Revista nº 809

Duque et al. Tolerability of tapentadol prolonged-release therapeutics in patients with chronic pain · 32 · Actualidad Médica · Número 809 · Enero/Abril 2020 Páginas 31 a 34 INTRODUCTION Chronic pain was defined as persistent or recurrent pain lasting longer than 3 months. Its incidence and fre- quency increase with age, number of comorbidities, as well as the number of medications. 1 The pain is usually nociceptive, neuropathic or a mixture of the two. 8 Opioid analgesics are recommended by the World Health Orga- nization analgesic ladder for the treatment of moderate- to-severe pain. 2 Their main mechanism of analgesic action is the µ-opioid receptor agonism. 3 However, the use of opioid analgesics has adverse reactions difficult to control such as nausea, vomiting, and constipation and are also associated with phenomena of analgesic tolerance and drug dependence. 3 These factors may contribute to the abandonment of opioid analgesics therapeutics. For the- se reasons, achieving and maintaining the balance between analgesia and safety difficult. 9 Tapentadol hydrochloride is a centrally acting analgesic indicated for the treatment of chronic severe pain that acts in two ways: through the agonism of µ-opioid receptors, atte- nuating the upward transmission in the pain pathway; and by inhibiting the reuptake of norepinephrine, leaving more free norepinephrine in the downward pain pathway which allows modulation of the painful stimulus. 3-5 The µ-opioid receptor binding affinity of the drug was considerably lower that of morphine in vitro, although its analgesic potency in animal models was only two- or three- times lower than that of morphine, highlighting the con- tribution of noradrenaline reuptake inhibitor activity to its analgesic effect. 9 The dual mechanism of action of tapenta- dol and its prolonged-release (PR) formulation reduces the intakes per day and allows for fewer drug side effects than equianalgesic doses of opioids. 3,5,7 This might increase the therapeutic compliance in treating chronic pain of diverse etiologies. 3,4 This simplification of the therapeutic approach increases the patient’s adherence and compliance to the therapy. While tapentadol is a weak μ-opioid agonist, its use has several benefits: less opioid side-effects with equi- potent analgesia, 3,4 does not have active metabolites, does not induce hepatic cytochromes, nor has important binding to proteins. 3 In addition, tapentadol PR low risk for intole- rance and its low incidence of adverse reactions allows a faster dose titration, and hence, a faster and more effective pain control. 7 This study aimed to characterize the introduction and tolerability of tapentadol PR therapeutics in patients with chronic pain, who attended a hospital-based outpatient unit for chronic pain over a period of 8 months, by asses- sing the prevalence of treatment discontinuation and dose reduction, the main reasons for tapentadol PR discontinua- tion, and the time to treatment discontinuation for each of the main reasons. MATERIALS AND METHODS In this cross-sectional observational study, we exami- ned the medical records of outpatients who attended the Chronic Pain Unit in an eight-month period following the introduction of tapentadol PR therapeutics. Consecutive patients previously diagnosed with chronic pain (i.e., pain that persists beyond the usual course of an acute disease or after a reasonable time for healing to occur; this healing period typically can vary from 1 to 6 months) 6 were included in the study. Inclusion criteria were: being 18 years old or older, and having at least one prescription for tapentadol PR. Patients were excluded if they had missing data regarding dates of initiation and/or discontinuation of tapentadol LR therapeutics, or died. Collected demographic and medical variables were age, gender, and etiology of chronic pain (i.e. oncologic or non-oncologic). Data collection regarding the analgesic therapeutics included maximum daily dose and duration of tapentadol LR therapeutics, and existence of concomitant analgesic medication. The outcome measures for tolerability of tapentadol LR were: treatment discontinuation (stopping the use of tapentadol LR); dose reduction of tapentadol LR; main reasons for the discontinuation or dose reduction of tapentadol PR therapeutics (e.g., lack of analgesic effect, reduction of analgesic need, or intolerability because of ad- verse reactions such as gastrointestinal, nervous system, skin or general disorders); and time to treatment discontinuation for each of main reasons. Categorical data were summarized as number (percentage) and continuous data as mean ± stan- dard deviation (minimum-maximum) or median (minimum- maximum). The statistical software SPSS version 22.0 for Windows (SPSS, Chicago, IL) was used to analyze the data. This study conformed with the principles outlined in the Helsinki Declaration and was approved by the Ethics Committee of Centro Hospitalar Tondela-Viseu. RESULTS Out of 135 patients who were attending the outpatient unit and have been treated with tapentadol PR for chronic pain between March and November 2014, 8 patients were excluded. Seven patients were excluded because of incom- plete data, and one patient died. The demographic char- acteristics of the 127 patients included in our study were: mean age of 63.0 ± 13.6 (32-91) years old, and mostly female (72.4%, n = 92). The most common cause of chronic pain was non-oncologic (84.3%, n = 107). At study entry, most pa- tients had switched from opioids to tapentadol PR and main- tained concomitant analgesic medications (93.7%, n = 119), whereas 8 patients were taking tapentadol PR as the first- choice medication for the treatment of chronic pain. The (20.5%) patients discontinued tapentadol PR treatment and 5 (3.9%) patients reduced their dose. The most frequently reported reasons for tapendadol PR discontinuation were adverse reactions – nausea or vomiting (32.1%), constipation (19.2%), dizziness (19.2%) – and lack of analgesic effect (30.8%). Discussion. Prevalence of treatment discontinuation and adverse reactions associated with the use of tapenta- dol PR are similar to the ones previously reported. Further studies are needed to improve the management of chronic pain patients with tapentadol PR in an outpatient setting. Conclusion. Patients with chronic pain in our study discontinued their tapentadol PR treatment at a low per- centage. We found that the most frequent reason for discontinuation of tapentadol PR was gastrointestinal disorders, followed by lack of analgesic effect, and dizziness. Tapentadol PR appears to be a well-tolerated for the control of chronic pain in patients attending an outpatient unit. Funding: Grunenthal S.A. contributed with a grant to support Scientific Toolbox Consulting regarding medical writing services.