DURAGESIC-25

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DURAGESIC-25 (DURAGESIC-25).

How it works

Fentanyl is a mu-opioid receptor agonist that produces analgesia and sedation by mimicking endogenous opioids in the central nervous system.

What the body does with it

Metabolism	Primarily metabolized via CYP3A4 to norfentanyl (major inactive metabolite) and other minor metabolites.
Excretion	Renal (75% as metabolites, <10% unchanged); fecal (9%)
Half-life	Terminal elimination half-life 22-25 hours (range 13-31 h) after 72-h transdermal application; prolonged in elderly, hepatic or renal impairment
Protein binding	~80-85% bound to plasma proteins (mainly albumin, also alpha-1-acid glycoprotein)
Volume of Distribution	6-10 L/kg (large, indicating extensive tissue distribution; Vd 6.4 L/kg in adults)
Bioavailability	Transdermal: ~92% absolute bioavailability (fentanyl absorbed through skin; compared to IV administration)
Onset of Action	Transdermal: 12-24 hours to achieve steady-state; initial analgesia may require 12-24 h after first application
Duration of Action	Transdermal: 72 hours (steady-state maintained during wear; residual absorption continues up to 24 h after removal)

Classification & Brands

Dosing & administration

Apply 25 mcg/hour transdermally every 72 hours; initial dose in opioid-naive patients: 25 mcg/hour is not recommended; use lower strength or immediate-release opioid first.

Dosage form	FILM, EXTENDED RELEASE
Renal impairment	For GFR 10-50 mL/min: start with 12 mcg/hour patch; for GFR <10 mL/min: avoid use due to accumulation of active metabolite; consider alternative therapy.
Liver impairment	Child-Pugh Class A or B: reduce starting dose by 50% (e.g., start with 12 mcg/hour); Child-Pugh Class C: avoid use or use with extreme caution and close monitoring.
Pediatric use	For children aged 2-16 years: initial dose based on opioid tolerance; typical starting dose for opioid-naive: 25 mcg/hour transdermal patch every 72 hours is not recommended; use lower strength or immediate-release opioids; refer to institutional guidelines.
Geriatric use	Start at lowest available strength (12 mcg/hour) and titrate cautiously; monitor for respiratory depression and constipation; avoid in frail elderly if possible.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for DURAGESIC-25 (DURAGESIC-25).

Breastfeeding	Fentanyl is excreted in breast milk; M/P ratio approximately 1.0. Limited data suggest low infant exposure with maternal therapeutic doses, but risk of sedation/respiratory depression in infants. Use with caution; monitor infant for drowsiness and feeding difficulties.
Teratogenic Risk	First trimester: Limited human data; animal studies show increased risk of malformations at high doses. Second/third trimester: Prolonged use may cause neonatal opioid withdrawal syndrome (NOWS) and respiratory depression at birth. Avoid unless benefits outweigh risks.

Warnings & precautions

■ FDA Black Box Warning

WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF DURAGESIC. Ensure accuracy when prescribing, dispensing, and administering DURAGESIC. Dosage errors can result in accidental overdose or death. Concomitant use with CYP3A4 inhibitors, potent CYP3A4 inducers, or the cessation of CYP3A4 inducers can cause fatal respiratory depression. DURAGESIC is contraindicated in opioid-non-tolerant patients and in acute or postoperative pain.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Opioid non-tolerant patients","Acute or short-term pain","Postoperative pain","Significant respiratory depression","Acute or severe bronchial asthma","Known or suspected gastrointestinal obstruction","Known hypersensitivity to fentanyl or any component of the system"]

Clinical Precautions

Precautions

["Life-threatening respiratory depression","Accidental exposure to children","Neonatal opioid withdrawal syndrome","Risks from concomitant use with benzodiazepines or other CNS depressants","Interaction with alcohol","Adrenal insufficiency","Hypotension and bradycardia","Severe hypotension","Risks in patients with gastrointestinal obstruction","Seizures in patients with seizure disorders","Life-threatening QT prolongation at high doses"]

Clinical Tips & Counseling

Drug interactions

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DURAGESIC-25

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DURAGESIC-25 (DURAGESIC-25).

How it works

Fentanyl is a mu-opioid receptor agonist that produces analgesia and sedation by mimicking endogenous opioids in the central nervous system.

What the body does with it

Metabolism	Primarily metabolized via CYP3A4 to norfentanyl (major inactive metabolite) and other minor metabolites.
Excretion	Renal (75% as metabolites, <10% unchanged); fecal (9%)
Half-life	Terminal elimination half-life 22-25 hours (range 13-31 h) after 72-h transdermal application; prolonged in elderly, hepatic or renal impairment
Protein binding	~80-85% bound to plasma proteins (mainly albumin, also alpha-1-acid glycoprotein)
Volume of Distribution	6-10 L/kg (large, indicating extensive tissue distribution; Vd 6.4 L/kg in adults)
Bioavailability	Transdermal: ~92% absolute bioavailability (fentanyl absorbed through skin; compared to IV administration)
Onset of Action	Transdermal: 12-24 hours to achieve steady-state; initial analgesia may require 12-24 h after first application
Duration of Action	Transdermal: 72 hours (steady-state maintained during wear; residual absorption continues up to 24 h after removal)

Classification & Brands

Dosing & administration

Apply 25 mcg/hour transdermally every 72 hours; initial dose in opioid-naive patients: 25 mcg/hour is not recommended; use lower strength or immediate-release opioid first.

Dosage form	FILM, EXTENDED RELEASE
Renal impairment	For GFR 10-50 mL/min: start with 12 mcg/hour patch; for GFR <10 mL/min: avoid use due to accumulation of active metabolite; consider alternative therapy.
Liver impairment	Child-Pugh Class A or B: reduce starting dose by 50% (e.g., start with 12 mcg/hour); Child-Pugh Class C: avoid use or use with extreme caution and close monitoring.
Pediatric use	For children aged 2-16 years: initial dose based on opioid tolerance; typical starting dose for opioid-naive: 25 mcg/hour transdermal patch every 72 hours is not recommended; use lower strength or immediate-release opioids; refer to institutional guidelines.
Geriatric use	Start at lowest available strength (12 mcg/hour) and titrate cautiously; monitor for respiratory depression and constipation; avoid in frail elderly if possible.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for DURAGESIC-25 (DURAGESIC-25).

Breastfeeding	Fentanyl is excreted in breast milk; M/P ratio approximately 1.0. Limited data suggest low infant exposure with maternal therapeutic doses, but risk of sedation/respiratory depression in infants. Use with caution; monitor infant for drowsiness and feeding difficulties.
Teratogenic Risk	First trimester: Limited human data; animal studies show increased risk of malformations at high doses. Second/third trimester: Prolonged use may cause neonatal opioid withdrawal syndrome (NOWS) and respiratory depression at birth. Avoid unless benefits outweigh risks.