OPVEE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OPVEE (OPVEE).
Opvee is a naloxone-containing nasal spray. Naloxone is an opioid antagonist that competitively binds to mu-opioid receptors, reversing opioid-induced respiratory depression and sedation.
| Metabolism | Primarily hepatic glucuronidation; metabolized by UGT2B7, UGT1A8, and UGT2B15. Minor metabolism via N-dealkylation by CYP3A4. |
| Excretion | Primarily renal excretion of unchanged drug (approximately 50-70%) and conjugated metabolites (glucuronide); the remainder is eliminated via biliary/fecal routes. Total renal clearance accounts for ~60% of systemic clearance. |
| Half-life | Terminal elimination half-life is approximately 2-4 hours (mean 2.8 hours) in healthy adults. Context: Despite short half-life, clinical antagonism of opioids can persist for 1-2 hours, potentially shorter than the opioid; repeat dosing may be needed. |
| Protein binding | Approximately 30-40% bound to plasma proteins, primarily albumin and a1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution at steady state: 2-3 L/kg (mean ~2.5 L/kg). Indicates extensive tissue distribution, consistent with rapid redistribution from brain to plasma, limiting duration of action. |
| Bioavailability | Sublingual: Not available. Intranasal: Approximately 40-60% (relative to IV). Intramuscular: Not established, but expected to be high (estimated >70%). Oral: <2% (extensive first-pass metabolism). |
| Onset of Action | Intravenous: 1-2 minutes. Intramuscular: 2-5 minutes. Intranasal: 5-15 minutes. Onset correlates with opioid reversal; full effect may take a few minutes longer for intramuscular/intranasal routes. |
| Duration of Action | Duration of opioid antagonism: 30-90 minutes, depending on dose and opioid involved. Context: Duration may be shorter than that of long-acting opioids (e.g., methadone, buprenorphine), requiring repeated administration or continuous infusion. |
| Molecular Weight | 339.4 |
2 mg intranasally as a single dose; may repeat every 2-3 minutes if response is inadequate; maximum total dose of 4 mg.
| Dosage form | SPRAY |
| Renal impairment | No dose adjustment required for renal impairment. |
| Liver impairment | No dose adjustment required for hepatic impairment. |
| Pediatric use | Weight-based dosing: For patients weighing 5-20 kg: 2 mg intranasally; for >20 kg: 2-4 mg intranasally. Repeat every 2-3 minutes as needed. |
| Geriatric use | No specific dose adjustment; use with caution due to potential comorbidities and concomitant medications. |
| 1st trimester | No adequate and well-controlled studies. Use only if potential benefit justifies risk. |
| 2nd trimester | Insufficient human data; animal reproduction studies not available. Caution advised. |
| 3rd trimester | May cause neonatal opioid withdrawal syndrome if used chronically. Avoid prolonged use. |
Clinical note
Comprehensive clinical and safety monograph for OPVEE (OPVEE).
| Placental transfer | Unknown. Nalmefene is a small molecule (MW 339.4 Da) and likely crosses the placenta, but no human data available. |
| Breastfeeding | Opvee (nalmefene) is minimally excreted in human milk. Due to low oral bioavailability, infant exposure is expected to be negligible. However, caution is recommended in breastfeeding women. |
| Lactation Rating |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to nalmefene or any component of the formulationSevere hepatic impairment (Child-Pugh Class C) or acute hepatic failure
| Precautions | Risk of recurrent opioid withdrawal due to short duration of action relative to some opioids; may require repeated doses, Risk of severe opioid withdrawal symptoms, Limited efficacy in partial agonist or mixed agonist-antagonist overdoses (e.g., buprenorphine), Not a substitute for emergency medical care; seek immediate medical assistance |
| Food/Dietary | No known food interactions. Opvee is administered intranasally and absorption is not affected by food intake. |
Loading safety data…
| L3 - Moderately Safe |
| Teratogenic Risk | Limited human data; animal studies show no teratogenic effects at clinically relevant doses. In first trimester, risk cannot be excluded; potential for fetal opioid withdrawal if used in third trimester. Avoid unless benefit outweighs risk. |
| Fetal Monitoring | Monitor for respiratory depression, sedation, and withdrawal symptoms in mother and fetus; fetal heart rate monitoring if used near term; assess for signs of neonatal opioid withdrawal syndrome post-delivery. |
| Fertility Effects | No known adverse effects on fertility in animal studies; no human data available. |
| Clinical Pearls |
| Opvee (nalmefene) is a pure opioid antagonist with a longer half-life (10.9 hours) than naloxone, providing sustained reversal of opioid effects. Administer intranasally (2.7 mg/0.1 mL) for suspected opioid overdose. Onset of action is 15-30 minutes; repeat every 2-5 minutes if no response. Monitor for withdrawal precipitation in opioid-dependent patients. Due to prolonged duration, medical observation for at least 4 hours post-administration is recommended to prevent recurrence of respiratory depression. Opvee is not for opioid use disorder treatment or opioid-induced constipation. |
| Patient Advice | Opvee is used for emergency treatment of an opioid overdose, reversing life-threatening breathing problems. · If you witness an overdose, immediately call 911, then give Opvee as a single spray into one nostril. · Stay with the person and give another dose every 2-5 minutes if they do not respond or wake up. · Side effects include opioid withdrawal symptoms such as nausea, vomiting, sweating, and rapid heart rate. · Keep Opvee available if you or a loved one use opioids or have a history of opioid misuse. · After giving Opvee, the person still needs emergency medical care because the drug may wear off before the opioid is eliminated. |