-Hydroxylase Inhibitors; Erythropoiesis; Prolyl Hydroxylases; Network Meta-Analysis; Hypoxia-Inducible Factor-Proline Dioxygenases; Anemia; Transferrin; Renal Insufficiency, Chronic; Iron; Hypoxia; Randomized Controlled Trials as Topic
PubMed: 37008953
DOI: 10.3389/fendo.2023.1131516 -
Drugs Jul 2021We conducted a narrative review of the literature to compare the pharmacological, efficacy and safety profiles of tapentadol and tramadol, and to assess the clinical...
We conducted a narrative review of the literature to compare the pharmacological, efficacy and safety profiles of tapentadol and tramadol, and to assess the clinical interest of tapentadol in adult patients. Tapentadol and tramadol share a mixed mechanism of action, including both mu-agonist and monoaminergic properties. Tapentadol is approximately two to three times more potent than tramadol and two to three times less potent than morphine. It has no identified analgesically active metabolite and is not significantly metabolised by cytochrome P450 enzymes, thus overcoming some limitations of tramadol, including the potential for pharmacokinetic drug-drug interactions and interindividual variability due to genetic polymorphisms of cytochrome P450 enzymes. The toxicity profiles of tramadol and tapentadol are similar; however tapentadol is likely to result in less exposure to serotoninergic adverse effects (nausea, vomiting, hypoglycaemia) but cause more opioid adverse effects (constipation, respiratory depression, abuse) than tramadol. The safety of tapentadol in real-world conditions remains poorly documented, particularly in at-risk patient subgroups and also in the ability to assess the risk associated with its residual serotonergic activity (serotonin syndrome, seizures). Because of an earlier market introduction, more real-world safety data are available for tramadol, including data from at-risk patient subgroups. The level of evidence on the efficacy of both tramadol and tapentadol for the treatment of chronic pain is globally low. The trials published to date show overall that tapentadol does not provide a clinically significant analgesic improvement compared to existing treatments, for which the safety profile is much better known. In conclusion, tapentadol is not a first-line opioid but represents an additional analgesic in the therapeutic choices, which some patients may benefit from after careful examination of their clinical situation, co-morbidities and co-medications.
Topics: Analgesics, Opioid; Cytochrome P-450 CYP2D6; Dose-Response Relationship, Drug; Humans; Liver Failure; Pain; Renal Insufficiency; Tapentadol; Tramadol
PubMed: 34196947
DOI: 10.1007/s40265-021-01515-z