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Journal ArticleDOI

Investigations Into the Drug-Drug Interaction Potential of Tapentadol in Human Liver Microsomes and Fresh Human Hepatocytes

01 Jan 2008-Drug Metabolism Letters (Drug Metab Lett)-Vol. 2, Iss: 1, pp 67-75
TL;DR: The new analgesic tapentadol was evaluated for induction and inhibition of several cytochrome P450 enzymes in vitro, and protein binding was assessed.
Abstract: The new analgesic tapentadol was evaluated for induction and inhibition of several cytochrome P450 enzymes in vitro, and protein binding was assessed. It was concluded that no clinically relevant drug-drug interactions are likely to occur through either mechanism.
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Journal ArticleDOI
TL;DR: In this article, the authors evaluated the long-term safety and tolerability of tapentadol extended release (ER) in patients with chronic knee or hip osteoarthritis pain or low back pain.
Abstract: Background: Tapentadol is a novel, centrally acting analgesic with 2 mechanisms of action: µ-opioid receptor agonism and norepinephrine reuptake inhibition. This randomized, open-label phase 3 study (ClinicalTrials.gov Identifier: NCT00361504) assessed the long-term safety and tolerability of tapentadol extended release (ER) in patients with chronic knee or hip osteoarthritis pain or low back pain. Methods: Patients were randomized 4:1 to receive controlled, adjustable, oral, twice-daily doses of tapentadol ER (100 to 250 mg) or oxycodone HCl controlled release (CR; 20 to 50 mg) for up to 1 year. Efficacy evaluations included assessments at each study visit of average pain intensity (11-point numerical rating scale) over the preceding 24 hours. Treatment-emergent adverse events (TEAEs) and discontinuations were monitored throughout the study. Results: A total of 1,117 patients received at least 1 dose of study drug. Mean (standard error) pain intensity scores in the tapentadol ER and oxycodone CR groups, respectively, were 7.6 (0.05) and 7.6 (0.11) at baseline and decreased to 4.4 (0.09) and 4.5 (0.17) at endpoint. The overall incidence of TEAEs was 85.7% in the tapentadol ER group and 90.6% in the oxycodone CR group. In the tapentadol ER and oxycodone CR groups, respectively, TEAEs led to discontinuation in 22.1% and 36.8% of patients; gastrointestinal TEAEs led to discontinuation in 8.6% and 21.5% of patients. Conclusion: Tapentadol ER (100 to 250 mg bid) was associated with better gastrointestinal tolerability than oxycodone HCl CR (20 to 50 mg bid) and provided sustainable relief of moderate to severe chronic knee or hip osteoarthritis or low back pain for up to 1 year.

195 citations

Journal ArticleDOI
TL;DR: Universal, user-friendly educational tools are required to familiarise physicians with pain mechanisms, sensitisation and multi-mechanistic management, and also to improve communication between physicians and their pain patients, so that realistic expectations of treatment can be established.
Abstract: Background: Although chronic pain affects around 20% of adults in Europe and the USA, there is substantial evidence that it is inadequately treated. In June 2009, an international group of pain specialists met in Brussels to identify the reasons for this and to achieve consensus on strategies for improving pain management.

142 citations

Journal ArticleDOI
TL;DR: Tapentadol, a schedule-II controlled substance, is well-suited for pain conditions requiring a strong opioid component—and it has the benefit of greater gastrointestinal tolerability compared to classical strong opioids.
Abstract: Introduction: Many opioid analgesics share common structural elements; however, minor differences in structure can result in major differences in pharmacological activity, pharmacokinetic profile, and clinical efficacy and tolerability. Areas covered: This review compares and contrasts the chemistry, pharmacodynamics, pharmacokinetics, and CNS ‘functional activity' of tapentadol and tramadol, responsible for their individual clinical utilities. Expert opinion: The distinct properties of tapentadol and tramadol generate different CNS functional activities, making each drug the prototype of different classes of opioid/nonopioid analgesics. Tramadol's analgesia derives from relatively weak µ-opioid receptor (MOR) agonism, plus norepinephrine and serotonin reuptake inhibition, provided collectively by the enantiomers of the parent drug and a metabolite that is a stronger MOR agonist, but has lower CNS penetration. Tapentadol's MOR agonist activity is several-fold greater than tramadol's, with prominent norepi...

138 citations


Cites background from "Investigations Into the Drug-Drug I..."

  • ...Thus, the expected variability in effectiveness across a patient population is smaller, and CYP P450-based drug--drug interactions are less likely [39]....

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Journal ArticleDOI
TL;DR: Clinical trial evidence in acute and chronic non-cancer pain and neuropathic pain supports an opioid-sparing effect that reduces some of the typical opioid-related adverse effects for tapentadol, which results in improved tolerability and adherence to therapy for both the immediate- and extended-release formulations of tapENTadol.
Abstract: Several mechanisms can be proposed to explain an apparent synergistic analgesic action between μ-opioid and α2-adrenergic receptor agonists. Combining both effects in a single molecule eliminates the potential for drug-drug interactions inherent in multiple drug therapy. Tapentadol is the first US FDA-approved centrally acting analgesic having both μ-opioid receptor agonist and noradrenaline (norepinephrine) reuptake inhibition activity with minimal serotonin reuptake inhibition. This dual mode of action may make tapentadol particularly useful in the treatment of neuropathic pain. Having limited protein binding, no active metabolites and no significant microsomal enzyme induction or inhibition, tapentadol has a limited potential for drug-drug interactions. Clinical trial evidence in acute and chronic non-cancer pain and neuropathic pain supports an opioid-sparing effect that reduces some of the typical opioid-related adverse effects. Specifically, the reduction in treatment-emergent gastrointestinal adverse effects for tapentadol compared with equianalgesic pure μ-opioid receptor agonists results in improved tolerability and adherence to therapy for both the immediate- and extended-release formulations of tapentadol.

106 citations

Journal ArticleDOI
TL;DR: Tapentadol appears to be a well-tolerated and effective analgesic for the treatment of moderate to severe acute pain.

93 citations

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