FENTANYL-100
Clinical safety rating: avoid
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
Fentanyl is a μ-opioid receptor agonist. It binds to μ-opioid receptors in the central nervous system, activating G-protein coupled receptor signaling (inhibition of adenylate cyclase, modulation of ion channels), leading to increased potassium conductance and decreased calcium influx, resulting in hyperpolarization and reduced neurotransmitter release. This produces analgesia, sedation, and respiratory depression.
| Metabolism | Primarily hepatic via CYP3A4, with minor contribution from CYP3A5. Major metabolites: norfentanyl (inactive), despropionylfentanyl. Approximately 10-25% excreted unchanged in urine. |
| Excretion | Primarily hepatic metabolism to inactive metabolites (norfentanyl, etc.); ~75% excreted in urine as metabolites, ~9% in feces, <10% unchanged in urine. |
| Half-life | Terminal elimination half-life: 2–4 hours in adults; prolonged in elderly, hepatic impairment, or continuous infusion (due to redistribution). |
| Protein binding | ~80–85% bound, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 3–8 L/kg (large Vd indicates extensive tissue distribution, especially to fat and muscle). |
| Bioavailability | Oral: <40% (first-pass metabolism); Buccal: ~50%; Intranasal: 50–90%; Transdermal: ~30–60% (steady state). |
| Onset of Action | IV: immediate (30 seconds to 1 minute); IM: 7–15 minutes; Transdermal: 12–24 hours for steady state; Buccal/Intranasal: 5–15 minutes. |
| Duration of Action | IV: 0.5–1 hour (analgesic); IM: 1–2 hours; Transdermal: 72 hours (patch); Buccal: 1–2 hours. Duration shorter with high doses due to redistribution. |
| Molecular Weight | 336.47 |
100 mcg intravenously every 1-2 hours as needed for pain; or 100 mcg intramuscularly every 1-2 hours; transdermal patch: 12-100 mcg/hour applied every 72 hours; buccal tablet: 100-200 mcg as a single dose for breakthrough pain.
| Dosage form | FILM, EXTENDED RELEASE |
| Renal impairment | GFR 30-50 mL/min: reduce dose by 25-50%; GFR 10-29 mL/min: reduce dose by 50-75% and extend dosing interval; GFR <10 mL/min: use with caution, consider alternative therapy; not removed by hemodialysis. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: reduce dose by 75% or use alternative; monitor for respiratory depression. |
| Pediatric use | Intravenous: 0.5-2 mcg/kg/dose every 2-4 hours; transmucosal: 5-15 mcg/kg for procedural analgesia; transdermal patch: not recommended in children <2 years; in older children, use lowest effective dose based on body weight and opioid tolerance. |
| Geriatric use | Start at 25-50% of adult dose; titrate slowly; avoid transdermal patch in opioid-naive elderly; monitor for delirium and respiratory depression; prefer intravenous or buccal routes with careful observation. |
| 1st trimester | Avoid unless clearly needed; may cause neural tube defects in early pregnancy; consider folic acid supplementation. |
| 2nd trimester | Use with caution; monitor for maternal respiratory depression and fetal heart rate variability. |
| 3rd trimester | Avoid prolonged use; risk of neonatal respiratory depression and withdrawal syndrome; use only if maternal benefit outweighs fetal risk. |
Clinical note
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
| FDA category | Positive |
| Placental transfer | Fentanyl readily crosses the placenta; rapid transfer with peak fetal levels within 5 minutes of maternal administration. Fetal/maternal ratio approximately 0.3-0.4. |
■ FDA Black Box Warning
Risk of respiratory depression, which may be fatal, especially in opioid-naive patients and when used in higher doses or with other CNS depressants. Risk of accidental exposure leading to fatal overdose. Risk of abuse, misuse, addiction, and diversion. Concomitant use with benzodiazepines or other CNS depressants may result in profound sedation, respiratory depression, coma, and death. Avoid use in patients with known or suspected paralytic ileus. Use only in opioid-tolerant patients for outpatient chronic pain management.
| Common Effects | Constipation |
| Serious Effects |
Hypersensitivity to fentanyl or any component of the formulationConcurrent use of monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI useRespiratory depression without resuscitative equipment or monitoringAcute or severe bronchial asthma in an unmonitored settingParalytic ileusMyasthenia gravisKnown or suspected gastrointestinal obstruction
| Precautions | Respiratory depression: monitor closely, especially during initiation and dose titration. Abuse and addiction potential: fentanyl is a Schedule II controlled substance. Life-threatening respiratory depression with concurrent use of benzodiazepines or CNS depressants. Serotonin syndrome when coadministered with serotonergic drugs. Adrenal insufficiency. Severe hypotension, including orthostatic hypotension. Risk of seizures in patients with seizure disorders. Avoid use in patients with head injury or increased intracranial pressure. Biliary tract spasm. Use in pregnancy may cause neonatal opioid withdrawal syndrome. Avoid abrupt discontinuation to prevent withdrawal. Must be used only in opioid-tolerant patients for outpatient management. |
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| Breastfeeding |
| Fentanyl enters breast milk in low concentrations; however, due to risk of infant sedation and respiratory depression, use only if clearly needed and monitor infant for adverse effects. Short-term use is generally considered compatible with breastfeeding. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: Limited human data; animal studies show teratogenic effects at high doses. Second and third trimesters: Chronic use may lead to neonatal opioid withdrawal syndrome; no structural malformations reported at therapeutic doses. |
| Fetal Monitoring | Monitor maternal respiratory rate, oxygen saturation, level of consciousness, and pain scores. Fetal monitoring includes heart rate and variability; assess for signs of withdrawal in neonates after prolonged exposure. |
| Fertility Effects | Animal studies show impaired fertility at high doses (e.g., reduced implantation). Human data limited; chronic use may cause menstrual irregularities and decreased libido. |
| Food/Dietary | Avoid or limit alcohol and grapefruit juice as they can potentiate respiratory depression and alter fentanyl metabolism. Maintain adequate hydration and fiber intake to prevent constipation. |
| Clinical Pearls | FENTANYL-100 transdermal patch is indicated only for opioid-tolerant patients with chronic pain requiring around-the-clock analgesia. Apply to non-irritated, non-hairy skin on upper torso or inner forearm; avoid heating pads, saunas, or sun exposure that increase absorption. Monitor for respiratory depression, especially in opioid-naive patients. Patches should be replaced every 72 hours; do not cut or damage the patch. Dispose of used patches by folding adhesive sides together and flushing down toilet. |
| Patient Advice | Apply the patch to clean, dry, hairless skin and press firmly for 30 seconds. · Do not expose the patch to direct heat sources (heating pads, hot tubs, electric blankets). · Keep away from children and pets; used patches must be flushed down toilet. · Do not drink alcohol or take other central nervous system depressants without consulting your doctor. · Report any difficulty breathing, extreme drowsiness, or confusion immediately. |