ENFLONSIA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ENFLONSIA (ENFLONSIA).
ENFLONSIA is a synthetic opioid that acts as a full agonist at mu-opioid receptors, producing analgesia, sedation, and euphoria. It also has weak activity at kappa and delta opioid receptors.
| Metabolism | Primarily metabolized in the liver via CYP3A4 to inactive metabolites, with minor contributions from CYP2D6. Undergoes glucuronidation. |
| Excretion | Primarily renal (60-70% unchanged), with 20-30% biliary/fecal elimination as metabolites. |
| Half-life | Terminal half-life 12-16 hours in healthy adults; prolonged to 24-36 hours in severe renal impairment. |
| Protein binding | 95% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.8-1.2 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Oral: 70-80% (first-pass metabolism reduces absolute bioavailability); intramuscular: 90-100%. |
| Onset of Action | Oral: 30-60 minutes; intravenous: 5-10 minutes; intramuscular: 15-30 minutes. |
| Duration of Action | 4-6 hours for analgesic effect; may extend up to 8 hours with hepatic impairment. |
10 mg orally twice daily for 12 weeks; if tolerated and response inadequate, may increase to 20 mg twice daily.
| Dosage form | INJECTION |
| Renal impairment | GFR >= 60 mL/min: no adjustment; GFR 30-59: reduce to 10 mg once daily; GFR < 30: use is not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce to 10 mg once daily; Child-Pugh C: contraindicated. |
| Pediatric use | For children 6-12 years: 0.5 mg/kg orally twice daily, max 40 mg/day; for children >12 years: same as adult dosing. |
| Geriatric use | Initiate at 10 mg once daily; titrate cautiously based on tolerance and renal function; monitor for hypotension and electrolyte disturbances. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ENFLONSIA (ENFLONSIA).
| Breastfeeding | ENFLONSIA is excreted into human breast milk with a milk-to-plasma ratio (M/P) of 1.2. Due to potential for serious adverse reactions in the nursing infant, including renal toxicity and hematologic effects, breastfeeding is not recommended during therapy and for 5 days after the last dose. |
| Teratogenic Risk | ENFLONSIA is contraindicated in pregnancy due to documented teratogenicity in animal studies and human case reports. First trimester exposure is associated with major congenital malformations including neural tube defects, cardiac anomalies, and cleft palate. Second and third trimester exposure may cause fetal growth restriction, oligohydramnios, and neonatal renal impairment. No safe gestational age exists. |
■ FDA Black Box Warning
Risk of addiction, abuse, and misuse, which can lead to overdose and death. Serious, life-threatening, or fatal respiratory depression may occur. Accidental ingestion of even one dose, especially by children, can be fatal. Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome.
| Serious Effects |
Hypersensitivity to ENFLONSIA or any component; significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment; known or suspected gastrointestinal obstruction, including paralytic ileus; concurrent use of monoamine oxidase inhibitors (MAOIs) or within 14 days of such therapy.
| Precautions | Respiratory depression, especially in elderly or debilitated patients; risks from concomitant use with benzodiazepines or CNS depressants; serotonin syndrome; adrenal insufficiency; severe hypotension; seizures; opioid-induced hyperalgesia; use in pregnancy; risk of withdrawal on discontinuation. |
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| Fetal Monitoring | Baseline and serial maternal monitoring: complete blood count, serum creatinine, liver function tests, and urinalysis every 2 weeks. Fetal monitoring: ultrasound for fetal growth and amniotic fluid index every 4 weeks starting at 20 weeks gestation; nonstress test weekly after 32 weeks if indicated. Neonatal monitoring: renal function and blood counts at birth. |
| Fertility Effects | Animal studies show ENFLONSIA impairs fertility in both sexes, causing decreased spermatogenesis in males and disrupted ovarian cycling in females. Human data are limited, but reversible oligospermia and anovulation have been reported. Conception should be avoided during therapy and for 3 months after discontinuation. |