FENTANYL-75
Clinical safety rating: avoid
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
Fentanyl is a mu-opioid receptor agonist, producing analgesia and sedation by activating G-protein coupled opioid receptors in the central nervous system, leading to decreased neurotransmitter release and hyperpolarization of neurons.
| Metabolism | Primarily hepatic via CYP3A4 to norfentanyl (inactive), with minor contributions from CYP3A5; also undergoes N-dealkylation and hydroxylation. |
| Excretion | Renal: ~75% as metabolites (primarily norfentanyl) and ~10% unchanged; fecal: ~9%; biliary: minor. |
| Half-life | Terminal elimination half-life: 3-12 hours (mean ~7 hours); prolonged in elderly, hepatic impairment, or continuous infusion. |
| Protein binding | ~80-85% bound, primarily to alpha-1-acid glycoprotein and albumin. |
| Volume of Distribution | Vd: 3-8 L/kg (mean ~6 L/kg); large Vd indicates extensive tissue distribution. |
| Bioavailability | Transdermal: ~92%; transmucosal (oral): ~50%; buccal: ~65%; intranasal: ~70%; IM: ~100%. |
| Onset of Action | IV: almost immediate (30 seconds); IM: 7-15 minutes; transdermal: 12-24 hours to steady state. |
| Duration of Action | IV: 30-60 minutes (single dose); transdermal: 72 hours per patch; duration increases with accumulation. |
| Molecular Weight | 336.47 |
Apply 75 mcg/h transdermally every 72 hours for opioid-tolerant patients; not for acute pain. Rotate application site.
| Dosage form | FILM, EXTENDED RELEASE |
| Renal impairment | GFR <30 mL/min: reduce dose by 50% or use alternative; monitor for respiratory depression. Not recommended in GFR <15 mL/min. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use. |
| Pediatric use | Transdermal fentanyl is not recommended for pediatric patients under 2 years. For opioid-tolerant children 2-12 years: initiate at 25 mcg/h, titrate based on 24-hour opioid requirement. Monitor closely. |
| Geriatric use | Initiate at lowest dose (12.5 or 25 mcg/h) and titrate slowly; monitor for respiratory depression, hypotension, and constipation. Avoid in frail elderly. |
| 1st trimester | Avoid use during first trimester unless clearly needed; associated with neural tube defects and congenital malformations in animal studies, limited human data. |
| 2nd trimester | Use only if maternal benefit outweighs fetal risk; may cause fetal respiratory depression and withdrawal with prolonged use. |
| 3rd trimester | Avoid prolonged use or high doses near term due to risk of neonatal respiratory depression, withdrawal syndrome, and low Apgar scores. |
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; fetal concentrations can reach 70-100% of maternal plasma levels. Rapid transfer occurs within minutes of IV administration. |
■ FDA Black Box Warning
Risk of respiratory depression, especially during initiation or dose escalation; risk of opioid addiction, abuse, and misuse; risk of neonatal opioid withdrawal syndrome with prolonged use during pregnancy; risk of fatal overdose from accidental exposure; risk of interaction with CYP3A4 inhibitors; risk of serotonin syndrome with serotonergic drugs.
| Common Effects | Constipation |
| Serious Effects |
Hypersensitivity to fentanyl or any componentAcute or severe bronchial asthma or respiratory depression without resuscitation equipmentConcurrent use or within 14 days of MAO inhibitorsSuspected or known paralytic ileusMyasthenia gravis (relative, but generally considered absolute for non-anesthetic use)
| Precautions | Respiratory depression, abuse potential, interactions with CNS depressants, serotonin syndrome, adrenal insufficiency, hypotension, seizure risk, biliary tract spasm, and increased intracranial pressure. |
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| Breastfeeding |
| Fentanyl is excreted into breast milk in low concentrations, but short-term use is generally considered compatible with breastfeeding. Monitor infant for respiratory depression, sedation, and poor feeding. Avoid breastfeeding for 4-6 hours after last dose if possible. Prolonged maternal use may lead to withdrawal in breastfed infants. |
| Lactation Rating | L3 - Moderately Safe |
| Teratogenic Risk | First trimester: Limited data; potential for neural tube defects based on animal studies. Second/third trimester: Fetal dependence and withdrawal syndrome with chronic use; risk of preterm labor, intrauterine growth restriction. Transplacental transfer occurs. Avoid in pregnancy unless benefit outweighs risk. |
| Fetal Monitoring | Maternal: Sedation level, respiratory rate, oxygen saturation, blood pressure, heart rate. Fetal: Heart rate monitoring (non-stress test, biophysical profile) for growth restriction or distress. Neonatal: Withdrawal symptoms (Neonatal Abstinence Syndrome) after delivery. |
| Fertility Effects | Animal studies suggest potential for reduced fertility and embryo-fetal toxicity. In humans, no conclusive evidence; however, chronic opioid use may disrupt menstrual cycles and hypothalamic-pituitary-gonadal axis, potentially impairing fertility. |
| Food/Dietary |
| Avoid alcohol and grapefruit juice as they can increase opioid side effects and risk of respiratory depression. |
| Clinical Pearls | FENTANYL-75 is a high-potency transdermal fentanyl patch delivering 75 mcg/h. Use only in opioid-tolerant patients due to risk of respiratory depression. Apply to non-irritated, non-hairy skin on chest, back, or upper arm. Avoid heat exposure (heating pads, hot baths) as it increases absorption. Onset of action is 12-24 hours; do not use for acute pain. Dispose of patches by folding adhesive sides together and flushing down toilet or returning to take-back program. |
| Patient Advice | Apply the patch to clean, dry, non-irritated skin on the chest, back, or upper arm. · Rotate application sites to avoid skin irritation. · Do not cut or damage the patch. · Avoid heat sources such as heating pads, hot tubs, or direct sunlight while wearing the patch. · Keep patches out of reach of children and pets; accidental exposure can be fatal. · Do not stop using the patch suddenly without consulting your doctor. · Monitor yourself for signs of overdose: slow breathing, severe drowsiness, confusion. |