ORPHENGESIC
Clinical safety rating
cautionComprehensive clinical and safety monograph for ORPHENGESIC (ORPHENGESIC).
ORPHENGESIC (oxycodone/naloxone) is a combination of an opioid agonist (oxycodone) and an opioid antagonist (naloxone). Oxycodone acts primarily on mu-opioid receptors in the CNS to produce analgesia; naloxone, at oral doses, has low systemic bioavailability but antagonizes opioid effects on gut opioid receptors to reduce constipation.
| Metabolism | Oxycodone is primarily metabolized via CYP3A4 and CYP2D6 to noroxycodone (major) and oxymorphone (minor). Naloxone is extensively metabolized in the liver by UDP-glucuronosyltransferases (UGT2B7) and also by CYP3A4 to naloxone-3-glucuronide. |
| Excretion | Renal: 70-80% as conjugates; fecal: 10-20% via biliary elimination; <5% unchanged drug in urine. |
| Half-life | 3-4 hours in adults; prolonged in hepatic impairment (up to 6-8 hours) and elderly (up to 5 hours). Requires dose adjustment in cirrhosis. |
| Protein binding | 90-95% primarily to alpha-1-acid glycoprotein and albumin. |
| Volume of Distribution | 2.5-3.5 L/kg; large Vd indicates extensive tissue distribution, including CNS. |
| Bioavailability | Oral: 40-60% (first-pass effect); Sublingual: 15-25%; Intramuscular: 70-80%; Rectal: 40-60%; Intravenous: 100%. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: 5-10 minutes; Intramuscular: 10-15 minutes; Rectal: 30-60 minutes. |
| Duration of Action | Oral: 4-6 hours; Intravenous: 3-4 hours; Intramuscular: 4-5 hours; Rectal: 4-6 hours. Extended-release formulations provide 8-12 hours. |
| Molecular Weight | 230.26 |
10 mg oral every 4-6 hours as needed; maximum 60 mg per day.
| Dosage form | TABLET |
| Renal impairment | GFR 30-50 mL/min: 5 mg every 6 hours; GFR 15-29 mL/min: 5 mg every 8 hours; GFR <15 mL/min: 5 mg every 12 hours; avoid in dialysis. |
| Liver impairment | Child-Pugh A: 5 mg every 6 hours; Child-Pugh B: 5 mg every 8 hours; Child-Pugh C: not recommended. |
| Pediatric use | 6-12 years: 0.5 mg/kg oral every 6 hours; 12-18 years: 5-10 mg oral every 6 hours; maximum 60 mg/day. |
| Geriatric use | Initiate at 5 mg oral every 6 hours; titrate cautiously due to increased sensitivity and risk of falls; maximum 30 mg per day. |
| 1st trimester | Avoid; associated with cardiovascular malformations and neural tube defects. |
| 2nd trimester | Avoid; risk of premature closure of ductus arteriosus. |
| 3rd trimester | Avoid; may cause premature closure of ductus arteriosus, oligohydramnios, and neonatal renal impairment. |
Clinical note
Comprehensive clinical and safety monograph for ORPHENGESIC (ORPHENGESIC).
| Placental transfer | Crosses placenta; fetal serum levels can reach up to 50% of maternal levels. |
| Breastfeeding | Excreted into breast milk in low amounts; potential for serious adverse effects in infants, including gastrointestinal bleeding and renal impairment. Use is contraindicated in breastfeeding. |
| Lactation Rating | L5 - Contraindicated |
| Teratogenic Risk | Orphengesic (orphenadrine citrate, aspirin, and caffeine) is contraindicated in pregnancy, especially during the third trimester, due to aspirin's association with premature closure of the ductus arteriosus, oligohydramnios, and increased risk of fetal intracranial hemorrhage. First trimester aspirin exposure may increase risk of gastroschisis and other malformations. Orphenadrine has limited data but anticholinergic effects could potentially cause fetal tachycardia or meconium ileus. Caffeine at high doses is associated with low birth weight and miscarriage. |
| Fetal Monitoring | If exposure occurs, monitor for signs of premature ductus closure (fetal echocardiography), oligohydramnios (ultrasound), fetal growth restriction (serial growth scans), and maternal bleeding tendencies (platelet count, clotting studies). For the neonate, observe for bleeding, thrombocytopenia, or anticholinergic effects (irritability, poor feeding). |
| Fertility Effects | Aspirin may impair ovulation by inhibiting prostaglandin synthesis necessary for follicular rupture; high doses can reduce fertility in women. Orphenadrine has theoretical anticholinergic effects that could affect cervical mucus or fallopian tube motility, but no human data. Caffeine at high doses may delay conception. Overall, orphengesic likely reduces fertility. |
■ FDA Black Box Warning
WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; and RISKS OF TREATMENT FOR OPIOID USE DISORDER (if applicable).
| Serious Effects |
Hypersensitivity to orphengesicActive peptic ulcer diseaseHistory of gastrointestinal bleeding or perforationSevere renal impairment (eGFR <30 mL/min)Severe hepatic impairmentThird trimester of pregnancyBreastfeedingConcurrent NSAID or aspirin use
| Precautions | Risk of addiction, abuse, and misuse, Life-threatening respiratory depression, Accidental ingestion (especially in children), Neonatal opioid withdrawal syndrome, Risks from concomitant use of benzodiazepines or other CNS depressants, Adrenal insufficiency, Severe hypotension, Seizures, Chronic use may cause physical dependence and withdrawal if abruptly discontinued |
| Food/Dietary | Avoid alcohol. No specific food restrictions, but high-fat meals may delay absorption. |
| Clinical Pearls | ORPHENGESIC contains orphenadrine, a centrally acting muscle relaxant with anticholinergic properties. Avoid in patients with glaucoma, urinary retention, or myasthenia gravis. Onset within 1 hour; monitor for sedation and anticholinergic effects. Not recommended in elderly due to fall risk. |
| Patient Advice | May cause drowsiness or dizziness; avoid driving or operating heavy machinery. · Avoid alcohol and other CNS depressants. · Report blurred vision, difficulty urinating, or rapid heartbeat to your doctor. · Swallow tablets whole; do not crush or chew. |
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