Fentanyl withdrawal

Epidural analgesia is frequently used for lower extremity procedures and pain (e.g., knee surgery, labor pain, and some abdominal procedures). Intermittent bolus or continuous infusion of preservative-free opioids (morphine, hydromorphone, or fentanyl) and local anesthetics (bupivacaine) may be used for epidural analgesia. Opiates given by this route may cause pruritus that is relieved by naloxone. Adverse effects including respiratory depression, hypotension, and urinary retention may occur. When epidural routes are used in narcotic-dependent patients, systemic analgesics must also be used to prevent withdrawal since the opioid is not absorbed and remains in the epidural space. Doses of opioids used in epidural analgesia are 10 times less than intravenous doses, and intrathecal doses are 10 times less than epidural doses (i.e., 10 mg of IV morphine is equivalent to 1 mg epidural morphine and 0.1 mg of intrathecally administered morphine).45... 

TABLE 33-7. Sample Regimen of Clonidine for Withdrawal from All Opioids Except Methadone and Fentanyl (Duragesic ) Patches... 

For withdrawal from any opioid including fentanyl (Duragesic ) patches. Data from reference 21. 

Discontinuation - Upon system removal, it takes 17 hours or more for the fentanyl serum concentration to fall by 50% after system removal. Titrate the dose of the new analgesic based on the patient s report of pain until adequate analgesia has been attained. For patients requiring discontinuation of opioids, a gradual downward titration is recommended because it is not known at what dose level the opioid may be discontinued without producing the signs and symptoms of abrupt withdrawal. 

In a 40-month-old boy a withdrawal syndrome with neurological symptoms was accompanied by thrombocytosis, which peaked at 1230 x 109/1 (45). Recovery from the withdrawal syndrome was accompanied by normalization of the platelet count. The relevance of this change in platelet count was not clear. The boy had also been given fentanyl, and the authors suggested that the combination of midazolam with fentanyl should be used with caution. 

Ducharme MP, Munzenberger P. Severe withdrawal syndrome possibly associated with cessation of a midazolam and fentanyl infusion. Pharmacotherapy 1995 15(5) 665-8. 

Depression of neuromuscular function occurred 10 minutes after the introduction of desflurane 1.3% in a 32-year-old man who had previously received midazolam, fentanyl, and thiopental for induction. On withdrawal his neuromuscular function returned to baseline (11). 

Movement disorders after withdrawal of continuous infusion, without the characteristic autonomic signs of opioid withdrawal, have been reported in children (SEDA-17,80). Fentanyl-induced seizures have been reported (10). Life-threatening complications have included raised intracranial pressure and critically reducing cerebral perfusion (11). 

A 55-year-old man was given fentanyl 0.05 mg for treatment of left chest pain and immediately developed an acute confusional state and fluctuating tetraparesis (12). The symptoms abated 12 hours after withdrawal. A provocation test confirmed that fentanyl 0.1 mg was enough to cause myoclonic and dystonic reactions with increased agitation. Administration of intravenous naloxone 0.8 mg improved the condition. 

TTS fentanyl is not useful in acute or postoperative pain, because of the risk of respiratory depression due to the long delay and decay time, which do not allow adequate dose finding (44). Some patients have acute symptoms of morphine withdrawal, in spite of adequate pain control, when they are converted from morphine to transdermal fentanyl. The mechanism has not yet been determined (48,49). 

Davies AN, Bond C. Transdermal fentanyl and the opioid withdrawal syndrome. Palliat Med 1996 10(4) 348. 

Zenz M, Donner B, Strumpf M. Withdrawal symptoms during therapy with transdermal fentanyl (fentanyl TTS) J Pain Symptom Manage 1994 9(l) 54-5. 

An interaction of itraconazole with fentanyl has been reported in a 67-year-old man with cancer on a stable dose of transdermal fentanyl 50 micrograms/hour (88). He took itraconazole 200 mg bd for oropharyngeal candidiasis, and 24 hours later developed signs of opioid toxicity, which was reversed by withdrawal of fentanyl and replacement with short-acting opioids. 

This drug is a full agonist at opioid receptors. It has excellent oral bioavailability, analgesic activity equivalent to that of morphine, and a longer duration of action. Withdrawal signs on abrupt discontinuance are milder than those with morphine (A) Fentanyl... 

The concurrent use of two opioid agonists may have enhanced effects, although acute opioid tolerance may also occur. Opioids with mixed agonist/antagonist properties (e.g. buprenorphine, butorphanol, nalbuphine, pentazocine) may precipitate opioid withdrawal symptoms in patients taking pure opioid agonists (e.g. fentanyl, methadone, morphine). 

An isolated report describes neuropsychosis in a patient who was given intravenous ciclosporin and morphine. A single case report describes a patient taking ciclosporin who developed opioid withdrawal on stopping low-dose, transdermal fentanyL... 

A patient taking ciclosporin following a stem cell transplant developed opioid withdrawal symptoms when transdermal fentanyl 25 micrograms/hour was discontinued. The authors suggested that elevation of fentanyl levels due to inhibition of the cytochrome P450 isoenzyme CYP3A4 by ciclosporin during concurrent use may have been a possible cause, as withdrawal symptoms are not usual with this dose of fentanyl. However, they also note that other factors may have played a role, such as the physical and mental status of the patient after the stem cell... 

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