Absorption profile, safety, and tolerability of a 200 μg dose of fentanyl buccal tablet (FBT) in opioid-tolerant cancer patients with or without oral mucositis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9053-9053
Author(s):  
L. Shaiova ◽  
J. G. Jiang ◽  
M. Darwish
Keyword(s):  
Cancer Patients ◽  
Oral Mucositis ◽  
Plasma Concentrations ◽  
Application Site ◽  
Maximum Plasma ◽  
Absorption Profile ◽  
Open Label ◽  
Fentanyl Buccal Tablet ◽  
Buccal Tablet ◽  
Study Results

9053 Background: Fentanyl buccal tablet (FBT) is an effervescent formulation of fentanyl indicated for the management of breakthough pain in opioid-tolerant cancer patients. This open-label study investigated the absorption profile, safety, and tolerability of FBT in cancer patients with or without oral mucositis. Methods: Patients self-administered a single 200 μg dose of FBT. Pharmacokinetic assessments, oral mucosal examinations, and measurements of vital signs were performed at intervals of up to 8 hours following FBT placement. Adverse events (AEs) were monitored throughout the study. Results: 16 patients (8 with, 8 without mucositis) received FBT and completed the study. Mucositis was mild (functional/symptomatic grade 1 for 7 patients, grade 2 for 1 patient; clinical grade 1 for all patients). The absorption profile of FBT was similar in patients with and without mucositis. Mean±SD Cmax values were 1.25±0.78 ng/mL and 1.24±0.77 ng/mL in patients with or without mucositis, respectively. Maximum plasma concentrations of fentanyl were achieved rapidly, and were not significantly different in the two groups: median (range) tmax 25.0 (15.0–45.0) min in patients with mucositis, 22.5 (10.0–121.0) min in patients without (p=0.79). FBT was well tolerated; 4 patients experienced =1 treatment-emergent AE. Dizziness (mild) was reported by 1 patient in each group, and resolved. One patient in each group experienced a treatment-related AE (dizziness). There were no deaths, serious AEs, or withdrawals due to AEs. No application site AEs or changes in oral mucosal assessments were reported. Conclusions: The absorption profile of FBT was similar in patients with or without oral mucositis, which suggests that dose adjustment of FBT is not required when mild oral mucositis is present. FBT was generally safe and well tolerated, and not associated with adverse changes in the oral mucosa. Further studies in patients with grade 3–4 mucositis are warranted. No significant financial relationships to disclose.

scholarly journals Breakthrough Pain (BTP) in Opioid-Tolerant Cancer Patients: A Pan-European Open-Label Multicentre Study with Fentanyl Buccal Tablet (FBT)

2012 ◽  
Vol 23 ◽  
pp. ix518-ix519
Author(s):  
S. Mercadante ◽  
A. Davies ◽  
J. Jarosz ◽  
U.R. Kleeberg ◽  
T. O'Brien ◽  
...  
Keyword(s):  
Multicentre Study ◽  
Cancer Patients ◽  
Breakthrough Pain ◽  
Open Label ◽  
Fentanyl Buccal Tablet ◽  
Buccal Tablet

A double-blind, randomized, placebo-controlled study of fentanyl buccal tablet (FBT) in opioid-tolerant patients with chronic cancer pain and breakthrough pain

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9057-9057
Author(s):  
N. Slatkin ◽  
F. Xie ◽  
T. Segal ◽  
J. Messina
Keyword(s):  
Breakthrough Pain ◽  
Study Drug ◽  
Controlled Study ◽  
Application Site ◽  
Open Label ◽  
Post Dose ◽  
Double Blind ◽  
Patients With Cancer ◽  
Fentanyl Buccal Tablet ◽  
Buccal Tablet

9057 Background: Episodes of cancer-related breakthrough pain (BTP) often peak in intensity in minutes. Pain relief with traditional, short-acting oral opioids is often not achieved for =30 min. Fentanyl buccal tablet (FBT) has a rapid onset of analgesia. This double- blind, randomized, placebo-controlled study evaluated the efficacy and safety of FBT in opioid-tolerant patients with cancer and BTP. Methods: After open-label titration to establish a successful dose of FBT, patients were randomized to prespecified, double-blinded sequences of 10 tablets (7 FBT, 3 placebo). Pain intensity (PI) was assessed from 5 to 120 min post dose. The primary efficacy measure was the sum of PI differences (PIDs) for the first 60 min (SPID60); secondary measures included PIDs, =33% and =50% improvements in PI, and global medication performance (GMP). Use of supplemental BTP medication and adverse events (AEs) were reported. Results: 129 patients were enrolled; 87/125 treated (70%) identified an effective FBT dose and entered the double-blind phase. SPID60 significantly favored FBT vs placebo (mean±SEM, 9.7±0.63 vs 4.9±0.50; p<0.0001). PID differed significantly vs placebo at 10 min (mean±SEM, 0.9±0.09 vs 0.5±0.09; p<0.0001) and at all time points through 2 hr (p<0.0001). Improvements in PI of =33% and =50% from baseline occurred in a larger proportion of episodes following FBT vs placebo from 10 min (16% vs 10% and 7% vs 4%, respectively; p<0.05) through 2 hr (74% vs 38% and 66% vs 28%; p<0.0001). Ratings of GMP were superior for FBT vs placebo at 60 and 120 min (p<0.0001). Supplemental opioids were required for approximately 3 times more BTP episodes following placebo compared with FBT. AEs were typical for opioids, e.g. nausea (13%), dizziness (11%), fatigue (8%), and constipation (6%). Application site-related AEs occurred in 12 patients (10%). A total of 11/125 (9%) patients had =1 serious AE; these were considered not/unlikely to be related to study drug. Conclusions: FBT was effective and well tolerated in the management of BTP in opioid-tolerant patients with cancer-related pain, with an early onset of analgesia and a sustained duration of effect. No significant financial relationships to disclose.

Absorption of Fentanyl from Fentanyl Buccal Tablet in Cancer Patients With or Without Oral Mucositis

2007 ◽  
Vol 27 (9) ◽  
pp. 605-611 ◽  
Author(s):  
Mona Darwish ◽  
Mary Kirby ◽  
Philmore Robertson ◽  
William Tracewell ◽  
John G Jiang
Keyword(s):  
Cancer Patients ◽  
Oral Mucositis ◽  
Fentanyl Buccal Tablet ◽  
Buccal Tablet

scholarly journals Safety and Tolerability of Luliconazole Solution 10-Percent in Patients with Moderate to Severe Distal Subungual Onychomycosis

2013 ◽  
Vol 57 (6) ◽  
pp. 2684-2689 ◽  
Author(s):  
T. Jones ◽  
A. Tavakkol
Keyword(s):  
Clinical Laboratory ◽  
Plasma Concentrations ◽  
Systemic Exposure ◽  
Application Site ◽  
Maximum Plasma ◽  
Open Label ◽  
Study Objective ◽  
Once Daily ◽  
Time Points ◽  
Limit Of Quantitation

ABSTRACTThe study objective was to evaluate the safety, tolerability, systemic exposure, and pharmacokinetics (PK) of 10% luliconazole solution (luliconazole) when topically applied once daily to all 10 toenails and periungual areas in patients with moderate to severe distal subungual onychomycosis. In this single-center, open-label study, 24 patients applied 20 mg/ml of luliconazole (twice the clinical dose) for 29 days with a 7-day follow-up. Complete PK profiles were determined on days 1, 8, 15, and 29. Safety/tolerability assessments included application site reactions, adverse events, vital signs, clinical laboratory findings, and electrocardiograms. Mean luliconazole plasma concentrations remained around the lower limit of quantitation (0.05 ng/ml) and were comparable on days 8, 15, and 29 (range, 0.063 to 0.090 ng/ml), suggesting steady state occurred by day 8. Every patient had undetectable plasma luliconazole levels for at least 11% of the time points, and 12 of the 24 patients had undetectable levels for at least 70% of the time points. The maximum plasma concentration of luliconazole (Cmax) observed in any patient was 0.314 ng/ml and the maximum area under the concentration-time curve from 0 to 24 h (AUC0–24) was 4.34 ng · h/ml. Five patients (21%) had measureable luliconazole levels in the plasma 7 days after the last dose. The median concentration of luliconazole in the nail at this time point was 34.65 mg/g (from 42 of 48 collected toenail samples). There was one mild incidence of skin erythema on day 5 that resolved on day 8, there were no reports of drug-induced systemic side effects, and there was no evidence of QT prolongation. Luliconazole, when applied once daily to all 10 fungus-infected toenails for 29 days, is generally safe and well tolerated and results in significant accumulation of drug in the nail. Systemic exposure is very low, with no evidence of drug accumulation.

Phase I/IIa, randomized, open-label, drug-drug interaction study of trabectedin and rifampin in patients with advanced cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13512-e13512 ◽  
Author(s):  
Arthur P. Staddon ◽  
Trilok V. Parekh ◽  
Roland Elmar Knoblauch ◽  
Chi Keung ◽  
Apexa Bernard ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Locally Advanced ◽  
Plasma Concentrations ◽  
Systemic Exposure ◽  
Maximum Plasma ◽  
Metabolic Clearance ◽  
Open Label ◽  
Time Curve ◽  
Elimination Half ◽  
Cyp3a4 Inducer

e13512 Background: Trabectedin (Yondelis; T) is a tetrahydroisoquinoline compound initially isolated from the marine tunicate, Ecteinascidia turbinata, and currently produced synthetically. It is primarily metabolized by the cytochrome P450 (CYP)3A4 enzyme. Thus, potent inducers or inhibitors of this enzyme may alter the plasma concentrations of T. This study assessed the effects of rifampin (R), a strong CYP3A4 inducer, on the pharmacokinetics (PK) and safety of T. Methods: In this 2-way crossover study, patients (≥18 years of age) with locally advanced or metastatic disease were randomized (1:1) to receive one of the 2 treatment sequences: sequence 1: R plus T followed 28 days later by T; sequence 2: T followed 28 days later by R plus T. During each sequence, R (600 mg/day) was administered for 6 consecutive days and T (1.3 mg/m2, IV) was administered over a 3 hour infusion. Dexamethasone (20 mg, IV) was administered before T administration. PK and safety of T were evaluated with and without coadministration of R. Results: Of the 11 enrolled patients, 8 were PK evaluable. Coadministration of R with T decreased mean maximum plasma concentration (Cmax) by approximately 22% and mean area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast) by approximately 31% (Table 1). Coadministration of R with T also resulted in 23% shorter elimination half-life. Overall, the safety profile of T was comparable when administered alone or with R. Conclusions: In comparison with T alone, coadministration of R resulted in reduced systemic exposure of T in these 8 patients, as measured by Cmax and AUClast. The coadministration of potent inducers of CYP3A4 with T may increase the metabolic clearance of T. Clinical trial information: NCT01273480. [Table: see text]

scholarly journals Pharmacokinetic Drug Interaction Study of Sorafenib and Morphine in Rats

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2172
Author(s):  
Agnieszka Karbownik ◽  
Danuta Szkutnik-Fiedler ◽  
Tomasz Grabowski ◽  
Anna Wolc ◽  
Joanna Stanisławiak-Rudowicz ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Kinase Inhibitor ◽  
Opioid Analgesic ◽  
Plasma Concentrations ◽  
Response To Therapy ◽  
Maximum Plasma ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Pharmacokinetic Drug Interaction ◽  
Pharmacokinetic Drug

A combination of the tyrosine kinase inhibitor—sorafenib—and the opioid analgesic—morphine—can be found in the treatment of cancer patients. Since both are substrates of P-glycoprotein (P-gp), and sorafenib is also an inhibitor of P-gp, their co-administration may affect their pharmacokinetics, and thus the safety and efficacy of cancer therapy. Therefore, the aim of this study was to evaluate the potential pharmacokinetic drug–drug interactions between sorafenib and morphine using an animal model. The rats were divided into three groups that Received: sorafenib and morphine (ISOR+MF), sorafenib (IISOR), and morphine (IIIMF). Morphine caused a significant increase in maximum plasma concentrations (Cmax) and the area under the plasma concentration–time curves (AUC0–t, and AUC0–∞) of sorafenib by 108.3 (p = 0.003), 55.9 (p = 0.0115), and 62.7% (p = 0.0115), respectively. Also, the Cmax and AUC0–t of its active metabolite—sorafenib N-oxide—was significantly increased in the presence of morphine (p = 0.0022 and p = 0.0268, respectively). Sorafenib, in turn, caused a significant increase in the Cmax of morphine (by 0.5-fold, p = 0.0018). Moreover, in the presence of sorafenib the Cmax, AUC0–t, and AUC0–∞ of the morphine metabolite M3G increased by 112.62 (p < 0.0001), 46.82 (p = 0.0124), and 46.78% (p = 0.0121), respectively. Observed changes in sorafenib and morphine may be of clinical significance. The increased exposure to both drugs may improve the response to therapy in cancer patients, but on the other hand, increase the risk of adverse effects.

Effect of fentanyl buccal tablet on pain-related anxiety: A 4-week open-label study among opioid-tolerant patients with chronic and breakthrough pain

2018 ◽  
Vol 7 (4) ◽  
pp. 297-308
Author(s):  
Lynn R. Webster, MD ◽  
John Messina, PharmD ◽  
Fang Xie, PhD ◽  
Srinivas Nalamachu, MD
Keyword(s):  
Breakthrough Pain ◽  
Anxiety Symptoms ◽  
Open Label ◽  
Serious Adverse Events ◽  
Fentanyl Buccal Tablet ◽  
Buccal Tablet ◽  
Titration Period ◽  
History Of ◽  
High Level ◽  
The Impact

Objective: To evaluate the effect of fentanyl buccal tablet (FBT) on pain-related anxiety in opioid-tolerant patients with chronic pain and breakthrough pain (BTP).Design: This study consisted of a screening visit, open-label titration period, and 4-week open-label treatment period.Setting: Thirty-one US study centers.Patients: Opioid-tolerant adults with chronic, persistent pain experiencing 1-4 BTP episodes per day at baseline. Two hundred eighteen patients were enrolled in this study; 180 completed the titration period; and 169 completed the treatment period.Intervention: Patients were treated with FBT (100-800 g) for BTP episodes for 4 weeks while continuing their around-the-clock opioid regimens.Main outcome measures: Change from baseline in the Pain Anxiety Symptoms Scale (PASS) total score at the final visit.Results: Based on a mean baseline PASS total score of 82.6, study patients had a high level of anxiety; 92 patients (42 percent) had a history of anxiety disorders. The change from baseline in PASS total score was not statistically significant (mean change, −1.6; p = 0.322). Numerical improvements were reported in some secondary measures (eg, Beck Depression Inventory total score [mean change, −1.1; p = 0.038]) and categorical measures (eg, Pain Flare Treatment Satisfaction, Patient Assessment of Function, and Clinician Assessment of Patient Function ratings). FBT was generally well tolerated, with no serious adverse events related to study drug.Conclusions: Four weeks of treatment with FBT did not reduce anxiety to a clinically meaningful extent, although improvement was reported in several secondary measures of functioning. Further research is needed to assess the impact of treatment for BTP on anxiety symptoms in opioid-tolerant patients with BTP.

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