|Patient, Sex, Age, Pathology||Fentanyl Administration Duration Before the Onset of Withdrawal Symptoms||Drug Therapy, Dosages, and Problems Referred by the Patients During the First Visit to the Pain Therapy and Palliative Care Unit of the Milan NCI||Pain Intensity|
aon Fentanyl Patch
|Onset and Type of Withdrawal Symptoms||Switching to Oral Methadone||Adverse Effects and/or Withdrawal Symptoms after Switching to Oral Methadone||Pain Intensity|
aon Oral Methadone
|CA Male 60 Kidney cancer Bone and lung metastases||5 months||Fentanyl patch: 75 μg/h every day↑to 100 μg/h and then to 150 μg/h every day with no analgesic benefit. Then↓to 75 μg/h every day + SRM 10 p.r.n. Dexamethasone 4 mg/day orally||“Severe/very severe”||After 18 hours from the application of new patch: tremors, profuse sweating, palpitations and anguish, insomnia, general malaise||Methadone 10 mg t.i.d. for 3 days, then, over a month, progressive↑of methadone till 20 mg t.i.d. + 20 mg of SC morphine twice a day as rescue medication||No adverse effects, no withdrawal symptoms||“None/very mild” at rest. “Moderate” on movement and consid- ered as satis- factory pain control by the patient|
|TM Female 58 Adenoid-cystic carcinoma of the palate||4 months||Fentanyl 25 μg/h every 72 hours. In the previous week she had↑the patch to 50 μg/h. However, as she had complained of severe drowsiness, she went back to 25 μg/h till the first visit||“None” for the first 2 days with 25 μg/h patch.||After 48 hours from the application of a new patch: pain, profuse sweating, tremors, agitation, anxiety, general malaise||Methadone 5 mg t.i.d. After 5 days↓4 mg t.i.d. Within the 1st month↓till to 1 mg t.i.d.||No adverse effects, no withdrawal symptoms||“None”|
|MA Female 42 Submandibular adenoid-cystic carcinoma||18 days||Fentanyl 25 μg/h every 60 hours after switching from 50 mg/day of SRM due to nausea, vomiting and constipation||“Mild/very mild”||After 24–26 hours from the application of the new patch: asthenia, distress, anxiety, profuse sweating, and general malaise. Symptoms disappeared with 30 mg of SRM||Methadone 5 mg t.i.d. + 30 mg of SRM p.r.n., then↓methadone to 2 mg t.i.d. and no rescue dose of SRM was required||No adverse effects, no withdrawal symptoms||“None”|
- 1.Published data show that TF application intervals have to be shortened to 48–60 hours in about 25% of patients9.and to 48 hours in 11–43% of patients;10.this is in agreement with the TF pharmacokinetics. In our patients, the patch was renewed every 24–48 hours.
- 2.The application systems are designed to deliver fentanyl at a constant rate over a period of 72 hours. The rate-controlling membrane of the drug reservoir delivery system controls the rate of delivery of drug to the skin and influences about 50% of the rate of transdermal absorption.9.investigators noted considerable inter- and intrapatient variation with respect to the expected and actual rate of fentanyl delivered from the reservoir over the range 25 to 125 μg/h. Moreover, the observed variation in individual bioavailabilities may indicate that absorption varies between patients.
- 3.A large intersubject variability has been found regarding fentanyl concentration and other pharmacokinetic parameters. Individual differences account for most of the variability. The pharmacokinetic variability may be explained partly due to different skin permeability, regional blood flow, protein binding, and partly due to different clearance. After several sequential 3-day (72 h) application intervals, steady-state plasma fentanyl concentrations are achieved, which can be maintained for as long as the TF is renewed.
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