FENTANYL-12

Clinical safety rating: avoid

CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.

How it works

Fentanyl is a synthetic opioid agonist primarily acting on mu-opioid receptors in the central nervous system, leading to analgesia, sedation, and respiratory depression.

What the body does with it

Metabolism	Primarily hepatic via CYP3A4 to norfentanyl and other metabolites; also undergoes N-dealkylation and hydroxylation.
Excretion	Primarily hepatic metabolism (N-dealkylation and hydroxylation) with <10% excreted unchanged in urine. Renal excretion accounts for ~75% of total elimination as metabolites; fecal excretion ~9%.
Half-life	Terminal elimination half-life is 3–12 hours (mean ~7 hours) in adults. Prolonged in elderly, hepatic impairment, and obesity (up to 20 hours). Context: half-life increases with continuous infusion (context-sensitive half-life).
Protein binding	Approximately 80–85% bound to plasma proteins, mainly to albumin and alpha-1-acid glycoprotein (AAG).
Volume of Distribution	Steady-state volume of distribution (Vdss) is 3–5 L/kg (range 1–6 L/kg). Large Vd indicates extensive tissue distribution (muscle, fat). Higher Vd in neonates and obesity.
Bioavailability	Transdermal: ~20–50% (variable due to skin factors). Intramuscular: ~100%. Oral transmucosal: ~50% (buccal absorption). Sublingual: ~50%. Intravenous: 100%.
Onset of Action	Transdermal: 12–24 hours for steady-state; acute effect onset is slow. Intravenous: 30–60 seconds; Intramuscular: 7–15 minutes; Oral transmucosal: 5–15 minutes. Note: Transdermal not for acute pain.
Duration of Action	Transdermal: 72 hours per patch (steady-state maintained). Intravenous: 30–60 minutes (single dose). Intramuscular: 1–2 hours. Clinical note: respiratory depression may outlast analgesia.

Classification & Brands

Dosing & administration

Transdermal: 12 mcg/hour applied every 72 hours. For opioid-tolerant patients only.

Dosage form	FILM, EXTENDED RELEASE
Renal impairment	CrCl less than 30 mL/min: Reduce dose by 50% and monitor for respiratory depression. No specific adjustment for CrCl >=30 mL/min.
Liver impairment	Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose by 50%. Child-Pugh Class C: Avoid use or reduce dose by 75% with close monitoring.
Pediatric use	Not recommended for pediatric patients due to risk of respiratory depression; use only in opioid-tolerant children >=2 years with careful titration, starting at 12 mcg/hour if body weight >=30 kg.
Geriatric use	Initiate at lowest dose (12 mcg/hour) and titrate slowly; increased sensitivity to respiratory depression and constipation.

Use during pregnancy

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

Clinical note

CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.

FDA category	Positive
Breastfeeding	Fentanyl is excreted into breast milk in low concentrations; M/P ratio approximately 0.23-0.5. Short-term use is generally considered compatible with breastfeeding. Monitor infant for sedation and respiratory depression.
Teratogenic Risk	First trimester: Limited human data; animal studies show increased risk of neural tube defects at high doses. Second/third trimester: Chronic use may cause fetal opioid dependence and neonatal abstinence syndrome. Avoid prolonged use near term due to risk of neonatal respiratory depression.

Warnings & precautions

■ FDA Black Box Warning

Risk of respiratory depression; Life-threatening respiratory depression in opioid-naive patients; Accidental exposure can cause fatal overdose; Concomitant use with benzodiazepines or CNS depressants increases risk; Neonatal opioid withdrawal syndrome with prolonged use during pregnancy.

Side Effect Profile

Common Effects	Constipation
Serious Effects

Absolute Contraindications

Hypersensitivity to fentanyl or any component; Significant respiratory depression; Acute or postoperative pain where opioid therapy is not indicated; Acute or severe bronchial asthma; Known or suspected paralytic ileus; Use in opioid-naive patients for transdermal patch.

Clinical Precautions

Precautions

Respiratory depression; Abuse potential; Addiction risk; Interaction with CNS depressants; Serotonin syndrome; Adrenal insufficiency; Hypotension; Bradycardia; Constipation; Withdrawal; Tolerance; Use in elderly/cachectic; Renal/hepatic impairment; Increased intracranial pressure; Biliary spasm.

Clinical Tips & Counseling

Drug interactions

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FENTANYL-12

Clinical safety rating: avoid

CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.

How it works

Fentanyl is a synthetic opioid agonist primarily acting on mu-opioid receptors in the central nervous system, leading to analgesia, sedation, and respiratory depression.

What the body does with it

Metabolism	Primarily hepatic via CYP3A4 to norfentanyl and other metabolites; also undergoes N-dealkylation and hydroxylation.
Excretion	Primarily hepatic metabolism (N-dealkylation and hydroxylation) with <10% excreted unchanged in urine. Renal excretion accounts for ~75% of total elimination as metabolites; fecal excretion ~9%.
Half-life	Terminal elimination half-life is 3–12 hours (mean ~7 hours) in adults. Prolonged in elderly, hepatic impairment, and obesity (up to 20 hours). Context: half-life increases with continuous infusion (context-sensitive half-life).
Protein binding	Approximately 80–85% bound to plasma proteins, mainly to albumin and alpha-1-acid glycoprotein (AAG).
Volume of Distribution	Steady-state volume of distribution (Vdss) is 3–5 L/kg (range 1–6 L/kg). Large Vd indicates extensive tissue distribution (muscle, fat). Higher Vd in neonates and obesity.
Bioavailability	Transdermal: ~20–50% (variable due to skin factors). Intramuscular: ~100%. Oral transmucosal: ~50% (buccal absorption). Sublingual: ~50%. Intravenous: 100%.
Onset of Action	Transdermal: 12–24 hours for steady-state; acute effect onset is slow. Intravenous: 30–60 seconds; Intramuscular: 7–15 minutes; Oral transmucosal: 5–15 minutes. Note: Transdermal not for acute pain.
Duration of Action	Transdermal: 72 hours per patch (steady-state maintained). Intravenous: 30–60 minutes (single dose). Intramuscular: 1–2 hours. Clinical note: respiratory depression may outlast analgesia.

Classification & Brands

Dosing & administration

Transdermal: 12 mcg/hour applied every 72 hours. For opioid-tolerant patients only.

Dosage form	FILM, EXTENDED RELEASE
Renal impairment	CrCl less than 30 mL/min: Reduce dose by 50% and monitor for respiratory depression. No specific adjustment for CrCl >=30 mL/min.
Liver impairment	Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose by 50%. Child-Pugh Class C: Avoid use or reduce dose by 75% with close monitoring.
Pediatric use	Not recommended for pediatric patients due to risk of respiratory depression; use only in opioid-tolerant children >=2 years with careful titration, starting at 12 mcg/hour if body weight >=30 kg.
Geriatric use	Initiate at lowest dose (12 mcg/hour) and titrate slowly; increased sensitivity to respiratory depression and constipation.

Use during pregnancy

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

Clinical note

CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.

FDA category	Positive
Breastfeeding	Fentanyl is excreted into breast milk in low concentrations; M/P ratio approximately 0.23-0.5. Short-term use is generally considered compatible with breastfeeding. Monitor infant for sedation and respiratory depression.
Teratogenic Risk	First trimester: Limited human data; animal studies show increased risk of neural tube defects at high doses. Second/third trimester: Chronic use may cause fetal opioid dependence and neonatal abstinence syndrome. Avoid prolonged use near term due to risk of neonatal respiratory depression.

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Common Effects	Constipation
Serious Effects