The Influence of Low Salivary Flow Rates on the Absorption of a Sublingual Fentanyl Citrate Formulation for Breakthrough Cancer Pain

Davies, Andrew; Mundin, Gill; Vriens, Joanna; Webber, Katherine; Buchanan, Alison; Waghorn, Melanie

doi:10.1016/j.jpainsymman.2015.11.018

Cited by 18 publications

(7 citation statements)

References 23 publications

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“…Contrasting results were found in a study in patients with salivary gland hypofunction [ 30 ]. Moistening the mouth with water or pilocarpine hydrochloride (a cholinergic agonist), before taking sublingually delivered fentanyl, led to higher C max and shorter T max compared to the situation of xerostomia without moistening [ 30 ]. Our study results might be explained by moistening the mouth before every sublingual fentanyl administration.…”

Section: Discussioncontrasting

confidence: 71%

Pharmacokinetics of Sublingually Delivered Fentanyl in Head and Neck Cancer Patients Treated with Curatively Aimed Chemo or Bioradiotherapy

Kuip

Oldenmenger

Hoop

et al. 2018

Cancers

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Over 90% of patients treated for head and neck cancer with curatively aimed chemo or bioradiotherapy will develop painful mucositis and xerostomia. Sublingually delivered fentanyl (SDL) is a rapid acting opioid to treat breakthrough pain. It is unclear how SDL is absorbed by the mucosa of these patients. Therefore, the aim of this study was to investigate the effects of mucositis and xerostomia on the absorption of SDL. Thirteen patients who received chemo or bioradiotherapy (RT), were given a single dose of fentanyl: Before start of RT, 3 and 6 weeks after start of RT, and 6 weeks after finishing RT. Pharmacokinetic samples were taken. The primary endpoint was the relative difference (RD) between systemic exposure to fentanyl (area under the curve; AUC) at baseline (AUCbaseline) and fentanyl AUC in the presence of mucositis grade ≥2. The secondary endpoint was the RD between AUCbaseline and fentanyl AUC in the presence of xerostomia, which were analyzed by means of a paired t-test on log-transformed data. Mucositis resulted in a 12.7% higher AUC (n = 13; 95% CI: −10.7% to +42.2%, p = 0.29) compared to baseline levels and xerostomia resulted in a 22.4% lower AUC (n = 8; 95% CI: −51.9% to +25.3%, p = 0.25) compared to baseline levels. Mucositis grade ≥2 or xerostomia caused by chemo or bioradiotherapy does not significantly alter the systemic exposure to SDL. Patients with pain during and after chemo or bioradiotherapy may be safely treated with SDL.

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Section: Discussioncontrasting

confidence: 71%

Pharmacokinetics of Sublingually Delivered Fentanyl in Head and Neck Cancer Patients Treated with Curatively Aimed Chemo or Bioradiotherapy

Kuip

Oldenmenger

Hoop

et al. 2018

Cancers

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“…Of interest, INFS and FPNS provided the fastest meaningful pain relief, even though administered at relatively lower doses, possibly due to their faster analgesic effect. The presence of more severe grades of mucositis was associated to the use of non‐oral transmucosal preparations, such as nasal fentanyl and parenteral morphine, possibly because mucositis could preclude or limit the use of oral transmucosal medications, as local absorption could be problematic and drug availability more unpredictable (Davies et al, ). For example, SLF was used in higher doses in patients with mucositis.…”

Section: Discussionmentioning

confidence: 99%

Factors influencing the use of opioids for breakthrough cancer pain: A secondary analysis of the IOPS‐MS study

Mercadante

Adile

Masedu

et al. 2018

European Journal of Pain

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Background Controversies exist about the choice and the doses of opioid medication in breakthrough cancer pain (BTcP). Methods The aim was to assess factors influencing the use and the doses of opioids prescribed for BTcP. There was performed a secondary analysis of a national, multicentre study that involving 32 centres performed in patients having BTcP. Diagnosis of BTcP was based on a definite algorithm. Patients using opioids for background pain and for BTcP were selected. Average pain intensity and opioids used for background pain and BTcP, and adverse effects were assessed, as well as patient’s satisfaction and the grade of mucositis. Results The analysis was performed in 2,771 patients. Opioid doses given for BTcP were significantly associated with those given for background pain. No relationship between adverse effects and the use and the doses of opioids used for BTcP was found. Drugs and doses were not correlated to the grade of oral mucositis. Nasal fentanyl preparations provided the fastest meaningful pain relief in comparison with other fentanyl transmucosal preparations or morphine preparations (P = 0.000). The majority of patients were satisfied with opioid medications given for BTcP. Only 2.8% of patients reported adverse effects related to opioid medication used for BTcP. Age and gender were independently associated with dosages of some fentanyl products. Conclusions Opioids for BTcP were effective and safe in a large sample of cancer patients with different stages of disease. Doses of opioids proportional to doses used for background pain seem to guarantee both efficacy and safety. Significance The use of opioids for breakthough cancer pain was effective and safe in a large sample of advanced cancer patients recruited in different stages of disease and settings. Doses of opioids proportional to opioid doses used for background analgesia, seem to guarantee both effectiveness and safety.

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“…Our experience with patients with advanced cancer has been of an adequate clinical response with immediate release oral opioids, but there is a paucity of evidence on the response of BTP to commonly used oral opioids such as oral morphine, which has not been specifically tested for management of BTP in cancer population except as a comparator [18]. Transmucosal agents have an important role in the management of breakthrough cancer pain when traditional analgesics have failed, but they also carry the risk of common side effects like somnolence, nausea and dizziness, and sufficient saliva is required for adequate administration and delivery of such sublingual and buccal preparations [12,33]. Current evidence on majority of such transmucosal preparations comes from data obtained from pharmaceutical industry-sponsored randomized controlled trials and needs to be reviewed in this context [15].…”

Section: Discussionmentioning

confidence: 99%

Response to Oral Immediate-Release Opioids for Breakthrough Pain in Patients with Advanced Cancer with Adequately Controlled Background Pain

et al. 2018

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Background There is limited evidence about the response of breakthrough pain (BTP) to the most commonly used oral immediate‐release (IR) opioids. Our aim was to determine response rate to oral IR opioids for BTP control in patients with advanced cancer. Materials and Methods In this prospective study, palliative care outpatients, with advanced cancer and adequately managed background pain, were asked to complete a self‐administered survey. We assessed patients’ baseline demographics, pain characteristics, alcoholism (CAGE questionnaire), tobacco and substance abuse, and Edmonton Symptom Assessment Scores (ESAS). We determined the effectiveness of oral IR BTP opioids by using a 7‐point Likert scale ranging from “very ineffective” to “very effective.” “Effective” and “very effective” were defined a priori as a good response to IR opioids for BTP. Results Of 592 evaluable patients, 192 (32%) had background pain of ≤3 (ESAS pain scale 0–10). Among these 192 patients, 152 (79%) reported BTP, 143/152 (94%) took oral IR opioids for BTP, and 127/143 (89%) responded to a median dose of 10% of the total morphine equivalent daily dose. In univariate logistic regression analysis, younger age (odds ratio [OR], 0.94 per year; p = .008), higher ESAS scores for pain (OR, 1.32; p = .012), anxiety (OR, 1.24; p = .017), and dyspnea (OR, 1.31; p = .007) had statistically significant association with poor response to IR opioids for BTP. In multicovariate logistic regression, adjusted for age, a higher ESAS dyspnea score was significantly associated with poor response to oral IR opioids (OR, 1.44; p = .002). Conclusion The vast majority of patients with advanced cancer with adequately controlled background pain reported a good response to oral IR opioids for BTP, supporting their use in clinical practice. Implications for Practice Oral immediate‐release opioids are standard treatment for cancer breakthrough pain. However, information regarding treatment response to these commonly used opioids is limited. This study provides information that the vast majority of patients with advanced cancer, with adequately controlled background pain, reported good response to oral immediate release opioids for managing their breakthrough pain episodes. Results of this study support the use of conventional oral immediate release opioids that are relatively inexpensive and readily available for management of breakthrough pain in patients with advanced cancer.

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The Influence of Low Salivary Flow Rates on the Absorption of a Sublingual Fentanyl Citrate Formulation for Breakthrough Cancer Pain

Cited by 18 publications

References 23 publications

Pharmacokinetics of Sublingually Delivered Fentanyl in Head and Neck Cancer Patients Treated with Curatively Aimed Chemo or Bioradiotherapy

Pharmacokinetics of Sublingually Delivered Fentanyl in Head and Neck Cancer Patients Treated with Curatively Aimed Chemo or Bioradiotherapy

Factors influencing the use of opioids for breakthrough cancer pain: A secondary analysis of the IOPS‐MS study

Response to Oral Immediate-Release Opioids for Breakthrough Pain in Patients with Advanced Cancer with Adequately Controlled Background Pain

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