FENTANYL-12
Clinical safety rating: avoid
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
Fentanyl is a synthetic opioid agonist primarily acting on mu-opioid receptors in the central nervous system, leading to analgesia, sedation, and respiratory depression.
| 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. |
| Molecular Weight | 336.47 |
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. |
| 1st trimester | Use only if clearly needed; risk of neural tube defects with prolonged use in early pregnancy. |
| 2nd trimester | Use only if clearly needed; may cause fetal dependence with chronic use. |
| 3rd trimester | Avoid prolonged use; risk of neonatal opioid withdrawal syndrome and respiratory depression at birth. |
Clinical note
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
| FDA category | Positive |
| Placental transfer | Rapidly crosses the placenta; detected in fetal plasma within minutes of maternal administration. |
| Breastfeeding |
■ 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.
| Common Effects | Constipation |
| Serious Effects |
Hypersensitivity to fentanyl or any componentSignificant respiratory depressionAcute or severe bronchial asthmaKnown or suspected gastrointestinal obstructionConcurrent use of MAOIs or within 14 days
| 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. |
| Food/Dietary |
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| Fentanyl enters breast milk in low amounts; use with caution, monitor infant for sedation and respiratory depression. |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| Fetal Monitoring | Monitor maternal respiratory rate, oxygen saturation, sedation level. For fetal assessment, monitor fetal heart rate and uterine activity if used during labor. Prolonged use requires neonatal monitoring for withdrawal. |
| Fertility Effects | Opioids may alter sex hormone levels, potentially impairing fertility in both sexes. Reversible upon discontinuation. No specific studies in humans for fentanyl. |
| Avoid alcohol and other CNS depressants (benzodiazepines, sedatives) as they increase risk of severe sedation and respiratory depression. Grapefruit juice may increase fentanyl levels via CYP3A4 inhibition; limit consumption. No specific food restrictions for fentanyl alone. |
| Clinical Pearls | FENTANYL-12 is a 12 mcg/hour transdermal fentanyl patch indicated for opioid-tolerant patients with chronic pain requiring around-the-clock opioid therapy. Do not use in opioid-naive patients. Apply to non-irritated, non-hairy skin on upper torso. Avoid heat sources (heating pads, hot baths) as they increase absorption rate. Monitor for respiratory depression, especially in elderly or cachectic patients. Onset of action is 12-24 hours after first application; titrate no sooner than every 72 hours. Dispose of used patches by folding adhesive sides together and flushing down toilet. |
| Patient Advice | Apply patch to clean, dry, non-hairy skin on chest, back, or arm. Avoid irritated skin. · Wash hands after handling the patch to prevent accidental exposure. · Do not cut or damage the patch; it releases medication over 72 hours. · Keep away from children and pets; accidental exposure can be fatal. · Do not expose patch to direct heat sources like heating pads, electric blankets, or hot tubs. · Do not suddenly stop using the patch; withdrawal symptoms may occur. Consult doctor before discontinuing. · Store used patches safely; fold sticky sides together and flush down toilet immediately. · Seek emergency help if you experience difficulty breathing, slow breathing, or extreme drowsiness. |