NORGESIC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NORGESIC (NORGESIC).
NORGESIC is a combination of orphenadrine citrate, aspirin, and caffeine. Orphenadrine is a centrally acting muscle relaxant with anticholinergic properties; its exact mechanism is not fully understood, but it may act via central atropine-like effects and inhibition of reuptake of norepinephrine and serotonin. Aspirin inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis, leading to analgesic, antipyretic, and anti-inflammatory effects. Caffeine is a central nervous system stimulant that may enhance analgesia via adenosine receptor antagonism.
| Metabolism | Orphenadrine is extensively metabolized in the liver via oxidative N-demethylation and hydroxylation; aspirin is hydrolyzed to salicylic acid, which is primarily metabolized in the liver by conjugation (glucuronidation and glycine conjugation) and oxidation; caffeine is metabolized in the liver via cytochrome P450 1A2 (CYP1A2) to paraxanthine, theobromine, and theophylline. |
| Excretion | Primarily renal (70% as unchanged drug and metabolites; 10% as unchanged) and biliary (30%) |
| Half-life | Terminal elimination half-life is 2–4 hours; clinical multiple dosing may require 4–6 hour intervals |
| Protein binding | ~90% bound to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 1.5–2.0 L/kg; indicates extensive tissue distribution |
| Bioavailability | Oral: ~70% (first-pass metabolism reduces absolute bioavailability); Intramuscular: ~100% |
| Onset of Action | Oral: 30–60 minutes; Intramuscular: 15–30 minutes |
| Duration of Action | Oral: 4–6 hours; Intramuscular: 4–6 hours; clinical effect lasts until drug concentration falls below therapeutic threshold |
1-2 tablets orally 2-4 times daily. Each tablet contains orphenadrine citrate 100 mg and acetaminophen 325 mg.
| Dosage form | TABLET |
| Renal impairment | GFR 30-59 mL/min: reduce dose by 50% (maximum 1 tablet twice daily). GFR <30 mL/min: avoid use due to risk of accumulation. |
| Liver impairment | Child-Pugh Class B: reduce dose by 50% (maximum 1 tablet twice daily). Child-Pugh Class C: contraindicated. |
| Pediatric use | Not recommended for patients under 18 years of age due to lack of safety and efficacy data. |
| Geriatric use | Start with 1 tablet twice daily; titrate slowly due to increased risk of anticholinergic effects (confusion, urinary retention). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NORGESIC (NORGESIC).
| Breastfeeding | Orphenadrine: excreted in breast milk; M/P ratio unknown; potential for anticholinergic effects in infant. Aspirin: excreted in breast milk; risk of Reye's syndrome if infant has viral illness; avoid breastfeeding while using aspirin. Caffeine: low levels in milk; generally considered safe in moderate amounts. Not recommended during breastfeeding. |
| Teratogenic Risk | Norgesic contains orphenadrine citrate, aspirin, and caffeine. Aspirin: First trimester: possible increased risk of miscarriage and cardiac defects; third trimester: premature closure of ductus arteriosus and oligohydramnios; avoid in third trimester. Orphenadrine: limited human data; animal studies not sufficient; avoid in pregnancy unless benefit outweighs risk. Caffeine: considered low risk at moderate doses. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to any component","Peptic ulcer or gastrointestinal bleeding","Severe renal impairment (creatinine clearance <10 mL/min)","Severe hepatic impairment","Bleeding disorders (e.g., hemophilia)","Concurrent use of anticoagulants or antiplatelet drugs (relative)","Children and teenagers with varicella or influenza-like symptoms (due to Reye's syndrome risk)","Glaucoma (angle-closure), prostatic hypertrophy, or gastrointestinal obstruction (relative, due to anticholinergic effects)"]
| Precautions | ["May impair mental and/or physical abilities required for driving or operating machinery due to anticholinergic effects (e.g., drowsiness, blurred vision)","Use with caution in patients with glaucoma, prostatic hypertrophy, or gastrointestinal obstruction due to anticholinergic effects","Aspirin component increases risk of bleeding, particularly in patients with bleeding disorders or on anticoagulant therapy","Reye's syndrome risk in children and teenagers with viral infections","Hypersensitivity reactions including anaphylaxis may occur","Renal impairment may increase risk of salicylate toxicity"] |
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| Fetal Monitoring | Monitor fetal growth and amniotic fluid volume with regular ultrasound, especially if aspirin used in third trimester. Assess for premature ductus arteriosus closure if used near term. Maternal monitoring: signs of bleeding, gastrointestinal effects, and anticholinergic adverse effects. |
| Fertility Effects | No specific data on orphenadrine or combination effects on fertility. Aspirin may inhibit prostaglandin synthesis involved in ovulation and implantation; possible reversible reduction in fertility. Caffeine at high doses may delay conception. |