Effects of Tapentadol Versus Oxycodone After Hysterectomy.

Summary

Opioids remain the first-line drugs for the treatment of moderate to severe postoperative pain, but the use is limited by well-known side-effects, most of which are dose-dependent.

The opioid oxycodone is standard therapeutic treatment for acute postoperative pain, either in immediate-release formulation, OxyNorm®, or as extended-release formulation, OxyContin®. Oxycodone provides analgesic effects through µ-opioid receptors in the central nervous system.

Tapentadol hydrochloride/depot (Palexia/depot®) is a novel, centrally acting, strong analgesic with a dual mechanism of action on µ-opioid receptors and noradrenaline reuptake in the central nervous system. Tapentadol is an active compound, devoid of active metabolites and not reliant on enzyme systems. For these reasons, it has a low drug interaction potential. This dual mechanism also translates clinically into less adverse effects than with pure opioid agonists like oxycodone. This is probably due to less µ-opioid receptor stimulation.

Tapentadol has been shown effective in models of acute, osteoarthritic, neuropathic and cancer pain. There is now an increasing use of tapentadol in postoperative pain treatment in Norway. However, there is a lack of broad-based evidence for the use of tapentadol in the post-surgical setting. So far, to our knowledge, there are only published studies on postoperative pain treatment after orthopedic and dental surgery, but none related to deep abdominal pain.

Tapentadol is shown in several studies on chronic pain patients to have comparable analgesic effects to traditional opioid pain medications like oxycodone and morphine, but with a more tolerable side-effect profile. In the postoperative setting after dental or orthopedic surgery, studies have shown less nausea and constipation. It has also been suggested a lower frequency of pruritus compared with oxycodone, but no difference in central nervous system symptoms such as sleepiness or dizziness. The most dangerous side-effect from opioids is respiratory depression with the potential of fatal outcome. The investigators have not found any publications from short-term postoperative pain management comparing the respiratory effect of tapentadol to the traditional opioids.

The aim of the study is to compare the analgesic effect and side-effects of this new analgesic, tapentadol, to the standard treatment to day, oxycodone, in the acute postoperative period after hysterectomy.

Conditions

• Pain, Postoperative
• Pain Uterus
• Pain, Acute
• Opioid Use
• Analgesics, Antipyretics, and Antirheumatics Causing Adverse Effects in Therapeutic Use
• Visceral Pain

Interventions

DRUG

Tapentadol

* Palexia depot 50 mg® (tapentadol depot 50 mg): Administered by the patient as oral premedication 1 hour before scheduled start of surgery. Palexia depot is repeated once after 12 hours. * Palexia 50 mg® (tapentadol 50 mg): Administered as oral rescue medicine. First possible administration in postoperative ward when the patient is awake and available for oral medication. Maximum 4 tablets/24-hour study period. Minimum 1 hour 15 minutes between tablets. The patient is instructed to take 1 tablet if pain is increasing and the minimum period since last tablet is exceeded.

DRUG

Oxycodone

* OxyContin 10 mg® (oxycodone extended-release 10 mg): Administered by the patient as oral premedication 1 hour before scheduled start of surgery. OxyContin is repeated once after 12 hours. * OxyNorm 10 mg® (oxycodone immediate-release 10 mg): Administered as oral rescue medicine. First possible administration in postoperative ward when the patient is awake and available for oral medication. Maximum 4 capsules/24-hour study period. Minimum 1 hour 15 minutes between capsules. The patient is instructed to take 1 tablet if pain is increasing and the minimum period since last tablet is exceeded.

Sponsors & Collaborators

• Oslo University Hospital

  lead OTHER

Principal Investigators

• Harald Lenz, MD, PhD · Oslo University Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-12-04

Primary Completion

2019-02-28

Completion

2019-02-28

Countries

• Norway

Study Locations