Pain? Buy Tapentadol Online

Opioid analgesics remain a standard option for managing moderate to severe acute pain following surgical procedures.
Among them, oxycodone—a drug primarily targeting the mu-opioid receptor—is widely used across the globe for postoperative pain control. However, its use is often linked to a range of adverse effects, such as constipation, sedation, respiratory depression, and delirium. These complications typically result from the drug’s action on mu-opioid receptors located outside the central pain-processing pathways, including regions of the brain involved in breathing and the gastrointestinal system.

In recent years, tapentadol overnight, an opioid with a dual mechanism of action—affecting both mu-opioid and noradrenergic receptors—has gained popularity. This shift may reflect a growing interest in reducing opioid-related adverse drug events (ORADEs), as tapentadol appears to carry a lower risk of such complications. A meta-analysis published in 2020, which included eight randomized controlled trials, found tapentadol to be as effective as oxycodone for acute pain, while showing a lower incidence of side effects like nausea, dizziness, and constipation.

However, the applicability of these findings to real-world patients may be limited. Many clinical trials exclude individuals with comorbidities such as renal or liver disease, seizure disorders, psychiatric conditions, diabetes, substance use disorders, and dysphagia—yet these patients frequently require opioid treatment for acute pain. Additionally, certain serious side effects like respiratory depression and delirium have not been sufficiently examined in earlier trials.

To address these gaps, the present study aimed to directly compare the rates of opioid-related adverse drug events, including respiratory depression and delirium, among adult surgical inpatients receiving either tapentadol or oxycodone during the acute postoperative period. Secondary outcomes included comparisons of length of hospital stay and 28-day readmission rates between the two groups. To reduce bias related to patient characteristics, propensity score matching was applied.

Methods and Study Design Med Consumers

This multicenter retrospective cohort study was conducted across three hospitals in New South Wales, Australia, between January 1, 2018, and December 31, 2021. The research protocol received ethical approval from the South Eastern Sydney Local Health District Human Research Ethics Committee (Reference: 2021/ETH12063), and the requirement for informed consent was waived due to the retrospective nature of the data collection.

Adult patients (18 years and older) who underwent surgery and were treated with either tapentadol only or oxycodone only (including oxycodone/naloxone) during their hospital stay were included. Exclusion criteria encompassed patients receiving opioids for cancer-related pain or opioid replacement therapy, those with a history of pre-admission constipation, same-day surgery, or multiple admissions for the same procedure.

Demographic and clinical data were extracted from electronic medical records using ICD-10-AM codes to identify comorbidities and adverse events. Comorbid conditions included a broad range of chronic diseases and mental health disorders, while ORADEs were identified based on established clinical coding systems and manufacturer-reported side effects.

The analysis defined ORADEs as the presence of any one or more of the following during hospitalization: constipation, nausea, vomiting, dizziness, somnolence, delirium, respiratory depression, pruritus, urinary retention, among others. Hospital stay duration and 28-day readmissions were also tracked.

To control for confounding variables, a propensity score matching approach was used, incorporating variables such as comorbidities, surgical procedures, pre-operative opioid use, and in-hospital medications.

Medication Exposure and Grouping Purchase Tapentadol Online

Medication administration data were retrieved from electronic records and included all inpatient doses of tapentadol, oxycodone (including oxycodone/naloxone), paracetamol, NSAIDs, gabapentinoids (gabapentin, pregabalin), benzodiazepines, laxatives, and several classes of oral medications known to increase the risk of delirium, such as anticholinergics, antidopaminergics, antihistamines, H2-receptor antagonists, and corticosteroids. Oral morphine milligram equivalents (MMEs) were calculated using established conversion methods. Any opioid labeled as extended-release (ER) was defined as a formulation with a modified-release mechanism.

Patients were categorized into two mutually exclusive groups:

1. Tapentadol group – patients who received only tapentadol, with no other opioid administered during the hospital stay.
2. Oxycodone group – patients who received any formulation of oxycodone (with or without naloxone) and no other opioids.

Study Outcomes

The primary outcome was the overall incidence of opioid-related adverse drug events (ORADEs) among adult surgical inpatients.
Secondary outcomes included specific adverse events (such as constipation or delirium), length of hospital stay, and 28-day hospital readmission rate.

Statistical Approach Order Tapentadol

Initial comparisons of baseline characteristics between the two groups were performed using univariate analysis. Categorical variables were analyzed using Fisher’s exact test, while continuous variables were evaluated with the Mann–Whitney U-test due to non-normal distribution.

To minimize confounding and account for differences in clinical profiles between groups, propensity score matching was implemented. Propensity scores were derived using a multivariable logistic regression model. Predictors included daily opioid dose (MME), patient age, sex, Charlson Comorbidity Index score, a wide range of comorbid conditions, substance use history (including alcohol and opioids), homelessness, prior opioid exposure, and concurrent use of co-analgesics or medications linked to delirium. Type of surgical procedure and use of extended-release opioids were also included.

Patients in the tapentadol group were matched to those in the oxycodone group using 1:2 nearest-neighbor matching without replacement, and a caliper width of 0.2 times the standard deviation of the logit of the propensity score. Patients without a valid match were excluded. The quality of the match was assessed using standardized mean differences (SMDs); an SMD < 0.1 was considered indicative of acceptable balance between groups.

Outcome Analysis

Following matching, binary outcomes such as ORADE incidence and readmission rates were compared using Fisher’s exact test. The difference in proportions was expressed with 95% confidence intervals. Hospital length of stay was again compared using the Mann–Whitney U-test.

To further explore the influence of extended-release opioid formulations, a sensitivity analysis was conducted by isolating patients who received only immediate-release (IR) tapentadol versus those given only IR oxycodone. The same statistical methods were applied, with the removal of ER opioid use as a covariate in this subgroup.

A p-value below 0.05 was considered statistically significant for all comparisons. Analyses were carried out using IBM SPSS Statistics v27 and R v3.1.2.

Study Population and Characteristics

Out of 114,410 surgical patients during the study window, 93,650 met the inclusion criteria. Within this group, 1,671 patients received tapentadol and 25,168 received oxycodone.

Before matching, there were notable differences between groups. Patients in the tapentadol group were older on average (62.5 vs 53.0 years), more often female, and had a higher comorbidity burden (Charlson Index 1.3 vs 0.8). Conditions such as atherosclerotic heart disease and sleep apnea were more frequent in the tapentadol group.

Co-administration of benzodiazepines (10.8% vs 6.2%), laxatives (62.9% vs 39%), and ER opioids (60.2% vs 29.6%) was also more common among patients who received tapentadol. Their median daily opioid dose in MMEs was notably higher (30 vs 15), suggesting that patients receiving tapentadol may have presented with more complex clinical needs.

Post-Matching Characteristics and Clinical Outcomes Cheap Tapentadol

Following propensity score matching, all standardized mean differences (SMDs) were below 0.1, confirming that baseline characteristics were well balanced between the tapentadol and oxycodone groups (Table 1, Supplementary Figure 1). The average age of patients was similar in both groups—62.3 years (SD 17.0) in the tapentadol group and 61.9 years (SD 17.9) in the oxycodone group. Males accounted for 43% of the tapentadol group and 45% of the oxycodone group. Both groups had a mean Charlson Comorbidity Index score of 1.3 (SD 2.1).

Comparable proportions of patients underwent major surgeries, including coronary artery bypass grafting (9.9% vs 7.7%), hip or knee replacements (6.5% vs 6.9%), and spinal procedures (5.6% vs 5.4%). Prior opioid use was also similar, reported in 40.3% of tapentadol patients and 39% of oxycodone patients. Laxatives were administered to 60.4% in the tapentadol group and 56.3% in the oxycodone group. Median daily opioid dosage (in MMEs) was slightly higher among patients receiving tapentadol: 27.9 mg (range 0.2–392) vs 24.5 mg (range 0.1–270) in the oxycodone group.

Adverse Events and Secondary Outcomes

As shown in Table 2, the overall incidence of ORADEs did not differ significantly between the two matched groups: 14.4% (220/1,530) in the tapentadol group vs 12.6% (349/2,775) in the oxycodone group (P = 0.100; 95% CI −0.35% to 3.95%). No adverse event category showed lower rates with tapentadol, including gastrointestinal events, which occurred at similar frequencies in both groups.

However, delirium was significantly more common among tapentadol users (2.7% vs 1.3%, P = 0.003), as were cardiac arrhythmias (3.4% vs 2.2%, P = 0.029). The median hospital stay was also longer for patients given tapentadol (5 days [range 1–201] vs 4 days [range 1–226], P < 0.001). There were no significant differences in 28-day readmission rates (P = 0.089).

Sensitivity Analysis: Immediate-Release Formulations Tapentadol Online

To control for the influence of extended-release formulations, a sensitivity analysis was performed using only patients treated with immediate-release (IR) versions of tapentadol or oxycodone. After matching, 652 patients in the tapentadol IR group were compared with 1,272 patients in the oxycodone IR group. Post-matching SMDs were again below 0.1, confirming well-balanced groups (Supplementary Table 5, Supplementary Figure 2).

Results revealed that total ORADEs were higher in the tapentadol IR group: 16% vs 11.5% (P = 0.006; 95% CI 1.18–7.82%). This difference was mainly driven by a greater incidence of central nervous system (CNS) adverse events: 4.4% vs 1.8% (P = 0.002).

Discussion

This large-scale real-world analysis found no overall reduction in opioid-related adverse events among surgical inpatients treated with tapentadol compared to oxycodone. Rates of gastrointestinal adverse effects were comparable between groups, which aligns with findings from a 2021 cohort study of orthopedic patients that reported no difference in GI adverse events between the two drugs.

However, these results contrast with a 2020 meta-analysis of randomized controlled trials (RCTs) suggesting a better safety profile for tapentadol. One possible reason for this discrepancy is that laxatives were routinely co-administered in both real-world studies—including the present one—while in the RCTs, laxatives were not part of the protocol. Therefore, the gastrointestinal tolerability advantage observed in controlled trial settings may not be clinically relevant when supportive care such as laxatives is standard.