ONSOLIS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ONSOLIS (ONSOLIS).
Onsolis (fentanyl buccal soluble film) is an opioid agonist that binds to mu-opioid receptors in the central nervous system, producing analgesia by increasing potassium conductance and inhibiting calcium channels, leading to reduced neurotransmitter release and hyperpolarization of neurons.
| Metabolism | Primarily metabolized by CYP3A4 to norfentanyl and other inactive metabolites |
| Excretion | Primarily hepatic metabolism via glucuronidation, with approximately 70% of the dose excreted in urine as metabolites and 10-15% in feces as unchanged drug. |
| Half-life | Terminal elimination half-life is approximately 3-5 hours in adults, providing sustained analgesic effect with multiple daily dosing. |
| Protein binding | Approximately 95% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Mean volume of distribution is 3.0 L/kg (range 2-5 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Buccal administration absolute bioavailability is approximately 50%, with interindividual variability due to buccal absorption and first-pass metabolism. |
| Onset of Action | Buccal administration: onset of analgesia occurs within 10-15 minutes, with peak plasma concentrations achieved at 30-60 minutes. |
| Duration of Action | Duration of analgesic effect is approximately 2-4 hours for breakthrough pain, with clinical notes recommending dosing every 4 hours as needed. |
Onsolis (fentanyl buccal soluble film) is indicated for breakthrough pain in opioid-tolerant patients. The initial dose is 200 mcg placed on the buccal mucosa; titrate to effective dose in 200 mcg increments across subsequent episodes. Maximum frequency: 4 doses per day. Allow at least 2 hours between doses.
| Dosage form | FILM |
| Renal impairment | For GFR 30-59 mL/min: initiate with 100 mcg; for GFR 15-29 mL/min: initiate with 50 mcg; for GFR <15 mL/min: not recommended. Titrate cautiously due to increased fentanyl exposure. |
| Liver impairment | For Child-Pugh Class A: no adjustment. For Child-Pugh Class B: initiate at 50 mcg; titrate slowly. For Child-Pugh Class C: not recommended. |
| Pediatric use | Safety and efficacy in pediatric patients under 18 years have not been established; use not recommended. |
| Geriatric use | Patients >65 years: initiate at 100 mcg. Titrate with caution due to increased sensitivity and potential for respiratory depression. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ONSOLIS (ONSOLIS).
| Breastfeeding | Fentanyl is excreted in human milk. The milk-to-plasma (M/P) ratio is approximately 0.43 for intravenous fentanyl. Oral transmucosal administration may result in similar transfer. Breastfeeding is not recommended during treatment with ONSOLIS due to the potential for infant sedation and respiratory depression. A nursing infant could be exposed to clinically relevant doses. |
| Teratogenic Risk | Fetal risk cannot be ruled out. No adequate and well-controlled studies in pregnant women. In animal studies, fentanyl (active ingredient) was embryocidal and reduced pup survival at doses within the human dose range. Risk in first trimester: Potential for neural tube defects. Second and third trimesters: Potential for fetal opioid withdrawal syndrome after prolonged use. Avoid use during labor and delivery due to risk of neonatal respiratory depression. |
■ FDA Black Box Warning
Risk of respiratory depression, especially in opioid-naive patients; contraindicated in acute or postoperative pain; must be used only in opioid-tolerant patients; risk of abuse, addiction, and diversion.
| Serious Effects |
["Opioid non-tolerant patients","Acute or postoperative pain","Significant respiratory depression","Paralytic ileus","Concurrent use of MAOIs or within 14 days","Known hypersensitivity to fentanyl or components"]
| Precautions | ["Respiratory depression","CNS depression","Addiction and abuse potential","Interaction with CYP3A4 inhibitors/inducers","Serotonin syndrome with serotonergic drugs","Adrenal insufficiency","Hypotension","Seizures"] |
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| Fetal Monitoring | Monitor for maternal respiratory depression, sedation, and hypotension. Fetal monitoring (non-stress test or biophysical profile) is indicated for prolonged use, particularly in the third trimester, to detect signs of fetal opioid withdrawal. Neonates should be monitored for respiratory depression and withdrawal symptoms (neonatal abstinence syndrome) after delivery if maternal use occurred near term. |
| Fertility Effects | In animal studies, fentanyl caused decreased fertility in male rats at doses 0.4 times the human dose equivalent based on AUC. Effects on human fertility are unknown but may include decreased libido, erectile dysfunction, and anovulation due to hyperprolactinemia from chronic opioid use. |