ONSOLIS
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 504.6 |
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 | Avoid use due to potential teratogenic effects; fetal risk cannot be ruled out. |
| 2nd trimester | Avoid use as fetal exposure may occur and risk remains unclear. |
| 3rd trimester | Avoid use; risk of neonatal withdrawal syndrome and respiratory depression. |
Clinical note
Comprehensive clinical and safety monograph for ONSOLIS (ONSOLIS).
| Placental transfer | Buprenorphine crosses the placenta; placental transfer has been demonstrated in animal studies and human data; cord blood concentrations are low relative to maternal plasma. |
| Breastfeeding | Buprenorphine is excreted into breast milk in low concentrations; monitor infant for sedation and respiratory depression; weight loss and withdrawal symptoms have been reported; consider benefits and risks. |
| Lactation Rating | L3 - Moderately Safe |
| 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. |
| 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. |
■ 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 |
Hypersensitivity to buprenorphine or any componentSignificant respiratory depressionAcute or severe bronchial asthmaKnown or suspected gastrointestinal obstruction, including paralytic ileus
| Precautions | Respiratory depression, CNS depression, Addiction and abuse potential, Interaction with CYP3A4 inhibitors/inducers, Serotonin syndrome with serotonergic drugs, Adrenal insufficiency, Hypotension, Seizures |
| Food/Dietary | ONSOLIS should not be taken with alcohol, grapefruit juice, or any foods/beverages containing grapefruit, as they can increase fentanyl levels and risk of respiratory depression. No other specific food interactions are known; however, patients should avoid consuming extremely hot or cold foods or beverages immediately before or during administration, as this may affect buccal absorption. Advise patients to maintain normal oral hygiene and avoid chewing or irritating the application site. |
| Clinical Pearls | ONSOLIS (fentanyl buccal soluble film) is a transmucosal immediate-release fentanyl formulation indicated for breakthrough pain in opioid-tolerant adults. Due to high bioavailability (~71%) and rapid absorption, it should not be switched on a mcg-per-mcg basis with other fentanyl products. Place the film on the inside of the cheek (buccal mucosa) with the pink side against the cheek; do not chew, suck, or swallow. The film must remain in place for at least 5 minutes to dissolve completely. Patients must be opioid-tolerant, defined as taking at least 60 mg oral morphine/day, 25 mcg transdermal fentanyl/hour, 30 mg oxycodone/day, 8 mg hydromorphone/day, 25 mg oxymorphone/day, or an equianalgesic dose of another opioid for one week or longer. Concomitant use with CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) can increase fentanyl levels and risk of fatal respiratory depression. Accidental exposure to a child is a medical emergency — immediately seek emergency care. |
| Patient Advice | ONSOLIS is a strong opioid pain medicine for breakthrough cancer pain in adults who are already taking other opioid pain medicines. · Keep ONSOLIS out of the reach of children; accidental use by a child is a medical emergency and can be fatal. · Use only when you have breakthrough pain; do not use more than 4 doses per day. · Place one film on the inside of your cheek with the pink side against the cheek, and let it dissolve for about 5-10 minutes; do not chew, suck, or swallow it. · Do not stop taking your around-the-clock opioid pain medicine while using ONSOLIS. · Do not drink alcohol or take other medicines that make you sleepy or slow your breathing while using ONSOLIS. · Store at room temperature, away from moisture and heat, and safely dispose of unused films via medicine take-back programs. · Seek emergency medical help if you have trouble breathing, extreme drowsiness, or if someone accidentally takes this medicine. |
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