A comparison between the administration of oral prolonged-release oxycodone-naloxonee and transdermal fentanyl in patients with moderate-to-severe cancer pain: a propensity score analysis

Abstract

BackgroundOpioids are the most important pharmacological treatment for moderate-to-severe cancer pain, but side effects limit their use. Transdermal fentanyl (TDF) and oral prolonged-release oxycodone-naloxone (OXN-PR) are effective in controlling chronic pain, with less constipation compared to other opioids. However, TDF and OXN-PR have never been directly compared.Patients and methodsCancer patients with moderate-to-severe chronic pain were consecutively enrolled in two prospective 28-day trials, received either TDF or OXN-PR, and were assessed at baseline and after 7, 14, 21, and 28 days. The primary endpoint was 28-day analgesic response rate (average pain intensity decrease ≥30% from baseline). Other outcome measures included opioid daily dose changes over time; need for adjuvant analgesics; number of switches; premature discontinuation; presence and severity of constipation; and other adverse drug reactions. To compare the efficacy and the safety of TDF and OXN-PR, we used the propensity score analysis to adjust for heterogeneity between the two patient groups.ResultsThree hundred ten out of 336 patients originally treated (119 TDF and 191 OXN-PR) were included in the comparative analysis. The amount of responders was comparable after TDF (75.3%) and OXN-PR administration (82.9%, not significant [NS]). The final opioid daily dose expressed as morphine equivalent was 113.6 mg for TDF and 44.5 mg for OXN-PR (p<0.0001). A daily opioid dose escalation >5% was less common after OXN-PR (19.3%) than after TDS administration (37.9%, p<0.0001). Opioid switches and discontinuation were similar in both groups. Severe constipation in the two groups was comparable (32.6% after TDF vs 24.7% after OXN-PR, NS). Nausea, vomiting, and dry mouth were significantly less frequent in the OXN-PR group than in the TDF group.ConclusionDespite a similar analgesic activity in moderate-to-severe cancer pain, OXN-PR is characterized by lower daily dosages, less need for drug escalation, and fewer side effects compared to TDF.

The role of peripherally acting mu-opioid receptor antagonists (PAMORA) in the treatment of constipation in palliative care

“…Jego stężenie w krążeniu centralnym jest bardzo małe, dlatego nie odwraca efektu analgetycznego równocześnie podawanego opioidu. Częstość zaparcia przy zastosowaniu preparatu oksykodonu i naloksonu jest podobna jak podczas leczenia fentanylem w systemie przezskórnym [19].…”

Uso de analgesia transdérmica en pacientes con necesidades paliativas

“…Se encuentran entre los beneficios del uso medicamentos transdermicos la administración controlada de opioides, mayor adherencia al tratamiento paliativo por parte de los pacientes, mayor beneficio del uso de buprenorfina transdérmica en comparación al uso de buprenorfina intravenosa en pacientes con cáncer, disminución del riesgo de sobredosificación, se minimizan los efectos adversos de los medicamentos, efectividad del uso de fentanilo transdérmico en pacientes con cáncer, lo que ayuda a controlar la intensidad del dolor y a mejorar la calidad de vida. La administración transdérmica y de opioides tópicos también se asocia con un menor riesgo de adicción en comparación con las vías oral y parenteral de la administración de analgésicos opioides 12,13,[17][18][19][20][21][22] .…”

“…El fentanilo transdérmico presenta una gran variabilidad en la absorción, esto en relación a la tasa de dosis estimada, el sitio anatómico de administración, el género y edad del paciente, el tipo de patología del cáncer representaron por ejemplo; más alto para el parche de 25 mcg/h comparado con el de 75 mcg/h, administración en el brazo en comparación con la pierna, en la población pediátrica podría tardar en alcanzar concentraciones séricas de fentanilo por lo cual podrían requerir dosis más altas 19 .…”

Opioid-induced constipation in palliative care: state of the art

“…Pain is one of the most experienced anxieties in cancer patients. Despite so many beliefs and fears about opioid use, old World Health Organization (WHO) publications¹ supported by recent international guidelines 2,3 for the pharmacological treatment of cancer pain in its moderate to severe stages, suggest that the use of opioids is the best therapy, evidencing the use of morphine 4 . Nevertheless, side effects such as opioid-induced constipation deserve highlighting 5,6 .…”

“…Research has reported that opioid-induced constipation is estimated at 40% to 70% of people receiving opioids. In contrast, there are constipation events in palliative care that are not related to the use of opioids, it is suggested that inappetence, nausea, and vomiting that reduce food intake, evolve to constipation 4,10,14 .…”