ABSTRAL
Clinical safety rating
cautionComprehensive clinical and safety monograph for ABSTRAL (ABSTRAL).
Fentanyl is a potent mu-opioid receptor agonist, producing analgesia and sedation by activating G-protein coupled opioid receptors in the central nervous system.
| Metabolism | Hepatic metabolism primarily via CYP3A4; major metabolites include norfentanyl (inactive) and other minor metabolites. |
| Excretion | Renal: ~70% as metabolites (primarily fentanyl conjugates and norfentanyl), ~10% unchanged; Fecal: ~9%; Biliary: minimal |
| Half-life | Terminal elimination half-life: 6-10 hours (mean 8 hours); prolonged in elderly and hepatic impairment |
| Protein binding | 80-85% bound primarily to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 4-6 L/kg; large Vd indicates extensive tissue distribution |
| Bioavailability | Sublingual: 70-90% (mean 80%); buccal: 50-65%; oral: ~30% due to first-pass metabolism |
| Onset of Action | Sublingual: 5-15 minutes; buccal: 10-20 minutes |
| Duration of Action | Sublingual/buccal: 2-4 hours; clinical titration: effect lasts 30-60 minutes, duration of pain relief shorter due to tolerance |
| Molecular Weight | 336.47 |
For breakthrough pain in opioid-tolerant patients: initial dose 100 mcg sublingual tablet, titrate across strengths (100, 200, 300, 400, 600, 800 mcg) as needed; maximum 2 doses per episode, minimum 2 hours between episodes.
| Dosage form | TABLET |
| Renal impairment | No specific GFR-based dose adjustment recommended; use caution in severe renal impairment (CrCl <30 mL/min) due to potential accumulation of fentanyl. |
| Liver impairment | For Child-Pugh Class A or B: no adjustment required; for Child-Pugh Class C: reduce dose and monitor closely for toxicity due to reduced clearance. |
| Pediatric use | Not approved for pediatric patients <18 years; safety and efficacy not established. |
| Geriatric use | Initiate at the lowest available dose (100 mcg) and titrate cautiously; elderly patients may have altered pharmacokinetics and increased sensitivity to fentanyl. |
| 1st trimester | Contraindicated due to risk of opioid withdrawal and potential teratogenicity; use only if benefit outweighs risk. |
| 2nd trimester | Contraindicated due to risk of fetal opioid dependence; prolonged use may cause neonatal withdrawal. |
| 3rd trimester | Contraindicated; risk of neonatal respiratory depression, opioid withdrawal syndrome, and preterm labor. |
Clinical note
Comprehensive clinical and safety monograph for ABSTRAL (ABSTRAL).
| Placental transfer | Fentanyl crosses the placenta readily; rapid transfer observed in animal and human studies. |
| Breastfeeding | Fentanyl is excreted into breast milk in small amounts; however, with short-term use of ABSTRAL (fentanyl buccal tablet), effects on the infant are likely minimal. Caution is advised due to potential for sedation and respiratory depression. Use only if clearly needed and monitor infant for signs of opioid toxicity. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: Inadequate human data; opioid analgesics are not associated with major malformations but may cause neural tube defects at high doses in animal studies. Second trimester: No specific malformation risk. Third trimester: Prolonged use can cause neonatal opioid withdrawal syndrome (NOWS) and respiratory depression at birth. |
| Fetal Monitoring | Maternal: Assess pain control, respiratory rate (target ≥12/min), sedation level, and bowel function. Fetal: For prolonged use, monitor fetal growth and amniotic fluid index. At delivery, monitor neonate for respiratory depression (Naloxone availability) and NOWS (Finnegan scoring). |
| Fertility Effects | In animal studies, fentanyl did not impair fertility. In humans, chronic opioid use may cause menstrual irregularities and hypogonadism, potentially reducing fertility. Reversible upon discontinuation. |
■ FDA Black Box Warning
Risk of respiratory depression, addiction, abuse, and misuse; risk of accidental ingestion; risk of medication errors resulting in fatal overdose; life-threatening respiratory depression in opioid-non-tolerant patients; risk of opioid analgesic drug interactions with CNS depressants; risk of neonatal opioid withdrawal syndrome with prolonged use during pregnancy.
| Serious Effects |
Hypersensitivity to fentanyl or any componentSignificant respiratory depressionAcute or severe bronchial asthmaParalytic ileusKnown or suspected gastrointestinal obstructionUse of monoamine oxidase inhibitors (MAOIs) within 14 daysManagement of acute or postoperative pain (including headache/migraine)
| Precautions | Respiratory depression, QT prolongation, serotonin syndrome, adrenal insufficiency, severe hypotension, seizures, biliary tract disease, gastrointestinal obstruction, withdrawal syndrome, and risk of overdose with alcohol or other CNS depressants. |
| Food/Dietary | Avoid grapefruit and grapefruit juice during treatment as they inhibit CYP3A4, increasing fentanyl exposure. No other significant food interactions; however, avoid alcohol due to additive CNS depressant effects. Maintain consistent meal timing relative to dosing to minimize variability. |
| Clinical Pearls | ABSTRAL (fentanyl sublingual spray) is a transmucosal immediate-release fentanyl (TIRF) formulation indicated for breakthrough pain in opioid-tolerant patients. Due to high bioavailability (~70%) and rapid onset (peak plasma concentration at 15-30 minutes), initial titration must start with 100 mcg, with dose escalation based on efficacy and tolerability. Weight-based conversion from other fentanyl products is not valid; utilize the provided conversion table. Patients must have a rescue agent (e.g., naloxone) available. Concomitant use with CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) or inducers (e.g., rifampin, carbamazepine) requires dose adjustment. Avoid use in opioid-naïve patients due to risk of respiratory depression. |
| Patient Advice | Use only for breakthrough cancer pain while on around-the-clock opioid therapy. · Do not switch from other fentanyl products based on dose; follow specific conversion instructions. · Spray entire dose into mouth; do not swallow or rinse for at least 10 minutes. · Store at room temperature, away from children and pets. · Dispose of unused units via drug take-back program or by flushing down toilet per FDA guidelines. · Never share this medication with others; death may occur. · Seek emergency if severe drowsiness, confusion, or slow breathing occurs. |
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