Fentanyl (transdermal system — patch) is a strong opioid analgesic, used to treat severe and persistent pain in opioid-tolerant patients when other options do not control the pain. The patch releases the medicine continuously over 72 hours. It has a high potential for dependence, abuse and overdose, and must only be used under close medical supervision.
Also known as: fentanil
Itraconazole (CYP3A4 inhibitor) increases fentanyl concentrations, with risk of sedation and respiratory depression.
Fentanyl is metabolised by CYP3A4 and itraconazole is a potent inhibitor of this enzyme: the itraconazole label classifies fentanyl as "not recommended during and 2 weeks after treatment with itraconazole", and the fentanyl label warns that co-administration with CYP3A4 inhibitors (such as the azoles) "can result in a fatal overdose of fentanyl", with prolonged or delayed respiratory depression. Avoid the combination whenever possible; if unavoidable, reduce the fentanyl dose, closely monitor sedation and respiratory rate (especially in the first days and in patients with sleep apnoea, obesity or lung disease) and keep naloxone available.
Fentanyl + itraconazole: itraconazole inhibits CYP3A4 and raises fentanyl levels, with a risk of fatal respiratory depression. Avoid (not recommended during and 2 weeks after itraconazole).
Fentanyl is mainly metabolised by CYP3A4; itraconazole inhibits this enzyme and reduces opioid clearance.
Sedation, respiratory rate and signs of opioid toxicity.
Respiratory depression requires temporary withdrawal and support with naloxone.
Reduce the fentanyl dose and monitor closely; avoid the combination if possible.
DailyMed/FDA (NIH/NLM) — approved Fentanyl label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e15a7e9b-8025-49dd-9a6d-bafcccf1959f ; approved Itraconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a4d555fa-787c-40fb-bb7d-b0d4f7318fd0 — with additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Fentanyl with sertraline increases the risk of serotonin syndrome.
The sertraline label explicitly lists fentanyl among the serotonergic drugs whose concomitant use increases the risk of serotonin syndrome; the fentanyl label reports cases of serotonin syndrome, potentially life-threatening, with concomitant use of serotonergic drugs, including SSRIs, and recommends immediately discontinuing fentanyl if the syndrome is suspected. Symptoms usually appear within hours to a few days of starting the combination: mental status changes (agitation, hallucinations, coma), autonomic instability (tachycardia, blood pressure lability, hyperthermia) and neuromuscular aberrations (hyperreflexia, incoordination, rigidity).
Fentanyl + sertraline: risk of serotonin syndrome (opioid + SSRI). Monitor symptoms; stop fentanyl if suspected.
Both raise CNS serotonin; fentanyl also lowers the seizure threshold that sertraline may influence.
Tremor, hyperreflexia, myoclonus, agitation, hyperthermia.
Severe serotonin syndrome requires immediate withdrawal of both drugs.
Monitor for signs of serotonin excess during the first weeks of combination.
DailyMed/FDA (NIH/NLM) — approved Fentanyl label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e15a7e9b-8025-49dd-9a6d-bafcccf1959f ; approved Sertraline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=91e24d17-ff0a-449c-9472-b9df74c98456 — with additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Alcohol potentiates the respiratory depression and sedation of fentanyl; simultaneous use may be fatal.
Alcohol is contraindicated during fentanyl treatment.
EMC-UK (MHRA) — approved Durogesic DTrans (Fentanyl) SmPC: https://www.medicines.org.uk/emc/product/6942/smpc
Fentanyl depresses the respiratory centre and is contraindicated in severe respiratory depression.
Contraindicated; use with caution and monitor respiration in chronic pulmonary disease.
EMC-UK (MHRA) — approved Durogesic DTrans (Fentanyl) SmPC: https://www.medicines.org.uk/emc/product/6942/smpc
Fever or external heat increases fentanyl release from the transdermal patch.
Advise avoiding heat sources (sauna, hot bath, sun) and monitor for overdose signs.
EMC-UK (MHRA) — approved Durogesic DTrans (Fentanyl) SmPC: https://www.medicines.org.uk/emc/product/6942/smpc
Fentanyl crosses the placenta and may cause neonatal withdrawal and respiratory depression near term.
Not recommended during pregnancy unless alternatives are unavailable.
Not recommended while nursing; wait 48–72 h after patch removal.
With chronic use, advise effective contraception.
EMC-UK (MHRA) — approved Durogesic (Fentanyl) SmPC: https://www.medicines.org.uk/emc/product/6942/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
High-potency mu opioid agonist (about 100x morphine), as a transdermal continuous-release system (72 h) for severe and persistent pain in opioid-tolerant patients. NOT indicated as an as-needed (prn) analgesic, acute or postoperative pain, nor in non-tolerant patients. Potentially fatal respiratory depression; metabolised by CYP3A4 (interactions with inhibitors/inducers). Half-life after removal ~20-27 h.
Opioid agonist that interacts predominantly with mu receptors, distributed in the brain, spinal cord and other tissues. Produces respiratory depression by direct action on brainstem respiratory centres, miosis, reduced GI motility, peripheral vasodilation and endocrine effects. Clinically significant histamine release is rare with fentanyl (up to 50 mcg/kg).
With the transdermal system, serum concentrations increase gradually over the first 72 hours of application. Heat over the patch increases mean exposure by 120% and maximum level by 61% — do not apply heat. After removal, serum concentrations decline gradually (continued skin absorption), falling ~50% in 20-27 hours.
Metabolised mainly by CYP3A4 (the major metabolite, norfentanyl, is inactive); about 75% of the dose is excreted in urine (mostly as metabolites) and 9% in faeces. Less than 10% is excreted as unchanged drug in urine. Hepatic impairment may reduce clearance — monitor.
Apparent half-life after IV infusion of approximately 7 hours (range 3-12 h); after patch removal serum concentrations fall ~50% in 20-27 hours (reflecting continued skin absorption, not drug elimination). In surgical patients the half-life is 3-12 h; in hepatic impairment 4-12 h.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
